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Gynecology Theory & Practice for Postgraduates

Q: Describe the conditions under which hysteroscopic myomectomy might be preferred over abdominal myomectomy for treating uterine myomas and the preparation required for this procedure.

Hysteroscopic myomectomy is typically preferred for managing small to moderate-sized submucous myomas, particularly when their protrusion into the uterine cavity is significant (over 50% of circumference). Preoperative preparation often involves 3 to 6 months of GnRH agonist therapy or cyclic use of contraceptive pills to reduce myoma size and improve anemia. The endometrial cavity is accessed with an operating hysteroscope, facilitating tumor removal via diathermy, resectoscope, or laser. Continuous irrigation and monitoring prevent fluid overload. As an outpatient procedure, it's less invasive than abdominal myomectomy and better suited for preserving uterine integrity and fertility in women wishing to maintain reproductive potential. Postoperative management involves further GnRH therapy if needed and monitoring for any complications, like intrauterine adhesion formation .

Q: Analyze the surgical approach to correcting an anterior wall cystocele and how each step contributes to the overall objective of the operation.

The surgical correction of an anterior wall cystocele targets the reinforced support of the bladder and anterior vaginal wall. The procedure involves making a transverse incision below the bladder sulcus and dissecting the anterior vaginal wall from the bladder base. The bladder is then mobilized upward to become retropubic. The pubocervical fascia is sutured together in the midline, creating support beneath the bladder. This incision also involves excising any redundant vaginal tissue, ensuring the strong vaginal tissue supports the bladder without excessive narrowing. Each step, from incision to suturing, stabilizes and provides a structural base for the anterior vaginal wall, mitigating the prolapse and potentially associated issues like stress urinary incontinence .

Q: Identify the key diagnostic and management principles in cases of myomata-associated infertility, particularly concerning myomectomy procedures.

In myomata-associated infertility, precise diagnostic imaging such as sonography or hydrohystersonography is essential to assess the size, location, and impact of myomas on uterine and tubal structures. These findings guide the need for and approach to myomectomy, with the aim of preserving or restoring fertility. During myomectomy, both the anatomical preservation of the uterus and the avoidance of intraperitoneal adhesions from extensive dissection are prioritized. Procedures should maintain reproductive potential by minimizing damage to the uterine lining and ensuring patency of the fallopian tubes. The choice between hysteroscopic, laparoscopic, or abdominal myomectomy depends on tumor characteristics like size and location, and the patient's reproductive goals .

Q: Explain the hormonal disturbances and their outcomes in individuals with Klinefelter’s Syndrome and how it affects their physical development.

Individuals with Klinefelter's Syndrome typically exhibit tall, eunuchoid features and genital hypoplasia due to their 47, XXY karyotype. Their testes are abnormally small and soft, sometimes undescended, with gonadotrophin levels being normal or elevated. This condition can lead to sparse body hair and gynecomastia after puberty. They may experience intellectual challenges or antisocial behavior, although intelligence can also be normal or even above average in some cases. Typically, individuals with mosaicism (47, XXY/46, XY) can be fertile and do not transmit the syndrome to offspring. The hormonal imbalances often result in an unusual physical development partly due to the disruption of normal testosterone production .

Q: How do the various types of estrogens differ in terms of their biosynthesis and the cells involved in their production within the ovaries?

Estradiol and estrone are primarily synthesized by the granulosa cells of the growing follicles in the ovaries. Estradiol is the main estrogen produced by the human ovary and is characterized by the presence of two hydroxyl groups. Estrone, with one hydroxyl group, is a much weaker estrogen and is produced in smaller quantities. When a preovulatory follicle becomes dominant, there's a spike in estradiol production, which peaks prior to ovulation and then decreases. The corpus luteum also contributes to estrogen production, though at lower levels than pre-ovulation. This process is regulated by the pituitary gonadotrophins FSH and LH .

Q: What are the implications of genital prolapse repairs on urinary and sexual function, and how might these surgeries address these issues?

Repairs for genital prolapse, such as cystocele corrections and anterior colporrhaphy, aim to restore normal anatomical function, thereby improving both urinary and sexual functions. The repair procedures typically involve repositioning and stabilizing the bladder and urethra to prevent urinary incontinence, often a consequence of prolapse. By supporting the anterior vaginal wall and reconstructing any weakened structures, the repairs provide an anatomical layout that allows for better urinary continence and more natural vaginal positioning, potentially reducing dyspareunia. Pelvic floor support is often reinforced to provide indirect support to the vaginal walls and resist further prolapse, which can have additional beneficial effects on urinary flow and sexual experience .

Q: Discuss the management strategies for chlamydial infections in women and the importance of such treatments in preventing reproductive complications.

Management of chlamydial infections in women focuses on prompt diagnosis and antibiotic therapy to prevent reproductive complications such as pelvic inflammatory disease (PID), tubal damage, and infertility. The high incidence of asymptomatic cases demands a vigilant approach, including regular screenings, especially for sexually active women. Laboratory tests using direct fluorescent antibody staining, ELISA, or tissue culture help confirm the diagnosis. Timely treatment with antibiotics like azithromycin or doxycycline is crucial in mitigating the risk of ascending infections that may cause severe conditions like PID or ectopic pregnancy. Effective management not only prevents individual reproductive health issues but also controls the spread of infection within the broader population .

Q: Evaluate the role of hCG levels and sonography in diagnosing and managing early pregnancy complications.

Human Chorionic Gonadotropin (hCG) levels and sonography play critical roles in diagnosing early pregnancy complications. A positive immunological pregnancy test generally corresponds with an hCG concentration of around 1000 mIU/ml. Following this, sonography can identify an intrauterine gestational sac as early as 33-35 days from the last menstrual period. For ongoing pregnancy viability, an hCG level of at least 20,000 mIU/ml by the 45th day is expected, signalling fetal heart activity. A consistent rise in hCG and embryonal growth through sonography indicates healthy pregnancy progression. However, a low progesterone level (< 20 mg/ml), slow hCG rise, or lack of embryonal growth suggests embryonal demise or ectopic pregnancy. Regular sonography and hCG assays are essential for monitoring such conditions and informing management decisions like intervention in ectopic pregnancy cases .

Q: Discuss the impact of Congenital Adrenal Hyperplasia (CAH) on the endocrine system and the resulting physical manifestations in affected females.

Congenital Adrenal Hyperplasia (CAH) primarily results from a deficiency in enzymes required for cortisol synthesis in the adrenals, typically the 21-hydroxylase enzyme. This leads to a lack of negative feedback on ACTH secretion by the pituitary, resulting in excessive ACTH production and subsequent adrenal gland hyperplasia. The hyperplasia causes overproduction of steroid precursors and diversion into excessive adrenal androgen production, such as androstendione, DHEA, and testosterone. In affected females, this causes varying degrees of masculinization of external genitalia, such as clitoral hypertrophy and fusion of the urogenital folds, leading to ambiguous genitalia. Despite normal antimullerian hormone levels allowing for internal female genital development (fallopian tubes, uterus, upper vagina), a Wolffian duct system does not develop due to the absence of high androgen levels required for its development .

Q: Evaluate the relationship between testosterone synthesis defects and their phenotypic manifestation in male pseudohermaphroditism.

Testosterone synthesis defects, often due to autosomal recessive inheritance of deficient 17 b hydroxysteroid dehydrogenase activity, critically impact male pseudohermaphroditism by disrupting normal male genital development. Phenotypic manifestations include typically female-like external genitalia despite male internal genitalia structures, as testosterone levels are decreased while androstenedione and estrogen levels are elevated. At puberty, limited virilization might occur depending on peripheral conversion of androstenedione to testosterone. Due to ambiguous genitalia and underdeveloped male characteristics, individuals are usually raised and identified as females. Early gonadectomy is recommended to prevent further complications or development of germ cell tumors from undescended testes, ensuring better psychological and physical outcome alignments .

This document is a comprehensive textbook on Gynecology for postgraduate students, authored by Mamdouh M. Shaaban. It covers essential topics in obstetrics and gynecology, including anatomy, physiology, clinical features, and various conditions affecting women's health, aimed at providing a reference for both postgraduate and undergraduate medical education. The book emphasizes practical skills required for different degrees and is based on the author's extensive experience in clinical practice and teaching.

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Gynecology Theory & Practice for Postgraduates

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GYNECOLOGY

FOR

POSTGRADUATES,
THEORY AND PRACTICE

Mamdouh M. Shaaban
Professor of Obstetrics and Gynecology
Assiut University
Volume I
• All rights reserved to the author
• No part of this book may be reproduced in any form or any electronic or
mechanical means, without a written permission from the author (address:
PO Box, 174, Assiut. Egypt, or Department of obstetrics and gynecology,
Assiut University, Assiut, Egypt.

• ISBN:……………………..
• Printed by:…………………..
• Address:………………………….
• Telephone:……………………… Fax:……………………………..
‫لماذا ‪...........‬؟‬

‫هذا الكتاب إفراغ للجعبة‪ ،‬وابراء للذمة‪.‬‬

‫ولعله يكون آخر فسيلة أبتغي به عند هللا وسيله‪.‬‬

‫فيه استقراء للخبرة والخبر‪ ،‬ومراجعة لما نشر‬

‫وكل أمر مستطر في الدوريات والزبر‪،‬‬

‫واستبعاد لما كان ونكر‪،‬أو ما فيه الخالف مستعر‬

‫وإثبات لكل أمر مستقر‪.‬‬

‫‪i‬‬
Preface
With the rapid increase of medical graduates in Egypt, there has been a great
demand on specialization. Postgraduate training has become to form a good part of the
academic responsibility of the faculty of medical schools. The postgraduate studies in
Obstetrics and Gynecology presently involve three degrees: Diploma, Master and
Doctorate. Lack of definition of the syllabuses of these three degrees has been, for many
years, a matter of concern to me. This book is a trial to define what is required from
postgraduate students.
The logarithmic expansion of basic science foundation and the many innovations
in Gynecological practice have urged me to put together a summary of them in one text.
The book covers the needs for the Master and gives a description of the practical skills
required from the Diploma candidates. The book also gives most of the knowledge that
should be required in Doctorate examinations and equivalent degrees. It can be a
reference text for undergraduates. The relevance to the Egyptian practice is emphasized
as has been amassed during forty-year experience in clinical practice and teaching.
Practicing gynecologists can find in this text many helpful hints, and guidance to their
clinical work.
I acknowledge the help I received from Omar M. Shaaban, M.D., in preparing the
book. I also acknowledge the secretarial help of Mr. Abdel-Haleem A. Aly and Ms.
Meiral A. Fayez.
Mamdouh M. Shaaban
Assiut, 2002

ii
LIST OF CONTENTS
Volume I:
1. Anatomy of the female genital system, 1-32
2. Physiology of reproduction in women, 33-72
3. Clinical features of the normal menstrual cycle, 73-82
4. Menopause, 83-95
5. Development of the female genital system, 96-101
6. Congenital abnormalities in the female genital system, 102-109
7. Normal and abnormal sexual differentiation- hirsutism, 110-142
8. Abortion, 143-169
9. Ectopic pregnancy, 170-186
10. Gestational trophoblastic tumors, 187-205
11. Genital prolapse, 206-241
12. Displacements of genital organs other than prolapse, 242-253
13. Urinary stress incontinence and detrusor instability, 254-268
14. Traumatic lesions in the genital tract, 269-299
15. Genital tract infections, 300-373
16. Carcinoma of the cervix, 374-406
17. Tumors of the corpus uteri, 407-454
18. Ovarian tumors, 455-515
19. Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva and vagina, 516-541

Volume II:
20. Infertility, 542-664
21. Amenorrhea, oligomenorrhea and hypomenorrhea, 665-696
22. Endometriosis, 697-712
23. Abnormal uterine bleeding (Dysfunctional uterine bleeding) (DUB), 713-739
24. Menstruation related symptoms, 740-748
25. Cytogenetics and molecular genetics, relevance to obstetrics and gynecology, 749-787
26. Sexual dysfunctions in women, 788-810
27. Hysterectomy, 811-874
28. Contraception and family panning, 875-1023
29. Clinical evaluation of a gynecological case, 1024-1047
30. Ethical aspects in gynecology, 1048-1067

iii
WHAT ARE YOU GOING TO LEARN
Detailed contents
Volume I:

1. Anatomy of the female genital system, 1-32

• Vulva
• Vagina
• Uterus
• Cervix
• Body (corpus)
• Fallopian tubes
• Ovaries
• Pelvic peritoneum
• Pelvic cellular tissue
• Pelvic ligaments
• Pelvic muscles
• Perineum
• Urinary bladder and urethra
• Pelvic ureter
• Rectum and anal canal
• Pelvic vessels
• Pelvic nerves
• Pelvic bones
• Anterior abdominal wall

2. Physiology of reproduction in women, 33-72

• Ovarian function
- Folliculogenesis and ovulation
- Ovarian hormones
• Pituitary hormones
• Hypothalamus
• Menstrual cycle
• Prostaglandins (Arachidonic acid Family)
• Assay of reproductive hormones
• Menopause

3. Clinical features of the normal menstrual cycle, 73-82

• Puberty, menarche and adolescence
• Precocious Puberty and delayed puberty
• Normal menstruation
• Ovulation

4. Menopause, 83-95
• Endocrinology of Menopause:
• Symptoms of the menopause
• Pathophysiological changes after menopause

iv
• Management of Menopause

5. Development of the female genital system, 96-101

• Genital ridge
• Wolffian system
• Mullerian duct
• Development of the vulva
• Development of the vagina
• Development of the urinary system

6. Congenital abnormalities In the female genital system, 102-109

• Ovary
• Mullerian Duct defects
- Imperforate vagina
- Mullerian aplasia
- Uterine hypoplasia
- Uterine cavity duplication
- Rudimentary horn
• Vulval congenital abnormalities

7. Normal and abnormal sexual differentiation- hirsutism, 110-142

• Normal sexual differentiation:
- Influence of chromosomal complement
- Hormonal production at the gonads
- Peripheral metabolism of sex steroids
- Pubertal and postpubertal hormone production
- Social influences
• Sex ratio
• Improper sexual characters
a. Conditions resulting from abnormal chromosomal complement.
1.1Gonadal dysgenesis
1.2 Triple X
1.3 Klinefelter syndrome
1.4 YY syndrome
1.5 Hermaphroditism
b. Conditions resulting from abnormal hormone production or action
2.1 Virilization of a female
i. Congenital adrenal hyperplasia (CAH)
a. Classical type
b. Salt-wasting type
c. Late-onset CAH
ii. Maternal disease and drug intake
iii. Placental aromatase deficiency
iv. Virilization of pubertal or adult females and Hirsutism: causes-diagnosis and
management
2.2 Feminization of a male
i. Androgen insensitivity syndrome (AIS)
a. Complete form (CAIS)
b. Incomplete from (IAIS)
ii. 5-reductase deficiency
iii. Abnormal androgen synthesis
iv. Testicular destruction
v. Estrogen influence

v
vi. Constitutional feminism
vii. Psychological or behavioral feminism
c. Non endocrine sexual ambiguity
• Diagnosis and management of ambiguous genitalia

8. Abortion, 143-169
• Definition
• Frequency
• Etiology
- Zygote / embargo / fetal abnormalities
- Uterine defects
- Maternal diseased conditions
• Stages and clinical types of abortion
- Threatened abortion
- Inevitable abortion
- Missed abortion
- Septic abortion
- Habitual abortion: causes and management
- Criminal abortion
• Induction of abortion

9. Ectopic pregnancy, 170-186

• Tubal pregnancy
- Incidence
- Etiological factors
- Pathology
- Clinical features and diagnosis
Acute syndrome
Subacute syndrome
Diagnostic aids
Diagnosis of undisturbed ectopic
- Treatment
Surgical
Medical
• Abdominal Pregnancy
• Ovarian Pregnancy
• Cervical Pregnancy
• Pregnancy in a rudimentary horn
• Heterotopic ectopic pregnancy

vi
- Pathology
- Clinical picture
- Diagnosis
- Stages
• Management of persistent trophoblastic tumors
- Chemotherapy
- Hysterectomy
- Prognosis
- Follow-up

[Link] stress incontinence and detrusor instability, 254-268

• Introduction and types of urinary incontinence
• Etiology of urinary stress incontinence
• Etiology of detrusor instability
• Diagnosis of stress incontinence and detrusor instability symptom, physical signs, urodynamic
workup
• Treatment of Detrusor Instability
• Treatment of genuine stress incontinence
- Nonsurgical
- Surgical

[Link] lesions in the genital tract, 269-299

• Perineal and vulval injuries
- Old tears

vii
Defective perineum
Complete perineal tear
• Cervical tears – and detachment
• Uterine perforation and rupture
• Urinary – genital fistulas
• Fecal fistulas
• Acquired atresia

[Link] of the cervix, 374-406

• Etiological considerations
- Epidemiological findings
- Natural history of cervical neoplasia: Pathogenesis
- Molecular biological considerations

viii
• Pathology
- Dysplasia, cervical intraepithelial neoplasia (CIN) and Carcinoma in situ
- Microinvasive carcinoma (superficial carcinoma)
- Invasive carcinoma
- Spread of cervical carcinoma
- Complications
- Staging
• Symptoms and physical signs
• Diagnosis of CIN
- Cytological screening
- Colposcopy
- Biopsy: colposcopically guided
- Auxiliary investigations
• Treatment of CIN
• Treatment of Invasive carcinoma
- Pretreatment evaluation
- Treatment plans
- Surgery
- Main steps
- Radiotherapy
- Brachytherapy: various approaches (Stockholm, Paris, Manchester, afterloading)
- External beam irradiation
- Complications of radiotherapy: immediate and late
- Combined radiotherapy and surgery
- Chemotherapy
• Stump carcinoma
• Carcinoma of the cervix in pregnancy
• Recurrent and advanced cancer

• Rare benign tumors: as hemangioma, cysts

• Adenomyosis
• Endometrial carcinoma
- Epidemiology - and possible etiological factors
- Pathology - spread
- Clinical picture
- Diagnosis
- Staging
- Prognostic factors
- Treatment
Surgery

ix
Radiotherapy
Hormonal therapy
Results
• Sarcoma

[Link] tumors, 455-515

• Introduction
• Classification
• Pathology of ovarian masses
- Functional cysts
- Inflammatory cyst
- Benign ovarian tumors
- Epithelial ovarian carcinoma
- Borderline ovarian neoplasia
- Germ cell tumors
- Tumors derived from specialized gonadal stroma
- Tumors derived from nonspecialized ovarian stroma
- Spread of ovarian cancer
- Metastatic ovarian tumors
• Epidemiology of ovarian tumors: etiological factors
• Clinical picture
- Symptoms
- Signs
- Special investigation
- Differential diagnosis
- Special problems: adnexal mass in postmenopausal women
- Screening for ovarian neoplasia
• Complications
• Ovarian tumors complicating pregnancy
• Staging of ovarian cancer
• Treatment of ovarian tumors
- Treatment of benign ovarian tumors
- Treatment of borderline ovarian carcinoma
- Treatment of invasive ovarian carcinoma
* Surgery
* Chemotherapy: single agents and combined therapy
* Hormone therapy and immunotherapy
* Radiotherapy: external beam and intraperitoneal agents
* Salvage therapy
• Prognostic factors and results
• Treatment of germ cell tumors
• Treatment of sex-chord stromal tumors
• Carcinoma of the Fallopian tube

[Link] epithelial disorders of the vulva and carcinoma of the vulva and
vagina, 516-541
• Nonneoplastic Epithelial Disorders (Dystrophy) of Vulval Skin and Mucous Membranes
- Squamous cell hyperplasia
- Lichen sclerosus
- Other dermatosis
• Vulval Intraepithelial Neoplasia (VIN)
• Clinical Picture - Diagnosing and Treatment
• Pruritus Vulvae

x
• Invasive Cancer of the Vulva
- Epidemiology
- Etiology
- Anatomy
- Pathology
- Clinical picture: symptoms, signs and investigation
- Prognostic factors
- Staging of carcinoma of the vulva
- Treatment
Surgical treatment
Classical radical vulvectomy - technique of radical vulvectomy
Recent modifications: limited skin excision
: Extent of lymphadenectomy
Postoperative radiotherapy
Preoperative radiotherapy
Preoperative chemotherapy
Results
• Uncommon Malignant Tumors of the Vulva
• Carcinoma of the Vagina
- Vaginal intraepithelial neoplasia VAIN
- Invasive carcinoma of the vagina
Incidence
Etiology
Pathology
Clinical picture
Treatment
Surgery
Radiation therapy

Volume II:
[Link], 542-664
• Infertility definition and prevalence
• Causes of infertility
- Female factors
- Male factors
• Investigation of infertility
- Clinical assessment
- Male factor
- Tubal and peritoneal factor
- Ovarian factor
- Cervical factor
- Endometrial uterine factor
- Unexplained infertility
• Treatment modalities in infertility
- Induction of ovulation
Clomiphene
Dopamine agonists
HMG
Pulsatile Gn RH
- Luteal phase deficiency
- Tubal/peritoneal factor
- Cervical factor abnormalities
- Uterine factor related infertility
- Male factor infertility
- Unexplained infertility

xi
- In vitro fertilization and other ARTs

[Link], 697-712
• General pathology
• Pathogenesis and predisposing factors
• Clinical picture
• Treatment
- Of infertility associated with endometriosis
- Of cases presenting for pain and other symptoms
Medical
Surgical

[Link] uterine bleeding (Dysfunctional uterine bleeding) (DUB), 713-739

• Introduction
• Clinical types
• Causes of abnormal uterine bleeding
• Dysfunctional uterine bleeding
- Mechanisms involved in DUB
- The endometrial histopathology in DUB
• Diagnosis of abnormal uterine bleeding
- Measurement of menstrual blood loss
- Abnormal uterine bleeding for Muslim women
- Steps in diagnosis
• Treatment of DUB
- General
- Medical
Hormonal
Other drugs

xii
- Surgical
D&C
Hysterectomy
Endometrial ablation
• Postmenopausal uterine bleeding

[Link] related symptoms, 740-748

• Dysmenorrhea
- Primary
- Secondary
• Premenstrual Tension Syndrome (PTS)
• Premenstrual Mastalgia
• Rare associations

[Link] and molecular genetics, relevance to obstetrics and gynecology,

749-787
• Historical Landmarks
• Cytogenetics
- Mitosis
- Meiosis
- Cytogenetic techniques – karyotype
- Cytogenetic bases of disease
- Indications for karyotyping
• Molecular genetics
- DNA
- Gene structure and functions
- Principal tools in molecular biology
• Clinical applications of molecular genetics
- Molecular biology in prenatal diagnosis
- Molecular biology in endocrinology/reproduction
- Molecular biology of gynecological cancer
• Glossary of common molecular biology terms

[Link], 811-874
• Introduction and evolution of hysterectomy

xiii
• Indications
- Benign disease
of the uterus
of the tubes and ovaries
- Premalignant and malignant diseases
of the uterus
of the ovaries and tubes
of other pelvic structures
- Obstetric problems
- Usual or questionable indications
- Elective hysterectomy
• Types of hysterectomies
• Counseling about hysterectomy
• Total versus subtotal hysterectomy
• Vaginal versus abdominal hysterectomy
• Management of the normal ovaries at hysterectomy
• Preparations of patients
• Technical details of abdominal total hysterectomy
- Possible difficulties
• Technical details of subtotal hysterectomy
• Complications of hysterectomy
• Technical details of vaginal hysterectomy
• Laparoscopically Assisted Vaginal Hysterectomy (LAVH)
- and laparoscopic Hysterectomy
• Changing trends in hysterectomy
- Change in indications
- Elective hysterectomy
- Alternatives to hysterectomy
- Improved morbidity
- Total versus subtotal hysterectomy
- Vaginal versus abdominal hysterectomy
- Removal of the normal ovaries
- Laparoscopic hysterectomies
• Ethical aspects
- The process of informed consent

28. Contraception and family panning, 875-1023

• Combined Oral Contraceptives
- Composition
- Mechanism of action
- Effectiveness
- Advantages and disadvantages
- Complications
- Eligibility criteria
- Procedural guidelines
• Progestogen-only-pill
- Mechanism of action
- Efficacy
- How to use
- Advantages and disadvantages
- Eligibility criteria
- Procedural guidelines
• Progestogen-only injectable contraceptive

xiv
- Evolution
- Effectiveness
- Mechanism of action
- Return of fertility
- Side effects
- Eligibility criteria
- Procedural guidelines
• Combined injectable contraception
- Formulation
- Effectiveness
- Mechanism of action
- Menstrual cycling
- Advantages and disadvantages
- Eligibility criteria
• Intrauterine Contraceptive Device
- Evolution
- Widely used methods and their methods of insertion.
- Mechanism of action
- Continuation of use
- Side effects and complications
- Advantages and disadvantages
- Procedural guidelines
- Eligibility criteria
• Emergency Contraception
- Introduction
- Possible mechanism of action
- Methods
- Side-effects
• Norplant
- Evolution
- Pharmacology
- Effectiveness
- Mechanism of action
- Side effects- metabolic changes
- Advantages and disadvantages
- Eligibility criteria
- Procedural guidelines
- Newer implant systems
• Spermicides and Barrier Methods
- Types and formulations
- Advantages and disadvantages
• Barrier methods
- Male condom
Advantages and disadvantages
- Diaphragm
- Female condom
• Natural Methods of Contraception
- Abstinence
- Coitus interrupts
- Periodic abstinence
- Lactational Amenorrhea method (LAM)
Evolution of the method
Effectiveness
Advantages ad disadvantages
Alternative contraceptive methods suitable for breast feeding mother.

xv
• Sterilization
- Female sterilization
Interval sterilization
Minilaparotomy
Laparoscopic sterilization
Effectiveness
Complications
- Vasectomy
Techniques
Complications
• New Contraceptives being developed
- Contraceptives for men
New techniques for vasocclusion
Hormonal contraceptives for men
- Contraceptives for women
Vaginal pill
Contraceptive vaginal ring (CVR)
Progesteron-only CVR
Combination-CVR
Contraceptive vaccines
Antiprogesterones

• Contraception for Family Planning

- Counseling on contraception
- Family planning for special stages of life, and special conditions
a. Newly married couples
b. premenopausal women
c. Breastfeeding Mothers
d. Postabortive
e. Smokers
f. Certain diseased conditions
g. Interaction with other drugs
• Health Rational for Family Planning
- Reduction of maternal mortality
- Reduction of maternal Morbidity
- Obviate the risks of high-parity
- Obviate the risks of pregnancy in elderly women
- Prevention of the risk of pregnancy in adolescents
- Child spacing
- Small families
- Non-contraceptive benefits of the contraceptive methods
- Avoidance of unsafe abortion
- Social and psychological benefits
• Demographic Aspects of Family Planning

xvi
Family history
• Examination:
- General considerations
- General examination
- Breast examination
- Local examination
Abdominal examination
Examination of external genitalia
Vaginal and bimanual examination
Speculum examination
Office tests
• Common investigations
• Diagnosis

xvii
THE AUTHOR

Mamdouh Mohammed Shaaban graduated from the school of

medicine Cairo University in the year 1959. In 1964, he joined the faculty
of medicine of the then newly initiated, Assiut university in Upper Egypt.
He was appointed professor of Obstetrics and Gynecology in this
university in the year 1973, a position he still keeps till the present time.
Professor Shaaban has been active as a clinician, educator, researcher
and scientific administrator. He traveled to many parts of the world both
for obtaining training and scientific contribution. He served as temporary
consultant to a number of international organizations.

The BOOK
The book covers the needs of Diploma and Master candidates in
Gynecology and Family Planning. It gives basic information required in
Doctorate examination. It can serve as a reference to an active
undergraduate. The book contains many practical points that guide the
gynecology specialists in their clinical work. It puts together a 40-year
experience added to an updated literature.
Anatomy of the female genital system

Chapter 1
ANATOMY OF THE FEMALE
GENITAL SYSTEM
Contents:

1
Anatomy of the female genital system

Vulva (external genital Structures)

The vulva comprises the external genital structures and is the internal entrance to the
female genital tract (Figure1). It consist of:
1. Mons veneris.
2. Labia majora.
3. Labia minora.
4. Clitoris.
5. Vestibule.
6. Hymen.
7. Bartholin gland.

Anatomy: Figure 1: Vulva

1. Mons veneris; 2. Labium majus; 3. Labium minus; 4. Vestibule; 5. Vagina; 6. Fossa navicularis; 7. Fourchette;
8. Gynecological perineum; 9. Anal orfice; [Link]; 11Clitoris; 12. Frenulum; 13 Uretheral meatus; 14.
Hymen (cresenteruc in shape) shaded.

2
Anatomy of the female genital system

Mons veneris :
It is the elevated skin and the underlying condensed vascular fatty tissue, which overly
the pubic bodies, and the lower part of the anterior abdominal wall. The mons is demarcated
above by a suprapubic skin crease (occasionally there are two creases), and merges below
with the labia majora. In a mature woman it is covered by dense hair. The upper limit of this
hair, the escutcheon is usually a transverse line. This is a feminine criterion; since in the male,
the hair tapers upwards towards the umbilicus, the male escutcheon.

Labia Majora :
Are two thick skin folds that extend backwards from the mons in the sides of the
vulva to merge into the perineum. The skin is hairy, mainly on the outer aspect and is sexually
sensitive (contributing to sexual arousal). The labium majus is formed of dense fibro-faty
tissue, which is richly vascular. In young girls, the labia majora stand separate; but after
puberty they enlarge and come in apposition.

Labia minora :
Are two thin fold of the skin that extend backwards from the clitoris on both sides of
the vaginal introitus. Their posterior ends merge to form the fourchette. Their outer surfaces
are sparsely hairy. The labia minora are richly innervated by sexually sensitive endings.
Underneath each labium minus there is a cavernous leach of vessels, the vestibular bulb that
becomes turgid with blood on sexual arousal.

Clitoris:
The clitoris is the miniature counterpart of the penis. It is situated between the
anterior ends of the labia minora. It is about 2 mm in length and has a small head and
a body. The anterior end of each labium minor divides in two folds: the upper one
meets its fellow from the other side to form a hood, the prepuce above the clitoris.
The lower fold fuses with its fellow to form middle line fold, the frenum that is
attached to the clitoris. The clitoris is formed of erectile cavernous tissue; and its skin
is highly rich in sexually sensitive nerve endings.

Female circumcision (occasionally called female sexual mutilation or female

genital cutting). In female circumcision variable parts of the anterior part of the vulva are
removed. The clitoris is usually partially or completely removed during this traditional
practice of female circumcision of girls. The adjoining parts of the labia minora are

3
Anatomy of the female genital system

occasionally removed. Occasionally only the prepuce is removed. Circumcision is a common

practice in Egypt and some other African countries. The Sudanese or Nubian version of
circumcision removes most of the vulva with suturing of edges around a stick. Female
circumcision aims at reducing sexual arousability of girls in an effort to preserve their
chastity. This assault on the sexual organs of the female should be abolished. Besides being
based on no solid religious (Islamic) basis, it is usually performed by barbers, dayans or
traditional healers. It has many immediate and late complications:

[Link]; primary and secondary, this can be severe and life threatening. 2.
Infections that can ascend to cause PID. 3. Ascending urinary tract infection. 4. Psychological
trauma; it is usually done without anesthesia in presence of relatives. This may leave the girl
with long-term fear from the approach to her organs; resulting in dyspareunia, vaginismus or
apareunia. 5. It diminishes sexual arousal, which may lead to marital disharmony. 6. It may
leave behind highly painful scar that leads to dyspareunia. 7. May diminish the stretchability
of the vulval ring during labor resulting in rupture of the circumcision scar and/or in perineal
tears. 8. It can leave the woman with a deep sense of organ missing. However, the great
majority of circumcised female can have normal orgasm.

Vestibule:
Is the oval area between the labia minora in which the urethra and vagina openinig. It
is limited behind by the fourchette, which is usually lacerated during first birth. The part of
the vestibule in front of the fourchette form a boat-like depression, hence the name fossa
navicularis

Hymen:
The hymen is a thin poorly vascular (or avascular) fold guarding around the vaginal
introitus. It is usually an anteriorly open crescent, but it can be annular; and rarely
anteropostenosly septate, cribrifor; and exceptionally imperforate.
The hymen usually (but not invariably) sustains minor one or two postesolateral
lacerations during first intercourse. This usually results in minimal pain and spotting, and the
wound heals over few days; or rarely causes heavy bleeding. Occasionally no bleeding occurs
at first intercourse (the hymen is mostly avascular). Severer bleeding occurs as a result of
more extensive lacerations of the vulva and or the vagina particularly when intercourse is
enforced upon the girl without her cooperation. Severe defloration injuries are rarely seen and
may amount to injuries of the urethra, bladder or rectum; and this result from brute force. In
certain rural areas, hymen deformation is done by the dayan, (TBA). At the first delivery the
remaining parts of the hymen is destroyed and its site is demarcated by thin skin tags.
Occasionally, the hymen is elastic enough to allow intercourse without being lacerated and

4
Anatomy of the female genital system

without being attended with bleeding. This may raise doubts of the bridegroom about
premarital chastity of the bride.
Gynecologists are occasionally asked to judge about the integrity of the hymen. This
question can be a medico-legal one, or can be asked by a bridegroom, whose unlucky bride
did not bleed to his satisfaction at the first intercourse. The doubt results from a belief that the
girl should bleed much at hymenal defloration. This preconceived idea dates back to the time
when defloration was done by ATBs using a sharp object e.g. a key covered by handkerehid.
The experienced TAB makes sure to come out with blood to satisfy all concerned parties ( the
bridegroom and relatives ) about the premarital chastity of the girl.
The question about integrity of the hymen needs a careful and discrete answer, but
before this; needs a careful examination done in good light; the cooperation of the girl is
required. The inner edge of the hymen may be corrugated; and in order to differentiate this
from an old tear, the hymen needs to be put to a stretch. One way to do this is to do a rectal
examination and bend the finger forward to open the introritus, stretching the edge of the
hymen.

Bartholin gland:
Bartholin gland is a racemose multiacinous gland about the size of a bean present
underneath the posterior part of the labium majus. The bartholin gland is partially covered by
the vestibular bulb. Its duct proceeds forward and inward to open in the angle between the
posterior part of the labium minus and the hymen. The gland is not normally palpable, and its
orifice is not seen. It produces lubricating discharge on sexual excitation.
The bartholin gland can be a primary site of gonorrhea when it swells and becomes
painful and tender, and its orifice become a red spot, the macula, one of the pathognonomic
signs of gonorrhea. However, not all cases of bartholinites are due to sexually transmitted
infection. Nonspecific inflection can be a cause of mild bartholinites, when the gland becomes
palpable and tender. The bartholin gland can be the site of an abscess (which is frequently
recurrent), or of a cyst formation.

Blood supply of the vulva:

The vulva is very vascular, and considerable bleeding can be caused by trauma
(including that of childbirth) and during surgical operations. The blood supply is mainly
coming from the internal pudendal vessels, but additional supply is given by external
pudendal, inguinal, and thigh blood vessels.

5
Anatomy of the female genital system

The vulva is rich in lymphatics with ample connections between the two sides. This
explains early spread of carcinoma of the vulva to the epsilateral and contralateral groups of
lymph nodes. These include the following groups of nodes:
1. The superficial inguinal, present along the pupart’s ligament.
2. The superficial femoral, present around the terminal part of the long great
saphenous vein, near the point where the latter vein pierces the cribriform fascia to
join the femoral vein.
3. The deep inguinal lymph nodes in the inguinal canal around the terminal portion of
the round ligament.
4. The deep femoral nodes present in the femoral canal on the medial side of the
femoral vein; usually it is one lymph node, called the node of Cloquet.
5. Thereafter, the spread occurs to the external iliac lymph nodes and the common
iliac nodes.
These groups are classically removed on both sides in the operation of radical
vulvectomy done for carcinoma of the vulva.
Nerve supply:
The vulva rich in nerve supply and mainly comes from the pudendal nerve ( S2 to S4 ),
but additional supply comes from the genital branch of the genito-femoral nerve, and the
posterior coetaneous nerve of the thigh. This explains the need for local infiltration of the
vulva by the anaesthetic besides pubendal nerve block in order to ensure painless producer,
e.g., repair of episiotomy.

Vagina
The vagina is a tubular muscular (smooth muscle) structure reaching from the vulva to
the cervix uteri. Its anterior wall is 8 cm long, and its posterior wall is 10 cm long. It is
directed upwards and backwards with accentuation of the backward curve above the perineal
body. The vagina is anteroposteriorly flattened with the anterior wall resting upon the
posterior wall and indirectly on the perineal structures. The cervix uteri projects in the upper
anterior wall creating anterior, posterior and lateral fornices. The posterior fornix is deeper
than the anterior one.

Relations (Figure 2):

Anteriorly, the vagina is related in its lower half to the urethra, which is actually
embedded in the fascial wall of the vagina. The base of the urinary bladder rests on the upper
half of the vagina, the two organs are separated by a condensation of pelvic connective tissue

6
Anatomy of the female genital system

called the pubocervical ligament or fascia. The latter stretches between the pubes and the
supravaginal cervix, and is the main support for the bladder base. When pubocervical
ligaments are weak or receding laterally, the bladder base herniates down, resulting in a
cystocele.
Posteriorly, the vagina is related, from below upwards to the perineal body, the
ampulla of the rectum, and then to the pouch of peritoneum called the pouch of Douglas (the
cul-de-sac). In the latter position, the posterior fornix has nothing intervening between it and
the peritoneal cavity. This is made use of to take samples from, or drain any peritoneal
collection (e.g., blood or pus); and to enter the peritoneal cavity in culdotomy and culdoscopy
procedures.
Laterally (Figure 3): the vagina is related from below upwards to two leashes of blood
vessels around the vaginal introitus called the vestibular bulbs, then to the triangular
ligament( urogenital diaphragm) which is inserted in the lateral vaginal wall shortly above the
introitus. The triangular ligament is a two-layered fascial sheet that obliterates the anterior
part of the pubic arch. Between the two layers are the muscle fibers of the constrictor urethra
muscle and the deep transversus perineii. The levator ani is inserted in the lateral vaginal wall
about 3 cm above the introitus. Outside the muscle there is the fat in the ischiorectal fassa.
Above this muscle, there is the pelvic cellular tissue, the paracolpos. The lateral fornix is a
site of insertion of the lower part of the Macendrodt’s ligament. This contains the uterine
vessels; and is posteroanteriorly pierced by the ureter. The latter lies 1.5 cm above and lateral
to the lateral fornix of the vagina. After piercing the ligament the ureter proceeds downward
and inward between the bladder and the anterior vaginal wall to reach the lateral angles of the
trigone of the bladder. The proximity of the ureter should be noted during vaginal and
abdominal surgery.

Anatomy: Figure 2 Sagittal section in the pelvis

1. Urethra; 2. Vagina; 3. Distended urinary bladder; 4. Uterus; 5. Rectum; 6. Ureter; CI: Common
Iliac Artery; II: Internal Iliac Artery; EI: External Iliac Artery; UA: Uterine Artery.

7
Anatomy of the female genital system

Anatomy: Figure 3. Coronal section in the pelvis.

1. Vagina; 2. Cervix Uteri; 3. Levator Anu; 4. Obturator Internus; 5. Parametrium and
Paracolpos; 6. Ischiorectal fossa; 7. Crus of Clitoris; 8. Vestibular bulb; 9. Urogenital
diaphragm; 10. Superficial transversus perenii; 11. Ischiocavernosus muscle; 12.
Bulbocavernosus muscle: IPR : Ischiopubic ramus.

Structures:
The vagina is a muscular tube formed mainly of smooth muscles roughly arranged in
outer longitudinal and inner circular fibers, covered by fibrous layer, and lined by the vaginal
skin. The latter is having a highly vascular subcutaneous layer. The vaginal lining has no
glands; its lubrication depends upon transudation from blood vessels and the cervical
secretion. The vaginal skin has transverse rugae and the rugosities are particularly dense in
the lower anterior wall. This latter part is richly supplied by sexually sensitive nerve endings,
and is important in sexual arousal; its rich subcutaneous blood vessels become turgid as a
result.

The vaginal skin (mucosa) is formed of stratified squamous non-keratinized

epithelium. Its thickness is enhanced by estrogens. This epithelium exfoliates the cells on its
surface in the vaginal transudate. This collects in a pool in the posterior fornix. The types of
cells in this vaginal fluid depend upon the extent of maturation of the surface cells attained
before exfoliation. This depends upon the level of estrogens reaching the epithelium. Under
estrogen stimulation the stratified epithelium attains its maximal maturation, and

8
Anatomy of the female genital system

consequently the cells in the vaginal fluid are all of the superficial type. These are large cells
with wafer thin esonophilic cytoplasm, and pyknottic structureless nucleus. When the effect
of progesterone is superadded after ovulation the maturation of the epithelium is less
complete, and some intermediate cells appear in the vaginal transudate. These have wafer thin
esonophylic cytoplasm but vesicular nuclei i.e. showing nuclear stipulation. Under conditions
of estrogen deprivation (as before puberty and after menopause), some of the parabasal cells
appear in the transudate. These are smaller rounded cells with thick cytoplasm that takes the
hematoxline blue stain and have vesicular nuclei.

Exopholiative vaginal cytology depends upon examination of smears of the cells in

the vaginal fluid that contains the cells on the surface of the vagina (obtained by light
scrapping). The cells need to be stained by a special procedure ( Papanikolao’s or Shor’s
methods ). The cytology specimen needs to be spread thinly on a slide and immediately fixed
by impressing in absolute alcohol ( or with a special spray ), since drying results in loss of
their staining properties.
Vaginal cytology can be used to assess the hormonal mileau in the body. During the
menstrual cycle, the ratio of superficial to intermediate and basal cells in the smear varies.
This ratio is called the maturation index: During the proleferative phase of the cycle this
index is 100: 0: 0 meaning no intermediate cells i.e. all the exopholiated cells are superficial.
During the bloom of the progestational phase, the index can reach 70: 30: 0 meaning that 30
% of the cells are of the intermediate type, and none of the parabasal cells. The parabasal cells
only appear in atrophic states. An alternative index is the pyknottic index. i.e. the percentage
of the cells having pyknottic nuclei, i.e., 100 % during good estrogen stimulation, and 70 %
during good progesterone effect.
Vaginal and cervical smears are mainly used, however to detect suspicious or
malignant cells in the smears i.e. on the surface of the epithelium; and these are used for
screening for early diagnosis of carcinoma of the cervix (and endometrium).

Blood supply:
The lower part of the vagina has the same supply as the vulva and the upper part is
mainly supplied by the vaginal artery, which can be either off the uterine artery or the internal
iliac artery itself.

Similarly the lymphatic drainage of the lower vagina is similar to that of the vulva,
while that of the upper vagina goes to the same draining glands like the cervix uteri.

9
Anatomy of the female genital system

Uterus
The uterus (the womb) is a pear-shaped muscular organ; about 7.5 cm in length. It has
a cervix and a body (corpus). The dome shaped fundus of the uterus rises above the sites of
continuity with the tubes; the cornue. The length of the uterine cavity is 6.5 cm, the cervix
forms one third of this length. The body is usually anteriorly flexed on the cervix;antiflexion.
The cervix project in the upper anterior vagina usually at an angle of ante-version. The
summation of anteversion and anteflexion results in an almost horizontal position of the body,
overlying the urinary bladder. In about 20% of the population these angles are posteriorly
directed resulting in retroversion-flexion. The peritoneum covering the uterus and the tubes
stretches to the lateral pelvic wall forming the broad ligament.

The cervix uteri

The cervix is barrel-shaped and projects by half of its length in the vagina; the portio
vaginalis. Above the vaginal attachment there is the supravaginal cervix. This latter part is
covered anteriorly by the urinary bladder and posteriorly by inseparably attached peritoneum.
The urinary bladder lies in front of the cervix and the Douglas pouch behind it. The
connective tissue in the base of the broad ligament on the sides of the supravaginal cervix is
condensed to form the cardinal or Macenrodt’s ligament, which contains the uterine vessels,
and stretches to the lateral pelvic wall. The ureter pierces this ligament postero-anteriorly
below the uterine vessels, and at this point the ureter is at a distance of 1.5 cm from the
cervix. This needs to consider during ligation of the uterine vessels. The posterior aspect of
the supravaginal cervix is attached by two fibrous ligaments to the sacrum, the uterosacral
ligaments that raises two peritoneal folds, which form the mouth of the Douglas pouch.
The cervical orifice, the external os feels as a rounded dimple in the nulliparous state.
During the first delivery the external os sustains a physiological laceration that makes it feels
and looks as a transverse slit, with anterior and posterior lips. The constriction at the upper
end of the cervical canal is the anatomical internal os.

The cervix is formed of fibromuscular tissue; the percentage of fibrous tissue

progressively increases as we approach the external os. This difference is explaining the
yielding of the upper cervix before the lower cervix during the first delivery; a process called
effacement. In a women with a previous delivery the effacement is accompanying the
dilatation of the external os, whose resistance have been already overcome by the laceration
sustained during the first labor. The structure of the collagen in the fibrous tissue of the cervix

10
Anatomy of the female genital system

is sensitive to hormonal changes (estrogens and progestogen) which align and loosen its
constituents to facilitate its dilatation.
The cervical mucous membrane lining the cervical canal has anterior and posterior
transverse fine rugosities the arbor vitae, which radiate from midline of the anterior and
posterior wall. One of these rugosities may entrap the tip of the uterine sound during the
operation of dilatation of the cervix, and this can be the starting point in perforating the
cervix. The same might happen during IUD insertion.

The vaginal portion of the cervix is covered by firmly attached stratified squamous
epithelium, while the cervical canal is lined by tall columnar epithelium. These latter
epithelial cells have basal nuclei, and secrete the cervical mucus. The mucous membranes is
thrown into a rich network of crypts, which in a cut section may look like glands; but they are
not true glands. The junction between these two types of epithelium is usually located at the
external os. However, this junction is not stationary, but is dynamic. The columnar epithelium
may creep out replacing the stratified epithelium. The former type being thinner will more
readily show the color of the blood in the vessels underneath, and therefore appearing red;
and this results in what is known as cervical erosion (which is not really a brake in the
continuity of the covering, hence the name is misnomer in fact). On the other hand the
stratified squamous epithelium may creep up in the cervical canal. This dynamic process
results in making this area of few square millimeters called the “ transitional zone”. This very
limited area of epithelium is the site of the beginning of a common cancer in the female,
carcinoma of the cervix.

The isthmus uteri is the upper few millimeters (2 – 3 mm) in vertical depth of the
cervical canal just below the internal os. This segment of the cervical canal is lined by an
epithelium more similar to endometrium, albeit with sparse short glands. The junction of this
type of endometrium-like epithelium with the tall columnar epithelium of the endocervix is
microscopically identifiable, and is called the histological internal os. The length of the
cervical canal between this latter level and the anatomical internal os above is called the
isthmus (waist) uteri; through it lacks any constriction in its outward look (Figure 4). It is
believed that this short segment of the upper cervix, the isthmus uteri tremendously unfolds
during pregnancy and labour to give rise to the lower uterine segment.

11
Anatomy of the female genital system

Anatomy; Figure 4: Coronal section in the uterus

Anatomical internal os; 2. Histological internal os; Isthmus; 4. Corpus uteri; [Link] ; 6. Cervix.

Corpus uteri (uterine body):

The uterine body is pear-shaped. The anterior wall of the uterine body is usually
related to the roof of urinary bladder; the uterovesical peritoneal pouch is intervening. The
posterior wall is related to the intestines and omentum.
The thickness of the uterine wall is about 0.5 cm, and is mainly formed of specialized
smooth muscles the myometrium, which is arranged in an outer longitudinal layer, middle
criss-cross layer and inner circular one. The peritoneum is inseparably attached to the
myometrium of the body of the uterus except for few millimeters on the lower part of the
anterior aspect. The lining, the endometrium, rests directly on the muscle wall without any
submucosa. In the unstimulated phase, the endometrium has low columnar epithelium and
contains tubular glands. The epithelium, glands, stroma and vasculature of the endometrium
undergo cyclic changes that end in menstruation (the menstrual cycle). In general the
endometrium is prolifirative during the first half of the cycle, and secretory during the second
half. These changes occur in response to the cyclic hormonal production of the ovaries
(ovarian cycle). During the cycle the thickness of the endometrium increases from 0.5 to 3
mm.
The endometrial cavity is a potential one, with the anterior lining in contact with the
posterior one. It is triangular in shape in the transverse plane, with the upper lateral angles
continuous with the lining of the interstitial part of the fallopian tubes. The latter traverses the
uterine wall at the cornu. To the outer surface of each cornu is attached the round ligament
anteriorly, and the ovarian ligament posteriorly.

12
Anatomy of the female genital system

Blood supply uterus

The vasculature of uterus is rich. It is of dual origin: the uterine vessels and the
terminal part of the ovarian vessels. The uterine vessels are branches of the anterior division
of the internal iliac vessels. The uterine artery courses from the lateral pelvic wall towards the
uterus in the base of the broad ligament surrounded by the upper part of the Macenrodet
ligament. One and half centimeter lateral to the supravaginal cervix it crosses at a right angle
over the ureter. After reaching the uterus it ascends on its side in a tortuous course to
anastmose with the termination of the ovarian vessels. The two uterine arteries send
transverse branches in the anterior and posterior walls of the myometrium. Consequently the
least vascular sites in the uterus are the middle-line of the anterior and posterior walls (
chosen site of incision in the uterine wall ). Radial arterioles arise from the latter arteries and
pierce the myometrium to reach the endometrium. These vessels are sensitive to ovarian
hormones and to the prostaglandins locally produced. The combined effects of these two
stimulation are important for menstruation. The cervix uteri is supplied mainly from the
vaginal branches of the uterine, together with branches from the superior vesical vessels.

Lymphatic drainage:
The uterus is rich in lymphatics. The cervix: drains to small inconsistent nodes in the
parametrium and then to the following groups of lymph nodes: 1) the external iliac group
around (upon, underneath and on both sides) the external iliac vessels, 2) the internal iliac
nodes around the vessels with this name, (sometimes called hypogastric ) 3) the obturator
group on the inside of the obtarator membrane ; and also spread to 4) the lateral sacral nodes
present behind the rectum on the anterior sacral foramina, and thereafter to 5) the common
iliac and para-aortic nodes.

The lymphatic drainage of the lower part of the uterine body is similar to that of the
cervix. The upper part of the body drains upwards to the upper paraostic group of lymph
nodes (similar to the drainage of the tubes and ovaries, the lymphatics course along with the
ovarian vessels).

Nerve supply of the uterus (see latter):

The cervix uteri is devoid of pain sensitive endings. However the area of the internal
os is sensitive to dilating force during uterine sounding and this results in sickening pain
(which may rarely result in syncope) if done without anesthesia. The myomertium is richly
supplied by both sympathatic and parasympathetic nerves.

13
Anatomy of the female genital system

Fallopian Tubes
The fallopian tube is 10 cm long. It is enclosed in the upper edge of the broad
ligament stretching between the ovary and the uterus. It is formed of four parts: the
interstitial, isthmic and ampullary portions and the infundibulum. The interstitial part is 1 cm
long and traverses the thickness of the myometrium opening in the upper lateral angle of the
uterine cavity by the uterine orifice. It is narrowest segment having a diameter of 1 to 2 mm.
Its cavity is encroached upon by closely opposed folds; the plicae. The isthmus is 2 cm long
forms the medial one third of the tube. It has a thicker wall and a narrow cavity of 2-3 mm,
which is encroached upon by close plicae. The ampullary portion is the wider lateral 2/3 rds
of the tube 3 to 5 mm in diameter. Its muscle wall is thinner; the mucosal plicae are widely set
and arranged longitudinally. The infundibulum is the trumpet-shaped lateral end which opens
backwards in the posterior aspect of the broad ligament. The part of the upper edge of the
broad ligament stretching between the infundibulum and the lateral pelvic wall is called the
infundibulo-pelvic ligament. The tubal opening is guarded by a number of finger-like
fimbriae. These fimbriae are in a very near proximity to, and one of them reaches the ovary,
the ovarian fibmbria. The integrity and freedom of the movement of the fimbriae are essential
for the ovum pick-up; and actually there is a sucking effect resulting from the inward
movement of tubal fluid, which creates a sucking-in effect ensuring that the ovum is not lost
in the peritoneal cavity. The process is also enhanced by peristaltic waves of contractions of
the muscle wall of the tube, which are most active at the time of ovulation. Any kincking or
destruction of the muscle wall or the endosalpinx will interfere with the ovum pick up, and
with the fertilization (which takes place in the ampulla ) resulting in infertility. These
abnormalities can also impede the movement of the fertilized ovum until a time when it has
acquired the invading trophoblast; increasing the chance of tubal pregnancy.

Structure:
The tube is covered by the inseparably fixed peritoneum, the perisalpinx, in the
uppear edge of the broad ligament. The lower edge has the ovarian vessels coursing to and
from the uterus between the leaves of this ligament. The smooth muscle wall is formed of
outer longitudinal and inner circular fibers. The endosalpinx has a scarse or no submucosa,
and is thrown into longitudinal folds, the plicae. These are few in the isthmus but branch in
the infundibulum. There are three types of tubal epithelial cells: 1) the wide-top ciliated cells,
2) the granular secretory cells, and 3) peg cells at the basement membrane not reaching to
inner surface. The first type ensures a ciliary movement, mostly in the direction of uterus of

14
Anatomy of the female genital system

the tubal fluid, which is produced by the secretory cells. The peg cells are reserve cells that
can form either of the other two types. The tubal fluid or milk nourishes the fertilized ovum.
From the above description it is apparent that the tube is not a simple pipe but it plays
essential and sensitive biological roles in human reproduction.

Vascular connections of the tubes are similar to those of the ovaries.

Ovaries
The female gonad is situated in the peritoneal cavity hanging from the lateral part of
the posterior leaf of the broad ligament by a peritoneal fold called the mesovarium. It is
almond-shaped 3.5 x 2.5 x 1.5 in length, breadth and thickness respectively. It has a glistening
white surface, which is usually wavy or corrugated. At a number of points there is bluish
bulging caused by the superficially located growing follicular structures. The medial pole of
the ovary is connected to the cornu by a fibrous band, the ovarian ligament that may raise the
peritoneum of the posterior leaf of the broad ligament.

Structure:
The ovary has a cortex and medulla, which are not visually demarcated, and is
covered by thin serous flattened surface germinal epithelium which is frequently incomplete.
The cortex is composed of ovarian follicles in various phases of development and atresia, and
stroma. Each ovarian follicle is having an ovum which is surrounded by granulosa cell and
theca cells merging into the stroma. The primitive or primordial follicles have a single layer
of flattened granulose cells. The embryonic fetal ovary is having few millions of ova. Most of
these are lost by a process of follicular atresia. At the time of birth, both ovaries contain
between them about one million ova. Theses are the maximal number of ova the woman
possesses. There is no new formation of ova by postnatal division. On the contrary, the
majority of the ova will be lost through a continuous process of atresia. Only about 500 ova
are destined to reach ovulation during the reproductive career of the woman, usually one in
each month.
Each month a crop of primordial follicles is recruited into a process of maturation.
This consists of enlargement of and multiplication of the granulosa cells. Some of the follicles
reach the antral phase by acquiring a cavity, the antrum. The growing follicles attain varying
stages of maturation before becoming atretic. The process of atresia is continuous up to
menopouse, consuming most of the ovarian follicles. The granulosa cells will become

15
Anatomy of the female genital system

hyalinized, and the ovum disappears. Menopause supervenes when all (or most) of the ova are
expired.
Each month, one (or two) of the growing follicles will reach the stage of a mature
Graafian follicle (Figure 5) and sheds the contained ovum. The growing follicles have a
cavity the follicular cavity, filled with the follicular fluid rich in compounds with endocrine;
paracrine, or apocrine effects. The endocrine effects are produced mainly by estradiol,
progesterone, and inhibins. Paracrine functions (producing local action on neighboring cells)
are produced by inhibins, activines and certain growth factors. The granulosa cells forming
the wall of the maturing follicles together with surrounding theca cells are active in hormonal
production. The ovum of the mature follicle is situated on one side of the follicular wall
surrounded by a clump of granulosa cells called the cumulus oopharicus. The innermost
granulosa cells of the latter are arranged around the ovum in a radiate fashion, hence called
the corona radiata. In the middle of the cumulus is the ovum, a large cell (120 microns) with
an eccentric nucleus and finely granular cytoplasm. The ova have begun the first meiotic
division and are arrested during prophase of this division. Covering of the ovum is a thick
structureless paler cell membrane called zona pellucida. The latter is not directly applied to
the cytoplasm but is separated from the ovum by a very thin subzonal space called the private
line space.
The maturing follicles are surrounded by specialized layers of specialized theca cells.
Its cells are spindle shaped and allingned circumfrentially. This is called theca interna while
the rest of ovarian stroma is called theca externa. The theca interna cells contribute to
hormonal production in collaboration with the granulosa cells.

The mature graafian follicle ruptures around the middle of the ovarian cycle releasing
the ovum carrying with it part of the cumulus. In its place, the corpus luteum forms. The wall
of the follicle collapses and its lining granulosa layer will become corrugated by infolding.
The theca interna cells invade into these folds and become vascularized (acquire fine blood
vessels). The two types of cells enlarge by accumulating cytoplasm becoming cuboidal in
shape. They are then respectively called the granulosa-lutein and theca-luteun cells. Again,
the two types of cells collaborate in producing estrogens and progesterone, the two hormones
produced by the corpus luteum during the second half of the ovarian (menstrual) cycle.
During this stage, days 4 to 10 after ovulation, the corpus luteum is about 1-2 cm in
diameter, may bulge above the general surface of the ovary, may have a cavity, and usually
have a grayish corrugated appearance on cross section. If there is no pregnancy in this cycle,
the corpus luteum will start to regress. Lipoid yellowish droplets start to accumulate in the
cytoplasm, hence the name corpus luteum (yellow body). However, if a pregnancy has been
initiated in this cycle and the fertilized ovum has been implanted, a hormonal message, the

16
Anatomy of the female genital system

chorionic gonadotrophin, which has an LH effect, reaches the corpus luteum preventing it
form regression and causing its further growth into the corpus luteum of pregnancy.

The ovarian medulla is mostly formed of fibrous tissue with blood vessels.
Occasionally, it contains microscopic tubular structures, which are vestigial rests, mainly of
wolffian origin. These vestigeal remnants which are called the rete overii, can be the origin of
very rare musculinizing ovarian tumors.

Anatomy; Figure 5: Matuer Grafian Follicle

1. Ovum; 2 Zona pellucida; 3. Corona radiata; 4. Antrum; 5. Granulosa layer; 6. Theca
interna; 7. Germinal layer; 8; Cumulus oophoricus; 9. Stroma.

Relation of the ovaries

The ovary hangs from the lateral part of the posterior leaf of the broad ligament. It is
in contact with the intestine and omentum. Directly lateral to it, but separated by peritoneum
is the ureter and the internal iliac blood vessels.

Vascular supply
The ovarian artery originates from the upper part of the abdominal aorta just below
the diaphragm and proceeds downwards on the posterior abdominal wall to reach the
infundibulopelvic ligament, and then proceeds underneath the tube to reach the cornu of the

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Anatomy of the female genital system

uterus to anastome with the uterine artery. The right ovarian vein ends in the inferior vena
cava while the left ends in the left renal vein. The lymphatic drainage goes to the nodes
around the upper part of the abdominal aorta. Drainage to pelvic lymph nodes can also occur.

Pelvic Peritoneum
The peritoneum leaves the anterior abdominal wall to cover the dome of the urinary
bladder from which it is dissectable. The uterovesical pouch intervenes between the front of
the uterine body and the dome of the bladder. The uterus is covered by inseparably attached
peritoneum. The uterorectal pouch referees to the wide pouch separating the rectum from the
back of the uterus. The Douglas pouch or the cul-de-sac specifically refers to the dimple of
peritoneum that separates the upper third of the posterior vaginal wall and the supravaginal
cervix from the rectum. The upper mouth of this pouch is formed by the two uterosacral
ligaments. The peritoneum leaves the front and the back of the uterus to extend laterally as the
double layered broad ligaments, which reach to the lateral pelvic wall. The lateral part of the
upper edge of the broad ligament, beyond the infundibulum, forms the infundibulopelvic
ligament.
The broad ligament contains 1) in its upper end, the tube with 2) the ovarian vessels
underneath, the base of the broad ligament contains the 3) uterine vessels and 4) the upper
part of the Macenrodet’s ligaments. 5) The ureter is present underneath the posterior leaf of
the infudibulopelvic ligament at the point of its reflection to the lateral pelvic. At this point
the ureter is vulnerable to injury during cutting and ligation of the infundibulopelvic ligament.
The broad ligament also contains 6) the round ligament. This stretches downwards and
laterally from the front of the cornu of the uterus to the internal inguinal ligament. Thereafter,
the round ligament traverses the inguinal canal emerging at the external inguinal ring where it
merges with the fibrous tissue in the mons. 7) The ovarian ligament raises a ridge in the
posterior aspect of the broad ligament reaching between the ovary and the posterior aspect of
the cornu. The broad ligament has 8) loose areolar tissue that contain occasional aberrant
vessels and 9) certain microscopical vestiges of the wolffian systems. These can underage
cyst formation.

Vestigial Structures
The epoophoron and paroophoron are present between the leaves of the brood ligment
and represent the remnants of the mesonephros and wolffian (Gartner) duct, whose vestige

18
Anatomy of the female genital system

passes into the uterine muscle about the level of internal os and continues downwards in the
anterolatral vaginal wall. These can result in cyst formation or rarely a special type of cancer.
The remnant of pronephros can result in formation of small, thin walled cyst hanging from the
fimbria (Hydatid cysts of Morgagni)

Pelvic cellular (Connective) tissue and

ligaments
The spaces between the pelvic organs and underneath the pelvic peritoneum are filled
by connective tissue. Theses are called the parametrium and paracolpos. This cellular tissue is
condensed around the organs to give them fascial coverings, e.g. vaginal, vesical and rectal
fascial layers. In certain plains this cellular tissue forms ill-defined ligaments that give
support to pelvic structures: There are three pairs of such ligaments that spread from the
supravaginal cervix and upper vagina like the spokes of the wheel towards the pelvic wall
(Figure 6).
1. The Macenrodet’s or cardinal ligament is the main support the uterus. It is attached to
the supravaginal cervix and lateral vaginal fornix then fans out from the middle line
laterally both in the vertical and anteroposterior planes to get attached to the fascia on the
muscles on the lateral pelvic wall. The looser connective in front and behind the cardinal
ligament is respectively called the paravesical and pararectal fossae. The cardinal
ligament is postero-anteriorly pierced by the ureter, which lies in what is known as a
ureteric canal, which has the uterine vessels at its roof.
2. Uterosacral ligaments stretch from the back of the supravaginal cervix at the mouth of
the Douglas pouch to the sides of the rectum to get attached to the second and third sacral
pieces. When the uterosacral ligaments are slackened and widely separated the Douglas
pouche yields underneath the weight of the pelvic viscera to from a hernia of the pouch of
Douglas.
3. Pubocervial ligaments (sometimes called fascia) spreads from the supravaginal cervix to
the pubis like two shelves that carry above them the base of the urinary bladder. When
these ligaments are slackened, rarified or widely separated the bladder base descends
causing a cytocele.
Besides these supportive ligaments there are number of ligaments and fascial
membranes in the pelvic cellular tissue which render no supportive functions. These
include the round and ovarian ligaments. The latter two ligaments are vestigial remnants
of the embryological structure called the gubernaculum. They stretch from the ovary to

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Anatomy of the female genital system

the cornu of the uterus ( the ovarian ligament ) and from the latter to the skin of the front
of the vulva after traversing the inguinal canal (the round ligament). Other fascial
formations that are met with during pelvic surgery include:
- The cervico-vesical fascia that needs to be incised to free the bladder from the
cervix. It is encountered and incised during total hystereclory and during anterior
colporrhaphy. The lateral parts of this fascia is sometimes called the bladder
pillars, which need to be incised during both operations; and usually contain
small blood vessels, which need to be secured by ligatures, or diathermized.
- The mesentery of the round ligament is a fascial sheet that stands up if one pulls
on the clamped round ligament during hysterectomy. When they are cut they lead
down to the uterine vessels.

The pelvic connective tissue is generally loose and offers relatively little
resistance to collections of inflammatory exudates; blood and pus. These can produce
dissecting infections and collections like spreading parametritis, and hematomata. The
collections can spread up the retroperitoneal tissue to reach up to the diaphragm.
Abscesses formed in this site can point to a number of outlets including the gluteal
region (through sciatic formation), to the inguinal region along the round ligament, but
can point also into rectum or the vagina.

Anatomy: Fig: 6: The main supporting ligaments of the uterus viewed from above.
1. The pubocervical ligment; [Link] Macenrodet’s ligment; 3. The Utero sacral ligment; 4; Paravesical
fossa; 5. Pararectal fossa.

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Anatomy of the female genital system

Pelvic muscles
The two levator ani
These are the main muscles of the pelvic floor which close the pelvis from below,
carry the weight of the viscera, and support and control the function of the organs which
traverse the pelvic outlet; namely the bladder (and the urethra), the vagina and rectum. They
are paired sheet-like voluntary muscles, which stretch from lateral pelvic wall to meet in the
middle line. Each levator ani has a broad origin from the back of the body of the pubis, from
the “white line” on the inner fascia of the obturator internus muscle and the ischial spine.
According to the site of origin the levator ani is subdivided into the pubococcygeus, the
iliococcygeus and ischiococcygeus. Its fibers proceed backward, downward and inward. It is
inserted, from before backwards, in the vaginal wall, decussates with its fellow of the other
side in the apex of the perineal body, in the rectal wall, in the anococcygeal raphae (a fibrous
middle line band stretching from the anal canal to the coccyx, and in the coccyx itself, (Figure
7).
Action
1. Supporting all pelvic structure including the rectum and vagina. It gives an indirect
support to the urinary bladder by supporting the vaginal walls on which the bladder
rests; few muscle fibers reach the bladder itself.
2. Controlling the function of the above organ, by constricting and kinking them.
3. Deciding the function width of the vagina and rectum.
4. Carrying the weight of pelvic and abdominal viscera.
5. It has an important role in deciding the mechanism of labor.

Nerve supply
(1) Directly from the sacral roots number 2, 3, 4 of the sacral plexus reaching
the muscle from above and (2) form the branches of the pudendal nerve reaching the
muscle from below. The complete relaxation of the muscle during operative vaginal
delivery can not be secured by pudendal serve block alone but can be achieved by
epidural conduction anesthesia. The latter increases the need to assist delivery of the
head by the ventouse or forceps because of loss of the strong bearing down reflex.

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Anatomy of the female genital system

Anatomy; Figure 7: Levator Ani

1. Symphysis pubis; 2. Obturator Internus; 3. The white line; 4. Ischial spine; 5. Piriformis ; 6.
Promontery of the sacrum; 7. Anterior sacrococcygeal ligment; 8. Dorsal vein of the clitoris; 9.
Urethra; 10. Vagina; 11. Rectum; 12; Anococcygeal ligament; 13 Pubpcoccygeus muscle; 14.
Iliococcygeus muscle; 15. Ischio coccygeus muscle.

Urogenital diaphragm
At a lower level, in the front of the pelvis is the urogenital diaphragm (also called the
triangular ligament). It is formed of two layers of fascia stretching between and attached to
the inferior pubic rami. It is pierced by the dorsal vein of the clitoris, the urethra and vagina.
Between the two layers lie the voluntary muscles, the compressor urethra and deep
transversus perinei muscles, the pundendal nerve and internal pundendal vessels.
Anatomically, the triangular ligament is the deep perineal pouch.
The superficial perineal muscles include muscles below the triangular ligament and
levator ani. These include bulbospongiosus muscle, which covers the vascular, leaches on the
undersurface of the urogenital diaphragm the vestibular bulb. They also comprise the
superficial transverses perinei, and the superficial external anal sphincter. Anatomically, the
structures below the triangular ligament are described to be in the superficial pouch.

22
Anatomy of the female genital system

Perineum
Gynecologicaly, the perineum refers to the skin and subcutaneous tissue intervening
between the vagina and rectum. The perineal body is a pyramidal mass of muscles above this
skin comprising superficial muscles like the superficial transverses perinei, and the constrictor
vaginae muscles (ill-defined muscle sheet); and has at its apex the decussating fibers of the
two-levator ani. The superficial external sphincter of the anus is a directly subcutaneous
muscle whose fibers surround the anal sphincter and causes the skin creases radiating from
the anus. It is usually having a high tone and maintains anal continence to flatus and fluid
stools. The perineum is vulnerable to laceration during childbirth.

Nerve supply:
1) Branches of pudendal nerves, 2) The genital branch of the genitofemoral nerve, and
3) the posterior cutaneous nerve of the thigh. Pudendal nerve block will not, therefore
guarantee a pain-free repair of an episiotomy; it needs in addition, local infiltration of
perineum to block the effect of the other nerve supply.

Urinary bladder
The urinary bladder is pyramidal in shape with the apex anterior. The dome is covered
by loosely attached peritoneum that allows elevation when the bladder distends. The two-
antrolateral walls are related to the pubic bone, the obturator interns and the levator ani. The
base is resting on the vagina and supravaginal cervix. The trigone is the lowermost part of the
base adjoining the internal urethral meatus. It is a right triangle having 3 cm length of each of
its bounders. The slit-shaped ureteric orifices open at its upper lateral angles. The mucosa of
the trigone is smooth and fixed to the underlying muscle.
The mucosa of the bladder is formed of transitional epithelium with columnar cells on
the surface. There is a rich submucosa that causes corrugations of the mucosa and allow for
distension. The muscle wall, the detrusor is formed of smooth muscle fibers arranged in outer
longitudinal and inner circular fibers.
The bladder is highly vascular and is supplied from the superior and inferior vesical
vessels, which are branches of the internal iliac vessels.

23
Anatomy of the female genital system

Nerve supply: (see below)

The female urethra
The female urethra is about 4 cm long, much shorter than the male urethra. It is
buried in the fascia of the vagina. Its mucosa is thrown into longitudinal folds that help to
keep the urethra closed. The muscle wall is formed of inner circular and outer longitudinal
fibers mixed with elastic and collagenous fibers. The tone of this layer is important in
maintaining continence. The external uretheral meatus is in the healthy state a small
protuberance with anteroposterior cleft. The tiny orifice s of the sken’s (paraurethral) ducts lie
just outside or inside the meatus.
Urinary continence is maintained by special sympathtic innervation of the urethra that
keeps the tone of the muscle wall. There is no anatomical sphincter at the uretherovesical
junction but a sort of functional sphincter furnished by innervation and arrangement of muscle
fibers around this point. These keeps the urethra closed until it is willfully allowed to relax. In
resting condition i.e. apart from the time of urination, there is an angle of about 90° between
the posterior aspect of the urethra and the bladder. It has been repeatedly shown by
cinematographic studies that maintenance of this angle under resting condition is important
for maintenance of continence. During urination the angle is lost. Women with stress
incontinence are not showing this angle at rest.

Pelvic ureter
The ureter enters the pelvis by crossing over the bifurcation of the common iliac
artery; a landmark for finding the ureter during surgery. At this point the ureter is
immediately behind the infundibulopelvic ligament (a risk site). The ureter dips in the pelvis
in front of the internal iliac artery coursing forward and downward; and here it frequently
found underneath the posterior leaf of the most lateral part of the broad ligament. It is directly
lateral to the uterosacral ligament (a second point of risk). After reaching to the level of the
ischial spine it courses forward piercing the Mackenradet’s ligament, passing in the ureteric
canal. The uterine artery crosses above the ureter at a right angle. At this point, the ureter is
1.5 cm above the lateral fornix and 1.5 cm lateral to the supravaginal cervix. (a third risk site
during ligation of the uterine artery in abdominal or vaginal surgery ). Beyond this point the
ureter passes downward and inward between the bladder base and the anterior vaginal wall,
then it tangentially pierces the bladder wall to reach the upper lateral angle of the trigone, (a
fourth risk site during dissection of the bladder from the vagina). The ureter is also vulnerable
for injury during to pelvic surgery if displaced from this course by a broad ligamentary

24
Anatomy of the female genital system

swelling, or by malignant infiltration in the parametrium. In such cases, the course of the
ureter needs to be followed down starting from the pelvic brim.
The pelvic ureter receives blood supply from small branches from the uterine and
internal iliac and occasionally from the common iliac arteries. During radical hysterectomy,
the ureter may be completely devascularized, and this results in a necrotic uretrovaginal
fistula. This is effectively avoided if the pelvic ureter is left hanging to the posterior leaf of
the broad ligament.

Main blood vessels of the pelvis

Surgeons doing major pelvic operations should be familiar with the blood vessels in
the pelvis.

Common Iliac vessels

The aorta bifurcates on the left side in the front of the body of the fifth lumbar
vertebra into the two common iliac arteries; i.e., the right common iliac is longer. Each runs
downward and outward for a distance of 4 or 5 cm (depending on the side) before dividing
into the external and internal iliac arteries. At the point of division the ureter lies in front and
the sacroiliac joint behind.
Behind the right common iliac artery are the terminations of the two common iliac
veins and the lowermost part of the inferior vena Cava. The common iliac veins lie partly
behind and partly on the inner side of the arteries. The left common iliac vessels have the
superior rectal vessels as an anterior relation.

External iliac vessels

The external iliac artery runs downwards and outwards just below the brim of the
pelvis to reach underneath the inguinal ligament where it passes to the thigh, and becomes
called the femoral artery. It is directly underneath the peritoneum. The external iliac vein lies
medial to the artery, and both are surrounded by rich lymphaticnetwork including the external
iliac lymph nodes. The femoral nerve lies lateral to the artery at the point of crossing under
the inguinal ligament. The external iliac vessels have no branches until just above the inguinal
ligament where the artery gives the deep inferior epigastric and deep circumflex iliac, and the
vein has corresponding tributeries. The inferior epigastric artery crosses over the external iliac
vein while the deep circumflex iliac vein crosses over the artery. In doing dissection of
external iliac lymph nodes, this should be carried down to this point of criss-crossing of thesis
branches.

25
Anatomy of the female genital system

The anterior relations of the external iliac vessels are the ovarian vessels and the
round ligament.

Internal iliac vessels (occasionally called the hypogastric vessels)

This artery descends from its origin from the common iliac artery into the pelvis as far
as the greater sciatic foramen where it usually divides into anterior and posterior divisions.
The ureter runs down its front aspect, while the internal iliac vein is behind and below the
artery. Further below there is the obturator nerve. The posterior division gives parietal
branches, which leave the pelvis to supply the muscles of the buttocks, including the
iliolumbar the superior gluteal, and lateral sacral arteries. The branches of the anterior
division of the internal iliac are the main supply of pelvic viscera. They comprise the uterine
artery, obliterated hypogastric (remnant of umbilical artery), superior middle and inferior
vesical, middles rectal, vaginal, obturator and the inferior gluteal arteries, before continuing to
the outside of the pelvis as the internal pudendal.
The obliterated hypogastric may have a common origin with the uterine. The
tributaries of the internal iliac vein are medial to the arteries but have extensive anatomical
variatration. They form thin walled plexus of big veins; many of them leave the pelvis
immediately. Injury of this plexus of vein is the most serious complication in radical
hysterectomy. It is a good wisdom that the internal iliac vein should be left severely alone. If
one of the tributaries are injured the bleeding mouthes retract outside the pelvis with blood
welling up. Attempt at clamping bleeding sites causes more injury of the venous plexus. The
best management is prolonged temponade by a pack, which usually results in cessation of the
ooze.

Uterine vessels: see above.

Vaginal vessels
The vaginal artery is usually a separate branch (or branches) from the internal iliac
artery but may come off the first part of the uterine artery. It passes forwards and inwards low
in the broad ligament to reach the lateral vaginal fornix. In the vaginal wall it anastmoses with
the azygos branches that come down of the circular artery of the cervix. The lower vagina is
also supplied from the middle and inferior rectal vessels and by branches from the internal
pudendal artery.

26
Anatomy of the female genital system

Internal pudendal vessels:

The internal pudendal artery is the terminal branch of the anterior division of the
internal iliac artery. It leaves the pelvis through the greater sciatic notch, and curls round the
ischeal spine and returns to the lateral wall of the ischio-rectal fossa through the lesser sciatic
notch. At this point it lies 4 cm above the ischial tuborosity, accompanied by the pudendal
nerve, being contained in what is called the Alock’s canal. It precedes forward giving
branches then entering between the two layers of the triangular ligament. It gives blood
supply to the vulva, lower vagina and perineum. It ends as the dorsal artery of the clitoris.

Ovarian vessels :( see above)

Venous plexuses
The veins of the pelvis accompany the arteries. Sometimes there are two veins for one
artery. In the broad ligament near the mesovaruim there can be a plexus of veins called the
pampinform plexus, which drains, in both the ovarian and uterine trunks. It is this plexus,
which sometimes become varicose and give rise to a pelvic or broad ligament varicocele.
There are plexuses of veins around the vagina, the urinary bladder, and rectum, which
freely communicate with each other. This is the route by which bilharzial ova in the vesical
venous plexuses can reach the genital tract; the vagina being the most commonly affected part
of the female genital tract.
The pelvic plexuses of veins also have communications with the presacral and lumbar
channels of the vertebral plexus, and in this way it is possible for blood, tissue cells, emboli
and organisms to travel to remote parts of the body without passing through the heart. This is,
probably, the explanation of the occurrence of metastatic growths in the spine or brain when
the primary is in the uterus.

Innervation of the genital system and

other pelvic organs
Somatic Nerves
The main somatic supply to the pelvic organs is the pudendal nerve, which is both
sensory and motor and has its origins in the S.2, S.3, and S.4 roots of the sacral plexus. The
nerve leaves the pelvis together with the internal iliac vessels through the greater sciatic notch
and curls around the ischial spine or sacrospinous ligament to enter to the lateral wall of the

27
Anatomy of the female genital system

ischiorectal fossa in the Alcock’s canal. It gives perineal branches before it enters between the
two layers of the triangular ligament.
The pudendal nerve supplies sensory nerve endings to the vulval structures, the
urethral meatus, the perineum and the lower vagina. It provides motor innervation to all
voluntary muscles in the pelvic outlet including the levator ani and the deep and superficial
perineal muscles including the superficial anal sphincter.
Additional nerve supply comes to the levator ani from above via branches from the
roots of the sacral plexus. Sensory supply reaches the mons venires and forepart of the vulva
from the ilioinguinal nerve and the genital branch of the genitofemoral nerve, both arising
from L.1 and L.2 roots of the lumbar plexus. The perineum and the posterior parts of the
vulva receive additional sensory supply from the posterior coetaneous nerve of the thigh (For
pudendal nerve block refers to Obstetrics).
The skin of the vulva is very sensitive to pain. The lower vagina is sensitive to pain
but the upper vagina and cervix have no or little pain nerve endings, explaining the painless
cervical cauterization.

Autonomic nerves
All the internal genital organs, together with urinary bladder, urethra, rectum and
colon have autonomic nerve supply which have sensory and motor functions and belong to
both the sympathetic (adrenergic) and parasympathetic (cholinergic) types:

Sympathetic supply:
Sympathetic nerves, arising from segment T.5 and T.6 in case of motor effects and
from T.10 to L.1 in case of sensory effects. The sympathetic nerves pass down from the celiac
plexus around the abdominal aorta. Over the bifurcation of the aorta and the promontory of
the sacrum they forma plexus of fine nerves which is collectively known as the presacral
nerve or the superior hypogastric plexus. From this, two main chains run on the sides of the
pelvis and are called the hypogastric nerves. These join again in the pelvic (inferior
hypogastric plexus of fine nerves, which are on both sides of the ampulla of the rectum. This
gives forward extension beneath the uterosacral and broad ligaments. These extensions are
called the Lee-Frankenhauser plexus. In addition, nerves to the ovaries and tubes travel from
the celiac plexus around ovarian vessels.

Parasympathetic supply:
The parasympathetic supply to the genital organs, bladder, urethra and rectum are
carried in S.2, S.3 and S.4 roots. This joins the pelvic plexus on the sides of the ampulla of the
rectum.

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Anatomy of the female genital system

Possible effects of autonomic nerve supply:

1. Sympathetic and parasympathetic nerves carry sensory impulses from the uterus, bladder
and rectum. These impulses comprise the pain resulting from dilatation of the cervix and
distension of the uterus. Nerves reaching the cervix pass through paracervical ganglia that
can be blocked by paracervical block.
2. The parasympathetic sensory supply to the cervix and parametrium run in the uterosacral
ligaments, and are referred to the lower back by the sacral routes.
3. Presacral neurectomy, i.e. extirpation presacral nerve, or diathermic cautarization of the
uterosacral ligament can effectively diminish dysmenorrheic pain. But this is not achieved
in all cases and may recur after sometime.
4. The cervix and body of the uterus are relatively insensitive to pain. Chronic cervicitis
causes pelvic pain, only when associated with parametritis. Cervical cauterization can be
done without anesthesia, and causes little discomfort. However, holding the cervix with a
volsellum can cause a momentary lower abdominal stabbing pain. Touching the internal
os by the tip of the sound or the IUD inserter rarely cause sickening pain, bradycardia,
syncope or very rarely collapse and neurogenic shock.
5. The tubes and ovaries receive additional nerve supply from sympathetic fibers
accompanying the ovarian vessels. Cutting crushing or cauterization of the fallopian tube
can cause some pain during tubal sterilization procedure done under local anesthesia.
6. Motor function for autonomic nerve supply to the uterus is not established. Inhibitory
action of adrenergic supply is possible. b-sympathomimetic drugs produce tocolysis of
the pregnant uterus. This does not however, prove a motor nerve supply to the
myometrium, since the division of all uterine nerves or of the spinal cord at high levels
does not affect uterine contractility of labor. Presacral neurectomy does not abolish pain
of labor or uterine contractility. To abolish all pains of labor it is needed to block the
spinal nerve roots below the level of T. 10, as in epidural anesthesia. This does not
interfere with process of labor or cervical dilatation. However prolongation of the second
stage of labor may result from loss of bearing down effect of the voluntary abdominal
muscles.
7. Sympathetic nerve supply carries sensation of bladder distension.
8. Sympathetic motor supply can cause inhibition of detrusor and improve the tone of the
urethra. This is the basis of administration of epinephrine ( and similar drugs ) to cases
with enuresis.

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Anatomy of the female genital system

Abdominal Wall
The anterior abdominal wall is bound superiorly by xiphisternum and the coastal
cartilage of the 7th - 10th ribs, and ends inferiorly by the iliac crest, anterior superior iliac
spine, inguinal ligament, and pubic bone. It consists of the following structures:

Skin
The fibers of the dermal layer of the abdominal skin are oriented in a transverse
direction following a gently curving concave upward line. This results on more tension on
edges of vertical incisions than on transverse ones. Subcuticular repair of the skin is easier in
transverse incision and sutures can be removed earlier in these incisions.

Subcutaneum
Contains a variable amount of fat and two ill-defined fascial layers: 1) Camper’s
fascia is the superficial layer and is continuous with the superficial fatty tissue of the
perineum. 2) Scarpa’s fascia a deep slightly dense membrane continuous with the deep fascia
of the thigh (fascia lata) and the Collies fascia in the perineum.

Muscles Five muscles

1. External oblique: Origin: the outer surfaces of ribs 5–12. Insertion: the fibers
radiate medially, anteriorly and inferiorly ending mostly in the external oblique
aponeurosis which is inserted into the anterior half of the iliac crest, the pubic tubercle
and the linea alba. The lower edge of the external oblique aponeurosis forms the
inguinal (Poupart’s) ligament. The superficial inguinal ring is a triangular cleft in the
lower medical angle of the aponeurosis just lateral to the pubic tubercle. This ring
transmits the round ligament, (which terminate in the skin of the front of the vulva).
2. Internal oblique: Origin: from the posterior layer of the thoracolumbar fascia, the
anterior two thirds of the iliac crest, and the lateral two thirds of the inguinal ligament.
The fibres fan out in an upward direction and are mostly perpendicular on the fibres of
the external oblique. Insertion in inferior border of ribs 10-12. The superior fibers of
the internal oblique form an aponeurosis which split near the middle line to enclose the
rectus abdominus muscle and join at the linea alba above the arcuate line. The most
inferior fibres join with those of the transversus abdominus muscle to insert into the
pubic crest and pectin pubis via the conjoint tendon.
3. Transversus abdominus: Origin from the inner aspect of the inferior six coastal
cartilages, the thoracolumbar fascia, the iliac crest, and the lateral third of the inguinal

30
Anatomy of the female genital system

ligament. It is inserted in the linea alba with the aponeurosis of the internal oblique,
the pubic crest and pectin pubis via the conjoint tendon.

The above three muscle compress and support abdominal viscera

4. Rectus abdominis : originates from the superior pubic ramus and the ligaments of
the symphesis pubis. It is inserted in the anterior surface of the xcphoid process and
the cartilage of the ribs 5-7. The muscle tensenes the anterior abdominal wall and
flexes the trunk.
5. Pyramidalis : is a small triangular muscle ( occasionally absent ) contained within
the rectus sheath anterior to the lower part of the rectus muscle. It is inserted on the
lania alba. Surgically it can define the middle line. It has insignificant function.

Rectus sheath:
The aponeurosis of the external and internal oblique and the transversus abdominis
combine to form a sheath for the rectus abdominis and pyramidalis, fusing medially in the
middle at the linea alba. Above the arcuate line, the aponeurosis of the internal oblique splits
into anterior and posterior lamella. Below this line, all the three muscles are anterior to the
rectus muscle. Below the arcuate line the rectus is directly upon the transversalis fascia.

Transversalis fascia:
The transversalis fascia is a firm membranous layer on the internal surface of the
transversus abdominis muscle. Beyond the latter muscles it extends to line all the
abdominopelvic cavity. It is the only component of the posterior rectus sheath below the
arcuate line. It is continuous with the fascial covering of the abdominopelvic viscera i.e. like
the peritoneum the transversalis fascia has a parietal and visceral component and is separated
from the peritoneum by a variable amount of fat.

Nerves and vessels of the abdominal wall:

The abdominal wall structures are innervated by continuations from the intercostal
nerves T4 to T11 and the subcostal nerve T12. The lower part of the anterior abdominal wall
receives additional nerve supply from the iliohypogastric and the ilioinguinal nerves (L1).
The blood supply mainly comes from 1) the superior epigastric artery, ( a terminal
branch of the internal thoracic artery), the inferior epigastric and deep circumflex iliac arteries
( both are branches of the external iliac artery ).
The inferior epigastric artery runs upward on the transversalis fascia to reach the
arcuate line, where it enters the rectus sheath. It is vulnerable to damage upon excessive

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Anatomy of the female genital system

lateral traction on the rectus or when the rectus is transected. The deep circumflex artery runs
on the deep aspect of the anterior abdominal wall just above the inguinal ligament.
The venous drainage of the lower abdominal wall goes mainly the saphenous vein.
Lymphatic drainage of the part above the umbilicus goes to axillary nodes and below it to the
inguinal nodes.

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Physiology of reproduction in women

Chapter 2
PHYSIOLOGY OF REPRODUCTION
IN WOMEN
Contents
• Ovarian function
- Folliculogenesis and ovulation
- Ovarian hormones
• Pituitary hormones
• Hypothalamus
• Menstrual cycle
• Prostaglandins (Arachidonic acid Family)
• Assay of reproductive hormones
• Menopause

Introduction
The reproductive function of women is characterized by cyclicity. The function goes
in monthly cycles, most characterized in the ovary - ovarian cycle. This is under control of the
anterior pituitary. The latter is controlled by the hypothalamus which has the biological clock
that determines the cyclically, but its function is influenced by feedback messages from the
ovaries, and may be, the pituitary; and by messages from other brain sites. The outward
manifestation of this cyclicity is the menstrual cycle which goes from the menarche till the
menopause. The subject is approached hereafter under four headings indicating the levels of
control:
I. Ovary,
II. Pituitary,
III. Hypothalamus,
IV. The menstrual cycle.

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Physiology of reproduction in women

I. Ovarian Function
The ovary has two functions: 1. Production of female germinal cells, the female
gametes, the ova, 2. Production of ovarian hormones.

1. Follicular development and ovulation

1.1. Female gametes, the ova
During early embryonic life the ovary receives the germ cells, the oogonia from, most
probably, the endoderm of the hind gut and the adjoining part of the yolk sac. During
embryonic and fetal life, the germ cells actively divide by mitosis and the ovaries of the
embryo can have up to 4 to 5 million ova. A process of depletion of ova starts from fetal life
and continues during prepubertal and reproductive life. At birth, the two ovaries have between
them about 1 million ova. This number is reduced to about 300,000 at the time of puberty. Of
these, only about 500 ova are destined to ovulation, the rest are progressively depleted by
follicular atresia up to the time of menopause. There is no division of the primary oocyte
(with 46 chromosomes) after birth. However, the first of the two maturation division (meiosis
I) necessary for formation of fertilizable female gamete, the ovum starts at birth, but the
process is arrested at the prophase of this division until the time of ovulation. Meiosis I
(which is a reduction division) and shedding of the first polar body is completed at the time of
ovulation when a secondary oocyte is formed which has 23 chromosomes. The second
maturation division, meiosis II, is similar to mitosis (i.e. with no further chromosome
reduction) resulting in the secondary oocyte is only completed (and the second polar body is
shed) after fertilization. The chromosomal material remaining in the secondary oocyte (ovum)
will fuse with the male pronucleus of the spermatozoon (also containing 23 chromosome) to
form the zygote whose nucleus contains the 46 chromosomes characteristic for the species.
1.2 Follicular growth; follicular phase
The structural units of the ovary is the ovarian follicle, each is formed of one ovum
surrounded by a supporting layer; the granulosa cells. The early follicle, the primordial
follicles have a single layer of cuboidal granulosa cells. Growth of follicles occurs in
overlapping cohorts. The process of follicular growth starts in fetal life and continues during
prepubertal age, but none of the follicles matures or ovulates. Instead, and at any of the
various stages of folliculogenesis, they degenerate in a process called follicular atresia by
which most of the follicles are exhausted. At variable stages of development they regress and
become hyalinzed. After puberty, and under effect of pituitary hormones, the process of
folliculogenesis becomes more active and organized. Early in each menstrual cycle, a cohort
of primordial follicles (several hundreds) is recruited in a process of follicular development.

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Physiology of reproduction in women

Follicular development involves growth of the ovum in size up to a diameter of 80-

120 micron and swelling and multiplication of the granulosa cells. The ovum becomes
surrounded by several layers of granulosa cells, cuboidal in shape. This is the preanteral
follicle. Small cavities form between granulosa cells (Call-Exener’s bodies); these fuse to
form the antrum of antral follicles. Many follicles reach this antral stage, but only one of
them surpasses the others, enters a phase of accelerated growth, follicular dominance to
reach the stage of preovulatory follicle (mature graafian follicle); the rest will go into atresia.
The preovulatory follicle moves by differential growth to underneath the surface of
the ovary and my bulge out from the ovarian surface. It reaches to about 20 to 30 mm in
diameter and is lined by several layers of granulosa cells and its cavity is filled by thin viscid
fluid rich in ovarian hormones. On one side of the follicular wall there is an accumulation of
granulosa cells; the discus proligerus or cummulus oopharicus surrounding the ovum. The
innermost layer of the discuss cells are radially arranged over the ovum forming the corona
radiata. The follicle is surrounded by the vascular theca interna formed of spindle-shaped
cells aligned around the follicle, these cells, together with the granulosa cells, are active in
formation of steroid hormones. This theca interna merges in a less vascular layer of theca
externa formed of flattened cells that are pushed aside and condensed by the growth of the
follicle. This layer belongs to the stroma and is not producing hormones.
The growing follicles are all active in hormone production, which is most active in the
dominant follicle (see later).
1.3 Ovulation
It is the discharge of the ovum (within part of the cumulus) of the mature graafian
follicle from the surface of the ovary. It occurs in the middle of the cycle; more exactly 14 2
days before the subsequent menstruation. The process is not a rupture but rather a release of
the ovum that takes some minutes. It is decided by occurrence of a mid-cycle peak of LH, and
ovulation usually occurs during the descending part of the sudden LH peak. The exact
mechanism of ovulation is not clear, but it involves pressure thinning of the tissue on the
surface of the follicle by a rapid increase in the fluid. Thinning out may be helped by the
contained antral hormones and enzymes. The possibility of locally produced prostaglandins at
the time of ovulation, and a stimulating contraction of fine myofibrils in the stroma has been
suggested. LH surge may trigger activation of certain proteolytic enzymes, like collagenase,
in the granulosa cells.
At the time of ovulation the trumpet-shaped infundibulum of the tube embraces the
surface of the ovary, in order to diminish the chance of the ovum being lost in the peritoneal
cavity. A fluid inward stream produced by active beating of the celia of the endosalpinx,

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Physiology of reproduction in women

sweeps in the ovum surrounded by corona radiata cells together with some of the cummulus
cells.
1. 4 Corpus luteum; luteal phase
The corpus luteum develops from the structures of the mature grafian follicle after
ovulation. The follicular wall collapses and becomes a crenated membrane. There is active
growth of both its granulosa layer and theca interna layer. They multiply and enlarge in size,
and both types become cuboidal with centeral nucleus. They are become called respectively:
granulosa lutein and theca lutein cells. The latter cells type are smaller and grow to fill the
folds under the crumbled follicular wall. Blood vessels then grow in these folds to vascularize
the granulosa lutein cell layer (which has been originally avascular). The corpus luteum at this
stage, beginning from the 3rd to 8th days after ovulation become fully functioning (see later).
It grows to a diameter of about one centimeter. It can get cystic and its filling fluid can be
hemorrhagic. On cut section, its lining looks crenated (convoluted), and to start with is
grayish in color. Later on, degenerative process starts in the cells and they acquire a yellowish
hue due to lipoid depositions; hence the name corpus luteum. The corpus luteum is a
caducous structure, which after serving its temporary function degenerates. The withdrawal of
leuteinizing-hormone support also contributes to this degeneration. It loses its staining and
become white and its cells are hyalinized and become called a corpus albicans. It may take
some weeks for the corpus luteum to disappear and completely revert back to ovarian stroma.
Therefore, the life of the corpus luteum is divided into the following phases : 1.
Proliferation, 2. vascularization, 3. Function, 4. Degeneration. The function of the corpus
luteum is the production of the hormones progesterone and estrogens which result in the
secretory transformation of the endometrium, in preparation for reception of the fertilized
ovum.
If the ovum which has been ovulated is fertilized and gets implanted, the chorionic
gonadotrophin produced by its trophoblast reaches, through the general circulation, to the
ovary, and due to its luteinizing-hormone-like action it preserves and causes further growth of
the cospus luteum; and its hormone production will increase. It become now called the corpus
luteum of pregnancy. This serves to support the early embryo, until the placenta takes over the
function of estrogen and progesterone production.
1. 5 Follicular atresia
Progressive loss of ovarian follicles by follicular atresia is a continuous process
throughout the prereproductive and reproductive life. It is not halted during pregnancy and
proceeds until the menopause when most of the ova are exhausted. Atresia occurs in any of
stage of follicular development. Preantral ova just revert to stroma after disappearance of the
ovum. But antral follicles undergo a process of hyalinization and fibrosis and may give rise to

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Physiology of reproduction in women

temporary cystic structures. Their granulosa and theca cells may remain active in hormone
production, and occasionally cause disturbed menstrual rhythm.

2. Ovarian hormones
The ovarian structures produce the following hormones
1. Steroid hormones: estrogens, progesterone and the androgens testosterone, androstendione
and dehydroepiandrosterone (DHEA).
2. Peptide hormone: inhibins; activins, follistatin
3. Growth factors e.g., Insulin-like growth factor, Epidermal growth factors. These latter
factors act locally i.e. paracrine or autocrine actions.
The production of this endocrine, paracrine or autocrine compounds are under the
control of pituitary gonadotrophins: FSH and LH.

2. 1 Ovarian steroid hormones

The ovary produces two estrogens estradiol and estrone, as well as progesterone. The
production of these is the principal endocrine function of the ovaries. It also produces small
amount of testosterone as well as weaker androgen androstendione and
dehydroepiandrosterone (DHEA). Estradiol (E2; so designated because of containing two
hydroxy groups) is the main estrogen produced by the human ovary. Estrone (E1, so
designated because of containing one hydroxy group) a much weaker estrogen and is
produced in smaller quantities than estradiol. The maturing graffian follicles also produce
small amounts of progesterone.

2. 1. 1 ESTROGENS
• Biosynthesis: Both estradiol and estrone are mainly produced by the granulosa cells of
the growing follicles. After dominance of one preovulatory follicle there is a spurt of
estradiol production, which reaches a peak value before ovulation. This peak drops to a
nadir before ovulation. After formation of the corpus luteum both granulosa-and theca
lutein cell produce estrogens. Their level rises to a plateau, which is lower than the
preovulating peak, but is maintained for 4 - 6 days during the bloom of function of corpus
luteum (Figure 1). This plateau is associated with marked increase in progesterone
production, which is produced by the same cells. Thereafter, when the corpus luteum
regresses there is an estrogen and progesterone withdrawal, which results in menstruation.

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Physiology of reproduction in women

Physiology of reproduction (Figure 1): Cyclic changes in ovarian and pituitary hormones.

• Structure of Estrogens and their Synthesis (Figure 2): Estrogens, like all steroid
hormones, have a basic structural ring called perhydro-cyclopentano-phenantherene.
The basic structure of this ring is composed of three 6-carbon rings, and one 5-carbon
ring. Estrogen nucleus comprises 18 carbon steroids and is called estrane nucleus. The
estrogens are synthesized in the producing cells from cholesterol (27 carbons).
Cholesterol is first converted to progesterone (21 carbons) which is converted to the
androgens: androstenedione and testosterone (19 carbons) which are converted
respectively to estradiol and estrone (18 carbons). This is a simplified scheme since other

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Physiology of reproduction in women

intermediaries are involved, and there is ready interconversion between steroid hormones
e.g., interconvertion between androstendione and testosterone, and between estradiol and
estrone (Figure 3). Many enzymes are involved in steroidogenesis, which generally
belong to the cytochrome P450 group of oxidases; these are widely spread in the tissues
of body.

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Physiology of reproduction in women

Physiology of Reproduction (Figure 3): The main steroid hormones: 1. Cholesterol; 2.

Progesterone; [Link]; [Link].

• Blood Transport of Estrogens: While circulating in the blood, sex steroids - both
estradiol and testosterone, are bound to a globulin; a protein carrier known as sex
hormone-binding globulin (SHBG). A very small percentage, only 1% of the hormoneis
unbound and is free; this is the directly active portion. This binding limits the biological
activity and protects the hormones from rapid metabolism i.e. ensuring a steady state of
action, through ensuring a big reservoir of bound hormone.
• Estrogen Receptors:
The free (unbound) estradiol readily enters the cells and diffuses into the nucleus. The
specific estrogen receptor proteins are intranuclear. To produce its effect the steroid
hormone needs to be grasped by receptors within the nucleus. Only the cells of estrogen-
responsive tissues contain these estradiol-specific receptors. The steroid-receptor complex

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Physiology of reproduction in women

interacts with nuclear DNA, and this reaction results in transmission of the hormone’s
message to nuclear gene structure, i.e. the formation of steroid hormone-receptor complex
regulates DNA expression. The result is the production of a messenger RNA, which is
transported to cytoplasmic ribosomes where it leads to protein synthesis, and the cellular
response characteristic of estrogen responsive cells. The particular cell response is
modulated by local cellular influences, e.g., availability of other endocrine, paracrine and
autocrine hormones (* Receptors of certin other steroidshormones, e.g., glucocorticoides,
when unbouund resides in the cytoplasm but after binding to the hormone needs to diffuse
into the nucleus to interact with DNA).
• Metabolism of estrogens
Estradiol is mainly metabolized in the liver by converting it to estrone and then to
estriol (E3: by virtue of having 3 OH or hydroxy radicals), which are moderately
effective and very weak estrogen respectively. Estriol is not produced in the ovary but
is a peripheral metabolite. However, during pregnancy, the fetoplacental unit produces
huge amounts of estriol. Estrogens are also “detoxicated” by conjugation to products
that are water soluble and excreted in urine and bile (sulphate- and glucourinate-
conjugates).
The conversion of estrogens in peripheral tissue is not always a process of
inactivation. Free androgens are peripherally converted to estrogens mainly estrone in
the skin and subcutaneous tissue. This process is more marked in women with trunckal
obesity. These estrogens can predispose to endometrial hyperplasia and may produce
postmenspausal bleeding.
• Functions of estrogens:
1. Estrus:
In lower animals, estrogen production induces sexual heat or estrus. This is the period of
sexual receptivity of these animals (mating season). In women estrogen plays a minor role
in sexual behavior, the latter is mainly neurological and is maintained throughout life.
Sexual desire and arousability continue after menopause, but may decline in later ages as
part of general senility.
2. Secondary Sex Characters
Estrogen is the main determinant of secondary sexual characteristics, like rounding
of certain parts of the body, deposition of fat in certain strategic sites, heavy scalp hair,
softness of the skin, shyness and sensitivity, ... etc. Axillary and pubic hairs are determined
partially by androgens of adrenal origin. An escutchoin of straight upper margin is a
feminine feature. The breasts develop under the effect of estrogens and progesterone, but
does not attain full development until pregnancy (see under physiology of lactation).

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Physiology of reproduction in women

3. Secondary Sex organs

a. Vulva: The estrogen increase after puberty results in increase of fat in the mons pubis,
and enlargement of the labia majora, which cover the labia minora and the introitus; i.e.
these internal structures are more readily seen in young prepubertal girls.
b. Vagina: All the components of the vagina, smooth muscles, fascia and epithelium
develop and reach full maturation under the effect of estrogens. The vaginal epithelium
becomes thicker and multi-layered and its cells reach full maturation. Under estrogen
effect, the desquamated vaginal epithelial cells become formed mostly of superficial
cells. Estrogens also enhance deposition of glycogen in the vaginal epithelial cells.
Clycogen in the desquamated epithelium is transformed by vaginal lactbacillus to lactic
acid, which is responsible for the acidity of the vaginal transudate (pH 4-5).
c. Cervix: The preovulatory peak of estrogen is responsible for the characteristics of the
preovulatory cervical mucous cascade: which is normally excessive, fluid, glassy clear
mucus and demonstrates spinnbarkeit and ferning phenomena. This type of mucus is
more readily penetratable by sperm. The addition of progesterone after ovulation
results in the mucus becoming scanty, viscid and heavily cellular and loses spinnbarkeit
and ferning characters.
d. Uterus: The uterus attains the adult dimensions and structure under the effect of the
increased production of estrogens after puberty. The myometrial muscles grow in
number and size. The endometrium is particularly sensitive to the effect of estrogens. It
is repaired after the disruption of menstruation. This is followed by proliferation and
addition of thickness. The glands become elongated, and in the preovulatory
endometrium the glands become tortuous and their epithelium become taller. They only
start to be functional i.e. secretory, after the addition of progesterone influence of the
corpus luteum. The progesterone can only exercise its effect on estrogen primed
endometrium.
e. Tubes: The tubes become more vascular and its epithelium hypertrophic, and the
celliary action becomes more active during the preovulatory rise in estrogens. The tubal
muscular peristalsis becomes more active during this time. These changes ensure ovum
pick-up.
4. Endocrine effects of estrogens
Ovarian estrogen exercises a feedback effect on the hypothalamo-pituitary axis by
modulating the production of gonadotrophin releasing hormones (Gn RH), and
consequently modulating the production of gonadotrophins. A direct effect of estrogens on
the pituitary is also possible. The increased production of estrogens in the early part of the
follicular phase exercises a negative feedback on the secretion of FSH and LH. However,
after the dominance of the preovulatory follicle, the consequent marked preovulatory spurt

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Physiology of reproduction in women

in estrogen level exerts a positive feedback which triggers a sudden midcycle-LH peak,
and a smaller FSH peak which immediately precede and determine the ovulation. The
plateaus of estrogens and progesterone produced during the bloom of function of the
corpus luteum are enhanced by LH secretion. However, these rises cause a decline in
production of the luteinising hormone through a negative feed back, which partially
determines the regression of the corpus luteum.
The withdrawal of estrogen after menopause is responsible for a marked rise in the
FSH and LH production particularly the former. In fact, the decline of estrogen and rise of
FSH level may begin in the few years preceding the menopause. The estrogen deficiency
is responsible for the menopausal flushes and sweating. However, the mechanism involved
in causing these vasomotor symptoms is not clear.
Estrogens increase the production of SHBG and increase the protein-bound iodine
and protein bound cortisol. They decrease glucose tolerance.
5. Bones:
Estrogen enhances bone mass by conserving calcium and phosphorus and
enhancing their deposition in bones through stimulating osteoblastic function. The
maximum gain of the bone mass occurs during adolescence. At puberty the beginning of
estrogen increase, first enhances the prepubertal spurt in growth of long bones and
addition of body height. But thereafter, the estrogen enhances closure of epiphysis of long
bone limiting any further growth of stature after establishment of puberty. After
menopause the lack of estrogens play a role in enhancing osteoporosis. Loss bone mass is
maximal in the few years following the menopause and continues thereafter, but at a lower
rate. Postmenopausal estrogen therapy can diminish osteoporosis.
6. Blood Component:
Estrogen increases the concentration and activity of certain factors of the
coagulation system like fibrinogen and factor VII, VIII and X, and increases platelet
number and aggregation.
7. General effects
Estrogen is anabolic, but much less so than testosterone. The lipoprotein
metaholion is affected by estrogens; the HDL cholesterol triglycerides are increased, and
total cholesterol and LDL cholesterol are diminished. The lesser liability of women to
coronary heart disease before menopause is ascribed to such effects on lipid metabolism
together with an effect of estrogen in enhancing coronary blood flow and cardiac output,
and diminishing the peripheral resistance. The incidence of coronary heart disease
increases after menopause rising gradually approaching the incidence in males. There are
indications that this risk may be prevented by postmenopausal estrogen administration.

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Physiology of reproduction in women

2. 1. 2 PROGESTERONE
Progesterone is a 21-carbon steroid that is produced mainly by the corpus luteum. The
granulosa and theca intern cells of maturing follicle produce small amount of progesterone.
After ovulation, progesterone is produced mainly by the theca lutein cells. After
vascularization of the granulosa lutein cells, they can also contribute to the increased
progesterone secretion, which occurs during the bloom of function of the corpus luteum. This
increased production of progesterone is an effect of mainly LH secretion but with a smaller
contribution of FSH activity. The rise in progesterone results in a negative feedback, which
determines a decline in LH secretion (Figure 1).
In the circulation progesterone is mainly bound to transcortin, a binding globulin
produced at the liver which carries, as well, cortisol and corticosterone, A small fraction
(10%) circulates unbound i.e. free, and this is the biologically active fraction, and the part
readily metabolized. Progesterone receptors are induced by estrogens (estrogen priming). The
receptors are intranuclear, and their binding to the hormone determines the rate of expression
of DNA in formation of messenger RNA.
Progesterone is metabolized in the liver into the biologically inactive pregrandiol,
which is excreted in urine as glucourinate salt. Pregnanedial account only for 10% of secreted
progesterone, the fate of the rest of progesterone is not clear. However, the urinary excretion
of pregranodiol consistently reflects the level of progesterone in the blood, i.e. urinary assay
of pregnandiol glucourinate can be a substitute of measuring plasma progesterone.

• Functions of Progesterone
In animals, progesterone is responsible for certain behaviors important for the
preparations for reception of the offspring e.g., preparation of the nest and migration of birds
and fishes. In man, there is no similar behavior. The main actions of progesterone are on the
genital tract and certain other target organs. However, a simultaneous or prior estrogen effect
is necessary (estrogen priming). This is brought about by estrogen stimulation of the
formation of the intracellular progesterone receptors.
1. The vaginal epithelium matures under the effect of progesterone only to the level of
intermediate cells which form some 30% of the cells desquamated in the vaginal
transudate during the luteal phase of the cycle.
2. The endometrium, which has been primed by estrogen, reacts to progesterone by secretory
transformation. The endometrial thickness increases, the glands become more tortuous,
and the vascularity of the endometrium is enhanced. The first evidence of secretion is the
appearance of subnuclear vacuolation, i.e. next to the basement membrane. Thereafter, the
secretory vacuoles become supranuclear and then the secretion is discharged into the
lumen. The inner edge of epithelium of the glands is frayed in the process of secretion.

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Physiology of reproduction in women

The gland lumen will be laden by glycogen-rich secretion. Simultaneously, the stroma
becomes edematous and infiltrated by mononuclear cells. The stroma under the surface
epithelium shows decidual reaction. Its cells imbibe water and their cytoplasm becomes
definite instead of being scanty. The decidua is an effect of pronounced progesterone
effect in the late luteal phase. It becomes more marked after nidation; a sort of mechanical
effect. The above sequence of events in the endometerium usually allows dating of the
endometrium in biopsies.
3. The myometrum grows under the combined effect of progesterone and estrogen.
Progesterone is responsible for myometrial proliferation in early pregnancy. Uterine
contractions, under the effect of progesterone, become less frequent but the amplitude
increases.
4. Progesterone enhances water and salt retention. Progesterone is thermogenic, and is
responsible for a slight rise of body temperature of 0. 3-0.5 degrees (C) during the luteal
phase; hence the biphasic body-temperature chart characteristic of ovulatory cycle.
Progesterone diminishes the tone of smooth muscles in the body and the marked rise in
the progesterone levels may be responsible for the constipation, varicosities in the lower
limbs and dilatation and stasis in the urinary tract during pregnancy. Progesterone cause
a decrease in HDL-cholesterol.

2. 2 Inhibin-Activin-Follistatin(peptide hormones)
Inhibins and activins are a family of peptides synthesized by the granulosa cells in
response to FSH. They are secreted in the follicular fluid and reach the general circulation.
Inhibin specifically inhibits FSH without inhibiting LH; an important feedback (a reciprocal
relationship). At the same time inhibin have a number of paracrine and autocrine effects that
ensure the spurt of growth of the dominant follicle. This relationship probably determines the
dominance of one of the growing follicles, the one destined to ovulate; while the other regress
by atresia. This is helped by activin autocrine action, which enhances the stimulatory effect of
FSH on the granulosa cells of the preovulatory follicle. Inhibin level in the blood rises slowly
during the follicular phase to reach a peak that coincides with the midcycle LH peak, and it
shows another higher peak during the luteal phase. Inhibin offers a means of modulating
folliculogenesis and ovulation and is expected to have future practical applic ation (e.g., in
contraception).
Activin is a peptide that is related structurally to inhibin but has an opposite action, i.e.
stimulation of FSH release. It has also paracrine and autocrine effects in enhancing FSH
action on the dominant follicle.

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Physiology of reproduction in women

Follistatin is a single chain, glycosylated peptide produced in the pituitary but is found
mainly in the preovulatory follicle. It binds activin thus removing their enhancing effect on
cellular activity.

2. 3 Growth Factors
Growth factors are polypeptides that modulate cell proliferation and differentiation
operating through binding to specific cell membranes receptors. They act locally by paracrine
and autocrine effects. Growth factors are also localy produced in a number of other sites
including the endometrium. Because growth factors are potent mitogens, they potentate the
prolefrative effects of granulosa cells of the ovary and the endometrial epithelium. Estrogen
stimulates the production of growth factors and the production of the receptors. The growth
factors mainly comprise the following
Insulin-like growth factors (IGFs) (also called somatomedins) are peptides, which are
structurally similar to insulin and modulate the action of growth hormone on certain target
cells. IGF-I is produced by the theca cells in the provulatory follicle and by granulosa lutein
cells of the corpous luteum. In human ovarian follicles IGF-I, in synergy with FSH,
stimulate protein synthesis and steroidogenesis (of both estrodiol and progesterone).
Epidermal Growth factor(EGF) is produced at the theca cells and has a mitogen
action on the granulosa cells (paracrine action) inducing their proliferation.

II. Pituitary Hormones

The function of the ovary and consequently the other genital organs and breast are
controlled by hormones produced by the pituitary gland (the hypophysis). However, the
pituitary is not the conductor (myestero) of the endocrine orchestra. The conductor is actually
the hypothalamus; the pituitary has the position of the leader of the orchestra (the first
violinist to the lefthand-side of the conductor). The anterior pituitary (the adeno-hypophysis)
produces, among other hormones three hormones important in reproduction: The follicle
stimulating hormone (FSH), luteinizing hormones (LH) and prolactin. The posterior lobe, the
neurohypophysis produces oxytocin and vasopressin.

1. Gonadotrophins
1.1. Synthesis and secretion:
FSH and LH are collectively called gonadotrophins. FSH acts mainly on the granulosa
cells of the ovarian follicle and on the Sertoli cells in the testis. LH, referred to in the male as

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Physiology of reproduction in women

the interstitial-cell-stimulating hormones (ICSH), acts on the preovulatory follicle and corpus
luteum in the female; and on the Leydig cells in the male.
Both FSH and LH are secreted by the same cell in the anterior pituitary; the basophil
(beta) cells. The acidophil cell produces prolactin. The chromophobe cells represent either
precursors of the chromophil cells or the latter cells after emptying their secretion.
The production of gonadotrophins is controlled by the hypothalamic hormone called
gonadototrophin-releasing hormone (Gn RH), and by the feedback effect of ovarian steroids,
and inhibin and activin.
Gonadotrophins are released from the pituitary in a pulsatile fashion, and this occurs
in response to a pulsatile secretion of the GnRH. Pulsatile secretion is essential for the action
of both GnRH and the gonadotrophins themselves. The pulse is more frequent but smaller in
amplitude during the follicular phase compared to the luteal phase. The LH pulse occurs
every  90 minutes in the early follicular phase and every about 200 minutes during the late
luteal phase. The pulsatile release of these peptide hormones serves to avoid down-regulation
(loss of sensitivity) of membrane receptors of these hormones.
1.2. Structure of gonadotrophins
Both FSH and LH are glycoproteins. They are dimers, each is composed of two
glycosylated polypeptide submits; the - and  submits which are tightly bound together.
FSH, LH, TSH and hCG share a common -chain (-subunit) formed of 92 amino-acids. The
-chain or -submits of these hormones differs from one hormone to the other; this difference
determines the biologic activity and their rate of metabolism. The half-life of FSH is 344
hours, while that of LH is approximately 20 minutes; this means that the latter is much more
rapidly eliminated. This is to be born in mind in the pharmacological action of preparations
that contains comparable amounts of FSH and LH, like the menopausal urine gonadotrophin;
the LH content means less of an effect because of its more rapid metabolism. The common -
subunit of the hormones FSH, LH, TSH and HCG determines cross-reactivity in
immunoassays used for their determination. The assay can be made specific to individual
hormones by utilizing antibodies raised for the individual -subunits, e.g., the -subunit
specific assay for HCG.
1.3. Mechanism of action of gonadotrophins
Gonadotrophins, being large glycopeptides, do not enter cells, but communicate with
target cells by joining with specific receptors on the target cell membrane. This binding
activates an enzyme in the cell membrane called adenylate cyclase. This enters the cytoplasm
and catalyzes the production of cyclic adenosine monophosphate (cyclic AMP) which acts as
a “second messenger”. The message brought to the surface by the genadotruptin is relayed to
cyclic AMP. Cyclic AMP initiates the process of steroidogenesis in target cells. The

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Physiology of reproduction in women

influence of certain paracrine and autocrine substances like inhibin, activin and growth factors
on cyclic AMP modulates the rate of hormone action. If the cell membrane receptors were
flooded by continuous availability of peptide hormone, the receptors would be exhausted or
internalized resulting in loss of responsiveness. This is the physiological basis for the need for
pulsatility of release of Gn RH and other trophic hormones. Continuous pharmacological
availability of the hormone results in what is called down-regulation (or desensitization) of
the trophic effect. This effect is utilized pharmacologically, most evidently in the use of Gn
RH agonists.
1.4. Cyclicity of gonadotrophin and their functions
In addition to pulsatility, there is cyclicity (Figure 1) of production of gonadotrophins
which determines the ovarian cycle. The cyclicity is determined by interplay of secretion of
gonadotrophin and feedback effects of steroid and peptide hormones produced by the ovaries.
This cycle is shown in figure: 1. The cycle actually begins in the later days of the previous
menstrual cycle. The decline of estrogen and progesterone secretion brought about by
regression of corpus luteum results in increased secretion of FSH during the early part of the
follicular phase of the subsequent cycle (including the days of menstruation). This FSH rise
results in recruitment of a crop of primordial ovarian follicules into development, with the
growth of their granulosa cells. There is, as a result, a gradual increase of estrogens secretion
from these cells. FSH is mainly responsible for this estrogen production but with a synergism
from LH. The gradual rise in estradiol, together with the increased production of inhibin,
cause negative feedback on the hypothalamus and pituitary, and consequently causing a
decline in FSH level. These actions are called respectively, the long and short loops of
feedback effects. LH continues to rise slowly during the follicular phase by a positive
feedback effect. The drop in FSH results in regression of most of the recruited follicles i.e.
atresia. However, one of the follicles escapes this depression due to endogenous capacity (of
yet undetermined nature) and continues to grow to the preovulatory follicle. This is the
dominant or leading follicle. This spurt of the growth of this leading follicle will cause a rapid
rise in estrodial secretion during the later part of the follicular phase to produce the
preovulatory estradiol peak. This estradiol peak determines the mid-cycle LH peak through a
positive feedback. The LH peak is attained during the declining limb of the estradiol peak and
is associated with another smaller FSH peak. It is the LH peak that determines ovulation.
After ovulation, estrogen, LH and FSH reach nadirs. During the subsequent luteal phase, LH
and inhibin will rise again to plateaus occurring with the period of the bloom of function of
the corpus luteum. On the other hand, FSH level continues to be low during the luteal phase.
Under the effect of LH the corpus luteum will produce increased amounts of progesterone and
estradiol. However, the corpus luteum is a caducous structure having a self-limited life span;

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Physiology of reproduction in women

after which it starts to regress (unless receiving the humoral maintaining message of HCG
from implanted fertilized ovum). The decline in progesterone estrogen will decide
menstruation and initiate the events of the subsequent cycle. This is a simplified scenario
which is influenced in addition by various apacrine and autocrine influences previously
referred to under ovarian function.

• Events in the luteal-follicular transition: The interface between

ovarian cycles:
1) The demise of the corpus luteum results in nadirs in the levels of E2, P and Inhibin.
2) The withdrawal of E2 and P causes endometrial shedding and menstruation.
3) The decreased inhibin removes the suppression of FSH secretion.
4) The decreased E2 and P allow a rapid increase of GnRH pulsatile secretion.
5) Consequently increased secretion of FSH occurs.
6) The increased FSH induces a new crop of follicular recruitment.

[Link]
2.1. Synthesis and secretion
Prolactin is a polypeptide containing 198 aminoacids, with a molecular weight of
22000. It has a great similarity in the aminoacids sequence to the pituitary human growth
hormone (HGH) and the placental lactogen (PL). This similarity had delayed the development
of a radoimmunoassay for prolactin, but now there is a quite specific assay for prolactin.
Prolactin is synthesized by the lactotrophes of the anterior pituitary (acidophil). Its
secretion does not go in a definite cycle like the gonadotrophins but its level is slightly higher
during the luteal phase than during the follicular phase of the cycle; and there is also a small
prolactin peak coinciding with the midcycle estradiol peak. Prolactin is produced in bursts,
with a definite pulsalility like that of LH. Prolactin secretion is highest during night sleep; the
bursts are higher during this time. There is progressive rise of prolactin during pregnancy.
During lactation the state of hyperprolactinemia is maintained by active breastfeeding; a
reflex arc.
Heterogeneity of prolactin: Discrepancy between measurable level of prolactin and
biological activity has lead to discovery of four distinct forms of prolactin:
1. Little prolactin (MW 22000) is the monomeric hormone that has high bioactivity.
2. Big prolactin (MW 50,000) which is dimeric.
3. Big-Big Prolactin (MW 100,000).
4. Glycosylated prolactin (MW 25000)

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Physiology of reproduction in women

The latter three types have low bioactivity, but are convertible to little prolactin.
However, they equally react in immunoassay. There is a great variability in the relative
concentration of the various types. This explains the occasional existence of measured
hyperprolactinemia in association with normal ovulatory cycle.
2.2. Action
Prolactin plays important reproductive functions in lower animals e.g., determining
seasonal migration of fishes and birds to habitats suitable for laying eggs. In man, its
reproductive function (other than promoting milk secretion) seems to be minimal under
physiological circumstances. However, states of hyperprolactinemia are associated with
suppression of ovarian function. The mechanism of this suppression is not fully understood.
The main function prolactin in man is in the growth of the breast in preparation for
lactation, and the initiation and maintenance of lactation. During pregnancy the population of
lactotrophes in the pituitary markedly increase in number and size. The rise of prolactin
during pregnancy contributes, together with placental estrogens and progesterone to the
completion of the development of the mammary gland. However, prolactin does not initiate
milk secretion during pregnancy because of a direct inhibitory effect of estrogens and
progesterone on the cells of the breast acini.
After delivery of the placenta and withdrawal of its estrogens and progesterone, the
pituitary prolactin can then exert a stimulatory effect on the breast acini; this initiates milk
secretion. Thereafter, lactation is maintained by breastfeeding, the higher the frequency of
breastfeeding, and the more intense the suckling; the higher the prolactin secretion, and the
more the milk secretion. This is mediated by a reflex arc, the afferent limb of which is neural,
initiated at the nipple and areola during suckling. The efferent pathway is the pouring of
prolactin from the anterior pituitary. The relay between the two limbs is in the hypothalamus
and is brought about by diminished sensitivity of the lactotrophes to the specific control of a
prolactin-inhibiting factor (PIF). PIF is most probably the neurotransmitter dopamine.
Maintenance of intense suckling determined by frequent and prolonged breastfeeding
maintains the stimulus for lactation for a long time. Weaning of breastfeeding caused by a
variety of circumstances like long intervals between suckling episodes, particularly during
night; or due to the baby’s sickness; or the introduction of substantial supplementation to
breastfeeding (by giving supplementary feeds including milk formula or solid foods) result in
diminution of milk secretion. A vicious circle will set in resulting in marked diminution of
milk yield and ultimately weaning.
2.3. Prolactin and gonadal function
The maintenance of a state of hyperprolactinemia during breastfeeding is associated
with suppression of pulsatility and cyclicity of gonadotrophin secretion. This results in

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Physiology of reproduction in women

suppression folliculogenesis and ovulation and inadequacy of corpus luteum function (when
ovulation is resumed). This suppression of gonadotriphic function associated with this
physiological hyperprolactinemia is due to inhibition of Gn RH pulse produced by the
hypothalamus. This does not seem to be an effect of prolactin secretion per se, but rather,
there is common denominator for both the suppression of dopamine and Gn RH release or
effects. This can be the result of increased production in the hypothalamus of -endorphins or
other brain opiates.
Breastfeeding women consequently can have prolonged lactational amenorrhea, the
duration of which is the function of breastfeeding intensity. Women tend to rely on this
lactational amenorrhea as a method of spacing of pregnancies i.e contraception. However, its
reliability as a contraceptive is not very sure, particularly if breastfeeding is prolonged and
supplemented. Under the latter circumstances, there is an escape of the hypathomo-pituitary-
ovarian axis from the inhibitory effect of breastfeeding. This escape is associated with both
time and weaning of suckling intensity. The first sign of escape is usually the resumption of
menstruation. However, the early resumed menstrual cycles tend to be irregular and
prolonged and are usually anovulatory. Even when ovulation is resumed, the corpus luteum
function is inadequate, and these effects may prolong lactational infertility for some months
after resumption of menstruation. The longer the duration of breastfeeding, the higher the
chance of ovulation preceding the first menstruation i.e. the higher the chance of pregnancy
occurring during lactational amenorrhea. The probability of this latter occurrence is very low;
less than 2% during the first six months of lactational amenorrhea, the probability gets
progressively higher with prolongation of lactation beyond this time. The less intense nipple
stimulation resulting from incomplete reliance on breast milk in feeding the infant also
increases the chance of resumption of menstruation and ovulation. (see under lactational
amenorrhea method of contraception-LAM).
2.4. Control of prolactin secretion
Among the pituitary hormones, prolactin shares with growth hormone the distinction
of operating without direct feedback controls by signal from peripheral target tissue.
However, prolactin is under direct hypothermic control through the following endocrine and
paracrine mechanisms:
1. Dopamine(DA): DA is secreted by the hypothalamic neurons into the portal circulation
that carries it to the lactotrophes of the pituitary. Dopamine inhibits prolactin secretion.
DA is the principal PIF. There are two types of dopamine receptors on the lactotrophes:
D1 and D2; D2 being more specific to inhibition of prolactin secretion.
2. Gamma-aminobutyric acid (GABA) is produced in the hypothalamus and acts also a PIF
but is much weaker than DA in inhibiting prolactin secretion.

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Physiology of reproduction in women

3. Thyrotrophin Releasing Hormone (TRH) has a stimulatory effect on prolactin secretion.

Under physiological condition this action does not exert a regulatory effect upon prolactin
secretion. However, hypothyroidism is associated with increased production of prolactin
due to the associated increase in the release of TRH by the hypothalamus. The
administration of thyroid hormone to hypothyroid patient suppresses this secondary
increased prolactin secretion.
4. Other neurotransmitter: Serotinin causes prolactin release, while histamine inhabits
prolactin secretion. Cimetidine, a specific histamine receptor-2 (H2) antagonist that
induces increased prolactin secretion.
5. Endogenous opioides: The role of  endorphin and other brain opioids in inhibit DA
action, and increasing prolactin secretion has been demonstrated in animal experiment.
However, the role of endogenous opiates under physiological and pathological condition
in man is not fully confirmed.

Posterior Pituitary
The posterior pituitary is a direct downward prolongation of the hypothalamus hence
the name neurohypophysis. (The anterior pituitary, the adenohypophysis, in contrast, arises
from an upward growth of the pharyngeal epithelium). Separate neurosecretory cells in the
supraoptic and paraventricular nuclei of the hypothalamus produce oxytocin and vasopressin
(also called the antiduretic hormone), the hormones of the posterior pituitary. These two
hormones descend in the axons of these nuclei to end in the posterior pituitary where they are
released into the general circulation. The secretion of these two hormones occurs in bursts.
Oxytocin and vassopressin are very similar in structure and consist of 9 aminoocids.
They have very short half-life of less then one minute, hence the difficulty in their
measurement in the plasma.
Oxytocin stimulates muscular contraction in the uterus and myoepithelial cells around
the breast acini. Maternal plasma oxytocin increases with gestational age; and further
increases during the first and second stage of labor; but declines during the third stage. It is
uncertain whether oxytocin plays a role in the initiation of labor and in the parturition process
itself (see under Obstetrics). Oxytocin level is increased in response to tactile stimuli resulting
from suckling; these are carried by T3 and T4 to the spinal cord and the hypothalamus. The
resulting increase in oxytocin secretion helps to express milk, both from the suckled upon
breast and from the other breast; through stimulating contraction of the myoepithelial cell
which help in evacuating the milk. This humeral response affects the suckled breast upon and
the other one as well leading to secretion of milk from the other breast (let-down effect). This
reflex is also the cause of the uterine contractions accompanying breastfeeding - the “after-

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Physiology of reproduction in women

pains” perceived by the mother during lactation. These contractions may help in evacuating
blood from the puerperal uterus, and its involution. It is noteworthy that this reflex will, after
some limited experience in suckling, become conditioned; the nipples discharge milk upon
seeing the baby or hearing its cry. Opioid peptides in the brain inhibit oxytocin release, and
this may be the mechanism through which stress, fear and anxiety inhibit milk output in
nursing mother.
Oxytocin is also released during coitus, probably by the Ferguson reflex and is
initiated by vaginal and cervical stimulation (also by olfactory, visual or auditory stimuli).
Oxytocin thus released is involved in pelvic muscle contraction during orgasm. In the male,
the release of oxytocin during coitus may contribute to sperm transport during ejaculation.
Vasopressin is a powerful vasoconstrictor and antiduretic hormone. Blood osmolarity
and volume regulate vasopressin release. Diabetes insipidus is a condition of marked diuresis
due to lack of vesopressin action on the tubules of kidney. Vasopressin is having a mild
uterotropic effect while oxytocin, if given in big doses can cause water retention.

III. HYPOTHALAMUS
The hypothalamus is at the base of the brain forming the floor of the third ventricle,
and is located just above the optic chiasma. It is this small part of the brain that conducts most
of the endocrine glands of the body through influencing the function of the pituitary gland.
These effects are expressed through the release of certain neurohormones and
neurotransmitters. The hypothalamic neurons produce a number of releasing hormones for
growth hormone, ACTH, TSH, gonadotrophin, besides the prolactin inhibiting factor (DA).
These neurohormones are secreted from the nerve endings into the portal circulation
connecting the hypothalamus with anterior pituitary i.e. the veins draining the hypothalamus
rebranche again into capillaries that surround the cells of the anterior pituitary. This vascular
arrangement ensures that these neurohormones reach the pituitary immediately after their
release and without being diluted in the general circulation. The posterior pituitary hormones
are synthesized in the hypothalamus.
There is one gonadotrophin-releasing hormone (GnRH) which stimulates the
formation and release of both FSH and LH. It is a decapeptide of a known amino-acid
sequence (which have be synthesized). It has a short half-life of 2 to 4 minutes. It is produced
by the arcuate nucleus of the hypothalamus in pulsatile bursts corresponding to the pulsatile
release of gonadotrophin. The secretion of either of FSH or LH is determined by a modulating
effect of the endocrine environment, specifically the feedback effects of steroid hormones
produced by the gonads. There is also a short-loop feedback determined by direct effect of

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Physiology of reproduction in women

gonadal hormones on the pituitary itself, modulating the secretion of FSH and LH. In
addition, the secretion of the Gn RH is influenced by neurotransmitter like norepinephrin
(stimulatory) and serotonine (inhibitory) and by brain opoids like Endorphin (inhibitory). The
hypothalamic dopamine exercises an inhibitory effect on the secretion of prolactin. The effect
of higher brain centers on the GnRH release is very evident in lower animals, as evidenced by
the effect of light and environmental temperature on reproduction. In man, a modulating
effect is only evident in case of fear, anxiety, pain, and the effect of certain neurotropic drugs
that can disturb the pulsatility and cyclicity of gonadotrophin secretion.

Synthetic GnRH agonists and antagonists:

The short half-life of GnRH is essential for the pulsatile effect, which ensures the
pulsatility of gonadotrophin secretion. The rapid degradation is determined by rapid cleavage
of bonds between the aminoacids. Thousands of GnRH analogues either antagonists (with
opposing effects) or agonists (with similar effects) have been synthesized, mainly by
substitution of aminoacids at the 6 position or replacements at the C-terminal. The agonists
have been more pharmacologically utilized. They are administered by a nasal spray or
injected subcutaneously or intramuscularly or in a sustained-release implants or pillets. They
produce an initial stimulatory effect or “flare effect” on FSH and LH secretion. After 1-3
week they downregulate the gonadotrophic secretion. This effect is produced by loss of
sensitivity of the membrane receptors on the surface of the gonadotropes or their
internalization. Thereafter, prolonged administration ultimately produces a state
hypogonadotrophic and hypogonadal state. This effect is widely utilized in various techniques
of assisted reproduction, in order to abolish the “noise” produced by endogenous
gonadotrophins during the stimulation by exogenous gonadotrophins; thus preventing
untimed ovulation. Suppression of pituitary secretion of gonadotrophin by GnRH agonists is
also utilized in the treatment of endometriosis, uterine myomas, precocious puberty, or the
prevention of menstrual bleeding in special clinical situations e.g., in the treatment of
thrombocytopenic patients
Various tumors contain receptors for GnRH, such as breast, pancreatic, and ovarian
malignancies, and they can be also influenced by this promising modality of treatment.
GnRH antagonists are produced by multiple amino acid substitution. The antagonists
bind to the GnRH receptors and provide competitive inhibition of the naturally produced
GnRH. Thus, they produce an immediate inhibition without an initial flare-effect. Their use
however, have been delayed by undesirable side effects mainly due to histamine-like reaction.
New antagonists are having less of side effects and are now increasingly used in assisted
reproduction approaches. They may be also utilized in contraception in the future.

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Physiology of reproduction in women

Combinations of GnRH antagonist and testosterone hold promise as a male contraceptive

method.

IV. Menstrual (Uterine) Cycle

Menstruation is a function peculiar to man and higher apes. It is the periodic shedding
of endometrium every approximately 28 days associated with bleeding. Clinically, the
menstrual cycle begins with the onset of one menstrual period and ends by the beginning of
the subsequent menstruation. Therefore, the first 3 to 7 day of the menstrual cycle is occupied
by the menstruation which is in effect the consequence of the previous cycle. The process of
repair of the endometrium begins early during menstruation, and the endometrium goes,
thereafter, into proliferation (profilerative phase). Ovulation occurs around the middle of the
cycle, more precisely 14  2 days before the beginning of the subsequent menstruation.
Thereafter, the corpus luteum is formed in the place of the ruptured graafian follicle, and this
corpus produces progesterone and estrodial which result in more of proliferation of the
endometrium, associated with secretory changes (secretory phase). If conception fails to
occur the corpus luteum regresses, an occurrence that precipitates the menstruation.

1. Proliferative Phase
More than two thirds of the endometrium is shed during menstruation and the
endometrial thickness is about 1mm during menstruation. Under the effect of estrogen
produced by the recruited follicles in the ovaries, the endometrial healing starts during the
later days of menstruation. The healing is produced from the basal parts of the glands of the
endometrium, which are left behind after menstrual shedding. The endometrial lining heals
and, to start with, cubical epithelium and the glands are scarce and parallel to the surface of
the endometrium. The proliferation is at first gradual, but attains a rapid phase of growth
during the later days preceding ovulation under the influence of enhanced estrogen secretion
from the dominant preovulatory follicle. It reaches a thickness of 3 to 5 mm just before
ovulation. The glands become perpendicular to the surface and their lining epithelium become
columnar with basal nuclei. Convolution of the glands becomes evident shortly before
ovulation. However, the glands are not exhibiting secretory actively. The stroma cells are
spindle shaped and shows compact arrangement.

2. Secretory Phase
During this phase the growth of the endometrium in thickmness is limited and
continues until it attains a thickness of 5 to 7 mm. However, as a result of growth the glands
in a limited thickness, the glands become longitudinally convoluted, hence they acquire
corkscrew appearance in longitudinal sections, and the lining become crenated (festooned) in

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Physiology of reproduction in women

cross sections. Secretory activity begins by appearance of subnuclear vacuoles that displace
the nucleus to the middle of the cells. Thereafter, the vacuoles become supranuclear
approaching the cellular apex. The apical part of the cells is lost during the discharge of the
secretion into the lumen. Therefore, the luminal edge of the cells appear frayed, hence the
moth-eaten appearance under the high power. The secretion in the cavity of the glands is rich
in glycogen, fructose, and glucose. This uterine “milk” has an important nutritive effect to the
pre implantation, and the early nidated fertilized ovum.
Coinciding with these glandular changes, the stroma become progressively edematous
and infiltrated with leucocytes. The stroma cells imbibe water and their cytoplasm become
more discernible, and assumes a rounded discoid shape, hence the name decidula (disc-like)
cells. These decidua cells are particularly more numerous and compact under the lining
epithelium. This decidual reaction becomes more marked if nidation has occurred due to the
effect of 1) continued increased progesterone, and 2) the mechanical effect in response to
nidation, being more marked near the implanted ovum.
The spiral arterioles in the endometrium (branches of radial arteries) increase in
number and become spiral (Figure 4). Each spiral arteriol seems to be feeding a limited
portion of the endometrium with little anostomosis between them. These spiral arterioles are
hormone responsive and are also influenced by local paracrine influences; being mainly
influenced by locally produced prostaglandins. The basal part of the endometrium is fed from
separate branches of radial arteries. The basal arterioles are not hormone sensitive.
The late luteal endometrium can therefore, be described to have three strata or zones:
1. The compact zone just under the surface epithelium containing the mouths of the
glands surrounded by compact decidua cells.
2. The spongy layer forming most of the thickness of the endometrium. This has a loose
edematous and vascular stroma with patchy leucocytic infiltration, which surround
secretion-laden glands.
3. The thin basal layer, which contains the inactive deeper part of the glands abutting
upon the myometrium (the endometrium has no submucosa). These parts of the
glands are not responsive to hormonal changes and show minimal secretary
transformation. It is from these parts of the gland that regeneration occurs after the
shedding of the two superficial layers during menstruation.

3. Menstruation
In the absence of fertilization and nidation, and the consequent lack of sustaining
effect of chorionic gonadotrophin from the trophoblast, the otherwise fixed life span of the
corpus luteum is completed, and estrogen and progesterone levels drop. The withdrawal of
effect of these two hormones result in three effects:

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Physiology of reproduction in women

1. Modest shrinking of endometrial height (compacting): This will enhance the

coiling of the radial spiral arterioles which induces tissue ischemia and decreases
venous drainage. This is associated with leucocycyte and red blood cell infiltration
and tissue necrosis.
2. Vaso constriction of the spiral blood vessels brings about tissue necrosis. This
vasoconstriction is probably mediated by enhanced local release of prostaglandins
(mainly prostaglandins E2 and F2 alpha) and endothelin-1 which are both increased in
the endometrium during menstruation. However, it is not clear whether the
vasospasm of the endometrial and myometrial blood vessel is the cause or the effect
of menstrual bleeding. It is postulated that without this vaso constriction women
bleed to death during menstruation. Menstrual flow stops as a result of combined
effects of a) vasoconstriction, b) tissue collapse, c) vascular stasis, and d) estrogen
induced healing.
3. Bleeding: The breakdown of the endometrium does not occur simultaneously in all
part of the endometrium, but occur in succession in different microscopic foci of the
endometrium. The bleeding occurs from broken (due to ischemia) arterioles, venules
and capillaries and forms small hematomas in the stroma of the immediate
premenstrual phase.
Menstrual blood does not clot; in fact, it is a lysed clotted blood. This lysis
occurs by a process of fibrinolysis. There is increased formation of tissue
plasminogen activator in the menstruating endometrium, which enhance breaking
down of fibrin. Fibrin degradation products are increased in the general circulation
during menstruation.
The mechanism of menstrual and other forms of endometrial bleeding is far
from being understood and is the subject of intensive research. The effect of the
various prostaglandins, endothelin-1, certain growth factor and angiotensins are
receiving investigation at present time.

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Physiology of reproduction in women

Physiology of Reproduction (Figure 4): Uterine vasculature in the secretory endometrium.

1. Uterine artery; 2. Arcuate artery; 3. Radial artery; 4. Spiral artery; 5. Basal artery; 6.
Compact zone of the endometrium; 7. Spongy layer; 8. Basal layer; 9. Venous lake; 10
myometrium; [Link] venule; [Link] endometrial gland.

V Prostaglandins, Thromboxanes
and Leukotrienes: The Arachidonic acid
Family
Contents
▪ Introduction
▪ Biosynthesis
- Prostaglandin and Thromboxane: Cyclo-oxygenase line
- Leukotrienes: Lipoxygenase line

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Physiology of reproduction in women

- Nomenclature
▪ Prostaglandin synthesis inhibition
▪ Metabolism
- 15-hydroxyprostaglanidin Dehydrogenase.
▪ Physiological roles related to Reproduction
- Prostaglandins
- Thromboxanes and Prostacyclin.
- Leukotrienes
▪ Prostaglandin use in Obstetrics:
- Prostaglandin E2 for cervical ripening
- Misoprostol for cervical ripening and induction of labor.

Introduction
Prostaglandins, thromboxanes and Leukotrienes are 20-carbon polyunsaturated fatty
acids derived from the essential fatty acid arachidonic acid. They have a hair-pin-like
configuration. The biologically active products of arachidonic acid are called eicosanoids.

Physiology of Reproduction (Figure 5): Arachidonic acid.

Eicosanoids act as intracellular mediators influencing important bodily functions.

They are produced in a wide variety of tissues. They are metabolized rapidly and therefore act
in paracrine or autocrine ways that influence human reproduction as well as other bodily
functions.

Biosynthesis
Prostaglandins (PGs), thromboxanes and leukotrienes are synthesized from the
essential fatty acid arachidonic acid. The latter can be directly obtained in the diet (mainly
meat) or by formation from linoleic acid (found in vegetables). The arachidonic acid is not
directly available for metabolism but is stored esterified in the cells. It is liberated from
the storage form by phospholipases, mainly phospholipase A2. The production of eicosanoids

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Physiology of reproduction in women

is substrate-dependant, i.e., the liberation of arachidonic acid from the storage state initiates
the formation of members of arachidonic family
There are two main pathways of enzymatic oxydation of arachidonic acid: one
pathway is catalyzed by the enzyme complex referred to as prostaglandin synthetase or cyclo-
oxygenase (COX), and this leads to the production of prostaglandins and the thromboxanes.
The other pathway is catalyzed by lipooxygenase and this leads to production of
leukotrienes. The tissue specificity determines the particular type of eicosanoid produced
depending on availability of subsequent enzymatic system. For example, the platelets
synthesize a relative abundance of thromboxane A (Th-A), a potent platelet aggregating
substance and vasoconstrictor. Prostaglandin I2 or prostacyclin is produced in considerable
quantities by the arterial wall and is an effective inhibitor, of platelet aggregation and
avasodilator. Prostaglandin E2 (PGE2) and Prostaglandin F2α (PGF2α) are produced by the
prostate gland and the uterus. Leukotrienes are the main eicosanoids that can be produced in
leucocytes, hence the name.

Cyclo-oxygenase (COX): prostaglandin synthesase

Cyclo-oxygenase- catalyzes oxidation of arachidonic acid resulting in production of
prostaglandins and thromboxanes. COX action primarily produces prostaglandin G2 and then
prostaglandin H2. The subsequent formation of prostaglandin is the result of activity of
specific synthases (PGE synthase, PGF synthase, PGI synthase and thromboxane synthase).
There are two COX isoforms: COX-I is a gene product that is expressed under normal
physiologic conditions, and its expression does not change after cellular stimulation. COX II
is an inducible enzyme that appears after stimulation of the cell by extracellular signals (e.g.
inflammation). Recent data have suggested that the prostaglandins generated by intrauterine
tissues during labor result from an expression of the COX-II isoform. COX-II specific
inhibitors have been produced which can be used as effective tocolytic agents without
significant fetal or maternal side effect. COX-II inhibitors are extensively used as non-
steroidal antiinflammatory drugs without inhibiting the COX-I-dependent physiologic
functions like inhibiting gastric acid secretion. Non-specific COX inhibitors have
antiinflammatory effects e.g. aspirin or prufen but have the side effects like enhancing gastric
acid secretion.
Lipoxygenases
Lipoxygenase particularly 5-lipooxygenase (5-LOX) catalyses the first steps of
synthesis of leukotrienes. The production of the various leukotrienes like leukotriene B4, C4,
D4 and E4 depends on availability of product- specific enzymes. Leukotrienes are involved
in leukocyte and esonophil activation, anaphylaxis, other forms of hypersensitivity, mucus

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secretion and smooth muscle proliferation. Leukotrienes can also have uterotonic effects, may
be through regulation of the local production of PGE2. They can also play a role in cervical
ripening (effacement). Certain leukotrienes may be involved in inhibition of thromboxane
synthesis.

Prostaglandin receptors:
A number of prostaglandin receptors have been identified for different prostaglandins. They
have been identified in the myometrium. PGF receptors are also expressed in the luteal cells
of corpus luteum.
Nomenclature
These substances were first extracted from the prostatic gland, hence the name.
Structurally all prostaglandins (PG) have a 'hairpin' configuration and are composed of a
cyclopentanone nucleus with two side chains.
Each group of prostaglandins is allocated a letter (A, B, C, D, E;, F, G, H or I) which
denotes particular changes in the functional groups of the cyclopentanone ring. The degree of
unsaturation of the side chains is indicated by the subscript numeral after the letter, thus,
PGE1, PGE2, and PGE3 have one, two, and three double bonds respectively. A description of
the stereochemistry at the position 9 in the cyclopentanone ring is denoted by the subscript 
or , thus PGF2 has the orientation of the 9-hydroxyl moity oriented below the plane of the
ring.
An almost similar nomenclature is used in description of thromboxanes and
leukotrienes.

Metabolism
A characteristic feature of the arachidonic family is the transient nature of their existence
within the body. This is why they principally act locally in a paracrine or autocrine fashion.
Prostaglandins are highly unstable in the mere presence of water.
The principal step in catabolism of prostaglandins is oxidation of the 15-hydroxyl
group, a reaction catalyzed by 15-hydroxy prostaglandin dehydrogenase. This enzyme is
widely available in different tissues. The 15-keto derivatives are converted to 13-14 dihydro-
15-keto compounds, which are oxidized to a variety of products that are excreted in urine.
Drugs that inhibit 15-hydroxy PG dehydrogenase (e.g. xylocaine and furosemide) enhance the
prostaglandin actions.

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Prostaglandin Inhibition
1. Corticosteroids are strong inhibitors of prostaglandins. The mechanism of this
inhibition is mainly through inducing the synthesis of proteins called lipocortins,
which blocks the action of phospholipase, thus limiting the availability of arachidonic
acid. This results in inhibition of both the cyclo-oxygenase and lipooxygenase
pathways, and this is how corticosteroids are very effective anti-inflammatory agents
and anti-hypersensitivity agents, especially in the treatment of bronchial asthma.
2. Aspirin is an irreversible inhibitor, selectively acetylating the cyclo-oxygenases,
which are, involved in prostaglandin and thromboxane A synthesis, hence the anti-
inflammatory, antipyretic effect and the reduction of platelet aggregation.
3. The nonsteroidal anti-inflammatory drugs such as indomethacin and naproxen are
reversible agents, forming a reversible bond with the active site in COX.

Both aspirin and the other nonsteroidal anti-inflammatory drugs are more potent
inhibitors of COX-I than COX-II. Other preparations like naproxen inhibit both enzymes
equally. The side effects associated with different anti-inflammatory agents are a reflection of
the degree of selectivity towards the two isoforms of the enzyme COX. Inhibition of COX-I,
the constitutive form, is associated with significant side effects, and inhibition of COX-II, the
inducible form, being the therapeutic. Part of the anti-inflammatory activity of corticosteroids
is due to inhibition of COX-I formation. The well known gastric ulceration effect of anti-
inflammatory drugs, including corticosteroids, is due to the facts that PGE2 protects the
gastric mucosa by inhibiting gastric secretion, and COX-I is the predominant enzyme in
gastric mucosa. COX-II-specific anti-inflammatory agents have been lately introduced to
practice; they have little gastric effect.

Physiologic roles of Prostaglandins

Significant findings
1. Since early reports that chronic indomethacin treatment during follicular phase
blocks ovulation, the mechanism for this has not been clear. GnRH release may be
regulated directly by intraneuronal PGE2 production. The estrogen stimulation of LH
secretion may be mediated through PGE2.
2. Prostaglandin is important for the process of ovulation in a number of species.
Elevated levels of prostaglandins in follicular fluid of preovulatory follicles have
been demonstrated. Prostaglandin may be a mediator for increasing local production

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Physiology of reproduction in women

of plasminagen activator in follicular cells. This releases plasmin, which induces

digestion of follicular wall. Prostaglandins may be involved in contractions of
follicular wall that result in follicular rupture process.
3. In the human, evidence is available that PGF2 is involved in luteolysis.
4. Prostaglandins have been implicated as tissue mediators in the processes of regulation
of ovum transport in fallopian tubes. In the intact human fallopian tube, PGE2
inhibits, and PGF2 stimulates tubal motility.
5. The nonpregnant human myometrium is generally stimulated by both PGE2 and
PGF2 . The effect is modified by the time in the cycle and by the hormonal milieu.
6. Primary (spasmodic) dysmenorrhea is probably caused by increased prostaglandin
production in the endometrium. PGE2 and PGF2 are increased in secretory as
opposed to proliferative endometrium. The decline of progesterone levels in late
luteal phase triggers phospholipase that releases arachidonic acid and activates the
cycle-oxygenase pathway. PGE2 and PGF2 are released because of lysis of
endometrial cell and cause myometrial contraction. The drugs of choice for treating
dysmenorrhea are nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit
progalandin synthesis.
7. Prostaglandins play an important role in human parturition. Although having not been
definitely demonstrated, increased estrogen levels, as well as a local decrease in
progestrone production are thought to increase prostaglandin production.

Evidence for a role of prostaglandins in parturition:

1. Prostaglandin levels (PGE2 and PGF2 ) in maternal blood and amniotic fluid
increase in association with labor.
2. Arachidonic acid levels in amniotic fluid also rise in labor.
3. Patients taking high dose of aspirin tend to go in post-datism.
4. Stimuli known to cause the release of prostaglandins (cervical manipulation,
stripping of membranes, and rupture of membranes) induce augment labor
contractions.
5. The process of cervical ripening is mediated by prostaglandins.
6. Prostaglandins and their analogues induce labor.
7. Prostaglandin inhibitors can inhibit premature uterine contractions.
With the onset of labor, there is increased production of prostaglandins,
particularly PGE2 in the fetal membranes as a result of activation of cyclo-
oxygenase pathway, particularly the COX-II activity. This activation is probably

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triggered by placental corticotropin-releasing hormone (CRH) produced at the

placenta (See under Obstetrics).
Prostaglandins induce contractions of the myometrial cells by increasing
intracellular calcium ions. The intracellular calcium concentration increases as a
result of inducing calcium influx through calcium channels and the release of
calcium from intracellular stores in the endoplasmic reticulum. Both mechanisms
are stimulated by prostaglandins. The intracellular calcium acts through activation
of an enzyme myosin light-chain kinasee (MLCK). The activity of this enzyme is
central to the process of muscle contraction, and most of the stimulatory or
inhibitory effects of drugs on uterine contraction occur through pathways that lead
to this enzyme. Uterotonic drugs act by increasing intracellular calcium
concentration that activates MLCK.
8. Prostaglandins enhance the process of ripening of the cervix uteri. This is a
process of softening and loss of resistance of the cervix. The cervical changes are
in response to estrogen / progesterone ratio and the local release of prostaglandin.
The mechanism of this action of prostaglandin is not yet clear, but PGE2 and the
PGE1 synthetic analogue, (misoprastol) have been found to be very effective in
inducing cervical ripening.

The predominant effect of prostaglandins on fetal cardiovascular system is to maintain

the ductus arteriosus in a relaxed dilated form. This prostaglandin effect is most marked in
late pregnancy beyond the 30th week. The importance of the ductus arteriosus to the fetus is
that about 60% of cardiac output flows through this connection between the pulmonary artery
and descending aorta. The use of prostaglandin inhibitors to inhibit premature labor can
induce narrowness of closure of the ductus arteriosus resulting in fetal pulmonary
hypertension and s right-sided heart failure. The effect is dose dependent and is rare if
prostaglandin inhibitors are given before the 30th week, thus these inhibitors are
contraindicated during the last trimester

Physiologic roles of Thromboxanes and Prostacyclins

Thromboxanes and prostacyclins can be viewed as opponent, each having powerful
biologic activity that counters or balances the other. Both are produced through the COX
pathway of arachidonic acid oxidation. Thromboxane A2 (TXA2) is a powerful
vasocinstrictor and a potent platelet aggregating substance, which is predominately,
synthesized in platelet, lungs and spleen. It has a very brief half-life time, a matter of seconds.
The action of TXA2 ensures control of blood leakage from injured blood vessels through

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vasoconstriction and clumping the platelets together and to the injury site, ultimately plugging
the defect.
On the other hand, prostacyclin (PGI2) is a potent vasodilator and inhibitor of platelet
aggregation. Prostacyclin is abundantly produced in the endothelium of blood vessels, the
heart and lungs and gastric mucosa. It has a short half-life of few minutes and ensures
prevention of platelets from clogging in the circulation and maintains the flow. A fine balance
is maintained between the actions of thromboxane and protacyclin in health and disease.
When endothelium is damaged, platelets gather, beginning the process of thrombus
formation. Prostacyclin is simultaneously released to check the process of vascular occlusion.
It has been suggested that preeclampsia may, in part, reflect an imbalance between
placental production of TXA2 and prostacyclin.
Thromboxane-prostacyclin imbalance may be involved in the predisposition to the
formation atherosclerotic plaques in certain blood vessels e.g. coronary and cerebral arteries.
LDL-cholesterol inhibits and HDL cholesterol stimulates prostacyclin production. Smokers
who use oral contraception have increased platelet aggregation and inhibition of prostacyclin
formation.

Physiologic roles of leukotrienes

Leukotrienes are potent lipid mediators generated from archidonic acid through 5-
lipoxygenase pathways. The physiologic roles of leukotrienes are less defined than those of
prostaglandins.
Leukotrienes display a number of biologic activities, which may contribute to airway
obstruction (bronchial asthma) including plasma exudation, anaphylaxis, allergy processes,
mucous secretion, esenophil recruitment, smooth muscle proliferation and cardiodepression.
Leukotrienes in fetal membranes and placenta increase during labor and in preterm
labor. Leukotrienes may be involved in the pathophysiology of pre-eclampsia and
antiphospholipid antibodies syndrome. They maybe involved in dysmenorrhea and
endometriosis. Anti-leukotriene drugs inhibit the formation or action of leukotrienes.

Therapeutic uses of prostaglandins in obstetrics

1. Prostaglandin E2 for preinduction cervical ripening

PGE2 is an effective agent for cervical ripening and are usually used in the
form of vaginal pessaries (controlled release) or intravaginal gel. The dose is
repeated after 6 hours. Labor may start under the effect of PGE2 treatment or may
need to be induced by oxytocin drip.

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Physiology of reproduction in women

The response to prostaglandins is variable in patients with unfavorable

cervices who begin labour during cervical ripening treatment. Good responders
tend to have 1) greater gestational ages, 2) more baseline uterine activity, 3) more
initial uterine activity in response to PGE2, 4) and lesser cesarean delivery rate
than those patients who do not begin labor during cervical ripening. However,
PGE2 should not be continued or administered when the patient is in active labor
because it may lead to hyperstimulation.

2. Misoprostol for cervical ripening and labor induction

Misoprostol, a synthetic prostaglandin El (PGE1) analogue, is a gastric
cytoprotective agent that has been marketed in different parts of the world,
including the USA for prevention of gastric ulcer. Studies performed in different
countries demonstrated that oral and vaginal administration of misopristol causes
uterine contraction in early pregnancy. It has been used as an adjuvant to RU486
(Mifepriston) for induction of early pregnancy abortion. Subsequent studies in
different parts of the world showed vaginal misopristol as effective for induction
of first-trimester and second-trimester abortion.
A number of published controlled trials have shown that misoprostol is an
effective method for cervical ripening and labor induction at term. The use of
misopristol vaginally results in reduction in cesarean section rate, shorter interval
to vaginal delivery, and a greater percentage of patients delivered within 24 hours.
No evidence so far, has documented an increase in perinatal mortality and
morbidity. The size of the experience with misopristol for induction of labor is not
big enough to exclude the occurrence of rare maternal morbidities like ruptured
uterus. It has to be remembered that misoprostol has never been registered for use
for its uterotropic effects; use for this indication is done under the obstetrician own
responsibility.
The usual dose of misopristol is 25 to 50 g vaginally; the dose is repeated 6
hourly until labor starts and up to a maximum of 200 g. No further dose is given
after beginning of labor contraction. After establishment of labor, giving further
augmentation by pitocin drip should be done with care to avoid excessive
stimulation. Use of misopristol to induce labor for patients with previous cesarean
delivery is not recommended until now.

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VI. Assays of Reproductive

Hormones
This section is a short review of the methodology of hormone assays which serves to
introduce the clinician to the main techniques used for assay hormone in urine, blood and
other body fluids. It can also introduce clinicians to the System International (SI) of units, and
gives the range of normal values of various reproductive hormones.
Biological assays: These were used for quite long time for the study of hormone
levels. Bioassays measure the dose response of certain organs and tissue to hormones in
laboratory animal. An important example is the biological pregnancy tests which were done
on a variety of animals, e.g., rabbit and frog. These assays are qualitative, and at the best
semiquantitative. They are relatively imprecise, insensitive, time consuming, and expensive
and require big volume of biological sample, which is not practical in case of blood assay.
They are not used now. However, certain bioassays still have a place in characterizing the
biological activity of different form of hormones that are not equally active. An example of
this situation is the assay of the family of heterogeneous prolactin molecules; the small, big
and big-big prolactin. They can be carried out on certain cell-lines in tissue cultures.
Chemical assays: These were used for a long time for measurement of the metabolites
of steroid hormones secreted in 24 hour urine specimen e.g., estrogen glucourinates,
pregnandiol, and 17 keto-(oxo) steroids. The endpoints are usually grades of color reaction or
spectrum absorption patterns as measured by colorimetery, spectrophotometery or gas
chromatography. They have been mostly replaced by measurement of the hormones
themselves in small samples of biological fluids by immunoassays.

Competitive Protein binding assays and Immunoassays

These assays ensured sensitivity, precision, and specificity, and allowed the use of a
small sample size (usually a fraction of a milliliter) in the measurement of hormones in blood
and other biological fluids. Competitive protein binding analysis depended first on selective
binding of the hormone to a natural specific protein. For example, the transcortin was used to
measure progesterone and costisol. However, these binders are now replaced by more specific
antibodies. The advance started by raising antibodies for protein hormones like the trophic
hormones e.g. gonadotrophins. These hormones are species-specific and if injected in another
animal, like sheep or rabbit will elicit the production of specific antibodies. The serum of
these animals (the antiserum) can be used in the laboratory to pick up and measure the
concentration of the hormones in blood of man. The steroid hormones are not species-
specific, but can be rendered like that by binding them to a certain human proteins, like

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Physiology of reproduction in women

albumin. The steroid coupled to the protein can then elicit the production of an antiserum in
animals which is specific to the individual steroid.
The immunological assays were first utilized in radioimmunoassays.
1. Radioimmunoassay (RIA)
The principles of radioimmunoassay depend upon competition of the hormone, which
is being assayed in the sample with another form of the same hormone that is tagged by a
radioactive radical upon a limited amount of antibody molecules. Either tritium or Iodine
125 are used for tagging. Chemically and immunologically the two forms of the hormone are
the same as regard their binding affinity to the antibody molecules, i.e., compete equally on
the binding sites. The amount of the tagged hormone bound to the antibody will be inversely
proportionate to the concentration of the hormone in the unknown sample. After completion
of the reaction the hormone bound to the antibody will be separated from the free form by a
variety of methods depending upon certain physical or biochemical characteristics like
weight, i.e., by centrifugation. The amount of radioactivity in the bound fraction, or in the free
fraction, is measured on special radioactivity counters; thus radioactivity in either fraction is
respectively negatively or positively proportionate to the hormone concentration in the
unknown sample. The assay run comprises a number of unknown samples (20 - 30) together
with a number of gradients of known amounts (masses) of the hormone. The results produced
by the known samples are used to construct a standard calibration curve upon which the
masses of the hormone in the unknown samples can be measured according to the amount of
radioactivity in the their bound, or free moieties.
This methodology was a breakthrough in the history of medicine, since it allowed
measuring substances like hormones, toxins, or drugs present in minute concentration in
blood. These are measurable in nanogram, picogram, or femtogram amounts (1/109 , 1/1012 or
1/1015 of the gramme respectively) per one millitre of the body fluid sample. The assays were
made to be, not only sensitive, but also accurate (producing reproducible results); and specific
to the measured hormones (i.e values are not increased by cross-reacting similar molecules).
The events in the menstrual cycle could then be characterized and many pathological
conditions could be diagnosed, e.g hyperprolactinemia, anovulation, ... etc.
2. ELISA technique
In spite of the risk being minimal and avoidable, there has been apprehension about
using radioactive isotopes on the health of technicians working in RIA labs. In order to avoid
this, and reduce the cost of the radioactivity counters, tagging of the hormones in
immunoassay by radioactive isotopes can be replaced by an enzyme tag e.g. horseradish
peroxides, that produce a certain color end point when mixed with a suitable substrate. The

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Physiology of reproduction in women

color changes are read on a simple colorimeter. This constitutes enzyme-immunoassay, which
has essentially the same steps as RIA.
ELISA stands for enzyme-linked immunosorbent assay. This is also known as the
sandwiched technique because another nonspecific second antibody (specific to the antibody
molecule) that is used to separate the bound fraction i.e. the hormone is sandwiched between
the specific binder protein and a nonspecific “separation” protein. This ensures the immediate
separation of bound from the free forms. ELISA and related assays has not completely
replaced RIA but are widely used to measure many biological substances like hormones,
drugs and immunoglobulins.
3. Qualitative tests
These depend upon set end-point giving a positive or negative test. Examples:
Agglutination inhibition test for diagnosis of pregnancy. Addition of urine containing HCG to
antiserum consumes the antibodies and prevents agglutination of latix particles or sheep
RBCs coated with HCG. A do-it-yourself kit is also available to detect the midcycle LH peak.
The test is set to diagnose the high LH level characteristic for the mid-cycle peak of LH. This
latter test needs to be repeated during the late follicular phase in order to "sense" the peak.
4. Monoclonal Antibodies:
Antibodies produced for a certain hormones eg. HCG are a heterogeneous population
of antibodies (polyclonal). By utilization of molecular biology techniques a process of
selection of the antibodies are selectively bind to specific beta subunit are generated. These
will not show a significant cross-reactivity in presence of hormones like FSH, LH, and TSH,
which share with HCG the alpha subunit. Therefore, a highly specific antibody is produced.
The gene coding the specific antibody protein is replicated by recombinant DNA technology
in a bacterial host (see under Genetics). The pure antibody (monoclonal) genes will produce a
specific antibody that is used for binding specifically to the HCG to the exclusion of other
hormones sharing the alpha subunit.
The International System of Units
The system international of units (SI units) has been adopted throughout the world in
all areas of science and industry. In Medicine, the major change is expression of
concentration of biological molecules as moles per liter (or its subunits) instead of the
conventional mass per volume (milligram per deciliter). Because we are in the midst of the
change, the following table gives the conversion factor. To convert from the conventional to
SI units multiply by the conversion factor, to convert from SI units to conventional units
divide by the conversion factor.

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Physiology of reproduction in women

Table 1:Approximate Biochemical Reference Range of Various

Hormones (and Conversion Factor):

Hormone conv. Values Values by SI Units

factor
Prolactin Male (24. 4) Male Up to 350 u/liter
Female Up to 425 u/liter

FSH (1. 0) Male 2 - 9 IU/liter

Female Follicular phase <10 IU/liter
Female Micycle phase up to 20 IU/liter
Female Luteal phase 2 - 10 IU/liter

LH (1. 0) Male 1.5-11 IU/liter

Female Follicular phase 1.5- IU/liter
Mid-cycle phase up to 60 IU/liter
Luteal phase 1.5-6 IU/liter

Estradiol (3. 67) Male 50-170 pmol/ ml

Female Follicular phase 110-180 pmol/ml
Mid-cycle phase 550-1650 pmol/ml
Luteal phase 550-850 pmol/ml
Postmenopaual 70-220 pmol/ml
Children 40-90 pmol /ml

Progesterone (3. 18) Follicular < 9 nmol/ml

Luteal phase 15-70 nmol/ml

Testosterone (0. 0347) Male 10-30 nmol/ml

Female 0.3-0.6 nmol/ml

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Physiology of reproduction in women

Androstanedione (0. 0349) Male 2-10 nmol/ml

Female 2-10 nmol/ml

DHAS (0.0027) Female 2.2-9.5u mol/Liter

TSH (1.0) up to 8 mU/litre

T3 (0.0154) 1.1-3.2 nmol/litre

(triiodothyronine)
T4 (free thyroxin) (0-1.29) 10-30 nmol/litre

17-oxosteroids (in 24 hour urine) Neonate up to 7 umol

up to 1 year up to 2 umol
1 - 5 year up to 6 u mol
6 - 10 year up to 10 umol
11 - 16 year up to 17 umol
male adult up to 30-80 umol
Female adult 15-60 umol

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Clinical features of the normal menstrual cycle

Chapter 3
CLINICAL FEATURES OF THE
NORMAL MENSTRUAL CYCLE
Contents
• Puberty, menarche and adolescence
• Precocious Puberty and delayed puberty
• Normal menstruation
• Ovulation

Important Figures Related to Normal Menstrual Function

Mean Range in Variability
different individual in the same individual
Age at menarche 12. 5 year 10 - 16 year
Length of menstrual cycle 28 days 21-35 days ± 3 days
Duration of menstrual period 3 - 5 days 2 - 7 day ± 1 day
Volume of menstrual blood 35 - 45 ml 5 to 80 mL/month
Age at menopause 51 years 40-55 years
Date of ovulation 14± 2 days before subsequent menstruation.

Puberty
- Definitions.
- Stages of puberty.
- Endocrine determinants of puberty.
- Management of puberty.
- Adolescence.
- Management of Adolescence.
- Precocious Puberty.
Causes and types.
Diagnosis.
Management.
- Delayed Puberty
Causes.
Management.

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Clinical features of the normal menstrual cycle

Menarche / Puberty / Adolescence

Menarche is an event in puberty; and puberty is part of adolescence.

• Menarche is the beginning of the menstrual function. It occurs between the age of
10 and 16 year with an average of 12.5 years. There has been a trend to earlier age
at menarche in Western countries over years from an average of 13.5 years to the
present figures over the last 100 years. This may represent an effect of improved
nourishment. There is a familial and ethnic effect. Delay in the age of menarche
beyond 16 year is followed by a chance of subsequent fertile reproductive life in
only one in 100 instances. The first menstruations are usually prolonged or brief
and the early cycles can be longer or shorter than usual, and usually represent
anovulatory menstruations. These pubertal menstrual irregularities can continue up
to the age of 18 years. These irregularities can be a cause of medical consultation
and usually does not need more than reassurance.
• Puberty is the accusation of the ability of capacity of procreation, and is associated with
certain characteristic changes that are sex-specific. It is a gradual process, which starts before
menarche and continues for the few years after it. Pubertal changes go through almost
defined stages. These are:
1. Beginning of roundness and plumpness of the trunk and limbs, usually evident in girls
after the age of two and make them look different from boys.
2. Thelarche: The first change is a prominent nipple followed by formation of conical breast
buds. These become apparent by a median age of 9.8 years.
3. Appearance of pubic hair; these appear earlier than axillary hair. This is frequently called
adrenarche, because such changes are caused by activation of the adrenal cortex.
Although the sequence may be reversed, adrenarche usually appears after the breast bud
(median 10.5 years). The activation of adrenal cortex is evidenced by increased
production of DHEA, DHEA-S and androstendione starting from age of 7 years.
4. Premenarchal growth spurt (during the year preceding menarche). This is an effect of
growth hormone and the ovarian insulin-like growth factor-I (IGF-I) which are determined
by the beginning of secretion of ovarian estrogens in small amounts.
5. Menarche is a late event in puberty (median age 12.8 years), occurring after the peak of
growth has passed.

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Clinical features of the normal menstrual cycle

6. Roundness and further growth of the breasts (Figure 1) which will have a rounded lower
margin. The area around the nipple is at first higher than the counter of the breast, then it
gets to the level of the rest of the breast counter when the development of the organ is
almost complete (Tanner staging) (Figure 1). This is usually associated with completion
of acquisition of feminine contour resulting from deposition of fat in certain areas of body.
This includes enlargement and coapitation of labia majora, which will hind behind other
internal structures of the vulva.
7. Menarche is closely followed by slowing of gain of height due to closure of the epiphysis
of long bones, which is determined by the increased production of ovarian estrogens.
8. Acquisition of adult-type of pubic hair with the characteristic female escutcheon.

Clinical features of normal menstrual cycle; (Figure 1): Tanner stages for breast development
around the time of puberty.

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Clinical features of the normal menstrual cycle

Endocrine Determinants of Puberty: (Physiology of Puberty)

The hyothalamo-pituitary ovarian axis remains quiescent during the first decade of life.
The pituitary and ovaries, are capable of responding, but their quiescence is determined by
absence of hypothalamic stimulation. This quiescence is caused by heightened sensitivity of the
hypothalamic nuclei to the negative feedback of small amount of estrogens produced by the
ovaries in children. This enhanced sensitivity of the hypothalamus is called the gonadostat. As a
part of brain maturation there is a decreased sensitivity of this gonodostat mechanism resulting in
beginning of the pulsatile release of Gn RH. This stimulates the production of the gonadotrophin
and ovarian functions( the Gonadarche). The secretion of FSH is increased before LH. The
secretion of the latter is first shown as a nocturnal increase; the latter occurrence is an indication
of approach of menarche. In the early phases of function of pituitary-ovarian axis the LH pulse is
irregular and this explains the postmenarchal irregularities in menstruation and higher frequency
of anovulatory cycles. The decline of the gonadostat is attended with increased activity of growth
hormone, IGF-I, and adrenal activity.
Sequence of endocrine events around puberty
1. All the components of the endocrine axis governing ovarian function are existing and
capable of functioning in infancy. But the axis is kept inhibited by heightened sensitivity of
the hypothalamas to small amount of ovarian estradiol. This gonadostat effect wans off
around the age of 9-10 years.
2. Moderate rise of FSH and LH-occurs. Beginning of LH pulse during sleep indicates
approach of menarche.
3. Low to moderate increase estradiol produces breast development, and cause the female fat
distribution. Low levels of estradiol stimulate growth hormone, which in turn stimulate the
production of ovarian IGF-I which are both responsible for prepubertal spurt of high.
4. Adrenal androgens are increased as a result of brain maturation process independent of
gonadarche.
5. Early after menarche the LH pulse is irregular and this results in irregular menstrual
function, which is usually anovulatory. Later the pulse become regular and determines a
positive feedback that precipitates ovulation. Acquiring adult levels of estrogens determine
closure of epiphyses of long bones, resulting in stoppage of gain in height.
Management of Puberty
This is a duty of the parent and school and ideally comprises the following:

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Clinical features of the normal menstrual cycle

1. Psychological preparation of the girl will ensure that she is not taken by surprise by the
beginning of the menstruation and other changes. This is mainly the role of the mother.
Frequently monthly mucoid discharge and lower abdominal cramps precede the menarche.
This introduction of the girl needs the emphasis of the normality, and provision help and
advice on how she will contain the menstrual flow. The girl should be encouraged not to
abstain from daily functions (other than those religiously determined), e.g. socializing, sport
activity and bathing.
2. The attending symptoms of may need reassurance from the consulted physician.
3. Menstrual irregularities are common in postmenarchal years and usually need nothing but
reassurance.

Adolescence
Adolescence is the transition from the carefree childhood to adulthood. It varies in
duration, but usually occurs during the teen-ages (hence the term teenagers); but may extend
beyond that in certain individuals. It comprises a number of changes related to psychological and
mental adaptation to pubertal changes and to acquiring reproductive functions. The changes are
tremendous and are likely to grow wrong if not correctly guided by the parents and the
community.

Management
1. Proper observation from the parents and school. This should take in consideration a
natural tendency for independence and heightened reactivity characteristic for this age. What
is needed is wise guidance rather than restrictions. The role of the parents is important.
2. Knowledge about reproductive health. This should comprise information about the certain
components of reproduction in the female: menstruation, sexual relation, childbearing and
rearing of the children. (The right dose in the right time is needed). Also needed is truth and
correct answer to querries. The role of school curricula is complemented by parent care and
information obtained from public media. If the correct information is not obtained from
qualified and well-informed sources, it can be got from less optimal source like through
chatting between peers.
3. Attention to physical activity to enhance fitness by ensuring physical exercise. Adequate
and balanced food is needed. This is the decade in the woman which the maximal bone

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Clinical features of the normal menstrual cycle

density is achieved. There can be a tendency for excessive gain in weight during this period.
The girl is to be advised to observe their weight.
4. In our community girls can be put to marriage in this stage. They may not be yet
psychologically or physically fit for the various functions of reproduction. They may sustain
injury during first intercourse. Their fertility may not be fully developed. They are more
likely to develop pregnancy complications like hypertensive toxemia and may have
obstructed labor due to small pelvis. The teenager mother may be still unprepared to care
about infants and children. Pregnancy outside marriage-bond is a problem of teenagers that
results in calamities, one of them is criminal abortion which can fully destroy the
reproductive career.

Precocious Puberty
Precocious Puberty is defined as the onset of the function of menstruation, which is usually
associated with pubertal changes, before the age of ten (or of eight in the opinion of some
authorities). The precocious puberty can occur as early as the age of two years. The girl is
usually shorter than normal due to premature closure of epiphysis (i.e. precocious bone age).
Intellectual and psychological development is however commensurate with chronological age.

Causes
1. Constitutional: About 90% of cases are not showing any etiology. They represent a
premature removal of the "gonadostat" and a premature maturation of the sexual
differentiation of the hypothalamus, and beginning of pusatile secretion of GnRH.
Constitutional precocity may be familial but is not essentially so. The pubertal changes
develop in the usual order. The diagnosis of constitutional precocity depends upon exclusion
of organic causes. However, in some case the causes can become evident upon repetition of
search in later life.
2. CNS problems leading to precocious puberty include :
a. Abnormal skull development due to rickets.
b. Brain tumors like hamartoma. Hamartoma is a hyperplastic congenital malformation in
the floor of the third ventricle. It is usually small lesion and is detectable only with
sensitive imaging system like magnetic resonance imaging. Other tumors include
cranipharyngeoma, gliomas and pineal body tumors.
c. Meningitis and/or encephalitis.

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Clinical features of the normal menstrual cycle

d. Fracture base of the skull. These last two lesion cause irritation and cellular reaction in
the area of the floor of the third ventricle.
3. Ectopic gonadotrophin production by rare tumors as ovarian choriocarcinoma and
dysgerminona.
4. Long-standing hypothyroidism can rarely produce precocious puberty. In addition to
short stature there can be galactorrhea, hyperprolactinemia and enlargement of the pituitary.
The usual puberty developments occur.
5. Functioning ovarian tumors like granulosa/theca cell tumors. Menstruation in these
cases tends to be irregular and heavy. A pelvic mass can be palpable or demonstrated by
USG.
6. Drugs containing estrogens e.g. accidental intake of the COCs of the mother.
7. Albreight's syndrome (polyostotic fibrous dysphasia). This is account for 5% of female
precocious puberty. The syndrome has three features 1: multiple minimal-trauma fractures,
which are caused by presence of fibrous foci in long bones. 2. Patchy pigmentations of the
skin with yellowish brown patches (café au lait spots). 3. Precocious puberty. In the past it
was presumed that the hypothalamus and pituitary are disturbed by sclerotic overgrowths at
the base of the skull. However, recently, it has become known that the precocity in this
syndrome results from early autonomous production of estrogen by the ovaries. This has
been suggested by the endocrine profile of these patients. A FSH and LH level are low,
respond poorly to GnRH stimulation, and there is absence of nocturnal LH pulse (like that
occurring in natural puberty). The defect is in the gonadal cell response to normal low
gonadotrophin. This explains the poor response to GnRH analogues in these cases (see later).
8. A rare cause is GnRH independent gonadal secretion of estrogen by crops of benign
follicular or luteal cysts. The cysts can be detected by USG, and enlarge and involute
irregularly so that signs of sexual precocity and vaginal bleeding remit and exacerbate.
9. Adrenal cortical tumors : The precocity in these cases can be isosexual but is usually
heterosexual, that is the female show precocious virilism. i.e. this represent a late onset
congenital adrenal hyperplasia (see under Intersexuality).
10. Androgenic tumors of the ovaries. These are very rare, and the precocity is heterosexual.

Diagnosis of precocious puberty

1. Rule out neoplasm of the ovary, brain, and adrenal by various diagnostic imaginings.
(USG, CT scan, and MRI).

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Clinical features of the normal menstrual cycle

2. Observe the velocity of change. If the condition appears to have stabilized there will be
no need for treatment.
3. Exclude hypothyroidism.
4. FSH, LH and estrogen assays (Increased in idiopathic and cerebral causes, but decreased
in gonadal, and adrenal cases, and in Albright's syndrome).
5. DHEA-S if there are heterosexual changes.
6. Thyroid function tests.
7. GnRH challenge test. A pubertal response is detected in idiopathic and cerebral
precocious puberty.

Management
1. Special parentral care for psychological support and protection is highly needed.
2. Arrest further maturation until the normal pubertal age: This can now be achieved by
the use of Gn RH analogues or agonists. These can be administered daily as a nasal spray or
as subcutaneous injections or depot subcutaneous depot injection given every 6 to 8 weeks
(see before). After an initial short-term "flare" stimulation of gonadotrophin release, down
regulation or desensitization will follow, resulting in profound reduction of gonadotrophin
and estrogen secretion. This will suppress ovarian function and allow some gain in height.
The dose can be monitored by measuring serum estradiol, this needs to be maintained below
10 pg/ml. Treatment is maintained until the epiphyses are closed or the chronologic age is
reached.
3. Surgical treatment of causing tumors likes localized brain tumors and ovarian tumor.

DELAYED MENARCHE
This delay of onset of menstruation after the age of 16 year. It has the same cause and
management as primary amenorrhea (see later).

OVULATION
Clinical features and assessment will be dealt with under infertility.

MENSTRUATION
During the active reproductive period menstruation occur every about 28 days. Each
woman has her own rhythm. Variation in the length of the menstrual cycle between women can

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Clinical features of the normal menstrual cycle

be from 3 to 5 weeks. Within the same woman month-to month variability of 3 days is normal.
In fact the normal cycle is not punctually regular by day. The duration of the menstruation is
most often 3 to 5 days with a possible within-the-same subject variability of one day.

Menstrual molimina
The majority of women experience some minor bodily, physical and nervous
manifestations with menstruation. The degree of disturbance is usually mild end does not disturb
the daily life. These disturbances occur mainly premenstrually and include feeling of lethargy,
tiredness, malaise, depression, excitability and irritability, headache, fullness and tenderness of
the breasts, poor concentration impaired efficiency, nausea, vomiting, lower back pain, and pelvic
heaviness. The pathogenesis of such manifestations is not clear. In some women the picture is
exaggerated (see under premenstrual syndrome.

Management of menstruation
1. The normalcy of menstruation and its associated symptoms should be emphasized on the
mind of adolescent.
2. The menstrual flow should be received in clean pads. If reusable, such pads should be
boiled before reuse. Using dirty rags may be a source of infection. Disposable pads are
increasingly used in the developed community, but is not affordable by the poor women. The
use of vaginal tampons have not been popular in the community, and they are not free from
complication: 1) part may be left in the vagina, 2) they are not enough to contain all the
blood, 3) cannot be used by virgins and it 4) has rarely resulted in toxic shock syndrome in
western societies.
3. There is no need for the woman to have an intravaginal douche after the end of
menstruation. The Moslem woman should have a certain (religiously prescribed) bodily
wash after the end of menses.
4. There is no harm in having a bodily bath during menses.
5. Sexual intercourse is not allowed (by Islamic doctrines) during menstruation. The
Moslem woman is not required or allowed to pray or fast Ramdan or carry or read from holly
Koran, or going in pilgrimage. Although she is required to fast for the same number of days
she missed during menstruation, she is not required to catch up on prayers she missed. The
above rules apply strictly to menstruation and do not extend to any other abnormal vaginal
bleeding whether cyclic (prolongation of the period for more than her usual time) or acyclic.

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Clinical features of the normal menstrual cycle

These abnormal bleedings are called "estehada", and does not prevent the woman from
observing the above obligations. The woman is sinning if she knows these rules but does not
observe the religions function e.g. prayers and fasting during this estehada.

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Menopause

Chapter 4
MENOPAUSE
Contents
• Endocrinology of Menopause:
• Symptoms of the menopause
• Pathophysiological changes after menopause
• Management of Menopause

The reproductive function of the human female does not continue into old age as
in other animals. It ceases when the ovarian endowment of follicles (ova) is expired.
This is mainly a result of a continuous progressive follicular atresia. When the number
of follicle decrease below a certain meager, cretical number, menstruatal function
ceases and this is called the menopause. Menopause is diagnosed after the lapse of one
year after the last menstruation, i.e. it is diagnosed retrospectively. The average age at
menopause is 51 years with a range of 45 to 55. This age may show ethnic variability.
There has be a tendency to delay in menopause in Western communities but it seems
that it has now stabilized. The age at menopause has been shown to be slightly
influenced by certain factors like:
1. Familial influence: women in certain family may tend to have early or late
menopause.
2. Diabetics tend to have later menopause.
3. Obesity particularly trunkal obesity may be associated with later menopause.
4. There has been suggestions that early menarche, and high parity may be
associated with slightly earlier menopause, while prolonged use of hormonal
contraceptives delays menopause. However, these suggestions remain to be
substantiated by more research.
The word climacteric is loosely used to cover the years of transition before and
after menopause; the five years before and the five years after the menopause. Changes
and symptoms attending this transition are described as climacteric.

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The cessation of menstruation may occur abruptly. However is frequently

preceded by a period of irregularity of menstruation usually taking the form of long
cycles and scanty periods. Less commonly, there is short cycles and/or prolonged and
occasionally heavy periods. The latter acyclic bleeding will need to be differentiated
from irregularities caused by organic causes. The years of menstrual functional
irregularity of menses preceding the menopause is sometimes described as the
perimenopause.
Menstrual cycles after the age of 40 years tend be increasily anovulatory, and this
a period of reduced fecundability. However, ovulation can occur, albeit sporadically up
to the menopause and even in the two years following menopause. The risk of
pregnancy is there, up to the establishment of menopause; and fecundability that is not
to be considered completely lost until there is repeated demonstration of high levels of
FSH after the cessation of menstruation.

Endocrinology of Menopause:
1. During the forties the incidence of anovulatory cycles progressively increases.
2. During this decade there is a progressive increase in FSH level. A rise in basal
level of LH is later; it occurs shortly before the cessation of menstruation. Estrogen
and inhibin levels on the other hand tend to drop in the years preceding the cessation
of menstruation. This drop results from diminution of the follicular load of ovaries
and is the cause of rise in the FSH levels.
3. The estrogen levels reach their minimum and FSH level reach their maximum
some 3-4 years after the last menstruation.
4. For individual women levels of steroid, peptide hormones and gonadotiophins
are variable (see table of levels). There is no correlation between levels of these
hormones and the age at menopause, or the incidence of menopausal symptoms or
the extent and rate of development of postmenopausal osteoporosis.

Symptoms of the menopause

1. Vasomotor symptoms
Hot flushes or flashes and night sweats are thermoregularitary disturbances which
are characteristic of the menopause. Night sweats are the night-time counterpart of hot

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Menopause

flushes experienced during the waking time. Insomnia is usually the result of night
sweating attacks.
Hot flush arises as a sudden feeling of heat in the face, neck and chest; this is
associated with diffuse or patchy flushing of the skin, profuse sweating and frequently
with palpitations. The feeling of heat spreads through the body and lasts for about 3
minutes. Flushes may be precipitated by nervous tension and are worse in warm
weather. Vasodilatation, as evident by rise in skin temperature, occurs in the skin with
the onset of the hot flushes and continues for at least 5 minutes after the symptoms have
subsided. Although flushes occur in women who are having low estrogens, the flushes
are not associated with any sudden change in any of the hormones. However, they are
definitely relieved by estrogen therapy, i.e. they are menopause-specific symptoms.
The prevalence of hot flushes associated with menopause varies in different
cultures. Flushes occur in 80% of North American and European women but their
prevalence is much lower in Chinese women. Cultural and social factor seem to
influence the extent the women are bothered by menopausal transition. Hot flushes are
more severs in women who undergo bilateral oopherectomy than in those who have a
natural menopause, particularly when the operation is done at young age.
Hot flushes may occur in women during to years preceding the menopause,
particularly when there are premenopausal menstrual irregularity (i.e. the
perimenopause). These are also relieved by estrogen administration usually combined
with progestogen.

2. Nonspecific symptoms
A variety of symptoms can be associated with menopause which are not specific
to it, and are not always or completely releaved by estrogen therapy. They include
depression, nervous tension, palpitation, headaches, dizziness, insomnia, lack of energy,
fluid retention (bloatedness), and difficulty in concentrating backaches and other bone
pains. They are not menopause specific and represent a psychosomatic reaction to the
transition and changing social role.

3. Urogenital atrophy
After the menopause the vaginal epithelium become thinner as a result of
estrogen deficiency. Basal and parabasal cells predominate in place superficial

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Menopause

estrogenized cells in vaginal smears. The vaginal pH is raised (5 to 6). These changes
are associated with vaginal dryness and may result in dyspareunia and senile vaginitis.
Sexual interest may decline after the menopause, but this reflects an aging process.
There can be deficiency in sexual arousability. These changes can result in marital
disharmony. However, most women continue to have satisfactory sex well beyond
menopause. While estrogen therapy will improve the condition of the vagina and
improves vaginal dryness and dyspareunia, it will not enhance libido or the sexual
arousability.
Urinary symptoms like frequency, urgency and urgency incontinence can occur
after menopause. These may be related to atrophy of the lower urinary tract mucosa
and chronic infection. However, these changes are also related to aging processes.
Stress incontiness may start or become more marked after the [Link]
symptoms can be improved by estrogen treatment
Genital prolapse is occasionally attributed to menopause and/or aging.

Pathophysiological changes after

menopause
These changes are not totally effects of withdrawal of ovarian functions, but they
are, at least partially, caused by aging.
1. Atrophy of the genital tract and other pelvic structures.
2. Tendency to obesity, which start by loss of waistline and addition of weight
which is mainly trunkal.
3. Loss of elasticity and flabbiness of the skin, which is more an aging effect.
Increased skin pigmentation may be manifest after menopause.
4. Osteoporosis: is a disease characterized by low bone mass and
microarchitectural deterioration of bone tissue, leading to enhanced bone fragility
and consequent increase in fracture risk. Osteoporotic bone is characterized by
excessive loss of mineral content with reduction in density and mineral content per
unit volume of bone. The primary fracture sites are in the long bones like fracture
of the neck of the femur and ulna, and also occur in vertebrae. The latter fractures
can result in upper back hump and decreased body height as a whole. Osteoporosis
is associated with increased rate of tooth loss.

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Menopause

The maximal bone mass is achieved around time of maturity, in late teenagers.
Thereafter, there is a slow but progressive loss of bone mass. The rate of bone mass
loss increases in the 5-10 years before and the few years after the menopause. This
acceleration of bone loss is mostly an effect of loss of ovarian estrogens. This
usually results from imbalance between formation and resorption. The mechanisms
of estrogen effect on osteoporosis include the following;
- estrogens inhibit osteoclastic resorption
- increase intestinal absorption of calcium
- increase in formation of 1,25 dihydroxy vitamin D
- support osteoblast.
A number of factors increase the likelihood of developing osteoporosis and minimal-trauma-
fractures, including:
1. Increasing age.
2. Female gender, osteoporosis being more marked in women relative to men..
3. White, tall women, with long femoral necks are more likely to develop femoral
fractures.
4. Women with early menopause and/or surgical menopause. Severe
oligomenorrhea and amenorrhea predispose to osteoporosis.
5. Certain constitutional predisposition which is most probably genetically
determine. Fractures are commoner in white women, relative to blacks.
6. Sedentary life and lack of muscular activity.
7. Low calcium and vitamin D intakes.
8. Alcohol consumption and heavy smoking.
9. Tendency to falling due to weak bodies muscles and ligaments.
10. Corticosteroid treatment, or prolonged intake of thyroid hormone, anticonvulsant
or heparin.
There is a big racial difference in predisposition to osteoporotic fracture. White
Caucasian women are more predisposed than Chinese and South African Bantu. The
situation in Egypt has not be determined.

Diagnosis of osteoporosis:
Osteoporosis can be diagnosed and monitored by certain bone mineral
densitometry (BMD). These include single-photon absorptiometry. The principle of
which is that ionizing radiation is absorbed in proportion to the amount of bone mineral

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Menopause

in its path. Dual-photon absorptiometry was an improvement but the technique

commonly used now is dual energy X-ray absorptiometry (DEXA). The dual systems
suites the absorption rate in bones surrounded by soft tissue; it utilizes two sources of
energy with different absorbance constants, one for soft tissue and the other for bone,
thus allowing for measurement of absorbance due to each tissue component. In DEXA
scan the radiation dose is much less than that of one standard X-ray chest. Quantitative
computed topography measuring bone density is also utilized. Recently,
ultrasonography (specialized apparatus for the purpose) is used to measure bone density
in the os calcanium of the foot. The decrease of bone density by one standard deviation
below the age-specific mean indicates an increased predisposition to fractures, i.e.
osteopenia, drop below 2SDs indicates established osteoporosis.
Biochemical markers of bone formation (osteocalcin and bone-specific
alkaline phosphatase) or of bone resorption (hydroxyproline/creatinine and
calcium/creatinine ratio in urine). These are neither sensitive nor specific, and are not
substitutes to denensitometry.
Indications for measurement of BMD:
1. to help physicians and patients to make the decision regarding the need for
therapy.
2. to monitore the response to the therapy.
3. to emphasize the need for postmenopausal hormone therapy in women
predisposed to osteoporosis like those with early menopause, surgical or otherwise
long-term treatment with corticosteroid, thyroid hormone, anticonvulsant and
heparine.
4. patient with minimal-trauma fractures.
5. Genetic markers of determinants of vitamin D receptors can be used to detect the
special predisposition to osteoporotic fractures.

5. Enhanced risk to cardiovascular disease (CVD) particularly coronary

insufficiency and acute myocardial infarction, and cerebral stroke. Coronary heart
disease is the main cause of death of women above the age of 50 years. Mortality
rate for CVDs in women are lower than those of men at all ages. After menopause
the incidence and mortality of CVDS progressively increase in women approaching
that of men. This trend in postmenopausal women is estrogen deficiency-related,
and has been ascribed to a number of strogen-deficency related metabolic and

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Menopause

vascular changes which predispose to atherosclerotic arterial disease. These are

including:
a. Changes in lipids and lipoprotein metabolism: a rise in total cholesterol, low-
density lipoproteins (LDL) and a decrease in the protective high-density
lipoproteins (HDL).
b. Increase homocysteine and endothelin-1 plasma levels, which increase the
tone of peripheral blood vessels, i.e. peripheral resistance.
c. Increase Ca-ion influx in endothelial cells of blood capillaries incresing their
tone.
d. Increase in blood fibrinogen and factor VIII, and plasminogen activator.
e. Enhanced insulin resistance.
f. Increased peripheral resistance.
These changes have been ascribed to estrogen deficiency and are mostly
reversed by postmenopausal estrogen treatment. Epidemiological studies have shown
that long-term administration of estrogen (for 5 years or more) diminishes the incidence
of coronary heart diseases. These protective effects are mostly not negated by a
concomitant use of small dose of progestogens. Recent epidemiological studies has
tended to negate this protective effect of estrogen on risk of CVDs.

6. CNS changes: Estrogen treatment after menopause has been shown to increase
cerebral blood flow, reduce the risk of stroke, and Alzheimer's disease, and improve
and maintain the cognitive functions particularly the memory. This improvement is
however, not a sure indication that these conditions are menopause related; they are
rather effects of aging.

Management of Menopause
Although about 80 percent of European and American women experience some
disturbance at the time of climacteric, only 25 percent need more than reassurance. The
corresponding figures in many other communities and cultures have not been
determined yet. The attitude of women to menopausal problems differs in different
population depending on cultural attitudes towards this stage of life and towards aging
as a whole; this may be determined an attitude of silent endurance. Individually, this
attitude is not only determined by severity of climacteric symptoms but also by the type

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Menopause

of social life and obligations in this stage of life. Women with the desired family size
completed or with other more pressing life obligations may bear with the climacteric
changes better, than other women. The menopause might have been recently
"medicalized". This may represent the vested interest of medical profession and
pharmaceutical companies, and consequently the unnecessary publicity of certain
claims. However, the majority of women will not need medications. The management
of menopause comprises:
1. reassurance; this if coupled to care in excluding any organic causes for any
complaints frequently works and are usually enough. Advice about diet and
physical activity are important.
2. Postmenepausal hormone therapy (PHT) : This is frequently called hormone-
replacement-therapy, (HRT) a name reflecting the trend towards "medicalization"
of the health of women. However, the present position in industrialized countries of
HRT is that is one of selective use, statistics indicates that PHT is used for some
time by no more than 20 percent of the population after menopause.
Postmenopausal estrogen therapy carries certain risks and inconveniences
particularly if used for a long time. These include:
1. Nausea, headache, breast tenderness and break-through bleedings. These tend to
diminish with prolonged use.
2. Increased risk of endometrial hyperplasia and endometrial cancer after long-tern
use of estrogen. This is effectively balanced by the concomitant administration
of a progestogen for at least 10-12 days each month. This counteracts the
proliferative, hyperplastic effect of estogens upon the endometrium.
Alternatively a small dose of a progestogen is added throughout estrogen use.
3. Slight increase in the incidence of carcinoma of the breast. This increase is
minimal (a relative risk of 1.3), and occurs after long use of more than 5 years. It
has not observed in women using PHT for less than 5 years or in past users. The
risk is much less significant than the benefits achieved, particularly from the
protective effect against fractures in old age and CVDs. The concomitant
progestogen administration does not influence this small risk of breast cancer.
4. Slight increase in the risk of venous thrombosis and embolism.

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Menopause

Indications for postmenopausal hormonal treatment or HRT

Indications for postmenopause hormone therapy (HRT) are either for
symptomatic i.e. therapeutic treatment or for preventive purpose, i.e.,
prophylactic treatment.
• Symptomatic treatment:
- Hot flushes and sweating.
- Urogenital atrophy.
- Perimenopausal cycle disorder (see under Abnormal Uterine Bleeding).
- Other climacteric complaints and symptoms, like irritability, headaches,
depression, ... etc.
• Preventive treatment :
- osteoporosis and esteoporotic fractures
- Cardiovascular diseases: mainly coronary heart disease and stroke.
- CNS effects.

• Symptomatic Treatment
There can be no difference in opinion that women with symptoms need hormonal
treatment. There is usually marked improvement in vasomotor symptoms, but the
improvement of the other climacteric complaints and symptoms are not always
successful. The management of the atypical symptoms of menopause like depression,
dizziness and headache will need consideration of other possible contributing
conditions and their management. The treatment should be continued for 6-12 months
and withdrawn gradually.
The management of perimenopausal cycle disorders will need first exclusion of
organic causes like tumors. Thereafter, cyclic estrogen and progestogen treatment can
be given for some months. If contraception is still required, these women can use low-
dose combined contraceptive if the patient is not at increased risk of CVDS on use of
such preparations i.e. if not having hypertension, diabetes mellitus or if she is not
cigarette smoker. The at-risk-women are better not to use the combined pill, which
contains the potent alkylated estrogen, ethinyl estradiol. For the contraceptive purpose,
these women are better to use non-hormonal methods like tubal sterilization or the IUD.
If they are having vasomotor complaints they can conjointly used hormonal regimens
containing the much weaker natural estrogens like the native estradiol or conjugated

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Menopause

equine estrogens. If contraception is not required symptomatic perimenopausal

women can better use combinations containing the less risky natural estradiol to which
a progestogen is co-administered.

• Preventive or Prophylactic PHT

In spite of demonstrated benefits of long term treatment not all women should
use postmenopausal hormone treatment. The cost is high and the implications of
supervision of such treatment can not be affordable by all women. In most
industrialized communities PHT is used for preventive purpose by, only 15 to 25
percent of the population, and in these, the long-term compliance is difficult to achieve.
Implications of preventive PHT:
1) cost, 2) need for long-term compliance, 3) a 30% increased risk of breast
cancer after prolonged use for 5 years, 4) slightly increased risk of thromboembolism,
5) the needs for medical surveillance with the aim for early detection of breast cancer
and avoiding delay in diagnosis of endometrial cancer, 6) the occurrence of bleedings.
These can be most objectionable with some elderly women.
Indication for preventive HRT includes the following list:
- Women with premature or surgical or radiation menopause.
- Women with a bone density value > 1SD below the age-specific mean.
Densitometry is resorted to in women specially predisposed to osteoporosis.
Calcium: 1 gm of elemental calcium is required to be added daily.
- Women with history of osteoporotic fractures.
- Women that have long used corticosteroids for conditions like bronchial
asthma.
- Women with existing CVDs.
- Women with risk factors for CVD, such as dyslipidemea, hypertension,
diabetes mellitus, smoking, family history of CHD, or familial dyslipidemia.
- Women who are interested in using PHT and can offered the required
surveillance.
Women under long-term hormone postmenopausal treatment should be put under
medical surveillance. This includes the following:
1. Twice-yearly clinical assessment particularly for irregular bleeding and breast
examination.

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Menopause

2. Once yearly cervical smear.

3. The woman should be taught self-examination for early detection of breast
cancer.
4. Once-a-year mammography particularly when self-examination is not reliable or
in cases of doubt.
5. Once yearly lipogram.
6. Twice yearly vaginal sonography to measure the thickness of the endometrium.
This should be <5mm "double thickens i.e. myometrium to myometrium. This is
only needed if the woman has repeated bleedings.
Contraindications for PHT
1. Present or past thrombosis or embolism, or marked varicose veins.
2. History of breast cancer. A family history of breast cancer is not a
contraindication.
3. Abnormal uterine bleeding until the cause is determined.
Hormonal preparations used in PH
1. Estrogens:
Estrogens can be given orally or parenterally. They are given daily without
interruption. The most widely used oral preparation is "conjugated equine estrogen", a
product prepared from the urine of pregnant mares and is containing a number of
biologically weak estrogens of which estrone sulfate predominates. The usual dose of
this natural estrogen is 0.625 mg daily, which is usually sufficient to ensure symptoms
relief and for the preventive purposes. Estradiol valerate can be also given by mouth in
a daily dose of 1-2 mg. Ethinyl estradiol is not to be used for HRT because it is too
strong and can cause unnecessary marked metabolic alterations. Estriol can be given in
the dose 1 mg daily. This may not be sufficient for symptom relief and its efficacy for
the preventive purposes has not documented.
Parenteral modes of estrogen (estrodial) administration include transdermal
preparation e.g. gels 3 mg/daily, patches of 50 or 100 µg daily, subcutaneous implants
(25 - 50 mg every 4 - 6 months), vaginal creams or rings and injectable preparations.
The transdermal patches are increasingly used particularly when oral administration is
not acceptable.
2. Progestogens:
For women with an intact uterus, progestogens are given in addition to estrogens
to prevent the estrogen-induced proliferation of the endometrium and the risk of

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Menopause

endometrial cancer. The most widely used oral progestogens are 19-acetoxy-
progesterone (pvovera) and, 19-nortestosterone derivatives like norgstrel and
norethindrone and micronized progesterone. Such preparations are used cyclically for
10-12 days per month with continuous estrogen. Progestogen of C-21 origin (derivative
of progesterone origin) are generally better than progestogen of C-19 origins derivative
of testosterone origin. The formers have less deleterious effects on lipids than the latters
A smaller dose of progestogen can be used continuously together with the estrogens i.e.
in all the days of estrogen intake. The progeestogens can be given orally or parenterally
i.e. in the form of skin patches, injection or vaginal rings.
The addition of the small dose progestogen does not detract from the preventive
effects of estrogen against cardiovascular disease and osteoporosis. It does not also
influence the risk of breast cancer.
Weak androgens e.g. dehydroepiandrosterone can be used in place of
progestogens to counteract the proliferative effect of estrogen on the endometrium.
Basic rules in preventive postmenopausal hormonal treatment
1. Estrogen treatment should be continuous. This progressively diminishes the
incidence of breakthrough bleedings, i.e., menstruation like bleeding are expected
during early months of use, but diminish with continuation of treatment.
2. Estrogen treatment must be comined with progestogen unless the uterus had
been removed.
3. In any combined E+P regimen, progestogen should be given for at least 10 days
per month.
4. A monthly sequentially combined regimen is the standard method. The
combined regimen, in which a progestogen is added in all days, has recently
introduced.
5. Natural estrogen should be given in the lowest possible dose; alkylated estrogens
like ethinylestrodiol should not be given.
6. Progesterone derivative e.g. provera or micronized progesterone are preferred
since they have lesser effect on the lipid metabolism than 19-nor-testosterone
derivatives e.g. norgestrel or norethindrone. The latters have more pronounced
effects on the lipogram.
7. A slight bleeding is expected during the early months of use. This is particularly
likely to occur at the time of transition from one package (cycle) of treatment to the
following. If bleeding is persistent or lasts for long, or develops de novo after some

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Menopause

months of amenorrhea, the cause will need to be investigated. Endometrial

thickness by vaginal sonography should be assessed and may be, other
investigation, e.g. endometrial aspiration or lavage cytology, D&C or hysteroscopy,
are needed.
3. Alternatives to hormonal therapy
Alternatives to hormonal therapy for the prevention of osteoporosis include the use of:
1. calcitonin as subcutaneous injections or as a nasal spray. This is a thyroid
hormone which inhibits bone resorption and enhance enhances intestinal
absorption of calcium. It is suitable for women with contraindications of use of
estrogens. It is expensive.
2. biophosphonates (etidronate). These are synthetic compounds, which suppress
osteoclastic bone resorption. These can result in increased bone density. It is
taken orally in the morning on an empty stomach. It can cause esogygeal reflux.
3. Vitamin D sterols. This is not effective alone.
4. Fluroids. Long-term safety has not been confirmed.
These alternative treatments are increasingly used to obviate the
problems of PHT but they are not cheep or free from side effects and their
efficacy in prevention of osteoporosis needs to be more substantiated. They do
not prevent the CVD risks. They are particularly needed for women with
present or increased risk of osteoporosis who have a contraindication for use of
PHT or dislike having any bleeding.
5. Recently selective estrogen receptor modulators (SERMs) have been used
instead of estrogen for preventive indication. Old SERMs like tamoxifen had
been used in the treatment and prevention of breast cancer. New SERMs like
Raloxifene have been used for PHT. They have been shown to have a positive
impact on bone density i.e. prevention of osteoporosis, and can improve the
lipogram. Raloxifene has no proliferative effect on the endometrium and may
not increase the risk of breast cancer. However, they can exaggerate or cause hot
flushes.
6. Tibolone a 19-nortestosterone steroid has been recently shown to be effective in
ameliorating hot flushes and in the prophylaxis against osteoporosis. It causes
atrophy of the endometrium, i.e. it does not cause bleeding. Its effect in CVD
prophylaxis is, however, not well established.

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Chapter 5
DEVELOPMENT OF THE FEMALE
GENITAL SYSTEM

Contents
• Genital ridge
• Wolffian system
• Mullerian duct
• Development of the vulva
• Development of the vagina
• Development of the urinary system

Most of the female genital and urinary systems develop from the two intermediate cell
masses. These are longitudinal elevations of mesoderm in the posterior aspect of the primitive
celom on either side of the mesentery of the gut. In each of these masses, three longitudinal
systems develop which are in a medial to lateral order, the genital ridge, the Wolffian system
and the Multerian duct. The three of them extend caudally to the fore-skin in front of the
cloacal membrane closing the caudal end of the cloaca (Figure 1). The urogenital sinus, which
is the sequestrated anterior part of the cloaca, develops in the lower parts of the urinary and
genital tract.

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Development of female genital system

Development of the female genital system; Figure 1: Cross section in the trunk of a 5-week
embryo. 1. coelomic cavity; 2. Gut; 3. Intermediate cell mass; 4. Mullerian duct; 5. Wallfian duct; 6.
Mesonephros; 7. Genital ridge; 8. Aorta.

Genital ridge:
This is a longitudinal thickening of the celomic epithelium and the underling
mesenchyme (mesoderm) on the medial aspect of the intermediate cell mass. It is the
forerunner of the gonad. The uppermost part of the ridge underneath the diaphragm is the site
of formation of the gonad, (figure 2). However, the germ cells (oogonia or spermatogonia)
responsible for reproduction do not develop in situ in this ridge. (They belong to either of the
two types of sex depending on the chromosomal endowment of the zygote, i.e. the presence of
XX or XY karyotype). These germ cells have their origin in the dorsum of the caudal part of
the yolk sac or the primitive hind gut. The germ cells migrate to the future site of the gonad.
Their arrival to this destination will ensite the differentiation of the celomic epithelium and
underlying mesoderm into the supportive structures of either the testis or the ovary, according
to the chromosomal sex. In case of the ovary the granulosa cells develop from the epithelial
element, and theca cells develop form the mesoderm. The gonadal cortex predominates in the
female. In case of the male the characteristic tubular system of the testis is formed from the
epithelial element and the leydig cells from the mesoderm. The medulla predominates in
male. The gonad will receive blood supply from the corresponding upper part of the
abdominal aorta.
The rest of the genital ridge caudal to the gonad will become fibrosed and is
called the gobernaculum, which contracts to drag the gonad downwards (caudally).
In the male the contracture is so marked that it brings the testicle to the outside of
the abdomen to the future site of the scrotum. In case of the female, the contracture
brings the ovary to only the level of the brim of the pelvis. The remainder of the
fibrous gobernaculum in the female forms the ovarian and the round ligaments
above and below uterine cornu respectively. The termination of the latter structure is
again at the front part of the labium majus. The descent of the gonad drags upon and
markedly lengthen the ovarian and spermatic vessels from their upper abdominal
origin (see also under normal and abnormal sexual differentiation).

Early degeneration and blighting of sex cells occurs in conditions where there
is only one X chromosome i.e. 45,X karyotype (or structural defect in one of the X-
chromosomes). This failure of formation of sex cells in sufficient numbers results in
failure of ensiting the formation of the gonad. The condition is called ovarian
agenes (failure of formation) or dysgenesis (imperfect formation). Since we, in fact,

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Development of female genital system

do not know whether an X or a Y is missing, the condition is better called gonadal

agenesis or dysgenesis (See under Normal and Abnormal Sexual differentiation).
This chromosomal abnormality results in a number of severe congenital
abnormalities. These had been clinically recognized, long time before the
chromosomal origin was recognized, and carried the name of Turner’s Syndrome.
The “individual” looks like a female (which seems to be the neuter sex, with
masculinity or completion of femininity as superadditions). However, “she” is an
incomplete female showing an underdeveloped vulva and internal genitalia and will
have primary amenorrhea. The secondary sex characters are not developed. Besides,
she shows a broad or webbed neck, increased carrying angle of the arm, and other
congenital deformations. The ovaries are absent and replaced by two white streaks at
the pelvic brim, streak ovaries (streak ovaries).

Wolffian system (Figure 2):

It is formed of a longitudinal tube, the Wolffian duct (also called paramesonephric
duct) that develops in the intermediate cell mass lateral to the genital ridge. It is joined by
three sets of transverse tubules; the pronephros, the mesonephros and the metanephros in this
order from the cranial to caudal end which develop also in this sequence. The metanephros
gives rise to the glomeruli and tubules of the kidney (the cortex of the kidney) in both sexes.
It is to be noted that the kidney originally develops in the pelvis, but moves upward to its final
site (acquiring a fresh blood supply from the upper part of the abdominal aorta).
In the male, tubules of the pronephros and mesonephros will form the connecting
tubules that join the seminiferous tubules and collect their products, the sperm, to a tube, the
Wolffian duct, which will give rise to the epididymis and vas deferens that end by opening in
the urogenital sinus.
In case of the female, the pro and mesosonephros will disappear together with the
Wolffian duct itself. Vestigial remnants of these structures may persist at its anatomical
course and rarely give rise to cyst formation either in the broad ligament, anterolateral wall of
the vagina or the site of the clitoris. Very rarely they give rise to a malignant tumor of special
histopathological type “Adenocarcinoma of mesonephric pattern”. This very rare neoplasm
occurs in young subjects and has been recognized to be associated with the mother’s use of
diethyl-stilbosterol (DES) during the pregnancy with this sibling. This rare occurrence is now
called DES syndrome. It has later been found that DES syndrome comprises other
manifestations besides cyst formation and this specific cancer. These include infertility (in the
female and male sibling), menstrual irregularities, anovulation and a small uterus with a
triradiate configuration of the uterine cavity. This DES syndrome is one of the iatrogenically

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Development of female genital system

caused congenital anomalies. This discovery raised a warning to the use of exogenous
estrogens (not only DES) in early pregnancy.

Mullerian duct (Figure 2):

This is a longitudinal tube that develops in the lateral part of the intermediate cell mass.
It is actually an evagination from the celomic epithelium that proceeds caudally. At the pelvic
brim it curves inwards and meets its fellow of the opposite side and the two proceeds caudally
side-by-side in the middle line. The middle line parts of the ducts fuse together to give rise to
the uterus. The unfused portions of the mullerian duct give rise to the fallopian tube, which
opens, into the peritoneal cavity. In its inward course, the mullerian duct crosses over the
gobernaculum and attaches to it. The part of the gobernaculum proximal to this point of
crossing (on the side of the ovary) gives rise to the ovarian ligament while the distal part gives
rise to the round ligament (see also under normal and abnormal sexual differentiation).
In the male the mullerian ducts atrophy and this is determined by production of an
antimullerian hormone produced by the fetal testes.

Development of the female genital system; Figure 2: Diagrammatic representation of the

female genital system in a 5-6 week embryo seen from the front: 1. Gonad; 2. Gobernaculum;
3. Mullerian duct; [Link] two mullerian tubercles (in a plain behind the urogenital sinus); 5.
Urogenital sinus; 6. Pronephros; 7. Mesonephros; 8. Walffian duct; 9. Metanephros.

Development of the vagina

The lower ends of the mullerian ducts will each send a downward solid rod behind the
urogenital sinus. {The urogenital sinus is the anterior half of the cloaca (hindgut). Thus
downward growth of the mesoderm proceeds from above downward reaching to the cloacal
membrane (the double-layered membrane formed of endoderm and ectoderm that closes the
cloaca caudally). The two-mullerian rods are called the mullerian tubercles since they raise
elevation in the back of the urogenital sinus. The two mullerian tubercles (originally solid)

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Development of female genital system

will get canalized and fuse together to give rise to the vaginal tube which opens forward in the
lower part of the urogenital sinus. The latter will give rise to the vestibule of the vagina. The
urogenital sinus will also send epithelium upward to form the lining of the vaginal tube up to
squmo-columnar junction at the external os. In other words, the vagina is of double origin, the
mullerian contribution furnishes most of the vaginal tube while the urogenital sinus furnishes
the lining together with the formation of the vestibule. The remnants at sides of the site of
fusion of the mullerian and urogenital contributions give rise to the hymen. Later, the cloacal
membrane breaks down opening the vagina to the exterior. The remnant of the cloacal
membrane on the sides of the vaginal opening gives rise to the labia minora. Breaking of the
cloacal membrane and formation of labia minora is an effect of the intrauterine hormonal
milieu. Androgenic influence like in congenital adrenogenital syndrome will result in the
fused labia minora. An alternative description gives the urogenital sinus the credit of forming
the lower third of the vagina(see under Normal and Abnormal sexual diffrantiation).

Development of the vulva:

An elevation of the skin and underlying connective tissue forms just anterior to the
cloacal membrane and is called the genital tubercle. This sends backward two folds of skin on
the sides of the membrane, the labioscrotal folds. The clitoris (or the penis) develops from the
genital tubercles while the two folds give rise to labia majora. The breaking down of the
cloacal membrane, a feminine phenomenon, gives rise to labia minora. The lower end of the
urogenital sinus forms the vestibule. The parts of this sinus proximal to this reshape itself in
the urethra and the urinary bladder. The hymen is the remnant at the site of opening of the
mullerian vagina into the urogenital sinus.
An alternative description for development of labia minora is; inside the labioscrotal
folds, develops two thinner folds called the urogenital folds. These remain separate in the
female and give rise to the labia minora. In the male, they fuse to form the floor of the
perineal and penile urethra (Figure 3).
The perineal body is formed of the mesodermal downgrowth that divides the cloaca
into an anterior segment, the urogenital sinus and a posterior segment, the anal canal and
rectum. Failure of this division is the origin of congenital rectovaginal fistula. The posterior
portion of the cloacal membrane( the anal membrane) breaks down, failure of this occurrence
results in an imperforate anus.

Development of the urinary system :

The structures in the cortex and medulla of the kidney develops from the metanephros.
The ureter renal pelvis have a different origin ; being formed from a bud which grows up

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Development of female genital system

from the lower end of the Wolffian duct (which ends in the urogenital sinus).This upward bud
forms at its end the renal calyces and collecting tubules of the kidney which joins the
metanephros contributions. Failure of this communication will result in congenital cystic
kidney. The lower end of the ureter, at the ureteric bud, and the adjoining lower end of the
Wolffian duct ultimately open up and get incorporated in the urogenital sinus. In this way the
openings of the Wolffian duct and of the ureter become separated, (Figure 4).
The urogenital sinus is modulated to form the urinary bladder and the urethra. In the
male the urogenital folds fuse to form the perineal urethra and extend underneath the phallus
to form the penile urethra.
In the male, the Wolffian duct persists as the vas deferens and epididymis. The seminal
vesicle is an outward growth of the Wolffian duct.

Development of the female genital system; Figure 3: undifferentiated external genitalia.

1. Genital tubercle; 2. Labioscrotal folds; 3. Urogenital fold; 4. Perineum; 5. Urogenital membrane
(closing the urogenital sinus from bellow); 6. Anal membrane (closing the anal canal from below)

Development of the female genital system; Figure 4 : The stages where by the lower part of
the wallfian duct is opened out and incorporated in the urogenital sinus. By this process the
duct and its ureteric bud come to have seorate opening into the sinus. UGS= Urogental sinus; WD=
Walffian duct; UB= Ureteric bud.

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Chapter 6
CONGENITAL ABNORMALITIES IN
THE FEMALE GENITAL SYSTEM

Contents
• Ovary
• Mullerian Duct defects
- Imperforate vagina
- Mullerian aplasia
- Uterine hypoplasia
- Uterine cavity duplication
- Rudimentary horn
• Vulval congenital abnormalities

Ovary
Ovarian agenesis or dysgenesis
This is a severe congenital abnormality resulting from sex chromosome monosomy,
whereby there is one X chromosome in the cells i.e. a karyotype of 45-X. This usually results
from the phenomenon of nondysjunction during the maturation division of one of the
gametes. It can be due to deletion of part of the Xs. A partial variant can also result from
mosiacism, whereby the body is formed of two cell-lines: one is 46-XX and the other 45- X.
Since in the case of 45X “individuals” the type of the missing chromosome is not
known, the condition is better called gonadal agenesis, and in order to accommodate the
mixed variants it can be called gonadal dysgenesis. Consequent on this chromosomal defect
the sex cells degenerate early in fetal life. The failure of the gonad to have these cells will
suppress its development. The condition is also discussed under Amenorrhea.

Clinical features: The condition has been called Turner’s Syndrome after the scientist
who described its clinical features. The “individual” is markedly stunted in growth; the height
is usually less than 150 cm, and has a feminine type of vulva (femininity is the neuter state of

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gender). The neck has a broad base or is webbed. The carrying angle of the arm (the angle
between the forearm and upper arm) is exaggerated, and there can be polydactyle or
syndactylae. Coarcitation of the aorta or other major congenital heart anomalies are frequently
present. At the expected time of puberty the “girl” fails to show the secondary sex characters
and fails to menstruate. No pubic or axillary hairs appear, and the breasts are absent “shield
breasts”. The internal genitalia is hypoplastic. Both ovaries are usually represented by two
white glistering streaks in the peritoneum at the pelvic brim (streak ovaries) which contain no
follicles. One of the ovaries may be a streak one and the other is markedly hypotrophic.
The levels of gonadotrophins are high and those of estrogens are very low, similar to
those of menopausal women. The girl has all features of menopause including flushes, and
increased propensity to osteoporotic fractures and coronary heart disease. Hormone
replacement therapy by continuous administration of a low dose of natural estrogen is the
treatment. This needs supplementation with progestogen during 10-12 days each month.

Hermaphroditism and Pseudohermaphroditism :

See under Normal and abnormal sexual differantion

Mullerian Duct defects

These vary from complete aplasia, hypoplasia, partial or complete atresia affecting
one or both sides of the mullerian ducts (figure 1). This process affects the distal parts of
mullerian structure before it involves the proximal part, i.e. it is exceptionally rare to have
tubal aplasia in the presence of a uterus. Failure of canalization or partial or complete
transverse septum can occur in the vagina. Another group of anomalies involves failure of
complete fusion of the two-mullerian halves resulting in duplication of the uterus and/or the
vagina or a septate or subseptate uterus (figure 2). Combinations of anomalies can occur, e.g.
double uterus with one horn hypoplastic or rudimentary. Mullerian duct anomalies are
frequently associated with urinary system anomalies e.g. a unicornuate uterus can be
associated with contralateral absence of the kidney. The following are the common mullerian
duct anomalies.

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Congenital abnormalities: (Figure 1) Example for Mullerian complete and incomplete aplasia. A=
Complete Mullerian aplasia; B= Complete Mullerian aplasia but the urogenital sinus contribution of
the vagina is present; C= A Hypoplastic uterus with absent vagina due to failure of Mullerian tubercles
to canalize; D= As C but the uterus is functioning resulting in hemato-metra and hemato-salpinex; E=
Imperforate vagina resulting in hematocolpos and hematometra; F= A congenital incomplete
transverse vaginal septum concealing the cervix.

Congenital abnormalities: (Figure 2) Example for faliuer of fusion of the two Mullerian. A= Uterus
Didelphys; B= Uterus Bicornis Bicorpis unicollis and septate vagina; C= Arcuate uterus; D=
Subseptate uterus; E= Septate uterus; F= Rudimentary horn; G= Uterus Bicrpis Bicollis with septate
vagina, one half of the vagina is imperforate resulting in hematocolpos, hematometra and
hematosapnix.

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Congenital abnormalities in the female genital system

Imperforate vagina
This is occasionally called imperforate hymen.
The commonest variant has a thin occluding membrane just above the hymen and
results from failure of establishment of the communication between the mullerian and
urogenital contributions of the vagina. The atresia can occur at higher levels resulting in the
presence of an occluding transverse septum of variable thickness at higher levels in the
vagina. The uterus is present and normal. It produces monthly menstruations. The menstrual
blood is bent up (hence the name cryptomenorrhea), and gets partially inspissated by partial
absorption of the water, leaving behind a thick chocolate-like material. This continues to
increase and distend the vagina resulting in a hematocolpos, which can reach huge
dimensions rising up in the abdomen. In case of imperforate vagina, the thin bluish septum is
seen on separating the labia. This presses on the urinary bladder resulting in frequency of
micturition. It will also cause a longitudinal stretching and attenuation of the urethra (which is
actually part in the anterior vaginal wall). This frequently results in episodes of acute
retention of urine, which occur at monthly intervals and is associated with pain due to the
fresh monthly additions to the hemotocolpos. In long-neglected cases a hematometra or
hemoatosalpinx can develop.
Imperforate vagina presents with one or more of the following: 1) delayed menarche,
2) monthly lower abdominal pain, 3) acute retention of urine, 4) failure of sexual intercourse
or dyspareunia, 5) lower abdominal mass formed by the hematocolpos plus the distended
bladder. The secondary sexual features are normally developed in accordance to age.
In the more usual condition of imperforate vagina a cruciate incision in the bulging
bluish membrane will result in gushing down of a big volume of a fluid similar to liquid
chocolate The septum usually needs to be excised and its base sutured to prevent subsequent
stricture formation.. The drainage of chocolate blood continues to drain for a number of days,
during which measures to prevent infection should be taken.
Cases with higher and thick vaginal occlusive depth will need confirmation by
ultrasound, CT or MRI. During excision of these thick septa, care should be exercised to
avoid injury of the bladder or the rectum. After removal of the occluding septum the upper
vagina is mobilized, avanced down and sutured to the lower part to avoid stricture formation.

Mullerian aplasia (Mayer-Rokitansky-Kustner Syndrome):

This is not uncommon. It is the second common cause of primary amenorrhea after
gonadal dysgenesis. The uterus and most of the vagina are absent. The vagina is usually
represented by just the vestibule. However, a dimple vagina can be formed by repeated
attempt at intercourse. The condition is confirmed by sonography, C.T. scan or MRI. The

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Congenital abnormalities in the female genital system

absence of the uterus can be confirmed by laparoscopy. The tubes are usually present and the
ovaries are normal; genital ridge development is normal in association with serious mullerian
anomalies. But one of the kidneys can be absent, hence the need for IVP examination.
Consequently the secondary sex characters are normally developed. Also, the karyotype is
normal 46-XX (The condition is also discussed under Amenorrhea).

Treatment : A number of plastic operations have been attempted. These include:

1. Mc Indo’s operation: in which a space is dissected between the bladder and
rectum, which is lined by a partial thickness skin graft. The graft is supported over an
acrylic mould. The functional results of this operation are usually poor particularly if
dilatation of the pouch (by a dilator or by intercourse) is not pursued long.
2. Williams’ operation: An external pouch can be fashioned by utilization of the
labial skin. The direction and the capacity of the pouch are not always satisfactory.
3. A whole thickness rotational skin graft can be utilized to fill the dissected pouch.
The source is from the perineum or the inner sides of the thighs. Generous flaps are
required. A supportive mould is used for about ten days. The results are more
satisfactory.
4. Progressive elongation of the vaginal pouch by an oval acrylic mould fixed to the
anterior abdominal wall by unabsorbable slings, which are progressively tightened
over a plate for a period of six to eight weeks.
In communities where suurogacy (surrogate mother) is permissible, IVF can
allow the couple to have their genetic sibling(s).

Uterine hypoplasia
Various grades of hypoplasia can occur ranging from a solid knob in the middle line
above the vaginal vault, to various degrees of undersized uterine cavity. The cervix is usually
of normal length, and the body to cervix ratio can be less than 2. Ovarian hypoplasia may be
associated, the condition is associated with hypomenorrhea, relative infertility and frequently
results in habitual abortion, miscarriages and preterm labor. The time at which the pregnancy
is expelled tends to lengthen with repetition of pregnancy. Cervical cerclage can improve the
outcome but this can not be guaranteed.

Uterine cavity Duplication

Various anomalies are common resulting from failure of fusion of the two mullerian tubes:
There are various types of doubling ranging from: 1) arcuate uterus with just a fundal
depression, 2) bicornuate uterus, 3) uterus bicorpis unicollis, 4) uterus bicorpis bicollis
(pseudo didelphys) and 5) uterus didelphys which have in addition a doubled vagina. There

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can be a disparity between the size of the two horns, and one can be rudimentary. The uterus
can be normal from the outside but is divided by a longitudinal anteroposterior septum that
can be incomplete i.e. subseptate or complete, i.e. septate. There can be a septate vagina with
a normal uterus. One horn can be completely absent, a unicornuate uterus. The kidney on the
side of the absent horn can be absent as well. These abnormalities in the mullerian ducts are
associated with normal ovarian function.
Possible Clinical manifestations
1. Dysmenorrhea,
2. Menorrhagia can be caused by the increased bleeding surface,
3. Dyspareunia can be caused by a vaginal septum.
4. Infertility is usually not the problem, but habitual abortion can be a problem.
Abortions are usually during the second trimester but early abortions can occur. They
can be caused by inability of the pregnant horn to expand as efficiently as a single-
cavity uterus. Abortion can be caused by a frequently associated cervical
incompetence. It can be also due to deficient placental development, if it happens to be
implanted on the septum.
5. Preterm labor is also common.
6. Abnormal lie (transverse or oblique lie and breech presentation are common.
Recurrence of these abnormal presentations should raise doubts about double-cavity
uterus.
7. Uterine inertia,
8. Obstruction of vaginal delivery by the nonpregnant horn can occur.
9. Retained placenta is more likely due to defective decidua formation over the
septum.
10. Postpartum hemorrhage and retained placental or membrane fragment are
commoner.
11. Repeated intolerance and expulsion of IUCD should raise suspicions about
abnormal shape of uterine cavity.
12. Pregnancy in a rudimentary horn. This is usually not communicating with the
uterus. It inevitably ruptures during second trimester causing severe internal
hemorrhage.

The diagnosis of abnormal uterine cavity can be made by hysterosalpingography.

However, the differentiation between a doubled uterus and septate uterus cannot always be
judged by the extent of separation of the shadows of the two uterine cavities;(Figure 3) a thick
septum can give a picture like that of doubled uterine bodies. The differentiation can be made

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Congenital abnormalities in the female genital system

by laparoscopy and CT scan. Hysteroscopy is important in the diagnosis (and management) of

septate uterus.

Congenital Abnormalities (Figure 3): A= Septae uterus with broad septum which on
hysterosalpingography looks as uterus Bicornis Bicollis, B.

Management
1. Excision of a longitudinal vaginal septum will give more room for intercourse and
may improve the chances of conception.
2. Cervical cerclage can help in habitual abortion and premature labour.
3. Hysteroscopic excision of a uterine septum is usually highly effective and is the
standard treatment. This can be done by the resectoscope utilizing diathermy or can be
done by YAG laser. Simultaneous laparoscopy can guide the depth of fulguration and
obviate perforation of the uterus. By dimming down the light on the laparoscopic side,
the extent of brightness of the hysteroscopic light through the wall of the uterus can
indicate the depth of encroachment on the uterine wall.
4. Strassmann’s utericuloplasty is rarely used nowadays, and has been largely
replaced by hysteroscopic resection. The uterine fundus is transversely incised to enter
in the two endometrial cavities. The anteroposterior septum is completely divided. The
fundus is sutured antero-posteriorly to keep the two uterine walls widely apart. Cases
with double uterine body who had repeatedly failed to carry a pregnancy to reasonable
maturity can be managed by an abdominal unification operation. The inner walls of
the two horns are excised and the two cavities are unified by two layers of interrupted
sutures. The resultant uterine wound is long, exposed to adhesion formations and not
very secure. There are many potential complications and such an operation should be a
last resort. After this plastic surgery for unification of uterine cavity, delivery by C.S.
should be done after the fetus has attained reasonable maturity.

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Rudimentary horn
One horn of a doubled uterus is rudimentary. The continuity with the main cavity is
usually absent. Pregnancy in this horn is rare and occurs by sperms crossing in the
peritoneum. It can carry a pregnancy for a short time usually few months before it ruptures.
This is attended by acute symptoms and massive internal hemorrhage.

Vulval congenital abnormalities

1. Cysts: see under remnant of Wolffian cyst.
2. Hypoplasia : see under ovarian agenesis.
3. Ambiguous external genitalia (see under Normal and Abnormal sexual
differentiation).
4. Hypertrophy of the labia minora: Dog-ear labia minora: these are hanging down
big labia minora which can be scuffled between the thighs. They are rarely
troublesome and when so they can be trimmed. More frequently they are acquired
phenomenon and have been ascribed to frequent masturbation however, this is not
evidence based.
5. Cliteromegaly-which is usually associated with other manifestation of virilism.

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Chapter 7
NORMAL AND ABNORMAL
SEXUAL DIFFERENTIATION-
HIRSUTISM
Contents
• Normal sexual differentiation:
- Influence of chromosomal complement
- Hormonal production at the gonads
- Peripheral metabolism of sex steroids
- Pubertal and postpubertal hormone production
- Social influences
• Sex ratio
• Improper sexual characters
a. Conditions resulting from abnormal chromosomal complement.
1.1Gonadal dysgenesis
1.2 Triple X
1.3 Klinefelter syndrome
1.4 YY syndrome
1.5 Hermaphroditism
b. Conditions resulting from abnormal hormone production or action
2.1 Virilization of a female
i. Congenital adrenal hyperplasia (CAH)
a. Classical type
b. Salt-wasting type
c. Late-onset CAH
ii. Maternal disease and drug intake
iii. Placental aromatase deficiency
iv. Virilization of pubertal or adult females and Hirsutism:
causes-diagnosis and management
2.2 Feminization of a male

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i. Androgen insensitivity syndrome (AIS)

a. Complete form (CAIS)
b. Incomplete from (IAIS)
ii. 5a-reductase deficiency
iii. Abnormal androgen synthesis
iv. Testicular destruction
v. Estrogen influence
vi. Constitutional feminism
vii. Psychological or behavioral feminism
c. Non endocrine sexual ambiguity
• Diagnosis and management of ambiguous genitalia

Normal Sexual Differentiation

The sexual differentiation depends upon multiple factors occurring in a sequence:

1. Influence of chromosomal complement

This is 46, XX for the female and 46, XY for the male. The type of the sperm
determines the sex of the zygote. The early embryo before the 5th week of gestation is
undifferentiated. It possesses two of each of undifferentiated genital ridges, Wolffian systems,
and Mullerian ducts and undifferentiated external genitalia and urogenital sinus. The
migration of primordial germ cells from the yolk sac to the genital ridge occurs between week
4 and 6 of gestation. When the germ cells are carrying a Y chromosome i.e. are XY, a testis is
produced in the genital ridge; the epithelial elements of the ridge form the seminiferous
tubules of supporting Sertoli cells, which support and organize the development of germ cells
in spermatogenesis; the mesenchymal elements form the Leydig cells; and the medulla of the
gonad persists to form the rete testis. The development of the testes specifically depends upon
a testis-determining factor (TDF), which is represented by a single gene located in the distal
end of the short arm of the Y chromosome. This sex-determining region of the Y
chromosome (SRY) has been recently characterized. The formation of the testicle precedes
any other sexual development in time, and the functional activity of the testes controls
subsequent sexual differentiation.
When the genital ridge receives primordial germ cells with an XX karyotype an ovary
is developed. This is actually a default effect resulting from the absence of TDF on the Y. In
the development of the ovaries, the cortical zone develops; the epithelial elements form the
granulosa cells, and the mesenchymal elements form the theca cells. The medullary portion

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regresses, with its remnants being the rete ovarii, compressed rests of tubular and Leydig cells
in the hilus of the ovary.
The germ cells proliferate by mitosis during fetal life. However, a simultaneous
follicular atresia begins in the ovary since early intrauterine life reducing the number of
primordial follicles to one or two millions at birth. Excessively rapid atresia (germ cell
attrition) occurs in individuals with 45, X karyotype resulting in streak gonads of gonadal
dysgenesis (Turner’s syndrome). A complete 46, XX chromosomal complement is necessary
for normal ovarian development i.e. the second X chromosome contains genetic elements
essential for ovarian maintenance; their deletion result in various grades of “streak” ovaries.
In the testes, mitosis of germ cells continues throughout life.
Certain autosomal genes are essential for coding steroidogenic enzymes, and
determining the peripheral action of certain hormones.

2. Hormones produced by the gonads

The testes are functionally active during intrauterine life. The fetal testes produce two
hormones, which are essential for the development of duct system and external genitalia, the
antimullerian hormone and testosterone. They determine development in the male direction.
Absence of their effect determines development in the female direction.
§ Antimullerian Hormone (AMH); (also known as mullerian inhibiting substance or
factor) is a glycoprotein synthesized by Sertoli cells shortly after testicular differentiation.
It is responsible for ipsilateral regression of the mullerian ducts (also known as the
paramesonephric duct) by the 8 th week in the male fetus.
The absence of AMH in the female fetus determines the development of the fallopian
tube, uterus and upper vagina from the ipisilateral mullerian duct. This development of
mullerian duct (the paramesonephric duct) requires the prior appearance of the
mesonephric ducts (the Wolffian system), and because of this, abnormalities in the renal
system are associated with abnormalities in the development of the tubes, uterus and
upper vagina, i.e., mullerian aplasia are associated with renal and ureteric anomalies.
Individual without a functional gonad like the 45, X gonadal dysgenesis are not
producing AMH and therefore will have tubes, uterus and vagina, albeit hypoplastic, i.e.
the internal genitalia possess an intrinsic tendency to feminize (femininity is the neuter
gender).
Transabdominal descent of the testes is also an effect of AMH, which determines
more marked gobernacular growth and contraction. Movement of the testes through the
inguinal canal and into the scrotum is an effect of testosterone produced in the testis.

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§ Testicular Androgens: the fetal testes secrete Testosterone soon after Leydig cell
formation. In the early embryonal and fetal life human chorionic gonadotrophin
stimulates testosterone synthesis; the stimulation reaches a peak at 15 – 18 weeks at the
time of maximal secretion of HCG. As HCG declines around the 20th weeks the fetal
pituitary takes over the control of testosterone secretion by Leydig cells. Testicular
androgens play certain functions essential for sexual differentiation:
a. Testosterone secretion stimulates development of the Wolffian duct system into
epididymis, vas deferens and seminal vesicles. This effect of testosterone occurs
as a paracrine effect influencing the adjacent ipsilateral wolffian duct i.e. this duct
differentiation depends upon the presence of an adjacent testis. Therefore, this
local paracrine action on the wolffian duct cannot be stimulated in a female fetus
exposed to adrenal (congenital adrenal hyperplasia) or iatrogenic androgen, i.e.
such fetuses will not acquire the internal duct system of the male. The testicular
testosterone does not need to be reduced to dihydrotestosterone (DHT) to exert its
effect on the internal duct system.
b. Testosterone also determines the differentiation of the external genitalia in the
male direction. Unlike the internal genitalia where both duct systems initially
coexist; the external genitalia are neutral primordia able to develop into either
male or female structures depending on the type hormonal stimulus received from
the gonad. These primordia comprise 1) the genital tubercle in the midline on the
lower end of the anterior abdominal wall, 2) the two labioscrotal folds (the genital
swellings) which spread backwards on the side of the fore-part of cloacal
membrane (which is closing the urogenital sinus), and 3) the two genital folds
(also called urogenital fold) developing inside the labioscrotal folds. Again, the
differentiation of the external genitalia in the female direction is a default effect
resulting from absence of androgen. Because of this absence the phallus remains
small giving rise to the clitoris and the labioscrotal fold and genital folds remain
separate giving rise respectively to labia majora and labia minora. [Alternatively,
the labia minora are thought to arise from the lateral remnant after breakage of the
cloacal membrane, which is closing the urogenital sinus]. The urogenital sinus
contributes to the development of the lower vagina. Estrogens produced in the
ovaries does not determine the type of external genitalia acquired, however they
are trophic to the external genitalia structure determining their full development
by the time of puberty.
Under the effect of fetal androgens the external genitalia develop in the male
direction. The phallus enlarges forming the penis. The genital or urogenital fold
fuse [or the cloacal membrane does not break down] to give rise to the penile

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urethra; and the labioscrotal folds fuse to form the scrotum, which receives the
testicles. The effect of testicular testosterone upon the external genitalia differs in
two aspects from its effect on the internal genitalia: First, the effect on the external
genitalia is endocrine, being carried by blood; The second, is being medicated by
dihydrotestosterone (DHT). To achieve this morphologic change, external
genitalia target cells must be equipped to convert testosterone to DHT by the
intracellular enzyme 5 a-reductase.
The masculinization of the external genitalia is completed by the 14th week.
It is difficult to ascertion the sex of the fetus by inspection before that time.
However, “old” women in our culture claim the ability of identifying a male
abortus before that time. In a male-oriented society, it gives more solace to the
aborting woman to know that she has aborted a female.
c. Besides determining the differentiation of the internal and external genitalia, the
testicular androgens may play a critical role in conditioning the development of the
brain of the fetus. This androgen effect program the central nervous system to
induce the potentials for male sexual behavior. Inappropriate fetal hormonal
milieu at a critical stage of fetal life may contribute to certain psychosexual
behavior seen in human. However, social and psychological influences play an
important role in “conditioning“ certain gender-specific behaviors.

3. Peripheral metabolism of sex steroids

A number of peripheral modulations of the action of sex steroid hormone determine
the type and degree of development of the secondary sex character. Such variability
contributes to the normal sexual differentiation and determines certain abnormalities in sexual
features (see below). These peripheral influences include the following:
a. Peripheral conversion of androgens to estrogens mainly in the skin, subcutaneous fat
and liver.
b. Conversion of testosterone to the more active dihydrotestosterone by the intracellular
enzyme 5 a reductase present in cell in certain target sites. In the male DHT mediates
the following effects: development of the external genitalia, prostate, growth of facial
and body hair, development of acne and temporal hairline recession.
c. Abnormalities in androgen receptors or the binding of androgen/receptor complex to
DNA. These abnormalities determine the development of the androgen insensitivity
syndrome (see below).

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4. Pubertal and postpubertal hormonal production

Under the effect of hypothalamic pituitary axis, the gonads produce their specific
hormone, which result in development of the secondary sex characters and full maturation of
the internal genital system.

5. Social influences
The gender role and a spectrum of social behaviors are strongly influenced by
assignment of sex, followed by certain social influence requiring a pattern of life including
clothing, bodily gestures, behavior and interaction with the other sex.

Sex Ratio
Statistically it might be expected that the random fertilization of the ovum by either an
X or Y carrying sperm would produce equal numbers of both sexes. However, it is frequently
stated (without much of solid basis) that sex ratio amongst very early embryos is 160 males to
100 females. It has been postulated that the lighter Y carrying spermatozoa have more vigor
and reach the site of fertilization in higher concentration. The sex ratio at birth however is
only 106 boys for 100 girls. The suggested explanation for this apparent deficit is that the
male zygote and embryo have special susceptibility to death in utero at an early stage of
development. By the time of adulthood, the sex ratio becomes even and by old age, the ratio
is in favor of females. The male sex is always the “weaker” and more vulnerable sex!

Improper Sexual Characters

Improper sexual features may develop during intrauterine life resulting in difficulty or
ambiguity in sex assignment of the newly born. The improper sexual feature may begin to be
evident during childhood, at puberty or during adulthood. The abnormality may be in the type
of the gonad present or in the duct system, the appearance of the external genitalia, in the
secondary sex characters, in the behavior, or in more than one of the above items.
There has been difficulty in classification of conditions of abnormal sexual
differentiation; the difficulty is mainly resulting from choosing the reference. They can be
referred to the chromosomal complement, the type of the gonad, or the sex assigned at birth.
In the past the term hermaphorditism and pseudohermaphorditism were frequently
used. Hermaphrodites, the Greek god with bisexual attributes, was the son-daughter of
Hermes, the god of athletic males, and Aphrodite, the goddess of love. True

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hermaphorditism should mean the possession of the reproductive apparatuses and functions
of both sexes. Such individuals are curiosities, and are designated when an individual possess
both ovary and testes. The ovarian and testicular tissue may be represented in one gonad or in
separate gonads on the two sides of the body. They represent very rare incidences of
maosaicism. An association of the gonads of one sex with the secondary sex organs of the
other is termed pseudohermaphorditism. If the gonads are testes, the individual is assigned as
male pseudohermaphrodite, if they are ovaries the individual is a female
pseudohermaphrodite. Such classification is a narrow one that does not cover all problems of
intersex. An alternative classification is as follows:
1. Conditions resulting from abnormal chromosomal complement (Gonadal abnormalities):
1.1 Gonadal dysgenesis
- Classical and mixed gonadal dysgenesis.
1.2 Triple X, and structural abnormalities in X chromosome.
1.3 Klinefelter syndrome.
1.4 YY syndrome.
1.5 Hermaphrodite.
2. Condition resulting from abnormal hormone production or action:
2.1 Virilization of a female
2.1.1 Congenital adrenal hyperplasia and its variants.
2.1.2 Maternal disease.
2.1.3 Drug intake.
2.1.4 Aromatase deficiency.
2.1.5 Hirsutism.
2.1.6 Psychological or behavioral virilism
2.2 Feminization of a male
2.2.1 Androgen insensitivity syndrome, complete and incomplete.
2.2.2 5 a-reductase deficiency.
2.2.3..Abnormal androgen synthesis.
2.2.4 Testicular destruction.
2.2.5 Excessive estrogen production, or drug administration.
2.2.6 Constitutional feminism.
2.2.7 Psychological or behavioral feminism.
3. Non endocrine sexual ambiguity

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1. Chromosomal abnormalities

1.1Gonadal Dysgenesis (see also under amenorrhea)

Individual with gonadal dysgenesis are usually designated at birth as female because
of possessing the female external genitalia. The abnormality is diagnosed by failure of
development of pubertal changes and primary amenorrhea. The condition may be suspected
during childhood because of presence of certain phenotypic features of Turner syndrome or
ambiguous external genitalia (in mixed gonadal dysgenesis). Approximately 60% of
individual with gonadal dysgenesis have one X chromosome i.e. are 45, X (occasionally
referred to as 45, XO), the remainder have either a structural abnormality in one of the two X
chromosomes in the whole body, or mosaicism with one of the two cell lines having either 45
O chromosomal complement or a defective X or a Y chromosome, and the other is normal 46,
XY.
About 98% of conceptuses with one X chromosome abort. The remaining 2% account
for an incidence of Turner syndrome in about 1 in 2,000 – 5,000 live born girls.
Individuals with 45, XO chromosomal complement result from nondisjunction or
anaphase lag (see under Genetics) occurring during the first meiotic (reduction) division of
either the primary oocyte or spermatocyte. The result is respectively a mature oocyte, which
may contain either two X chromosomes or no sex chromosome at all, and a spermatozoon
with either XY or no sex chromosomes. When fertilization takes place, the outcomes, which
are possible, are zygotes whose chromosome make-up is 45, X; 45, Y (never found in live
birth); 47, XXX (superfemale) and 47, XXY (Klinefetter syndrome).
Sometimes in the course of the meiotic division, part of a chromosome may be lost by
deletion or fragmentation (see under Genetics). One or two of the arms of an X (on the
chromatides), may be lost or link with an autosome (translocation). Another possibility is for
a chromosome to divide across their centromere instead of longitudinally to produce
isochromosome formation. Fertilization involving a gamete with such structural abnormalities
in the sex chromosome can results in gonadal dysgenesis, but usually not showing all the
features displayed in 45, X individuals. The latter are commonly referred to as having mixed
gonadal dysgenesis.
Errors of the above types may also occur at a very early stage of segmentation (by
mitosis) of the zygote, and the outcome is the formation two or more cell lines in the whole
body i.e. mosaicism. The possible combinations are endless but the commonest encountered
are 46, XX / 45, X; 46, XY / 45, X; 46, XX / 46, XX. Such mosaics can have mixed gonadal
dysgenesis.

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In cases of mixed gonadal dysgenesis, the ultimate effects on the gonad, the genital
tract and the phenotype depend on the extent of chromosomal loss and the relative numbers of
the different cells. It seems that the loss of part of the short arm of one X determine short
stature and other stigmata of Turner syndrome, while the loss of the distal long arm of one X
are associated with streak gonads.
Two groups of cases of gonadal dysgenesis can be characterized:
- The classical Turner syndrome usually results from a single cell line of 45 X
chromosomal composition, and the patient have bilateral streak gonads, normal
mullerian complement (albeit hypopalstic) and external genitalia, a wide spectrum of
phenotypic features (see under Amenorrhea) and congenital cardiac and renal
anomalies.
- Mixed gonadal dysgenesis or (asymmetrical gonadal dysgenesis) This variant of
gonadal dysgenesis is common and comprises mainly those cases with 45, X / 46, XY
mosaics, and those with structural defects of X chromosome. These may have a streak
gonad on one side of the body and a testis on the other. The latter can have varying
grades of endocrine function and the patient can show varying grades of
masculinization of the external genitalia.
For full description of Gonadal Dysgenesis, the reader is referred to the chapter on
Amenorrhea. Three points need to be emphasized here: The first, is that gonadal tissue having
any Y chromosome complement in a phenotypic female requires removal of the gonad as
soon as the diagnosis is made to avoid the risk of malignant gonadal tumors. The commonest
tumor is a gonadoblastoma, less commonly dysgermenoma and rarely yolk sac tumor or
choriocarcinoma. The second, that patients with gonadal dysgenesis are more likely to have
autoimmune disorder such as Hashimoto’s thyroiditis, Addison disease, alopecia, and vitiligo.
The third, pregnancy in a patient with Turner syndrome might be achieved utilizing donor
oocytes in settings that permit this practice. This however should be difficult because of
hypoplasia of the uterus.

Noonan’s Synndrome (or Ultrich syndrome)

These are very rarely encountered individual with normal male or female
chromosomal complement (i.e. either 46, XX or 46, XY) who show the phenotypic features
of Turner syndrome. Their external and internal organs are those of the female, but they are
short, with shield chest, webbed neck and congenital heart disease. Pulmonary artery stenosis
is most frequent in Noonan syndrome as opposed to aortic coarctation in Tuner syndrome.
The are likely to have mental retardation and autoimmune Hashimoto’s thyroiditis. The
syndrome is due to autosomal gene abnormality. Noonan’s are fertile and transmit the disease
to offspring as an autosomal dominant trait, but with variable expression.

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1.2 Multiple X females

One per 1000, women of European stock have 47, XXX chromosome make-up, this
being the result of non-disjunction during oogenesis. These were originally described as super
females, which are a misnomer since they are actually infertile, and suffer from
oligomenorrhea, secondary amenorrhea, and genital tract hypoplasia. Other features of the
triple X syndrome are low intelligence, and sometimes gross mental retardation or psychoses.
Some of them are fertile and do not pass the trait to the offspring..

1.3 Klinefelter’s Syndrome (47, XXY), Primary micro-orchism

The 47, XXY karyotype is only found with a male phenotype. It is not rare being
found in 2 per 1000 men of European stock. The typical effect combines tall, eunuchoid
features; and genital hypoplasia. The testes are very small and soft and may be undescended.
The gonadotrophin secretion is normal or high. The body hairs are scares and gynecomastia
develops after puberty. They may be mentally retarded and may have antisocial behavior.
Occasionally they have normal or increased intelligence. Mosaics with 47, XXY / 46, XY can
be fertile and do not pass the trait to their offspring.

1.4 YY Syndrome
They are very rare individuals with more than one Y-chromosome. They may result
from non-disjunction during spermatogenesis, or they are mosiacs. The YY males are
excessively tall and have antisocial aggressive behaviors. They are fertile.

1.5 Hermaphorditism (see above)

2. Conditions resulting from abnormal hormone production

or action

2.1 Virilization of a female

2.1.1. Congenital adrenal hyperplasia (CAH) (The adrenogenital syndrome):
This is the most common and potentially serious abnormality of sexual differentiation at birth.
It most commonly results from deficiency of certain enzyme involved in the synthesis of

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cortisol in the adrenals. Consequently, there is deficiency of the negative feedback on ACTH
secretion by the pituitary, which is produced in excess. The result is adrenal hyperplasia with
excessive production of the steroid precursors. These are deviated to excessive production of
adrenal androgens: androstendione, dehydroepiandrosterone (DHEA), DHEA sulphate and
testosterone. Females with congenital adrenal hyperplasia develop varying grades of
masculinzation of the external genitalia. This takes the form of hypertrophy of the clitoris and
varying degrees of fusion of the urogenital folds and anatomical changes in the lower urethra
and vagina. These result in ambiguity of the external genitalia at birth and difficulty in sex
assignment. Because the secretion of antimullerian hormone is normal (not increased) in the
females with CAH, the fallopian tubes, uterus and upper vagina develop normally. Since
Wolffian duct development depends on high local (apacrine effect) androgen levels provided
by the male gonad, the excessive adrenal androgens in CAH in a female do not stimulate the
development of this Wolffian duct system. CAH occurs at an equal incidence in males but
does not result in any recognizable abnormalities in the external genital organs of the male,
but can result in metabolic abnormalities. The latter abnormalities occurs in both sexes when
the resulting hypertrophy can not make good the deficiency of corticosteroids, and take the
form of salt-losing wastage (in 60% of cases), hypertension (5%) and rarely hypoglycemia.
Types of enzymatic defects:
a. The most common enzymatic defect causing CAH is deficiency in 21-hydroxylase,
which is present in 90% of cases. This is an adrenal specific enzyme and its
deficiency results in defective synthesis of cortisone and cortisol and increased
availability of progesterone and 17-hydroxyprogesterone, which are deviated to the
production of excess of DHEA, androstenedione and testosterone. Severe cortisol
deficiency, uncompensated by adrenal hyperplasia leads to salt-losing wasting.
b. Deficiency of 11-b hydroxylase is a much less common cause of CHA. Another
adrenal specific enzyme which catalyzes the final formation of corticosterone and
results in excessive production of adrenal androgens. This type of deficiency is more
likely to lead to hypertension in later life. Deficiencies in other enzymes like 17-a
hydroxylase, 3b hydrosteroid dehydrogenase and cholesterol cleavage enzyme are
very rare. Since they are not specific to the adrenal (also important for gonadal
synthesis of steroids), the affected fetuses are having deficiency of cortisol, androgens
and estrogen. They result in various grades of genital ambiguities in males and female
fetuses.
c. These enzymatic defects are inherited as autosomal recessive trait transmitted from
the mother or father. The gene determining the commonest type (the 21-hydroxylase
deficiency) is located on the short arm of chromosome 6 in close proximity to gene

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determining the human leucocyte antigen (HLA) complex. Consequently, deficiency

of HLA can be associated, and HLA typing can be used to determine the carrier status
in family members and for early prenatal diagnosis before virilization. This diagnosis
can be the basis of early prenatal therapy to prevent virilization of female fetuses.
The incidence of 21-hydroxylase deficiency is in the region of 1 per 14,000
births. When one offspring is affected, the ratio in future offspring is one affected to
three unaffected offspring. Patients with treated CAH have a chance of 1 in 200 to
produce an offspring with CAH.

Normal and abnormal sexual differentiation; Figure 1: Steroid synthesis in the

adrenal:
Enzymes:
2. Cholesterol side-chain cleavage enzymes
3. 17a hydroxylase
4. 17,20 desmolase
5. 3b hydrosteroid dehydrogenase ]
6. 21-hydroxylase
7. 11-b hydroxylase
8. 17- Hydroxsteroid dehdrogenase
9. Aromatase

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Clinical picture of CAH

Three clinical forms of CAH can be recognized:
1. Simple virilization of female fetus.
2. Salt-losing wastage.
3. Late onset adrenal hyperplasia: also called non-classic, attenuated or acquired adrenal
hyperplasia.

1. Simple virilization: Female pseudohermaphorditism

High fetal androgens result in variable grades of fusion of the urogenital folds in the
female fetus (but the male fetus with CAH does not show any abnormality in its external
genitalia). Urogenital fusion beings posteriorly and proceed forward; the earlier the
development of hormonal abnormality the greater the fusion anomaly. The spectrum ranges
from partial to complete fusion up to extension, of fused labial folds under the enlarged
clitoris (thus simulating a male fetus with hypospadias). Variable degrees of clitoromegraly
are present. The gonads are generally intrabdominal. In extreme cases, the absence of
palpable testes may be the only clinical marker suggesting female pseudohermaphroditism.
Variable grades of virilization can be manifest when more than one female offspring are
affected in the same family.
If untreated, the female child with CAH will develop signs of virilizing precocious
puberty. Pubic hair appears by the age of 2 – 4, followed by axillary hair, then a beard. Bone
age is advanced in early childhood, but because of early epiphyseal closures, a short stature is
expected in adulthood. Progressive masculinization of the body built, deepened voice, acne,
amenorrhea, and infertility can occasionally be the presenting abnormalities.
2. Salt – losing form
About two-thirds of infants (females and males) develop hyponatremia, hyperkalemia,
high urinary sodium, and low serum and urinary aldosterone levels; and as a result high
plasma rennin activity. Infants with salt wasting first demonstrate poor feeding and may
develop diarrhea and lethargy before the full-blown Adisonian crises and death. The male
infants with salt losing CAH are more likely to be missed because of absence ambiguity of
the external genitalia. Early diagnosis is crucial to avoid this fatal outcome.
3. Late-onset adrenal hyperplasia
Late onset adrenal hyperplasia or Nonclassic 21-hydroxylase deficiency is almost only
manifest in females. They show no intersex disorder at birth. It shows itself in early
adrenarche with premature appearance of pubic hair, but usually present as cases of rather
advanced polycytic ovary syndrome. They have amenorrhea, hirsutism and clitoromegaly.
The condition is diagnosed by presence of marked elevation of 17-hydroprogesterone, DHEA
and DHEA sulphate. They need corticosteroid therapy to correct their endocrine abnormality.

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Diagnosis of CAH
a. Perinatal diagnosis
This is indicated in families having previously affected offspring. The prenatal
diagnosis of CAH can be achieved by either amniocenthesis or chorionic villus sampling. In
the former elevated level of 17-hydro-progesterone and androstenedione can be demonstrated.
Chorionic villus sample can be processed by DNA probes. The diagnosis can allow either
early termination of pregnancy, or initiating corticosteroid therapy of the mother, using
multiple daily doses of dexamethasone. This treatment can prevent, if initiated early in the
second trimester, virilization of female external genitalia and androgenic conditioning of the
fetal brain. Given that only one in four sibling are at risk and one half will be female, the
treatment will be required in only 1 out of 8 fetuses.

b. Postnatal diagnosis:
This is required in newly born with ambiguous genitalia with no palpable scrotal or
inguinal gonads, and in infants shoving evidence of salt-losing wasting.
The diagnosis depends upon demonstrating high level of plasma or serum 17-
hydroxyprogesterone (17-OHP). With the 21-hydroxylase or 11-b hydroxylase deficiencies,
the 17-OHP level will be 50–400 folds above the normal; a concentration 3,000 to 40,000
ng/dl (90–1,200 nmol/L) can be found. DHEA, DHEA-S and testosterone are also elevated. In
many countries, the measurement 17-OHP is done routinely for all newborn infants to detect
subclinical types of enzyme abnormality.
Buccal smear and karyotyping are done in all infants with ambiguous external
genitalia. Cases of CAH are chromatin positive and have normal 46, XX karyotype.
To diagnose salt-losing abnormality-blood electrolytes are measured together with
determination of plasma rennin activity, which can be markedly elevated. This is required in
all infants with ambiguous genitalia, also in male infants when there has been a previously
affected sibling and even when there is a history of unexplained neonatal death.
For the diagnosis of late-onset or adult type of adrenal hyperplasia, the level of 17
OHP can be not very high, but a level higher than 200 ng/dl (6 nmol/L) is highly suggestive.
The measurement is done early in the morning to avoid later elevations due to the diurnal
pattern of ACTH secretion. In borderline cases an exaggerated rise of 17-OHP after
administration of ACTH bolus can be demonstrated. The blood levels of DHEA, DHEA-S
androstenedione may be elevated.

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Treatment of CAH
a. Medical treatment
Treatment of congenital adrenal hyperplasia is to supply the deficient glucocorticoid,
cortisol. This will suppress ACTH secretion and the production of adrenal androgens. This
therapy needs to be initiated shortly after birth, and combined with salt retaining
mineralocorticoids in order to avoid the fatal outcome of salt-losing wasting. The usual
treatment is the daily administration of 10 mg of hydrocortisone (e.g. Cortef, Pharmacia,
Upjohn) and 100 µg of 9-fluorohydrocortisone. The treatment should be monitored by
measurement of 17-OHP, androstenedione, testosterone and plasma rennin activity at monthly
(or more frequent intervals in salt losers) until the levels stabilize. The target is a level of 17-
OHP 500 to 1000 ng/dl in order to avoid both under or over-treatment. The treatment is
maintained lifetime. Under-treatment increases the likelihood of Adisonian crisis, and over-
treatment results in Cushingnoid manifestations. Major stress like that of surgery needs
boosters of glucocorticoids.

Surgical treatment
Correction of the abnormality in the external genitalia should be done in the first year
of life in order to avoid psychological injury of the child. The labial fusion separated by
careful plastic surgery to ensure normally appearing external genitalia. Clitoridectomy can be
complete or partial (conserving the glans).
Normal sexual and reproductive performance is expected, particularly with good
compliance with medical treatment. Cesarean delivery may be required if the vulva is
severely scarred by previous plastic surgery. With the low, nearly physiological dose of
corticosteroids, a teratogenic effect of the therapy on the fetus is not expected. Aside from the
liability associated with genetic transmission of this syndrome (1 in 200), the children born to
patients with CAH can be normal.

2.1.2 Masculinization due to elevated maternal androgens

Elevated maternal androgens can occur in the following conditions:

- Leuteoma of pregnancy is in itself rare but is the most common tumor associated with in
utero masculinization of a female fetus. The patient has 5a reductase activity. Luteoma is
a solid small-to moderate sized tumor of the ovary, which develops during pregnancy,
stimulated by HCG, and usually disappears after pregnancy. The virilization of the
external genitalia is not usually marked. The pregnant woman also shows evidence of
virilization.

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- The rare maternal androgen producing tumors like arrhenoblastoma or Leydig – cell
tumor, very rarely complicate pregnancy since they are associated with amenorrhea. They
can then result in masculinization of a female fetus. These tumors can have excess of 5 a-
reductase enzyme, which transforms testosterone to dihydrotestosterone (DHT). DHT is
not aromatizable by placental aromatase and can reach the fetus.

- Exogenously given androgens for such conditions as endometriosis. Inadvertent

continuation of drugs like danazol during pregnancy very rarely causes mild
masculinization of the female fetus. Synthetic progestogens derived from nortestosterone
are rarely implicated in masculinization of the female fetus, since they are non-
aromatizable.

2.1.3 Placental Aromatase deficiency

The placenta has the capacity to aramotize native androgens like DHEA-S (which is
produced in excess by the feto-placental unit) to estrogens, which will not have any
masculinizing effect on the female fetus. Rarely, conditions exist in which this “neutralization
“effect of placental androgens either does not occur or is bypassed and a female fetus is
masculinized.
Placental aromatase deficiency is a very rare enzymatic abnormality of the placenta.
The pregnant woman will have very low estrogen levels in blood and urine in absence of fetal
distress. Because of deficiency of aromatase, the great amounts of DHEA and DHEA-S are
not converted to estrogen, and instead are converted to the more potent testosterone and DHT.
Consequently, both the mother and her female fetus will be masculinized.

2.1.4 Virilization of pubertal or adult females

- Manifestations of virilization
Virilization does not always indicate increased androgen production, but can result
from variation in the sensitivity of target organs and tissue. This sensitivity may depend on a
high or low capacity of the local tissue to convert testosterone to its active end product
dihydrotestosterone (DHT). Therefore, manifestations of virilization can occur singly or in
various combinations. They comprise, first, defeminization, then positive virilization or
masculinization manifestations. Defeminizations include amenorrhea, hypotrophy of the
breasts and internal genitalia. Virilization manifestations comprise hirsutism, acne, temporal
baldness, angular muscular body built, hypertrophy of the clitoris and certain personal and
social behaviors. The virilizing manifestations are grouped as follows:

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1. Sex organs
Hypertrophy of the clitoris and hypoplasia of the breast and atrophy and dryness of
the vagina. These are associated and frequently preceded by infertility, amenorrhea and
failure to lactate.
2. Secondary sex characters
Virilism can be indicated by coarse features, acne, a heavy angular built, well
developed muscles, broad shoulders and narrow hips, striding gait, and deepening of voice.
Exceptional athletic achievement can be rarely based on intersexual states. Some of the
Olympic female athletes have been disqualified on this basis or because of intake of
androgens.
3. Hirsutism
Hirsutism indicates the growth of coarse and dark (terminal) hair on sites unusual for
the female. This condition should be held distinct from growth of down, fine, pale vellous
hair, which normally grows on the upper lip, back, and limbs of many normal females. Also,
hirutism should be distinct from hypertrichosis, which simply implies generalized increase in
body hair. Hirsutism mainly refers to midline hair growth – that is, facial hair, hair on the
cheeks (sideburns), on the upper lip (mustache), on the chin (beard), chest intermarry area,
male escutcheon, on the inner aspects thighs, interscapular region of the back reaching down
to the intergluteal region. This is occasionally associated with temporal recession of scalp hair
or generalized baldness. A moderate amount of hair on the forearms and legs should not be
abnormal. Hirsutism may be associated with acne, which is part of excess of androgen effects
on the pilosebaceous units (PSU).
The distribution of body hair and its density is commonly constitutional, and rarely
indicate hyperandrogenic state. Both are strongly influenced by ethnic and racial factors.
Asian, light-skinned Caucasian and some black African have less hair; while subjects of
Mediterranean origin tend to be hairy. Body hair is also influenced by immediate genetic
factors, with family members (males and females) being exceptionally hairy. Elderly,
postmenopausal women often have increased facial hair, which may be associated with
diminution of pubic and axillary hair.
Apart of form this “constitutional” majority; hirsutism can be a manifestation of
virilization, the causes of which will be given later.

Growth phases of hair

Hair does not grow continuously but rather in a cycle consisting of:
- A growth phase – Anagen.
- A rapid involution and shedding phase – Catagen.
- A quiescent phase – Telagen.

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The hair grows from the papilla, and the length of hair is determined by the duration
of the anagen; this is longest in scalp hair (3 years) and shortest in forearm hair.
Androgens can influence hirsutism in three ways:
- Androgens induce terminal hair growth i.e. stimulate the transition from telagen to
anagen. Once this induction has occurred the cycle of hair growth will repeat
itself even after withdrawal of the androgen effect.
- Androgens prolong the time spent in anagen.
- 5-a reductase activity within PSU modulates the androgenic signal by
transforming testosterone to the more potent dihydrotestosterone.
Any medical treatment for hirsutism will take a long time to show its effect – the
time lag required to halt the hair growth cycle and keep the hair follicle in telagen.

4. Personality and behavior

Masculine behavior include a forceful manner, disregard to feminine appearance (e.g.
hair cut) and dress, an assumption of male attire and habits and weak maternal instinct. These
behavioral features represent social or occasionally psychological influence rather than an
excess androgen effect. Under the same category, weak or absent heterosexual impulse and
homosexual impulses or lesbian behavior may be included.

§ Sources of androgen excess in adults

Androgen production in women takes place in three compartments: the ovary, adrenal,
and peripheral tissues:
1. The ovary normally produces small amounts of testosterone, androstenedione and
dehydroepiandrosterone (DEHA). These are mainly produced in theca interna cells and
ovarian stroma. This production is mainly stimulated by LH. Excess LH activity as in
PCOS increases ovarian androgens. This ovarian androgen production is also potentiated
by a paracrine action of the insulin – like growth factor 1 (IGF-I). Insulin activates IGF-I
and this can be the basis of association between hyperinsulinism and hyperandrogenicity.
2. The adrenal produces androstenedione and DHEA sulphate. ACTH stimulates such
secretion. More than 90% of DHEA-S is of adrenal origin but the presence of increased
DHEA-S levels does not completely exclude an ovarian origin. Another adrenal androgen
is 11-b hydroxyandrostenedione may present a better marker of adrenal origin, since the
ovary does not have 11-b hydroxylase activity. Approximately two-thirds of serum
testosterone in the female results from the conversion of weaker precursor androgens like
androstenedione.

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3. The peripheral compartment contributes to the conversion of testosterone to

dihydrotestosterone DHT. This mainly takes place in the skin and is mediated by the
enzyme 5-a reductase. Testosterone is unable to produce its biological effects on the skin
(Pilosebaceous units) and external genitalia until it is converted to DHT. Since the
conversion occurs at target tissue, the level of DHT in blood is not an effective indicator
of androgen excess.
4. Postsecretion modulation of androgens: Most circulating testosterone (85%) is bound to
sex–hormone–binding globulin (SHBG). This bound fraction is biologically inactive.
About 10 to 15% is loosely bound to albumin, and 1 to 2% is circulating as unbound
testosterone. Only the last fraction is biologically active. Conditions that lower SHBG
will be associated with elevated free hormone concentrations. SHBG production is mainly
enhanced by thyroid hormone and estrogens, while it is lowered by the androgens. Insulin
also inhibits SHBG production. Conditions of hyperinsulinism as seen in some cases of
PCOS result in higher free testosterone level, thus causing hyperandrogenic state.

§ Causes of hyperandrogenic state of adult, virilization, and/or Hirsutism:

1. Constitutional: Idiopathic
Virilism of minor degree and hirsutism are usually an inherent constitutional trait;
hirsutism shows strong familial and racial tendencies, particularly in women of Mediterranean
ancestry. These idiopathic cases account for a good majority (about 90%) of cases of
hirsutism seen clinically. In this very common disorder, hirsutism is associated with regular
normal menstrual cycles and fertility and normal levels of testosterone and DHEA–S; i.e.
there is usually no other associated manifestation of virilization.
No particular gene abnormality has yet been identified to explain this constitutional
hirsutism. Two plausible hypotheses have been suggested to explain this “idiopathic“
hirsutism, but still without definite evidence:
- Relative increase in free or non – SHBG bound fraction of testosterone.
- Altered androgen action at the PSU due to increased 5-a reductase activity resulting in
augmented androgen effect.

2. Polycystic ovary syndrome

In its broadest definition, PCOS is a very common disorder, which can be associated
with hirsutism. PCOS consists of a combination of chronic anovulation and androgen excess.
The condition results also in oligomenorrhea, amenorrhea, dysfunctional uterine bleeding,
mild hirsutism and occasionally obesity. Insulin resistance and hyperinsulinism have been

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demonstrated in some cases of PCOS particularly in overweight patients. The condition

usually dates since menarche, which can be late. The serum level of LH is raised relative to
FSH level. Testosterone level is usually normal or mildly elevated. Levels of DHEA-S and
11-OHA are occasionally increased suggesting an adrenal component of excess androgen.
Raised IGF-1 (or low IGF binding protein) has also been demonstrated in some cases. These
latter change can, through a paracrine effect enhance LH effect on ovarian theca cells in
stimulating synthesis of the androgen. Some of the patients are having a gray-brown
pigmentation of the skin usually in the chin, neck, groins and axilae (Acanthosis Nigricans).
Vaginal sonography usually shows a necklace appearance the ovaries in the form of
subcapsular small cystic follicles, < 8 mm in diameter.

3. Stromal hyperthecosis of ovaries

This can be a variant of PCOS. Hyperthecosis results from differentiation of ovarian
stroma into testosterone-producing luteinized theca cells. It is particularly seen in cases with
marked PCOS clinical stigmata, particularly in those with acanthosis nigrigans and marked
insulin resistance and hyperinsulinism. Vaginal sonography can suggest the condition by
showing bilateral enlargement of the ovaries that are more solid, with little cystic changes.
These are usually marked elevation of serum testosterone, and the condition needs to be
differentiated from the rare virilizing ovarian tumors.
The condition can be temporally treated by Gn RH analogues. It may ultimately
require laparoscopic drillings to diminish the mass of ovarian stroma.

4. Abnormal adrenal androgen production

Abnormal androgen production from the adrenal cortex can result from one of the
following conditions:
a. Late-onset, (adult or nonclassic) congenital adrenal hyperplasia (CAH) is usually
caused by a partial deficiency in the activity of 21-hydroxylase. This is a genetic
disorder determined by recessive autosomal inheritance affecting members of the
same parents but to variable degrees (see above).
In most cases, the clinical presentation of late-onset CAH is similar to that of
PCOS. The diagnosis of CAH depends upon:
- A marked elevation of serum 17-OHP of early morning samples.
- An exaggerated production of 17-OHP after ACTH bolus.
- Elevated DHA-S levels
- CAT and MRI showing adrenal enlargement.

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b. Adrenal adenoma or carcinoma: These rare tumors usually result in a rapid

progression of manifestations of defeminization and virilization. Most commonly,
androgen-producing adenoma or carcinoma shows very high levels of DHEA-S,
DHEA, and rarely testosterone (through peripheral conversion). The tumors can be
associated with other manifestations of Cushing’s syndrome. Diagnostic imaging by
IVP, CAT scan and MRI demonstrate the tumor. The final diagnosis can require fine
needle biopsy.
c. Cushing’s syndrome
Cushing’s syndrome is quite rare. It arises from excessive production of
glucocorticosteroids due to either 1) increased ACTH secretion which results in
bilateral adrenal hyperstimulation, 2) an adrenal adenoma or carcinoma or 3) ectopic
production of adrenal steroids from bronchogenic carcinoma.
The clinical features of Cushing’s syndrome include: trunkal obesity;
hirsutism, abdominal striae; supra clavicular and nap pads of fat, muscle wasting and
weakness; easy brusing of skin, fine lanogo hair on the face, back and extremities;
hypertension; diabetes; osteoporosis; and psychosis. Serum cortisol levels are raised
with loss of diurnal cyclicity. Dexamethasone suppression test is useful for the
diagnosis: Dexamethasone (1. 0 mg) is given orally at 11 p. m., and plasma cortisol is
measured at 8. 0 a.m. in the next morning. If cortisol is suppressed to less than 5
µg/dl, Cushing syndrome is ruled out. Mild cases of Cushing’s syndrome need to be
differentiated from PCOS.

5. Virilizing ovarian tumors

Certain rare tumors of the ovary such as androblastoma and hilus cell tumor are
androgenic. They usually occur in young adults and cause first defeminization evident by
amenorrhea and breast atrophy; followed by virilization evident in hypertrophy of the clitores,
and deepness of voice. The tumors are small and may escape clinical examination. They may
be seen by vaginal sonography. If serum testosterone is higher than 1.5 ng/ml a virilizing
ovarian tumor is possible. CAT scan and MRI can be helpful.

6. Androgen excess during pregnancy

This is exceptionally rare. When virilization occurs during pregnanacy it usually
reflects either:
a. Luteoma of pregnancy (see above).
b. Hyperractio-luteinalis. This is similar in many aspects to luteoma of pregnancy.
However, hyperreactio-luteinalis results in enlargement of both ovaries during
pregnancy, but without definite tumor formation; but with multiple cystic formation.

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It is more common in primigravidas and is often associated with increased HCG

levels. Although the mother is virilized there is no reported cases of virilization of
female fetus. The condition regresses after delivery.
c. Deficiency of placental aromatase (see above).

7. Drugs
Apart from androgens, other hormones and drugs such as ACTH, progestogens,
corticosteroids danazol and anabolic agents can sometimes cause acne, hirsutism and some
other manifestation of virilization. There is great personal variability in the sensitivity to
these androgens.

Diagnostic workup of hirsutism, and of adult virilization:

1. Clinical assessment: This should determine the need for further investigation:
a. Assessment of the distribution and extent of abnormal hair growth. The patient is
commonly overreacting to a normal variation of hair growth. A male type
escutcheon and hairy limbs are seen in 30% of normal menstruating female. The
patient should be asked about a similar tendency to hairy skin in other members
of the family. The rate of development of hirsutism should be asked about; a
rapid development suggests androgen-producing tumor.
b. The association with functional manifestation of hyperandrogenic state, like
oligomenorrhea, amenorrhea, dysfunctional uterine bleeding, breast atrophy, or
increased libido.
c. Other manifestation of virilization: like acne, oily skin, baldness, temporal
recession, cliteromegaly.
d. Other endocrine abnormalities like obesity, hypothyroidism diabetes mellitus, or
other stigmata of Cushing’s syndrome.
e. History of drug and hormone intake.

2. Vaginal ultrasonography
- Can reveal a small ovarian tumor, the typical picture of necklace appearance of
PCOS, or enlarged dense ovaries of hyperthecosis.

3. Hormone assays
- Serum LH/FSH ratio: elevation suggests PCOS
- Serum DHEA-S: It specially indicates adrenal origin of hyperandrogenic state
particularly when markedly elevated (>700 ng/mL). Serum androstenedion or 11-b
hydroxyandrostenedione - can be also raised.

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- Serum 17-OPH – first thing in the morning. Levels greater than 200 ng/mL suggest
late- onset CAH; the condition is confirmed by a sharp rise after ACTH stimulation.
- Serum testosterone: Levels > 8 ng/mL are expected in women with hirsutism and
anovulation. The unbound fraction can exceed 2% of the total. If testosterone level
exceeds 15 ng/mL, an androgen-producing tumor must be suspected.
- If Cushing syndrome is suspected it can be confirmed by elevation of 24-hour
urinary free cortisol excretion (10 – 90 µg) or by late evening serum cortisol level of
> 5 µg/dl. A single dose of dexamethasone 1 mg at night will not suppress early
morning serum cortisol to less than 5 µg/dl; usually a level greater than 10 µg/dl is
obtained.
- To assess hyperinsulinism and insulin resistance, the ratio of fasting glucose to
fasting insulin is measured; low values suggest hyperinsulinism. The cut-off value
varies in different labs.

4. Imaging
- Sonography (see above).
- CAT scan: Abdominal, pelvic, pituitary and rarely lung scans.
- MRI: This is particularly valuable in suspected adrenal tumor, or hyperplasia.
- Selective angiography with venous sampling for measurement of adrenal and
ovarian steroid. This is difficult and not free from risk.

5. Laparoscopy adds little value to the finding of vaginal sonography in the diagnosis of small
ovarian tumors.

Treatment of Hirsutism:
1. Constitutional (idiopathic) hirsutism: reassurance:
Hirsute women who are regularly menstruating and ovulating should be encouraged to
bear with the condition if they are keen to get pregnant. This is a proper advice after careful
exclusion of any endocrine abnormality. Various lines of treatment of hirsutism frequently
interfere with ovulation and are potentially teratogenic if pregnancy occurs during therapy.
They should be encouraged to rely on depilatory practices until they achieve the desired
pregnancy. Thereafter, they can be helped by the various measures of inhibition of ovarian
and adrenal androgen. Suppression of normal levels of androgens to which their PSUs are
over-reactive can benefit patients with idiopathic hirsutism not planning an immediate
pregnancy.
2. Treatment of PCOS

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The basic treatment of the patients of PCOS keen to achieve pregnancy is clomiphene
citrate. Some non-responsive cases can benefit from laparoscopic surgery (ovarian drillings).
These two lines frequently correct anovulatory disturbance but rarely improve the hirsutism
(see under Amenorrhea). Obese patients with evidence of hyperinsulinism should be strongly
advised to attempt drastic weight reduction. This will also protect them from developing frank
diabetes and hypertension.
3. Combined oral contraceptives
- Mild or moderate hirsutism, which is judged to result from ovarian
hyperandrogenism, is frequently treated by combined oral contraceptives. This
treatment will suppress LH secretion, which is stimulatory to ovarian androgen
production. The estrogen component raises the level of SHBG thus decreasing the
proportion of free testosterone. The patients should not expect an appreciable effect
before six months of treatment. The effect on hirsutism is modest and does not occur
in all cases; but the effect on acne may be more evident.
- It may be better to use in this indication the newer formulations containing the newer
progesterone: gestodene, desogestrel and norgestimate. These progestogens have
stronger progestational effect and weaker androgenic effects than older progestogens
like norethindrone and levonorgestrel.
- Women who have a relative contraindication for use of COC can be put on depo-
provera (DMPA) injectables; a 150 mg injection is given 3-monthly.
4. Cyproterone acetate (CA)
- Cyproterone acetate is a potent progestogen that both inhibits gonadotrophin
secretion and blocks androgen action by binding to the androgen receptor
(competitive inhibitory action).
- CA is given orally in a dose of 50 mg daily. It can be teratogenic, and the patient
should have contraception.
- Diane – 35 is a combined oral contraceptive that contains 2 mg of cyproterone
acetate plus 35 µg of ethinylestradiol and available in 21 tablets. This COC is
advantageous for use by hirsute women. In more marked cases of hirsutism, daily
tablet of 50 mg of CA is added during the last 10 days of intake of Diane –35.
- This treatment is not effective in all cases.
- This treatment is more costly than the usual COCs, and may cause edema, fatigue,
weight gain, diminished libido or mastalagia.
- The effect is not appreciated before 6 months, and a relapse may start some months
after its discontinuation.
5. Spironolactone (Aldactone)

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- Spironolactone is an adlosterone – antagonistic diuretic. It inhibits the ovarian and

adrenal androgens, competes with androgen for receptors in PSUs of the skin, and
inhibits 5a-reductase activity.
- Spironolactone is given in an initial oral dose of 200 mg daily, and the dose is
reduced to 50 mg daily after the first 3 months.
- It is not effective in all cases. The effect is not appreciated except after 6 months of
treatment.
- Possible side effects are unacceptable diuresis, fatigue dysfunctional bleeding. For
fear of teratogenic effect on the fetus, the patient should be simultaneously
contracepting, possibly by an IUD or COC.

6. Dexamethasone
- Dexamethasone suppresses ACTH and is used in women with evidence of adrenal
production of androgens.
- Dexamethasone 0.5 mg or predinsolone 5 mg are given in a single tablet at night to
coincide with peak activity of ACTH during sleep.

7. Flutamide
- Flutamide is a nonsteroidal antiandrogen that is given in a daily oral dose of 250 mg
to inhibit hair growth.
- It needs to be combined with contraceptive.

8. GnRH agonists
- GnRH agonist inhibits LH-dependant androgen production.
- GnRH cause temporary ovarian “ablation“.
- It is particularly useful in patients with marked ovarian hyperthecosis and obese,
insulin resistant case of PCOS.
- It is given usually in depot preparations given monthly.
- An estrogen add-back is needed to avoid osteoporosis or it can be combined with
cyclic use of COCs.
- It is an expensive treatment, and if prolonged can cause osteoporosis

9. Cosmetics
This is indicated mainly in cases of hirsutism without definite organic cause
(idiopathic), and as an adjuvant to other previously described lines treatment for various

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clinical entities. They comprise various depilatory wax, sandpaper glove and razor shaving.
Electrolysis of hair follicles is sometimes used but is painful and may leave scars.

2.2 Feminization of a male (male pseudohermaphorditism):

2.2.1 Androgen insensitivity syndrome (AIS) (see also under Amenorrhea).
This condition of male pseudohermaphorditism is most marked example of
feminization of a chromosomally male individual. The individual is having 46, XY
chromosomal complement and consequently functioning testes but is phenotypically a female.
The syndrome is due to a maternal X-linked recessive genetic abnormality. As a result, there
is deficiency in androgen receptors, or the androgen is post-transcreptionally expressed in the
target cells as estrogens. Consequently, the following changes typically occur in the fetus:
1. Due to the normal chromosomal influence, the gonads are testes. These are usually
undescended, inguinal or abdominal.
2. Androgen induction of Wolffian duct development does not occur, and the individual
will not have the duct system of the male.
3. Due to normal production of antimullerian hormone by the testes, the mullerian duct
does not develop i.e. there is no tubes uterus or upper vagina. The lower vagina,
which develops from urogenital sinus, is present.
4. Due to the absence of an androgenic effect, the external genitalia differentiate in the
female direction. Usually there is no problem in sex assignment of the individual as a
girl.
5. Testosterone levels in blood are normal for men or slightly elevated, the estrogens are
“normal“ for the male, LH and FSH secretions are normal or elevated.
6. At puberty, the typical feminine secondary sex characters will all develop in the usual
way. Even the “girl” will have normal or abundant breasts and may tend to be tall.
However, the pubic and axillary hair will be scarse. She is reared as a female and
usually presents for primary amenorrhea or coital problems due to short vagina.
7. There is complete insensitivity to androgen administration. Usually, it is wise not to
try to change the sex of the individual or inform “her “that she is genetically a male.

Androgen insensitivity syndrome accounts for about 10% of all cases of primary
amenorrhea, third most common after gonadal dysgenesis and congenital mullerian agenesis
(Mayer – Rokitansky – Kustner Syndrome). The absent uterus in a normal appearing female
is encountered in only two conditions: androgen insensitivity syndrome and mullerian
agenesis.

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The “sisters” of the affected individual are also likely to be affected. However, this
typical picture is not always present in all affected individuals. Two types of androgen
insensitivity syndrome are described: the complete form and the incomplete form.

- Complete Androgen Insensitivity (CAIS) – Testicular Feminization Syndrome: (See

under Amenorrhea)

- Incomplete Androgen Insensitivity Syndrome (IAIS)

IAIS is far rarer than the complete form (one tenth). Except for the presence of
cliteromegaly and partial fusion of the labioscrotal folds, the condition is similar to the
complete form, and the infant is usually reared as a female. At puberty, the breasts may be
underdeveloped. A vaginal pouch is present but there is some incomplete development of the
Wolffian duct system. In rare instances of IAIS more marked masculine characters are present
at birth and a male child with hypospadias is diagnosed.
The Reifenstein’s syndrome is a much rarer subtype, in which a 46, XY karyotype is
associated with a male external genitalia albeit with a small phallus with hypospadias. The
male pubertal changes are incomplete and there can be gynecomastia. The male is subfertile,
or infertile. The syndrome can also comprise as well the undervirilized but fertile male. He
has a small penis, decreased body hair and gynecomastia.
All these subtypes represent X – linked recessive trait with variable appearance in the
family members. Molecular biology studies have indicated that the mutation is in the
androgen receptor gene. As a result, the androgen – androgen receptor complex cannot bind
to the DNA to elicit the response (see under Genetics).

2.2.2 5-a reductase deficiency

A rare form of male pseudohermaphorditism results from deficiency of the enzyme 5-
a reductase that transforms testosterone to the more potent dihydrotesterone (DHT). It is due
to autosomal recessive genetic defect. Female offspring are normal and fertile but male
offspring show variable grades of feminization. These are similar in their clinical features to
cases with incomplete androgen insensitivity syndrome.
Because of inadequate DHT formation at the target tissue the following changes will
occur:
1. The external genitalia will be incompletely masculinized: There are a small penis, extreme
hypospadias, the scrotum is bifid and there can be small vaginal pouch. The testicles are
undescended being usually inguinal. Consequently, the gender is usually assigned to the
female sex.

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2. Development of the wolffian duct system which is dependent on testosterone will occurs
normally. The individual will have the epididymis vas deferens, and ejaculatory duct.
However, structures dependant of DHT: the external genitalia, urethra and prostate do not
develop along the male line or are underdeveloped.
3. The mullerian duct will not develop i.e. there are no tubes ovaries and vagina. There is no
deficiency of AMH.
4. In difference from IAIS the individual is masculinized at puberty: the phallus enlarges the
breast remains male; facial hair develops albeit scantier than normal; and there is no acne.
The body is macular and there is inclinications to the female sex.
5. Exogenous androgens are moderately effective – in contrast to cases of androgen
insensitivity syndrome.
6. Some development of seminiferous tubules can occur after puberty, but they are grossly
defective due to the undescendent location of the testes.
- The karyotype is 46, XY.
- The condition simulates IAIS and is differentiated by elevated T: DHT ratio, particularly
after HCG stimulation.
- The individual is better off as a female. Estrogen administration can induce breast
development, and augment pubertal changes in the feminine direction. Gonadectomy is
necessary to avoid: (1) neoplastic development in the undescended testes and (2) the
pubertal virilizing manifestations.

2.2.3 Defective Androgen Synthesis

This is a very rare cause of male pseudohermaphorditism resulting from defective
synthesis of testosterone in the testes and adrenal. These defects are inherited as autosomal
recessive trait resulting mainly in deficiency of the activity of 17 b hydroxysteroid
dehydrogenase. Consequently, there are usually low testosterone levels and elevated
androstenedione and estrogen.
The external genitalia are of the female type, but there is a male internal genitalia, no
mullerian duct organs and the testes are undescended. At puberty, there may be limited degree
of virilization depending on peripheral conversion of androstenedion to testosterone. In these
individuals, who are raised as girls, early gonadectomy is required.

2.2.4 Destruction of the testes

Removal of the testes before puberty results in eunuch who has a tall feminine figure.
Cases of Kinefelter syndrome also result in a similar phenotype. He will also show soft
hairless skin, a high-pitched voice, and weak or absent heterosexual interest. The effect of
castration in later life is less obvious but gynecomastia can occur.

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The undescended testes or the ones damaged by orchitis usually preserve their
endocrine function; even though it does not produce spermatozoa.

2.2.5 Excessive estrogen production or administration of drugs

These can result in feminizing manifestations. The condition can result from:
1. Rare estrogen – producing adrenal cortical tumors.
2. Inadvertent or intentional administration of estrogens.
3. Liver cirrhosis.
4. Chronic renal failure or renal dialysis.
5. Psoriasis, and eczema.
6. Bronchogenic carcinoma.
7. Chronic cimetidine, intake.
8. Chronic and excessive Gynsing intake.
9. Rarely results from reserpine and phenothiazine derivative.

2.2.6 Constitutional feminism

An inborn weakness of masculinizing genes (of as yet undetermined nature) can
account for gynecomastia, weak beard, small penis and high-pitched voice. These are the
counterparts of constitutional hirsutism. They are usually associated with normal heterosexual
behavior and fertility.

2.2.7 Psychological or behavioral feminism

Many examples of effeminate behavior and appearance have an entirely psychological
basis. Homosexuality (Gay behavior), bisexuality and transvestism are gross forms (See under
Problems of sex and marriage).

3. Nonendocrine sexual ambiguity

Isolated defects of the genitalia seen at birth and not related to abnormality in the
usual mechanism of sexual differentiation are very rare. These might be related to viral
infections during pregnancy like rubella, or amniotic bands. There can be isolated
abnormality in one component like absence or duplication of the penis, epispadias, anteriorly
placed scrotum (in front of the penis) or cloacal formation. The karyotype and hormonal
indices are normal.

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Diagnosis and Management of Ambiguous Genitalia

Diagnosis of ambiguous genitalia at birth

This is a difficult clinical situation that faces the obstetrician and the parents when
the external genitalia of a newborn infant is neither that of a typical female or a typical
male. This is quite a dilemma for all parties and needs urgent decision. The ambiguity can
comprise one or more of the following features:
1. Testes not found in the scrotum.
2. The phallus is too small for a male or too big for a female child.
3. There is various grades of fusion of the urogenital and labioscrotal folds. Since
the fusion normally proceeds from behind forwardly, the defect varies from a
bifid scrotum to fused folds with hypospadias.
The possibilities include the following:
1. Congenital adrenal hyperplasia in a female child. This should be the first
possibility since it is actually the commonest cause of ambiguous genitalia and
because there can associated metabolic abnormalities that can be life–
threatening. Therefore, this diagnosis needs either confirmed or ruled out from
the start.
2. Incomplete androgen insensitivity syndrome.
3. Mixed gonadal dysgenesis.
4. 5a-reductase deficiency.
5. True hermaphorditism.
6. Abnormal androgen synthesis.
7. Elevated androgens in the maternal circulation.
8. Very rarely, isolated nonendocrine abnormalities.

Diagnostic workup
This should be rapid but organized. The aims of the clinico–laboratory study are to (1)
assign the infant to the appropriate gender; (2) identify life – threatening condition; and (3)
begin the necessary medical, surgical and psychological interventions. However, the
diagnosis should be definite to avoid the grave consequence of the need for future change in
gender identity; some delay may be occasionally mandatory. The scheme of diagnosis should
proceed in the following order.
1. Maternal (and may be cord) blood should be drawn to rule out the presence of androgen
producing conditions, e.g . luteoma, ovarian or adrenal tumors of the mother, or placental
aromatase deficiency.

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2. History about the following points:

a. History of a previously affected relative (mainly sisters) may aid in the diagnosis of
incomplete androgen insensitivity syndrome.
b. History of a previous sibling with genital ambiguity or a previous unexplained
neonatal death strongly suggests the possibility of congenital adrenal hyperplasia.
c. History of maternal intake of drugs like danazol or anabolics or progestational
steroids for some time during the pregnancy.
3. Clinical evaluation of the external genitalia of the newly born.
a. Palpation of the testes: This is the most important point in the clinical examination.
Gonads in the inguinal regions or in the scrotal fold are almost certainly testes;
ovaries never herniated outside the abdominal cavity. Palpable testes rules out the
diagnosis of CAH of a female. The testicles however, may be intrabdominal. If the
testicles are not palpable, the infant should be considered to have CAH until proved
otherwise. One should remember that testes do not normally descend until after 32 to
34 weeks of gestation. Postnatal evaluation of a premature infant may be required.
b. Palpation of the phallus: The phallus should be stretched to elongate it, and its
length is measured. The normal newborn clitoris measures less than 1 cm long. The
stretched penile length is 2.8 – 4.2 cm in length; a length less than 2.5 cm in a term
fetus is abnormally small (2 cm for 36 week fetus and 1.5 cm for 32 week fetus).
Moreover, the penis has a midline ventral frenum, while the clitoris is covered on the
above by a fold extending from the anterior ends of the labia minora.
c. Position of the urethral meatus: The urethral meatus can range from a mild
hypospadias to perineal meatus. Hypospadias is usually associated with fixed ventral
flexion due to presence of fibrous chordee, an abnormality that makes the phallus
looks smaller.
d. Extent of fusion of the labioscrotal folds: The abnormality can range from unfused
labia majora of a normal female through labia with variable degree of posterior
fusion, a bifid scrotum, to a fully normal appearing scrotum of a male infant (usually
with absent testicles). The distance from the anus to the edge of the posterior, vaginal
introitus divided by the distance from the anus to the base of the clitoris is a ratio,
which is normally less than 0. 5 in female newborns. A ratio greater than 0.5 indicates
some degree of labioscrotal fusion. A bifid scrotum has corrugated skin due to
presence of the dartos muscle, a feature absent in labia.
Sometimes, a female infant or a young child is brought by her mother who
has noticed labial fusion. Postinflammatory adhesion of the labia should first be
ruled out by stretching apart the labia minor that separate easily usually with a slight
bleeding.

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e. Presence of a vaginal (urogenital sinus) pouch: For this sake, the perineal orifice
can be probed anteriorly with a pediatric catheter. Once urine is obtained (indicating
presence in a urethra), an infant feeding tube is passed into the orifice posterior to the
catheter in attempt to identify the presence of another canal, which is the vagina. If it
contains mucus, this indicates that the other tube is mullerian. The condition can be
confirmed by lateral X-ray view after injecting urographin in the second tube.
f. Presence of a uterus: little finger rectal examination can usually allow palpation of
the uterus that is normally hypertrophied by maternal estrogens.
4. Examination for other bodily features: These include:
a. Features of Turner syndrome: webbed neck, low hairline on the nap, edema of hands
and feet and cardiac or renal anomalies. These suggest mixed gonadal dysgenesis.
b. Hyperpigmentation of the areola or scrotum may be associated with increased
production of ACTH in CAH (due to the associated increased production of
melanocyte stimulating hormones).
c. Presence of congenital inguinal hernia can be associated with IAIS.
5. Diagnostic imaging with rectal ultrasound probe or MRI can indicate the presence of the
uterus or abdominal testes. X-ray with injection of urographin in the perineal orifice may
outline the vagina in a lateral view.
6. Chromosomal and genetic studies. This is an essential step for the final diagnosis. This
includes (1) examination a buccal smear for the X-chromoatine, (2) leucocyte culture for
karyotyping, and (3) molecular biology studies, which should be initiated immediately.
The results may take some time to be completed but this should not delay the subsequent
investigation. The physician should exercise great care and tact in relating the results of
karyotypic to the parents in certain conditions, mainly AIS.
7. Electrolytes measurement: There is an immediate need to diagnose the salt-loosing forms
of CAH. All infants without palpable testes should be considered to have CAH until
proved otherwise. It needs to be remembered that newborn with normal male external
genitalia can be suffering from CAH, and be affected by salt wasting. The possibility
should be considered when a previous sibling had been affected or died neonatally. The
diagnosis of salt-wastages depends upon demonstration of hyponatremea, hyperkalemia,
high urinary sodium concentration, low serum or urinary aldosterone levels. The tests
need to be repeated after few days. Salt-wastage will be evident clinically in failure to
feed, diarrhea, apathy, and acidosis.
8. Hormonal assays
- Serum 17a hydroprogesterone (17 OHP) is the single most important hormone to be
measured in the infants with ambiguous external genitalia. A level higher than 3000
ng/dl is diagnostic of CAH with 21 hydroxylase or 11-b hydroxylase deficiency, and

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a level higher than 200 ng/dl is highly suggestive in presence of 46, XX karyotype.
Nowadays assay of 17 OHP in blood has replaced the measurement of the 24 hours
urinary excretion 17 oxosteroids.
- In the less common types of CAH 3b - hydroxysteroid dehydrogenase or 17–
hydroxylase blocks, the 17-OHP will not be elevated but DHEA and DHEA sulphate
will be raised.
- Elevated levels of 11-deoxycorticosterone and 11-dexoxy cortisol are found in 11b
hydroxylase deficiency. Tests for these hormones are not widely available.
- Normal or elevated testosterone suggest incomplete androgen insensitivity syndrome
if coupled with 46, XY karyotype. This is associated with a normal 17-OHP.
- High testosterone: dihydrotesterone ratio indicates 5-a reductase deficiency. However
the enzyme deficiency may be present in target sites e.g the skin, without the altering
the above ratio in blood samples.
- Provocation tests may be occasionally required: Administration of ACTH may
accentuate an elevation of 17 OHP in partial enzymatic deficiency in CAH while
HCG administration accentuate T: DHT ratio in 5-a reductase deficiency.
9. Laparotomy: In very rare instances laparotomy with gonadal biopsy is required for
finalization of the diagnosis in a difficult case of intersexuality. Laparoscopy is
inadequate because the gonads are very small or can be hidden in the inguinal canal. It
will be advantageous if rapid frozen section can identify testicular structures in the
abdomen that needs removal (see above). This laparotomy is required either in:
(a) An XY infant with ambiguous genitalia, without palpable gonad and normal
androgens. The possibilities are:
- Incomplete androgen insensitivity.
- Mixed gonadal dysgenesis.
- 5 a reductase deficiency.
- True hermaphroditism.
(b) An XX infant with ambiguous genitalia, normal OHP and androgens and no
maternal androgen intake. The possibilities are:
- Mixed gondal dysgenesis.
- True hermaphroditism.

Treatment of ambiguous genitalia

See under various types.

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Chapter 8
ABORTION
Contents
• Definition
• Frequency
• Etiology
- Zygote / embargo / fetal abnormalities
- Uterine defects
- Maternal diseased conditions
• Stages and clinical types of abortion
- Threatened abortion
- Inevitable abortion
- Missed abortion
- Septic abortion
- Habitual abortion: causes and management
- Criminal abortion
• Induction of abortion

Bleeding in early pregnancy: the possibilities

1. Abortion.
2. Ectopic pregnancy.
3. Trophoblastic tumors.
4. Local lesion in the genital tract e.g. polyps, tumors ulcers, etc …
5. Menstrual irregularity, i.e. a period of amenorrhea, wrongly presumed as pregnancy
followed by bleeding. This is particularly common in women anxious to get pregnant,
recurrence of these episodes leads to the assumption of habitual abortion.

Definition
Abortion or miscarriage denotes the termination of pregnancy by any means before
the fetus is sufficiently developed to survive, i.e. before the arbitrary time of viability.
According to Egyptian rules this time is the 28th week of pregnancy. In countries where the
standards of neonatology care have substantially improved e.g. the United States this time has

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been moved to the 20th week’s gestation based upon the date of the first day of last
menstruation. This corresponds to a fetus-neonate weight of 500 g.
If the fetus issues forth from the mother after the set arbitrary time of viability it is
considered a birth and entered in vital records of births. If it is expelled dead it is considered
and recorded as a stillbirth. (All still - births need to be burried). Still - birth is defined as the
one not showing a sign of life, particularly breathing. A neonate delivered before the 25th
week but has shown sustained breathing for some time (duration of which is not defined)
should have a live-birth certificate and entered in vital statistics as such.

Frequency
Negligence to record abortion or socially determined secrecy result in underestimation
of the frequency of abortion. Moreover, when the pregnancy is early, of 2 to 3 week duration,
the abortion may be mistaken for a heavy menstruation. In fact using chemical markers e.g. -
hCG assay of blood during the later days of menstrual cycle has shown that positive tests is
quite common; with abortion occurring in about 20% of such chemically diagnosed gestation.
Moreover, the fertilized ovum (zygote) may be lost before it is implanted i.e. before the time
it can produce chorionic gonadotrophins into the maternal circulation.
Excluding the discards of zygotes before implantation and the early abortions, which
are mistaken as menstruation, clinically recognizable abortion has the incidence of 10 to 15%
of pregnancies. Women of an age of 40 years plus have a higher incidence of abortion of
20%. Eighty per cent of clinically recognized abortion occurs before the 12th week of
pregnancy.

Pathology
Before the 12th week, the pregnancy sac tends to be expelled in pieces, rarely as one
mass. After that time the abortion often resembles labor; the membranes rupture, the fetus is
expelled followed by the placenta and membranes. Retention of the placenta or part of it, and
of the membranes is more likely to occur in this abortion.
Early abortion is more commonly preceded by embryonal or fetal demise than in
second trimester abortion when the fetus is more commonly expelled live. In early abortion
the embryo is frequently grossly abnormal. Frequently it is rudimentary or even absent
altogether. The latter condition is called blighted ovum. Hemorrhage into the decidua basalis
and necrosis of adjacent tissue is usually the earliest manifestation of this abortion process.
The gestational sac becomes separated in part or as whole and becomes distorted in contour.
The hemorrhages may be repeated over time and older clots may get partially organized to
form a fleshy or carneous mole. This consists of multiple layers of variably organized blood.

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The mass has a small distorted sac in its middle. This frequently contains no embryonal mass.
With this type of pathology repeated episodes of slight or moderate bleeding occur.
In abortion occurring after the fetus has attained a considerable size. Fetal demise is
followed by sings of maceration. This consists of softening and collapse of the skull bones,
and the long bones take grotesque attitudes due to softening of the joints. The fetus is dull red
in color and the epidermis of the skin easily peels off. The amniotic fluid is dull brownish in
color and contains shreds of epidermis. If one of a twin pregnancy dies, the amniotic fluid
gets absorbed and the fetus is compressed in one side of the growing sac of the other twin and
gets flattened: fetus compressus. Occasionally the fetus become dried and mummified, and
gets compressed to resemble a parchment paper: fetus papyraceous.

Etiology
Frequently there is no detectable cause for an abortion to give to the worried couples;
and they frequently can not appreciate such defect in medical knowledge.
Abortion can be caused by a defect in the zygote - embryo - fetus, or in its local
container, the uterus; or its general environment of the mother’s body. The first possibility is
by far, much commoner; Sometimes more than one etiological level are involved.
Therefore, the diagnostic workup should not stop at finding one abnormality.

A. Abnormal Zygote / Embryo / Fetus

Marked malformations of embryo or its membranes can frequently be detected by
sonographic and or pathological examination of the abortus. Gross anomalies of various
severity may be seen, In severe forms, the embryo is represented by a lump of disorganized
tissues; and the severest degree is the blighted ovum. Vesicular molar changes may be
affecting part or the whole of the placenta or the chorion.
Chromosomal anomalies can be detected in karyotyping of 50 to 60 of early
abortuses. The highest rate of chromosomal abnormalities is seen in early pregnancy
abortuses, with the rates declining after the embryonic period. Abnormal number of
chromosomes, aneuploidy is very frequent. Of this aneuploidy, autosomal trisomy is by far
the most frequent. This can result from an isolated nondisjunction occurring in meiotic
division of one of the gametes.
Monosomy X (45X) is the next common, and this, is rarely compatible with live birth
with Turner’s syndrome. Triploidy is the next frequent karyotypic abnormality in the abortus
and is commonly associated with hydropic degeneration of the placenta (partial vesicular
mole). Chromosomal structural abnormalities are rare in abortion specimens. Abnormal
karyotype can be detected by banding technique. Genetic mutation seems not be an important

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cause for abortion, but can cause fetal anomalies compatible with long intrauterine survival.
Consanguinity can result in increased incidence and recurrence of abortion due to single gene
defect.
There is an ongoing research in areas involving molecular mechanisms that may be
abnormal in abortion. These can, for example, involve mechanisms of histocompatibility of
the mother to the pregnancy allograft, or predisposition to influences of environmental
factors.
Abnormal placentation like molar degeneration, circumvallate placenta and true cord
knots can be rarely associated with abortion.

B. Uterine defects
1. Myomas may be associated with abortion. The nearer the myoma to the uterine cavity, the
higher the probability of causing the abortion, mainly through interfering with proper
placentation. However, big subserous myomas are compatible with term pregnancy;
therefore not all cases of abortion associated with myoma need surgery.
2. Developmental defects in the form of septate or marked bicornuate uterus predispose to
abortion. These can be diagnosed by hysterosalpingography and hysteroscopy. Septate
uterus is best managed by hysteroscopic surgery. Doubled uterus rarely needs corrective
surgery in the form of unification operation; the complications of the later operation are
serious, and the functional results are poor. It has to be remembered that successful
pregnancy can be achieved in about two-thirds of untreated recurrent abortion with
uterine abnormality. The role of corrective hysteroscopic surgery needs more evidence-
based validation. Some of the cases of doubled cavity are associated with cervical
incompetence and may benefit from cerclage operations.
3. Intrauterine adhesions: These are usually caused by curettage of an infected or missed
abortion or by postpartum curettage. Synechias are caused by destruction of basal part of
the endometrium. Uterine synechias cause hypomenorrhea or amenorrhea and recurrent
abortion. They are diagnosed by hysterosalpingography but better by hysteroscopy. They
are managed by hysteroscopic resection following by insertion of an IUD. Estrogen /
progesterone treatment is given to enhance re-growth of the endometrium without
recurrence of the adhesion.
4. Incompetent cervix: This condition results from weakness and dilatation of the upper part
of the cervix, which normally supports the weight of the pregnancy. The cervix has no
anatomical sphincter at the internal or, but the upper part of the cervix is relatively richer
in muscle fibers, the tone of which keeps the canal closed until labor contractions begin.

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Abortion due to cervical incompetence is characterized by being: 1) a second trimester

abortion. Up to the 12th week of pregnancy, the gestational sac is not completely filling the
uterine cavity and is not putting any weight on the cervix. Cervical incompetence can also
cause preterm labor. 2) The abortion process itself is relatively painless and begins by bulging
down of the amniotic sac, which ruptures, and this followed by easy expulsion of the fetus. 3)
This is expelled alive or freshly dead. 4) Usually there is no other cause for the abortion. The
diagnosis of cervical incompetence mainly depends on recurrence of such typical history in
two or more pregnancies. Attempt to anticipate the abortion by repeated sonographic
assessment of the width and length of the cervical during pregnancy is not always a reliable
predictor of abortion. The full bladder abdominal approach is more valuable then transvaginal
sonography, and the most reliable indication is the projection of the amniotic sac down the
cervical canal. In the interval between pregnancies the cervix can be found deeply torn. One
or both of its lips can be defective due to prior avulsion or necrotic sloughing out during
operative or obstructed labor. The passage of no. 6 or 8 Hegar without resistance is suggestive
but not conclusive evidence. Hystrography may show funneling of the upper cervix.
However, the correlations of these findings in the non-pregnant cervix with its weak
performance during pregnancy are not always consistent.
Etiology of cervical incompetence: previous trauma to the cervix is the usual underlying
cause. This includes forceful or excessive dilatation of the cervix for gynecological
indications. Dilatation of the cervix should be always deliberate, utilizing a set of half a mm
grading of dilators; and there is usually no need to dilate to more than 10 mm preferably no
more than 8 mm. The injury can be sustained during labor particularly as result of use of
strong ecbolics, or the application of the ventouse (or even the forceps) before full dilatation
of the cervix. In these cases the portiovaginal may or may not sustain an overt laceration, the
injury may just leave the upper cervical canal wide and week. Amputation of the cervix or
conization may be high enough to remove a good part of the upper cervical musculature and
leave behind an incompetent cervix. The worst case results from expulsion of the pregnancy
from above a cervical cerclage, which is not removed in time (see later). This results in a big
defect in the upper cervix, i.e., a cervicovaginal fistula. Another bad case is when there have
been a necrotic annular separation of cervix in difficult prolonged labor. The majority of cases
of cervical in incompetence are acquired but occasionally one sees constitutional cervical
incompetence (congenital cases), which have primary habitual abortion without any history of
traumatizing the cervix.
Treatment of cervical incompetence: Repair of cervical tear does not work in
inferring competence during pregnancy. The treatment is by a cerclage operation, consisting
of reinforcement of the weak cervix by some type of encircling purse - string suture. It is best
performed after the first trimester, preferably before cervical dilatation of 2 cm is reached.

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Bleeding, uterine contractions, or ruptured membranes are contraindications for this surgery.
Vaginitis if present should be treated before the operations. Three types of cerclage
operations can be done:
1. McDonald’s cerclage: This is a purse-string which takes repeated bites in the vaginal
mucosa and the underlying muscles around the upper part of the portio-vaginalis using a
mono-filament no: 1 silk or nylon thread. The suture is tied anteriorly with a no: 5-dilator
in the cervical canal (This is in order to avoid pressure necrosis of the tissue included
within the purse-string and the string cutting through in the cervical thickness).
2. Shirodkar’s operation is more elaborate: The anterior fornix is transversely incised and
the bladder is pushed up from the front of the cervix. A double-needled tape of Merseline
(or similar material) is used for the purpose. A bite is taken high at the level of the
internal os. A posterior transverse incision is made at a corresponding level to the anterior
one, and this is used to receive the needles, which are passed on the sides of the cervix. It
is the practice of the author to pick up the vaginal mucosa on the side of the cervix
between the jaws of an Allis’ forceps to facilitate the passage of the cerclage (Figure 1).
The encircling tape also takes a bite in the posterior lip to prevent it from downward
displacement and cutting through the mucosa. The two ends are tied posteriorly with a
number 5 dilator in the cervical canal. The ends are left long to facilitate the removal. The
vaginal mucosa is then run with chromic suture to bury the cerclage.

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Abortion; Figure 1: Modified Shirodkar’s operation.1. Urinary bladder; 2. Supravaginal

cervix; 3. Double needled Merseline tape; 4. Allis forceps applying traction on the angle of
anterior and posterior wound in order to facilitate passing of the cerclage suture

It is advisable to do the operation under a running infusion of a tocololytic drug to

prevent stimulation of uterine contractions by the anxiety and the operative
manipulations. Neither prophylactic antibiotics nor oral tocolytic drugs have been proven
to be of value. Repeated follow up of the cervical canal by sonography is frequently
reassuring during early postoperative months. The cerclage is better to be removed 2 to 4
weeks before term to allow for some effacement of the cervical canal before the
beginning of labor. Some patients opt for keeping the cerclage and having cesarean
delivery. The presence of the ligature will not prevent occurrence of future pregnancy and
saves the patient the need for repeating the cerclage.
3. Abdominal cerclage is rarely needed in situations when the vaginal operation has
repeatedly failed, and when the cervix is severely deficient. The cerclage tape is fixed
anteriorly after reflecting the bladder down the cervix. The tape is passed underneath the
uterine vessels on the sides and tied behind the cervix. The best time to do the operation is
the 12th week; delaying the operation after that will cause difficulty caused by a big
cumbersome uterus. This patient is to be delivered by cesarean section; the cerclage tape
may be left behind.
C. Maternal diseases and environmental conditions
These diseases and conditions frequently result in fetal demise, which is followed by
its expulsion, but occasionally the fetus is expelled alive. The following are the maternal
conditions, which may contribute to abortion: (Their management is also incorporated where
relevant).
1. Chronic hypertension.
2. Chronic glomerulonephritis.
3. Systemic lupus erythrematosis is associated with habitual abortion, recurrent
preeclampsia, IUGR and intrauterine fetal death.
4. Diabetes mellitus. Well-controlled diabetes however, is not a risk factor for recurrent
miscarriage.
5. Hypo- and hyperthyroidism.
6. Only severe under-nutrition can cause abortion. Deficiencies of micro-nutrients like of
certain vitamins e.g. foliates and minerals e.g. zinc have been incriminated as causes for
abortion.
7. Acute cardiac or respiratory failure can cause fetal asphyxia and death through fetal
hypoxemia.

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8. Maternal hyperpyrexia due to malaria or enterica can cause fetal demise due to
stimulatory effect of the pyrexia on the uterine contractions.
9. Incompatibility between blood groups of the fetus and the mother, resulting in rhesus and
other types of isoimmunization. This rarely kills the fetus before 28 weeks.
10. Maternal infections: Infections can be transmitted from the mother to the embryo and
fetus (vertical transmission) and may cause abortion or fetal death. A long list of
infections have been incriminated in causing abortion, occasionally without real evidence:
a. Syphilis: can cause late fetal death through infecting and causing lesions in the
placenta after the 16th week of pregnancy. Such infection is becoming a rare cause in
present time practice. (See under Infections)
b. Brucellas are a well-known cause of abortion in cattle, but are not a cause of abortion
in human.
c. Toxoplasmosis is an illness caused by Toxoplasma gondii, an intracellular protozoon.
Toxoplasmosis is a most questionable cause for abortion.
In the last few years, there has been renewed interest in this infection
among obstetrician in Egypt because of availability of diagnostic tests; many of
them are unfortunately unreliable. The cat is the definitive host of this parasite,
and it excretes the oocyst of the parazite in their feces. Cats get infected by eating
the meat of mice or other animals having the vegetative from of the disease.
Human infection is usually feco-oral and may be acquired by consuming food
contaminated by the oocysts from the feces of an infected cat. The occyst are
transmitted by hands or insects to the human mouth or food. Another much less
likely mode of human infection is eating raw under cooked meat of animals
containing toxoplasma vegetative forms though this is questionable. Once
infected by oocyst, the person may experience a parasitemia during which fetal
infections may occur if it happens in pregnant women. The acute infection may
cause a flu-like condition or pass unnoticed. It has been estimated that the chance
of transmitting the disease to the fetus during recent infection is less than 10% of
infected pregnant women. Old infection pauses no danger to the fetus.
− Acute toxoplasmosis has been associated in the literature with abortion, but
the evidence are most inconclusive. It is definitely not a cause of habitual
abortion, unless re-infection occurs, which is rare. Congenital toxoplasmosis
can however cause:
- Nothing; in more than 50% of cases.
- Chorioretinitis (most important manifestation).
- Intracranial calcification
- IUGR.

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- Microcephaly.
- Hydrocephaly.
- Hepatosplenomegaly: rare
− Preventive measures during pregnancy 1) hand washing after handling cats, 2)
having someone else change litter box daily, 3) not permitting indoor cats to go
outside and not allowing stray cats in house, 4) not feeding raw meat to cats, 5)
avoiding eating under cooked meat.
− Serological test for toxoplasma immunoglobulins Ig and IgM are most unreliable
(because of poor specificity). They can be of value if there are circumstantial
evidence of contracting the infection e.g. close association with cats, and only if
there is high titer of IgM that is indicative of a recent infection, or if there is a
markedly rising titer of IgG (done in one lab utilizing the same patches of
reagents). The antibodies particularly of IgG subtype persist in the blood for a
long time, and may be for the whole life. Their presence indicates no risk.
If maternal infection is highly probable, the diagnosis of fetal infection
can be made by positive PCR test for the antigen done on a samples of amniotic
fluids. This has replaced chord blood sampling. The mother is better treated by
spiramycin (Rovamycin) for one month (1.5 MIU tablets 3 times daily), the
treatment is better repeated during the last month of pregnancy. This treatment
diminishes but dose not completely eliminate the possibility of congenital
infection. An alternative or additional treatment is with a combination
pyrimethamine plus triple sulfonamides. This latter type of therapy should be
avoided in early pregnancy for fear of teratogenesis.
In all these recently infected cases the cord blood of the newlyborne
should be examined for the organism and its antibodies, and the appropriate
treatment should be given to infected infants. For women with confirmed first
trimester acute toxoplasmosis, the risk and state of uncertainty of diagnosis and
treatment should be fairly discussed with the couple, and termination can be a
possibility.
d. There is no evidence in humans that Listeria monocytogenes can produce abortion.
e. There is no reliable evidence that chlamydia trachomatis infection can cause
abortion. However, it is well known that infants born to mothers with chlamydial
infection of the cervix are likely to become infected with C. trachomatis and
develop inclusion conjunctivitis and/or pneumonia. The effect of maternal
chlamydial infection on perinatal complications such as preterm labor, PROM and
postpartum endometritis has not been conclusively confirmed.

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f. Herpes simplex and cytomegalovirus infections have been suggested as causes of

increased risk of abortion, but evidence are not conclusive (see under STDs).
g. An association of maternal infection with Mycoplasma hominis and ureaplasma
urealyticum and single and habitual abortion has been suggested. Prophylaxes by
treatment with erythromycin and doxacyclin in habitual aborters have been reported
but this was based upon uncontrolled trials.
h. The outcome of pregnancy dose not seem to abnormal in women with HIV/AIDS in
spite of the high probability of transmission of the virus to the fetus and newborn
infant.

11. Chronic debilitating diseases like advanced tuberculosis or carcinomatosis are associated
with increased abortion, preterm labor and pre-maturity.
12. Progesterone deficiency. Progesterone deficiency during the luteal phase and early
pregnancy has been repeatedly suggested as a cause of abortion because of the known
supportive effect of ovarian and placental progesterone on the decidua. Reduced levels of
this hormone in patients with threatened are usually the consequence rather than the
cause of irreversible damage to the fetoplacental unit. As yet, there is no conclusive
evidence in well-controlled, randomized studies that progesterone therapy is efficacious
in preventing abortion. On the contrary metaanalysis of available studies have shown that
exogenous progesterone supplementation in early pregnancy does not improve
pregnancy outcome.
13. Polycystic ovaries and hypersecretion of LH: The association between PCO, elevated
concentration of circulating LH and adverse reproductive performance, including early
abortion has been recently emphasized. This has been suggested by the finding that more
than half of women who have had recurrent abortion are having ultrasonographic
evidence of PCO and/or abnormally high LH levels during the mid-follicular phase of
the menstrual cycle. It seems that this endocrine abnormality results in a poor quality
ovum and poor quality embryo. These findings promoted treatment studies of use of
GnRH analogs in the treatment of such case of PCO associated with history of recurrent
abortion. This necessitated the concurrent treatment by exogenous gonadotrophins.
However, a recent study has shown no beneficial effect of such regimens on improving
the outcome of pregnancy in these patients. However, it is still possible that weight
reduction is a method of correcting this poorly understood abnormality together with its
consequences, including early pregnancy loss.
14. Cigarette smoking has been associated with increases risk of abortion; and there is
evidence of a dose effect; the probability is higher in heavy smokers.

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15. Spontaneous abortion is increased when alcohol is consumed even in moderation. Again,
dose effect has been demonstrated for alcohol consumption.
16. Caffeine: Coffee consumption greater than 4 cups per-day appears to increase the risk of
abortion.
17. Radiation in sufficient doses (> 5 rad) delivered in early days after implantation is
abortifacient and embryotoxic.
18. Oral contraceptive and spermicidal gels or creams do not seem to cause abortion if used
in early pregnancy. They do not cause increased incidence of congenital anomalies.
Intrauterine devices, however, are associated with increase incidence of septic abortion
after contraceptive failure. A better outcome is achieved if the IUD is pulled out; but this
only when the thread is visible. (see under Contraception).
19. Anesthetic gases have been implicated as causing abortion, but the evidence is not
conclusive.
20. Environmental toxins: There is little valid information to indict any specific environment
pollutant in causing abortion, however, there is good evidence that arsenic, lead,
formaldhyde, benzyne, ethyline oxide may cause abortion if taken in substantial doses.
Long exposure to video-display system and exposure to the accompanying
electromagnetic field do not increase risk of abortion. Short waves and ultrasound do not
increase the risk of abortion in physiotherapists who are exposed to these physical
agents. Long hours in front of computer screen have not been shown to have harmful
consequences on pregnancy.
21. Immunological Factors in Abortion
1- Systemic lupus erythromatosis is associated with increased abortion and fetal death.
The disease is diagnosed by the clinical and laboratory evidence (high antinuclear
antibodies and lupus antibodies). The prognosis of the pregnancy is particularly bad
when there is marked kidney affection.
2- Antiphospholipid antibodies: Pregnant women possessing these antibodies have
increased risk of spontaneous abortion, early development of preeclampsia IUGR,
preterm birth, stillbirth and venous and arterial thrombosis. The etiology of the
condition is not known. It is an autoimmune disease in which the produced antibodies
react with specific tissue sites causing their inflammation and destruction. These
specific targets include the vascular endothelium and the platelets. Antigen antibody
reactions cause vascular damage, vascular spasm and thrombosis and activation of
platelet aggregation. These effects collectively put an increasing part of the placenta
out of function, thus resulting in fetal compromise. The condition is closely similar to
SLE but antiphospholipid antibodies can exist without the other manifestations of this
systemic collagen disease.

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Antiphospholipid antibodies include both lupus antibody (LA) and

anticardiolipin antibodies (ACA) types IgG and IgM. As a result of increased, levels
of these antibodies there is a prolongation of the activated partial thromboplastin
time (APTT). Anticardiolipin antibodies of Ig G and Ig M types are measured by
specific ELISA tests. To diagnose primary antiphospholipid syndrome (PAPS) the
LA or ACA should be detected on at least two occasions, 8 week apart. This is
because the antibodies can be transiently produced by viral infection like influenza.
After antiphospholipid syndrome is diagnosed as the cause of recurrent
pregnancy wastage, successful treatment is possible by one or more of the following
therapies:
1- Low dose aspirin 75mg daily throughout the pregnancy. This can inhibit
prostacyclin production from the damaged endothelium, which is contributing to
vasospasm.
2- Heparin therapy in the dose of 5000 unites [subcutaneous] every 12 hours
starting from early pregnancy and continuing up to few weeks before labor. This
inhibits the increased tendency for thrombotic changes (initiated, by platelet
damage and endothelial changes) in the choriodecidual space. This dosage of
heparin does not usually require monitoring. Heparin does not cross the placental
barrier. The above two drugs can be used together and give good pregnancy
outcome
3- High dose of corticosteroids treatment. This may cause side effects. This is
rarely used.
4- Immunoglobulin therapy is being used recently.
The first two lines of treatment have given gratifying results.
The patients with primary antiphospholipid syndrome should have close
observation throughout pregnancy because they are liable to hypertensive toxemia of
pregnancy and IUGR.
Alloimmune Mechanism for abortion:
The human fetus is an allogenetic transplant distinctive from the maternal
genome in its paternal component. The mother tolerates it for reasons that are
incompletely understood. It seems that a degree of tissue incompletely is physiological,
and deficiency of histoincompatibility between the mother and fetal tissue can cause
pregnancy wastage!
Since human has a hemochoreal placentation, they’re a direct and intimate
contact of fetal tissue with maternal blood. Anatomically, the villous trophoblast is the
fetal tissue in contact with maternal circulation. Factors, which seem critical for fetal “
graft ”survival include.

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1- The nature and quantity of histocompatibility locus antigen (HLA) on the

trophoblast,
2- Circulating blocking antibodies. These blocking antibodies to paternal antigens
appear to be essential to maintain of pregnancy. Failure of syntheses of these
blocking antibodies that protect the fetus from maternal antibodies directed against
paternal antigens in the fetal tissue might result in an abortion.
3- Antileukocytotoxic antibodies increase in the maternal blood. It may be that the
failure of development of these antibodies that result in recurrent abortion.
4- Local suppressor factors. Their lack may cause abortion.
There is strong evidence that a certain degree of maternal-fetal
histoincompatibility is essential for maintenance of pregnancy, and its deficiency may
cause recurrent abortion. The diagnosis of an abnormal Allo-immunological reaction as a
cause for habitual abortion occurs mainly after exclusion of other causes, and when the
tissue HLA typing of the couple shows an unusual conformity between the parents, i.e.
there is an increased matching leukcocyte HLA types between the couple.
Therapeutic approaches for correction of abnormal immune responses are
directed at inducing normal maternal immune responses to paternal antigens inherited by
the fetus from his father. This is achieved by paternal leukcocyte transfusion given to the
mother. Promising results have been reported. Alternatively transfusion of leucocytes
from a third-party male donor or transfusion of whole blood from a blood group-
compatible male donor is used.
22. Trauma; physical and psychological: can occasionally result in abortion. The severity of
this trauma is most variable. Women tend to ascribe the pregnancy wastage to such
accidents without much proof. However, the value of rest, reassurance and enthusiastic
kind of medical support is a borne out experience in care of habitual abortions. Tender,
loving care (TLC) sometimes works in these patients. TLC usually comprises frequent,
two weekly, medical consultation, repeated ultrasonographic demonstration to the
patients of viability of her fetus, physical rest and avoidance of sexual intercourse. These
measures should continue until after the time the patient had used to abort.

Stages and Clinical Types of abortion

A. Threatened Abortion
This diagnoses is made when:
1. A woman known to have or suspecting having pregnancy develops bleeding.
2. This bleeding is slight but may be repeated.
3. This is associated with no or slight lower abdominal pains.

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4. Pelvic examination reveals signs suggestive of pregnancy; the size of the uterus is
conforming with the duration of gestation.
5. The cervix is closed.
6. Immunological pregnancy test is positive.
7. Sonographic examination shows an intact intrauterine pregnancy.
Vaginal sonography shows an intrauterine gestational sac as early as 33 to 35 days
from the first day of the last menstrual period. This is usually associated with of a serum
chorionic gonadstrophic concentration of about 1000 mIU/ml. The latter titer is consistent
with positive result in most commercial urinary pregnancy tests. One week later (40-42 day
pregnancy) an embryonal mass should be seen in the gestational sac, and by the 45th day the
fetal heart action is discernible. By this time, titer of hCG should have reached at least 20,000
mIU/ml. A single positive pregnancy test in a patient with threatened abortion does not
confirm that the pregnancy is viable or even intrauterine. If symptoms persist and the uterus
does not feel growing, the hCG assays and sonographic examinations should be repeated to
exclude embryonal demise or an ectopic pregnancy. A serum progesterone level of less than
20 mg/ml is not consistent with intrauterine pregnancy. If sonography does not indicate
embryonal growth and the titer of hCG is not rising, pregnancy demise is suspected. If a slow
rise in hCG titer or a flat curve is coupled with empty uterine cavity, the diagnosis of ectopic
pregnancy should be considered (see under Ectopic pregnancy).
The alternative diagnosis for threatened abortion include; ectopic pregnancy,
vesicular mole, an associated gynecological lesion like a polyp, or that the patient is not
pregnant; and the condition is a functional episode of bleeding. Making the last diagnosis will
save the patient the disappointment of having had pregnancy wastage.
About 50% or more of cases of threatened abortion will continue with the pregnancy,
regardless of treatment. However the expectations for such pregnancy are not fully normal.
There is slightly higher than normal incidences of preterm labor, IUGR and perinatal death in
these cases, and the treating obstetrician should be alert to these future developments.
Management: Reassurance and repeated sonographic assessment is all that can be
done. Controlled trials have indicted no value of progesterone treatment, and this if given for
some time may delay expulsion of the conspectus if pregnancy demise has already occurred.
The patient should be instructed to examine and to show her doctor any tissue expelled.
Rhesus negative women with threatened abortion (whatever the outcome) should
receive ant-D immunoglobulin, unless already isoimmunized. Threatened abortion can be
associated with fetomaternal hemorrhage that can initiate the process of isoimmunization.

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B. Inevitable Abortion:
Inevitability of abortion is indicated by:
− Severity of bleeding.
− Severity of uterine cramping.
− Dilatation of the cervical canal.
− Downward protrusion of the conceptus into the cervix.
− A gush of water may be the first indication of abortion in the first half of pregnancy,
particularly when recurrent.
The management is evacuation of the conceptus. This can be accomplished
operatively in the early weeks of pregnancy. Syntometrine (5 unit of oxytocin + 0.5 mg of
methylergometrine) is given if there is substantial bleeding. If the pregnancy is more
advanced and the membranes are ruptured, oxytocin drip should be instituted and continued
until the fetus and the placenta are expelled.

C. Incomplete abortion:
Early abortion may be expelled piecemeal. The retention of parts of the conceptus
interferes with the strong hemostatic contraction of the uterus and results in excessive
hemorrhage, which can be life-threatening. The uterine cramps are severe and the cervix is
opened. An injection of syntometrin or methergine is given, and resuscitative measures
should be initiated while the patient is prepared for immediate evacuation of the uterus.
Cervical dilatation is usually not needed and the uterine contents can be finger separated and
then evacuated by a ring or ovum forceps. Light curettage by a blunt curette is then done. It is
advisable to get the uterus contracted through intravenous injection of methergine to obviate
the possibility of perforating the soft relaxed uterine wall. The completion of evacuation of
the content is indicated by marked diminution of the bleeding and by the feeling of the grip of
the uterus upon the curette. Halothane anesthesia may cause atony of the uterus and brisk
bleeding. If the evacuation is attended with heavy bleeding the main possibility is that there
are still remaining parts in the uterine cavity, and these are to be searched for by a ring
forceps.
The ultimate indications of completion of abortion are 1) recovery of all the
components of the conceptus 2) the contraction of the uterus, 3) closure of the cervix, 4)
progressive diminution until complete stoppage of bleeding within few days after the
abortion, 5) the progressive involution of the uterus, 6) The final proof is return of
menstruation 4 to 6 weeks after the abortion. 7) If there is doubt about completion of abortion
sonographic examination can be used to confirm emptiness of uterine cavity. This can be
done intraoperatively. After completion of early abortion, ovulation may occur within 2 to 3

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weeks, indicating the need for early initiation of contraception. Persistence of postabortive
bleeding should indicate sonographic examination and repetition of D&C. Excessive
curettage should be avoided in order not to remove the basal endometrium, which can lead to
the production of uterine synechias. The content curetted out in cases of postabortive bleeding
should be always submitted to histopathological evaluation to exclude the development of
trophoblastic neoplasia. The Immunological pregnancy usually gets negative within two
weeks of the abortion. Persistence of positive pregnancy test should indicate the diagnostic
workup for exclusion of incomplete evacuation and for the early detection of trophoblastic
neoplasia.
Antibiotic treatment should be given if there is any suspicious of any criminal
termination or if the process of abortion has been protracted for some days. Anti D
immunoglobulins should be given to all Rh-negative nonsensitized patients.

D. Missed Abortion
A missed abortion is defined as retention of dead conceptus in utero for some weeks,
rarely for longer than one month. The symptoms of pregnancy may abate and the breast
changes regress. There are usually recurrent episodes of vaginal bleeding, but these do not
necessarily occur. The uterus usually ceases to grow in size. Confirmation of pregnancy
demise can be made by sonographic examination. Sometimes retention of a dead conceptus is
prolonged for some weeks. The determinant of such retention is not clear. However, the
prolonged use of progesterons in an attempt to treat threatened abortion may delay the
expulsion. Usually there is no harm of this long retention of dead conceptus. However
prolonged retention of the dead fetus may occasionally produce serious consumptive
coagulation defect. This is more likely to occur if the pregnancy had reached the second
trimester before fetal death. The patient may notice unexpected bleedings from the nose or
gums. This should indicate a diagnostic workup of coagulation defect (measurement of
clotting time, fibrinogen and fibrin degradation products), and this is also indicated if the dead
fetus had been retained for several weeks (> 4 weeks).
Management: Conservation and waiting for spontaneous expulsion usually end in the
occurrence of spontaneous expulsion. This course of action is emphasized in a primigravida
because of difficulty and dangers of dilating the nulliparous cervix. However, if the patient
gets unduly worried by the idea of carrying in her body a dead fetus and would like to resume
her normal life, if the process is delayed for some weeks or if there is a possibility of
beginning of coagulation defect, evacuation of missed abortion is resorted to either surgically
or medically (see below).

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E. Septic abortion
Septic abortion is the most serious complication of abortion and the most common
cause of related mortality and morbidity. It may account to 25% of maternal mortality in
some communities. Sepsis can complicate any of the above types of abortion, but is
particularly common with incomplete abortion. Septic abortion should raise suspicion of
criminal interference to terminate pregnancy and this should be ascertained together with the
circumstances in which this attempt has been made. The possibility of a concomitant injury of
the genital tract should always be considered in severe cases. However, sepsis can complicate
spontaneous abortion; the presence of a big open placental “wound” and the presence of
necrotic content of the uterus predispose to infections of the open uterus. The anemia
secondary to bleeding undermines the resistance of the patient.
Bacteriology: The organisms most commonly responsible for septic abortion are either
aerobic or anaerobic bacteria: Escherichia coli, Pseudomonas, - hemolytic streptococcus,
staphylococcus aureus and enterococcuus fecalis. Anaerobic streptococcus, clostrium welchii
and proteus vulgaris can be involved. Commonly, combination of these bacteria are involved.
The organisms nearly always reach the vulva, vagina and the uterus by way of one of
the following modes of infection:

- The hands of the attendant and the instruments, dressing, gause used.
- Droplet infection from the upper respiratory tract of attendants.
- Atmospheric dust.
- Direct or indirect contact with another patient or individual having infection anywhere.

Pathology: The process usually begins in, and may be localized to, the uterine contents.
Virulent infection usually results in septic endometritis and metritis. Parametritis,
salpingoopharitis, pelvic and general peritonitis can follow. Septicemia can occur at any stage
and has serious consequence. Bacteremic (endotoxic) shock may occur. This result from entry
of bacterial toxins in large amounts into the general circulation causing an antigen - antibody
reaction of an anaphylactic type. The organisms involved can be E. choli, proteus vulgaris or
hemolytic streptococcus. In severe cases bilateral adrenal hemorrhage may occur and
markedly accentuate the shock. Acute renal failure resulting in oligouria or anuria occurs in
severe cases. This is produced by a combination of hypovolemia, defective perfusion,
bacteremia and endotoxemia. The latter is common in clostridium infection. Certain
abortificients used in criminal abortion like soap solution or Lysol can cause shock if they get
into the circulation, they cause an anaphylactic shock or blood haemolysis. There is usually
both tubular and glomerular necrosis of variable degree; and consequently this damage can be
temporary or permanent.

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Clinical picture:
▪ Pyrexia is the commonest and the earliest sign. However in severe cases with bacteremic
shock it can be absent or even the temperature is subnormal.
▪ Tachycardia is a more important sign, particularly when it is not explainable by the
amount of blood loss.
▪ Hypotension can result from blood loss or bacteremic shock.
▪ Offensive discharge. Cl. Welchii can cause foul frothy discharge.
▪ Tenderness of the uterus, parametrium and /or both adnexa
▪ Lower abdominal or general abdominal tenderness and guarding occur when peritonitis
develops.
▪ Peritoneal fluid can result from peritonitis, but the possibility of injury of the genital tract
and hemoperitoneum resulting from perforation or injury of the intestines should be
suspected.
▪ Ileus, distension and vomiting.
▪ Severe pallor and prostration.
▪ Oligourea or anuria.

Management:
1. Initiate broad-spectrum antibiotics parenterally. A combination of ampicillin and
aminoglucoside is the first combination to be used. If criminal attempt is suspected, and
in severe cases metronidazole should be added. An upper vaginal swab should be taken
early for proper bacteriological diagnosis. The antibiotic combination can then be
modified accordingly.
2. Begin blood transfusion.
3. Big doses of corticosteroids are required when bacteremic shock is suspected.
4. Evacuate the uterine content. Improvement of sepsis is not expected until the infected
contents of the uterus are evacuated; this will also control hemorrhage. Oxytocin drip
should be kept running unless there is oliguria. During evacuation of the uterus care
should be exercised not to perforate the uterus, and attention should be made to ascertain
the absence of serious injuries.
5. Gastrointestinal suction can be initiated if there is ileus.
6. Monitoring blood volume and electrolyte balance should be initiated.
7. Effective renal dialysis in cases of anuria should be initiated early before metabolic
deterioration becomes severe.

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8. When perforating injury of the genital tract or injury of bowels are suspected exploratory
laparotomy is needed. The peritoneum is drained, the uterus may need to be removed if
the damage is severe, or the patient is not interested in another pregnancy.

Habitual (recurrent) abortion

This diagnosis is made when there have been three consecutive spontaneous
abortions. Previous statistical calculations have estimated that the chance of aborting a
subsequent pregnancy was high (> 50%). More recent data, indicate that the chances of a
fourth abortion is no more than 15 to 30%; i.e. is not much higher than in women how have
not had such sequence. The abortion can however, be followed by preterm delivery, IUGR or
stillbirth. The risk of recurrent abortion is higher in women have not had given birth to a live
birth before the sequence of repeated abortion. These figures should be kept in mind in
evaluating the success rate of any management approach to habitual abortion. Any approach
to treat this problem should be tested in controlled, double-blind trials in order to be able
ascribe the result to the treatment, and to rule out the contribution of bias and to defactor the
effect of psychological support coming from the mere reception of medical attention.

Investigations:
1. Carefully examine the history of the patient in order to confirm that she has had
abortion(s), and not just episodes of amenorrhea alternating with functional bleeding.
Many who present for recurrent abortion have never been pregnant before.
2. Examine the evidence of the presence of any of the etiological causes listed above.
Evidence of death of the fetus before its expulsion cannot usually be ascribed to uterine
abnormality. Intrauterine fetal death is more likely to be caused by general maternal
disease or recurrent chromosomal abnormality.
3. Assess the consanguinity of the couple; the experience of the author indicates that strong-
consanguinity of the couple (a common social trend in upper Egypt) is associated with
higher frequency of recurrent pregnancy wastage. This subject needs to be highlighted by
epidemiological research.
4. Investigate for possibility of PCOS and increased secretion of LH.
5. Karyotyping study of the couple, comprising examination by the banding technique. The
presence of a paternal chromosome abnormality indicates prenatal chromosome studies in
next pregnancy. This is also indicated if a chromosome anomaly has been detected in the
abortus. However, paternal chromosomal abnormality is expected in no more than 5% of
cases of habitual abortion.
6. Blood count; (severe macrocytic anemia) and urine analysis (proteinuria, glucosuria).

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7. Examine the possibility of primary antiphospholipid syndrome.

8. Serological test for syphilis in the couple in case of late pregnancy loss.
9. Blood grouping and Rh-typing.
10. Glucose tolerance curve.
11. Assessment of kidney functions.
12. Thyroid function profile.
13. Estimate blood foliate level.
14. Check the possibility of systemic lupus erythrematosis (antinuclear antibodies and other
confirmatory tests).
15. Assess evidence of cervical incompetence.
16. Sonographic assessment of the uterus for any focal lesion.
17. Hystrosalpingoghy.
18. Hysteroscopy to exclude abnormality in the uterine cavity.
19. Examine for HLA tissue typing of the couple.
It can be most disappointing to the couple when no cause can be ascertained, the
couple frequently require to find something to blame for previous pregnancy wastage.

Treatment:
1. Treatment of any cause (see above). These should be given only when there is evidence
of a specific cause. Many cerclage operations done are unnecessary, many expensive
antibiotic courses are unindicated, and the failure can accentuated the psychological
disturbance.
2. Empirical management.
▪ Delaying a subsequent pregnancy for some months (3 months). This gives time for
recovery from psychological trauma, and for improvement of the general health. This
includes correction of folate deficiency by administering of multivitamins including
folic acid, 5 mg t.d.s. for some months. The latter should be continued during early
pregnancy’s since there are evidence that this type of therapy diminishes the
incidence of central nervous system abnormalities of the fetus.
▪ Rest during subsequent pregnancy is a most accepted advice. This includes avoidance
of coitus and traveling particularly during the first month. Bed rest is not warranted.
▪ Psychological support by a caring, trustworthy physician can be helpful. Repeated
sonographic examinations and demonstrating to the patient the viability of her fetus
and its progressive growth can be most reassuring (TLC - refer to above).
▪ Adequate balanced diet.
▪ Progesterone and hCG treatment have been frequently given both during the luteal
phase and early pregnancy have been frequently prescribed but such approach has not

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been proven to be effective in proper randomized trials. They can be of value in

supporting early pregnancy after IVF and ET and similar ARTs.

Criminal Abortion
The Egyptian law, except for maternal conditions that make the continuation of the
pregnancy a threat to the health or life of the mother, does not allow induction of abortion by
any medical or surgical approach. A second qualified opinion is usually warranted.
However, criminal abortion is sometime done for social and personal reasons. Outside
legality of induction of abortion, such abortion are done by personnel who are not adequately
qualified, and are usually performed under most unfavorable circumstances. This results in
serious consequences and in certain countries such abortions contribute to an important
proportion of maternal mortality. There are no reliable data to the extent of this problem in
this country. Certain countries have moved to legalization of abortion, mostly on the patient’s
demand, as a way of avoidance of consequence of criminal abortion and as a means of giving
the woman the right over her body (pro-choice). The right of the fetus to life is the counter-
argument (pro-life) in the ever-continuing hot debate on this problem.

Indication for induction of abortion: (therapeutic abortion: see later, Medical Disease
Complicating Pregnancy).

Techniques for induction of abortion:

These include:
A. Surgical techniques:
1. Dilatation ring forceps evacuation and curettage.
2. Suction curettage.
3. Menstrual aspiration.
4. Hyserotomy (Occasionally hysterectomy).
B. Other mechanical methods:
Laminaria tent
Bougies, Foley, and Metreurynters.
C. Medical:
1. High dosage Oxytocin intravenously.
2. Intra-amniotic hyperosmotic fluids:
a. 20% saline.
b. 30-40% uresa
3. Prostaglandins E2, F2a, E1, and their analogues:

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These are used either as;

a. Intra-amniotic injection.
b. Extra-ovular injection.
c. Vaginal pessaries.
d. Parenteral injections.
e. Oral administration.
4. Antiprogestins - RU48C (mifepristone).
5. Hydroxysteroid dehydrogenase: Epostane.
6. Various combinations of the above.
D. Quack treatment: these have comprised introduction in the uterine cavity of certain
instruments, injection of lysols or soap solutions and other measures, all of which pose
serious trauma, intoxication, hemolysis, infection shock, and usually a combinations of all
of these.
1. Dilatation and evacuation: To avoid consequences of forceful dilatation of the pregnant
uterus (which carry risk of injury, bleeding and subsequent cervical incompetence) two
measures have been used: The first is the priming and initiation of dilatation of the cervix.
This can be achieved by:
1. Insertion in the cervical canal of laminaria. This is manufactured from certain
seaweeds. It has a strong hygroscopic property, which makes them swell resulting
in initiation of cervical dilatation. Similar synthetic substances have been also used.
Lamicel is a similar, but synthetic polyvinyl polymer in the form of sponge
impregnated by anhydrous magnesium sulfate – Lamicel swells in the cervix by
absorbing cervical mucus.
2. Prostaglandin pessaries. (See later)
3. The antiprogestin, mifepristone can be used orally to induce cervical ripening in
conjunction with prostaglandins.
2. Vacuum suction evacuation. This should now replace dilatation and ring-forceps
evacuation and curettage. This is because suction evacuation does not require substantial
dilatation of the cervix; rarely requiring dilatation of the cervix for more than 10 mm. Then,
the suction (electric or manual) curettage is then used to aspirate pregnancy products. It
ensures more completion of evacuation than forceps evacuation. The vacuum aspirator is
moved over the surface systematically in order to remove all the contents. Thereafter, a sharp
(but broad tipped) curette is used to gently remove the decidua.

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Complications of evacuation operation:

1. Uterine perforation is the most serious complication of surgical evacuation. It can readily
occur in inexperienced hands. Perforation of the gravid uterus can occur either in the
cervix or in the fundus. Cervical perforation is especially likely to occur in primigravidas
where the internal os may offer greater resistance than the softened cervical wall. A false
passage can be initiated if the tip of the uterine sound is trapped in cervical plicae.
Perforation of the fundus can occur when the cervical resistance yields suddenly to the
pushing of the dilator. This accident can be avoided be holding the dilator with the index
finger placed on dilator at a distance from its tip corresponding to the estimated length of
the uterine cavity. The rest of the hand will be held by the vulval ring preventing pushing
the dilator too far. The perforation may result in introducing the ring forceps into the
peritoneal cavity and its holding upon the intestines or omentum and injuring them.
Intestines may be brought down through the cervix. Perforation can be easily diagnosed
when the sound or dilator can pass in the uterus to a length more than what can be
expected from the length of the cavity. The operation should be stopped and exploratory
laporotomy is needed to estimate the extent of the damage. Repair of the rent or
hysterectomy are the alternative management that can be done.
2. Bleeding during evacuation of pregnancy can be severe due to cervical injury or uterine
atony. The latter is usually due to incomplete evacuation; the remaining contents
preventing the hemostatic contraction of the uterus; the bleeding will stop once the
evacuation of the uterus is completed. Atony may be caused by halothane causing uterine
atony.
3. Incomplete evacuation results in recurrent bleeding and infection. If suspected,
sonographic assessment can confirm the suspicion. The gestational sac may be missed
altogether and pregnancy proceeds after the alleged evacuation (The gestational sac is
occupying a corner of the uterine cavity and is missed by the process). The continuing
pregnancy can have a normal outcome.
4. Infection usually complicates incomplete evacuation. It can result in endometritis,
metritis, parametritis and peritonitis (see under Septic abortion).
5. Consumptive coagulopathy can occur especially if fetal death has preceded the
evacuation.
6. Cervical incompetence and habitual abortion can result from excessive and forceful
dilatation.
7. Uterine synaechiae due to over curettage.

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3. Menstrual aspiration
In reality this is a disguise of induction of abortion. If is an aspiration of the
endometrial cavity using a flexible 5 to 6 mm Karman canula and a syringe. This is done
within 1 to 3 weeks after failure to menstruate in time. Its drawbacks are that the procedure
may not be necessary when the patient is not pregnant, the implanted pregnancy may be
missed by the curette and rarely uterine perforation can be produced. Incomplete abortion will
necessitate evacuation.

4. Abdominal hysterotomy
Is rarely used, if the pregnancy is more advanced than 12 week, particularly when
tubal sterilization is contemplated upon. However, it needs to be remembered that the time of
evacuation of an unwanted pregnancy may not be the best time to make the decision of
terminating the fertility by sterilization.

B. Other Mechanical methods:

Bougies, Metraurynters and Balloon
Bougies are large, soft rubber catheters that are used to dilate the cervix.
Metreurynters are intrauterine balloons that are inflated with a sterile solution and connected
to traction, resulting in mechanical dilatation of the cervix. Foley’s catheters with a 30-ml
balloon have replaced the above devices. It is used mainly for induction of second trimester
abortion. Catheters work through stretching of the cervix and lower segment, leading to
release of endogenous prostaglandins. The use of the catheters is usually augmented by giving
ecbolics (oxytocin infusion or prostaglandins) to shorten the induction-abortion interval.

C. Medical:
1. Oxytocin infusion
Big doses of oxytocin is needed e.g. 100 units in 1000 ml of Ringers solution and start
by an infusion rate at 50 mU/min and progressively increase the rate and the dose gradually.
The success rate is not high and the procedure may overload the circulation with electrolytes
and may result in cervical lacerations.
2. Prostaglandins (PGD)
Prostaglandins differ from other ecbolics in being much more effective in inducing
contraction of the early or midtrimester pregnancy uterus. Prostaglandins are lso highly
effective in producing effacement of the cervix by inducing enzymatic changes that promote
collagen breakdown and rearrangement of collagen fibers. They are strong ecbolics through

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enhancing Ca ion influx in myometrial cells. However, prostaglandins produce unpleasant

side effects like abdominal cramps, diarrhea and vomiting.
Compounds commonly used are prostaglandin E2, prostaglandin F2, prostaglandin E1
and certain of their analogues. Prostaglandins can be administered as:
1. Vaginal suppository, the most commonly used approach. It diminishes but does not
eliminate the occurrence of side effects.
2. A gel administered through a catheter [trancervical] into the lower uterus
[extraovularly] i.e. outside the gestational sac.
3. Intramuscular injection.
4. Injection in the amniotic sac.
The effect is not always successful and the process of abortion can need to be
completed by other approaches.
The most commonly used preparations for induction of abortion include: 1) Prostin, a
PGD E2 derivative vaginal suppositories given in the dose of 20 mg every 4 hours for no more
than 6 doses. 2) Carboprost, a PGD E2 derivative given as intramuscular injections of 250 g
every 3 hours. 3) Misoprostol (Cytotec) a derivative of PGD E2. It is given either orally or
vaginally in a dosage of 100 g every 6-12 hours.
3. Intra-amniotic hyperosmotic solutions
This is particularly used for termination of second trimester pregnancy. Either 20 to
25% saline or 40 to 60 percent urea is used. They act by inducing local prostaglandin
production by the decidua.
The procedure is not free of risk particularly when hypertonic saline is used, which
can cause severe disturbance in electrolyte balance and heart failure if it gets into the maternal
circulation. These procedures usually kill the fetus, and this may be their advantage. Usually
hyperosmotic urea instillation needs to be augmented by pitocin infusion or prostaglandin
suppositories.
4. Antiprogesterone RU486 (Mifepristone)
The effectiveness of this steroid drug as an abortifacient is based upon its high
receptor affinity for progesterone binding sites causing blockage of the pregnancy supporting
effect of progesterone on the decidua (i.e. competitive binding). The pregnancy is thus
deprived of decidual support. A single 600 mg oral dose of mifepristone administered prior to
6 week from the date of the last menstrual period results in an 85% abortion rate. The addition
of various oral, vaginal or injected prostaglandins to this treatment results in abortion rates
over 95%. After this stage of pregnancy, this treatment is progressively less effective. Side -
effect of RU 486 include nausea, vomiting and gastrointestinal cramps. It may accentuate
bronchial asthma. Hemorrhage can occur due to partial expulsion, and the process may need

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completion of abortion by operative interference. RU486 has not yet been accepted for
therapeutic use in Egypt.
5. Epostane is a 3  hydroxysteroid dehydrogenase inhibitor: that blocks the synthesis of
endogenous progesterone. If administered within 4 weeks of the last menstrual period, the
drug will induce an abortion in approximately 85% of cases. This drug is not widely
available. It can cause nausea, vomiting and diarrhea.

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Ectopic pregnancy

ECTOPIC PREGNANCY
Contents
• Tubal pregnancy
- Incidence
- Etiological factors
- Pathology
- Clinical features and diagnosis
Acute syndrome
Subacute syndrome
Diagnostic aids
Diagnosis of undisturbed ectopic
- Treatment
Surgical
Medical
• Abdominal Pregnancy
• Ovarian Pregnancy
• Cervical Pregnancy
• Pregnancy in a rudimentary horn
• Heterotopic ectopic pregnancy

Ectopic pregnancy results from implantation of the pregnancy in sites other than the
endometrial cavity. More than 95 % of ectopic pregnancies are tubal. Other types include
ovarian, abdominal, cervical and pregnancy in a rudimentary horn of biocnuate uterus. A
heterotypic tubal pregnancy is a very rare combination of intrauterine and ectopic pregnancy.

Tubal Pregnancy
Incidence:
The worldwide incidence of tubal pregnancy ranges between 0.25 and 1.4 % of all
pregnancies. The incidence seems to be increasing in recent time. This has been mainly
associated with increased incidence of pelvic infection secondary to STDs. Moreover, the rate
of ectopic pregnancy after in vitro fertilization and embryo transfer can be as high as 5%.

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Etiological factors:
A. Mechanical delay in the passage of fertilized ovum along the tube, until the time the
blastocyst has acquired an invasive trophoblast. This delay can result from:
1. Salpingitis not severe enough to block the tubes: This is the main etiological factor.
Chlamydial salpingitis is an important cause of this type of pathology. The tubal
pathology is usually bilateral and this explains why after treatment of an ectopic
pregnancy, the recurrence in the contralateral tube can be reported to be as high as 10
to 15 %. The pathology in the tube varies between luminal narrowing, amulgamation
of folds of the endosalpinx, loss of cilia or fibrosis of the muscle wall interfering
with normal peristalsis. Perisalpingitis that results from puerperal or postabortal
infections or appendicitis can cause peritubal adhesions that kink the tube and
narrow its lumen.
2. Past tubal surgery restoring patency but not resulting in full normal function. This
applies to conservative surgery for past tubal pregnancy, failure of tubal sterilization
and the various types of salpingoplasty operations.
3. Tumors distorting the tubes like cornual uterine myoma or parametric masses.
4. Developmental abnormalities of the tube like diverticulae, accessory ostia, or tubal
hypoplasia.

B. Functional delay of passage of the fertilized ovum in the tube

1. Ectopic pregnancy is commoner in smokers. As much as 20 % of ectopic pregnancy
in the USA can be attributed to smoking. This can be due to disturbance of tubal
motility resulting from hormonal imbalance.
2. Failed contraception:
- Numerous studies have reported no increased absolute risk of ectopic pregnancy
amongst current contraceptive users; the absolute incidence actually diminishes.
- However, the use of contraceptives, other than traditional and barrier methods,
prevents intrauterine pregnancy more efficiently than ectopic pregnancy.
Consequently, women who get pregnant while using these contraceptives due to
either method or use failures have increased relative incidence of ectopic to
uterine pregnancy. This applies to the IUD, progesterone-only-pills (POP),
combined oral contraceptive pills (COCs) and emergency contraception. This is
particularly apparent in POP users who have higher method failure rate than
users of COC. This increased risk in ectopic pregnancy ratio is attributable to
irregular or delayed tubal motility during the use of such methods, which can be

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due to hormonal effects. Since contraceptives as Norplant and injectables have

lesser failures, the phenomenon is not apparent among their users.
- Past use of hormonal contraceptives is not followed by increased risk of ectopic
pregnancy. Pervious use of IUD however, appears to slightly increase the risk of
ectopic pregnancy. This is due to occurrence of pelvic inflammatory disease that
may result from IUD use.
3. Hormonal imbalance may also be the cause of the reported higher risk of ectopic
pregnancy associated with infertility treatment by ovulation induction. This applies to
clomiphene and gonadotrphins treatment, IVF/ET or GIFT. The occurrence of
multiple ovulations and the nonphysiological hormonal milieu can both be
contributing to the increased chance of implantation of the fertilized ovum in the
tube. In IVF/ET and other ARTs more than one embryo are transferred increasing the
chance of ectopic pregnancy. With these methods of assisted reproduction, there is
increased occurrence of the very rare occurrences of heterotypic tubal pregnancy (1%
incidence in cases of IVF and similar techniques), abdominal and cervical
pregnancies.
4. External migration of the ovum: i.e. when the ovulation has occurred from the ovary
contralateral to the tube in which fertilization occurs. This is a questionable cause of
ectopic pregnancy but this is presumed when the corpus luteum is in the ovary
contralateral to the side of ectopic pregnancy. There may also be an increased risk of
ectopic pregnancy for woman with one oviduct wherever she ovulates from the
contralateral ovary. However, this is not an enough reason for removal of the
epsilateral ovary along with salpingectomy done for treatment of ectopic; one can not
guarantee that the single ovary left behind can adequately carry out the function of
the two ovaries.
C. Ectopic endometrial patches in the tubal mucosa (tubal endometriosis): enhancing the
receptivity of the tube to implantation of the blastocyst is a possibility, which is
suggested by histopathological examination of the excised tube on few occasions.

Pathology of ectopic pregnancy

The ampulla of the tube is the most frequent site of tubal pregnancy, which can be as
peripheral as fembrial. The isthmic portion is the next common. Interstitial pregnancy is very
uncommon (3 %). From these primary sites, certain secondary forms of tubo-ovarian, tubo-
abdominal and broad ligament pregnancies occasionally develop. Ectopic pregnancy can be
primarily ovarian, or abdominal; and can occur in a rudimentary horn of a bicornuate uterus
(Figure 1).

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Ectopic pregnancy

Ectopic pregnancy; Figure 1: Sites of ectopic pregnancy.1. Ampullary; 2. Fimbrial; 3.

Isthmic; 4. Interstitial; 5. Ovarian; 6. Broad ligament; 7. In a rudfmentrry horn; 8. Cervical;
9. Secondary Abdominal;10. Primary abdominal.

Wherever the implantation of ectopic pregnancy, it is usually doomed due to the following
reasons:
1. There is no decidua in the ectopic sites: In the absence of invasion-checking influence
of the decidua, the trophoblast invades deeply in the tubal wall reaching the muscle or
peritoneum; the tube has no submucosa. The deeper invasion opens bigger blood
vessels causing hemorrhage that separates the conceptus (tubal abortion), or breaks
through the tubal wall (tubal rupture).
2. The muscle wall of the tube is thin and does not evolutes in any way similar to that of
the uterus. Consequently, the tube either tries to expel its contents through its
abdominal ostium or it ruptures.
3. Due to relatively defective blood supply, embryonal demise occurs early.
4. Severe embryonal abnormalities are common in ectopic gestation including a blighted
ovum.
One of the following consequences can develop as a result:
1. Tubal abortion: This occurs when the tube tries to expel the pregnancy towards the
abnormal ostium. This occurs in ampullary pregnancy. Initially, recurrent episodes of
slight bleeding may occur into the peritoneum in a stage equivalent to threatened
abortion. Severe bleeding can cause acute syndrome associated with severe internal
hemorrhage (Figure 2). In other occasions the slight recurrent bleeding occurs in
episodes. This results in the subacute clinical picture. Paratubal hematoma or a pelvic
hematocele can be formed because of collection of the blood. The complete extrusion of
the conceptus from the ostium is followed by diminution of intraperitoneal bleeding. If
the abdominal ostium is agglutinated, a sausage-shaped hematosalpinx develops.
Occasionally tubal mole can develop; and it is similar to the carneous mole in uterine

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abortion. This mole result from repeated small episodes of bleeding around the sac, which
get partially organized forming a fleshy mass that has a small sac in its middle.

Ectopic pregnancy; Figure 2: Tubal abortion. a: with minimal bleeding and subacute
clinical picline; b. with severe internal hemorrhage and acute clinical picture.

2. Tubal erosion or rupture: The process of breaking through the tubal wall into the
peritoneal cavity is usually gradual i.e. erosion, resulting in recurrent episodes of
intraperitoneal bleeding. A paratubal hematoma or pelvic hematocele can be developed as
a result. These attract omental and intestinal adhesions around. Sudden tubal rupture
(Figure 3) is less common but particularly occurs in pregnancy in the narrow tubal
isthmus, and is associated with acute symptoms. This usually occurs early within few
days or weeks of missing the period. Interstitial tubal pregnancy can proceed to longer
time and can reach 8 to 16 weeks due to the greater thickness and dispensability of the
surrounding myometrium. However, once rupture occurs the internal bleeding is usually
very severe, and may prove fatal due to the big vessels (at the site of anastmosis of the
uterine and ovarian vessels) rupturing.

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Ectopic pregnancy

Ectopic pregnancy: Figure 3: Tubal rupture

Pelvic hematocele can become chronic, getting partially organized and resulting in a
mass behind the uterus. This presses upon and irritates the rectum and/or the bladder.
Pelvic hematocele can get infected by organisms reaching it from the surrounding gut and
cause pelvic abscess. This if neglected can open and discharge pus either in the rectum or
the vagina or rarely in the bladder.
Uterine changes: Associated with ectopic pregnancy, the uterus gets softened and
enlarged due to formation of a thick decidua, causing the wrong diagnosis of uterine
pregnancy. Once the ectopic pregnancy gets disturbed and the hCG level in the maternal
blood drops, the support of the decidua is cut off, and consequently it is shed. This is the
cause of uterine bleeding associated with disturbed ectopic. Sometimes the thick decidua is
shed in big sheets or a big cast which can lead to the mistaken diagnosis of uterine abortion.

Broad ligament pregnancy:

When tubal erosion or rupture occurs towards the mesosalpinx; the content of the
gestational sac may be extruded into a space formed between the two layers of the broad
ligament. This usually terminates in fetal death and the formation of a broad ligamentary
hematoma. Rarely, the pregnancy may maintain its original attachment, and continue for
some more weeks in the broad ligament. This sac may later rupture into the peritoneal cavity,
or form an abscess.

Abdominal pregnancy:
This is a very rare condition. Typically abdominal pregnancy is secondary to tubal or
ovarian pregnancy. After tubal rupture the placental attachment may be rarely maintained and
it grows out and beyond the tube to get attached to the neighboring peritoneal surfaces,
usually in the back of the broad ligaments and the uterus, omentum, or intestines. Meanwhile,
the intact gestational sac continues to grow into the peritoneal cavity. Rarely, the conceptus
appears to have completely escaped after tubal rupture into the peritoneal cavity to gain a
fresh implantation site anywhere on the peritoneum. This primary implantation of the
fertilized ovum on peritoneal surface is possible but most exceptional. In this case the tubes
and ovarian on both sides appear separate from the implantation site and have no evidence of
recent or remote injury.
Fetal viability in abdominal pregnancy is most exceptional; the fetus usually
succumbs due to defective placentation. The placenta may be partially separated causing
severe internal hemorrhage. If the fetus dies after reaching an appreciable size, it can form an
abscess. Bacteria reach the sac from surrounding intestines. The abscess can open in the

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rectum, or abdominal wall discharging pus, may be, with small bones. Rarely the fetus may
get mummified or undergo saponification (adipocere formation) and is discovered long time
later during a laparotomy done for another indication.

Clinical Picture and Diagnosis of Ectopic Pregnancy

The clinical presentation of ectopic pregnancy is most variable. It is a great simulator in
clinical gynecology. However, ectopic pregnancy essentially presents in three broad
syndromes with occasional combinations:
1. The acute syndrome associated with severe intraperitoneal hemorrhage.
2. The subacute syndrome associated with mild, usually recurrent episodes of intraperitoneal
hemorrhage.
3. Recently emphasis is put on the diagnosis of undisturbed ectopic pregnancy, particularly
after important diagnostic aids have become available. Conservative approaches of
management (which preserve the affected tube) have become increasingly possible for
this case, emphasizing the need for diagnosis at this stage.

1. Acute syndrome:
This occurs with severe interperitoneal hemorrhage, usually resulting from tubal
rupture, or abortion. This is the less common presentation. The patient presents with acute
pain that the patient describes as lower abdominal or pelvic, stabbing or bursting in character.
She is usually unable to localize the pain to one side. This pain is associated with syncope and
followed by vaginal bleeding. The latter is not heavy enough to explain her prostration and
shocked state. The pain usually occurs before the bleeding. She usually reports missing her
period for some days or weeks, but not invariably so. The patient may say that her last menses
was unusual in timing or duration. Some patients may be unaware of being pregnant. She may
complain of neck or shoulder pain, due to diaphragmatic irritation by intraperitoneal blood.
Pallor is usually marked. Tachycardia is usually present, but not invariably. The blood
pressure may be lowered or gets lowered after re-measuring the blood pressure after sitting
up. The abdomen is tender particularly the lower part, and usually with a rebound. Guarding
abdominal wall can usually be appreciated. Shifting dullness may be elicited in massive
hemorrhage. The cervix is tender on moving. There may be fullness to one side, but this can
be absent. Pregnancy test can be positive but a negative test dose not exclude the diagnosis.
The picture indicates an acute abdominal emergency and suggests the need for
exploratory laparotomy. The differential diagnosis include mainly:
- Acute appendicitis. However, here, the manifestations are mostly right-sided, the
temperature is raised, and there is no shock.

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- Rupture torsion or hemorrhage of an ovarian cyst. This also includes hemorrhage

from a functional corpus luteum cyst. The cyst if big may be felt. But in the case of
rupture of a corpus luteum the picture is not drastic because of minimal internal
hemorrhage, and the cyst is not palpable.
- Acute salpingitis; the tenderness is bilateral and the temperature is high. Usually
bilateral tender masses can be felt.
- Other causes of internal hemorrhage like ruptured spleen, perforating peptic or
intestinal ulcer are rarely confused with ruptured tubal pregnancy.
- Other causes of acute abdominal pain like ureteric or biliary colic may be confused
with disturbed ectopic, particularly if concurrent with a uterine pregnancy.
If the condition of the patient allows some diagnostic time, aspiration of blood from
the Douglas pouch transvaginally may be attempted by a wide-bore spinal needle. (The
needle should be introduced into the posterior fornix parallel to the posterior uterine wall). In
case of internal hemorrhage, the blood comes down freely.
Ultrasonography is not very helpful except for confirmation of presence of a
significant amount of fluid in the peritoneal cavity and emptiness of the uterus.

2. Subacute syndrome:
This is the commoner presentation of ectopic pregnancy, and results from repeated
episodes of mild intraperitoneal hemorrhage. It can result from tubal abortion or from tubal
erosion not opening big vessels. The prospects of early diagnosis depend upon 1) having a
high index of suspicion, and 2) utilization of accessory aids for diagnosis.
In this group the pain is intermittent or continuing for some time with episodes of
exacerbations. The severity of pain varies. The vaginal bleeding is characteristically
persistent but usually not marked. This blood is usually brownish in color but can be red. This
bleeding may be taken by the patient and occasionally her physician, as indicating a delayed
menstrual period albeit with unusual characters. Alternatively, the condition is taken as
representing an abortion; this misdiagnosis is contributed to by the expulsion of some tissues,
which are in fact decidual sheets or a full decicual cast. Occasionally, uterine curettage is
done to “complete” this abortion. The persistence of bleeding after this abortion should
heighten the suspicion of ectopic pregnancy. If the pregnancy test is positive and the patient is
having a suggestive feature of ectopic an ultrasound exam, preferably TVS should be done.
The temperature is usually normal or slightly raised (<38 °C) due to blood product
absorption. This is unless there is secondary infection of a hematoma when marked pyrexia
develops.

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Ectopic pregnancy

The patient may have mild syncopal attacks associated with the pain exacerbation.
Symptoms of rectal heaviness or irritation or bladder irritation may develop. Lower
abdominal tenderness, occasionally with a rebound, may be present. This is usually more
marked on one side. Tenderness can be elicited on moving the cervix. Vaginal examination
should be done gently; care should be exercised in order not to further disturb the ectopic
pregnancy and precipitate severe internal hemorrhage. An ill-defined mass can be felt
[posterolaterally] to the uterus.
The differential diagnosis of this subacute syndrome include a variety of conditions; but
mainly:
- Intrauterine pregnancy in various stages of abortion.
- Rupture of a corpus luteum.
- Complicated ovarian cyst, with or without an associated intrauterine pregnancy.
- Appendicitis or diverticulitis .
- Salpingitis.
- Perforating peptic or intestinal ulcer.
- Renal or biliary colic with or without an early pregnancy.
-
Diagnostic aids:
1. Pregnancy test can be helpful. If positive it can diagnose that the patient is pregnant with
either intrauterine or ectopic pregnancy. If sonography shows the uterus empty, the
suspicion of ectopic should be heightened. However, since the concentration, hCG in the
blood of patients with ectopic pregnancy tends to be lower than that in intrauterine
pregnancy, and the sensitivity of pregnancy tests varies, a negative urinary pregnancy test
should not exclude the diagnosis of ectopic. The urinary latex agglutination inhibition
slide test has a range of sensitivity of 500 to 1000 mIU/ml (of the accompanying blood
concentration). Tests using ELISA technique and utilizing antibodies specific for b-
subunit of hCG are much more sensitive e.g. 50 mIU/ml (of the associated blood
concentration). These may miss a very small proportion of pregnancies. If suspicion of
the condition is high, serum assay of b-hCG should be done. This excludes ectopic
pregnancy if it is < 10 mIU/ml.
2. Ultrasound Scanning showing a definite gestational sac in the uterus usually excludes
ectopic pregnancy (except for the very rare heterotypic tubal pregnancy). However, it
needs to be remembered that a small irregular central sac - like appearance (< 3 cm) in the
uterus can result from accumulation of blood in the uterine cavity. TVS is particularly
valuable in this situation; it can usually shows a definite gestational sac, usually in one
side of the uterine cavity in uterine pregnancy as early as 35 days after the first day of the

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Ectopic pregnancy

last menstrual period. In contrast, the conventional abdominal ultrasound may not show a
definite sac until 5 to 6 menstrual weeks (i.e. 35-42 days). Extrauterine sac, even with an
embryonal pole may be occasionally detected in the adnexa, but this is unusual.
Sonography may show ill-defined mass in the adnexa.
3. Vaginal color and pulsed Doppler ultrasound: This can identify the site of implantation
of the pregnancy whether it is uterine or extrauterine. The site of the implantation shows
increased blood flow that is seen as the so-called “ring of fire” appearance, and a high
velocity, low impedance flow pattern is detected in this site. If this pattern is seen outside
the uterus, which shows instead a “cold” blood flow pattern, the diagnosis of ectopic
pregnancy is apparent.
4. Quantitative b-hCG blood assay can help the diagnosis of subacute disturbance of
ectopic pregnancy if combined with sonography whether abdominal or transvaginal, in
what is called the discriminatory b-hCG values. This latter approach is particularly
valuable in the diagnosis of undisturbed ectopic. Essentially, the discriminatory b-hCG
values cover the gap between having a rise in serum b-hCG and the time at which
visualization of the gestation sac is possible by ultrasonography (lag-time). One of the
following combinations can exist:
1- When the b-hCG in the blood is above 6,000 mIU/ml and the abdominal
sonography shows an intrauterine sac; or alternatively when the b-hCG is between
1000-2000, and the more sensitive TVS shows a sac in the uterine cavity, normal
pregnancy, absence of ectopic, is almost certain.
2- If the above levels of b-hCG are associated with empty uterine cavity, an ectopic
pregnancy is almost certain.
3- When the b-hCG are below this discriminatory values and a definite intrauterine
sac of pregnancy is identified, then spontaneous abortion is very likely.
4- When the b-hCG values are raised but below the above levels and there is an
empty uterus, no definitive diagnosis can be made. Two alternatives are possible:
1) Ectopic pregnancy, or 2) an intrauterine pregnancy which is too young to
produce the above biochemical and sonographic criteria (due to a mistake in
dating the last menstruation or occurrence of late ovulation). There is two possible
courses of action for this latter situation:
a. When there are other clinical manifestations suggesting ectopic pregnancy, one
should proceed to laparoscopy.
b. In absence of such clinical evidence, one can wait for some days repeating the
b-hCG assay and sonography every two days. The doubling time of b-hCG
level is 48 hours in normal pregnancy. Failure to attain this rate of increase

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Ectopic pregnancy

along with empty uterus is suggestive of ectopic pregnancy, but an early

demise of a uterine pregnancy is also possible. Laparoscopy is needed in such
situations
5. Culdocentesis: can identify hemoperitoneum. The cervix is pulled forward and a long 18-
gauge needle is inserted in the cul-de-sac. In chronically disturbed ectopic, brownish fluid
containing fragmented clots is obtained. Unclottd blood is obtained in case of acute
syndrome or whenever a blood vessel is inadvertently punctured.
6. Laparoscopy has markedly improved the diagnostic capability of ectopic pregnancy and
should be used liberally in order to diagnose undisturbed ectopic or early disturbance of it.
It has the additional value of its utilization in the treatment of ectopic.

Diagnosis of undisturbed ectopic

Diagnosis of ectopic pregnancy before it is disturbed can be achieved through:
1. Having a high index of suspicion in high risk cases i.e. in patient who are predisposed
have an etiologically factor (see above).
A woman with any of the risk factors should be investigated for the possibility of ectopic
pregnancy whenever she misses her period, particularly if this is associated with pelvic
pain. This may be followed by bleeding; this suggests that disturbance has begun. The
patient may describe having an usual period which can be few-days delayed, scanty and/or
prolonged. The pain is colicky and slight. Immunological pregnancy test is the first
investigation and this is followed by:
2. Daily quantitative b-hCG.
3. Serum progesterone; values below 15 ng/ml may suggest ectopic pregnancy. Repeated
assays showing declining levels support the diagnosis.
4. TVS is helpful, in fact, TVS has revolutionized the non-invasive diagnosis of ectopic
pregnancy.
5. Utilization the approach of Discriminatory bHCG values. The quality of both the assay
and sonography are obviously critical. (see above)
6. The resort to laparoscopy should depend on the result of above diagnostic aid. Exposure of
a patient with a highly valuable pregnancy as those resulting after tubal surgery or assisted
reproduction procedures to the trauma entailed on laparoscopy should be based on sound
grounds.

Treatment of tubal pregnancy

This comprises the following items:
1. Correction of shock and blood loss.

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Ectopic pregnancy

2. Surgical management:
a. Operative laparoscopy: (should be increasingly utilized).
b. Laparotomy.
3. Medical management.
4. Possibility of expectant management.
5. Anti-D immunoglobulin .
6. Plan for future pregnancy.

1- Blood transfusion can be life saving in acute cases. However, one may not wait for the
complete resuscitation before laparotomy is begun; the control of intraperitoneal bleeding
is associated with improvement of shock. Acute intraperitoneal bleeding is one of the
situation in which autotransfusion can be used, with red blood cell-sieving devices. The
procedure can be helpful.
2- Surgical treatment:
- Either salpingectomy or salpingotomy (consveration of the tube) can be done. These
can be done either by laparotomy or by laparoscopy. The latter approach is
increasingly used. With earlier diagnosis of ectopic pregnancy, conservative surgery
is utilized more frequently.
- Salpingectomy is done when the tube is severely damaged. Ipsilateral oophorectomy
is not advisable. It has been argued that removal of this ovary may decrease the
likelihood of subsequent ectopic pregnancy and improve fertility by having ovulation
consistently occurring in the ovary opposite to the available tube. However, one can
not guarantee that the remaining ovary can efficiently carry the function of the two.
- Salpingectomy can be done by laparoscopic surgery in a hemodynamically stable
patient: Initially pelvic irrigation and aspiration is done. The simplest technique is the
use of pre-tied endoloop suture to snare, the affected fallopian tube prior to excision.
Alternatively, bipolar electrosurgery and scissors, Nd:YAG laser or staplers can be
used for salpingectomy. The procedure end with repeated peritoneal lavages.
- If childbearing has been completed tubal sterilization can be done on the other side.
In the rare interstitial pregnancy, abdominal hysterectomy is the usual treatment.
- Salpingotomy: is resorted to if future childbearing is required and the tubal damage is
minimal or when the tubal pregnancy is undisturbed. It can be done by laparotomy. A
small linear incision, 2cm in length or less is made on the antimesenteric border of
the tube, and the ectopic pregnancy is extruded. Usually the bleeding stops
spontaneously but occasionally needle diathermy coagulation is required for bleeders
at the edge. The wound in the tube is usually left unsutured. However, if the incision
is too long the tubal wound can be closed by few-interrupted suture using 7-0 vicryl.

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- Milking of the pregnancy and its “fimbrial evacuation” through the abdominal ostium
has been tried in distal tubal pregnancy. This is not advisable since the tube may burst
at the weak point. Moreover, it is associated with an ectopic recurrence rate twice
that of salpingotomy. There is a high rate of surgical re-exploration for recurrence of
internal bleeding after this milking procedure; the tone of myosalpinx is weak and
may not maintain hemostasis.
- Salpingotomy can be done by laparoscopic surgery. This is used to remove small (<2
cm) pregnancy in the lateral third of the tube. After stabilization of the fallopian tube,
monopolar diathermy cautary, or laser is used make an incision in the antimesenteric
border of the tube over the ectopic pregnancy. Bipolar diathermy is safer option than
monopolar as the current only flows between the blades of the forceps and there is
much less risk of injury of other pelvic structure. However the bipolar can only
cauterize the tissue; which then has to be incised by scissors. (A bipolar cauterizing
forceps fitted with a scissors are now available). After extrusion of the ectopic
gestation, its bed is zoomed upon to ensure the removal of all trophoblastic tissue.
Closure of salpingotomy is not necessary. The laparoscopic approach in trained hands
carries no increased risks relative to open surgery and it gives equivalent future
fertility. This is besides shorter stay in hospital and lesser cost.

3- Medical management:
Methotrexate has been used for this purpose and it is given either by local
injection in the ectopic pregnancy site or by systemic administration. This may be used
in hemodynamically - stable patients and in undisturbed ectopic and with normal liver
and kidney functions. The systemic treatment consists of intramuscular methotrexate
injection in the dose of 1.0 mg/kg body weight on alternate days for four injections.
Preferably, these are accompanied by intramuscular injection of citrovarum factor
(citrovarum rescue) in the dose of 0.1 mg/kg given on the alternating days. The treatment
is monitored by daily measurement of serum B-hCG. If there is no drastic drop in the
concentration of this hormone after the four methotrexate injections, the course can be
repeated but after 7 days recovery period. The complications of the therapy should be
monitored by repeated assessment of the peripheral hemogram, and the liver and kidney
function. In addition, acute internal hemorrhage can occur any time during medical
treatment. The patient should be always kept in hospital because of the risk of tubal
rupture or abortion at any time, which can cause acute hemorrhage. The use of the
antiprogesterones like mifipristone has also been suggested. Because of the risks,
medical treatment requires extreme caution in selection and follow up of patients and is
only possible in special centers.

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4- Expectant management:
Spontaneous absorption or abortion of tubal pregnancy without marked
intraperitoneal hemorrhage is possible, but should be rare. Though the expectant
management has been suggested it can not be relied upon except in few cases and in
special centers. It has been suggested if there is low and falling levels of HCG, where
there is no evidence of internal bleed and the diameter of the ectopic pregnancy is less
than 3.5 cm.
5- Anti D immune globulin is needed in all Rh-negative non-sensitized patients.

Plan for future pregnancy

§ Ovulation can be resumed before the patient has her first period. Contraception should
therefore be ideally commenced at the time of hospital discharge. The IUD is not a good
option for these patients because of the possibility of flaring up of the inflammation in the
other tube.
§ Excluding patients unwilling to conceive, unilateral salpingectomy reduces the chances of
pregnancy by approximately one-half. Ova produced at the ovary whose tube has been
removed are having a poor chance to get fertilized through external migration. This has
been used as an argument to remove the ovary on the side of salpingectomy; with this
monthly ovulation will take place at the ovary on the side of the intact tube. However,
this argument is not acceptable (see above), particularly in the timeof IVF/ET.
§ The patient should know that her chances of having an ectopic recurrence is between 10
to 15 % and should consult with her gynecologyist whenever she misses her menstruation
or has an “unusual” menstrual period.

Abdominal pregnancy
This is very rare (see under-pathology) 0.1 in 25,000 birth. The pregnancy has a very
small chance to proceed to viability. Abdominal pregnancy is very dangerous; serious
hemorrhage can occur at any time from the placental site.

Diagnosis: is suggested by:

- The patient may recall symptoms suggestive of ectopic pregnancy early along the course
of the pregnancy.
- Abdominal discomfort and gastrointestinal disturbances are the usual presenting
symptoms. The patient is usually anemic.

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- Abnormal fetal lie.

- Unexpected ease of palpation of fetal parts can be appreciated by the physician. However,
such feeling can occur in normal intrauterine pregnancy in a multipara with thin
abdominal wall. However, the latter situation can be differentiated by rubbing the uterus
into a contraction, which will conceal fetal parts within the uterus. Oxytocin stimulation
test will not show any uterine contraction detectable by a sensitive abdominal strain
gauge.
- Sonography is helpful in demonstrating the absence of a uterine wall around the
pregnancy and the abnormal site of placental implantation. An empty uterine cavity can
be occasionally seen below or to one side of the gestational sac.
- CT Scan and MRI should be helpful.

Treatment:
Immediate termination and removal or the pregnancy should be done; one should
never wait for more fetal viability. Four or six units of blood should be ensured, because
severe bleeding is expected. The best management is removal of the fetus and tying the cord
flush with the placenta, which is left behind undisturbed. This is usually followed by severe
toxemia resulting from absorption of necrotic placental tissues and occasionally ends in
abscess formation. However, these consequences are much better than the severe bleeding
which will occur from the placental bed. If there is severe bleeding resulting from partial
separation of the placenta, time should not be wasted in attempts to control it; the surgeon
should proceed to removal of all the abdominal organs on which the placenta is inserted.
Selectively embolization of feeding arteries can be attempted in some cases.

Ovarian pregnancy
The condition is usually difficult to differentiate preoperatively or even
intraoperatively from disturbed tubal pregnancy. The intraoperative criteria for diagnosis of
ovarian pregnancy (Spiegelberg criteria) are:
1- The tube on the affected side is intact.
2- The gestational sac occupies the site of the ovary.
3- The pregnancy sac is connected to the uterus by the ovarian ligament.
4- Definite ovarian tissue is found upon the gestational sac.
Oophorectomy is the usual treatment; however partial wedge resection is rarely
possible in an early case.

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Ectopic pregnancy

Cervical pregnancy
This case can occur spontaneously, but may complicate IVF/ET. The condition causes
severe, usually painless bleeding. The cervix is soft and ballooned. The condition is
diagnosed by sonography. The condition is attended with severe bleeding due to poor
contractility of the cervical wall.
Hysterectomy is the best treatment. However if future pregnancy is required, light
packing, or tampoonading the bleeding area by inflated balloon of Folly’s catheter is done.
Alternatively, upper cervical cerclage may diminish the bleeding. Selective embolization of
the uterine artery after pelvic angiography under the C-arm and the artery is embolized using
small pieces of Gelfoam carried in the angiography dye.

Pregnancy in a rudimentary horn

It is quit rare. Since the rudimentary horn is usually not communicated with the cavity
of the developed horn, fertilization occur by external wandering of the sperms. The thick
muscle wall allows enlargement of the pregnancy for some weeks (10 or 12) before the horn
ruptures. This results severe internal hemorrhage. The ruptured horn is excised together with
its tube.

Heterotypic Ectopic Pregnancy

This is a tubal pregnancy associated with an intrauterine pregnancy. The condition is
rare, but it is more likely to be encountered following induction of ovulation and IVF/ET and
other ARTs in which a number of embryos are transferred.
The clinical picture is atypical for either uterine abortion and ectopic pregnancy. The
diagnosis of the heterotypic ectopic pregnancy is considered in:
1- Pregnancy resulting from ARTs; 1% of such pregnancies are heterotypic tubal.
2- With two or more corpus luteum.
3- If a gestational sac is found in both the uterus and adnexa.
4- Absence of vaginal bleeding with symptoms and signs of ectopic pregnancy.
5- Persistence or rising titer of BHCG after evacuation of uterine pregnancy.
6- Development of symptoms and signs of ectopic pregnancy after evacuation of a
uterine pregnancy.
Laparoscopy and/or laparotomy are required when the condition is suspected. In
addition to ectopic pregnancy, the uterus is showing manifestation of pregnancy.

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Chapter 10
GESTATIONAL TROPHOBLASTIC
TUMORS
Contents
• Vesicular (hydatidiform) mole
- Incidence
- Etiology
- Pathology
- Clinical picture
- Treatment
- Follow-up
• Persistent Gestational Trophoblastic Tumors
• Invasive mole
• Placental – site Trophoblastic tumor
• Choriocarcinoma
- Pathology
- Clinical picture
- Diagnosis
- Stages
• Management of persistent trophoblastic tumors
- Chemotherapy
- Hysterectomy
- Prognosis
- Follow-up

Types:
Gestational trophoblastic tumors (GTT) are tumors, which arise in the trophoblast of
the pregnancy. They do not include the very rare primary choriocarcinoma of the ovary,
which arise as teratoma and are not related to a gestational event. They do not include the
very rare trophoblastic tumors arising from other sites, e.g. carcinoma of the bronchus,
bladder, cervix or colon. GTTs are all: potentially malignant on malignant tumors. They
comprise the following spectrum:

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1. Vesicular (Hydatidiform) mole. This comprises the complete and partial moles.
2. Chorioadenoma destruens (Invasive Mole).
3. Placental-site trophoblastic tumors.
4. Choriocarcinoma.
Although the last four conditions more commonly follow a vesicular molar pregnancy,
they may ensue after other gestational events, including spontaneous or induced abortion,
term pregnancy or ectopic pregnancy.

Vesicular Mole
Incidence :
In Europe and North America, the incidence of vesicular molar pregnancy is 1 in
every 2000 - 2500 pregnancies. In Southeast Asia, the incidence is much higher: 1 in 200 -
300 births. There are no reliable figures about the incidence in Egypt but the general
impression is that it is on the high side.

Etiology :
§ The higher incidence vesicular mole in certain parts of the world can represent ethnic or
racial difference. It can also be related to the type food; being commoner in rice - eaters.
Areas with high incidence of molar pregnancy have a high frequency of vitamin A
deficiency. There is also an increased incidence of persistent GTT in the women in the
predisposed regions of the world.
§ Maternal age above 40 predisposes to all types of GTTs. The aging ova of older women
may be more susceptible to abnormal fertilization or division (see below).
§ Recurrence of vesicular mole pregnancy in subsequent pregnancy is observed in certain
couples. It has been suggested that trophoblastic tumors may be more likely to arise as
consequence of pregnancies from a certain husband. The author has seen four consecutive
molar pregnancies occurring in a young multipara, one of them (the second) proceeded to
choriocarcinoma. However, recurrence is not a must, and vesicular mole can precede or
follow one or more normal pregnancy. The notion that the molar pregnancy in such
incidence has resulted from extramarital sexual relation is not upheld by most
observations, particularly in our community.
§ The group A woman married to a group A man is at the least risk of developing GTTs.
The group A women with a group O husband, and the woman whose blood group is AB,
are at the greatest risk.
§ Histocompatibility between the couple may diminish the ability of the wife for rejection
of the paternal chromosomal components in the gestational trophoblast. There have been

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reports of matching leukocyte HLA types between the couple in molar pregnancy. The
occurrence of a trophoblastic tumor can be regarded as the result of breakdown in the
complicated host- invader balance.
Cytogenetic studies have shown that most complete vesicular moles have a 46 XX
karyotype (sex - chromatin positive), and molar chromosomes are entirely of paternal origin
(from the father). About 10% of complete moles are 46 XY; again all chromosomes are
paternal. However, the molar mitochondrial DNA is of maternal origin. It has been
suggested that this abnormal pregnancy results from fertilization of an ovum by two sperms
(diaspermia); the alternative is that the haploid 23 X sperm nucleus duplicates its own
chromosomes while the oval nucleus may either be absent or is inactivated (Figure1). In a
sense, the formation of molar pregnancy can be viewed as a “biological cloning”.

Gestational Trophoblastic Tumors; Figure 1:Karyotype of complete vesicular mole.

Partial mole (when molar change is affecting part of the placenta) commonly shows a
triploid karyotype; 69, XXX, 69 XXY or 69 XYY - with one maternal and usually two
paternal haploid components: when a fetus is present in conjunction with a partial mole, it
generally exhibits the stigmata of tryploidy, including abortion, growth retardation and
multiple congenital malformations. Some cases of partial moles may be example of twin

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pregnancy with only one conceptus affected by molar change. Partial mole may represent a
distinct pathology and, in fact, malignant transformation is rare in partial mole.

Gestational TrophoblasticTumors; Figure 2:Karyotype of Partial vesicular mole.

Pathology :
A vesicular mole is a neoplasm of the trophoblast, which involves both
epithelial layers the cyto- and syncitiotrophoblast. It consists of pathological
transformation in chorionic villi. The stromal core of each villus is at first
edematous, but soon becomes structureless and fluid, with characteristic absence of
the vessels. The villi swell to form grape - like cyst. The chorion thus becomes
converted into a mass of grape - like structures, each attached to the other by a fine
stalk to form clusters. The vesicles vary in size between a pin’s head to that of a
big grape. The amount of vesicles can be very huge. Usually there is no amniotic
sac and no embryo is present. The absence of chorionic vasculature explains the
absence of the embryo. The bunches of vesicles contain amongst them altered
blood.

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Histologically the tow types of trophoblastic epithelium show variable degrees of

irregular proliferation and hyperplasia, the whole mass of trophoblastic epithelium is
increased. The nuclei show pleomorphism, and are hyper-chromatic; and actively mitotic.
Grant multinucleated or mononucleated cells are frequent; various parts of the mole may have
varying grades of trophoblastic overgrowth. The latter is more commonly seen in curettings
while the expelled vessels may be having thin trophoblastic covering.
In spite of early demise (or non - existence) of the embryo the mole generally continues
to grow and reaches a size usually larger than that of a normal pregnancy of corresponding
age. However, the mole may die and its size can occasionally be corresponding to for
smaller than the gestation age. As a result of deeper invasion of the active trophoblast,
bigger blood vessels are opened and bleeding usually precipitate the process of expulsion.
Most of the interior of the uterine cavity is involved, and this is a huge potentially bleeding
surface compared to a placental site. The attendant hemorrhage can consequently, be life-
threatening. Masses of molar pregnancy may rarely get detached and embolize in the lungs.
These emboli usually disappear after evacuation of the mole, undoubtedly as a function of the
immune system of the body.
The over-activity of the trophoblastic epithelium results in increased production of
chorionic gonadotrophin. This increased production of hCG has been the basis of diagnoses.
This can also result in excessive luteinization of the ovaries and the formation of multiple
theca lutein cysts. There is a variable degree of enlargement of the ovaries, which have many
small cysts. The ovaries may reach huge dimensions, as big as a man’s head. However, this
cystic enlargement of the ovaries is functional, and rapidly disappears after evacuation of the
mole. Placental lactogen and other placement proteins like Sp 1 (a beta glycoprotein),
estradiol and progesterone are also produced in excess. However, the level of estriol is low for
gestational age (estriol is a product of the fetoplacental unit, a mechanism which is absent in
vesicular mole).
The excessive growth of the mole and the consequent overgrowth of the uterine size,
and the excessive production of chorionic gonadotrophin and the consequent ovarian
enlargement are all risk factors for subsequent malignant transformation into
choriocarcinoma. After expulsion and evacuation of the mole, the remaining fragments of
molar tissue, which is inevitably left behind in the uterine wall atrophy due to the activity of
the natural immune mechanism. However, the chance of development of post-molar
choriocarcinoma is variably estimated to be 3 to 10 %. The risk is higher when the patient is
more than 40 years of age or has had three or more children. In these classes of women the
chance of subsequent choriocarcinoma is 15 %. The histological appearance is however, not a
strong predictor of the clinical course of the disease.

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Clinical picture of vesicular mole

§ Amenorrhea with symptoms suggestive of pregnancy, uterine bleeding usually begins,
during the first few weeks of pregnancy; rarely the pregnancy reaches the second
trimester. The symptoms of pregnancy are usually marked. Vomiting is marked and
may reach toxic stages of hyperemesis. The patient looks ill, pale and has tachycardia.
Hypertensive toxemia is more likely to occur and appears unexpectedly early; but
strangely dose not culminates in eclampsia.
§ Recurrent vaginal bleeding usually results in a diagnosis of threatened abortion. The
blood can be dark brown, but can be red particularly when it gets heavy. When the
process of expulsion of the mole begins the bleeding gets severe and vesicles can be
expelled with the blood. The bleeding associated with expulsion can be very severe.
Rarely, disseminated intra-vascular coagulopathy complicates the condition.
§ Excessive uterine size is observed in about 50 % of cases due to rapid growth of vesicular
mole. Occasionally however, the uterus is found corresponding to the gestational age,
or is even smaller than this age. The latter condition occurs when the mole is dead.
The uterus feels doughy due to absence of the amniotic sac, which is responsible for
the characteristic “plastic” feeling of the normal pregnant uterus. The ovaries may
be left enlarged if they are the seats of theca lutein cystic formations. These are
bilateral and can reach a size bigger than the uterus. They can cause distending pelvic
pain.
§ No fetal parts could be felts, and no fetal pulse could be detected by Doppler fetoscope
with a size of the uterus that normally allows detection of these signs.
§ Ultrasonography can usually indicates the diagnosis of vesicular mole by showing the
picture of snow – storm, snowflakes or cotton fluffs hanging in the air. This picture is
characteristic for molar pregnancy; it can only be simulated by marked hyaline
degeneration of a fibroid. Blood clots look as homogeneous area of enhanced
echogenicity. Deep inversion in the myometrium at one point can be occasionally seen.
No amniotic sac or embryo is detectable. The enlarged ovaries can also be seen.
§ Immunological pregnancy test is positive, even when the urine is diluted 100 to 500
times. Serum (and urinary) hCG levels can reach very high levels > 100 000 m IU/ml.
However, some of the moles are not active in hormone production; the levels may be not
that high, particularly after the mole has died.
§ Hyperthyroidism: Clinically evident hyperthyroidism is observed in few (5%) cases of
the vesicular moles. These women may present for tachycardia, arrhythmia, warm skin,
and tremors. The diagnosis can be confirmed by detection of elevated free thyroxin (T4)
and triiodothyronine (T3). Thyrotoxic crisis can be precipitated by the preoperative

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excitation. Administration of b-adrenergic blocking agents rapidly reverses these

metabolic effects. After evacuation of the mole, these manifestations rapidly disappear.
Attempts to demonstrate that vesicular mole produces thyrotropic hormone have
generally failed. The increased thyrotropic effect associated with some moles may be
explained by the fact that thyrotropic hormone and chorionic genadotrophin share a
common alpha - sub-unit of their structures, i.e., the excess hCG itself can be the cause of
this thyroid stimulation.
§ Respiratory distress caused by trophoblastic embolization can complicate few cases of
vesicular mole. This is especially likely when there is excessive uterine enlargement and
markedly elevated hCG, and may follow upon evacuation of such moles. The patient can
have chest pain, tachypnea, dyspnea, tachycardia, cyanosis and rarely marked respiratory
distress requiring assisted respiration. The chest may have diffuse rales and X ray chest
may demonstrate bilateral pulmonary infiltration. The severe cases are exceptional and
are likely to develop after evacuation, in patient with hyperthyroidism or preeclampsia
and may follow upon massive fluid infusion. Cardiopulmonary support is then required;
most exceptionally mechanical ventilation is necessary.
Natural history of vesicular mole :
After evacuation of complete vesicular mole the risk of local invasion of the
uterus (invasive mole) or metastaic choriocarcinoma is higher in certain high-risk
cases. These include:
1. Older women above the age of 40 year.
2. Women with a parity of 3 +.
3. Patients with big moles: 20 weeks or more in size.
4. Pregnancy advanced to more than 12 week of gestation.
5. High hCG levels: > 100.000 mIU/ml.
6. Theca lutein cysts > 6 cm in diameter.
7. Group AB patients.
On the other hand, patients with partial vesicular mole are having much lower
risk of these malignant transformations than those with complete mole.
Treatment of vesicular mole :
Once diagnosed, vesicular mole needs to be evacuated. If the process of expulsion has
started, the process invariably needs exploration of the uterine cavity to evacuate remaining
parts by suction or vacuum aspiration. Even when a big mass of molar tissue has been
expelled, there is usually a big mass of remaining tissues in the uterus. After the suction has
become unproductive, careful sharp curettage is required to remove the decidua with the
invading molar tissue. This is to be done with care in order to avoid perforating the uterus.

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Blood transfusion should be ready because heavy bleeding is expected. A second curettage is
usually done four weeks after the evacuation, in order to ensure removal of the remaining
molar tissue.
If the condition is diagnosed before beginning of expulsion, the cervix can be ripened by
prostaglandin peccaries (particularly in nulliparous patients). This is followed by cervical
dilatation and suction evacuation. The latter procedure has facilitated evacuation of vesicular
mole regardless of its size. Dilatation of the cervix up to 10mm is enough for introduction of
the suction canula. The direction of the suction opening of the canula is turned around to all
the directions by the external knob on its handle. Patience is required in order not to miss part
the mole. A running pitocin drip will diminish the blood loss. Blood transfusion should be
ready because blood loss can be heavy and hysterectomy setup should be ready in case of
uncontrollable bleeding.
After availability of suction evacuation, hyserotomy for evacuation of a mole has
become very unusual.
After the suction ceases to be productive, the uterus is massaged into a contraction and
the uterus cavity is sharp - curetted. Intraoperative sonographic examination may be used in
order to ensure complete evaluation. A second curettage, 4 weeks later is advisable.
Abdominal hystestony is reaquired under the following circumstances:
1. When severe bleeding develops during vaginal evacuation.
2. If invasive mole is suspected by ultrasonographic examination.
3. If perforation complicates vaginal evacuation.
4. Inavailability of vacuum aspirator and the uterine size is bigger than 16-week
pregnancy size.
5. Partial mole with a fetus of more than 10-week size.

Abdominal hysterectomy:
This is resorted to in elderly women with completed family size. The uterus is usually
removed with the mole in situ; the blood loss is less than with the alternative of abdominal
hysterotomy followed by hysterectomy. The hysterectomy for molar pregnancy needs care in
order to avoid injury of the dilated blood vessels of the pelvis. There is usually no point in
removing the ovaries, even if they are the seat of marked cystic enlargement, this enlargement
rapidly subsides after removal of molar tissue. After hysterectomy the same postoperative
follow - up is required as after the vaginal evacuation.
Adjuvant chemotherapy
Preoperative single - agent course of chemotherapy has been advised in high-risk
cases in order to diminish the chance of vesicular molar embolization during operative

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evacuation. However, the merit of this approach over the postoperative treatment has not
been proven.
Post - operative chemotherapy
This is advisable in high-risk cases (see above) after evacuation of mole in order to
diminish the risk of malignant transformation. This is particularly required if effective
follow up is not possible. A single agent is used usually in the form of methotrexate or
methotrexate plus citrovorum rescue. However, actinomycin D has been shown to be equally
effective. Five-day courses at 7 - 14 - day intervals reed to be given until hCG level gets
negative and one additional course may after this occurrence. Chemotherapy needs follow-up
for the possible side effects (see below).
Follow up after termination of molar pregnancy:
After evacuation of a vesicular mole, the patient should be kept under observation the
aim of which is the early detection of persistence of gestational trophoblastic tumor. The
follow-up is both clinical and biochemical. This is done at weekly intervals for 8 weeks then
at monthly intervals for 3 months, bimonthly for 6 more months, and thereafter every three
months up to the complstion of two years. This comprises:
a. Clinical follow up: At each of the follow-up visits, the patient is evaluated
for persistence of bleeding and the regularity of menstruation. Persistent
bleeding after evacuation of a mole or in fact any post abortive bleeding,
should indicate D&C and biopsy. The uterine and ovarian size are assessed.
Ultrasonography should be done if abnormality in menstruation develops, or
if enlargement of the uterus or the ovaries are detected. A suitable
contraception is advised during these two years of follow up, the best for the
purpose is combined oral contraception since this produce the best menstrual
rhythm. However, COCs should not be initiated until the mole has been
completely evacuated. The IUD is not suitable because of the possibility of
causing bleeding, which will complicate the picture.
b. Biochemical follow up: After molar evacuation, patients should be monitored with
weekly determination of b-hCG levels until these are normal (< mIU /ml) for 3
consecutive weeks. The average time to achieve the first normal hCG is about 9
weeks. At each subsequent visit, a specific and sensitive b-subunit pregnancy test is
performed. With the presently available urinary pregnancy test which are specific and
have sensitivity of 50 to 100 mIU /ml, they are enough for routine follow up after the
b-hCG has become negative. At the completion of follow-up pregnancy may be
allowed.

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Persistent Gestational trophoblastic Tumors (GTT)

The term persistent gestational trophoblastic tumor is used to desirable trophoblastic
neoplasias, which follow a gestation. The antecedent pregnancy is an evacuated vesicular
mole in 50 % of cases, and in the remaining, it is an abortion, spontaneous or induced, ectopic
pregnancy; or a term delivery. The prognosis is worst when GTT follow upon delivery The
tumor may immediately follow upon the antecedent pregnancy or there can be an interval of
months before the manifestations of GTT develop. The risk of this development is highest
during the first year after the antecedent pregnancy but is rare after the lapse of 2 years.
Persistent GTT presents with one or more of the following manifestation:
1) Irregular bleeding.
2) Uterine subinvolution or irregular enlargement.
3) Persistence of ovarian enlargement.
4) Persistently elevated serum HCG.
Four possible pathological finding are possible.
1. Left behind parts of benign mole.
2. Invasive vesicular mole; chorioadenoma destruens
3. Placental-site trophoblastic tumor.
4. Choriocarcinoma.
In the first possibility, the symptoms and signs will abate after repeating the D&C, and
the HCG titer will progressively drops.

1. Invasive Mole, Chorioadenoma Destruens, Malignant

Mole
These are synonyms, which indicate a mole, which invade deeply into the myometreuin.
The invasion can reach the peritoneum causing internal hemorrhage and invasion of
surrounding structures: the parametrium, the adnexa, the bladder or intestines. The condition
is locally invasive but metastases in the lungs are rare but can develop. The condition may be
diagnosed during hysterectomy that is necessitated by severe bleeding or perforation of the
uterus during evacuation. The condition is similar to the choriocarcinoma, but with two
essential differences: 1) presence of vesicles on histological examination, and 2) a better
clinical course of invasive mole relative to choriocarcinoma in which such vesicular
formation is absent. The management of this condition is essentially similar to that of
choriocarcinoma, but the prognosis of its treatment is better.

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2. Placental - site trophoblastic tumor :

This is an uncommon, but important variant choriocarcinoma, which consists
predominantly of anaplastic cytotrophoblast epithelium. It is commonly preceded by a
delivery. The lesion may be microscopic in size or form a soft brownish, partly hemorrhagic
polyp, which can also infiltrate the myometrium. It presents with bleeding or amenorrhea,
associated with uterine sub-involution; or enlargement; sonography will show the infiltrating
polyp. The clinical course of the disease is variable from a slow progression to a highly
malignant cause with rapid progression.
Two features characterize this condition:
1. Low production of hCG.
2. Low sensitivity to chemotherapy. Hysterectomy is usually required for its treatment.

3. Choriocarcinoma
This is a highly malignant neoplasia, which formed of sheets or columns of both
anaplastic syncytio - and cytotrophoblast with no attempt at vesicle formation together with
intervening blood clots. The tumor has fragile vascular spaces; the malignant tissues are
actually present in maternal vascular spaces. Therefore, blood carried metastases are early in
this malignancy.
In Britain and North America the incidence of choriocarcinoma is only once in every
50.000 pregnancies. In south East Asia, Africa and Middle East the incidence is much
higher, one case for every 5000 to 6000 pregnancies. Relative to other types GTT, women
affected by choriocarcinoma tend to be relatively older, more in parous and of poor general
health.
The interval between pregnancy, molar or otherwise, and the development of
manifestation of choriocarcinoma may be as long as 5 year but is rarely longer than 2 years.
The latter the development of choriocarcinoma after the antecedent pregnancy the worst is the
prognosis. The growth begins in islets of trophoblast remaining dormant in the uterine wall
after the end of the previous gestation. The malignant transformation is most probably
determined by a breakdown in the natural host immunity, which has been checking the
growth of these islets for the time of the interval.
Pathology
The primary growth is usually in the uterine wall, and this can be in the form of multiple
nodules of tumor, which are apparently separate. These nodules protrude into uterine cavity.
Occasionally, the tumor is a nodule in the myometrium, not reaching the cavity. This latter
form can be associated with amenorrhea and results in a negative D & C. The tumor nodules
are soft highly vascular and necrotic. They can form hemorrhagic polyps into the uterine

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cavity. It also invades deeply into the myometrium and can reach the peritoneum causing
internal hemorrhage or results in invasion of neighboring structures like parametrium, bladder
and intestines. Rarely, the primary lesion is in the cervix or even the vagina.
Blood stream metastases are common and early, but can occur with other GGT including
vesicular mole, but with a much lesser rates: The most common sites of metastases are the
lungs, vagina, liver and brain.
Choriocarcinoma is usually functional and secretes hCG in large quantities reaching to
concentrations in the order of 100 000 mIU/ml of serum more. However occasionally the
output of hCG is low. The ovaries can be the seat of luteinization and may be markedly
enlarged because of formation of multiple theca - lutein cyst. Such ovarian enlargement may
be absent.
Clinical picture :
§ Irregular uterine bleeding is the leading symptom and can get very heavy. This can be in
the form of persistenence of the bleeding after evacuation of a vesicular mole, but it can
follow an abortion or delivery. It needs to be remembered that about 50 % of cases of
choriocarcinoma follow upon an abortion or delivery; therefore, it should be the routine
practice to submit the material curetted in cases of post abortive bleeding or secondly
postpartum hemorrhage to histopathological examination in order not to miss this
occurrence. There can be an interval of regular menstruation for some months between
the antecedent pregnancy, molar or otherwise, and the development of choriocarcinoma.
This interval is rarely longer than two years and usually occurs within the first year.
Vaginal nodules can result in severe bleeding that needs immediate excision
§ Rarely the condition presents with amenorrhea (intramyometrial nodules).
§ Vaginal discharge is also associated and can be foul smelling.
§ Cachexia can be marked.
§ Commonly, the condition is suspected during the follow up after the end of molar
pregnancy when the titer of hCG fails to decline or starts to increase after becoming
negative.
§ The uterus is usually enlarged, and feels irregular in shape and soft in consistency;
however, it can feel normal. The enlarged ovaries may be felt.
§ Occasionally the disease presents with metastases. These are associated with symptoms
suggesting a gynecological origin, but may occur without such symptoms. Patients with
pulmonary metastases have chest pain, cough, hemoptysis, dyspnea but can have no
indicative symptoms of pulmonary involvement which is detected only by X ray chest
which should be always done. Rarely manifestation of acute respiratory distress or
pulmonary artery occlusion develops. The radiographic features can be either:
1. Discrete rounded densities: Canon - ball metastases.

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Gestational trophoblastic tumors

2. Diffuse “ snow storm ” pattern.

3. Pleural effusion.
4. Picture of pulmonary embolism.
Vaginal metastases can be present in the fornices or in the lower part of the anterior
vaginal wall; i.e. posturetheral. They are carried to these sites by anastomostic connection
between the uterine and vaginal vessels. They can bleed vigorously when biopsied.
Liver metastases occur in advanced disease, usually with metastases in other sites. They
cause epigastric pain and a tender mass in this region. Hemorrhage from the lesion causes
acute abdomen.
CNS metastases cause focal lesions in the brain, which present in the form of headache or
epileptic seizures or focal paralysis.
Diagnostic Workup includes:
1. History and physical examination.
2. Pretreatment b - hCG titre (assays).
3. Ultrasound examination of the pelvis.
4. Chest X ray or chest CT scans.
5. Histopathological examination of uterine curettings.
6. Ultrasound or CT scans.
7. Fine needle biopsies from metastatic lesion, guided by USG or CT scan.
8. IVP.
9. Peripheral hemogram.
10. Serum chemistries: renal and hepatic functions.
11. Occasionally Thyroid function.
Stage :
A Clinical / anatomic staging system for GTT has been adopted by the
International Federation of Gynecology and Obstetrics (FIGO) in order to allow for
assessing the prognosis and choice of strategy of management; but mainly to allow
comparison of results from different centers.
Table 1, FGO Staging of persistent GTTs
Stage I Disease confined to the uterus
Stage I a Disease confined to the uterus with no risk factors *
Stage I b Disease confined to the uterus with one risk factor
Stage I c Disease confined to the uterus with two risk factor

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Stage II Disease extending outside the uterus but limited to genital

structures( Adnexa, vagina, brood ligament).
Stage II a The above with no risk factors
Stage II b The above with one risk factors
Stage II c The above with two risk factors
Stage III Disease extending to the lungs with or without known genital
involvement.
Stage III a The above with no risk factors
Stage III b The above with one risk factors
Stage III c The above with two risk factors
Stage IV All other metastatic lesion
Stage IV a with no risk factors
Stage IV b with one risk factors
Stage IV c with two risk factors
* Risk factors: 1) hCG > 100,000 mUI/ml 2) Duration of disease longer than 6 months
from termination of antecedent pregnancy.
In addition to anatomic staging, it is important to consider other variables that predict the
likelihood of response to chemotherapy. The following scoring system has been suggested
by WHO, the higher the score, the greater the likelihood of poor response and the more the
need for multi-agent therapy; the dividing line is a score of 8 or more.

Table 2: Scoring System Based on Prognostic Factors:

0 1 2 4
- Age (years). < 39 > 39
- Antecedent pregnancy. Vesicular Abortion Term
mole.
- Interval between end of the
antecedent pregnancy and start
of chemotherapy (months). <3 4-6 7 - 12 > 12
- hCG in serum( mIU/ml). < 103 103 – 104 104-105 >105
-Largest tumors including the
uterine (cms). <3 3–5 >5
- Site of metastasis. Lung, spleen Gastrointestina Brain
and kidney l tract, liver
- Number of metastases. 0 1-3 4-8 >8

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-Prior chemotherapy 1 drug ³2 drugs

The total score for a patient is obtained by adding individual scores.
A total of < 4 = low risk; 5 - 7 = middle risk; 8or more= high risk.

Management of persistent GTT

§ Chemotherapy:
It is the primary treatment of persistent trophoblastic tumors and is given to all
stages of the disease. A single - agent therapy is used from the start in early cases,
stage I and II. Combination chemotherapy is used in patients with advanced disease,
stage III and stage IV. This combination therapy is also used initially in stage I, and
II if the score is > 8, or secondary if single agent therapy has failed.
In stage I cases and some of stage II hysterectomy is done in addition if the
patient is not keen to preserve fertility. This diminishes the load that needs to be
dealt with by chemotherapy and the body immune system. The first course of
chemotherapy is given before surgery to reduce the likelihood of disseminating
viable tumor cells - during surgery. Surgery is also indicated in cases of placental
site trophoblastic tumors (see above).
Chemotherapy dose not influence much brain and liver secondaries, and these
are treated by radiation therapy; a total dose of 3000 rads is needed (usually in 10
fractions).

Single agent chemotherapy:

Chemotherapy has been the first malignant disease to be successfully treated by
chemotherapy. This has depended upon methotrexate an anti-metabolic drug, which inhibits
transformation of folic acid to folinic acid, which is part of the synthesis of nucleic acid, and
synthesis of DNA and RNA necessary for cell division and function. Methotrexate is mainly
active in the S phase of cell division. Repeated short courses of methotrexate are the standard
treatment for early cases of choriocarcinoma. However, if liver functions are abnormal,
methotrexate is better to be avoided because the drug is metabolized in the liver. Actinomycin
D (Dactinomycin) has been shown to be equally effective as methotrexate. The administration
of methotrexate with folinic acid (citrovorum factor) in GTT has been advocated to limit the
systemic toxicity of the treatment (citrovorum rescue).
Conman single agent chemotherapy used:
1. Methotrexate 0.5 - 1.5 mg/kg, IM every day for 5 day(repeat after 7 days if possible).
2. Actinomycin D 10 - 12 mg/kg IV every day for 5 day (repeat after 7 days if possible).

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Gestational trophoblastic tumors

3. Citrovorium rescuer: methotrexate 1mg/kg IM on days 1, 3, 5 and 7 + Folinic acid

(leukoverin calcium) 0.1 mg/kg IM on days 2, 4, 6 and 8 (repeat after 7 days if possible).
The pulsed treatment is continued until after a negative b- hCG test (< 10 mIU/ml) is
obtained and one a two additional courses are given.
Monitoring chemotherapy of GTT
The response to treatment is monitored by weekly measurement of bHCG in blood. A
declining curve is reassuring. Remission is defined as a three consecutive weekly normal b-
hCG (< 10 mIU/ml). If the b-hCG, plateaus, or the titer rises, or if new metastases develop
the dose is increased. Shifting to other chemotherapy, usually multiple - agents is considered.
Monitoring side effects: The chemotherapy has deleterious effects on the rapidly
dividing tissues of the body. These are the hepatic renal, hemopoeitic tissues, gastrointestinal
epithelium and hair follicles. The patient develops anorexia, mouth ulcers and may be
diarrhea and febrile courses. Thinning down of scalp hair can develop and in some sensitive
patient alopecia develops. The courses should not be repeated until:
1. WBC > 3000 /cu mm.
2. Polymorphs > 1.500/cu mm.
3. Platelet > 100.000 /cu mm.
4. BUNS, SGOT, SGPT are normal.

§ Combination chemotherapy
Triple therapy with Methotrexate, Actinomycin D and chlorambucil, MAC therapy has
been extensively used with good success. The doses are:

MAC chemotherapy

- Methotrexate 25 mg IM every day for 5 days.

- Actinomycin 10 - 12 ug/kg/kg IV every day for 5 days.
- Chlorambucil 10mg P.O. every day for 5 days.
This triple chemotherapy is repeated at 12 - 14 day intervals provided the above
indicators of toxicity have reached to acceptable levels. Cerebral or hepatic metastases are
concurrently treated with radiotherapy.
Recently Vincristine, etoposide and/or Cis. Platinum has been added or have been tried
in different regimens. Bagshow’s multiple agent therapy gives 7 days in combination to the
both regimens. This is usually combined with citrovorum rescue. This regimen is referred as
EMA/CO (Table 3). Such types of resistant and advanced cases should be dealt with in
specialized centers capable of dealing with side - effects.
The EMA/CO schedule

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Gestational trophoblastic tumors

Week 1
§ Day 1
- Actinomycin D (e.g. Cosmegem, MSD), 0.5mg IV bolus
- Etoposide, (e.g. Etoposide, Pharmacia & Upjohn) 100mg/m2 IV In 500ml
normal saline over 30 minutes.
- Methotrexate, 300mg/m2 IV in 1 liter normal saline over 12 hours.
§ Day 2
- Actinomycin D, 0.5mg IV bolus
- Etoposide, 100mg/m2 m500mg normal saline over 30 minute
- folinic acid (e.g. Leucovorin, Pharmacia & Upjohn): 15mg/m2, IV, 12-
hourly X 4 doses starting 24 hours after commencement of methotrexate
Week 2
§ Day 1
- Vincristine (Oncovin) (e.g., Vincristine, Pharmacia & Upjohn), 1.4mg/m2,
IV bolus (maximum 9mg)
- Cyelophosphamide (e.g. Endoxan-ASTA), 600mg/m2 iv in 500 ml normal
saline over 30 minutes.

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Gestational trophoblastic tumors

Gestational Trophoplastic tumors; Figure 3: gives the Normogrom for calculating body
surface area.

Prognosis:
With the management outlined above the expected cure rate in Stage I cases is 90 - 100
%. In stage II and stage, III cases a successful treatment can achieved in 80 - 90 % of cases.
In patient with advanced disease a 30 % success rate was reported but specialized centers
are reporting much better results of complete remission achieved in more than 70 % of cases.

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Gestational trophoblastic tumors

Follow - up of treated cases

After obtaining a negative bHCG in three consecutive weekly measurements, an extra
course is advisable. Thereafter thebhCG assay is repeated monthly for one year and
bimonthly for another year. During the follow up the patient with a uterus should use a
contraceptive, preferably combination oral contraceptive. She can then be allowed to get
pregnant. It is reassuring that the frequency of congenital anomalies is not increased. It seems
that the ova affected by chemotherapy will be expired during the course of follow-up. Early in
the subsequent pregnancy, a sonographic examination will confirm absence of recurrence of
molar pregnancy.

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Genital prolapse

Chapter 11
GENITAL PROLAPSE
Contents
• Etiology
1. Predisposing factors
2. Precipitating conditions
• Anatomical types of genital prolapse; physical signs and complications
of prolapse
• Symptoms
• Nonsurgical management of prolapse
• Preoperative preparation
• Surgical management of different types of genital prolapse, some
details of certain common operations are given
• Postoperative care
• Complications

Genital prolapse refers to the descent of the uterus and/or the related
structures or organs. It can be called procidentia (Latin). It is quite common and
frequently and unnecessarily endured by women in silence without complaining.

1. Etiology
1.1 Anatomical considerations
Anatomical considerations (see also under Anatomy): In the erect posture the genital
system is hanging in the hiatus of the pelvis and is carrying above it the weight of the
abdominal viscera which even at rest is considerable, and is very frequently accentuated
during bearing down efforts. The genital tract is prevented from yielding in front of this
weight by a number of anatomical considerations:
A. The uterus is mainly carried by the transverse cervical ligament, which is also called
the cardinal or Mackenrodt’s ligament. It is a condensation of the pelvic cellular
(connective) tissue in the base and below the broad ligament. Cutting of the ligaments
during hysterectomy allows easy mobilization of the uterus. Stretching and attenuation

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of the cardinal ligament is the main pathology in uterine prolapse. The uterosacral
ligament lends support to the uterus only when short, if it is lax or long it lends no
support. The pelvic diaphragm (i.e. the two levator ani and the underlying perineal
muscles) lends indirect support to the uterus, i.e. keeping it up when it is pushed down
by rise in intraabdominal pressure. The anteverted anteflexed uterus lies horizontally
in the pelvis at right angle with the axis of the vagina. The uterus can only descend
into the vagina or to the exterior when it is retroverted to get in line with the axis of
the vagina, and hence can telescope itself into it. The other uterine ligaments (the
broad and round ligaments) lend no support to the uterus.
B. The vagina is kept in place by
1. The uterine ligaments described above are attached to the vaginal vaults as well,
and support the upper vagina.
2. The pelvic diaphragm, i.e. the levator ani and the perineal muscles give a direct
support to the lower vagina by being inserted in most of its circumference.
Actually, these muscles decide the functional width of the vagina, and when
defective, mainly as a result of trauma of labor, descent of the vaginal wall occurs.
3. The posterior angulation of the upper third or fourth of the vagina renders some
support to upper vagina. Above the level of the levator ani the vagina is bent
backward to rest upon the rectum and then upon the anococcygeal raphe (the
middle line fusion of the two levators ani behind the rectum). In the erect posture,
the upper third of the vagina is in fact horizontal and directed towards the third or
fourth sacral pieces, and will not take the weight of the abdominal contents upon
its axis but in fact the weight is taken by the pelvic diaphragm.
4. The middle line opening of the pelvic diaphragm between the levator ani is
divided into two hiatuses: the urogenital and rectal hiatuses, which are separated
by decussation of the two levators behind the vagina in the apex of the perineal
body. Women with genital prolapse are having a big single midline defect in the
pelvic diaphragm due to weakness and lateral recession of the muscles and
merging of the two hiatuses (due to perineal laceration and relaxation) in one big
defect that more readily yields under weight of viscera.
5. The vagina is also self-supporting itself by its smooth muscles and the fibroelastic
components of its walls. When these walls get thin and atrophic after menopause
the vagina is more likely to prolapse.
6. With the vagina directed upwards and backwards, the anterior vaginal wall is
carried upon the posterior vaginal wall and hence, indirectly upon the perineal
body (hence the need for posterior colpo-perineorrhaphy in all types of genital
prolapse).

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7. Moreover, there is a condensation of the pelvic cellular tissue that forms the
pubocervical ligaments (or fascia). These ligaments stretch between the pubic
bodies and the supravaginal cervix. The two ligaments form together a sort of a
shelf intervening between the base of the urinary bladder and the upper anterior
vaginal wall. The pubocervical fascia is attached laterally to the white line on the
obturator internus muscle (the Archus tendineus). In reality, the pubocervical
ligaments are not definitive separate sheets but, like all other pelvic ligamentary
supports of the genital tract, are stress-determined condensations of the pelvic
cellular tissue. During dissection of the space between the bladder and vagina in
anterior coloporrhaphy, the pubocervical fascia usually comes with the bladder
base. When the pubocervical fasciae are weak or when they recede laterally the
bladder base herniates down between them causing a cystocele. Other than this
central defect, a lateral defect in the attachment of the pubocervical fascia has
been recently identified. This result in obliteration of the antro-latral sulcus of the
vagina (Figure 1).

Genital prolapse; Figure 1: Paravaginal defect due to detachment of the pubocervical

fascia from its lateral attachment (coronal section). 1. Urinary bladder; [Link]
internus muscle; 3. Pubocervical fascia; [Link] ani; 5. Vagina; 6. Rectum; 7. Paravaginal
defect.

C. The urethra is normally tucked to the symphysis pubis by the urogenital diaphragm
or triangular ligament (anatomically referred to as the deep perineal pouch). It is
formed of two strong fibrous sheaths filling the anterior part of the subpubic angle and
has striated muscles in between. This diaphragm should be left alone if there is no
urethrocele. The urethro-vesical junction lies above the diaphragm. It is supported and
tucked to the lateral pelvic wall by the fibers of pubocervical fascia.

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Genital prolapse

The musculofascial walls of the bladder and urethra support these structures and,
together with the pubocervical ligaments prevent them from sagging down below the
level of the pelvic diaphragm. In case of the urethra the tone of the musculafacial wall
keeps it closed and maintains the intraurethral pressure higher than the intervaginal
pressure preventing leakage of urine under sudden increases in the intraabdominal
(and hence, intravesical pressure). The cortical control of urinary continence is mainly
exercised through the neuromuscular controls of the tone of the urethral muscle wall
(the urethral closing pressure). They are allowed to relax under will when it is
convenient to pass urine (see under Stress incontinence). There is no dissectable
sphincter at the urethro-vesical junction.
D. The rectum and anal canal are supported, and their function width is controlled by the
(1) tone of their musculofascial walls, (2) the recto-vaginal fascia intervening between
the ampulla of the rectum and the vagina (a layer of variable thickness reaching from
the Douglas pouch to the apex of the perineal body. (3) The levator ani muscles,
which are, inserted in the lower rectum and loop around the back of anorectal junction
and (4) the superficial perineal muscles. One of the latter muscles, the subcutaneous
superficial anal sphincter plays the major role in maintaining rectal continence. Its
fibers are inserted in the skin around the anal sphincter, hence the radiating
corrugations (puckering) of the skin around the anal orifice. When this muscle is torn
in complete perineal tear, continence over stools and/or flatus is lost or become
markedly weakened.
Adequate appreciation of the above anatomical considerations is important for
understanding of the pathophysiology of prolapse and the basis of the various
operations done to correct genital prolapse and allied conditions.

1.2 Predisposing factors:

A. Constitutional (congenital) predisposition: Certain women are having constitutional
weakness in the supportive structures of the uterus and/or the related organs. These
women are going to have prolapse, usually through the effect of addition of the
influence of other etiological factors like obstetric trauma or postmenopausal atrophy.
Women without this constitutional predisposition will not develop prolapse in spite of
all other influences like traumatic labor, marked postmenopausal atrophy of the genital
organs and/or having causes for chronic straining like chronic asthmatic bronchitis or
chronic constipation. On the other hand, women with marked weakness of the
supportive structures may have marked prolapse before getting pregnant, or even
during childhood. Congenital prolapse at the time of birth is quite rare. Such women

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Genital prolapse

are having general flaccidity and weakness of the musculofibrous tissues of the pelvis,
abdomen or the whole body. They are more likely to have abdominal wall hernias,
rectal prolapse, viscroptosis and pendulous abdomen. In girls with “congenital”
prolapse, the presence of a spina bifida occulta should be searched for; it can be
causing defective innervation of pelvic muscles. When the supports are very weak,
one easy delivery is followed by a marked uterine prolapse, acting like the “straw that
has broken the camel’s back”.
B. Effect of pregnancy and labor; First, it needs to be stated that a woman can go
through a highly dense and difficult obstetric career without getting any degree of
genital prolapse. However, the effect of gestational softening of the walls and their
support during pregnancy, and the stretching and traumatization during childbirth
predispose to genital prolapse. Certain types of trauma are particularly associated with
prolapse, like perineal tears, bearing down before full dilatation of the cervix, return to
heavy work early during puerperium, ventouse application before full dilation of the
cervix, and vigorous squeezing down of the uterus in an attempt to deliver the
placenta. However, the extent of contribution of some of these traumas to prolapse is
difficult to size up and may be hypothetical.
C. Surgical trauma: is a rare cause for prolapse. Hysterectomy abdominal or vaginal and
the entailed severing of the ligamentary supports of the uterus is not in reality a cause
for prolapse. The development of vaginal vault prolapse after such operations rather
represents an overseen original weakness of the support or missing a low Douglas
pouch i.e. a cul-de-sac hernia. It is a good prophylactic practice during total abdominal
or vaginal hysterectomy to fix the vascular pedicles containing the ligaments to the
vaginal vault by slowly absorbable synthetic sutures. It is also a good practice to look
for a low Douglas pouch in all abdominal hysterectomies and indeed all pelvic
surgeries and to obliterate it when deep, by a series of sutures (see later under
treatment of enterocele).
Again, after a vaginal hysterectomy, the finger should be hooked into the
posterior leaf of the peritoneum to diagnose a hernia of Douglas pouch. If found, it
should be dissected, highly ligated and excised and thereafter, the two uterosacral
ligaments are approximated by slowly absorbable sutures (paying attention not to
contain the ureters or kink them).
D. Postmenopausal atrophic changes: After the menopausal estrogen withdrawal, there
is atrophy of the genital tract walls and their supports which predispose to various
types of genital prolapse; but, again only in those, who are constitutionally
predisposed. With the increasing population of women who age after the menopause
(graying of nations), there is an expected increase in the demand for pelvic surgery to

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Genital prolapse

treat uterine or vaginal prolapse. It has to be noted that most of these women will
continue to be sexually active, and an adequate vaginal width, and integrity should be
maintained. The operations should take into consideration that husbands are having
declining potency. A tight vagina after the operation is difficult to correct. It remains
to be demonstrated whether postmenopausal hormone therapy diminishes the
likelihood of genital prolapse.

1.3 Activating factors

These include chronic constipation, and anal stricture, chronic cough and asthmatic
bronchitis, marked ascitis and other conditions that result in chronic increase in the
intraabdominal pressure. These conditions will need to be treated or improved as far as
possible before the operative treatment of prolapse.

[Link] types of prolapse; physical signs:

1.2 Anterior vaginal wall prolapse:
It is either a cystocele, urethrocele or both. A cystocele occurs when the upper two
thirds of this wall descends below their normal level with or without straining (figure 2). The
pouch in the anterior vaginal wall contains a displaced pouch of the posterior bladder wall,
hence the name cystocele. The descent of the trigone stretches the lower parts of the ureters
and frequently kinks them at the point where they pierce the Machenrodt’s ligament, hence
the development of backpressure on the upper urinary tract. This backpressure can simply
result from chronic increase in the interavesical pressure. A urethrocele is described when the
lower third of the anterior vaginal descends from its position behind the symphysis pubis; the
urethra is displaced downward and backward. It needs to be emphasized again, that
urethrocele is not always associated with cystocele. In absence of a urethrocele the dissection
of the anterior vaginal wall in anterior colporrhaphy should leave alone the lower part,
particularly so because the dissection will be a sharp one and the paraurethral tissue is very
vascular.
A well-marked anterior vaginal wall descent shows three horizontal sulci: 1. the
posturethral sulcus 2mm above the urethral orifice, 2. the traverse vaginal sulcus 1.5 cm
above the urethral meatus; this is representing the attachment of the triangular ligament (see
above). The vaginal mucosa (skin) between the two above-mentioned sulci is rugose and
thick. The third (faint) sulcus is called the bladder sulcus situated few millimeters below the
vaginal attachment to the cervix. It marks the upper limit of the opposition of the bladder and
the vagina (Figure 3).

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Genital prolapse

Paravaginal defect resulting from detachment of the pubocervical fascia from the
white line results in obliteration of the anterolatral sulcus of the vagina. This type of cystocele
is more commonly on the right side. It needs be looked for since it needs special treatment.
In examinations for anterior vaginal wall prolapse the presence of the symptom
and demonstration of stress incontinence need be assessed (see under Stress Incontinence).

Genital prolapse; Figure 2: Cystocele (1) with first degree uterine decent.

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Genital prolapse

Genital prolapse; Figure 3: The three sulci on the anterior vaginal wall in a big
cystocele. The two labia minora have been sutured away from the operation filed.

2.2 Posterior vaginal wall prolapse

The descent of the lower 3/4th of the posterior vaginal wall always contains a pouch of
the anterior rectal wall, hence the name rectocele. Descent of the upper fourth of the posterior
vaginal wall may contain (but may not contain) a downward descent of the Douglas pouch,
hence the name Douglas pouch (= cul-de-sac, the name in French) hernia. Since loops of
intestines are contained in this hernia, the name enterocele can be used (figure 4). This is a
real hernia, since it is an outward protrusion of the peritoneum through the parities. Like any
other hernia, the Douglas pouch hernia has a sac i.e. the peritoneal bulge, for which a fundus
and neck are described. The covering of the hernia is simply the vaginal wall. The neck of the
hernia, the aperture through which herination has occurred, is the mouth of the Douglas pouch
bound on the sides by the uterosacral ligaments, anteriorly by the supravaginal cervix and
posteriorly by the anterior rectal wall. The contents of the hernia can be intestinal loops
and/or the omentum. It needs to be remembered that not all instances of prolapse of the
posterior fornix are containing a hernia, and on the other side, a hernial sac can dissect its way
down between the lower vaginal wall and the rectum. One should be always look to the
possibility of the presence of a hernia in posterior vaginal wall descent.
Three physical signs must be fulfilled in the diagnosis of a hernia of Douglas pouch:

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Genital prolapse

1. Expansile impulse of the prolapsed vagina on coughing i.e. three-dimensional increase

on coughing i.e. ballooning, not a simple tug or descent which can be demonstrated in all
other types of prolapse.
2. Gurgling sensation (gas in water) on palpating the hernia due to the presence of loops
of intestines.
3. Combined PR (by the index finger) and PV (by the thumb) will demonstrate the
intervention of the hernia pouch with its contents of intestinal loops between the vaginal
and rectal walls. In contrast, a simple rectocele will not have any structure intervening
between the vagina and rectum.
In the assessment of a rectocele the degree of the defect in the perineum should be
assessed as well as the integrity of the superficial and sphincter and the presence of prolapse
of rectal wall through the anal orifice.

Genital prolapse; Figure 4: Rectocele (1) and Enterocele (2)

2.3 Uterine prolapse

A marked uterine descent is inevitably associated with vaginal descent or eversion. The
use of the descriptions as uterovaginal or vaginouterine prolapse depends upon which of the
uterus or vagina appears first on asking the patient to bear down. Practically speaking, there is
no difference between the two types.

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Genital prolapse

The extent of uterine prolapse is assessed in degrees (Figure 5), which are described after
asking the patient to strain down fully:
- First degree uterine descent: The cervix descends below its normal level opposite
the ischial spines, but does not protrude outside the vagina.
- Second degree descent: when the cervix protrudes below the vulva but the fundus
is still above this level.
- Third degree uterine descent: (occasionally described as complete procidentia):
when the whole uterus up to its fundus gets outside the vulva.
To differentiate between second and third degree prolapse of the uterus, you ask the
patient to strain down maximally and then take hold of the prolapsed structure just below the
vulva between the index finger behind and the thumb in front the mass. If you feel between
the two (everted) vaginal walls the cylindrical cervix, it is a second degree. But, if you can
approximate the two fingers with nothing intervening between the vaginal walls, and with the
rounded funds below the fingers it is a third degree. One should not mislead by the size of the
prolapsed structure; a second-degree prolapse can be a big structure due to the hypertrophy of
the portio-vaginalis and the elongation of the supravaginal cervix (see later).
It needs to be remembered that women may find difficulty in demonstrating the full
extent of their prolapse after being kept in bed for some days in the hospital due to temporary
recoil of the ligaments. These women can be helped by asking them to bear down strongly
while supporting the anus to prevent the escape of flatus. Some women cannot demonstrate
their prolapse except while standing or squatting and these should be allowed to do so.

Genital prolapse: (Figure 5): degrees of uterine descent.

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Genital prolapse

2.4. Vaginal vault prolapse;

This term is used to describe major prolapse involving the vaginal vault. It can occur
with the uterus present, and with the uterus removed by a previous surgery. It
frequently contains an enterocele. With the uterus present, vault prolapse occurs in women
with marked constitutional weakness of the uterine ligaments as in congenital prolapse
present in infants, children, unmarried or women with limited parity. This type of genital
prolapse poses a particular problem since the sexual and reproductive capabilities need to be
preserved. This will be a formidable task in the absence of any support to utilize or enhance.
The recurrence rate is expected to be high unless pexy-types of operations are used.

If the uterus had been removed the vagina vault has weak supports and gets
progressively everted like a stocking. Again, in this condition there are usually nothing left of
the ligaments to utilize in repair process. However, commonly the sexual function is not
needed and pencil narrowing of the vagina or its obliteration can be utilized. If sexual
intercourse is needed a vaginal suspension - pexy-type operation is needed.
In both situations, a hernia of pouch of Douglas should be searched for and corrected.
On the whole, vault prolapse should be left to experienced surgeons.

3. Symptoms of genital prolapse and their pathogenesis

There is a great degree of variability between patients in the extent and severity of their
complaints. Marked prolapse may not be bothering much a certain patient while a minimal
degree of descent or vaginal laxity may be bitterly complained of. The reasons for this are not
clear. The symptoms include:

3.1. The patient describes a swelling in the vulva or vagina or a feeling of not being
well supported or having pelvic heaviness or weakness. Frequently a patient can recognize
that her vagina or uterus is descending. Some women complain of laxity of the vagina, while
it is actually a complaint of the husband.

3.2 A dragging sensation in the epigastrium is described frequently as dragging on the

heart. There is no clear explanation for such description.

3.3 Low backache: is a frequent complaint of women, but it can be ascribed to prolapse
only when there is a marked uterine descent; the stretch of the uterine ligaments may stretch
some of the peripheral branches of sacral nerves resulting in vague pain referred to the lower
back. The woman cannot be promised that he back pain will be relieved by the surgical
correction of the prolapse and should be encouraged to resort to orthopedic consultation and
to correct her daily habits like sitting on low chairs and in bed or repeated straining of the

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Genital prolapse

back. A ring pessary test is usually used to demonstrate to the patient, that her prolapse is not
responsible for the back pain.

3.4 Urinary symptoms, which can be truly ascribed to prolapse including

frequency of micturition, and difficulty in evacuating the bladder which, frequently lead to
urinary tract infection.
- Frequency, to start with, is diurnal only, and is explained by descent of the bladder
trigone that causes reflex isometric contractions of the bladder resulting in frequent urges
during daytime. Lying down relieves this sagging of the bladder base, and hence the
frequency is much less marked during the night. Nocturnal as well as diurnal frequency of
micturition becomes marked after cystitis develops. With severe infection, the urinary
urges become painful and there is scalding micturition.

- Difficulty of micturition is caused by descent of the bladder base below the level of the
urethrovesical junction; urine needs to go uphill against gravity to reach the urethra; and
in order to evacuate such vesical pouch below the urethral level stronger contraction of
the detrosor is required. Frequently the woman learns to elevate her anterior vaginal wall
in order to be able to start the act of micturition. As a result of stronger contraction of the
bladder the intravesical pressure is chronicly raised and there will be hypertrophy of the
bladder wall. This can be appreciated during cystocopy by seeing trabiculation of the
bladder mucosa resulting from hypertrophy of the detrosor.
- Inevitably chronic retention of urine will develop. This usually cannot be sensed by the
patient (is not a symptom) but there is increased volume of residual urine i.e. the amount
of urine remains in the bladder after the micturition. This can be diagnosed by passing a
catheter after micturition or demonstrated by post-micturition pelvic sonography. The
normal volume of residual urine is < 50 ml and its increase predisposes to bladder
infection i.e. cystitis. The urine normally contains many bacteria which filter into the
urinary tract through the rich lymphatic connectionc with the colon which lies upon the
renal pelvis and ureters. The colonic bacteria like E. coli reaching urine are washed out in
the ongoing stream of normal micturition before they have enough time to significantly
multiply. The chronic retention associated with cystocele gives these organisms a chance
to multiply since the urine is a good culture medium for these colonic organisms. When
they reach a high population usually above 100,000 per ml (significant bacteria), they
gain virulence i.e. ability to invade the wall of the bladder and upper urinary tract.
Urinary tract infection usually starts by cystitis but readily spreads up the lumen to the
ureter and renal pelvis resulting in pyelitis and pyelonephritis.

- There is another long-term adverse effect on the urinary tract: The high intravesical
pressure is reflected upon (conducted to) the ureters and renal pelvis causing hydroureter

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and hydronephrosis. Moreover, the ureter itself can get kinked, usually at the level of
traversing the ureteric canal in the upper part of Mackenrodt’s ligament. This is caused by
dragging down upon the lower ureter by the descending bladder base. The suprapelvic
part of the ureter and renal pelvis can be markedly dilated. This continues insidiously and
ultimately results in progressive loss of renal parynchyma and renal function. The loss of
kidney cortex is accentuated by chronic pyelonephritis, and as a result, the patient with
long-standing prolapse can have hydronephrosis and pyonephrosis and ultimately
becomes uremic. Uremia should be expected in long-standing prolapse; and due to its
unspecific manifestations, can be missed during the preoperative assessment of the
patient.
- Stress incontinence of urine is a common associated symptom with genital prolapse.
This symptom is due to loss of urethral tone and the weakness of the functional sphincter
at the bladder neck. This weakness is not dependent on the pathological anatomy of
prolapse (like the frequency, difficulty and infection). It is caused by pathological
considerations independent of the prolapse, and is a common underlying weakness of the
tone of the musculo-fascial tissue of the pelvis. The upper urethra has a weak tone and a
low internal pressure which can be overcome by the rise of intravesical pressure during
sudden stress i.e. rise of intra-abdominal pressure during coughing, sneezing, laughing or
sudden movement. Consequently, few drops of urine leak hence the name stress
incontinence. This weakness of tone of the urethrovesical junction is the main cause of
stress incontinence. However, the weakness is accentuated by the downward sagging of
the urethrovesical junction below the level of pelvic diaphragm. Consequently, the rise of
intraabdominal pressure occurring during these sudden stresses is influencing the bladder
but not the upper urethra, and urethral resistance is thus easily overcome.
The fact that stress incontinence is not a genuine symptom of prolapse but rather an
associated condition is born out by the observation that a marked cystocele may not be
associated with stress incontinence. On the other hand, marked stress incontinence can
occur in absence of prolapse or with mild grades of prolapse. Even, stress incontinence
can develop for the first time after the surgical correction of the prolapse. Such latter
occurrence may be explained by the fact that in the presence of a big cystourethrocele the
weak urethra might have been kinked, something that had been preventing the escape of
urine on sudden stress. When the urethra and the bladder base are straightened by anterior
coporrhaphy, the urethral tube comes in line with the base of the bladder and is left to its
own weakness.
The corollary of the above consideration is that the associated stress incontinence will
always need surgical correction for its own as described later (see under Stress

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Genital prolapse

Incontinence) which can be added to the anterior coporrhaphy, lest the complaint should
persist or become accentuated.

3.5 Rectal symptoms; these results from the difficulty in evacuating the downward
bulge of the anterior rectal wall in the rectocele. The patient may, again learn the need to raise
the posterior vaginal wall or massage it in order to open her bowel. However, this difficulty
frequently results in formation of big hard fecolith and laziness and loss of bowel rhythm
resulting in constipation. Anal fissure will develop and accentuate the vicious circle further.
3.6 Vaginal discharge; Due to chronic congestion of the vagina resulting
from its descent and exposure, there is increase in the vaginal discharge i.e.
leucorrhea. Later on, the discharge becomes infected and purulent when trophic
ulcerations occur (see later). These ulcers can also cause bleeding and bad odor.

4. Complications of genital prolapse

4.1. Urinary tract complications:
- Infection: cystitis, pyelonephrosis.
- Back pressure leading to hydroureter and hydronephrosis. These need to be looked
for during clinical examination and by intravenous pyelography.
- Uremia.

4.2. Local complications:

- Elongation of the supravaginal part of the cervix to several times the normal length.
Elongation seems to be due to dragging down on the cervix by the prolapsed vagina.
If the elongation is overlooked prolapse will persist or recur after operative repair. It
is assessed by sounding the cervix and uterine cavity. If the internal os is patulous
dilator of number 4 or 5 can be used.
- Hypertrophy of the portiovaginalis of the cervix because of chronic congestion and
exposure.
- Keratinization of the exposed vagina: This appears as a white patch of keratin over
the exposed part of the vaginal mucosa. Occasionally, brown or black pigmentation
occurs, the explanation of such development is not clear.
- Trophic ulcerations: These develop on the lowermost part of the prolapsed structure.
They are similar to the decupitus ulcer that develops on the medial maleolus with
longstanding varicose veins of the lower limbs. The trophic ulcer is superficial and
has a clean-cut edge, a margin covered by keratin plaques, a red floor that can be

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Genital prolapse

covered by pus, and a soft base. This ulceration is caused by chronic congestion and
accumulation of metabolic waste. The congestion is caused by kinking of veins of the
upper vagina (which reach from above). Friction between the thighs may contribute to
ulcers on the sides of the prolapsed vagina, but these are uncommon; usually the ulcer
occurs on middle line areas, which is the most congested by dependency.
Postmenopausal thinning out of the vaginal mucosa can also contribute to ulceration
in elderly patients. That congestion is the main etiological factor of trophic ulcer is
evidenced by their effective treatment by keeping the prolapse reduced by a pack of
gauze. This corrects the kink of vessels and improves venous drainage. The sterile
packs are changed daily and the effect is readily appreciated; the ulcer gets clean and
heals within few weeks without any additional treatment. In postmenopausal patients,
healing can be enhanced by estrogen cream or by systemic administration of this
hormone.
- Incarceration of the prolapse is rare and occurs when marked prolapse becomes
irreducible. This occurs in senile women who neglect reducing their prolapse for a
long time. The consequent congestion increases the bulk of the mass and makes it
irreducible. If the patient is kept in bed for some days, the congestion subsides and the
prolapsed bulk can then be reduced and subsequently kept inside by a vaginal pack
and fixing an indwelling catheter. Prophylactic antibiotic and anticoagulant will need
to be administered. The latter is needed because of prolonged recumbency.
In spite of long standing exposure and irritation, the probability of cervical
carcinoma is not increased.

4.3 Pregnancy with prolapse

Genital prolapse does not cause sterility and pregnancy can occur. The building
congestion and enlargement of the uterus increase the symptoms particularly heaviness. After
the uterus enlarges, it uterus will be supported upon the pelvic brim and the cervix rises into
the vagina. Labor is rarely complicated by the prolapse. Dilatation of the cervix proceeds
normally, but a hanging down anterior lip can get caught between the pubis and the head and
hangs down below the head. By gentle manipulation during the second stage this hanging
cervix can be eased up out of way.

Differential Diagnosis of Prolapse

1. Vulval and vaginal cyst: like Bartholin cyst or Gartner’s cyst are easily
differentiated from prolapse by their location and the fact that they are irreducible. A
sound in the bladder can clinch the diagnosis.

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Genital prolapse

2. Cervical tumors and polyp and uterine polyps protruding.

3. Elongation and hypertrophy of the portiovaginalis of the cervix..
4. Urethral diverticulum - can be differentiated by a sound in the urethra..
5. Chronic inversion of the uterus.
6. Varicosities of the vulva and vagina.
7. Inversion of urethral mucosa.
8. Urethral caruncle.
9. Rectal prolapse.
10. Acute vaginitis can cause a sense of heaviness and weight.

5. Treatment of Prolapse
5.1 Prevention
1. Avoidance of predisposing causes (see above under etiology).
2. Repair of perineal tears.
3. Encouraging pelvic floor exercise during puerperium.
4. At hysterectomy: a) fixation of the vascular stumps to vaginal vault; b) detection
and treatment of an associated hernia of the pouch of Douglas and any rectocele.

5.2. Therapeutic treatment

5.2.1. Non-surgical treatment
- Pelvic floor exercises: are particularly helpful during the puerperium, but the effect is
limited. Instruct the woman to uplift her anus by regular contractions of her levator ani
several times, each contraction lasts for 5 seconds at least 20 times in each session, 3
sessions per day. Kegel perineometer is a pneumatic tube that is put in the vagina and the
patient trains herself in raising the pressure in the connected pressure gauge to the
maximum. This is a way to organize and encourage training and the hypertrophy of the
levator ani.
- Pessary treatment is a temporary measure, which can be utilized, in the following
situations:
1. During pregnancy.
2. Postpartum period.
3. If the patient is planning a pregnancy in the near future.
4. To give time for treatment of a temporary contraindication to surgery, like chest
infection, temporary cardiac ischemia.
5. To promote healing of an atrophic ulcer.

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Genital prolapse

6. Patient’s refusal of surgery.

7. Pessary test to see whether the symptoms e.g. backache can be ascribed to prolapse.
A ring plastic or vulcanite pessary is used. The correct size is chosen by trial. The ring is
retained above the pelvic diaphragm and hence only usable if the pessary can be retained. The
patient is taught to insert the pessary and remove it every few days for washing. It has to be
emphasized to the patient that the pessary does not cure the prolapse.

5.2.2. Operative treatment

A. Choice of operation:
Almost all cases of genital prolapse should be treated by surgery. A patient with
marked prolapse should be persuaded to have the operation, in order to obviate the
complications. There are many operations that can be used, some of them are very simple and
can be done under local anesthesia.
Operations for correction of genital prolapse are commonly done by any specialist but
they require good judgment and frequently experience. The choice of the operation depends
upon:
1. Proper appraisal of the particular anatomical pathology present; a most important
consideration.
2. The degree of pathology.
3. The functional width of the vagina is planned depending upon the interest of the
patient in sexual intercourse. One should consider that the husband may be having a
declining potency and tightening of the vagina too much may interfere with penetration.
The surgeon has to exercise common sense in sacrificing any part of the vaginal wall;
what is cut is difficult or impossible to compensate for.
4. Interest in having further pregnancy.
5. Availability of natural anchoring points to suspend the uterus and vagina to.

B. Preoperative preparation
1. Treatment of any trophic ulcer (see above) should precede the operation. The presence
of ulcer means two things: the first is that the tissues in which the surgery will be
performed are infected, and second they have poor healing because of devitalization and
congestion. The time lost in improving the condition of the vagina is gained in ready
postoperative healing. Postmenopausal women will need estrogen treatment, either
locally (Premarin cream) or systemically when the vaginal skin looks thin and atrophic.
The estrogen treatment enhances the coagulation of blood, and anticoagulant can be
initiated (in proper dosage) preoperatively and continued after the surgery particularly if it
is expected that the patient will remain in bed for a long time.

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2. Treatment of urinary tract infection is necessary and should be based on culture and
sensitivity of the infecting organism(s).
3. The general condition of the patient should be corrected particularly anemia, chest
infection and diabetes.
4. Any cause of chronic straining e.g. chronic cough should be corrected before the
operation.

6. Operations for treatment of genital prolapse

The following discussion will go through a repetitive scheme:

§ Cystocele and cystourethrocele

a. Pathological anatomy:
1. Weakness, stretch and lateral recession of the two-pubocervical ligament or fascia
and the downward herination of the base of the bladder in between. Occasionally
the descent is more marked in the lateral parts of the anterior vaginal wall. During
1980s Richardson has emphasized the importance of this antrolatral or paravaginal
defect and described an operation for correcting it through abdominal retropubic
approach,
2. Stretch, weakness and redundancy of the anterior vaginal wall in the middle line.
3. Weakness of the pelvic floor, which indirectly carries the anterior vaginal walls.
b. Principles of the operation of anterior coporrhaphy:
1. The anterior vaginal wall is dissected from the base of the bladder.
2. The bladder is mobilized upwards until it becomes retropubic.
3. A buttress or shelf is created under the bladder by suturing together the two
pubocervical fascia in the middle line.
4. Excise the weak stretched redundant vagina in the middle line and bring inward
unstretched strong vagina in the middle line under the bladder.

5. Pelvic floor, repair lends indirect support to the anterior vaginal wall. It should be
done even if there is no descent of the posterior vaginal wall.
c. Operative detailes:
1. Spinal anesthesia is preferred in all vaginal operations if acceptable by the patient;
it induces vasopasm in pelvic vessels rendering the operative field dryer. Carful
examination asseses the pathological anatomy present.
2. Infiltration of submucosa with saline containing adrenaline or petressin is
unnecessary and may confuse the planes.

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Genital prolapse

3. A transverse incision is made just below the bladder sulcus (in reality anatomically
above the sulcus - the anatomical landmarks of the everted vagina are upside down
reversed). The incision cuts the vaginal wall with the vaginal fascia. This ensures
entering into the proper less vascular vaginovesical plane.
4. The vagina is separated from the bladder by blunt dissection utilizing the tip of a
blunt curved scissors which is inserted closed and then opened and withdrawn with
the blades separated. Pulling down upon the cervix will help in keeping to the
correct plane.
5. If there is no urethrecele and the transverse vaginal sulcus is evident, the lower
vagina should not be lifted from the urethra. The presence of the above sulcus
indicates that the triangular ligament containing the compressor urethra muscle
(striated muscle) tucks the urethra forward. The unnecessary dissection (which is a
sharp one) will damage this ligament and will induce venous bleeding; since this
part of the anterior vaginal wall is especially vascular.
6. The anterior vaginal wall is divided in the middle line.
7. The bladder is apparent in the wound, and its lateral parts are covered with the
pubocervical ligaments (or fasciae). These normally separate with the bladder if the
dissection is in the correct plane (figure 6). No attempt should be made to separate
the pubocervical ligament from the bladder. Blunt dissection of the anterior vaginal
flaps should be continues laterally to fully expose the bladder. However, it is better
not uplift the vagina until the pubic arch is reached, since the lateral angles are
vascular and bleeding in this angle may take time to control.
8. Lifting the bladder with a toothed while still pulling upon the cervix will identify
the cervicovesical ligament in the middle line, which is cut with a scissors. Thus,
the vesicocervical space is entered and it can be noted that it is an avascular plane.
The bladder is easily bluntly dissected upward in the middle line. However,
laterally the bladder is held to the cervix by the bladder pillars. These contain blood
vessels and need to be clamped before cut. This is done with the bladder lifted up.
9. The cutting of the bladder pillars allows upward mobilization of the whole bladder
until it is completely retropubic. The peritoneum of the uterovesical pouch can be
then identified; but this is not necessary to see.
10. The most lateral unstretched parts of the pubocervical fascia (while still upon the
bladder) are approximated in the middle line by a series of interrupted sutures of
chromic catgut or braided Dixon. No. 2-0 (Figure 7). If there is a urethrocele the
paraurethral tissue are approximated. The approximation of the pubocervical
ligaments is continued until the most posterior stitch, which is made to bite upon
the supravaginal cervix. In that way a complete shelf or buttress is created under

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Genital prolapse

the bladder base, made of the approximated pubocervical ligaments preventing its
redescent from its retrophic position. Hemostats is ensured; few diathermic
fulgurations can be done.
11. The excised part of the anterior vaginal wall is usually triangular with the apex at
the urethra and base at the cervix. However, an elliptical part can be removed in a
big cystocele. The extent of trimming of the vagina depends upon its redundancy
and should not be excessive to avoid undue narrowing of the vagina. Excessive
shortening of the anterior vaginal wall will leave the cervix near the introitus, i.e.
causing recurrence of prolapse.
12. The vagina is closed in the middle line by a series of interrupted sutures of [Link]
Dixon or Vicryl. You should leave an adequate length of the anterior vaginal wall
to avoid pulling the cervix down to the vaginal introitus. Careful approximation of
edge (frequently by vertical mattress suture is necessary to avoid formation of
granulation and tender scar. The sutures in the vagina should be cut long.
13. Pelvic floor repair (posterior colpoperineorrhaphy) is always necessary but this
should not narrow the vaginal tube too much. You depend upon the support gained
by approximation of the levator ani rather than excessive unnecessary trimming of
the posterior vaginal wall, unless required for correction of pelvic rectocele.

Genital prolapse: (Figure 6): anterior colporrhaphy. 1. Urinary bladder; 2. Pubocervical

ligament adherent to the surface of the bladder; 3. Blunt upward mobilization of the bladder;
4. Supravaginal cervix.

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Genital prolapse

Genital prolapse: (Figure 7): Anterior colporrhaphy. 1. The two pubocervical; ligaments
sutured together in the middle line underneath the bladder;2. The last suture is passed in the
supravaginal cervix; 3. Supravaginal cervix.

§ Repair of paravaginal defect:

a. Pathological anatomy:
1. Avulsion of the anterolatral attachment of the pubocervical ligament from the
arcus tendineus.
2. As a result, descent of the bladder and the urethra occurs. This results in a lateral
cystocele (usually in the right side) which can be associated with stress
incontinence. The classical repair of midline defects usually gives unsatisfactory
results.
b. Principles of paravaginal repair of cystourethrocele:
Essentially the operation consists of suturing the lateral vaginal wall at the level of
urethrovesical junction to the Archus tendineus.
c. Operative detailes:
- Dorsal lithotomy positioning and abdominovaginal drapping.
- An abdominal approach through a Pfannensteil incision.
- If the uterus needs removal this is completed first.
- If there is a deep Douglas pouch, it is obliterated by Moschovitz or Halban
plication of the uterosacral ligaments (see later).
- Enter the space of Retizus.

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Genital prolapse

- The bladder is reflected medially exposing the lateral vaginal wall.

- A finger in the vagina at the level of the urethro-vesical junction raises the lateral
vaginal wall. Then place a “Key” strategic stitch opposite the vesical neck in the
antrolatral vaginal sulcus.
- Pass the needle through the arcus tendineus at about 1.5-2 cm below the obturator
foramen.( This action complete the key suture)
- Similarly, place two to four similar sutures distally and one or two sutures
proximally.
- Tie down all the sutures at one time i.e. after all them have been placed (Figure 8)
- Use permanent 2-0 dacron suture material and small needle.
- Try to avoid the antrolateral vessels on the vaginal wall.

Genital prolapse: (Figure 8): Retropubic paravginal repair; Retropubic approach.

1. Obturator nerve and artery; 2. Obturator internus muscle; 3. White line (arcus Tendineus);
4. Vagina; [Link]; 6. The Key suture passed through the vagina and the white line at the
level of the bladder neck; 7. A Sponge on a holder pushing the bladder medially.

§ Rectocele
a. Pathological anatomy comprises:
1. Stretch, weakness and lateral recession of the levator ani, and loss of the middle line
decussation at the apex of the perineal body. This is the main pathology.
2. Stretch, weakness and redundancy of the posterior vaginal wall and the fascia in the
middle line.
3. Defective perineum and scarring can be present as a result of an old tear.

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Genital prolapse

b. Principles of the operation of posterior colpoperineorrhaphy or pelvic floor repair

(PFR):
1. Dissection of the posterior vaginal wall from the anterior wall of the rectum.
2. Approximation of the two-levator ani in the middle line. This is the main step; it
shortens the muscles, reestablishes the division of the pelvic hiatus into tighter
ureogenital and rectal hiatuses, and supports both the vagina and rectum.
3. Excision of the weak, stretched and redundant vagina in the middle line, bringing in
place fresh unstretched vagina from the sides.

c. Operative details:
1. The surgeon assesses the extent of widening of the vulval hiatus and the defect in the
perineum present. The desired trimming can be judged by placing two Allises at the
posterior ends of the identifiable remnants of the labia minora, approximate the two
forcepses in the middle line to judge the desired width of the introitus. This should
admit at least two fingers above the approximated Allises. The presence of hernia of
the pouch of Douglas should be excluded.
2. With the assistant(s) pulling upon the Allises laterally the edge of the mucocutaneous
junction is excised. Occasionally, scarred tissue needs to be removed. Inclusion
dermoids present at the scar of previous tear or repair can be present. These should be
removed intact without spoiling the field by their sebaceous content, such spillage
increases the liability of reoccurrence of such cyst which can be tender and cause
dyspareunia.
3. The posterior vaginal wall is lifted from the perineal body and rectum by blunt
dissection. Entering in the right plane is indicated by ease of separation and minimal
bleeding. It is not at all necessary to put a sponge or a finger in the rectum; this will
contaminate the operation field. If there is doubt about the correctness of the plane in
the middle line, one starts by the dissection on the sides away from the front of the
rectum until the rectovaginal space is entered and then proceeds to the middle line.
This is particularly necessary if there is scarring in the middle line. The dissection
should be continued laterally until the levator ani are adequately seen and felt in the
lateral angles of the field. Few bleeders may need be secured and diathermically
coagulated. The upward extent of the dissection is determined by the size of the
rectocele.
4. The two-levator ani (not just the covering endopelvic fascia) are then approximated in
the middle line by No. 2-0 chromic catgut. The rectum should be depressed and moved
to the other side by the index finger of the left hand during placement of the suture

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Genital prolapse

needle. The bites should be adequate. The height of the upper stitch is critical and
depends upon the desired width of the vagina planned upon. After placing of this first
approximating stitch, you pull the threads and insert two fingers above it. Thus, you
can decide whether you need to start from more forward or backward stitches. Two or
three stitches are enough.
5. Before tying the levator ani stitches, you excise the redundancy in the posterior
vaginal wall. Usually a triangular part based at the mucutaneous incision is removed,
the apex reaches in the vagina as high as judged by the size of the rectocele.
Occasionally an elliptical part needs to be removed, the wide part is opposite the
ampulla of the rectum.
6. If the ampulla of the rectum is voluminous, this indicate weakens of the rectovaginal
septum. This big forward projection can be reduced by a series of plicating sutures
biting upon the muscle wall only. It needs to be emphasized that the surgeon should be
sure that there is no hernia of Douglas pouch. In case of doubt, a finger (with an
additional glove) is passed in the rectum. After these provisions, the levator stitches
are tied, just ensuring approximation rather than crushing the included muscle fibers
by the ligature; something that will transform the muscle into weaker fibrous tissue.
7. The vaginal edges are approximated in the middle line. Proper coapetation will
diminish the chance of formation of painful granulations and inclusion dermoid. These
can be the cause of contact bleeding and dyspareunia respectively. Another possible
problem with suturing of the posterior vaginal wall is leaving behind a hanging
bulging upper extremity of the suture line that can be a cause of patient’s
dissatisfaction. This can be avoided by removal of the correct amount of vaginal at the
middle of vaginal length.
8. The superficial perineal muscles under the levator ani are brought together by two or
three stitches, leaving no dead space.
9. The skin is closed in the middle line using under the skin fine buried subcuticular
continuous suturing of fine Dixon.

Indications for PFR: 1. Rectocele, 2. in conjunction with the repair of all other types of
genital prolapse, 3. Perineal tear or broken repair of episiotomy, 4. Patulous vagina, 5. Repair
of certain rectovaginal fistulae, 6. And in conjunction with repair for stress incontinence.
Classical repair: is the term used to describe anterior coporrhaphy plus posterior
colpoperineorrahaphy.

§ Enterocele or Hernia of the Pouch of Douglas

a. Pathological anatomy:

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Genital prolapse

See under anatomical consideration.

b. Repair of an enterocele
Can be done either vaginally or abdominally
c. Operative details:
The vaginal repair is more frequently used and has the same principles like those of
repair of any hernia.
1. Incision of the covering; in this case it is merely the vaginal wall.
2. Dissection of the sac up tills its neck.
3. Opening of the fundus of the sac and reducing the contents.
4. Excision of the sac at its neck (Figure 9).
5. Closure of the ring, i.e. the aperture through which peritoneal bulging has occurred, by
approximating the two-uterosacral ligaments in the middle line.
6. Reinforcing the closed neck by coverage by PFR.

Genital prolapse: (Figure 9): Vaginal repair of a hernia of Douglas pouch; 1-The cut edge of
the neck of the hernia; 2. Uterosacral ligment; 3. Levator ani; 4. Rectum

The Abdominal repair is used if laporotomy is done for another purpose. The
principles of the operation are obliterating the Douglas pouch by a series of delayed -
absorbable sutures. Two types of operation are possible: In Moschcowitz’s operation,
several tires of purse-string circumferential ligations are inserted. They start at the depth of
the pouch and proceeding upward, the last tire passes into the uterosacral ligament. This
approach has three possible problems: 1) Tying the top stitch is difficult, and if any central
opening remains, the hole can provide access to a loop of the small bowel and may cause an

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Genital prolapse

internal hernia and intestinal obstruction. 2) It inadequately supports a prolapsed vagina and
3) The upper stitch may include one or both ureters or kink one or both of them.

In the alternative Helban’s operation, five or six stitches are passed through the
peritoneum of the pelvic floor in the saggital plane. The most anterior one bites in the
posterior vaginal fornix and back of the cervix. The sutures are tied after having them all in
place. When they are securely tightened, they effectively obliterate the Douglas pouch
without compromising the position of the ureters.

§ Uterine Prolapse:
a. Pathological anatomy
1. Weakness, stretch and elongation of the Mackenrodt’s ligaments.
2. Retroversion - flexion of the uterus.
3. Associated vaginal prolapse.
4. Elongation of the supravaginal cervix and hypertrophy of its portio-vaginalis, in some
cases.
5. Weaknesses of pelvic floor mainly the levator ani.

A number of operations are possible:

1) Fothergill’s or Manchester operation:
A. This operation is applicable to all cases of prolapse of uterus. The principal steps are:
a. Dilatation and curettage: The dilatation is essential for the latter step of covering
the stump of the amputated cervix by vaginal mucosa, using stitches passed from
the inside of the cervical canal. The curettage serves to diminish the amount of
subsequent menstruation and to exclude associated endometrial pathology.
b. Anterior colprrhaphy, if an associated cystocele is present.
c. Amputation of the cervix to remove the elongation of the supravaginal portion
when presents. The Mackenrodt’s ligaments on the sides of the cervix can then
become more defined.
d. Plication of the two Mackenrodt ligaments and fixing them to the front of the
cervix. This is the main step of the operation and will serve to absorb the
elongation in these ligaments that will carry the cervix up. It will also push the
cervix backward thus allowing the body to fall forward in anteflexion, preventing
the uterus from telescoping into the vagina.
e. Covering the cervical stump by vaginal skin.

f. Posterior colpoperineorrahaphy.

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b. Operative details:
a. Avoid excessive shortening of the cervix. (see under complications).
b. The Mackenrodt’s should be bitten by the shortening stitch not just lateral to the
cervix. This is in order to absorb or take in an effective part of its elongation. To
obviate passing through the ureter the bladder needs to be effectively elevated
and retracted upward and laterally by a long narrow right-angled retractor before
biting the ligament with the suture. This suture approximating the Mackenrodt
should then be passed in the lower part of the remaining portion of the cervix to
ensure carrying it up in the pelvis when tied. The stitch should not be tied except
in the later part of the operation before completing the closure of the anterior
vaginal wall. Tighing this stitch will raise upward the cervical stump away from
easy reach. In order to avoid the possibility of the stitch cutting through the tissue
and becoming ineffective, another one is put above it. If these sutures are
properly placed it will be noticed that the cervix will rise up in the pelvis, once
they are tied. Combining the last stitch in the vagina with these Mackenrodt’s
stitch is called Fothergill’s suture, but is not actually essential to combine these
two steps (figure 10)..
c. The covering of anterior lip of the amputed cervix is done by inverting the
sutured anterior vaginal wall into the cervical canal – the Stumdorff’s suture. A
bite is taken in the vaginal skin is made by NoO Dexon thread and the ends are
left long. Each end is passed in the substance of the cervix from inside out. Tying
the two ends on the outside of the cervix will carry up the vaginal skin to cover
the anterior lip. The posterior lip is similarly covered.
d. Search for an enterocele and correct it if present.
e. Exercise care in covering the stump by the vagina. At least two in-out stitches
should be done. This will prevent excessive scarring and cervical stenosis.
f. PFR is advisable.
Avoid excessive shortening of the vagina.

Complications of amputation of the cervix:

1. Stenosis of the cervix may cause infertility.
2. Cervical incompetence and second trimester abortions may result from removal of
the muscular part of the upper cervix.
3. Precipitate labor.
4. Cervical dystochia due to failure of the cervix to dilate during labor. If the
operation is properly done, particularly when care is exercised in coverage of the

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stump, failure of dilation will not occur. Cesarean section is not necessary in the
following pregnancy. However, adequate episiotomy will be needed.
g. If the cervix is not elongated there is no need to amputate the portio-vaginalis.
However, if it is elongated this step cannot be omitted.

Genital prolapse: (Figure 10): Fothergill’s operation; 1. Mackenrodt’s ligment;

[Link]’s suture plicating the two Mackenrodt’s ligament and fixing them to the front of
the cervix; 3. The cervical stump after amputation; 4. Covering the posterior lip of the
cervical stump by vaginal skin; 5. Fascial shelf under the repaired cystocele.

2) Vaginal hysterectomy plus pelvic floor repair:

This is an alternative operation to Fothergill’s operation for treatment of uterine
prolapse, which can be used under the following circumstances:
a. Postmenopausal women, or women above forty years with completed family size.
b. Marked uterine prolapse.
c. If there is an associated pathology in the uterus, like premenopausal bleeding,
endometrial hyperplasia or endometrial or cervical carcinoma (Shawta’s
operation done for malignant tumors).
d. Vaginal hysterectomy can be done in a multiparas who is not having prolapse
when there is an indication to remove the uterus for benign disease.

The operation will be an easier alternative to Fothergill’s operation if the uterus is small
and markedly prolapsed, when the operation can be very simple. However, if the cervix is

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Genital prolapse

markedly elongated several clamps will need be applied to each side, and Fothergill’s
operation is then better suited, unless there is an associated uterine pathology.
It needs to be borne in mind that the uterus is not the cause of the prolapse and that the
vaginal vault needs to be supported to obviate a subsequent vault prolapse that is difficult to
correct. To prevent this, the following measures need to be taken:
1. The stumps containing the vessels and ligaments of the uterus need to be
collectively tied together by delayed-absorbable suture, the ends of which should be
left long to be passed through the vaginal vault and tied at the end of the operation.
2. An associated cystocele and hernia of pouch of Douglas should be corrected.
3. A good PFR should be done at the end of the operation.

Operative hints:
1. Dissect the anterior vaginal wall from the bladder and raise the latter to a retropubic
position.
2. Complete the circumferential incision in the vaginal vault posteriorly and dissect
the vagina off the back and sides of the supravaginal cervix.
3. While retracting the bladder, upward apply the first two clamps on the side
of the uterus. This contains the lower part of the Mackenrodt’s and the
uterosacral ligaments. Once these are cut, the uterus can be more readily
pulled down. The clamped tissues on each side are transfixed and sutured by
No.1, Vicryl or chromic catgut (Dixon is too slippery to be entrusted to these
coming ligatures of important pedicles). One end of the ligature is left long.
4. Now the Douglas pouch is opened and a marking thread is put in its
posterior leaf.
5. The Mackenrodet’s ligaments are now bluntly dissected from the front and
the behind and the second pair of clamps on the side of the uterus are applied
while retracting the bladder upward and laterally. They include the upper
parts of the Mackenrodet’s ligaments and the uterine vessels. Once these are
cut, the uterus can be markedly pulled down. The included tissues are
transfixed and sutured. One of the strings is cut and the other tied to the long
thread of the preceding ligature. Again, one of the pair are tied together; one
end of the string is cut and the other left long.
6. Now, by inserting two fingers in the Douglas Pouch, the fundus of the uterus is
bent forward into the uterovesical, which can now be opened, and the anterior edge is
marked by a marking thread. The fundus is delivered into the opened
uterovesicovaginal pouch.

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Genital prolapse

7. The third pair of clamps is applied to the uppermost part of the structures on the
sides of the uterus that comprise the tubes, ovarian vessels and the broad ligament. The
clamped structures are transfixed and sutured. One end is cut, the other left long and
tied to the long thread left behind in the previous ligature. The result of this serial tying
of the ligatures on each side is gathering together the stumps including the ligaments
of the uterus on each side in one knot with two long strings. At the end of the
operation, these two strings are passed through the vaginal vault and tied. This will
uplift the vaginal vault, prevents its inversion particularly after the pedicles have
become fibrosed, and shortened.
8. If the cervix is markedly elongated, more than these three classical clamps will
need be applied to each side of the uterus.
9. After severing the uterus, the peritoneal leaves carried on the markers are sutured
by a continuous suture.
10. Anterior coporrhaphy is completed.
11. Search for and correct any associated hernia of Douglas pouch.
12. The vaginal vault is closed by interrupted sutures in a transverse plane. This is after
fixing the gathered pedicles to the vaginal vault.
13. Pelvic floor repair is needed in all cases.
(For more details and figures, refer to the chapter on hysterectomy).

3) Le Fort Operation
This is a partial colpocleisis. It is a simple short operation, which can be done under
local anesthesia. It is suitable for senile women not fit for bigger operations, and who are not
interested in sexual intercourse.
A rectangular area of the anterior vaginal wall about four centimeters breadth is
removed reaching from the fornix down to one centimeter above the urethral meatus. A
corresponding rectangular area of the posterior vaginal wall reaching down to the perineum is
also removed. The two areas are united together by a series of interrupted sutures starting
from below the cervix and progressing down the two sides till the perineum. The sutures are
tied on the outside of the vagina. Plication mattress sutures may be placed beneath the bladder
neck and across the lower anterior rectal wall. A pillar is thus created under the uterus
supporting it and obliterating most of the vagina leaving two narrow tunnels on the sides for
the escape of any future bleeding.
Disadvantages of LeFort operation: 1. Coital function is lost. 2. The uterus can be a
seat of future pathology that will be difficult to diagnose. 3. By fixing the base of the bladder

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to the rectum, the urethrovesical angle is lost leading to stress incontinence. 4. An enterocele
may be missed.

§ Vaginal Vault Prolapse or Massive Eversion of the vagina

a. Pathological anatomy
1. This is a marked prolapse in which the vaginal vault is everted inside out.
2. The uterus may be present or had been removed either abdominally or vaginally (see
under etiology).
3. The supporting of ligaments of the vaginal vault and the uterus are absent (severed) or
very weak, due to severe constitutional weakness (see under etiology). The patient can
be elderly or old, not interested in having further pregnancy or in sexual intercourse.
On the other hand, she can be young needing to preserve her sexual and reproductive
functions as in case of prolapse occurring in children, young unmarried or married
women.
4. There is usually an enterocele.

b. Prevention of vault prolapse after hysterectomy: see above

c. Operative options
1. Ventifixation was used in the past but it carried many disadvantages:
- Recurrence is almost certain.
- The recto-uterine pouch is widened and enterocele will develop or progress.
- In the event of pregnancy, posterior sacculation will develop leading to aborting or
rupture uterus.
2. Vaginal hysterectomy + vaginal excision of the enterocele + total vaginectomy or
marked narrowing of the vaginal tube. Thus sexual function is compromised.
3. Transvaginal sacrospinous colpopexy. The upper vagina is suspended to the
sacrospinous ligament on one side using a fascial graft. Coital and reproductive
functions are preserved. The operation can be used whether the uterus is present or
absent.
4. Abdominal sacral colpopexy: This is an alternative to the preceding operation, which
is resorted to if there is another reason to open the abdomen.
5. Abdominal anterior colpopexy to the anterior rectus sheath: This is a less favorable
alternative to the preceding operation because of: 1) shifting the vaginal axis forward and
of: 2) increasing the width of the mouth of the Douglas pouch predisposing to an
enterocele.

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Genital prolapse

§ Transvaginal sacrospinous colpopexy (Operative hints):

This operation need special set of instruments, but the author has repeatedly done a
number of such operations utilizing a pair of right-angled long narrow retractors.
1. The posterior vaginal wall is longitudinally incised and the vaginal wall is dissected
from the anterior rectal wall as high as possible.
2. If an enterocele is present the sac is dissected, excised and the uterosacral ligaments
are sutured together in the middle line by delayed absorbable sutures.
3. Having the rectum displaced to the left side, and the rectal pillar on the right side (the
sheath of fascia extending from the rectum to the lateral pelvic wall) is entered by the
tip of a long curved artery forceps. The opening is bluntly widened to expose the
ischial spine and the sacrospinous ligament and the overlying coccygeous muscles that
can be seen or else palpated.
4. At a point 2 - 3 cm (a finger breadth) medial to the tip of the ischial spine, the
coccygeous muscle/sacrospinous ligament complex is penetrated by the blunt tip of
the long-handled aneurysm needle holding the full length of a delayed absorbable
suture (Dixon or Vicryl, size 1 or 2). One side of the suture loop is picked by a long
hook or artery forceps and brought out, and then the suture carrier (aneurysm needle)
is withdrawn along the other side of the suture loop (figure 11). Pulling on the two
long ends will assure its fixation to the strong musculoligamentary structure i.e. it can
rock the pelvis in a lean patient. Care should be made during passing this suture to
avoid piercing the ligament near the tip of the ischial spine which has on its outside at
this point, the pundendal nerve and internal pundendal vessels. To avoid piercing them
the surgeon puts the tip of his left index finger medial to the spine and passes the tip of
the aneurysm needle medial to this finger. A second stitch is placed medial to the first
one and its tips are again left long. Placing of these two sutures is not a problem if the
correct instruments and retraction is made. There is no need to repeat the procedure on
the other side.
5. The ends of each loop of suture are threaded to two needles, which are passed through
the uppermost part of the trimmed posterior vaginal wall. Tying of these sutures
should carry the posterior vaginal fornix and fix it to the ischial spine. This tying
should however, be postponed until completing the anterior part of the vaginal repair
(anterior coporrhaphy).
6. Pelvic floor repair is done.
7. It can be noticed that this operation preserves the normal backward direction of the
vagina.

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Genital prolapse

Genital prolapse: (Figure 11): Transvaginal sacrospinus clpopexy;1. Coccygeous muscle/

sacrospinous ligament complex; 2. Edge of the sacrum and the coccyx 3. Aneurysm needle
transfixing the muscle ligament complex; 4. Dexon threaded on the aneurysm needle; 5. One
side of the thread being hooked down; 6. The index finger of the left hand of the surgeon put
medial to ischial spine to safe guard the nerve and vessels on its back

§ Abdominal Sacral Colpopexy

1. The patient is put in dorsal/lithotomy position and the buttocks are brought to the
edge of the table. The abdomen and perineum are drapped.
2. If there is a cystocele or rectocele, these will need to be repaired vaginally before
proceeding to the abdominal part.
3. The abdomen is opened by a middle line, subumbilical incision.
4. The front of the anterior rectal sheath on one side is cleaned of fat. A Strips of this
sheath 10 cm long and 2.5 cm broad is excised and kept in gauze soaked in saline.
5. The abdomen is opened and explored. If there is deep uterovesical pouch it needs
to be obliterated by either the Moscowitz’s or Halban’s technique.
6. If the uterus had been removed, the vaginal vault is pushed up by a ball of gauze
carried on an Allis to help identification of the peritoneum on the vaginal vault. This
peritoneum is removed to expose 3x4 cm area of the vaginal apex and the bladder is
dissected from the top of the vaginal apex.

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Genital prolapse

If the uterus is present, the anchoring sutuers are placed in the posterior vaginal fornix
and the supravaginal cervix.

7. Four delayed absorbable sutures (Dixon or Vicryl) size No. 1 are passed deep in the
muscle of the vaginal vault and their ends are kept long. No harm will result from
inclusion of the whole thickness of the vagina. The ends of the sutures are passed in
one end of the anterior rectus sheath graft.
8. A longitudinal incision is then made in the peritoneum of the posterior pelvic wall
to the right of the sigmoid colon opposite S3 and S4. Three sutures of delayed
absorbable sutures are passed in the anterior sacral fascia and periosteum of these
vertebrae in the middle line and the ends are left long. These are passed in the fascial
graft at a length that ensures the proper pulling upon the vaginal apex. The sutures are
then tied over the flap and its redundant part excised. The peritoneum of the pelvis and
front of the sacrum is now sutured. It is appropriate to leave no dead space under the
graft by anchoring it to the now-raised and obliterated Douglas pouch. Instead of
anterior rectus sheath sling, a merselin mesh or tape can be used to suspend th e
vaginal vault to the sacrum.

7. Postoperative care of vaginal operation of prolapse

1. The vagina should be tightly packed by a length of gauze in order to prevent
reactionary hemorrhage. Foley’s catheter is put in the bladder. Both the pack and
catheter are removed after 24 hours. If an additional operation has been done for
stress incontinence the catheter is left for four days because retention of urine is
expected (see under Stress Incontinence). The catheter may need to be left longer
e.g. 6 days in patients who had had long standing prolapse. Before discharging the
patient sonographic examination should demonstrate absence of chronic retention
of urine.
2. The patient will need to be seen 2 and 4 weeks after surgery. If the wounds look
soundly healed, then intercourse can be allowed. Using a lubricating cream can
facilitate the early attempts. Some patients tend to postpone resumption of
intercourse for a long time because of fear or tenderness. This should be
discouraged since it may result in fibrosis stenosis of the vagina. The couple should
receive the proper support to resume marital life.
3. Pregnancy is not contraindicated after prolapse operation. Labor usually proceeds
uneventfully with the exception of the need for episiotomy. However, repeated
pregnancies and deliveries after the repair may predispose to recurrence. Cesarean
section may be required for patients that have undergone Fothergill’s operation.

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Genital prolapse

8. Results and complications of prolapse operations

In general, well-chosen and properly done operations give satisfactory results.
However, for some women the operative treatment is a beginning of suffering:
1. Dyspareunia: is mainly caused by undue narrowing of the introitus and the vagina.
This is a problem, which should not occur, one should err towards a wider vagina rather
than a pencil-like tube. The correction of the latter is most difficult. The problem may be
in the husband who is having a declining potency and is not ready to bear with the
difficulty in the early attempts at intercourse. For the unfortunate patient the operation
might represent the end of the sexual life.
Sometimes dyspareunia results from tender granulations or broken wound or rarely due to
formation of inclusion dermoid at the site of the operation.
The vagina can be atrophic in postmenopausal women; estrogen creams or systemic
estrogen can be helpful.
2. Stress incontinence may develop de novo after the operative correction of the prolapse
(see above).
3. Problems in subsequent pregnancy and labor (see above).
4. Recurrence of prolapse:
The causes can be
1. Ill-chosen operation, not addressing the pathologic anatomy (see above for
examples).
2. Faults in the operation e.g. a) neglecting to do the proper pelvic floor repair; b)
missing a hernia of Douglas pouch; c) neglecting to trim the elongated or
hypertrophied cervix; d) shortening of the anterior vaginal wall leaving the cervix near
the introitus e) failure to support the vaginal vault after hysterectomy resulting in vault
prolapse f) use of early absorbable suture material, which results in recurrence.
3. Chronic straining e.g. constipation, chronic cough.
4. Early resumption of strenuous type of life after the operation.
5. Repeated pregnancies after the operation
6. Postmenopausal atrophic changes.
Management:
1. Treat any activating cause.
2. Proper consideration of pathologic anatomy and resort to the proper operation e.g.
Fothergill’s, pexy-type of support or vaginal hysterectomy plus PFR. The future
sexual interest of the patient should be respected.

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Displacements of the genital organs other than prolapse

Chapter 12
DISPLACEMENTS OF GENITAL
ORGANS OTHER THAN PROLAPSE
Contents
• Upward and forward displacement of the uterus
• Backward displacement of the uterus
• Retroversion flexion of the uterus
- Etiology
- Possible symptoms
- Treatment
• Torsion
- Uterus
- Ovary and tubes
• Inversion
- Acute inversion
- Chronic inversion

Upward and Forward displacement of the uterus

Causes:
- Operative fixation of the uterus to the anterior abdominal wall. This is sometimes seen
after repeated cesarean sections.
- Displacement of the uterus by a vaginal or paravaginal tumor.
- Cervical or broad ligament myoma, and any other tumor impacted in the Douglas pouch.
- Collection of the pus or blood in Douglas pouch.
Clinical Picture:
- The clinical findings are those of the cause.
- The patient may be complaining of recession of the cervix out of her reach (during
douching).
- Infertility is rarely associated with postoperative fixation. The cause is usually associated
with peritubal or periovarian adhesions.

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Displacements of the genital organs other than prolapse

Treatment:
- This is usually directed to the cause.
- In the investigation of associated infertility, laparoscopy is needed but this requires
special care because of associated adhesions. Laparoscopy may be required for
microsurgical correction of associated pelvic adhesions. The uterus is then released from
its fixation to the back of the abdominal scar.

Retroversion and Retroflexion (RVF)

Retroversion implies that the axis of the cervix is directed upwards and backwards in
relation to the long axis of the body. Retroflexion implies that the long axis of the corpus
uteri is bent backwards on the axis of the cervix (Figure 1). The two conditions are commonly
associated. In the first-degree retroversion flexion, the uterus is in the axis of the vagina. In
the seconddegree, the corpus is bent behind this axis. In the third degree the corpus is behind
the posterior fornix. In the latter degree the anterior fornix gets shallow i.e. the anterior lip is
flush with the anterior vaginal wall.

Chocleate uterus is an unusual constitutional variation in which the cervix is

retroverted while the corpus is acutely anteflexion resulting in the whole uterus having a c-
shape configuration (Figure 1).

Displacement Other than Prolapse; Figure 1: Uterine version and flexion. a. Anteversion
anteflexion; b. Retroversion; c. Retroversion reflexion;d Cochleate uterus.
Etiology:
A. Constitutional
Retrodisplacement of the uterus is most commonly constitutional (congenital). Fifteen
percent of the female population are having this position of the uterus, usually without any
symptom or any interference with their reproductive function.

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Displacements of the genital organs other than prolapse

B. Acquired
Tumors or adhesions in the pelvis pushing or pulling upon the uterus backward. The
uterus is fixed in the retroverted flexed position.
C. Puerperal
The uterus during the third to the sixth week of the puerperium is unusually mobile
and may acquire a temporary retroverted flexed position. This is spontaneously corrected
when the processes of involution of the uterus and its ligaments are completed.
When the uterus remains permanently retrodisplaced after pregnancy, this generally
represents a return to a prepregnancy position.

Clinical Picture
Many symptoms and disabilities have been ascribed, without real basis, to
retroversion-flexion. A mobile retrodisplacement of the uterus is nearly always symptomless.
If the uterus is fixed backwards, symptoms can be present and these are those of the
cause of this retrofixation, be it inflammatory adhesion, endometriosis or a tumor.
The following are the symptoms that have been traditionally ascribed to RVF of the
uterus and are still lingering in the minds of some gynecologists :
1. Infertility: It is suspected that a RVF uterus has its cervix away from the usual seminal
pool in the posterior fornix. However, there is no evidence of this presumed association
and there is no sound basis of advising the couple to resort to coital positions that result in
deposition of semen in the anterior fornix. Surgical correction of marked RVF is most
exceptionally indicated in cases of infertility, this should be after exclusion of any other
cause.
2. Low back pain and chronic pelvic pain: The association of such common complaint with
mere retroposition of the uterus is most questionable. It can possibly be associated with
temporary puerperal RVF. This disappears after involution of pelvic ligaments and joints
and the subsidence of any mild existent puerperal infection.
3. Pelvic congestion syndrome consists of ill-defined, inconsistent symptoms ascribed to
congestion of the pampiniform plexuses in the broad ligaments. Such varicosities have
not been conclusively demonstrated in all cases. The symptoms comprise secondary
congestive dysmenorrhea, ill-defined pelvic ache, low backache, dyspareunia,
menorrhagia and polymenorrhea. These symptoms can be equally associated with retro or
ante position of the uterus. The management of these syndromes is difficult and may be
incomplete. It consists of careful attention to all causes of pain in this area whether they
are in the pelvic joints, genital system, urinary bladder or rectum. Pain in one of these
structures is readily referred to neighboring organs. The patient can be having anxiety and

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Displacements of the genital organs other than prolapse

neurosis. It is not safe to resort to surgical treatment without demonstrating the cause and
effect relationship of the chronic pelvic pain and the RVF position of the uterus.
4. Dyspareunia: This is usually related to the causative agent, e.g. endometriosis or
salpingo-opharitis. An associated prolapse of the ovaries in the Douglas pouch can cause
deep sickening dyspareunia.
5. Abortion: Single or recurrent abortion has been frequently ascribed without basis to RVF
of the uterus. The abortion is not necessarily associated with impaction of retroverted-
flexed gravid uterus in the pelvis. Some cases of recurrent abortion benefit from surgical
correction of RVF but there is lack of controlled trials.

Management
No treatment is required for the majority of cases of mobile RVF. For fixed RVF the
treatment should be directed to the cause. The many operations that have been described for
“correction” of retroposition of the uterus are very rarely used in modern-time gynecology.
However, anterior suspension of the uterus can be done during a laparotomy performed for
management of other conditions like endometriosis. The suspension of the uterus is done
mainly to carry the ovaries away from Douglas pouch.
A pessary test is usually required in order to demonstrate, or more commonly to rule
out the cause and effect relationship between the patient's complaints and the RVF of the
uterus. The mobile RVF uterus should be easily put by the physician in anteverted flexed
position by simple stroking of the cervix upwards and backwards; the fundus should readily
fall forwards. However, after removing the fingers from the vagina the RVF position returns
back. To keep the uterus in the “corrected” posture a Hodge pessary is used.
Hodge pessary (available in sizes) is rectangular in the transverse plane and S-shaped
in the longitudinal axis (Figure 2). It is made of hard rubber or vulcanite. It is used during
“correction” of the RVF position. The upper end of the pessary is carried on the index and
middle fingers into the vagina in front of the cervix. The cervix is pushed backward and the
top of the pessary slides across the cervix into the posterior fornix. The fingers are then used
to carry the lower edge of the pessary to above the symphysis pubis (Figure 3). The pessary is
thus wedged between these two points applying traction on the uterosacral ligament, which
will hold the cervix backwards allowing the corpus to fall forward. The woman is asked to
report the effect on her symptoms of having the pessary. If the symptoms are not relieved, the
RVF is blameless. If the symptoms are relieved, the pessary treatment is continued for three
more months. Then the pessary is removed after assuring the patient that the displacement has
been permanently corrected. If the symptoms recur, operative correction should be
considered. Usually the symptoms “expire” during the course of the pessary test.

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Displacements of the genital organs other than prolapse

Displacement Other than Prolapse; Figure 2: Hodge pessary and method of its insertion.
SP= Symphysis pubis.

Indications: (These should be few)

1. When the displacement has been proved by pessary test to be causing the patient's
symptoms.
2. Dyspareunia caused by prolapse of the ovaries in Douglas pouch.
3. As part of another operation to treat endometriosis or myomas.
4. In some cases of repeated abortion or rarely infertility (otherwise unexplained).

Operative treatment of RVF of the uterus:

Of the many operations described the modified Gilliam's operation has been the one
more commonly done. It consists of bringing out a loop of each round ligament through the
internal inguinal ring and suturing it to the back of the anterior rectus sheath.
- A small laparotomy is done.
- The round ligament is plicated by unabsorbable (Dakron or silk) suture, the ends of which
are left long. This is repeated on the other side.
- A long curved forceps (e.g. Buzman's uterine packing forceps) is passed between the
rectus and its anterior sheath through the internal inguinal ring into the broad ligament
(Figure 3).

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Displacements of the genital organs other than prolapse

Displacement Other than Prolapse; Figure 3: Gilliam’s [Link] round

ligament; [Link] rectus sheath; [Link] muscle.

- The anterior leaf of the broad ligament is nicked to allow the forceps to pick the ends of
the stuture strings. These are pulled out and fixed to the back of the anterior rectus sheath
(Figure 4).Ventrisuspension can be carried out by operative laparoscopy.

Displacement Other than Prolapse; Figure 4: Gilliam’s operation (cont). See text.

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Displacements of the genital organs other than prolapse

Retroverted gravid uterus

This should be a common occurrence, given the 15% prevalence of the retroposition
of the uterus. In almost all cases the uterus corrects itself to a vertical position when it grows
up in the abdomen by the 10th week of pregnancy. Rarely abortion occurs. However, the
cause and effect relationship between RVF and abortion is not established.
Exceptionally, the retroverted gravid uterus gets impacted in the pelvis. This is likely
when the posterior wall is firmly fixed by adhesion or fibroids in the pelvis. An overhanging
promontory of the sacrum of contracted pelvis may also predisposes to this occurrence. The
uterus grows to fill the pelvis. Pressure on the bladder results in irritation and frequency of
micturition, while rectal pressure results in constipation. Acute retention of urine ultimately
occurs as a result of stretching and attenuation of the urethra as a result of stretching and
elongation of the anterior vaginal wall. The inability of the urethra to descend prevents the
occurrence of the reflex contraction of the detrusor, which initiates the act of micturition. The
retention can result in cystistis and pyelonephritis.
Most exceptionally, the pregnancy continues through sacculation of the anterior (now
upper) uterine wall. The wall gets thinned out and may rupture. The latter accident is
precipitated during attempts at correction.
Treatment
The immediate treatment is to catheterize the bladder by a Foley's catheter. This is left
for some days during which the patient is advised to keep in bed in an exaggerated lateral
position. In the few cases of impaction of a retroverted-flexed gravid uterus the above
management is generally sufficient. If this fails, a vaginal pack or a large sized ring pessary is
inserted to gently press upon the posterior fornix. Manipulation under anesthesia may be
required to push the uterus upwards on one side of the promontory while applying gentle
traction on the cervix. Care is required not to rupture the uterus.

Torsion of pelvic organs

A. Uterus
§ Torsion of the normal uterus
A minor degree of rotation of the uterus around its axis is common. This is
specially seen during pregnancy when a partial twist to the right is common. The
condition is insignificant.
§ Torsion of a diseased uterus
- Torsion of the whole uterus occurs in asymmetrically enlarged uterus which is the
seat of myomas. The uterus can also be held by an adhesion to an abdominal organ.
This creates a fulcrum around it the first turn occurs. The condition accentuates itself

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Displacements of the genital organs other than prolapse

by the hemodynamics of blood flow in the uterine vessels. The twist occurs at the
level of the supravaginal cervix. The uterus gets deeply congested, and surface blood
vessels may rupture causing internal hemorrhage, and ultimately the organ gets
gangrenous.
- The condition presents with acute abdomen associated with profound shock and is
diagnosed during laparoscopy. Gangrenous uterus needs to be removed.
Hysterectomy in this case can be most easy because the several pedicles of the uterus
are now gathered in the twisted pedicle of torted organ. It can be difficult if adhesions
are present.
- Torsion of pedunculated subserious myoma is quite common (see under myoma).

B. Ovary and tubes

§ Torsion of normal ovary: alone is exceptional, but torsion of the normal fallopian tube
with or without the ovary is not very rare. The torsion may be partial and can also undo
itself to recur again. In the complete torsion, several turns can occur resulting in acute
congestion and bleeding from surface veins. Ultimately gangrene sets in.
The clinical picture is an acute abdomen similar to torsion of ovarian cyst but no
tumor is felt. The diagnosis is made at laparotomy. It may be possible to untwist the torsion
but it is rarely possible to salvage the tube.
§ Torsion of an ovarian tumor
This is a common occurrence since the tumor is pedicled. Moreover, adhesions are
common between the surface of the tumor and abdominal structures. These create the fulcrum
around which the torsion starts. The condition rapidly accentuates itself by the hemodynamics
of the blood flow in the pedicle; several twists can develop in no time.
Predisposing factors:
1. Long pedicle.
2. Small or moderate size.
3. Adhesion to abdominal structures.
4. Pregnancy and pueperium: These result in a rapid change in the position of the
tumor, which can serve to initiate the first twist.
5. The condition may be precipitated by sudden movement of the trunk, turning in
bed or straining during defecation or parturition.
6. Many cases have no cause.
Clinical picture:
The case presents for acute abdomen. The tender mass is felt in the lower
abdomen.

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Displacements of the genital organs other than prolapse

Management:
The type of the operation is decided by the age of the patient, the need for further
pregnancy and the findings at laparotomy. The choice is between ovarian cystectomy,
salpingo-oopherectomy and total hysterectomy and bilateral salpingo-ooperectomy
(see under Ovarian Tumors).

Inversion of the uterus

Inversion is a rare but serious condition. Inversion is a condition in which the uterus
turns inside out, the fundus prolapses through the cervix. Inversion varies in degree from
dimpling of the fundus to turning of the whole uterus and the cervix inside out, like turning
the stocking (Figure 5). Inversion can be acute or chronic.

Displacement Other than Prolapse;Figure 5: Chronic inversion. A. Early inversion; b.

marked inversion; u= uterus;
A. Acute inversion
This occurs during the third stage of labor. This serious complication is rare. It can be
precipitated by traction on the cord and/or pressure on uncontracted fundus; but can occur
spontaneously. The cervix is open and can allow through the downward descent of the
fundus. If the inversion is marked, the fundus appears outside the vagina. The placenta may
be still attached. In partial inversion, the fundus is still in the vagina and can be felt during
examination.
The condition is associated with severe hemorrhage and profound shock. The latter is
partially neurogenic due to traction on the peritoneum.

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Displacements of the genital organs other than prolapse

This is an obstetric emergency needing immediate management by reduction under

anesthesia. Delay costs life. The placenta is peeled off and the inversion is reduced starting at
the periphery i.e. reducing the part that came down last. The last part that returns should be
the fundus. With this, measures to resuscitate shock are being done.

Chronic inversion
Causes:
1) Puerperal
Partial inversion can be overlooked at the time of delivery or diagnosed as atonic
postpartum hemorrhage. The condition accentuates itself by continued squeezing of the
myometrium upon the dimpled fundus. The condition is discovered few weeks after delivery
because of significant secondary postpartum hemorrhage. The mass is discovered in the
vagina coming out of the cervix. It has a friable bleeding infected surface. It can be mistaken
for a placental or fibroid polyp.
2) Inversion caused by a pedunculated polypoidal tumor
Pedunculated myoma or rarely sacroma can draw upon the fundus and initiate a
dimple in the fundus which is squeezed out by time. The endometrium on the mass gets
infected and ulcerated. It is always necessary to exclude the presence of inversion in
association of a big uterine polyp by measuring the length of the uterine cavity (Figure 6).
3) Senile
Spontaneous chronic inversion can occur in old women. The condition may be
mistaken for ulcerated prolapse.

Displacement Other than Prolapse; Figure 6: Chronic inversion caused by pedunculated

submucous myoma.

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Displacements of the genital organs other than prolapse

Clinical picture:
Excessive bleeding and discharge are the presenting complaints. Foul smell of the
discharges is due to heavy infection. The patient is anemic and may look toxic. The tumor in
the vagina is heavily infected with ulcerated bleeding cervix. The uppermost circumference of
the mass is surrounded by a collar of the cervix. Careful sounding of the uterine cavity
between the cervical collar and the mass reveals a compromised or absent uterine cavity.
Management:
- The first objective is to clear up the infection by resting the patient in bed and repeated
antiseptic vaginal douches. Sterile vaginal pack is changed daily. This may result in
spontaneous reduction of the chronic puerperal inversion.
- After clearing the infection special repositor has been tried (Aveling repositor). This has
not been available to us.
- Surgical Management:
a. Hysterectomy (abdominal or vaginal) is indicated whenever there is no intention of
further childbearing, and if there is a malignant neoplasm.
b. Abdominal correction: Haultain's operation : The upper ring of the inversion cup is
dilated by the fingers. Then trial is made to correct the inversion of the uterus by
applying traction on the round ligaments. This is not very likely to work because of
the cervical constriction at the mouth of the inversion cup. This needs be
longitudinally incised all through its thickness. This incision is preferably done in the
middle line posteriorly (Figure 7). Anterior incision risks extension into the bladder
base. Reduction is then possible through a combination of vaginal manipulation and
traction on the round ligaments. The incision in the myometrium, which may enlarge
during the correction, is carefully sutured in two layers.

Displacement Other than Prolapse; Figure 7: Haultain’s operation for abdomic correction
of chronic inversion. The arrow indicates the site of the incision of the upper ring of the
inverted cup.

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Displacements of the genital organs other than prolapse

c. Vaginal correction: Spinelli's or Kustner's operations: These have the same principles
as the Haultain's operation but the procedure is done through a posterior colpotomy
opening the Douglas pouch. The posterior wall of the cervix and the back of the
inverted corpus is incised until it allows reposition of the uterus. The incision in the
posterior wall is carefully sutured in two layers, before closure of the posterior
colpotomy.
After the above operative correction of the inversion pregnancy is possible but
the liability to rupture of the scar must be carried in mind. Cervical cerclage is
necessary in order to prevent abortion or premature labor due to cervical
incompetence.

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Chapter 13
URINARY STRESS INCONTINENCE
AND DETRUSOR INSTABILITY
Contents:
• Introduction and types of urinary incontinence
• Etiology of urinary stress incontinence
• Etiology of detrusor instability
• Diagnosis of stress incontinence and detrusor instability symptom,
physical signs, urodynamic workup
• Treatment of Detrusor Instability
• Treatment of genuine stress incontinence
- Nonsurgical
- Surgical

Introduction (types of urinary incontinence):

There are five clinical types of urinary incontinence which may be confused together:

A. True urinary incontinence:

There is a continuous dribbling of urine, which depends upon the presence of an abnormal
communication between the urinary tract and the exterior, i.e. a fistula. The commonest type is a
vesicovaginal fistula; less common types include uretrovaginal, urethrovaginal, vesicouterine,
vesicocervical and uretrocevical fistulae. True incontinence can be either complete when all the
urine is emptied involuntarily and the patient has no need to empty herself of urine in the toilets.
This is typical for vesical fistulae. Partial incontinence is described when the patient in spite of
continuous dribbling of urine has the need to go to the W.C. to evacuate urine. This occurs in
uretrovaginal fistula and small, high or valvular vesicovaginal fistulae. The subject of Urinary
Fistulae will receive a separate discussion under traumatic lesions.

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Urinary stress incontinence and detrusor instability

B. Stress incontinence:
The patient describes involuntary escape of few drops of urine on sudden stress like
coughing, sneezing, laughing, sudden movement or even turning in bed. The involuntary escape
is not preceded by an urge to pass urine and can occur when the bladder is not full. Only when
the condition is frequent and interfering with her daily activity, she will seek medical help.
The term genuine stress incontinence (GSI) is used to describe the involuntary loss of urine
when the intravesical pressure exceeds the intrauretheral pressure in the absence of detrusor
activity, this diagnosis is being made after urodynamic evaluation.

C. Urgency incontinence:
The patient describes that once she has the urge, she cannot withhold the urine until it is
convenient to pass it. If this is not available to her, she will involuntary pass a good volume of
urine or completely evacuate her bladder. This condition is commonly heralder by an urge but
occasional precipitated by postural change like rising from bed or the sound of running water. It
is caused by irritability of the muscle wall of the bladder, the detrusor, hence the name Detrusor
Instability. Urodynomically, detrusor instability is defined as the condition in which the detrusor
is shown objectively to contract, either spontaneously or on provocation, during bladder filling
whilst the subject is attempting to inhibit micturition.

D. Overflow incontinence:
It results from acute retention of urine. After suffering from intense urge for sometime, the
urge will disappear due to overdistention and overstretching of nerve ending in the bladder wall
which will lead to temporary less of their sensitivity. The distention continues until the maximal
capacity of the bladder is reached when the urine will involuntarily dribble continuously from the
urethral meatus. Therefore, the occurrence can raise suspicion of a fistula but on the inspection of
the vulva the urine can be seen coming out of the urethral meatus, the condition is sometimes
described as false incontinence. The diagnosis is easily made because the distended bladder can
be palpated suprapubically and it is frequently treated by leaving an indwelling catheter in the
bladder for a day or two. Acute retention of urine can result from many causes. It is common
postoperatively or postpartum due to fear of pain at the site of the urethra meatus which causes
reflex retention. Severe infection can cause acute retention. Tumors in the urethra or around it can
obstruct the urine flow as in cases of hematocolpos, tumors incarcerated in the pelvic, big pelvic
hematocele or pelvic abscess, cervical fibroid or fibroid polyp..etc.

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Urinary stress incontinence and detrusor instability

E. Enuresis:
Nocturnal incontinence of urine (Bed-wetting is the rule in children, until they have
developed the cortical control needed to inhibit the automatic action of the bladder during sleep
as well as during consciousness. It continues for a variable number of years and can persist in the
adolescents or adults, mainly depending upon variation in the rate of development of the cortical
control.

The first four types of urinary incontinence may occasionally be confused one for the
other. Extreme stress incontinence may result in so frequent escapes of urine that true
incontinence is suspected. On the other hand, a high and/or vulvular vesical fistula may result in
infrequent escapes of urine related to posture to an extent that stimulates detrusor instability or
stress incontinence. Most importantly, detrusor instability may be mistaken for stress
incontinence and in this case, operation to correct the latter condition will not be effective and
may make the situation worse. Indeed the two latter types of incontinence may coexist. For the
above reasoning stress incontinence and detrusor instability (or urgency incontinence) will be
dealt with together in this chapter.

Etiology of stress incontinence

Anatomical considerations: The pathogenesis of stress incontinence is not fully understood; no
one theory could explain all cases. Normally, urine is allowed to pass when convenient to the
individual, and the urethra is kept closed and only allowed to open under will. This control is
ensured through the following mechanisms:
1. Urethral sphincters: There is no dissectable anatomical sphincter around the bladder neck
like the pyloric sphincter of the stomach. A certain involuntary sphincter action has been
suggested through a special arrangement of the smooth muscle fibers around the bladder
neck. Two decussating loops have been suggested, one opens anteriorly and another opens
posteriorly. These loops raise the urethrovaginal junction and compress it at the time of
detrusor contraction or rise of its tone. However, careful dissection has failed to validate the
presence of such arrangement. A voluntary sphincter is afforded by the striated muscles in
the triangular ligament, which is called the compressor urethrae muscle. This voluntary
sphincter plays a much less effective and secondary role; one does not need to exercise his
will to keep himself dry. However, the voluntary sphincter comes to action when there is
escape of urine under inappropriate conditions. This can halt the escape, and is the
mechanism that keeps the involuntary escape to few drops, a characteristic feature of stress

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Urinary stress incontinence and detrusor instability

incontinence. In addition, this is the explanation of the woman not losing these few drops
when she is expecting the coughing or sneezing.
2. The intrinsic tone of the urethral wall insured by its muscle, elastic and collagenous fiber.
This keeps a resting intraurethral pressure (closure pressure) higher than the intravesical
pressure even when the latter is increased by stresses. This tone also needs an intact nerve
supply. Women with stress incontinence have a reduced maximum urethral closure pressure,
which reduces the ability to resist urinary leakage under pressure of the bladder. Recent
investigation has shown that some cases of stress incontinence are associated with defective
innervations of the urethral wall. Some cases of GSI were shown to have areas of thinning of
musculofaschial wall of the urethra.
3. Urethral length: Women with stress incontinence may show funneling of the bladder neck in
cystourethrogopraphy, but the length of the urethra does not play a major role in maintaining
continence. This is shown by the observation that the removal of a considerable segment of
the urethra during radical vulvectomy does not result in loss of continence.
4. The pelvic muscles and fascia: The pubococcygeal part of the levator ani does not reach the
bladder neck but sends fascial condensation to it. This serves to maintain a posterior
urethrovesical angle. It has been shown by cystourethrography that under resting condition.
There is an almost right angle between the posterior wall of the bladder and the urethra and
that this angle is maintained during bearing down. This angulation also ensures that the
bladder neck is kept above the pelvic diaphragm. The rise in intravesical pressure occurring
during stress or straining is equally associated and counteracted by a rise in the urethral
closure pressure. During micturition, the associated relaxation of the pelvic diaphragm allows
sagging down of the urethrovesical junction, and the bladder base and upper urethra will
move down to a position below the pelvic diaphragm and escape from the rise in the
intraabdominal pressure. This is usually associated with loss of the posterior urethrovaginal
angle (as demonstrated in cinomatographic cystourethrography ). This angle is normally lost
at the time of initiation of micturition but may be regained during the act. Women with stress
incontinence have a downward sagging of the bladder neck and a wider posterior
urethrovesical angle at rest, or the angle is lost during rise in intraabdominal pressure,
bringing the urethra in line with the posterior bladder wall i.e. simulating the posture attained
at the time of initiation of the act of micturition. This observation is the basis of a number of
operative interferences used for treatment of stress incontinence as buttressing the
urethrovaginal junction (Kelley’s stitch), cystourethropexy (Marshal-Marichetti-Krantz
operation), colpourethropexy (Burch’s operation) and sling operations e.g. Albridge or
Goebell-Fragenheim-Stoeckel fascia lata strap.
It has to be remembered, however, that simple buttressing of the bladder base in anterior
colporrhaphy is not enough to correct the sagging of the urethrovesical junction and may

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even bring the bladder neck in line with the urethra or interfere with bladder neck mobility
causing development of stress incontinence de novo.

Predisposing conditions for stress incontinence:

1. Constitutional weakness of the musculo-fascial structures in the pelvis: This explains
the common association between urinary stress incontinence and genital prolapse, but
does not mean that the latter causes the former. In fact, extreme stress incontinence may
not be associated with any prolapse and vice versa.
2. Pregnancy and labor: Stress incontinence may appear temporarily or become
accentuated during pregnancy. The reason is not clear, but may be contributed to by the
softening of the pelvic connective tissue associated with pregnancy or the weight of the
gravid uterus. It may appear following labor, not necessarily difficult or traumatic. Such
patients are already predisposed.
3. Postmenopausal atrophy due to estrogen deprivation. The condition getting increasingly
distressing in old women.
4. Electromyographic studies suggest that much of the lower urinary tract dysfunction
previously described as idiopathic has a neurogenic origin i.e. due to muscle
denervation. This denervation is a normal accompaniment of aging and appears to be
increased by pregnancy and parturition. The neuritis associated with long-standing
uncontrolled diabetes mellitus can result in loss of tone of the urethral wall and stress
incontinence.
5. Any factors, which produce chronic rise in intraabdominal pressure, can precipitate
stress incontinence e.g. intra-abdominal tumor or ascites, chronic cough.

Etiology of urgency incontinence (Detrusor instability)

No single explanation can explain all cases detrusor instability.
Many conditions contribute to irritability of the bladder wall:
1. Neurogenic causes: most importantly multiple sclerosis and Parkinson’s disease,
diabetic neuropathy, prolapsed lumbar disc or spinal cord trauma. Urgency incontinence
can be part of cerebral dementia and Alzheimer’s disease. Bladder denervation can result
from radical hysterectomy or abdominoperineal resection of the rectum and causes
detrusor instability. It can result from operations for stress incontinence.
2. Detrusor instability may have psychogenic features in some women.

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Urinary stress incontinence and detrusor instability

3. There is increasing trend for considering the detrusor instability resulting from increased
ability of conduction of the electrical potential between muscle cells. This has been the
basis of come of the pharmacological approaches to treatment.
4. Cystitis: Urinary tract infection needs to be searched for and treated because it is
frequently the underlying cause of detrusor irritability. Evident urological conditions
like, ulcer bladder, diverticulum, granuloma or bladder tumor may present with urgency
incontinence.
5. Postmenopausal atrophic changes are associated with thinning out of the bladder
mucosa and its chronic infection. In such cases, the urgency incontinence will benefit
from estrogen therapy.
6. Weight on top of the bladder caused by tumors diminishes the bladder distensibility.

Diagnosis of Stress Incontinence and Detrusor Instability

1. Careful history taking: Anamnstic data are important in the diagnosis. Stress
incontinence is characterized by its relation to sudden stress, the escape of few drops of
urine and the absence of preceding urge. On the other hand, detrusor instability is
characterized by escape of a big volume of urine, heralded by an urge and not necessarily
preceded by rise of intraabdominal pressure. However, urgency incontinence may
reflexly occur after a movement like rising from bed or stretching the body thus
simulating stress incontinence. It needs to be emphasized that the two conditions may be
associated together which will complicate the diagnosis. The cause of detrusor irritability
needs to be treated first and if stress incontinence persists to be troublesome, then
surgical correction is resorted to. Detrusor instability is commonly associated with
frequency nocturia and incontinence at orgasm.
2. Full neurological examination to exclude causes mentioned above.
3. Urine examination: Chemical microscopic and bacteriological examination is an
essential part of examination of the patient. A clean catch sampling and bacterial count
are essential. Sonographic examination of the urinary tract and intravenous pylography
are important.
4. Physical examination:
Demonstration of stress incontinence: In this respect some women find it difficult to
demonstrate stress incontinence while lying on their back. It is therefore imperative to study
these women while standing or squatting. Bonney’s test for stress incontinence means a light
pressure applied on the vaginal wall immediately to the sides of the upper urethra without
compressing it, i.e. just uplifting this region may result in absence of the leak. The positive

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Urinary stress incontinence and detrusor instability

test indicates a probable correction of the complaint by operative procedures supporting this
angle. However, the test is not always significant.
5. Uroflowmetry: This involves measurement of the urinary flow rate. The normal adult
voids at a rate of > 20 ml/second resulting in complete bladder emptying. Reduced
urinary flow and incomplete emptying (residual urine > 50 ml) indicate detrusor and/or
sphincter dysfunction.
6. Cystometry: Cystometry implies the recording of the intravesical pressure during filling.
This is achieved by passing into the bladder a fluid-filled manometer system or microtip
pressure transducer. Isotonic saline at body temperature is then infused into the bladder
by a catheter at rate of 50 ml/min and recording the pressure during filling. The
intravesical pressure recorded represents the sum of the detrusor generated pressure and
the intraabdominal pressure. To establish the intrinsic detrusor pressure, a balloon
catheter is also placed in the rectum to record the intraabdominal pressure as conducted
to the rectum and the system automatically subtracts the intraabdominal pressure from
the total pressure; This system is thus called the “reduced cystometry” (Figure 1). In a
normal woman, the first urge (i.e. the first sensation of desire to void) will be perceived
at 100 - 250 ml filling. This is easily inhibited by will but when the volume reaches 450 -
750 ml the desire will become intense. The intravesical pressure rises during the filling to
full do not exceed 10 ml of water. In normal woman, this pressure does not rise by
standing, walking, loughing or coughing. A similar pressure tracing is obtained in
patients with stress incontinence, but urine may escape on superimposed coughing.
Patients with detrusor instability show a rise of the “reduced” intravesical pressure
during filling amounting to 15 cm of water or more. The first urge and the maximal urge
will occur at a lower filling which varies according to the severity of the condition, the
urge may be precipitated by provocations like standing or hearing water running down.
Such urodynamic studies are not indicated in all patients; they are particularly needed
when 1) there is doubt as whether the problem is stress incontinence or detrusor instability,
2) when there is doubt of an association of the two conditions and 3) when it is needed to
assess the extent of the weakness in case of genuine stress incontinence. Extreme
weakness will suggest primary resort to more elaborate supportive surgery.

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Urinary stress incontinence and detrusor instability

Stress incontinence & detrusor instability: Figure 1: Twin channel cystometry

Other more elaborate urodynamic tests such as lateral radiological cystourethro-grahy or

videocystourethrography (Figure 2) or urethral profilometry are only used in difficult cases.

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Urinary stress incontinence and detrusor instability

Stress incontinence & Detrusor or instability Figure 2: Video cystouretherography (VCU)

7. Electromyography: This is used when there is a suspicion of defective innervations of bladder

and urethral wall.
8. Cystourethroscopy is used if there is an indication of organic lesion in the bladder or urethra.
9. Radiological investigations: these include IVP, CT scan and MIR imaging to diagnose a
spinal cord lesion or prolapse of intervertebral disc.

Treatment of Detrusor Instability

The following measures can be used to alleviate urgency incontinence:
1. Treatment of urinary tract infection or any other pathology in the bladder or urethra.
2. Hormone replacement therapy if atrophic urethritis or cystitis is suspected.
3. Drugs of use in treatment of detrusor instability
a. Anticholinergic drugs, (to inhibit reuromuscular transmission): like methanthaline
or probantheline (ProBanthen, Searle) or emepronium bromide (ceteprin). They can
cause dryness of mouth and are contraindicated if there is glaucoma.
b. Terodiline hydrochloride ( e.g. Detrusitol, Pharmacia & Upjohn) 2mg twice daily by
mouth. It has side effects more than antichlonergic drugs
c. Terodiline hydrochloride. (Detrusitol, pharmacia & Upjohn 2mg mg turice daily
d. Antispasmodic like dicyclomine hydrochloride (Buscopane), rarely effective.

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Urinary stress incontinence and detrusor instability

e. Tricyclic antidepressant, like imipremine hydrochloride (Tofranile).

f. Prostaglandin synthetase inhibitors as mefanamic acid. The results of such therapies
are generally partial and side effects e.g. dry mouth, constipation and blurred vision need
to be tolerated.
4. Bladder drill regimens in attempt to reestablish cortical control over bladder function,
gradually lengthening the time, that micturition can be postponed. The patient’s baseline
voiding pattern should be established by urinary diary. Then she is encouraged to schedule
voiding by the clock during daytime starting from what she believes able to manage. The
schedule should be rigid and after she has managed to carry out for one week, the interval
can be prolonged by 15 minutes. The drill should be patient and gradual and the patient
needs the support of the physician. At night, she should not follow the schedule. Good
results are possible. The drug treatment should be continued during and after the drill.
5. Consultation with an urologist is required at some stage of treatment.
6. Electric stimulation, in specialized units.
7. Major surgery such as cystoplasty to increase bladder capacity. The latter two lines are
reserved for severe cases.

Treatment of stress incontinence

§ Nonsurgical measures should be tried in mild cases; the patient should not be pushed to
surgery unless she feels it necessary. Nonsurgical approach depends upon physiotheraputic
training to improve the tone of the compressor urethra muscle and the levator ani. The
patient should train herself to interrupt urine flow during voiding. The patient is instructed
to learn to contract her levator ani for 5 seconds x 20 times, three times daily. Kegel’s
perineometer is an instrument to organize levator ani drill. Drugs that may improve the tone
of the bladder neck include impiramine ephedrine. Such drugs have some side effects like
accentuating hypertension.
§ Surgical treatment: Many operations have been described for the treatment of stress
incontinence:
A. Anterior colporrhaphy plus Kelly’s plication: This is frequently used particularly if
a cystocele exists. It gives a high initial success rate in mild cases, but the improvement is
usually temporary; and it is not enough for advanced cases. The dissection of the anterior
vaginal wall is continued downward to just behind the meatus and laterally to the pubic
arch. The balloon of a Folley’s catheter defines the urethrovesical junction. The paraurethral
fascia is plicated behind the urethra reaching up to above the urethrovesical junction. The
bites should be bold and using a series of transverse mattress suture that include tissue on
both sides. Slowly absorbable suture of Dixon or Vicryl of 2/0 size should be used. A series

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Urinary stress incontinence and detrusor instability

of three stitches of this type are enough. Before they are tied, the assistant raises the urethra
by a curved artery forceps to avoid trapping the urethral wall in the suture. One should
exercise sound judgment in order not to excessively copperas the urethra. The cystocele is
then repaired as usual.
Good early results of paravaginal repair of lateral cystocecel associated with GSI
have been reported (see under genital prolapse), although long-term results are poorer.

B. Bladder neck suspension operations (Figure 3).

Stress incontinence & Detrusor instability: Figure 3: Points of reattachment of

the endopelvic fascia during the various types of suprapubic bladder neck
suspension .(A) Arcus tendeneus pelirs; B. periosteum of the os pubis; C. Cooper
ligament (iliopectineal ligament); [Link] internus fascia; 1. urethra, 2.
Bladder 3. Parauretheral fascia; 4. Inguinal ligament; 5. Superior pubic ramus, 6.
Obturator vessels and nerve, 1/ Reflected peritoneum.

1. Burch suprapubic colpourethropexy

This essentially hangs the vaginal wall just lateral to the bladder neck to the
Cooper’s ligament, (the reflected part of the inguinal ligament). This raises the
urethrovaginal junction to above the pelvic diaphragm. It can be the primary
procedure if there is no cystocele, the complaint is marked and specially if there
is another indication for laporotomy.
- The patient is placed in a dorsal lithotomy position (Allen Universal position) and
Folley’s catheter is fixed.
- Pfennensteil incision is used.

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Urinary stress incontinence and detrusor instability

- The space of Retzius is entered by blunt dissection in the middle line on both side in the
middle line and continued to below the inflated balloon of the Folley’s catheter (Figure
4).

Stress inconlinence & Detrusor Instability: Figure 4: Burch colpopouretheropexy. Suture:

are placed into the endopelvic faseia along the bladder edge down to the level of bladder neck.
The ends are then passed in the cooper ligoment.

Stress incontinence & Detrusor Instability Figure 5: Burch operation. Placement

of sutures for Burch colposuspension operation. Sutures are placed into the
endopelvic fascia along the bladder edge down to the level of the bldder neck and
tied. The ends of the sutures are then passed through cooper ligment. When tied, the
bladder neck is elevated, but free space remains between the bladder neck and the
back of symhsis pubis

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Urinary stress incontinence and detrusor instability

- The surgeon inserts one finger into the vagina to elevate the parts lateral to the balloon.
A No. 0/0 permanent suture (merseline) is inserted by double bites in the full thickness
of the vaginal wall missing the mucosa, at the level of and lateral to the urethro-vesical
junction. Another similar one is placed distal to the first. A higher, third suture may be
placed in the lateral fornix if there is a cystocele.
- These stitches are anchored to Cooper’s ligament. The Cooper’s ligament proceeds
laterally from the attachment of the inguinal ligament to the symphysis, and is easily
identified above the body of the pubis (Figure 5).
- The procedure is repeated on the other side.
- While elevating the vaginal wall the sutures on both sides are tied. It will not be
possible to pull the vaginal wall all the way to the Cooper’s ligament, nor should one
try, a suture bridge is always left. Drainage of the cave of Retzuis may be needed if
there is an ooze.
2. Loparsocopic colpasuspension
Laparscopically performed Burch procedure has been described but is not widely
popular. Reports of RCTs comparing laparoscopic procedure with open procedures are
still lacking.
3. Marshal-Marchetti-Krantz urethrocystopexy: is another similar abdominal
operation for treatment of stress incontinence. The elevating stitches are placed in fascia
on the side walls of the bladder neck and the upper urethra and anchored to the
periosteum of the back of the pelvis. (Figure 6). Pubic osteitis can occasionally
complicate the surgery. It gives no help if a cystocele is present.

Stress incontinence & Detrusor Instability Figure 6: Maershal-Marchetti Kruntz

Operation.

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Urinary stress incontinence and detrusor instability

4. Needle-Suspension Pereyra Operation: An alternative to open retropubic bladder

neck suspension by a combined vaginal and abdominal approach in which the space of
Ritzus is traversed by a long needle which carries the suture with it. The suture is then
fixed to the perivesical fascia at the bladder neck and to the anterior rectus sheath.
C. Sling operations: These abdominoperineal operations are utilized in marked, recurrent
cases with fibrosed urethra. The posterior aspect of the urethrovesical junction is strapped
by a sling derived from the external oblique apeneurosis (Aldridge operation) (Figures 7),
Figure 8). The two transverse straps raised from this apeneurasis are left anchored to the
middle line; the ends are sutured from the vaginal side around the bladder neck.
Alternatively, a fascia lata strap can be used. The sling will serve to raise the bladder neck at
the time of contraction of the abdominal wall with any stress. They require a good deal of
judgment as regards the amount of uplifting and need be left to experts.

Stress incontinence & Detrusor Instability Figure 7: Aldridge Operation( after

Show Operative Gynecology). A pair of forceps has been passed from the vaginal
incision lateral to the bladder neck and upward into the retropubic space close to
pubic bone. The tip of the forceps will emerge in the region of the medial attachment
of the fascial strip through a tunnel previously made in the anterior abdominal wall.
The lateral free end of the fascial strip is then grasped and passed down throug the
tunnel by withdrowing the forceps towerds vaginal incision. The other fascial strip
is treated similarly and the two are then united by sutures so as to form a fascial
sling underneath the urethra.

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Urinary stress incontinence and detrusor instability

Stress incontinence & Detrusor Instability (Figure 7): Aldridge Operation: The
operation completed.

D. Tension-free vaginal tape (TVT procedure): This relatively new technique is still not
universally accepted. However, is attractive due to its simplicity. It is based on the premise
that stress incontinence results from failure of the pubouretheral ligaments in the mid-
urethra. The TVT procedure uses a knitted prolene mesh placed behind the mid-urethra. The
tape is inserted via a small trochars, due to the weave of the tape it is self-retaining. The
insertion can be placed under local anesthesia. The aim is to have the tape lying free at rest
(hence tension free) and to only exert sufficient pressure on the urethra during cough to
prevent leakage of urine.
All operation for significant stress incontinence should be combined with pelvic
floor repair.

Postoperative care of operations for stress incontinence

- A catheter is left for 4 days. After removal on the fifth day repeated sterile catheterization
should be done twice daily until residual urine comes down to < 100 ml.
- Detrusor, instability, may arise de-novo in 10-20 % of patients postoperatively Hernia of
pouch of Douglas may result from elevation of the anterior vaginal wall.
- Cesarean section is needed for subsequent deliveries.

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Chapter 14
TRAUMATIC LESIONS IN THE
GENITAL TRACT
Contents
• Perineal and vulval injuries
- Old tears
Defective perineum
Complete perineal tear
• Cervical tears – and detachment
• Uterine perforation and rupture
• Urinary – genital fistulas
• Fecal fistulas
• Acquired atresia

Vulvo-Vagino-Perineal Traumatic Injuries

Causes
1. Obstetrical injuries
This is the commonest cause of trauma of the vagina, vulva and perineum. Some
degree of lacerations of the vulva, vagina and perineum are expected in more than 70% of the
first childbirth. Marked lacerations may occasionally occur in abnormal and operative
deliveries and cause severe hemorrhage, hematoma and sepsis. Prevention and management
of these injuries are dealt with in the Obstetric part. Old tears result in patulous vagina and
various degree of defective perineum and are dealt with here.
2. Circumcision
Female genital cutting (FGC) is a common practice in Egypt; in certain areas of the
country 100% of the female population are circumcised. A recent demographic survey
indicated that more than 95% of the female population were circumcised. FGC is usually
done during childhood, usually before puberty. This practice is an old social custom. A
religious background is not certain. Circumcision is frequently done by nonmedical personnel
as the dayas or barbers. The procedure is done without anesthesia and under most unfavorable

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conditions - no experience, no light, and no asepsis. Therefore, it frequently results in many

immediate and remote complications.
The degrees of genital cutting varies:
a. First degree: when the hood (prepuce) of the clitoris and/or the anterior
parts of the labia minora are removed. This is the commonest type in
Egypt and is called the "Suna circumcision".
b. Second degree: when the clitoris is removed completely or partially with
or without removal of all or parts of the labia minora.
c. Third degree: This is a prevailing practice in Nubian and Sudanese
communities (occasionally called pharaonic circumcision). It entails
removal of all the external genitalia; clitoris, labia minora, labia majora;
and stitching of the sides together leaving a small opening for urine and
blood to pass from.
Complications:
1. Bleeding can be primary or secondary and can be severe and life threatening. This
bleeding is a common daily emergency coming to the RR of all hospitals.
2. Infection is frequent and causes pain, reflex retention of urine and secondary
hemorrhage. The girl can contract tetanus through use of unsterilized instruments or
the applications used to stop the bleeding.
3. Circumcision is frequently done to a number of girls in the household as a group
ceremony. The same instruments are used without sterilization. Certain viral
infections as hepatitis or HIV can be transmitted that way. An Rh-negative girl may
thus get isoimmunized.
4. Urinary tract infection and stone formation,
5. Damage to the urethra.
6. Neuroma at the site of circumcision.
7. 7- Inclusion dermoid.
8. Interfere with sexual arousability, resulting in marital dissatisfactions or frigidity.
9. Dyspareunia.
10. Psychological problem that may predispose to frigidity, and vaginismus. The girl may
feel that her feminity is damaged.
11. Rupture of the circumcision scar at the time of birth.
12. Increase the liability to perineal laceration due to fibrosis and inelasticity of the
anterior part of the vulval ring putting more strain on the perineum.
3. Coitus
Tearing of the hymen is almost inevitable with defloration and is sometimes
accompanied by a small tear in the fourcette. These generally cause slight bleeding which

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Traumatic lesions in the genital tract

ceases spontaneously. Sometimes no bleeding occurs at all; this may raise doubts in the mind
of the groom about his bride’s premarital chastity. Occasionally a rather large vessels is torn
and can bleed so profusely that the woman becomes exsanguinated to the extent requiring
blood transfusion.
In rural areas, “traditional defloration” is still occasionally practiced. A daya does the
job using a hard object e.g. a door key covered by a handkerchief to demonstrate to the
relative the bleeding that resulted from defloration of an intact hymen, thus testifying for
premarital chastity of the bride. A resisting frightened young bride can occasionally be
injured.
Rough coitus as rape can also severely injure the frightened resisting girl. The groom
may be drugged and ill informed about the anatomy of the female. The injury can vary from a
perineal tear, vaginal vault injury as shuffling of the whole urethra or perforating into the
rectum or Douglas pouch.
The management starts by careful examination under anesthesia to determine the
extent of the damage. Bleeding vessels are secured and other injuries are specifically treated.
The raped girls needs investigation for STDs. Prophylactic antibiotic are needed.
4. Accidents
Injury to the vulva and vagina may result from accidents involving fractures of the
pelvis or impalement injury (falling astride a sharp object). Young girls are sometimes
brought by their mothers after having some vulval bleeding after an accident. The concern is
on the integrity of the hymen. Frequently, this anxiety is found unnecessary. The introitus is
deeply situated and the injury usually involves only external parts.
Severe accidental injuries may involve the adjacent structure like the bladder and
rectum and careful assessment under anesthesia is frequently required.
See also under Anatomy.

Old Perineal Tear (Defective Perineum):

A defective perineum is the end result of an unsutured obstetrical tear, or breaking
down of sutured tear or episiotomy. Sometimes, the skin remains intact but the perineal and
pelvic floor muscles sustain a subcutaneous injury in the form of hidden tear, or become
permanently lax and atonic. In either case, the introitus becomes lax and unacceptably wide.
This results in a rectocele and predispose to piles. It can result in sexual dissatisfaction;
however, the cause and effect relationship is not easy to ascertain. Weak perineal support
predisposes to prolapse of the anterior vaginal, the cystocele. However, this is not always the
case; a markedly defective perineum may be not associated with cystocele.

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The perineal tears are classified into 3 degrees

a. The first-degree perineal tear means deficiency in the anterior edge of the perineum.
b. The second degree perineal tear means deficiency of most of the perineum and perineal
body, i.e. extending to near the anal orifice but stops short of loss of the external anal
sphincter.
c. The third degree (complete) perineal tear is one which involves skin, perineal muscles,
and the superficial anal sphincter. It may extend to involve a variable part of the anterior
anal or rectal wall; when it may be called fourth degree tear. Upon healing, the vaginal
skin gets continuous with the anal mucosa at the upper end of the defect. The superficial
external sphincter is only present posteriorly and is indicated by the radiating wrinkling of
the skin, which are only seen there. The sites of the torn ends of the sphincter are
sometimes indicted by two skin dimples on the sides of the anal orifice, usually
asymmetrical in position. A finger can be passed in the anal orifice without any
resistance.
Clinical picture
Women vary in their reaction to defective perineum. Some women with complete
perineal tear may endure a complete perineal tear for the rest of their life without
complaining. Others with second-degree tear complain of pelvic insecurity heaviness and
tiredness on standing for long time. The loss of tone of the pelvic floor muscles may diminish
the sexual enjoyment of the patient and her husband. Some women complain of vaginal flatus
(garrulitas vulvae): The gaping introitus allows air to enter the vagina in a certain posture, for
example kneeling for prayers to subsequently come out, may be with a sound on changing the
posture. This causes the woman embarrassment or feeling that she has lost her wodoa.
Women in our culture tend to endure such disabilities silently, and may be shy to mention
them.
Complete perineal tear usually results in incontinence of flatus and fluid stools.
However, most patients train their levator ani to contain solid stools. However, soiling of the
underwear becomes a frequent occurrence.
Treatment
The disability caused by incomplete perineal tear can be diminished by pelvic floor
exercise (see under Stress Incontinence), particularly if started shortly after delivery.
However, pelvic floor repair should be offered to these patients.
Repair of complete perineal should be done immediately at the time of delivery. If this
opportunity has been missed it is better to postpone the operation for 3 months until healing
of infected granulation tissue has occurred and the tissues has become strong enough to hold
the sutures. Attempts to repair the defect between these two times e.g. 10-14 days after the
injury (secondary suturing) is likely to fail.

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Traumatic lesions in the genital tract

Preoperative preparation
- During the 72 hours before the operation, the patient should be placed on fluid, little
residue diet; milk and diary products.
- During this time neomycin or streptomycin 1 g. plus erythromycin 500 mg 8 hourly.
- In the evening before the surgery, the bowel is empted by an enema that is repeated
until the return is clear.
The standard repair operation consist of the following principal points
1. Dissect the vagina from the rectum.
2. Repair of the anterior recto-anal wall.
3. Identifying and suturing together the torn ends of the external sphincter.
4. Approximating in the middle line the levator ani and then the superficial perineal
muscle.
5. Suturing the vaginal and perineal skin in the middle line.
Operative steps
- A roughly H-shaped incision is made (Figure 1). The transverse bar of the H excises the
sharp edge of fusing together vaginal mucosa and rectal mucosa, between points a and b
(see figure). The vagina is separated from the rectum, by blunt dissection.
- The upper limbs of the H-shaped incision extend from the former two points forward to
the posterior extremities of the remnant of the labia minora, point c and d. These two
points will be the posterior edge of the neo-vaginal introitus, therefore they need to have
in front of them the required vaginal width. This can be judged by approximated two
Allis forceps holding these two points and passing two or three fingers in front.
- The separation of the rectum and vagina is more developed and extended to the sides to
expose the levator ani muscles.
- The lower limbs of the H (which are shorter) extend from the points a and b backward
and laterally along the most anterior wrinkling in the perineal skin to reach points e and
f, which are on the skin dimples overlying the torn ends of the external sphincter.
- Suturing of the anterior recto-anal wall (Figure 2) starts from a point above the middle
line. Suturing is by continuous inverting method (missing the rectal mucosa) using 3-0
delayed absorbable material (braided Dixon or Vicryl). The suturing takes good and
equal bites from the sides. Two to four overlying interrupted sutures form another layer,
which strengthen the closure of the recto-anal wall.
- The torn ends of the external sphincters are identified and held by two Allis forceps. To
test that the proper muscle bundles are held, the two forceps are approximated in the
middle line in front of the neo-anal orifice. This carries the fan of skin wrinkling
forward. A double-gloved index finger inserted in the anal canal will testify of the
presence of the desired tone. If necessary, the Allises an be moved deeper in order to

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Traumatic lesions in the genital tract

incorporate more of the retracted muscle bundle until the constricting effect of the
sphincter is demonstrated. Then, the torn ends are stitched together in the middle line by
two delayed-absorbable no 3-0 sutures. These sutures are the main point in deciding the
functional result of the operation.
- The levator ani are approximated in the middle line by two or three interrupted suture.
The superficial perineal muscles are also approximated.
- The vaginal and perineal skins are sutured in the middle line: Points c and d will form
the posterior edge of the vaginal introitus. Points a and b will be on the anterior middle
point of the new anal orifice (excessive narrowing of the orifice should be avoided)
while points e and f will converge to a point slightly in front of the anal orifice (Figure-
3).

Traumatic Lesions; Figure 1: Complete perineal tear repair. The H-shaped incision, the ab,
cd, and ef points (See the text).

Postoperative care:
- The oral antibiotic should be continued for 7 days.
- Fluid diet is continued for 5 days in order to ensure minimal fecal residue.
- Paraffin oil 15 ml 3 times daily is started once the postoperative nausea is over. This
ensures soft semi-fluid fecal masses, which will not disrupt the suture. This is better than
constipating the patient for five days which can result in bulky, hard fecal mass which
may cause failure of the operation. The encouragement of early motion obviates this
occurrence.
The patient can subsequently deliver vaginally but with deep mediolateral episiotomy.

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Traumatic lesions in the genital tract

Traumatic Lesions; Figure 2: Repair of complete perineal tear. The suturing of rectal
defect (R) ends in apposition of points a and be. The levator ani (LA) are approximated in
front of the rectum. The torn ends of the superficial external sphincter ani are present at
points e and f.

Traumatic Lesions; Figure 3: Repair of complete perineal tear. The approximation of

points e and f restores the anterior corrugation of the anal orifice. The approximated points
c and d for the posterior edge of the neovaginal introitus.

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Traumatic lesions in the genital tract

Alternative operations are rarely required when there is a great loss of tissue or when the
standard operation has failed. A flap of the posterior vaginal wall is reflected down to fill the
defect in the anterior rectal wall (Warren’s operation), or the anterior rectal wall is mobilized,
advanced down and sutured to the perineal skin.
The results of the standard repair operation, performed at the proper time are
satisfactory. Sometimes anatomical correction is not associated with full continence of the
flatus.
Repair of the hymen: Hymenorrhaphy is occasionally requested in our culture. It is
almost impossible to repair the hymen. Frequently all what can be done is suturing together
the posterior parts of the labia minora by fine sutures, i.e. advancement of the fourchette. This
operation raises some ethical considerations.

Cervical Tears
Causes:
I. Obstetrical injuries:
A physiological degree of tearing of the external os occurs during the first childbirth
resulting in the external as taking the shape of a transverse slit rather than a rounded hole.
Pathological tearing results from delivery by the ventouse or forceps or breech
extraction before full dilatation of the cervix. It can be caused by precipitate labor or the use
of strong ecbolics, or results from tearing of a cervix scarred by previous repair or
amputation.
Obstetrical tears are usual radial, more commonly on the left side, at 3 o’clock. This
is because of the commoner right tilt of the body of the uterus, which pushes down during
contraction more towards the left side. There can be bilateral or multiple, stellate tears. A
lateral tear may extend up and reach the lower uterine segment opening in the broad ligament
i.e. becoming an incomplete rupture uterus.
Obstetrical trauma may result in a hidden trauma at the level of the internal os
resulting in permanent weakness and incompetence. This causes second-trimester abortion or
premature labors in subsequent pregnancy. Cervical incompetence may or may not be
associated with tears in its portiovaginalis. The functional competence does not always
correlate with the appearance of the cervix.
An unusual obstetrical injury is the detachment of either the anterior lip or the whole
circumference of the portiovaginalis of the cervix annularly. This results from pressure
necrosis of the cervical wall if nipped between the fetal head and the bony pelvis. This also
occurs in a case of prolonged labor complicated by cervical rigidity. The fetal head fits tightly
onto and a thinned-out cervix and this undergoes ischemic necrosis at and below to pressure

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ring. Separation is completed by retraction of the uterus acting against the downward thrust of
the head. An annular detachment may rarely occur i.e. complete amputation of the cervix.
A rare injury of the cervix causes a cervicovaginal fistula. This is seen when the fetus
is delivered precipitously through a tear in the cervix above the unremoved suture of cervical
cerclage or above an external as scarred as a result of previous surgery.

II. Surgical injuries:

Forceful dilatation of the cervix during gynecological surgery or for induction of
abortion may result in: 1) brisk bleeding, 2) creation of a false passage and may be perforating
injury, 3) overt laceration, or 4) cervical incompetence in subsequent pregnancies. Cervical
incompetence may result from balloon inflation in the cervical canal done for induction of
second-trimester abortion. Other injuries are intentional (therapeutic), like conization or
amputation of the cervix.
Complications of cervical injuries:
1. chronic cervicities.
2. parametritis.
3. ectropion (see under Cervicitis).
4. distortion and scarring of the cervix, leading to infertility.
5. cervical incompetence.
6. cervical dystocia.
Clinical feature:
Cervical tear causes bleeding which can be severe if a big blood vessel is opened. The
hemorrhage may be primary or secondary. Old tears are usually symptomless, unless
associated with cervicitis and parametritis.
Habitual abortion and premature labor result from cervical incompetence.
Treatment:
Primary repair is indicated to stop postpartum hemorrhage (see in Obstetrics).
Old tears rarely require correction. This is unless the tear is causing pain or
dyspareunia due to associated cervicitis and parametritis. Repair of torn partio-vaginalis of the
cervix does not usually correct cervical incompetence, which is better managed by cervical
cerclage of either the Shirodkar’s or McDonald’s type done during pregnancy. Certain
apprehensive women dislike having disfigured cervix and will not be satisfied until it is
corrected. The operation is indicated for deep tears exposing the endocervix and if suspected
to contribute to infertility.
The operation of trachelorrhaphy: consists of:
- dilatation of the cervix.

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- removal of two opposed rectangular strips on the lateral sides of the anterior and
posterior lips of the cervix.
- the scar tissue at the apex of the tear needs be excised. This is an important
component in order to remove the scarred, chronically infected tissue at the apex.
- the two rectangular areas are approximated by two or three vertical mattress sutures,
utilizing number 0 braided Dixon or Vicryl. Each traverses the substance of the
cervical lips opposing the bared areas.
- if the tear is bilateral the other-side’s suture are placed before the sutures of the two
sides are tied.
Cervical cerclage: see under Abortion.

Uterine perforation and rupture

Rupture of the uterus is mainly an obstetric accident dealt with elsewhere.
Perforation of the uterus is a common accident during dilatation and curettage (D&C),
evacuation of pregnancy, or rarely during insertion of an IUD. Perforation of the uterus is
predisposed to by the softening of the pregnant uterus, the thinness and atrophy of the
postmenopausal uterus; the friability of infected uterus and the uterus, which is a seat of
cancer or pyometria. The firm resistance of the nulliparous cervix may result in dilatation
being carried out in a false passage. This occurs when the internal os offers more resistance to
the sound or dilator than the thickness of the cervix.
Consequences of perforation and its management:
1. There are little consequences of perforation of a nonpregnant empty uterus. Once
suspected (the sound invading too deeply) the operation should be stopped. The
patient is kept under observation for development of lower abdominal pain and
tenderness.
2. Unrecognized perforation may result in injury of the bowel if attempts are made to
evacuate uterine contents. The intestines are brought down by the ring or ovum
forceps into the uterus or vagina and severely damaged.
3. Spread of infection if uterine contents are infected.
4. Spread of malignancy.
In the latter three situations, an exploratory laparotomy is required. Hysterectomy is
the best treatment if the uterus is not needed. If however, needed, the contents of the uterus
(usually pregnancy) are evacuated and the rent is carefully repaired. Sterilization by tubal
ligation can be done if further childbearing is not planned.

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Traumatic lesions in the genital tract

Genito-Urinary Fistulas
These are abnormal communications between the urinary and genital tract. The
possible types include:
- uretrouterine, uretrocervical and uretrovaginal fistulas.
- vesicouterine, vesicocervical and vesicovaginal fistulas.
- urethrovaginal fistula.
Of these, vesicovaginal fistula is the commonest. It results mainly from obstetrical
injuries. The frequency of fistulas in the practice has declined but is still occasionally seen.
Causes of urinary fistulas :
1- Obstetrical injuries account for the majority of cases seen in our practice (>90%). Two
types of causation are possible:
(a) Direct injury of the urinary tract: The urinary bladder or urethra may be injured
during forceps application or forceps rotation or by slipping and perforation of the bladder
by the craniotomy scissor.
The bladder may rupture together with rupture of the lower segment of the uterus,
particularly when the rupture occur in the scar of previous L.S.C. section or is torn during
dissecting the bladder off the lower uterine segment.
When direct injury occurs to the bladder, the incontinence of urine starts immediately
after the delivery.
(b) Necrotic injury: This can result from nipping of the bladder between the presenting
fetal head and the pelvic wall in prolonged or obstructed labor. Prolonged compression of
the trigone will result in necrosis and when the necrotized part sloughs the incontinence
will begin, usually 7 or 10 days after the delivery. The resulting fistula is a bad one
because it involves the trigone (near the ureteric orifices), and is associated with marked
vaginal scarring making exposure of the fistula difficult. The edges of the fistulas are
fibrous and may show poor healing capacity. This type of fistulas is rarely seen in the
present practice.
A similar necrotic fistula may occur due to enclosure of the base of the bladder in the
sutures of the lower uterine segment cesarean section. The ureter may included in clamps
applied to control bleeding occurring as a result of lateral extension of the lower segment
wound into the blood vessel bundle on the side. This can only occur if the bladder has not
been adequately mobilized down from the lower segment, particularly at the lateral
angles.
With increasing use of cesarean section and particularly the need for more repeat
sections. Post-cesarean fistulas are now increasingly seen. These have the unfavorable

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Traumatic lesions in the genital tract

feature of being high. However, they have the better feature of being away from the
trigone (and ureters) and are associated with minimal vaginal scarring.
2- Surgical injuries:
This is the commonest cause of urinary fistula in developed countries where the above
obstetrical fistulas are rare. In many gynecological operations one part or another of the
urinary tract is in danger of injury.
(a) The bladder may be injured during difficult total hysterectomy; cervical myoma
displacing the bladder upward predisposing it to injury; or radical Wertheim’s
hysterectomy. It can be also injured during repair of prolapse or vaginal hysterectomy.
The bladder can be mistakenly included in sutures applied to the vagina, or parametric
tissues.
Primary repair of bladder injury: If an injury to the bladder is recognized and repaired
properly at the operation, a vesicovaginal fistula can be avoided. Every gynecologist
should be able to repair the injured bladder.
The extent of the injury and its proximity to the ureteral orifices should be
assessed. Usually the ureteral orifice is away from the common site of injury in the upper
part of the base of the bladder. If the ureteric orifices cannot be located easily, 5 mL of
5% indigo carmine are given intravenously; blue urine spurts from the orifices in 5-
minute time. A ureteral catheter may be passed up the ureter when it is near to the site of
injury. The bladder wall is closed by continuous inverting suture missing the mucosa
utilizing 3-0 delayed absorbable material. The operator should be certain of suturing the
whole length of the wound. A second reinforcing continuous suture is done. If there is
doubt of complete closure, the bladder is distended from below by 200 mL of diluted
methylene blue solution. The suture line is then peritonized. The bladder should be
maintained empty for 10 to 12 days by a transurethral Foley’s catheter. A suprapubic
catheter is only necessary if the injury involves the bladder neck.
Bladder injuries during vaginal surgery can be usually adequately repaired
transvaginally, if the whole wound is within reach.
(b) The ureter is vulnerable to injury during a number of abdominal and vaginal
gynecological operations. There are at least seven possible types of operative trauma to
the ureter:
1. crushing by a clamp.
2. ligation with a suture.
3. transection (cutting) either partial or complete.
4. kinking with secondary obstruction.
5. Ischemia that results from stripping the ureter from its blood supply (multiple
blood supply reach the pelvic ureter including branches from common iliac or

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Traumatic lesions in the genital tract

from the aortic bifurcation, internal iliac, uterine, vaginal, superior vesical and
hemerhoidal. There is rich communications between these vessels in the
connective tissue covering the ureter, which is lost if the ureter is skletonized
during dissection).
6. resection of part of the ureter, which can be intentional during removal of a
malignant lesion.
7. diathermy fulguration during operative laparoscopic procedures.

Sequela of ureteral injury:

1. collection of urine in extraperitoneal space forming a pelvic mass after the
operation.
2. spontaneous resolution is possible if the ureteral injury is just a kink or edema.
3. silent renal atrophy without sepsis.
4. uretrovaginal fistula.
5. pyonephrosis.
6. uremia
Prevention of ureteral injury:
The gynecologists should always be ureter conscious. The attempt to prevent
ureteral injury comprise the following:
(a) Intravenous pyelography, ultrasonography, CT scan or MRI should be done before
surgery for any pelvic tumor, which is likely to impinge upon or displace the ureter.
These will alert the surgeon to presence of ureteric displacement and back pressure
upon the kidneys.
(b) Catheterizing the ureter is rarely necessary except in cases when extensive adhesions
are anticipated. Lighted or flashing ureteral catheter are sometimes cystoscopically
inserted during laparoscopic surgery in order to avoid fulgurating the ureter by
diathermy or its ligation – e.g. during laparoscopic hysterectomy. This will add to the
expense of the operation.
(c) Early identification of the ureter during an operation that may endanger it. The ureter
is easily identified at the point of crossing the bifurcation of the common iliac artery
to enter the pelvis. It can be traced underneath the posterior leaf of the broad ligament
for some length. During difficult removal of pelvic tumors, the ureter should be
traced and kept visualized or frequently inspected.
(d) Avoidance of injuries at certain key sites and points during abdominal gynecological
operation. The dangerous points include:
1. At the pelvic brim the ureter is just behind the infundibulopelvic ligament. It can
be included during clamping of this ligament particularly when the anatomy is

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distorted by presence of an adnexal mass like an ovarian tumor or a pyosalpinx, a

broad ligament cyst or tumor (e.g. fibroid) or adhesion between the pelvic colon
or cecum and back of broad ligament (the latter is common after appendectomy).
The ureter sometimes needs be identified. The ovarian vessels are usually lifted
by the index finger passed underneath through the opened broad ligament. This
raises the pedicle away from the ureter before the clamp is applied.
2. The ureter is loosely adherent to the underneath of the posterior leaf of the broad
ligament. It is vulnerable during removal of an adnexal or broad-ligament masses
particularly when involved in adhesions. The ureter may be on top of or
underneath the mass; the latter situation is commoner. The ureter should be traced
down to this site starting from the point of crossing upon the common iliac artery.
The ureter may be included in sutures peritonenizing the pelvic floor after
hysterectomy.
3. The ureter is a direct lateral relation to the uterosacral ligament and may be
injured during cutting and transligature of the ligament. It can be kinked by
sutures placed to obliterate the Douglas pouch, in repair of an enterocele.
4. The commonest site of injury of the ureter is on the side of the supravaginal
cervix. Here it is just 1.5 cm lateral to the uterus and the uterine vessels cross at a
right angle above it. The ureter can be injured during clamping of the uterine
vessels in total hysterectomy. This accident is preventable by taking the following
measures:
- Adequate downward mobilization of the bladder particularly at the lateral
angles. Frequently the fibers of the bladder pillars need be cut. These may
contain small vessels that cause some bleeding; they can be secured (by utilizing
suction) and cauterized.
- The uterine vessels can be visualized on the side of the uterus by cutting the
fascial band known as the mesentery of the round ligament. This stands up on
pulling on the lateral secured end of the round ligament. This fascial band
(usually avascular) when cut will lead to the uterine vessels on the side of the
uterus.
- Utilizing traction and countertraction; the uterus with the uterine vessels are
pulled up and to the contralateral side while the ureter is pushed down and to the
ipsilateral side by a swab on a holder.
- The clamp is applied to the uterine vessels at a right angle to them near to the
supravaginal cervix at approximately the level of the internal os (intrfascial
hysterectomy).

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5. In the same site, the ureter is vulnerable to injury during Wertheim’s

hysterectomy, at this point the ureter pierces the cardinal ligament in what is
called the ureteric canal which is roofed by the uterine vessels. Mobilization of
the ureter may be restricted by inflammatory and or malignant infiltration and it
is at a real danger during dissecting it from the parametrium. It is always
advisable to ligate the uterine artery at its point of origin from the internal iliac
artery and to lift the stump medially towards the uterus, which will expose the
ureter. The dissection of the ureter is then completed behind and in front of the
point of crossing.
6. Another vulnerable segment of ureter is the final few centimeters between the
uterine crossing and the entrance in the urinary bladder. At this site it is
vulnerable to injury during transfixion/ligature of the vaginal angle in total
hysterectomy. This is avoidable if additional mobilization of the structures in
front of this angle is made before clamps are applied. The author have always
found it helpful in total hysterectomy to open first the higher posterior fornix,
insert two fingers in the upper vaginal to lift the anterior and lateral fornices and
then complete mobilization of the bladder and ureter upon the pushing fingers.
The vaginal angle clamps are always applied on the inner side of the uterine
stump.
7. At any of the above sites the ureter is injured as a result of an unexpected
displacement by a broad ligamentary tumors or cervical myoma. To safeguard
this injury it is a good practice to incise the broad ligament and the capsule of the
myoma and enucleate it outside its bed. This will facilitate dissection of the
bladder and ureter frequently under vision, before clampes are applied to the
uterine (see under Hysterectomy).
8. Devascularization of the ureter during Wertheim’s hysterectomy may result in
necrotic fistula. The ureter has a rich blood supply from multiple sources. During
radical surgery the ureter may be devascularized by removal of its fascial
covering containing the anastomostic blood vessels. To avoid this it is advisable
not to separate the ureter from the posterior leaf of the broad ligament, or dissect
away the connective tissue covering the final few centimeters of the ureter before
piercing the bladder. These contain valuable anastomosis with vesical vessels.
9. The ureters are sometimes injured when the surgeon is trying to control
intraoperative bleeding by placing clamps blindly on bleeding vessels deep in the
pelvis in a pool of blood. In this situation, application of hot packs to the bleeding
site will give a breathing space for the surgeon to be composed and organized. It
gives time to ask for the needed retractor, suction, the suitable clamping

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instrument, light at the proper angle, the required suturing material and to push
blood transfusion. After at least 5 minute packing pressure the bleeding will be
found to have stopped by blood vessel retraction and clot formation, if not, the
source can be identified and secured without endangering surrounding structures.
10. The ureter may be included in clamps or ligature during attempt to control
bleeding resulting from extension of a lower segment caesarean incision which
opens the vascular bundle on the sides of the uterus. To safeguard this, the
bladder angles must be pushed down before transverse mattress sutures are
placed at the side of the lifted up uterus.
11. In vaginal operations, the ureters are also vulnerable. This can be avoided by
entering in the correct vesicovaginal and vesicouterine planes, and the adequate
displacement of the angles of the bladder away from the uterus by proper
retractor before application of clamps or ligature. The proper bladder
mobilization needs clamping and cutting the bladder pillars stretching between
the sides of bladder and uterus on each side of the vesicouterine space. These
steps allow the ureter to escape up out of harm.
Recognition and repair of ureteral injury:
The venial sin is injury to ureter; the mortal sin is failure of recognition (Higgins).
Careful inspection of the pelvis after difficult pelvic surgery is needed and – may be
– there is a need for intravenous infection of indigo carmine or methylene blue. An
intravenous injection of a diuretic may accentuate the urine leak in the wound.
The treatment include when a clamp or ligature are discovered intraoperatively it
should be removed and if the ureter looks severely damaged transcystoscopic
catheterization for 10 days is needed. Extraperitoneal drainage is also need.
If the ureter is cut or severely damaged end-to-end anastomosis or uretrovesical
implantation is done usually with transcystoscopic ureteric catheterization and
extraperitoneal drainage. Extensive ureteral injuries at the pelvic brim need to be
reanastmosed to a rolled up flap of the bladder (Boari’s operation).

3- Accidental trauma:
These accidental trauma may result from road accidents and are increasing in
frequency. Injuries of the urinary tract, usually the bladder must be primarily repaired before
causing fistula.

4- Coital trauma exceptionally causes vesical and or urethral injury (see above).

5- Impalement: falling on a spike may pierce through the vagina and the bladder.

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6- Extension of malignant disease

Carcinoma of the cervix and vagina is an important cause of vesical fistula. Fistulation
usually represent a relief of the patient from the severe dysuria, strangury, urgency and pelvic
pain, which is caused by extension to the bladder. The ureters are compressed by the growing
malignancy but, strangely, are not infiltrated by the growth.

7- Rdiotherapy
Brachytherapy for carcinoma of the cervix can cause a vesicovaginal fistula. This can
represent overdosage or result from misplaced applicator but can occur in properly carried out
direct therapy particularly when augmented by external beam radiation. The fistulation results
from devascularization and slow ischemic necrosis. The process is slow and may occur
several years after successful therapy.

8- Congenital malformation like aberrant ureter opening in the vaginal vault and persisting
urogenital sinus are exceptionally rare.

9- Foreign bodies in the vaginal and chemical burns are rare causes.

10- Infective fistula are very rare may result from genital or bladder tuberculosis or
bilharziases.

Clinical picture and diagnosis of urinary fistula:

- Continuous dribbling of urine is the presenting symptom. True incontinence is diagnosed
by seeing urine coming from the vagina and not from the urethral meatus. The disability is
severely distressing, and results in the patient avoiding any social contact and sexual
intercourse. True incontinence can be complete when all the urine passes out involuntarily
or partial when the woman, in spite of continuous dribbling of urine needs to void urine.
Partial true incontinence suggests a ureteral fistula or vesicovaginal fistula, which is small,
high and valvular (opening on certain posture).
- Careful interrogation of the patient about her incontinence is most important to
differentiate true incontinence from extreme cases of stress incontinence and detrusor
instability. In the latter two conditions, when severe, the involuntary escape of urine can be
occasionally so frequent to the extent suggesting a true incontinence occurring on any
movement or the slightest rise of intraabdominal pressure. The relation of the escape to
coughing sneezing, movement, or change of posture and complaints of urgency or dysuria

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through doubt on the diagnosis of the fistula. Overflow incontinence resulting from acute
retention of urine can create an unnecessary alarm when occurring after a traumatic labor
or difficult pelvic surgery by suggesting injury of the urinary tract. In this, sometimes
called “false incontinence” the bladder may be felt as a big tender pyriform swelling, and
the urine is seen dribbling out of the urethra.
- Menu-uria is a rare condition that may result from vesicouterine fistula. This specially
develops after cesarean section. The patient is continent but presents for sake of escape of
menstrual blood with urine at monthly intervals. The communication is high in the bladder
and the internal os of the is preventing the escape of urine, but menstrual blood passes to
the bladder.
- Unless involving the upper half of the urethra, a urethrovaginal fistula does not cause
incontinence but the woman notices the urine stream is mal-directed and splashes down
her thighs. Some drops left behind in the vagina may come down after standing.
- A big fistula may be palpable on vaginal examination. A big fistula is associated with
prolapse of the opposing or neighboring bladder wall through the fistula; this big fistula
may not be the more difficult to repair, the opposite is usually the case. A small fistula
needs to be seen. To accomplish this the patient should be put in Sims’ position* or better
in knee-chest position in order to be able to visualize the anterior vaginal wall; the
posterior vaginal wall is retracted by a Sims’ speculum. Urine can be seen coming from
the opening. A metal catheter inserted in the bladder can help locating the fistula and
assessing its width. The vagina can sometimes be so scarred and stenosed to make
visualization of the fistula difficult. In such cases 200 mL of a dilute solution methylene
blue is injected into the bladder through a urethral catheter and can be seen coming out of
the fistula. A defect in the urethra may be found. In some obstetrical fistulas, the urethra
may be found completely destroyed or not communicating with the bladder.
- A special helpful test in such situations is as follows. Three or four balls of cotton wool
are placed in the vagina. The bladder is distended with 200 mL of diluted methylene blue
solution. The catheter is removed and the patient is asked to walk around for sometime.
Thereafter, the vaginal balls of cotton wool are examined: If only the lower ball is soaked
with methylene blue, a urethral fistula is suggested. If the middle and lower balls are

* Sims’ position is an exaggerated left lateral position, in which the left arm is behind
the body and the right arm is on the front. The left thigh is extended, while the right is well
flexed on the abdomen. In such posture, the pelvis is tilted upside down and the abdominal
contents fall away from the pelvis creating a negative pressure which allow opening of the
vagina when a Sims’ specimen is inserted in the vagina pulling on the posterior vaginal wall.

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colored, a vesicovaginal fistula is suggested. If none of the balls is stained with the dye but
the upper ball is soaked with urine, a ureteral fistula is suggested.
- Examination under anesthesia is usually needed to delineate the defect, to do cystoscopy,
and decide the type of operation needed.
- Cystoscopy is an integral part of diagnostic workup of urinary incontinence. Indirect
cystoscopy can be achieved by plugging the fistula by a pack, or else direct cystoscopy is
done. Cystoscopy shows the site of the defect and its relation to the ureteric orifices. This
is highly important in low fistula involving the trigone in order to avoid including the
ureteric orifice in the bladder repair. The urine can be seen coming out of ureteric orifices
in spurts. If these are not seen, 5 mL of 5% indigo carmine solution is intravenously
infected. In five minute time the dye can be seen coming down the ureteric orifices.
Catheteritization of the ureter may be needed and catheter may be left in place. Cystoscopy
can diagnose previously unsuspected double fistula. Cystoscopy mainly shows any
associated bladder pathology like cystitis, stone, ulcer or diverticulum. It is essential to
have all these conditions treated before any repair of the fistula.
- Urine assessment microscopically, chemically and bacteriology. Infected alkaline urine is
usually associated with presence of triple phosphate crystal. Such infection is occasionally
multimicrobial and involves anaerobes. Culture is needed to identify the infecting
organism(s) and sensitivity to antibiotics.
- Intravenous pyelography is mandatory to assess the upper urinary tract. It can
demonstrate backpressure on the kidney and dilatation of the ureters. It gives good idea
about kidney function by judging the time of visualization of the dye and its density.
- Kidney function tests are required if there is doubt of deterioration of renal functions.
- During the above diagnostic workup the condition of vulva and perivulval skin should be
observed. Frequently the skin is infected as a result of continuous soaking with urine, and
have multiple phosphatic encrustations (of alkaline phosphate deposits), their removal
leaves superficial ulcers. Such vulval dermatitis needs be corrected before repair of the
fistula. The encrustations are scrapped and the skin around the orifice is continually kept
covered by plenty of Vaseline ointment to separate it from the urine. This frequently
results in rapid improvement.
- In addition, attention should be directed to the general condition of the patients. The
patient has gone through a most traumatic labor or difficult surgery. She can be anemic
and undernourished. She can be having Sheehan’s syndrome as a result of postpartum
hemorrhage, which has been inadequately managed. Milk had failed to come down in the
breasts (alternatively due to loss of the baby in the traumatic labor), and she is having
amenorrhea. If the possibility of panhypopituitarism is overlooked, the patient may
develop adrenal cortical crisis during surgery. The presence of the fistula and the

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Traumatic lesions in the genital tract

distressing incontinence of urine may however be the cause of amenorrhea; the

menstruation may return after successful repair of the fistula. The patient can also be
having unsuspected uremia.
Management of urinary fistula:
Repair of vesicovaginal fistula:
A. Non-surgical management:
It is in the form of 3 to 4 weeks drainage by fixing a Foley’s catheter rarely works
even if immediately initiated after sustaining the trauma.
B. surgical management:
§ Preoperative preparation:
The urinary and genital sides of the fistula should be brought to the best possible
condition as well as the general health of the patients along the lines indicated above. The
time spent upon this is in no way wasted.
§ Vaginal versus abdominal repair
Most of vesical fistula can be repaired better transvaginally; abdominal repair is
indicated in the following situations:
1- most ureteric fistulas.
2- stenosed severely scarred vagina.
3- high fistulas which cannot be brought down to within reach from below.
4- when vaginal repair has repeatedly failed.
5- trigonal fistula near one or both the ureteric orifices (still possible vaginally after
catheterizing the ureters).
6- vesicouterine fistula.

§ Standard vaginal repair of vesicovaginal fistula: This is described as flap-splitting or

dedoublement operation since it involves splitting the edge of the fistula into the bladder
and the vagina separately.
Operative hints:
- Lithotomy position.
- Examination under anesthesia assessing the nearness of the fistulous edge to the
ureteric orifice. Occasionally the ureteric orifice is seen at the very edge of the
fistula. Here, a ureteric catheter is passed transurthrally and then threaded under
direct vision or cystoscopically into the ureter.
- The fistula can be brought down by a stay suture passed in the vagina above the
fistula.

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Traumatic lesions in the genital tract

- A circular incision is made in the vaginal skin just outside the opening of the fistula.
The edge of the fistula is put in stretch by a metal catheter or sound passed
transurethrally, the knife cuts on the tip of the sound (Figure 4). One better starts in
the distal (posterior) edge of the fistula to avoid masking the field by blood coming
from an anterior dissection. The circular incision is enlarged by two anterior and
posterior vertical incision. The vaginal flaps are carefully raised by sharp dissection;
the metal catheter in the bladder is a useful landmark. Infiltration of saline around
the fistilous edges is not necessary and may mask the plane of cleavage. The
splitting is carried wide enough to allow for containing two tires of sutures in the
bladder. More than that leaves unnecessary dead space in which blood may ooze
postoperatively.
- There is no need to excise the scarred edge of the bladder defect. This can render
the defect much bigger and can cause brisk bleeding.
- The bladder defect is closed usually in a transverse plain i.e. with transversally
placed stitches (Figure 5).
- The best suture material is a delayed absorbable synthetic threads (braided Dixon or
Vicryl) no 3-0 attached to eyeless needle.
- The stitches are interrupted, inverting Lembert’s sutures, missing the bladder
mucosa and fulfilling the following criteria: good bites, and equal bites on both
sides and emerging at the very edge of the bladder defect (Figure 6). This ensures
leaving behind an even edge towards the bladder, having no suture material on the
vesical side that may favor phosphatic encrustation. The stitches must be reasonably
spaced and started just outside the defect and should not be causing any puckering
of the suture line. A second layer of continuous suturing invert and supports the first
line. This is not always done. Repair of vesicovaginal fistula is an exercise of
patience and attention to details; occasionally it is a tough exercise. An assistant
with an untiring back is of great help. Occasionally it is not possible to allow him to
see the field all the time.
There is usually no need to inflate the bladder by methylene blue solution, to test for
perfect closure.
- Small rounded fistula may be closed by a purse-string suture.
- The vaginal wound is approximated longitudinally by interrupted sutures using the
same material.
The operation for repair of vesicovaginal fistula is occasionally easy, but commonly
difficult particularly in presence of excessive scarring. A widening deep “episiotomy” may be
needed. Vertical relief incisions lateral to the fistula may help to make the fistula accessible.

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Traumatic lesions in the genital tract

Traumatic Lesions; Figure 4: Flap-splitting operation for repair of vesicovaginal fistula.

The circular incision which separates the vagina from the bladder.1- A sound introduced in
the urethra; 2- the circular incision in the vagina; 3- the tip of the sound putting the edge of
the fistula to stretch; 4- the upper lower extension in the vagina.

Traumatic Lesions; Figure 5: Flap-splitting operation for repair of vesicovaginal fistula.

The sutures are inserted in the bladder wall: They are of the inverting Lembert’s type. 1- The
reflected vaginal edge; 2- the bladder wall.

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Traumatic lesions in the genital tract

Traumatic Lesions; Figure 6: The method of suturing the bladder edges by inverting
Lembert’s sutures: Good bites, equal bites immerging at the edges. 1- the vaginal edge; 2-
the bladder edge.

§ Latzko repair for vault vesicovaginal fistula after hysterectomy

The fistula in this case is high and surrounded by dense vaginal scarring. The
operation involves partial colpocleises, obliterating the upper few centimeters of the vagina.
- Four stay-sutures are applied well away from the fistula serve to bring down the
opening.
- A circular incision is made around the opening in the usual way.
- Four incision radiate from this circle at 2, 4, 8, 10 o’clock points. The four vaginal
flaps in between are dissected enough to mobilize the bladder wall (Figure 7).
- There is no need to excise the scarred edge of the opening in the bladder; this will
enlarge the defect and cause troublesome bleeding. The bladder defect is sutured
antroposteriorly in the usual way as described above.
- The four vaginal flaps are excised leaving a square defect in the vault. The musculo-
fascial wall of the vagina is approximated by one or two layers under the bladder.
The more the vagina is mobilized and approximated the securer is the repair but the
shorter the vagina left behind.
- The vaginal defect is finally sutured by vertical mattress sutures.
§ Modified Sims repair:
This is needed in recurrent a fistula with fibrosis of the edges which make flap
splitting difficult. The edges of the fistula are excised by longitudinal, broad beveled cut

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Traumatic lesions in the genital tract

down to but not including the bladder mucosa. This is described as saucerization of the fistula
i.e. leaving saucer-like vaginal wound and a small bladder opening in its center. This wound
is closed by a single layer of vertical mattress sutures missing the bladder mucosa, and using
No. 5 Nylon (Marion Sims originally used silver wire sutures). The ends of the knot are left
long to allow their removal 3 weeks later.
§ Transvesical repair of vesicovaginal fistula:
This approach is the one favored by urologists. Suprapubic cystotomy is made in the
usual way, and the fistulous opening and the ureteric orifices are identified. Four stay suture
in the bladder wall raise the fistula. A circular incision is made in the bladder wall around the
fistula reaching down to the vesicovaginal space. The bladder wall is mobilized from the
vagina. The opening in the vagina is closed by a purse-string suture and invaginated by
another layer. The vaginal wall may be lifted by the assistant fingers placed in the vagina.
However, if the vaginal has retracted away it can be repaired from below or even left to heal
by granulation. The bladder wall is sutured in two layers: The first approximate the musculo-
fascial layer and is made by 2-0 chromicized cat gut and the second approximates the mucosa
of the bladder by 3-0 plain cat gut. Having observed urologists doing it, and having done
himself few, the author is of the opinion that the transvesical approach is not as simple as it is
described, and there can be troublesome bleeding. Suprapubic drainage is usually required.
There have not been controlled trials that can settle this dispute between urologists and
gynecologists.
§ Transperitoneal repair of vesicovaginal fistula:
This may be needed in high vaginal or cervical fistulas.
The peritoneum on the vesicovaginal pouch is opened, and the vesicovaginal space is
opened and dissected until the fistulous track is completely defined all around. The tract is
excised. The opening in the vagina is closed in two layers. The opening in the bladder is
closed by inverting Lambert’s sutures, which are reinforced by a second layer. The vagina is
separately closed. The peritoneum is dragged to interpose between the two viscera.
Extraperitoneal drain is needed as well suprapubic drainage of the bladder for 10 days.

§ Postoperative care of fistula operations:

1- Vaginal pack is removed after 24 hours.
2- Continuous drainage for 12 days by Foley’s catheter. The urine flow should be
kept under observation to diagnose blocking of the ureters. This can result from
blood clot or phosphatic encrustation. It is necessary to avoid any distension of
the bladder during the time required fro healing. Retrograde flow of urine should
be avoided (by raising the urine bag during its evacuation) this carries in
infections.

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3- The urine is kept acidic by oral administration of ammonium chloride 1g t.d.s.

This inhibits growth of the bad urinary pathogens.
4- The antibiotics for the infecting organism(s) identified in the preoperative culture
should be continued until the removal of the indwelling catheter.
5- Coitus is not permitted for two months.
6- Cesarean delivery of any subsequent pregnancy.

Urethrovaginal fistula:
This is a rare and difficult fistula. The posterior urethral wall is absent, the anterior
urethral wall is however usually discernible and the bladder is opening directly into the
vagina. This is the type that causes urinary incontinence. Lower fistulae involving the lower
half does not result in incontinence.
The urethrovaginal fistulas can be caused by:
1- obstetric trauma.
2- coital trauma.
3- after anterior colporrhaphy.
4- construction of artificial vagina in mullerian agenesis.
5- resection of the urethra for vulval carcinoma.
The principal steps of the operation are to borrow tissue from surround vagina and
vulva to construct the posterior wall of the urethral tube. This can be achieved by an inverted
U-shaped incision demarcating the future urethra. The transverse bar of the U is above the
opening in the bladder and the vertical arms are on the sides of the rudiments of the anterior
urethral wall and should be widely apart, enough to allow rolling up the vaginal skin in an
ample urethral tube. The upper angles of the neo-posterior urethral wall are sutures to the
vaginal hood above the vesical opening. The urethral tube is fashioned around a Foley’s
catheter and should be reinforced by a second inverting layer in the musculofascial wall of the
urethra. Two transverse mattress stitches of delayed absorbable suture material at the level of
the bladder neck will tighten the urethrovesical junction in attempt to prevent stress in
continence. Then the mobilized lateral edges of the U-shaped vaginal incision are sutured in
the midline above the neo-urethra. Stress incontinence is expected after such operation. If
severe enough a sling operation is done at a subsequent session.
In case of marked damage of the anterior vaginal wall, the posterior wall of the
urethra is borrowed by turning down the vaginal skin from behind the bladder, keeping the
flap attached above the opening in the bladder. (Interested reader should consult textbooks of
operating gynecology or gynecological urology).

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Traumatic lesions in the genital tract

Vesicouterine and vesicocervical fistulae

These two types of fistulae are increasingly seen as a result of increasing use of
cesarean section. Although the injury may result from other obstetrical trauma, vesicouterine
and vesicovaginal fistula follow upon injury during cesarean section, or from rupture of the
bladder base associated with dehiscence of lower segment scar. The bladder may be injured
during extraction of the head from the lower uterine segment wound. If the bladder has not be
adequately mobilized downwards, particularly on the sides, its wall can be included in the
sutures of the lower segment wound.
The condition frequently results in total urinary incontinence. Occasionally this is
partial when the fistula is high or intermittent incontinence develops when the internal os
exercise a sphincteric mechanism on the escape of urine. The patient may be completely
continent but complaining of menouria – monthly hematuria at the time of menstruation. On
examination, no fistula is seen in the anterior vaginal wall but urine may be seen coming
down from the external os.
Vesicocervical or vesicouterine fistulas can be repaired vaginally if the cervix can be
pulled down enough, or else, via a transperitoneal approach. The fistula can be reached
vaginally through a transverse incision at the vagino-cervical junction. In both routes, the
uterus is carefully dissected from the bladder (without further injury of the usually adherent
bladder) until the fistulous tract is identified and transected. The bladder and the uterus are
repaired separately in the usual way. The latter should be securely repaired after refreshing
the edge in order to leave behind a strong scar that can be distended in the event of
subsequent pregnancy. If transperitoneal approach is used the vesical peritoneum is
interposed between the two organs. Hysterectomy is done if the patient is not interested in
further pregnancy (which carry increased risk of dehiscence of uterine scar). This makes the
bladder repair easier but is not necessary for the repair of the fistula.

Repair of uretrovaginal fistula:

Two types operations can be used for this type of injury.
a- Submucosal-tunnel uretrocystostomy:
This operation is possible if the damage of the ureter involves the lower end of the
ureter. The submucosal tunneling is made in attempt to prevent vesico-uretral reflux of urine
which predisposes to recurrent pyelonephritis.
The distal segment of the ureter is ligated by unabsorbable material. The proximal
segment is longitudinally slit. To each half, a fine delayed absorbable stitch is fixed and the
ends of the two stitches are left long. The bladder is opened transversely. The most dependant
part of the posterior bladder wall that can be easily reached by the proximal segment of the
ureter is chosen for the anastomosis. Two fine transverse mucosal stabs are done in this

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segment of the bladder 1.5 cm apart. A submucosal tunnel is made between the stabs by
inserting a curved artery forceps. The upper stab is pierced through the whole thickness of
bladder wall. The ureter is entered into the bladder at this upper stab and is pulled through the
tunnel to the lower stab. The long ends of the stitches in its slit edge are brought out
separately through the wall of the bladder to fix the ureter to the bladder wall. Another
anchoring suture from the outside fixes the ureter to the bladder preventing it from pulling
out. Care should be exercised not to put the ureter on any stretch. When the bladder fills the
segment of the ureter in the tunnel will be compressed, thus diminishing the chance of urine
reflux.
b- Boari operation:
This is done when a long segment of the pelvic ureter has been damaged. The
operation depends on raising a rich flap from the dome of the bladder leaving it laterally
attached by its base to the rest of the bladder. The flap is rolled up and fashioned by suturing
its edges in a tube around the ureter which is fixed to its inside. Alternatively, a vascularized
segment of the lower ileum is used as a conduit joining the ureter to the bladder.

Rectovaginal fistula
Causes:
1- Obstetrical injuries:
The majority of cases of rectovaginal fistulas represent the end result of incomplete
healing of obstetrical complete perineal tear. These can be spontaneous or instrumental
injury. The rectum may be included in a stitch in the repair of tears. Rarely, a necrotic
rectovaginal fistula develops as a result of prolonged compression of the rectal and vaginal
walls between the head and the sacral promontory in cases of obstructed labor. The resulting
fistula is high and is surrounded by fibrosis.
2- Surgical injuries:
The rectum may be injured during abdominal or vaginal operations like hysterectomy,
myomectomy for cervical myoma, excision of inflammatory masses, drainage of pelvic
abscess, or during trans-vaginal dissection of the vagina from the rectum. If rectal injury is
not recognized and repaired a fistula results. The injuries can usually be effectively repaired
without any consequences. If the injury is extensive , resection anastomosis is done. Rarely
temporary colostomy is required.

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3- Coital trauma: as in rape injury.

4- Impalement accidental injury:
5- Foreign body: e.g. neglected forgotten pessary in an old demented woman.
6- Extension of infection: This is rare. A pelvic abscess (e.g., secondary to appendsitis or
diverticulits) can open both in the rectum and vagina. A perianal abscess may open in the
perineum. Tuberculosis and lymphgrnuloma inguinale can rarely cause rectovaginal
fistula.
7- Malignant extension:
This frequently represents an extension of rectal cancer. Cervical cancer itself rarely
involves the rectum because of intervention of the Douglas pouch between the rectum and the
cervix. Vaginal carcinoma is rare, and low malignant fistula is usually rectal in origin.
8- Radiotherapy: Radiological fistula is a common type of rectovaginal fistula. This can
result from brachytherapy particularly if combined with external beam therapy. The
injury is caused by slowly developing obliteration of arteries and fibrosis. The fistula
develops months or years after the radiation therapy and is commonly associated with
distal stenosis of the rectum.
9- Congenital fistulas: are rare and represent partial or complete failure of formation of the
perineal body and results in perineal anus or vaginal anus.
Clinical picture and diagnosis:
Incontinence of the feces and/or the flatus. A big fistula is felt while a small one is
difficult to demonstrate amongst adhesion. The elucidation of the track of the fistula may
need examination under anesthesia, use of a blunt probe, proctoscopy or sigmoidoscopy.
Observation of flow of a colored fluid or radioopaque dye through the fistula may be needed.
Treatment:
The preoperative and postoperative care are the same as with complete perineal tear.
Difficult high fistula e.g. radiological fistula may need be preceded by temporary
defunctioning colostomy. The operative procedures for rectovaginal fistulas comprise:
- For low rectovaginal fistula resulting from imperfect healing of repaired perineal tear, the
fistula is transformed in complete perineal tear by incising the tissue between the anal
canal and vagina in the middle line and up to the fistulous site. Then the wound is
repaired as described before for complete perineal tear.
- For a small low rectovaginal fistula with a fistulous track, the Vernon David’s method is
used. A circular incision is made through the vaginal skin around the fistulous opening.
The fistulous track is mobilized, taking care not to injure the rectum. A pursestring of
delayed absorbable suture is done around the vaginal opening of the fistulous tract. Before
tying the pursestring one end of it is passed through the eye of an eyed probe inserted

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through the anus into the fistula. After tying the knot this string is pulled out the anus to
invert the fistulous track. The dimple in the wall of the anal canal is reinforced by another
layer of suture. The vaginal wound is then closed.
- For a rectovaginal fistula involving the middle portion of the vagina and the ampulla of
the rectum, a flap splitting operation similar to that done for vesicovaginal fistula can be
done. The anal sphincter should be manually dilated in order to impede the first motions.
- In high fistula involving the posterior fornix, a combined vaginal and abdominal approach
is frequently required to mobilize the fistula (and may be dissecting it from adherent
bladder if hysterectomy had been done). A temporary defunctioning colostomy may be
needed in difficult cases. For radiological fistulas, a prior biopsy from the edge should be
done to ascertain cure of the malignant disease.

Acquired Atresia (gynatresia) and Stenosis in the Genital

Tract
Apart from congenital atresia (see under Congenital Abnormalities) obliteration or
stenosis of different levels of the genital tract may result from trauma, infections, tumors, or
radiotherapy.
Vulval stenosis:
Causes:
- Fused labia can be a feature of congenital adrenal hyperplasia.
- Female circumcision or genital cutting can remove a good part of vulval structure as
in infibulation (Sudanese circumcision). This can also result from postinflammatory
fusion of labia.
- Obstetric trauma particularly overenthusiastic narrowing of the introitus during repair
of perineal tear or episiotomy.
- Operative trauma: Overenthusiastic pelvic floor repair or excision of vulvar tumor or
vulvectomy.
- Burns cause contracture of vulval and perineal structures.
- Vulvitis in infancy result in agglutination of the labia minora. This is easily broken by
drawing the vulval sides apart, however, if neglected may result in permanent fusion.
- Senility: Contracture of the introitus is a common feature of senile atrophy and can be
accentuated by infrequent use and superimposed vulvitis.
Clinical picture:
- Dyspareunia or apareunia.
- Vulval wound during first intercourse.

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- Dysuria.
- Dystocia and birth injuries.
Treatment:
- Dilatation: through encouraging intercourse with the help of lubricating creams.
- Provision with metal or plastic dilators.
- Surgical correction breaking of bridging adhesion, or doing a vertical incision which
is sutured transversely.

Vaginal stenosis or atresia:

Causes:
- Obstetrical trauma is the commonest cause. Vaginal lacerations may result in
contractures. Improper repair may compromise the width or completely obliterate the
vagina.
- Operative trauma: Poor judgment during repair of genital prolapse may result in bad
stenosis of the vagina, which is difficult to correct. Adhesion can result between
anterior and posterior wall wounds usually as result of infection.
- Sterile vaginitis can result in agglutination of the opposed vaginal wall.
- Radiotherapy: Brachytherapy can result in vaginal stenosis or closure.
Clinical picture:
- Dyspareunia or apareunia. This may be accentuated by declining libido and potency
of the husband. In contrast, young couple frequently overcomes stenosis by frequent
dilatation of the scarred vagina through intercourse.
- Hematocolpos.
- Difficult or obstructed labor.
Treatment:
- Dilatation, and provision with dilator.
- Breaking of adhesion.
- Longitudinal incision sutured transversely.
- Plastic surgery using rotation flaps from labia majora or perineal skin.
Acquired cervical stenosis:
Causes:
- Electric or diathermic cautary.
- Repair of obstetrical cervical tears.
- Conization, trachelorrhaphy or amputation.
- Cervical carcinoma and or radiotherapy.

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Clinical picture:
- infertility – due to faulty cervical factor.
- Hematometra or pyometra.
- Cervical dystocia – cervical laceration.
Uterine synaechia: (see under Uterine Factor Infertility).
Fallopian tube block or stenosis: (see under Tubal Factor Infertility).

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CHAPTER 15
GENITAL TRACT INFECTIONS
Contents
• Natural defenses against genital infection
• Vaginal microflora - Factors influencing this flora
• Sexually transmitted diseases
- Gonorrhea
- Chlamydia
- Mychoplasma
- PID
- Genital Herpes
- Syphilis
- Chancroid
- Lymphogranuloma venerum
- Donovanosis (granuloma inguinale)
- Genital Warts (condylomata acuminata)
- Molluscum contagiosum
- Trichomoniasis
- Vulvaginal candidiasis
- Human immunodeficiency virus (HIV) infection, including AIDS
- Urinary tract infection
• Genital tuberculosis
• Schistosomiasis
• Infections in specific parts in the genital tract
- Vulvitis
Bartholiniti
- Vaginitis
Vulvovaginitis in infancy and childhood
Atrophic (senile) vaginitis
Trichomonas vaginalis vaginitis
Candida (monilial) vaginitis
Bacterial vaginosis
Other causes of vaginitis

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- Cervicitis - acute and chronic

- Endometritis
- Salpingo-oopharitis
Acute Salpingo-oopharitis
Chronic salpingo-oopharitis
Pelvic inflammatory disease (PID) as a clinical entity

- Pelvic peritonitis, acute and chronic

- Parametritis

Natural defenses against genital tract infection

The genital tract is a continuous channel leading from the exterior to the peritoneal
cavity. Its external orifice, the vulva is in near proximity to the urethra and anus through
which excreta carrying pathogenic organisms are passed. Therefore, the genital tract needs to
be provided with defenses against infection, and indeed the occurrence of infection is much
less than the opportunity. Sexual intercourse, delivery and abortion are good opportunities to
carry in infection to the genital tract. Bacteriolytic and bateriostatic effects have been
suggested for the transdutes and secretion at various levels.
The possible defense mechanisms comprise:
At the vulva:
- The apposition of the labia after puberty keeps the vulva closed.
- The secretions of the apocrine glands may have fungicidal or bacteriolytic
components. Wounds in the perineum readily heal in spite of the fact that
they are not covered and are frequently contaminated.
At the vagina:
- The apposition of the anterior to the posterior wall.
- The several-layered stratified squamous epithelium, which contains no
glands, is difficult to be invaded by bacteria.
- Vaginal acidity (a pH of 4.5) inhibits the growth of most pathogens. The
acidity is a product of the action of the Gram-positive aerobic lactbacilli,
which breaks down the glycogen contained, in the expholiated vaginal
epithelium into lactic acid. Lactbacillus grows in an acid medium and keeps
the ecology suitable for its own growth and not suitable for the growth of
other organisms. The acidity of the vaginal transudaute depends upon the
glycogen content of the epithelium, which is a function of the ovarian
estrogen.

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At the cervix
- Functional closure.
- Cervical mucus may have bacteriolytic effect.
At the endometrium
- Monthly shedding at menstruation does not allow infection to gain hold.
At the fallopian tubes
- The ciliary current mainly sweeps medially towards the uterine cavity.

Vaginal microflora
The microbiology of the female genital tract is complex. Isolates found commonly in
the lower genital tract include a variety of aerobic and anareobic bacteris, yeasts and
parasites. Influences upon these microbes include the phase of the menstrual cycle, sexual
activity, contraceptive use, pregnancy, childbirth, abortion, surgery and antibiotic use. The
upper genital tract is usually sterile, but bacteria from the lower genital tract may ascend into
the uterine cavity or fallopian tube.
Table 1 includes a classification of microorganisms commonly found in the female
genital tract in asymptomatic and diseased woman.
In asymptomatic woman the microflora of the vagina can comprise the
following organisms:
1. Lactobacillus (also called Doderlein Bacillus) species are the most frequent
component, or can be occasionally the only component of the normal vaginal
flora in women of reproductive age. The strains produce lactic acid which plays a
major role in controlling vaginal flora. The lactobacillus species are gram positive
aerobes and are generally nonpathogens.
2. Gardnerella vaginalis (formerly known as haemophilus vaginalis). These are
aerobic gram-negative cocco-bacilli, which cause bacterial vaginosis (see later),
but may also be found in vaginal culture of as many as 40 - 60% of asymptomatic
women.
3. Group B Streptococci (GBS). GBS are gram-positive aerobes, and can be
considered part of the normal vaginal flora since they can be recovered in 5 - 35%
of normal pregnant women. They are a major cause of neonatal sepsis and
puerperal sepsis. Group A streptococci which is an important cause of puerperal
sepsis (particularly its hemolytic subtype), is not however part of the vaginal flora
in asymptomatic women.

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4. Staphylococci: a gram-positive aerobe is isolated in 5 to 10% of genital tract

cultures. It rarely caused genital infection but has been incriminated in toxic
shock syndrome.
5. Listeria monocytogenesis: a gram-positive aerobe, which is present in the vaginas
of fewer than 5% of healthy women. It has been incriminated in intramniotic
infection, preterm labor and neonatal sepsis.
6. Clostridia: Clostridia gram positive, spore forming anaerobes, which may be
isolated from the vaginal secretion of 5 - 10% of asymptomatic women.

Table 1: Microorganisms commonly found in the female genital tract

• Bacteria • Intracellular bacteria
Aerobic bacteria - Chlamydia trachomatis.
Gram-positive cocci • Mycoplasma
- Mycoplasma hominis.
- Group A Streptococci, including
- Ureaplasma urealyticum.
• S. hemolyticus.
• Viruses
- Group B Streptococci.
- Cytomegalovirus.
- Enterococci.
- Herpes simples virus.
- S. Viridans.
- Human papilloma virus.
Gram-positive bacilli
1 - Human immunodeficiency virus (HIV)3.
- Lactobacillus
- Hepatitis B virus3 .
- Corynebacterium species1
- Hepatitis C virus3 .
- Gardnerella vaginalis2
- Listeria monocytogenes • Yeasts
- Diphtheroids 1 - Candida Albicans.
Gram-negative cocci - Other candidas.
- Neisseria gonorrhea • Parasites
Gram-negative bacilli - Trichomonas vaginalis.
- Escherichea coli. - Other trichomonades.
- Kleibsiellas.
- Gardnerella Vaginalis2.
- Proteus group.
- Pseudomonas areuginosa.

Anaerobic bacteria
Gram-positive cocci
- Peptostrepococci.
- Mobiluncus
Gram-positive bacilli
- Actinomyces species.
- Clostaridium species.
Gram-negative bacilli
- Bacteroides
1 = species generally with low virulence.
2 = G. vaginalis is a coccobacillus.
3 = these viruses are not common in the genital tract, but the genital tract is a portal of entry.

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7. Candida albican is yeast, which can be isolated from the vagina of 25% of
asymptomatic women. Its growth is kept checked by other organisms. C.
Albicans thrives on carbohydrates and also in an acid medium (pH 4.5 - 5.5).
Candida albicans vaginitis is therefore, flared up in uncontrolled diabetes mellitus
and during pregnancy, and after systemic antibiotic treatment.
8. Trichomonas vaginalis: a flagellated parasite, which is found in the vaginal
secretion of approximately 6% of women and is responsible for about 25% of
cases of vaginitis. It is frequently a sexually transmitted disease.
9. Chlamydia Trachomatis: Chlamydia is obligate intracellular bacteria. From 2 to
25% of women have a positive cervical culture for C. trachomatis. It is
transmitted through sexual intercourse and is an important cause of pelvic
inflammatory disease.
10. Mycoplasmas: These are cell-wall-deficient microorganisms, which are distinctly
different from bacteria. Mycoplasma hominis and Ureaplasma urealyticum, the
main infectants, are isolated from less than 5% of asymptomatic women. The role
of genital mycoplasma in causing adverse pregnancy outcomes and PID is still
controversial (see later).
11. Viruses: Cytomegalovirus (CMV) is the most common virus found in female
genital tract. It is found in the cervix in 3 - 18% of pregnant women in the USA,
more commonly in indigent, young, primigravidous women. Serologic evidence
of past infection is found in 20 - 70% of adults in this country. Genital infection is
asymptomatic. Infection can be rarely passed to the offspring either by
transplacental transmission or acquired during delivery through the birth canal.
(look under viral infections in pregnancy).
Herpes simples virus is present in < 1% of asymptomatic women but the
infection is mostly sexually transmitted.
Human papilloma visrus (HPV) is the cause of genital warts. Certain types
are involved in the pathogenesis of carcinoma of the cervix. The virus can be
grown from the vagina of asymptomatic women.

Changes in vaginal microflora

The vaginal microflora is not in a static situation. It is influenced by a number of influences:
- Age: There are important interactions between the hormonal milieu and vaginal
colonization. At birth, the vagina is sterile. Secondary to maternal estrogen effect, the
growth of lactobacilli is enhanced in a short time. After few weeks, the estrogen effect
wans and lactobacilli disappear and are absent until the onset of puberty. During infancy

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and childhood, the vagina is susceptible to infection by pathogens introduced from the
outside. During the reproductive years, the vaginal microflora is predominantly formed of
lactobacilli. After menopause the lactobacilli diminish and the vagina gets susceptible to
atrophic or senile vaginitis.
- Sexual activity: Sexual intercourse increases the chance of infection by certain pathogens
such as N. gonorrhea, C. trachomatis, G. vaginalis, herpes virus, CMV, HPV and
mycoplasma. Some of such infections are asymptomatic.
- Menstruation: Menstruation diminishes vaginal acidity encouraging infection by
pathogens like T. vaginalis and other STDs. The absence of cervical mucus and presence
of blood may also contribute to infection.
- Pregnancy, childbirth and abortion: There is an enhanced growth of lactobacilli during
pregnancy and enhanced acidity. This favors growth of endogenous yeast infection.
Following childbirth and abortion, the vagina is much less acidic or even alkaline and
contains blood and necrotic debris rendering it more easily colonized by a number of
pathogens introduced from the outside. These include the aerobes: group A streptococci
(an important cause of puerperal sepsis), group B streptococci, E. Coli, Proteus species.
Anaerobic bacteria are likely to produce infection in the presence of traumatized or
devitalized tissues and often produce a feculent odor. There is marked increase in
anaerobic species by the third postpartum day. Anaerobic bacteria are major pathogens in
obstetric and gynocologic infection. They include the Gram-positive, spore-forming
Clostridia and the Gram-negative bacteroides.
- Surgery: Major procedures such as hysterectomy lead to a wide, bur temporary changes
in the vaginal flora including decrease in lactobacilli and increase in aerobes, mainly E.
Coli, and anaerobes aerobes, mainly bacteroides.
- Antibiotics: Prophylactic or therapeutic antibiotics given for any indication result in a
decrease in susceptible flora including lactobacilli and a corresponding increase in
resistant organisms including C. albicans and T. vaginalis.
- Contraception: (1) The use of oral contraceptives appear to have minimal effect on the
vaginal microflora. (2) On the other hand, use of intrauterine devices increase the number
of anaerobic bacteria in the cervix, thus increase the chance of PID. Careful studies
showed that this increased risk is mainly occurring in the few weeks following insertion
and diminishes thereafter. The chance of development of PID after IUD use is markedly
influenced by the sexual relations, being definitely related to frequent intercourse, and the
various other factors predisposing to STD. (3) Barrier methods mainly the male condom
play an important role in prevention of transmission of STDs including HIV infection.
- Vaginal washes and douchings: The Egyptian woman is of the habit of “cleansing” and
douching the vagina. This social behavior, which has been frequently passed from one

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generation to the next, has no health or religious basis. However, frequent vaginal
douches can disturb the hemostatic mechanism that maintains the stability of vaginal
flora. This can result in frequent removal of the acidic vaginal discharge reducing the
vaginal acidity and enhancing the growth of pathogens, which are introduced by hands,
and the equipment used for the purpose. It has been shown that vaginal douching is a risk
factor for PID, chlamydial infection and other STDs.
- Poor personal hygiene: like the use of unboiled or dirty rags (or none at all) to contain
menstrual blood can result in a higher contamination of the lower genital tract. The use of
certain intravaginal tampons has been associated with toxic shock syndrome.

Sexually Transmitted Diseases

These were called venereal diseases, after Venus, the Greek goddess of love. They are
specific infections whereby a microbial agent is causing a specific pathology. They are
acquired during heterosexual or homosexual intercourse with an infected partner. Over the
last decade, there has been a revival of interest in sexually transmitted diseases (STDs)
particularly after the development of the worldwide pandemic of human immunodeficiency
virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). Common sexually
transmitted infections are pelvic inflammatory disease (PID), gonorrhea, chlamydia,
lymphogranuloma venerum, donovirus and AIDS. The incidence of STDs is rising in many
parts of the world, and no community can consider itself exempted from this risk.
Consequently, there is a great emphasis put nowadays on the prevention of gynecologic
infection and STDs.

Prevention of Gynecologic infections:

Prevention and control of STDs are based on few major concepts:
1. Educating young people how to protect themselves: The most effective way is to refrain
from intercourse with a potentially infected partner.
2. If abstinence is not possible, the use of barrier methods like the male (and recently the
female) condom is an effective method when consistently used. However, they are not so
effective in preventing skin-to-skin contact. Failures of condoms to prevent transmission
of infection are often the result of improper and inconsistent usage.
3. Refraining from douching may reduce the risk of genital infections (see above).
4. Notification and the counseling of the sexual partner. An efficient system for tracing
contacts can limit the spread of STDs. Ethical aspects need be considered.
5. Active treatment directed to the patient and her or his sexual partner.

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6. Vaccination against vaccine preventable diseases. Vaccination is one of the most

effective, yet underused methods of disease prevention. Although vaccination against
hepatitis B is available only, a small percentage of the population utilizes it. The medical
community is still awaiting the development of other vaccines notably for HIV infection.

Gonorrhea
Gonorrhea is one of the most important STDs. However, this diagnosis is not common
in our practice; we may not be adequately searching for the disease.
Causative organism: The Gram-negative aerobic diplococcus - Neisseria gonorrhea
(the gonococcus). It grows best in carbon dioxide and is sensitive to drying and to extreme
temperature. The organism commonly infects columnar and transitional epithelium and
cannot invade the stratified sqamous epithelium. Therefore, it primarily infects the urethra,
including the paraurethral, Skein tubules; the ducts and acini of Bartholin’s glands and the
endocervix. It can infect the anorectal mucosa during anal intercourse, or the pharynx as a
result of fellatis with an infected partner. Infection can occur in multiple sites.
Usually gonorrhea is transmitted through sexual intercourse. An infected male partner
can transmit infection through vaginal intercourse with an efficiency of 50%. The incubation
period is 2 to 5 days but can be as long as 10 days.
Coninfection with other STDs like chlamydia, Trichomonas and symphylis is possible.
Clinical picture
- Gonorrhea in women is frequently asymptomatic (in 80% of infections). The symptoms
may not be so dramatic to call the attention of the patient. The seriousness of this is that
the disease is likely to spread to upper genital tract, and an asymptomatic woman can
transmit the disease to other partners over several weeks. The presenting symptoms are
either or both of acute development of purulent vaginal discharge and frequency of
urination. On examination, the cervix is covered by purulent discharge and may be
congested and a discharge can be milked down by urethral massage. An episode of uterine
bleeding may be precipulated. Infection of the Bartholin gland may be indicated by
reddening of the orifice of the Bartholin duct, the macula that is seen on the inner side of
one labium minus. Barthlonitis frequently results in abscess formation, which may open or
need to be incised. However, it needs to be mentioned that Barthlonitis is not always
gonorrheal.
- Rectal gonorrhea frequently causes no symptoms, but may cause tenesmus, mucoid
discharge and may be bleeding from the rectum.
- Gonorrhea in the oropharynx is frequently asymptomatic but may cause acute pharyngitis.

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Genital tract infections

- In severe cases the vulva may be reddened and sore, or the vaginal lymph nodes may be
enlarged and tender.
- Coinfection with trichomonas is associated with development of itching, which should
not mask the possibility of gonorrhea.
- Generally, the disease usually remains in the lower genitourinary tracts and
manifestations are self-limited.
- Ascent of infection to the upper genital tract develops in 10 - 20% of women with
cervical gonorrhea, and results in acute endometritis and salpingitis. The spread is
transluminal and causes acute endosalpingitis and severe damage of the tube. Acute
salpingitis is frequently bilateral and can result in formation of pysosalpinx on one or both
sides (see under salpingitis). Pelvic peritonitis may develop, but general peritonitis is rare.
The pathologies in the upper genital tract is not solely produced by the gonococcus but is
frequently multimicrobial.
- A minority of cases of gonorrhea (5%) develop manifestations of disseminated
gonococcal infection (DGI). This is particularly liable to occur if the infection
complicates pregnancy. DGI may take one of two forms: a systemic illness or septic
monoarticular artheritis. The systemic illness comprises fever, chilliness, malaise,
asymetric polyarthralgias and painful skin lesions. The joint pains affect peripheral limb
joints and is due to tenosynovitis. The skin lesion classically appears as a slightly raised
red papule with a central pastule and often appears on the limbs.
Gonococcal artheritis is an important type of septic artheritis developing in young
adults. Knees are most often involved but elbow, wrist or ankle may be involved.
Patients with DGI may lack the symptoms of genital gonorrhea. DGI may rarely cause
endocarditis, pericaditis, hepatitis or meningitis.
Diagnosis:
1. The diagnosis may be suggested by symptoms, circumstantial evidence (following a
particular sexual contact), but may be indicated by symptoms or a diagnosis of disease in
the sexual contact, or the occurrence of another STD. The diagnosis is made by one of the
following means.
2. Gram-stained smears of the cervical or urethral discharge may show intracellular gram-
negative diplococci in polymorphnuclear leucocytes. This is only positive during acute
infection.
3. Culture of discharge obtained from the cervix or urethra. The swabs should be
immediately inoculated in warmed plates of chocolate agar or Thayer-Martin medium. If
the swab needs to be transferred to the lab, this should be done in one of the transport
media such as Stuart’s agar. Specimens should be advantageously obtained from multiple
sites, endocervix, urethra, rectum and pharynx.

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4. Fluorescent monoclonal antibody slides or enzyme assay.

5. Chemiluminescent DNA probe assays have been recently introduced and may have high
sensitivity and specificity.
Screening of asymptomatic women for subclinical gonorrhea is only justified in
communities with high prevalence (e.g. prostitutes).
Treatment
The present time treatment of gonorrhea has been modified by two important
considerations:
1. The emergence of penicillin (the standard treatment in the past) resistant gonococci:
These comprise mainly the b-lactamase (penicillinase) producing N. gonococci.
Resistance to other antibiotics like tetracyclines and to fluoroquinolones are possible but
not widely spread.
2. The other consideration is association of C. trachomatis infection in 30 to 50% of cases of
gonorrhea.
Therefore, multiple-drug therapies for treatment of gonorrhea which take in account
chlamydia are now standard. The combinations usually comprise a combination of one of the
cephalosporins or quinolones and azythromycin or doxycycline.
Uncomplicated urethral, cervical or rectal infection can be treated by a single oral
dose of cephalosporin like Cefixime (e.g. Suprax 400 mg) or a quinolone like Ofloxacin (e.g.
Tarivid 400 mg) or Ciprofloxacin (e.g. Cibrobay 500 mg) followed with azithromycin (i.e.
Zithromax 1g) single oral dose or doxycycline (e.g. Vibramycin) orally in the dose 100 bid x
7 days (to cover for chlamydia). The quinolones are contraindicated during pregnancy.
Cases with DGI or acute salpingitis should be admitted to hospital for complete rest,
observation and parenteral antibiotics. These can comprise Ceftriaxone (e.g. Cefizon) 1g IV
or IM qid or Cefotaxime (e.g. Ceftax) 1g IV 8 hourly or Ofloxacine 500 mg IV every 12
hours. Parenteral therapy should continue until the patient has been afebrile and asymptomatic
for 48 hours. Oral therapy with same drugs should then be continued to complete a total of 7
days, and to this is added oral treatment with azythromycin or doxycycline as described
above.
The patients who have received any of the above combined regimens do not need to
return to be tested for cure unless there are persistence of symptoms. They should refrain
from intercourse until completely treated. The sexual partner needs to be investigated even if
he is asymptomatic.

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Chlamydia
Epidemiology
Chlamydia infection is the commonest STDs in the United States and many Western
European countries with an estimated 90 million cases annually [Link] prevalence
can vary from 2 to 25% depending on the area and targeted population. Chlamydia is often
associated with gonorrhea; approximately 30 to 50% of the time. Residual symptoms after
treatment of gonorrhea is frequently caused by chlamydia. In the Western communities
chlamydia infection accounts to about 50% of tubal factor infertility, and is an important
cause of the upper genital tract or pelvic inflammatory disease (PID) and ectopic pregnancy.
There are indication that genital infection with chlamydia is not rare in Egypt. C.
trachomatis has long been known as the cause of trachoma, an eye disease which is endemic
in Egypt and is the leading cause of blindness. In addition, chlamydia is the pathogen long
known to cause inclusion conjunctivitis in newborn and lymphogranuloma venereum.
Causative organism
C. trachomatis is an obligate intracellular bacteria (it has a cell wall, contains both
DNA and RNA and responds to antibiotics). It infects the columnar and transitional
epithelium. In the past, it was a recognized cause of lymphogranuloma venereum, but
presently it is realized to cause a variety of infection in the female genital tract. The genital
disease is mainly contracted during sexual intercourse.
C. trachomatis has many serologic types. Serotypes D, E, F, G, H, I, J and K (D
through to K) are responsible for genital infections described below. Serotypes L1, L2, L3 are
responsible for lymphogranuloma venerum and serotypes ABC for endemic blinding
trachoma.
Clinical picture
- The incubation period for C. trachomatis infection is probably 6 - 14 days, which is
considerably longer than that for N. gonorrhea, making it difficult to associate the
symptoms to a particular sexual intercourse.
- As many as 70% of women colonized with C. trachomatis are asymptomatic or have
mild, uncharacteristic symptoms. Such asymptomatic women act as a reservoir of
spreading the infection.
- C. trachomatis can cause endocervicitis which may or may not be symptomatic.
Chlamydia cervicitis tends to be hypertrophic appearing as a central friable ectopy covered
by mucopus. Endocervical mucus appears yellow against the cotton-tipped endocervical
swab, and on microscopic examination it contains numerous pus cells.

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- The acute urethral syndrome is defined as acute dysuria and frequent micturition in
women with pyuria but whose voided urine is sterile or contains fewer than 105
microorganisms per ml.
- Chlamydia can cause bartholinitis.
- It can also cause late postpartum endomtritis.
- Genital infection can cause neonatal conjunctivitis.
- C. trachomatis is an important cause of upper genital tract infection. This infection
usually passes clinically undetected, and causes tubal damage that results in
tuboperitoneal-factor infertility or predispose to ectophic pregnancy. Chlamydia infection
is an important cause of the group of mild or moderate symptoms and signs collectively
known as pelvic inflammatory disease (PID). However, if laparoscopy is done in these
cases, unexpectedly severe pathology may be discovered, ( see under Pelvic Inflammatory
Disease ).
- Acute perihepatitis and formation of perihepatic adhesion (Fitz-Hugh-Curtis syndrome)
may result from chlamydial infection and cause acute right upper quadrant abdominal
pain.
- Infection with C. trachomatis during pregnancy may result in late onset puerperal sepsis,
inclusion conjunctive in the newborn, neonatal sepsis including pneumonia. It has been
repeatedly suggested that C. trachomatis infection predisposes to abortion, intrauterine
death, preterm labor and premature rupture of membrane. However, all such associations
are still in need of further wide-scale confirmatory studies. Also there has been an
indicator of relationship to cervical cancer which needs further validation.
Diagnosis
1. High index of suspicion is a key-element in diagnosis of chlamydial infection of the
genital tract and for avoidance of the serious late sequelae like infertility.
2. Measurement of chlamydial antibodies in the serum either of IgG or IgM is unreliable
because of high false positive results, and the persistence of the antibodies in the
circulation after any chlamydial infection.
3. Currently the diagnosis of chlamydia infection depends upon examining the cervical
mucus by one of the following laboratory tests which aim at detection of the bacterial
antigen by monoclonal antibodies:
a. Direct fluorescent antibody slide staining (DFA).
b. Enzyme-linked immunosorbent assay technique (ELISA).
c. DNA probe system.
These are rapid and less expensive, but less sensitive, than other tests described below:
d. Tissue culture (TC) has been the “gold standard” for the diagnosis of C.
trachomatus infection. But it requires a specialized lab, is more expensive and has

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a 2 - 7 day turnaround time. It has been now replaced by the following group of
tests.
e. Nucleic acid amplification tests:
Polymerase chain reaction (PCR) has been used to detect C. trachomatis in
endocervical samples and appears more sensitive and more rapid than cell
culture.
f. Ligase chain reaction (LCR) done on first void urine (FVU) has also been used.
These latter tests have a high put-through and are now being utilized for
screening purposes.
Screening programs
Genital chlamydia infection fulfills the WHO criteria that make a disease deserving
screening efforts:
1. It is an important public health problem: common and serious.
2. The majority of infections are asymptomatic with the partner affected in 70% of cases.
3. Availability of effective treatment.
4. Availability of suitable tests. In countries that can afford it, this should be one of the DNA
amplification tests e.g. LCR. The sample is conveniently obtained e.g. FVU or vulval
sampling. These tests have high sensitivity (> 90%) and specificity 100%. Alternatively,
ELISA can be used but with less sensitivity and specificity.
5. Ethically, the potential harm resulting from a positive result is balanced by protection
from serious long-term health consequence like infertility, ectopic pregnancy and chronic
pelvic pain.
The screening program may be targeted to the risk group who are liable to develop
STDs e.g. recent marriage or change of sexual partner, symptoms of urethritis, cervicitis or
PID. They should also comprise women whose sexual partner is having urethral discharge or
any STD. Screening should be also directed to other possible STDs.
Health education programs should precede and follow any screening for the sake of
prevention.
Treatment
- Basically, the choice is between doxycycline (e.g. Vibramycin), erythromycin (e.g.
Erythrocin) and azithromycin (e.g. Zithramax). The former is cheaper but is associated
with poor compliance because of long treatment course (100 mg PO BID x 7d).
- A major advantage of azithromycin, a long-acting macrolide, is its single dose (1g PO x 1
dose), and the directly observed therapy. However, it is more expensive. Erythromycin is
used during pregnancy (500 mg PO, QID x 7d).
- Patients who are not pregnant treated by either doxycycline or azithromycin do not need a
test of cure. The patient should refer her sexual partner for evaluation and treatment.

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- Empirical treatment of all young women at high risk for disease is another strategy of
prevention of the disease and its consequences.

Genital Mycoplasmas
The mycoplasmas are a unique group of microorganisms that commonly inhabit the
mucous membranes of the respiratory and genital tracts. The two main species that inhabit the
genital tract are Mycoplasma hominis and ureaplasma urealyticum. Over the last 20 years
these genital infections have been associated with a variety of clinical conditions including
low-birth-weight infants, spontaneous abortions, stillbirths, postpartum infections,
chorioamnionitis, pelvic inflammatory disease, and infertility. Genital mycoplasmas are
uncommon in prepubertal girls, but the frequency of colonization of the lower genital tract by
mycoplasmas markedly increases after the beginning of sexual life (15 - 75%). The recent
evidence has suggested, however, a limited role of this ubiquitous organism in the above-
mentioned reproductive disorders.
Organism
Mycoplasmas are the smallest known free-living organism. Phylogenetically, they fall
between bacteria and viruses. Like the former, mycoplasmas, grow in cell free media and are
susceptible to antimicrobial agents that inhibit protein synthesis. However, unlike bacteria,
mycoplasmas have no cell walls. They differ from viruses in containing both DNA and RNA
and in growth in cell free media.
Diagnosis
Diagnosis of genital mycoplasma does not depend on any specific clinical
manifestation ; it is diagnosed by laboratory tests done in patients with any of the clinical
problems suspected to be related to this infection. The diagnosis of mycoplasma infection
may be based on isolation of the organism from sites of infection on a special media. Various
serologic tests are available including agglutination, complement fixation, indirect
hemagglutination, metabolic inhibition and ELISA.
Clinical manifestations
At the present time, the implication of genital infection with either M. hominus or U.
urealyticum in the following clinical entities varies between weak, moderate and strong:
- Spontaneous abortions and stillbirths: weak evidence.
- Chorioamniotitis and intraamniotic infection: weak or moderate evidence.
- Low-birth infants: weak evidence.
- Postpartum infection: strong evidence.
- Pelvic inflammatory disease: weak evidence.
- Infertility: weak evidence.

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Genital tract infections

Factors detracting from firm evidence include the common presence of mycoplasmas
in the genital tract and a variety of possible confounding factors pertaining to the type of
sexual relations of the subjects involved in epidemiological surveys.
Treatment
Since mycoplasmas lack cell walls, they are resistant to cell-wall-active antimicrobial
agents like penicillins and cephalosporins. The antimicrobial agents that inhibit protein
synthesis like tetracyclines and clindamycin (Dalacin) are effective against genital
mycoplasma. In absence of strong evidence of implication of mycoplasma in causation of the
above-mentioned obstetric and gynecological problem, the use of the antimicrobial agents
like tetracyclines or clindamycin in the management of these conditions is empirical. This
should not detract from consideration of other etiologic causes. Their course is not fully
characterized, and are usually prolonged for 3 to 4 weeks.

Pelvic Inflammatory Disease

PID is one of the most frequent and important infections seen in nonpregnant
reproductive age women in western communities. Acute PID is the acute clinical syndrome
attributed to ascending spread of microorganisms from the vagina and endocervix to the
endometrium, fallopian tubes, and/or contaguous structures. Because of its close association
with STDs, a discussion of PID is included in the present discussion of STDs. There is,
however, an unavoidable overlap over and repetition of information given on the section on
“Salpingo-oopharitis and pelvic peritonitis” that will be dealt with later. By definition PID is
an acute infective condition; the discussion will not include chronic infective conditions.

Epidemiology
PID is a disease of sexually active menstruating women. It is an important cause of
gynecological consultation in the USA and many other countries. With liberation of sexuation
practice in may parts of the world, PID is increasing in incidence and its long-term Sequelae
are increasingly recognized.
Some risk factors for the occurrence of PID have been delineated and include the following:
- Age: Young age is a risk factor but the risk is dependant on sexual vulnerability.
- Sexual activity: The risk is largely confined to women who are sexually active.
Multiplicity of sexual partners, recent marriage, or a recent sexual partner are risk
factors.
- Poor socioeconomic level, associated with poor personal hygiene.
- Previous or concomitant STD including gonorrhea and chlamydia infection.
- Bacterial vaginosis.

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- Repeated vaginal douching.

- Contraceptive use.
Barrier methods, particularly the male condom use protect from PID.
Oral contraceptives diminish the risk of PID.
The use of IUD increases the risk of PID particularly in women with increased risk
for STDs.
- Invasive gynecological procedures such as hystrosalpingography endometrial
biopsy, dilatation and curettages (D&Cs) and cervical cautary predispose to PID.

Causative organisms
Most incidences of PID are caused by microorganisms that ascend from the lower
genital tract through the cervix, along the endometrium to the normally sterile tubes. Infection
also may be carried to the tubes and ovaries through the parametric blood vessels and
lymphatic. PID is usually a polymicrobial infection and involves organisms sexually
transmitted and organisms that are part of the normal endogenous microflora of the lower
genital tract.
More than half of PID diagnosed in the USA are caused by gonococcus, and/or C.
trachomatis. The situation in Egypt is undetermined.
Mixed aerobic and anaerobic bacteria are involved in about two thirds of
incidences of PID. The aerobes comprise E. Choli, staphylococci, and streptococci,
including enterococci. The anaerobes comprise peptococci, bacteroides and rarely
clostridia. As a result of devitalization produced by the initial infection e.g.
gonococcal or chlamydial, other organisms become involved as a secondary infection.
Genital mycoplasma is a possible infective organism in PID.
Determining the organism(s) involved in PID depends upon the demonstration of their
presence in the cervix and vaginal swabs and in tubal exudate, biopsy specimen, or cul-de-sac
fluid obtained at the time of laparoscopy or laparotomy; the latter 3 sources are not always
available.
Diagnosis
The clinical diagnosis of PID is frequently inaccurate and unsatisfactory. No
symptoms or signs are pathognomonic of PID; and the diagnosis usually depends on algorism
of manifestations. However, because of the seriousness of the possible consequences of PID,
it is wiser to err towards the positive side; even with the expense of overdiagnosis of the
condition. The criteria present in the Table 2 have been suggested for making the diagnosis of
PID.

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Even with these criteria, the clinical diagnosis of PID can be in error and may not be
confirmed by laparoscopy. The latter is the “gold standard” against which other diagnostic
criteria are measured. However, it is not practical to do laparoscopy for all suspected cases.
For the majority of cases in which PID is erroneously made, no pelvic pathology can be seen
with laparoscopy.
Diagnostic laparoscopy should be performed (1) when the differential diagnosis of
pelvic pain is either PID or a surgical condition e.g. ectopic or appendicitis, (2) in case of
nonresponding or recurrent clinical disease and (3) when is not associated with an obvious
precipitating cause. In other cases the use of laparoscopy can be individualized. Laparoscopic
criteria of acute PID include erythema and/or edema of the fallopian tube, exudate from
fimbria, presence of poygenic membrane on the serosa, limited movability of tube, fimbrial
agglutination and the presence of inflammatory masses.
Endometrial biopsy may help to establish the diagnosis of PID in women with pelvic
pain. In cases of PID particularly that caused by C. trachomatis, plasma cell endometritis or
acute suppurative endometritis may be found.
Approximately 5% of women with PID have an association with perihepatitis, known
as Fitz-Hugh-Curtis syndrome. The syndrome comprises inflammatory fibrinous bands of
adhesion. It is associated with acute pain and tenderness in the upper right quadrant of the
abdomen that may simulate acute cholecystitis. The liver functions may be slightly impaired.
Eventually thin fibrous bands (violin strings) develop between the dome of the liver and
diaphragm. These can be recognized during subsequent laparotomy or laparoscopy.

Table 2. Criteria for the diagnosis of PID an Algorism

All the following three should be present:

1. History of lower abdominal pain and the presence of lower abdominal
tenderness, with or without rebound.
2. Cervical motion tenderness.
3. Adnexal tenderness.
One or more of these should be present
1. Temperature > 38 C.
2. Leukocytosis > 10,000 WBC/mm3.
3. Presence of an inflammatory mass noted on pelvic examination or
sonography.
4. Erythrocyte desementation rate > 15 mm/hr, or elevated C-reactive
protein.
5. A culdocenthesis yield peritoneal fluid containing white blood cells and

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bacteria.
6. Evidence of presence of N. gonorrhea and/or C. trachomatis in the
cervix:
- Mucopurulent cervicitis.
- Gram stain with Gram-negative intracellular
diplococci.
- Positive chlamydia antigen test (ELISA).
- >10 WBC/HPF on Gram stain.

The clinical presentation of PID may differ depending on the primary pathogens involved:
a) Gonococcal PID tends to be more acute and dramatic and develops within few
days of the beginning of abnormal vaginal discharge. Abscess formation is rare
and response to antibiotics is rapid.
b) Chlamydial PID usually involves moderate symptoms, and follows a more
protracted course with poor response to antibiotic treatment. The laparoscopic
appearance of the tubes is more serious than indicated by the clinical picture.
c) Nongonococcal, nonchlamydial PID is suggested by the age of the woman, if she
is older than 30 years; protracted course; delayed response to antibiotics; multiple
recurrences; and tubovarian abscess formation.
However, there is a good deal of overlap between clinical pictures, and frequently
more than one etiologic organism is involved.
Long-term Consequences of PID: There are 4 long-term sequelae of PID:
1. Recurrent disease despite adequate therapy. It seems that the devitalized tube is more
vulnerable to repeat reinfection from the lower genital tract.
2. Chronic pelvic pain: The pain may be related to menstruation or coitus or is continuous.
The pain may be distressing enough and persistent to call for hysterectomy.
Approximately 20% of abdominal hysterectomies done in the USA are solely or partially
indicated by chronic pelvic pain.
3. Infertility: About 20 to 30% of infertility cases are caused by tubo-peritoneal
postinflammatory pathology.
4. PID leading to abnormalities in the fallopian tubes, which are not severe enough to cause
their block, predispose to ectopic pregnancy.

Treatment
Because of the seriousness of the consequences of PID, the treatment needs to be
active and as comprehensive as possible. The therapy comprises four items: 1) frequent

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observation for response, 2) properly chosen antibiotics, 3) notification and counseling of the
husband (sexual partner) and 4) treatment of complications.
1. Hospitalization is indicated in severe disease (peritonism, tuboovarian abscess, or severe
illness), when the diagnosis is in doubt, if the patient is intolerant or nonresponsive to oral
antibiotics, if efficient observation on outpatient basis is difficult, if pregnancy is
suspected or the patient is immunosuppressed. Hospitalization allows observation,
parenteral fluid and frequent parenteral antibiotic administration.
2. Antibiotic treatment should depend on multiple drug therapy. Table 3 gives the latest
recommendations of the Centers for Disease Control (CDC) of the USA for antimicrobial
therapy in PID.
3. The patient and her sexual partner should be screened for STDs and treated.
4. Medical treatment should be instituted for TOA. Small abscess resolve under multiple
agent antimicrobial therapy. Surgical treatment is only indicated in the following
circumstances: (1) When there is evidence of spreading peritonitis despite adequate
antibiotic treatment; (2) rupture of tuboovarian absence, (3) formation of pelvic abscess,
(4) intestinal obstruction resulting from adhesion; (5) if the diagnosis is in reasonable
doubt. If laparotomy does reveal salpingitis, it is generally wise to leave the pelvic organs
untouched, except for taking a swab from any pus for bacteriological assessment. Pelvic
abscess or pyosalpinx can be aspirated transvaginally with sonographic guidance.
Chronic PID is dealt with under chronic salpingo-oophoritis.

Table 3. CDC 1998 Recommendations for antimicrobial treatment of PID

Inpatient therapy
A. Uncomplicated acute salpingitis*
Cefotetan 2g IV q 12 hr.
or
Cefoxitin 2g IV q 6 hr.
plus
Doxycycline 100 mg IV or PO q 12 hr.
B. Complicated salpingitis (tuboovarian abscess or peritonitis)†
Clindamycin 900 mg IV q 8 hr.
plus
Gentamycin loading dose of 2 mg/kg IV or IM followed by maintenance dose
of 1.5 mg/kg q 8 hr.

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Genital tract infections

Outpatient therapy
A. Ofloxacin 400 mg PO q 12 hr x 14 d.
plus
Metronidazole 500 mg bid x 14 d.

B. Ceftriaxone 250 mg IM x 1 dose.

or
Cefriaxone 250 mg IM x 1 dose.
or
Cefoxitin 2 g IM plus probenecid 1 g PO in a single dose.
plus
Doxycycline 100 mg bid x 14 d.

IV, intravenously; IM, intramuscularly ; q, every ; PO, by month ; bid, twice a day qid, four
times a day.
* Parenteral therapy may be discontinued after signs of clinical improvement, and oral
therapy should thereafter continue for a total of 14 days.
† Parenteral therapy should continue for at least 4 days. Subsequent oral therapy of
clindamycin 450 mg PO qid or doxycycline 100 mg PO bid should be given for a total of
14 days.

Herpes Simplex Virus Infection

Genital herpes is one of the most common sexually transmitted diseases in the USA. It
is caused by herpes simplex virus, types 1 and 2 (HSV-1 and HSV-2). Symptomatic genital
herpes is a common cause of painful lesions of the lower genital tract of women in many
western countries, mainly the USA. Herpes infection has been implicated in the pathogenesis
of cervical carcinoma, albeit with no final proof. In addition, contact with genital herpes
during passage through birth canal has been associated with systemic neonatal infection,
which carries high mortality and morbidity rate.
The exact prevalence of genital herpes is difficult to estimate because there is a high
proportion of asymptomatic disease, and because not all cases with symptoms disease seek
medical care. However, there is strong evidence that the evidence of genital herpes is
increasing in western countries. The condition is not commonly diagnosed in our practice,
maybe due to low index of suspicion.
Organism
Herpes simplex virus contains an inner core of double-stranded DNA surrounded by
an envelope of glycoprotein. There are two major closely related types of HSV, type 1 (HSV-
1) and type 2 (HSV-2). HSV-2 is the cause of the majority of herpetic genital infection. HSV-
1 causes oropharyngeal disease.

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Genital tract infections

The majority of genital herpes infections are transmitted through sexual contact, but
transmission by other types of contact is possible. The incubation period is 2 - 40 days. The
clinical course of the disease is self-limited but is characteristically recurrent; during the
periods of latency the virus resides in the dorsal roots of sacral ganglia.
Clinical picture of genital herpes
The majority of HSV infections are asymptomatic but such carriers are occasionally
infective.
The clinical manifestations of genital HSV infections occur in three distinct
syndromes: The first episode of the disease may represent a primary or nonprimary infection.
Recurrences of genital herpes are common. The implications of herpes to pregnancy need be
considered:
1. First-episode primary genital herpes is the initial HSV infection in an individual without
circulating antibodies. This type is associated with severe local symptoms with multiple
painful lesions that progress from vesicles to an ulcerative stage. The ulcers are severely
painful, shallow, multiple, occasionally coalescent. Inguinal adenopathy, and systemic
effects as fever, malaise, headaches and nausea may be associated. The ulcer involves the
vulval structures, vaginal skin, the cervix and urethra. Cervical lesions are common and
cause friability, ulcerative or necrotic lesions and marked increase in cervical discharge.
Complications: of initial herpes infection develop more often in women than men and
include: 1) acute pharyngitis, 2) herpetic lesion in the buttocks and thighs, 3) hepatitis 4)
aseptic meningitis, and 5) autonomic nervous dysfunctions e.g. acute urinary retention.
The primary lesions are much severer in women.
2. First-episode nonprimary genital herpes is the initial clinical episode of genital HSV of
patients who have circulating antibodies to the virus secondary to a prior asymptomatic
infection. Its clinical course is similar to recurrent genital herpes; being less severe and
comprising few, short-lived lesions.
3. Recurrent genital herpes: The lesions are few; cervical lesions are uncommon.
Lymphadenopathy is absent or mild and systemic manifestations are absent. The lesion
persists for few days. Prodroma may precede the recurrence and take the form of tingling
sensation and itching or hyperasthesia of the genital area. The herpeticulcers heal usually
within 15 days. A new crop of lesion appears after variable periods of time. The patient is
highly infectious until the lesion starts to heal (for 12 days).
The frequency of recurrent disease and length of the interval between recurrences of
active infection are highly variable. The average number of recurrences in women is
generally 5 to 8 per year. Recurrence may be cyclic and related to menstruations. HSV-1
is less likely to cause recurrent disease in the genital tract and the recurrences are less
severe.

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Genital tract infections

Diagnosis: depends upon

1. The clinical picture is highly suggestive.
2. Virus isolation by tissue culture (the gold-standard), but this is not widely available.
3. Cytological smear (Tzanck smear) is a less sensitive (only 50% positivity) but simpler
method. Scrapings of the lesions are spread on a slide and stained by Wright’s or Giemsa
stain. Positive cases show multinucleated giant cell, intracellular inclusion, atypical
keratinocyte, and ground-glass cytoplasm.
4. Monoclonal antibody staining methods of scrapes from the lesion improve the sensitivity
to 75%.
5. ELISA tests for herpetic infection are so far, not sensitive enough.
6. Recently, PCR is used to detect HSV DNA in the culture material and direct lesion
samplings with very high sensitivity and specificity.
7. Antibody testing is of no value in diagnosis of genital herpes infection. The presence of
antibody represents past exposure that could have been asymptomatic. About 50% of
adult population in the USA are having antibodies for HSV-1 and about 25% have
antibodies for HSV-2. False positive results are also common. The test is of value only
when it is negative at the onset of suspected lesion, and antibodies develop during the
course of illness.
Treatment
Acyclovir has been the most widely used treatment. It is an effective agent in reducing
the time needed for disappearance of lesions, ameliorating the symptoms, reducing viral
shedding i.e. infectiousness, preventing frequent recurrence. However, it cannot always
eradicate the disease. Limitations of acyclovir are the limited bioavailability after oral
administration necessitating multiple daily doses. Famciclovir and valacyclovir have similar
effect like acyclovir but with larger bioavailability after oral administration.
For first-episode genital herpes, the usual recommended dose acylovir (e.g. Zovirax)
is 200 mg orally five times daily for 10 days, or alternatively of famciclovir (e.g. Famiver)
250 mg orally three times daily, or of valacyclovir (e.g. Valtrex) 1 g orally twice daily.
Intravenous acyclovir sodium (Zovirax I.V.) is used in severe genital infection. Topical
acyclovir ointment (e.g. Clovir or Supravirin) may help to ameliorate the genital lesions but is
not a substitute to systemic treatment.
Supportive symptomatic treatment like frequent sitz-bathes, topical anaesthetic or use
of electric-blow hair dryer (on cool), and treatment of secondary candida infection.
Oral aclyclovir can be used to prevent recurrences in the dose of 200 mg three times
daily or 400 mg twice daily for 6 to 12 months.

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Genital tract infections

Follow-up and prevention

The patient should be counseled about the natural history of the disease and about the
measures to reduce transmission. Condom should be always used for quite a long time.
However, because of varied location of infection its use is not 100% effective. She should
relate the information to her obstetrician in order to prevent neonatal herpetic infection. An
effective HSV vaccine is not yet available.

Genital Herpes in pregnancy and neonatal Herpes infection

The prevalence of herpes in the genital tract of pregnant women has been estimated to
be in the region of 1% (USA data). The infection is usually asymptomatic. However, primary
episodes may be more severe during pregnancy.
The herpetic infection can be transferred to the fetus in two ways:
1. Transplacental (intrauterine) infection is rare. It only occurs as consequence of first-
episode primary infection occurring during pregnancy. The consequences are
devastating, including severe skin herpetic affection and neurological complications
like microcephaly, hydrocephaly, and microophtholomia.
2. Intrauterine (perinatal) infection resulting from contact with an infected maternal
lower genital tract. The chance of neonatal infection is high in the presence of
primary genital herpes (40%) but should be low (< 4%) in recurrent disease. Rarely,
the source of infection can be the oropharunx or hands of the patient or attendants.
Cesarean delivery has been shown to reduce the chance of perinatal infection, but
cannot completely rule it out (particularly when the CS is done several hours after
rupture of membranes).
Neonatal infection may take one of three forms:
1. Disseminated disease in the form of generalized neonatal sepsis causing pneumonia
and gastroeneritis and rapid prostration and high mortality and morbidity.
2. Central nervous neonatal infection, which has low primary mortality but high long-
term morbidities in spite of antiviral therapy.
3. Skin-eye or mouth only infection, which has both low mortality and morbidity,
particularly when antiviral therapy is given.
Acyclovir can be given during later pregnancy for treatment of genital infection. This
may help to prevent transplacental and perinatal transmission.
In 1988 the American College of Obstetrician and Gynecology (ACOG) issued
recommendations for management of HSV infection during pregnancy: Excerpts include:
1. Culture should be done when a woman has active HSV lesion during pregnancy
to confirm the diagnosis.
2. If there are no visible lesions at the onset of labor, vaginal delivery is possible.

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Genital tract infections

3. There is little need to repeat culture (as previously recommended) or to perform

amniocentesis to confirm fetal infection.
4. A culture may be obtained from the neonate to confirm whether he or she has
been infected.
5. Term patients who have visible lesions and are in labor or have ruptured
membranes should undergo cesarean delivery ... even with membranes ruptured
for more than 24 hours.

Syphilis
Syphilis is rarely seen in our practice in Egypt, but it remains a significant STD in
many developing countries, and in some areas of North America and Europe. In these
countries there is evidence that the incidence is increasing. The increase is strongly associated
with increase in the use of illicit drugs and of HIV infections.
Organism
Syphilis is caused by Treponema pallidum (Spirocheta pallida) and this organism is
found in all lesions-primary, secondary and tertiary. Infection is mainly through sexual
contacts. Other types of contact rarely transmit the disease, but this requires contacting an
open syphilitic lesion by injured hands, a risk to which doctors and nurses are especially
exposed.
The incubation period ranges from 9 to 90 days with an average of 3 weeks.
Clinical pictures
Syphilis exists in 3 stages: primary, secondary and tertiary.
Primary syphilis: The lesion of primary syphilis is the chancre. This develops on the
site of inoculation, usually on the labia, the fourchette, the cervix or the vagina, and rarely on
the lips, pharynx or anal canal (as a result of extravaginal sexual contacts). The chancre is
usually solitary and begins as a firm papule which breaks down to form a painless well
demarcated ulcer, with raised well defined serpigenous rolled edges, red or brownish floor,
hard base and uninflammed margin. The inguinal lymph nodes may be enlarged. The lesion is
characteristically painless, may not be that typical in the female and may escape notice.
Lesion on the cervix may look like erosion. Spirochettes are found in the floor of the ulcer
and the chancre is infectious. If untreated, chancres heal spontaneously in 2 to 6 weeks.
Secondary syphilis: The manifestations of secondary syphilis develop 6 to 12 weeks
after exposure and result from hematogenous dissemination. Secondary syphilis has
mucocutaneous and systemic manifestations:
The cutenous lesions are in the form of generalized rash which can be macular,
maculopapular, papular, pastular or discoid. Typically the face is spared and the palms and

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Genital tract infections

soles are involved. Alopecia may result. Similar lesions may develop on the mucous
membranes. Another classic cutaneous lesion is the condyloma latum which is a confluence
of raised moist, flat topped, exuberant necrotic soft lesions that occur in moist areas like the
perineum, groins, or axillae. All these lesions are infectious. Generalized bilateral
enlargement of lymph nodes is common - symmetrical enlargement of the epitrochlear hymen
nodes is characteristic (because it is rarely enlarged otherwise).
General manifestations like fever, malaise, headache, sore throat, arthralgias,
leucocytosis and occasionally splenomegaly may develop. Rarely meningitis or hepatitis may
develop.
Tertiary or late syphilis: After resolution of signs of secondary syphilis, the infection
enters a latent period of one to five (occasionally more) years, before manifestations of
tertiary or late syphilis develop. They take the form of:
1) Single or multiple organ lesions affection by the gumma. A gumma is a chronic
necrotic destructive, painless lesion that may involve the skin, mucous membranes,
liver or other viscera, long bones and joints.
2) Cardiovascular syphilis prominently involves the aorta, resulting in aortic
insufficiency and in thoracic aortic aneurysms.
3) Neorosyphilis may be asymptomatic, may resemble meningitis, and may result in
gradual deterioration of intellectual and motor capacity. Neurosyphilis is particularly
common in patients with AIDS.
Congenital syphilis: Syphilis can be transmitted to the fetus at any stage of pregnancy
and can result in deformations, intrauterine fetal death, or acute neonatal illness and late
manifestation of the disease. Therefore, prenatal screening of women for syphilis is necessary.
(This is not warranted in our practice).
Diagnosis
1. A dark field examination of expressed secretion from cleaned lesion can demonstrate the
spiral spirochetes.
2. Serology: Serologic tests for syphilis are of two types: nontreponemal and treponemal.
The nontreponemal tests most widely used are the Venereal Disease Research laboratory
(VDRL) slide tests. These tests detect the presence of cardiolipin, a nonspecific antigen
produced during syphilitic infection. These tests are qualitative, but decreasing serial
titers may be used to judge therapeutic responses. These tests are not specific for syphilis.
Positive results can occur in various collagen disease (SLE, or rheumatoid), lymphomas,
sarcoidasis and acute infectious monouleosis, Mycoplasma infections, HIV infection, and
other febrile conditions).
The treponemal tests are specific and include the fluoroscent treponemal
antibody absorption test (FTA ABS) and microhemagglutination T. pallidum tests (MHA

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TPS). The treponemal antibodies will always persist in the circulation after cure of the
disease. The treponemal test will be positive in all patients with late syphilis while the
nontreponemal tests may be negative in 30% of cases.
In patients with late syphilis a lumbar puncture can demonstrate the spirochetes
in patients with neurosyphilis that can remain asymptomatic. This is particularly
indicated in all patients with AIDS.
Treatment
Penicillin is still the standard treatment of syphilis. Primary, secondary or early latent
syphilis are treated with benzathine penicillin 2.4 million units intramuscularly in a single
dose. Alternatively a 2 week course of doxycycline 100 mg orally twice a day or tetracycline
500 mg orally four times daily can be used in penicillin-allergic patients who are not
pregnant. Syphilis of more than 1 year’s duration is treated with the above penicillin dose
once per week for 3 successive weeks or with a 4-week course of doxycycline or tetracycline
in the doses given above. Patients with neurosyphilis are given aqueous crystalline penicillin
G, 3 to 4 million U intravenously every 4 hours for 10 to 14 days, other forms of pencillin do
not cross the blood-brain barrier. Penicillin-allergic patients who are pregnant or have HIV
infection or neurosyphilis may need be hospitalized for densitization and treatment with
parenteral penicillin for optimal therapy.
After treatment, nontreponemal tests revert to normal in a large percentage of patients.
Partners of patients diagnosed with syphilis at any stage should be notified and evaluated
clinically and serologically.

Chancroids
Chancroid is endemic in many sub-Saharan African countries. It is a sexually
transmitted disease, which is commoner in men than women and is related to prostitution, use
of illicit drug, lack of cleanliness in uncircumcised males.
The infection is caused by the gram-negative streptobacillus Hemophilus ducreyi
which is transmitted during sexual intercourse. The incubation period is 2 - 5 days.
The lesions begin as multiple small papules or vesicles, which rapidly break down to
form acutely painful shallow ulcers, which discharge offensive pus. The lesions can be on the
labia majora or minora, the fourchette, around the anus and may involve the vagina, urethra or
the cervix. The ulcers have undermined edges, red grayish floor that easily bleed, soft base
and red edematous margin. The inguinal lymph nodes are enlarged, painful, and frequently
get confluent and suppurate forming a unilocular abscess. This points out forming indolent
discharging sinus. The infection remains localized in the groin and may be associated with
malaise and pyrexia.

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The diagnosis is suggested by the clinical presentation. It simulates chancre, herpes

infection or Behcets ulcer. It is confirmed by demonstrating the bacilli in scraping of the
edges or aspirate of the inguinal abscess. They can be demonstrated in culture on specific
media. The coccobacilli are Gram negative and arranged in cluster giving the “school of fish”
pattern. Mixed infection can occur. The diagnosis can be confirmed with immunofluorescent
stain.
Treatment is possible by sulfa and tetracycline. Occasionally the organism is resistant
to these two antimicrobial agents. Current CDC-recommended treatment includes a single
dose of 1 g oral azithromycin or a single intramuscular injection of 250 mg of ceftriaxone.
Successful treatment is possible with this treatment. Suppurating abscess can be aspirated or
incised. The sexual partner should be treated even if he is not symptomatic.

Lymphogranuloma Venerum (LGV)

Lymphogranuloma venerum is an STD caused by C. trachomatis serotypes L1, L2
and L3. LGV is rarely seen in Egypt, but it is common in tropical areas and endemic in West
Africa, India and South East Asia.
The clinical picture of LGV is divided into primary, secondary and tertiary stages.
Following an incubation period of 3 - 21 days, the primary lesion takes the form of painless
papules or vesicles in anogenital region, which may ulcerate but generally, heal within few
days. They may pass unnoticed.
The secondary stage develops 1 - 4 weeks later and takes the form of adenopathy that
may be associated with systemic manifestations of fever, malaise and myalagia. The inguinal
and femoral lymph nodes are most commonly involved (bubo); other groups may be later
involved. The enlarged nodes are painful matted and commonly suppurate resulting in
discharging sinuses.
The tertiary stage involves the external genitalia and anorectal areas by progressive
tissue destruction, ulceration, scarring and elephantiasis. Stricture formation follows after
months or years.
The clinical picture is not very pathognomic. Frei intradermal test was the standard
method of diagnosis, but it is not specific. Culture of scrapings or aspirates for chlamydia is
used in specialized centers. Monoclonal antibodies can be used to identify the organism.
Serological tests for chlamydia antibodies can be used in the form of microimmuno-
fluoroscence (MIF) test.
The recommended treatment is doxycycline 100 mg orally twice a day for 21 days.
Alternatively erythromycin orally: 500 mg x 4 x 21 days.

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Granuloma Inguinale (Donovanosis)

Donovanosis is caused by an encapsulated gram-negative bacillus
colymmatobacterium granulomatis that characteristically results in the formation of Donovan
bodies in tissue preparations stained by Giemsa stain. Donovan bodies are clusters of
mononoclear cells containing large numbers of encapsulated bacilli. The disease takes the
form of ulceration with spreading granulomatous infiltration of the vulva and inguinal region
but without lymph node involvement.
The disease is usually sexually transmitted but can result from other types of
prolonged contact with patients. It is common in certain endemic areas, in the Caribbean,
India and tropical Africa.
The disease has a very insidious onset (incubation period 2 - 4 months) beginning
with painless papules on the vulva, perineum or inguinal regions. This is followed by
ulcerations, which have well defined border, clean floors with exuberant, velvety granulation
tissue. The lesions undergo repeated granulomatous formations, ulcerations and scarring;
eventually extensive tissue destruction takes place.
Diagnosis is established by demonstration of Donovan bodies in tissue preparations.
The usual treatment is doxycycline orally 100 mg x 2 x 21 days.

Papillomavirus infection; Genital warts

Genital warts, caused by human papillomavirus (HPV), are not uncommonly seen in
our practice. They are among the most common STDs seen in the United States. The viral
infection can affect a big sector of the population, since the majority remains asymptomatic, a
minority develops the warts. HPV has many serologic subtypes; HVP 6 and 11 are seen in
most patients with genital warts.
Once they are transmitted, genital warts have an incubation period ranging from 3
weeks to 8 months. Old lesions are less infectious. The major risk for acquiring genital HPV
infection involves the sexual behavior including the multiplicity of sexual partners and
multiplicity of the partners of the partner.
Any part of the vulva may be affected. The mons, the perineum, perineal areas may be
involved, as may be the vagina, the cervix and anal canal. The growth of the warts seems to
be stimulated by heat and moisture.
Typical genital warts (clondylomata acummate) are multiple exophytic growths that
appear as papillary, pink or white, frondlike or cauliflower-like lesions. They tend to grow in
clusters or they may coalesce into large masses. Some warts may look as discrete flat-topped,
hyperkeratotic papules. These flat lesions are specially common on the cervix. The lesions are

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usually not painful, but may cause pruritus. Warts may get necrotic and secondarily infected
causing a fetid odor bleeding and discharge.
Autoinoculation may cause spread of the lesion. Some HPV warts grow markedly
during pregnancy to regress after delivery. Spontaneous remission may occur. Women with
diabetes mellitus or immunosuppression may experience massive growth of warts.
HPV has been associated with epithelial dysplasia and with carcinoma of the cervix
and vulva. HPV types 16 and 18 are particularly incriminated in the process. It is thought that
HPV 16 and 18 encode for two transforming gene products, the E6 protein, which causes
rapid degradation of the p53 tumor suppresses protein, and the E7 protein, which binds the
retinoblastoma susceptibility gene product. These changes may play a role in the pathogenesis
of lower genital tract cancer. HPV vaccines have been developed and are being tried.
Diagnosis
The diagnosis of genital warts is suggested by the gross appearance of the lesions.
Vaginal cytology (koilocytic changes) or colposcopy may be suggestive but not
conclusive (see under CIN). The Pap smear can show koilocytes. These are exfoliated
superficial or intermediate cells with wrinkled nucleus surrounded by perinuclear halo.
Colposcopy shows conylomata on the surface of the cervix; flat or spicked.
Histological features of HPV infection include papillomalosis, acanthosis, and
parakeratosis with vacuolization of epithelial cells.
To characterize histologically equivocal lesions, specific HPV, DNA detection probes,
in situ hybridization and PCR can help.
Treatment
Genital warts are treated by either one of the following approaches:
1. Local application of cytotoxic agents.
2. Wart ablation.
3. Antiviral immunomodulatory agents.
1. Local application of 10 to 25% podophllin in benzoin (prepared by the pharmacy), an
antibiotic agent that causes sloughing of the warts. The applications are kept for 2 to 3
hours before washed away. They need be repeated at weekly intervals for big warts. The
treatment is usually effective. The treatment is contraindicated in early pregnancy.
2. Cryocautary, laser or electrocautary are needed for ablation of big pedicted warts.
Recurrence may occur after some time. Large warts, and the presence of dysplastic
epithelium may require excision with a safety margin.
3. Interferon is an antiviral immunomodulatory agent, is recently used for chodylomata
acuminata, can be used either systematically or topically. An alternative agent is
imiquimod a potent inducer of interferon and other cytokine can be used. These two
treatments are expensive and may cause systemic side effects.

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Patients with genital warts need regular screening for cervical cancer. The vulva and
perineum should be kept dry and the underwear should be porous and frequently changed.

Molluscum contagiosum
Molluscum contagiosum is a rare benign viral skin infection caused by a DNA-
containing poxvirus. It is transmitted by close skin-to-skin contact. When it affects the
vulvoperineal skin it is transmitted by sexual intercourse and may be associated with other
STDs.
Characteristic molluscum lesions are small (2 to 5 mm), flesh-coloured firm chronic
papules. They have umbilicated centers. They can be present in crops anywhere on the body.
They often spontaneously resolve in 6 to 9 months. Autinfection of other sites is common.
The diagnosis is usually made by clinical appearance. Excision biopsy stained by
Wright’s or giemsa stain shows molluscum bodies in infected epidermal cells. These are
ovoid acculations of replicating virus within the cytoplasm. The lesion projects into the
dermis but does not break the basement membrane.
The lesion can be curetted or excised by cryocautary or laser ablation. However, most
molluscum lesions resolve if left untreated.

Skin parasitic infections: Ectoparasites

• Scabies
Scabies is caused by itch mite, Sarcoptes scabiei.
Scabies manifests itself with pruritic, pleomorphic rash that has an insidious onset and
a characteristic pattern of involvement that includes wrist, finger webs, elbows, axilla,
genitalia and buttocks. Itching is worst at night. The physical findings include the presence of
pathognonomic burrows, which are 5 - 10 mm long, wavy, dirty line and have the worm
which may be seen as a liny brown and white speck at the inner end. This is associated with
papular erythematous rash and persistent pruritic excoriated nodules.
The condition in better referred to a dermatologist for prescription of proper local
therapy of all areas possibly affected.

• Pediculosis pubis
Pediculosis affects the pubic hair bearing area of the mons and is caused by crab
louse, phthirus pubis. Clothings or close bodily contact including sexual intercourse transfers
the infection. The bites of the lice cause intense irritation and pruritus. The moving lice can be
seen.

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• Human Immunodeficiency Virus (HIV) infection and Acquired Immunodeficiency

syndrome (AIDS)
Acquired immunodeficiency syndrome (AIDS) is the most advanced stage in a
continuum of clinical manifestations caused by the human immunodeficiency virus (HIV).
This virus specifically causes profound alterations and deficiency of the immune mechanisms
that eventually leads to death. A progressively expanding pandemic of HIV infection have
seized the world causing unique medical, societal, legal, economic and other dilemmas.

Epidemiology
AIDS is a new disease first described in 1981 among communities of homosexual
men. There are indications, however, that the disease had existed before that for some years in
sub-Saharan Africa. The number of cases of AIDS and HIV infection has then been rapidly
rising in most parts of the world, particularly in women and children. It has been estimated
that worldwide more than 40 million persons infected with HIV by the year 2000, most of
them are women and children. The infection is transmitted by three modes: blood/blood
products, intimate sexual contact and perinatal transmission from infected mothers.
Intravenous drug use with shared needles is a major means by which the virus is
transmitted from the infected person. The infection and the disease are commoner in drug
users. Medical blood transfusion and transfusion of blood products account for a small
proportion of AIDS. Careful screening of blood/blood products has reduced this possibility.
Transmission of HIV during sexual activities is a major means of infection. Semen
and cervical and vaginal secretion can contain the virus. The disease was first described in
homosexual males. Anal intercourse is associated with the highest risk infection. The
presence of skin or mucous membrane abrasion greatly enhances infectivity. Vaginal
intercourse can also lead to infection. Transmission via heterosexual activity is, however, the
usual method of infection in the worldwide pandemic; both male-to-female and female-to-
male transmission can occur. Male-to-female transmission is, however, more efficient. An
exact risk of transmission associated with oral sex is not definitely known.

Risk factors associated with transmission of infection in heterosexual intercourse

includes young age, unmarried state, nonintravenous cocaine use, heavy smoking, multiple
sexual partners, unprotected sex, specifically the lack of use of condom, sex with a male
partner who himself has multiple sexual partners, or has not been circumcised, bisexuality,
history of or current STDs, particularly STDs associated with disruption of skin and mucous
membranes (e.g. syphilis, chancroid, genital herpes, genital warts).
The prevalence of HIV infection among pregnant women is rising in many parts of the
world, mainly in sub-Saharan Africa, and may reach figures as high as 20% to 30%.

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Pregnancy dose not accelerate the clinical course of AIDS. However, the main concern of
HIV infection during pregnancy is the risk of transmission to the infants - vertical
transmission. This transmission can occur through three possible routes: 1) transplacental, 2)
intrapartum exposure of the fetus to blood and other body fluids, or 3) breastfeeding. The
three routes are possible, the second being more probable. The vertical transmission rate has
been variably estimated between 20 to 40%. The risk factors for this transmission include
advanced maternal disease, acute primary HIV infection, high titer of HIV antigenemia, and
decreased CD4+ lymphocytes concentration.

Organism:
HIV is a newly evolved human pathogen. It belongs to retroviruses that contain
genomic RNA and the reverse transcriptase enzyme. The latter enzyme allows the viral RNA
to be transcribed into a DNA copy which is then integrated into the genome of the infected
cells and replicates with their division. The virus causing the majority of HIV infection is now
designated as HIV-1 after characterization of another closely similar viral antigen HIV-2 that
has caused some cases of AIDS.
HIV primarily infects the cells that express a certain surface antigen, CD4 antigen,
predominantly CD4-positive T lymphocytes and monocytes / machrophages, Langhans’ cells
of the skin and some brain cells. An envelope glycoprotein of HIV binds to CD4 in very
specific avid method. The CD4 acts as a receptor of the virus. Following viral entry into the
cells, and under the effect of the reverse transcriptase the viral RNA is transcribed into a
proviral DNA that is brought to the nucleus and integrated into host cell chromosome. After
integration of the proviral DNA in the genome of the infected cells, the infection remains
latent for a long time in the genome of these cells. These latently infected cells can elude the
immune system for many years, resulting in the long incubation period and latent phase
associated with AIDS. The latently infected cells may later be activated by factors that are not
yet clearly known and enter the productive stage with active viral replication.
Once activation occurs, the proviral DNA makes viral RNA and proteins that are
subsequently assembled at the cell surface, and released as infectious viral bodies through
budding. With the onset of HIV replication, the CD4+cells (T-helper lymphocytes) are killed.
The HIV envelope glycoprotein is believed to have a major role in killing CD+cells. This
destruction of these lymphocytes leads to cell-mediated immunologic deficits that results in
the opportunistic infections associated with AIDS.

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Clinical features of HIV infection

HIV infection produces a wide spectrum of disease. While AIDS is the lethal end
stage of this spectrum. AIDS is the tip of the iceberg, representing the minority of HIV
infected individuals.
1. Primary infection is characterized by high-grade viremia. After an average 14-week
incubation period, many patients experience symptoms of primary infection, a self-
limited febrile nonspecific illness that resembles mononucleosis. This comprises
pharyngitis, general lymph node enlargement, artherlgia, myalgia, lethargy, anorexia and
malaise. It may comprise neurologic manifestations including headache/ retroorbital pain,
meningioencephalitis, and peripheral neuritis. Skin manifestations may be associated
including erythematous maculopapular rash, diffuse urticaria, alpopecia. Nausea and
diarrhea may occur.
2. After this the HIV infection remains asymptomatic for a long but variable duration of
time called the latent phase. Typically this lasts for 7-11 years (can be longer) before
development of overt immunodeficiency. In these patients there is little formation of HIV
virus by the infected cells. These patients are, however, seropositive for HIV and
constitute the largest group of infected individuals. They may show generalized
lymphadenopathy or thrombocytopenic purpura. All of them are eventually going to
develop AIDS related complex (ARC), or AIDS.
3. The last stage of HIV infection is AIDS. A person is said to have AIDS when the absolute
CD4+cell count is less than 200/dl or when one of a list of illnesses associated with
immunosuppression is diagnosed despite the lack of an underlying reason for this
suppression such as age, malignancy, or immunosuppressive medication. These illnesses
include key infections such as Pneumocystis carinii pneumonia, disseminated viral
infections, unusual protozoal and helminithic infections, and typical and atypical
mycobacterial infections (including tuberculosis). They also include atypical
malignancies such as Kaposi’s sarcoma (a rare skin malignancy), non-Hodgkin’s
lymphoma, primary brain lymphoma, and a number of other clinical findings and diseases
indicative of a defect in cell- mediated immunity. This may be associated with dementia
and wasting syndrome, intractable diarrhea and fever. Persistent vulvovaginal candidiasis
bacterial vaginosis, invasive and severe cervical CIN and PID have been added to the list
of HIV-related conditions. It is assumed that all infected persons will eventually acquire
AIDS and die of it despite maximal efforts to control associated conditions and attempts
to prolong the life by antiretrovirus drugs.

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Studies have not confirmed that the course of progression of the disease is influenced
by pregnancy. Women with AIDS are however more likely to have increased incidence of
preterm labor, low birth weight, and still birth.

Diagnosis
- The diagnosis may be suggested by the clinical symptoms and signs, e.g. unexplained
wasting, generalized lymphoadenopathy and rare infections and malignancies. However,
the majority of cases are diagnosed by screening of asymptomatic individuals who have
an increased risk of HIV infection. Diagnostic tests for HIV include antibody testing,
antigen detection, viral culture, polymerase chain reaction (PCR), and immune function
tests.
- Antibodies against HIV can be detected by enzyme-linked immunoabsorbant assay
(ELISA), or immunofuorscent antibody (IFA). The ELISA test is highly sensitive and
specific. However, to cover for the rare false positive diagnosis a confirmatory test is
required e.g. Western blot. The latter is a gel chromatography that spreads apart the
different antigens in the virus and allows their detection by specific antibodies.
- Viral culture is expensive and not widely available.
- Tests for detection of certain antigenic proteins in the viral genome, utilize mainly
monoclonal antibodies. The common antigen searched for is the p24 antigen utilizing the
anti-p24 antibodies. These are highly sensitive and of special value in detection of vertical
transmission in the newborn. Vertical transmission cannot be diagnosed by presence of
viral antibodies in the infant blood; maternal antibodies can persist in the blood of the
offspring up to 15 months.
- PCR is an amplification of viral DNA and allows a rapid detection of a small amount of
HIV.
- Suppression of cellular immunity is assessed by counting the CD4+ cells in peripheral
blood. Count of CD4+ lymphocytes of <500 is associated with increased risk of
developing HIV related manifestation, counts less than 200 is present in patients with
AIDS.

Management and prevention

At the present time, prophylaxis and treatment of HIV are not very effective, hence
the rapidly spreading pandemic.
Prophylaxis includes means to prevent transmission of disease, and comprises the
following measures:
- Careful screening of donated blood and blood products.
- Avoidance of reuse of injection needles and syringes.

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- Safe sexual practices.

- Condom use is the most effective means of preventing sexual transmission.
Female condom is less effective.
- Screening high-risk groups.
- Health education - and careful counseling of infected persons.
- An effective vaccine has not been yet developed.
- Zidovudine (AZT) was the first antiretroviral drug used for treatment of patients
with HIV infection. AZT is a thymidine analogue that inhibits the reverse
transcriptase enzyme of HIV and reduces the rate of HIV replication. Zidovudine
reduces the frequency and severity of opportunistic infection, the rate of vertical
transmission and early mortality of AIDS. However, it cannot achieve permanent
cure and is an expensive treatment, not available to big masses of patients in
developing countries.
- Prophylaxis against opportunistic infection including screening for these diseases
and vaccinations (hepatitis B, pneumococcal and influenza and frequent cervical
smears).

Other sexually transmitted diseases

- Trichomoniasis (see later under vaginitis).
- Vulvovaginal candidiase (see later under vaginitis).
- Urinary tract infection (see later).
- Hepatitis B virus (HBV) infection.

Specific non-sexually transmitted Infections

A specific infection causes a specific pathology. Most sexually transmitted infections
are specific infections. Two other important specific infections of the genital tract, which are
not sexually transmitted, remain to be discussed: tuberculosis and schistosomiasis.

Tuberculosis of the genital tract

§ Organism and Mode of infection
Tuberculosis is caused by Mycobacterium tuberculosis. Two types of tuberculosis
bacillus are involved. The bovine bacillus is transmitted through cattle milk and the portal of
entry is the intestine. The human type is an airborn infection and the lung is its portal of entry
in the body. Tuberculosis of the female genital tract is common amongst all communities
where pulmonary and other forms of extragenital tuberculosis are prevalent, like in Egypt.
Genital tract infection is commonly caused by the human subtype of M. tuberculosis. After

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wide use of specific antituberculous chemotherapy there had been a decline in the incidence
of tuberculosis in many parts of the developed countries. However, there is a resurgence of
tuberculosis in recent years, which may be secondary to the pandemic of HIV infection and
the associated compromised immunity, and appearance of resistant strains.
Genital tuberculosis nearly always represents a spread from a focus elsewhere in the
body, but the spread to the genital tract takes place at a very early stage of the disease -
usually in adolescence or early maturity. At least 50% of cases of genital tuberculosis
represent a postprimary infection i.e. spread from a primary focus (which results from the
first encounter with this infection). In communities where tuberculosis is prevalent, like in
Egypt, a good percentage of the population has a primary focus at young age. This focus can
be in the lung or mediastinal lymph nodes, intestines or mesenteric lymph nodes (that is why
the majority of the population are tuberculin positive). Such lesions rapidly heal
unrecognized. However, a postprimary bacteremia may occur and the organism may settle in
the genital tract usually in the fallopian tubes. There, the infection remains dormant for some
time until it flares up in a subsequent stage of life due to undermined bodily resistance.
However, about 50 percent of affected women with genital tuberculosis give a present
or past history of recognized extragenital infection, usually pulmonary. These represent
secondary tuberculosis i.e. resulting from a second encounter with tuberculosis infection,
after having the primary focus healed.
The tubercle bacilli reach the genital tract by one of the following mechanisms:
1. Bloodstream
This mechanism accounts for the majority of cases; the spread occurs from a
primary or secondary lesion in the lungs, mediastinal or mesenteric lymph nodes,
urinary tract, bones and joints in that order.
2. Descending
In this type, the infection reaches the pelvic organs by direct or lymphatic
spread from infected adjacent organs such as the peritoneum, bowel and mesentric
nodes.
3. Ascending
This is a rare and may be hypothetical mode of infection caused by sexual
intercourse with a male having genital tuberculosis.
§ Pathology
Any part of the genital tract can be affected but the common sites are the fallopian
tubes, the endometrium and ovaries. The tubes are involved in at least 90% of cases. The
infection seems to begin in the submucosa of the lateral part of the tubes, which is richly
vascularized, and then gradually spreads inwards towards the endometrium which is involved

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in 50% of cases. The finding of endometrial tuberculosis almost always means the presence of
tuberculous salpingitis.
The genital infection is usually indolent and may remain unrecognized for a long time
until discovered during investigation of infertility. A rapid or acute course is rare. This is
occasionally seen in the postpartal period when the disease appears to have occurred de novo,
has an acute course, and is frequently associated with tuberculous peritonitis.
The following parts of the genital tract may be affected by tuberculosis:
Fallopian tube
The pathology is almost always bilateral. The appearance of tuberculosis salpingitis
varies widely and depends upon whether the main brunt of affection is on the endosalpinx, on
the serosal covering or on all the layers. Endosalpingitis occurs when the infection is blood
born while perisalpingitis occurs when there has been spread from peritoneum and intestines.
- The tube may look externally normal but usually has a medial block.
- The tube may look inflamed, red, edematous and swollen.
- Tubercles may be seen on the peritoneal surfaces. These can appear in crops or
patches or have a miliary spread over the pelvic peritoneum. Tubercles on the
peritoneal surfaces seen during laparoscopy and laparotomy suggest the diagnosis of
tuberculosis but does not always mean so ; they can be caused by schistosomiasis,
oil granuloma following hystersalpingography or talc granulomata resulting from
surgical gloves at a previous laparotomy, or ascending from the vagina from
examining gloves. Biopsy is needed to confirm the tuberculous nature of tubercles
(unless associated with other evident tuberculous pathology) before initiating the
long-term antituberculous treatment.
- The tube can be fibrosed and shrunken.
- Variable amount of pelvic adhesions can be found.
- The tubes may be patent.
- However, tubal block is common and is usually multiple resulting in the tubal wall
appearing thickened and shotty.
- Sometimes a localized closure at the outer end results in the formation of
hydrosalpinx or pyosalpinx with thick fibrous wall, which can be calcified. A
tuberculous pyosalpinx can reach a big dimension and may result in the patient
having a pelvi-abdominal swelling.
- Salpingitis isthmica nodosa can be a feature of tuberculous salpingitis. The
juxtauterine part of the tube is thickened, shotty and fibrous.
- Secondary infection is often present and may itself account for symptoms or for
exacerbation of the disease.

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Uterus
Tuberculous endometritis is usually recognized by histological and bacteriological
examination of endometrial biopsy. Rarely typical tuberculous ulcer is seen in hysterectomy
specimen. Extensive tuberculous of the uterus associated with fibrous obliteration can result
in tuberculous pyometra or multiple abscess formation.
Ovaries
The ovaries are involved in at least 30% of cases of tuberculous salpingitis. The
disease can take the form of surface tubercles, adhesions and thickening of the ovarian
capsule, retention cysts and rarely caseating abscess.
Vulva Vagina and cervix
Tuberculosis in these sites is rare and is frequently ulcerative. The tuberculous ulcers
are indolent, and superficial with undermined edge, soft base and ischemic margin. A
hypertrophic lesion, which easily bleeds and simulates cancer is a rare type.

§ Clinical picture
Genital tuberculosis is not an uncommon diagnosis in our practice in Egypt and is
increasingly made after the advent of laparoscopy in the investigation of infertility. The
disease is often silent and may be present for 20 years without producing any symptoms, the
woman remaining in apparently excellent health. The pelvic organs also feel normal on
bimanual examination. The following features may, however, suggest the disease:
1. Sterility
The presence of genital tuberculosis is usually made during investigation of
infertility. It is usually a primary infertility and is usually caused by damage of the tubes
and ovaries.
2. Menstrual disturbance
In approximately 50% of cases the menstrual function is normal. In the others the disease
can cause amenorrhea and rarely menorrhagia. The mechanisms involved in causing such
menstrual abnormalities are not clear and may be related to certain tuberculous toxins,
and ovarian or endometrial involvement. Dysmenorrhea is rare.
3. Intermenstrual discharge may be associated due to pelvic congestion or endometrial
involvement. It can be blood tinged.
4. Chronic pelvic pain is suggestive if it cannot be otherwise explained and dates back to
adolescence. Commonly such young women give the history of appendectomy done on
the basis of atypical clinical picture.
5. General disturbance of malaise, loss of weight, mild grade chronic pyrexia and night
sweats are rarely seen, and only during active phase of the disease.

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6. Acute or subacute postpartum pelvic or generalized peritonitis is a rare clinical

presentation, but has been repeatedly showing in the author’s practice.
7. History of healed tuberculosis elsewhere - (healed tuberculous sinuses over inguinal or
supraclavicular lymph nodes).

§ Diagnosis
- Gynecologists in Egypt should have a high index of suspicion for tuberculosis of
genital tract. The condition should be suspected in 1) cases of primary infertility, 2)
cases of amenorrhea for which other causes are not present, 3) chronic pelvic pain or
PID in absence of the possibility of sexually transmitted infection and 4) chronic
salpingitis or chronic peritonititis which fail to respond to ordinary antibiotics.
- Hystrosalpingography may show suggestive but not conclusive features (see under
Infertility). However, if tuberculosis is suspected hystrosalpingography is
contraindicated; it can result in flaring up of salpingitis.
- The diagnosis of genital tuberculosis is done during laparoscopic investigation of
infertility. This needs to be documented by histological and bacteriological
examination of peritoneal surfaces and endometrial biopsy (obtained by D & C). The
material obtained in these two types of biopsy should be divided into two portions:
One portion is fixed and sectioned for microscopic study. The finding of
epithelioid clusters with giant cells is highly suggestive but not conclusive evidence
unless tubercle bacilli can also be demonstrated in specially stained preparation (Zeel
Nellsen stain).
The other portion is sent for culture and guinea pig innucleation; and
antibiotic sensitivity of isolated bacillus.
Material for bacteriological examination can be also obtained through
peritoneal washing, or endometrial suction lavage or from the first-day menstrual
discharge. However, with such specimens a negative result is less conclusive.
- X ray chest and a search of urine for tuberculous bacillus are required.

§ Treatment
Hospitalization is only required in an active pelvic disease and when there is active
tuberculosis elsewhere. The husband is frequently worried about the possibility of sexual
transmission. He can safely reassured that this is exceptionally rare.
Antituberculous antibiotics should be given for at least 12 months. Three drugs are
usually given at the beginning because tests of sensitivity to antibiotic are usually lacking.
This is in order to avoid the risk of development of bacterial resistance. Patients are usually
given isoniazid (INAH), 600 mg daily, rifampicin, 600 mg daily (these are usually combined

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Genital tract infections

in one capsule e.g. Rimactazide 300), and either ethambutol, 1000 mg daily or streptomycin 1
g daily by injection. If the last is used, it is discontinued after 3 months for fear of an effect on
the eighth nerve. After 3 months of treatment maintenance is possible by using two drugs
only. Incidentally, patients under rifampicin should be warned that their urine and other body
secretion should become orange or red colored.
After the end of treatment repeat laparoscopy and D & C biopsy are required to ensure
cure.
Surgical intervention is occasionally needed. The indications are:
1. Progression or persistence of active symptomatic disease despite adequate medical
treatment.
2. Presence of large inflammatory mass - pyosalpinx, ovarian abscess pyometra.
3. Persistence of bleeding and/or pain despite adequate medical treatment.
4. A localized hypertrophic lesion in the vulva or cervix that fails to resolve.
5. Salpingoplasty for blocked tubes is rarely indicated because the pathology of
tuberculosis is multiple and destroys several layers of the tubal wall. Correction of
tuberculous perisalpingitis may rarely be attempted. Moreover, if tubal potency is
established, ectopic pregnancy is a likely consequence. IVF-ET is usually required
after completed medical treatment. Any hydrosalpinx should be removed before IVF-
ET.
Contraindications to surgery
- Active tuberculosis elsewhere in the body.
- Presence of dense adhesion around the pelvic organ may render surgery really difficult.
Technique
For tuberculosis of upper genital tract requiring surgical management, total
hysterectomy and bilateral salpongooopherectomy is required unless the patient is younger
than 45 -- when one ovary may be left if it looks normal. Drains should not be left in the
wound. Treatment with antituberculous drugs should be given for 2 months before the surgery
and for 12 months after.

Schistosomiasis (Bilharziasis) of genital tract

Bilharziasis of the female genital tract is relatively uncommon. Schistomyasis is
endemic in Egypt and is more frequently seen in Lower Egypt than in Upper Egypt.. The sites
of predilection in the genital system of the female are the vulva, cervix and vagina, while the
body of the uterus, fallopian tubes, ovaries and pelvic peritoneum are rare sites.
Causative organism: The disease is caused by a bisexual nematode schistosoma that
inhabit the vascular system of man. Two species exist in Egypt: Schistosoma hematobium,

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Genital tract infections

which inhabits the vascular system of the urinary tract and is one usually causing genital
schistosomiasis. Schistosoma mansoni has its habitat in the portal circulation. S. mansoni is
rarely seen in Upper Egypt, while the two types are prevalent in the Delta depending on the
presence of certain fresh water snails. The bilharzial ova are passed in the urine and feces of
patients. In fresh water the ova hatch and yield mercedia which infect certain snails which are
their secondary hosts. S. hematobium inhabit the snail Bullinus truncatus, while S. mansoni
inhabit the snail Planorbis boissyi. In the snail the parasite asexually multiplies to produce a
big number of tailed cercaria, which are passed to water, and is the infective stage to man.
Man is the definitive host where sexual proliferation occurs. Girls and women in rural areas
frequently come in contact with fresh water during washing their clothes or utensils or
playing in the water of ditches and drains. The cercarias pierce the skin and travel in the veins
towards the right heart, and through the lungs to the arterial side. Only the cercaria that
manage to reach the liver survive; the rest perish. In the portal circulation the worms reach
maturity. The coupled female and male travel (the female is accommodated in a groove in the
body of the male) in the portal blood vessels against the blood stream towards a hollow viscus
like large bowel and rectum and through anastomostic channels to the vesical venous
plexuses. When the veins become too narrow to accommodate the couple, the finer female
progresses alone to lay its eggs in terminal venules near the lumens. The eggs are deposited in
the wall of the hollow viscera where they cause the bilharzial lesions and can be passed to the
exterior to complete the life cycle of this organism. The rich communications between vesical
and vaginal venous plexuses (and to a lesser extent with papiniform plexuses) allows some
worms and ova of S. hematobium to reach the genital tract mainly the vagina, vulva and
cervix. The anastmoses between hemorrhoidal venous plexus communicate with the
uterovaginal venous plexuses and can rarely carry S. mansoni ova to the genital tract.

Pathology
The presence of ova in the tissue causes intense local reaction. Bilharzial pathology
classically passes into three stages:
1. Stage of cellular infiltration: This takes either a localized or a diffuse picture:
a. The localized lesions consist of multiple bilharzial tubercles. Each has a
bilharzial ovum in its center, which is surrounded by epithelioid cells, giant
cells, esonophils and lymphocytes, usually with an outer zone of fibroblastic
proliferation. Old tubercles get progressively fibrotic. Aggregation of
bilharzial tubercles forms a bilharzial nodule, which projects into the lumen
of the vesicus. The overlying mucosa becomes hypertrophied, hyperemic and
edematous, nodules coalesce to form papilloma. A patch of Calcified ova just

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beneath the surface mucous membranes give the appearance of “sandy

patches” i.e. the appearance of sand under water.
b. Diffuse lesions -- (bilharzial granulation tissue): This is a diffuse
granulomatous inflammatory reaction. It is the type seen in the endometrium.
2. Stage of ulceration: The development of bilharzial ulceration results from either
fibrosis or endarteritis obliterans or from secondary infection. The first
mechanism results in small superficial ulcers that readily heal. The second
mechanism gives rise to deep ulcers that heal with difficulty and spread to
underlying tissue.
3. Stage of fibrosis: The bilharzial granulation tissue and the infected ulcers slowly
heal and result in excessive fibrosis and stricture formations.

Clinical picture
The patient is usually from a rural background and gives history of contact with water
ditches and drains. There can be symptoms of associated urinary bilharziasis.
Bilharziasis of the vulva
The vulva is the second common site of bilharzial affection. The lesion is usually
hyperytrophic (or papillomatous) and less commonly ulcerative.
1. The papillomata may involve the labia majora, labia minora, perineum, clitoris or mons
venerium. They are usually multiple dendiritic, occasionally cauliflower-like, firm in
consistency, occasionally gritty. Young lesions are congested, red and bleed on contact
and may be associated with edema. Long-standing lesions are white, fibrotic with
occasional areas of gritty calcification. They resemble chondyloma accuminate (venereal
warts) and may be mistaken for vulval carcinoma. They cause discharge and bleeding and
occasionally intense itching. The relation of vulval bilharziasis to carcinoma is not
definite.
2. The ulcerative variety presents with multiple ulcers, which have wet, gritty floors i.e.
sandy patches and is seen on the labia majora and minora. They cause intense itching and
soreness.
Bilharziasis of the vagina
The vagina is an uncommon site of bilharziasis. The lesions are usually hypertrophic,
papillomatous and involve the upper vagina. Sandy patches and infected ulcer with granular
floor may be seen. The condition causes serosanguinous discharge, soreness, itching, and
dyspareunia besides the swelling. Old lesions may cause strictures in the vagina; urinary
fistulas of bilharzial origin have been described.

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Bilharziasis of the cervix uteri

The portio-vaginalis of the cervix is the commonest site of genital bilharziasis. The
lesions are either papillomata or ulcerative. Bilharzial pappilomata may be red,
granulomatous or firm, fibrotic. They are multiple and present in groups. The lesion may
simulate cancer. It causes discharge, which is infected, blood tinged and foul smelling. They
can cause severe bleeding.
The ulcers may be solitary or multiple and are usually superficial. When secondary
infected, they become deep, indurated and readily bleed upon contact; thus simulating
carcinoma.
Bilharziasis of the uterine corpus
Bilharziasis of the uterine corpus is a rare entity. Bilharzial tubercles are occasionally
reported in endometrial biopsy, but this is rare. The serosa of the uterus may be involved as
part of miliary bilharzial tubercles in the pelvic peritoneum.
Bilharziasis of the tubes, ovaries and pelvic peritoneum
This is an uncommon affection. It simulates chronic salpingooophoritis and is
detected in biopsy specimens obtained during laparoscopy done in investigating infertility
when a bilharzial nature is detected. Multiple tubercles are seen on serosal surfaces of the
tubes, ovary and pelvis. The multiple tubercles are white and firm and are associated with
perisalpingitis. Bilharzial nodules may also involve the muscle wall of the tube and the
substance of the ovary.

Relationship of genital bilharziasis and cancer

Carcinomas of the cervix, vulva and vagina have been repeatedly reported in
association with bilharzial pathology. However, a causal relationship, as that in the case of
carcinoma of urinary bladder, has not been established.

Diagnosis
- The diagnosis is suggested by association of bilharziasis in the urinary tract and rectum.
- Bilharzial ova can be found in scrapings from lesions or found in vaginal smears or
colposcopic examination.
- Bilharzial lesion can be detected in biopsy specimen obtained from lesions of the
endometrium, tubes or peritoneum (during laparoscopy).

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Treatment
As a result of preventive measures, and encouragement of mass treatment of
population in endemic areas, bilharzial lesions are becoming less commonly seen in our
practice.
a. Medical treatment
Praziquantel (Biltricide) is the usual treatment, and is effective against both
types of schistosomal infection. The dose is 40 mg/kg as a single oral dose. The dose
may need be repeated after one month in patients with extensive pathology.
Antibiotics are given for secondary infections.
b. Surgical management
Excision is required for residual masses and infected lesion. Surgical
correction of stricture in the vagina (a rare entity) may be met with.

Infections as they Affect individual

organs
Vulvitis
a. Infantile and Senile vulvitis and vulvovaginitis:
When the vulval and vaginal epithelium is inactive and thin, as in childhood and old
age, any of the organisms to which it is normally resistant can cause vulvitis and
vulvovaginitis. Lack of cleanliness predispose to the infection. The vulval parts are red
excoriated and covered by discharge. Vaginal discharge is excessive, purulent, foul smelling
and may be blood tinged. There is soreness and rarely pruritus. Scalding micturition and
urgency of micturition may be present.
In infants and children the labia minora may stick to each other and appear as if fused.
However, the labia can be easily separated by gentle traction, exposing congested inflamed
vaginal introitus.
Infantile and senile vulvovaginitis requires administration of estrogen, both
systemically and as local cream or peccaries. This builds up the thickness and resistance of
the epithelium. Antibiotic treatment is frequently not required (see also under senile
vaginitis).
b. Frunculosis
Infection of vulval hair follicles leads to boils and carbuncles, which are sometimes
recurrent. The infecting organisms are usually staphylococci, but other organisms may be

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Genital tract infections

involved. The condition is predisposed to by lack of cleanliness and by diabetes mellitus. In

presence of active lesion, a full course of antibiotics is needed after identifying the infecting
organism. To prevent recurrences scrupulous attention to cleanliness is required including
boiling of underwear and frequent changes. Local antiseptic creams of e.g. chlorhexidine are
used.
Single abscesses frequently represent infection of a sebaceous cyst, which have the same
treatment like a boil. Recurrence in the same site suggests the need for excision of existing
cyst.

c. Tinea Cruris
This skin condition is common in obese women and in hot climates. It is caused by a
variety of species of tinea, mainly Epidermophyton inguinale. The skin of the vulva
perineum, mons and inner side of the upper thighs become dark in color and sodden; the
advancing edge may be red and slightly raised. The patient complains of irritation, soreness
and may be of a bad smell. Similar affections can be present in other skin folds -- under the
breasts and axillae, or other mycophytic infection like tinea pedis or paronychia may be
associated. Similar affections may be present in the husband. The condition is chronic and
difficult to eradicate.
Treatment can be achieved by local application of miconazale nitrate (or other
antimycotic drugs; cream or powder) twice daily for at least one month, or for one week after
disappearance of the lesion. Systemic (oral) use of antimycotic drugs (with one of the orally
active azoles) is needed in lesions in multiple sites and when compliance with topical
treatment is difficult. The treatment needs to be continued for two weeks or longer.
d. Recurrent (cyclical) buccal and vulval ulcerations
This is not an uncommon condition. Superficial ulcers, which are painful, occur singly
or in crops in the mucous membrane of the mouth and inner vulva. They may be recurrent and
may be cyclic coinciding with menstruation. The ulcers, though similar to herpetic ulcers, are
not sexually transmitted. The etiology is not clear and there can be an element of allergy.
Their treatment is usually unsatisfactory and includes attention to general health, local
antiseptic and astringents, antihistaminics, corticosteroids, and antiviral drugs e.g. Cyclovir.
When recurrent buccal and genital ulcers are associated with recurrent iridocyclitis
this constitutes Behcet’s syndrome.
e. Candidal vulvitis
Cadidiasis involves both the vulva and vagina (see later). The vulval skin affection causes
intense pruritus. The appearance of the skin varies from erythema, purple appearance, to
pallor and edema. The condition is predisposed to by diabetes mellitus (diabetic vulvitis),
since presence of sugar in the area of the vulva favors the growth of candida albicans.

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Candidiasis frequently follows the use of antibiotics, which interfere with normal flora of the
vagina and bowel, allowing the growth of candida not affected by the antibiotics.
f. Sexually transmitted infections (see above).
g. Bilharzial lesion (see above).
h. Tuberculosis lesions (see above).
i. Elephantiasis of the vulva
This condition is rarely seen in our practice. It represents chronic lymphatic edema,
which is associated with thickening and hypertrophy of the vulval skin. The skin is rough,
warty and sodden. True elephantiasis is caused by parasitic infestation with the worm
Wuchereria bancrofti. False elephantiasis can be caused by any cause of chronic lymphatic
obstruction. Chronic infection that heals with fibrosis can cause elephantiasis e.g. bilharziasis,
tuberculosis, lymphgranuloma venereum of syphilis.
If the condition is severe enough to cause discomfort and if persisting after specific
treatment of the cause, the affected parts can be excised. However, recurrence is likely unless
antihelminthic treatment is given.

Bartholinitis
Etiology
Bartholinitis are one of the lesions of gonorrhea, but can also be caused by E. coli,
Staphylococcus, Streptococcus fecales, Clamydia trachomatis, Trichomonas vaginalis, and
may be other organisms.
Pathology and clinical picture
Both the duct and glandular acini are involved in the acute inflammation. The mouth
of the duct can be seen as a small red spot, the macula on the inner side of the labium minus.
The gland gets swollen and the overlying vulval skin is edematous, red and very tender. The
condition causes severe pain, dysuria and may be urinary retention. Acute bartholinitis may
resolve spontaneously but frequently an abscess forms and ultimately discharge, usually
through the lower vaginal wall. After the acute phase resolves the infection may go in a
chronic phase which can take one of two forms:
1. Chronic bartholinitis in which the gland gets indurated and may be tender and can be
felt as a small pea underneath the posterior part of the labium major; a palpable
bartholin gland is a chronically infected one, or rarely indicates a neoplasm.
2. Bartholin cyst: As a result of postinflammatory fibrosis, the duct can get closed and
the secretion accumulates resulting in a cyst formation that can reach the size of a hen’s
egg. The cyst opens up the folds of labia minora and majora and displaces the vulval
slit to the other side - resulting in S-shaped appearance of the vulva.

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The two types of chronic bartholinitis predispose to acute recurrences of acute

bartholinitis that can be repeated until the gland has been excised.

Treatment
Acute bartholinitis is treated with broad-spectrum antibiotics, hot fomentation and sitz
bathes. Once an abscess has formed, it should be drained by incision made on the outside of
the vulva before it opens on the inside of the vagina; this can leave behind a tender scar that
may cause dyspareunia.
Marsupialization of the edges of the abscess cavity to the skin may be done in order
to provide permanent drainage preventing cyst formation.
Excision of the gland is done after subsidence of the acute phase. This is indicated for
recurrent bartholinitis or bartholin cyst. The cyst is better excised intact. The area is vascular
and a small drain is better left for few days. The operation is not as simple as expected from
the superficial location of the lesion; the area is very vascular.

Vaginitis
Vaginitis is the most common gynecological complaint.
The common types of vaginitis include:
1. Vulvovaginitis in infancy and childhood
The common age is 1 to 5 years. The condition is predisposed to by thinness and weak
resistance of the vaginal skin and lack of glycogen content in the epithelial cells.
Consequently the vaginal pH is less acidic. This allows growth of pathogens carried to the
area by the hands or dirty clothes. A variety of organisms can be involved including
staphalycocci, streptococci, E. coli, pneumococci, C. trachomatis, trichomonas vaginal,
candida albicans or even gonococci. Threadworms (Enterobius vermicularis) can infect the
vagina, migrating to it from the anus. This can result in intractable type of vulvovaginitis until
the parasitic infestation is suspected and treated with specific antihelmenthic oral treatment.
Occasionally the basis of resistant vulvovaginitis of an infant is the presence of a
foreign body e.g. a matchstick self-introduced by the child during playing, or shreds of
clothing.
Clinical picture
The child is usually presented for purulent discharge. She may complain of soreness,
itching (causing her to scratch the area) or scalding micturition. The vulva is reddened,
sometimes edematous or bathed with discharge. If the discharge is blood-tinged, care should
be made to exclude: 1) presence of foreign body, 2) cervical polyp, 3) bilharzial papilloma or
4) even the rare sacroma botryoidis. The labia minora may be stuck together. They can be
easily separated apart leaving red, inflamed surfaces.

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Genital tract infections

Diagnosis
- On examination, the condition is clinically evident.
- Fine swab may be needed to detect the infecting organism.
- Rectal (little finger) examination is done if a foreign body is suspected. This can be
verified by ultrasonography.
- Examination under anesthesia may be rarely needed and utilizing a fine laparoscope
may help to verify an internal lesion.
- Recurrences need special attention and stool examination for parasites should be
done.

Treatment
- Treatment consists of administration of systemic antibiotics or antifungal treatment. A
very small dose of a weak estrogen like estriol, (50 mg half a tablet of Ovestine) may
be given daily for 10 days in order to build up the thickness and resistance of the
vaginal skin. The mother should be alerted to the possibility of occurrence of vaginal
bleeding.
- It is necessary to take steps to prevent spread of infection to other children or the
patient’s eyes.

2. Senile (atrophic) vaginitis

The condition is caused by the atrophy and loss of resistance of the vaginal skin that
occurs in some women after the menopause. The vaginal pH becomes less acidic. This allows
invasion by pyogenic organisms.
Pathology
The vagina shows numerous red specks against a pale general ground. Purulent
vaginal discharge is seen covering the vagina; mobbing it out may leave superficial
excoriations. Senile vaginitis should not be diagnosed on the basis of presence of specked
vagina alone for this can be a normal climacteric change. The anterior and posterior vaginal
walls may rarely stick together, but these can be readily broken apart leaving oozing surfaces.
The condition can be associated with vulvitis commonly resulting in narrowing, or
endometritis, which may result in pyometra.
Clinical features and diagnosis
- Postmenopausal yellowish discharge that can be copious, and may be blood tinged.

- Vaginal soreness, heaviness or weight, and dyspareunia.

- Frequent, burning, urgent micturition, may be complained of due to associated

atrophic cystitis.

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Genital tract infections

- Slight vaginal bleeding may be associated. Such bleeding should not be ascribed to
atrophic vaginitis alone until after the exclusion of endometrial pathology like senile
endometritis and endometrial cancer. Such cases should receive the usual diagnostic
workup of postmenopausal bleeding including transvaginal sonography, examination
under anesthesia and D & C. Even if vaginitis is present, the patient may still have
endometrial cancer as well.
Treatment
- Estrogen (e.g. primarine 0.625 mg) can be given orally for 4 weeks. This builds up the
thickness and resistance of the vagina. The course may need be repeated twice or thrice
after one week interval during which the patient expects to have vaginal bleeding.
- Antibiotics are not needed.
- The need to diagnose an associated endometrial cancer is reemphasized.
- The opportunity can be taken to consider the need for a long-term prophylactic
postmenopausal hormone therapy (see under menopause). This will need addition of a
progestogen dose during at least 10 - 12 days of estrogen intake, if not continuously, in
order to prevent the risk of causing endometrial hyperplasia and carcinoma.

3. Bacterial Vaginosis
Bacterial vaginosis (BV) formerly known as Gardnerella vaginalis vaginitis and
nonspecific vaginitis is the commonest type of vaginitis. It is characterized by excessive
discharge and odor. Despite the fact that BV is predominantly seen in sexually active
premenopausal women, it does not appear to be transmitted by sexual intercourse; it is not
considered as one of STDs.
Etiology
Bacterial vaginosis results from a shift in the bacterial flora from the normal
predominantly-lactobacilli one to a polymicrobial flora including high concentrations of the
following bacteria:
- Garderella vaginalis (formerly called haemophylus vaginalis): an aerobic gram-negative
coccobacillus.
- Anaerobic gram-negative bacilli like bacteroides species.
- Anaerobic gram-positive cocci like Peptostreptococcus species and Mobiluncus species.
- Mycoplasma hominis, and Ureaplasma urealyticum.
Many of the above members of microfloral mixture are present in low concentration
in the normal vaginal flora of asymptomatic women, and without attaining a critical
concentration these bacteria will not cause symptoms. The cause of this shift in the vaginal
flora is not clear. It cannot usually be ascribed to specific sexual contact. It may follow upon
acute illness and may be related to undermining of body resistance.

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Genital tract infections

The infection is a superficial mucosal one not causing defined pathological changes in
the vaginal wall.

Clinical features
1. No symptoms: as many as 50% of women with the above vaginal flora can be
asymptomatic.
2. Vaginal discharge: is the main symptom and is usually excessive, white, creamy, or
milky and homogenous, evident at the introitus and frequently of unpleasant, fishy odor.
The smell may be only noticeable at intercourse i.e. being a complained of the husband
(not noticed during clinical examination).
3. Itching is not present and local irritation is not marked.
4. When the discharge is mobbed away, the vagina looks normal.
Diagnosis
1. The clinical picture is suggestive.
2. The pH of the discharge is greater than 4.5.
Amine test: When one drop of KOH is added to one drop of the discharge, a foul
amine odor is produced (amine whiff).
3. Clue cells in direct wet preparation: a drop of normal saline is added to the discharge,
which is covered by a coverslip and examined by the high power of the microscope.
Such smear shows paucity of WBCs and predominance of clue cells. These are
vaginal epithelial cells, which are so heavily stippled with bacteria that the borders
are obscured; epithelial cells with few bacteria and clear borders should not be
identified as clue cells.
In clinical practice, the above three features are enough to make the diagnosis
and start the treatment in symptomatic women (see table).
4. Gram staining of vaginal secretion may be helpful. It shows numerous mixed bacteria
and paucity of lactobacilli. Clue cells may be seen. Mobiluncus may be identified as a
crescentic shaped rods
5. Bacterial cultures are not really helpful.

Table 4:Characteristics of the appearance of the vaginal discharge in normal women and
patients with various types of vaginitis; and the associated manifestations.

Feature Normal Bacterial Trichomonas Candida

Vaginosis
Appearance White, scanty, Whitish, creamy, Gray, yellow or white, Scanty, thick,
hetero-geneous, or milky, excessive curdy,
folecular ; high homogeneous, homogeneous, frothy White, adherent.

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Genital tract infections

viscosity. excessive. or milky/ creamy.

Vaginal skin Normal Normal Congested, edematous Congested and
edematous
PH < 4.5 > 4.5 > 4.5 < 4.5
Amine odor Absent Present Absent Absent
Clue cells Absent Present Absent Absent
Trichomonaes Absent Absent Present Absent
Mycelia Absent Absent Absent Present
Other _______ Odor Pruritus vulvae, odor, Pruritis vulvae
symptoms, or flea bitten
signs

BV has been associated with urinary tract infections, the use of vaginal diaphragm or
vaginal contraceptive sponge PID and posthysterectomy infections.
BV has been associated with complications of pregnancy, including, preterm labor,
premature rupture of membranes, intraamniotic infection and postpartum sepsis and PID.
However, these associations are not at all evidence-based. Clinical trials indicate, however
that in pregnant women who are at high risk of preterm delivery and who have had a
diagnosis of BV, giving treatment of BV may reduce the risk for prematurity.

Treatment
- Metronidazol 500 mg twice daily for 7 days.
OR
- Metronidadazole or secnidazole 2 g orally in one dose.
OR
- Metronidazol gel 0.75% twice a day for 5 days.
OR
- Clindamycin (e.g. Dalacin)vaginal cream 2% at bedtime for 7 days.
OR
- Clindamycin 300 mg orally twice a day for 7 days.

The CDC (Center for Disease Control in the USA) recommended a regimen for the
treatment of BV in pregnancy is metronidazole 250 mg orally three times daily for 7 days.

4. Candidal Vaginitis: Candidiasis

Candidal vaginitis is the second most common type of vaginitis in the childbearing
period.

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Genital tract infections

Etiology and Epidemiology

The condition is caused by the yeast-like organism, candida albicans. It is a gram-
positive fungus, which exists, in two associated forms: segmented mycelial threads and
clusters of spores. Other candida species may be rarely involved, notably C. glabrata. The
fungus thrives on carbohydrate containing acid medium; a pH < 4.5. C. albican is commonly
present in the vaginal flora of asymptomatic women (in 30 to 80%). The symptoms develop
when the growth of the fungus flares, i.e. a change from the carrier stage to infected stage.
Although instances suggestive of sexual transmission are apparent in the practice, candidiasis
is not considered an STD. This is because of high frequency of asymptomatic carriers,
The common predisposing factors for candidiasis include:
1. Glycosuria and diabetes mellitus.
2. Pregnancy; the mechanism is not clear -- may be the increased glycogen content of
the vaginal epithelium, or increased acidity of the vaginal transudate or the hormonal
milieu.
3. Obesity.
4. Recent use of antibiotics like ampicillin, tetracyclines or cephalosporins. These
suppress normal bacterial population and allow opportunistic colonizations of the
antibiotic-insensitive yeasts.
5. Corticosteroid therapy.
6. Immunosuppressive therapy including chemotherapy for cancer. Patients of AIDS
are having frequent recurrences of candidiasis.
7. An association of candidiasis and the use of combined oral contraceptives (COCs)
has been suggested, but has not been proven for low dose COCs.
8. Wearing tight nonporous underwear have been associated, and ascribed to increasing
local heat.
9. The first appearance of candidal vaginitis is frequently in the premenstrual period --
something suggesting an effect of hormonal milieu on the natural cellular immunity.
However, the symptoms may be temporarily relieved during menstruation itself
because of the alkalinity of menstrual blood.

Clinical picture
Candidal vulvitis or vulvovaginitis causes intense itching with minimal discharge. It
causes red areas on the vulva and vagina, which may be associated with edema. There is
white, thick, curdy (like curds of milk) discharge sticking to the vagina. Removal of the
discharge may leave behind superficial excoriations or fissures.
Diagnosis
- The clinical picture is usually sufficient.

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- PH is acid, < 4.5

- The diagnosis is confirmed by seeing the characteristic glistening micelial threads in
potassium hydroxide wet preparation: To a drop of the discharge on a slide a drop of
10% KOH is added and covered by a cover slip. The normal cellular elements are thus
lysed allowing the branching threads and buds of candida to be seen. This test may be
falsely negative in 30% of cases.
- Culture on special medium e.g. Sabouraud’s agar, is needed in recurrent cases.
Treatment
- Nystatin vaginal tablets administrated daily for 14 days has been the classical cheap
treatment of candidiasis, but is being increasingly replaced by the use of one of the azoles,
either topically or orally.
- Various Imadozoles (like clotrimazole, miconazole, butoconozole) and triazole are also
effective as 1 to 7 days pessary or cream treatment; with the shorter courses utilizing
higher dosage. All regimens seem to be equally effective with cure rate of 80%. Shorter
courses cause more rapid cure, and ensures compliance but may be associated with
increased rate of local allergy.
- Oral azoles can be used instead of topical treatment: either Ketoconazole for 5 days or a
single dose of Fluconazole. They are equally effective but the ketoconazole may cause
occasional mild hepatotoxicity. Oral azoles are contraindicated in pregnancy. Some
women prefer oral treatment to vaginal pessaries or creams.
- Initial good response is expected in the majority of cases but recurrence may occur in
about 20% of cases.

Recurrent vulvovaginal candidiasis (RVVC): is defined as four or more episodes of

symptomatic candidiasis per year. The causes for recurrences are not always clear and
include:
- Glycosuria and diabetes.
- Pregnancy
- Depression of cellular immunity.
- Recolonization from the intestinal tract.
- Reinfection from the husband.
- Enhanced local allergic response to candida.
- Infection by nonalbicans species like C. glabrata ; the treatment of this infection
requiring longer regimens of azoles.
- Harboring the candida in a reservoir in the cervical crypts.
The following lines can be used for management of RVVC:

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- Oral plus topical treatment by azoles.

- Longer courses of oral azoles in reduced dose, e.g. ketaconazole 100 mg daily or
fluconazole once weekly for 3 to 6 months.
- Simultaneous treatment of the husband.
- Cautary of the endocervix may be rarely resorted to.
- Boric acid in gel capsules or vaginal douches.
- Application of gentian violet (1% in water) directly to the vaginal vault at weekly
interval may work in recurrent cases. However, the color is messy and frequently
unacceptable.
- Investigation and correction for any state of immunosuppression. Interest of RVVC
has been maximized after HIV pandemic.

5. Trichomonasis vaginalis vaginitis: Trichomoniasis

Epidemiology
This is the third most common type of vaginitis in the childbearing period. It is one of
the sexually transmitted diseases, though this is not always the case. Other STDs may be
present as well, notably gonorrheal and chlamydial infection. Risk factors associated with
sexual activity like a new partner, multiple partners and multiple partners for the sexual
partner increase the chances of contracting trichomonas.
Trichomonas vaginalis can be present in the vagina of 2 - 3% of asymptomatic
women, but the prevalence is much higher in high-risk groups, e.g. the attendees of the
venereal disease clinics. Trichomoniasis is occasionally also associated with BV.

Etiology
Trichomonas vaginalis is a member of a large group of other trichomonades which
does not cause vaginitis. T. vaginalis is a flagellated protozoon which is ovoid, 15 - 20 um in
length and 8 - 10 um in width, with four anterior flagellae and an axostyle which
longitudinally traverses its body to end in a spike. In vaginitis the parasite is invariably
accompanied by staphylococci, streptococci or coliform organisms but it is the trichomonas
which causes the vaginitis.
Three modes of infection are possible:
1. The infection is often contracted during intercourse with a male harbouring the
organisms in the urethra, or prostate. This male is usually symptom-free. The
incubation period is approximately 20 days.
2. Vaginal trichomoniasis is not always a sexually transmitted condition. It is not
uncommon among children and unmarried and old women. Transfer of the organism

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from one individual to another by indirect contacts through domestic towels, bed
linen, personal clothing, lavatory seats, bath tubs and swimming pools is possible.
The infection can be transferred from one client to another in a gynecological clinic,
which does not utilize sterilized or disposable specula and gloves.
3. Change from a carrier state to vaginitis can be determined (as in case of candidiasis)
by undermining of the bodily resistance associated with an intercurrent disease or by
the intake of broad-spectrum antibiotics.
Trichomonas vaginitis often first manifests itself during or afterimmediately
after a menstrual period during which time the vaginal pH is raised. The optimum pH
for the trichomonades is 5.5 - 6.5, and this pH is usually found in the vagina when the
disease is present.

Clinical picture
The onset is usually sudden with onset of discharge, which often dates from a
menstruation. The discharge is copious, homogeneous, and may be malodorous. Its color can
be gray, or yellow-green. This discharge has been frequently described as frothy, but in fact
this feature is uncommon. Intense pruritus is commonly present, but sometimes there is only
soreness. Sense of vaginal heaviness or dyspareunia can be present. There can also be dysuria
in cases associated with urethritis and cystitis.
The cervix and upper portion of the vagina may show many slightly raised tiny
hemorrhages -- the flea bitten cervix. There can be vulval edema. The pH of the discharge is
greater than 5.5. Great variation of the clinical picture can occur particularly when the
infection is not acute.

Diagnosis
1. Clinical picture: is not always surely indicative.
2. Wet mount preparation: one drop of the vaginal discharge is mixed with one drop of
slightly warmed normal saline on a slide and covered by a coverslip and examined
under the microscope. Because trichomoniasis may produce a heavy
polymorphnuclear infiltrate it is easy to miss the trichomonads. One must examine
the preparation in areas with relatively few white cells. The trichomonads are
recognized by their shape, size (larger than the pus cells but less than half the size of
a vaginal squame), but mainly by their highly active flagellae and rotatory movement.
The wet mount test may miss a big proportion (30% or more) of cases of
trichomoniasis.

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3. Culture is currently considered the best method of diagnosis. It utilizes specific media
such as Diamond medium or Tichosel broth.
4. Papanicolau smears may show trichomonades but an infective state needs to be
confirmed in patients without symptoms.
5. A search for other STDs may be needed.

Treatment
The most effective therapy is oral metronidazole: either in the dosage of 500 mg twice
daily for 7 days or 2 g as a single dose. The single dose is equally effective but it may
occasionally cause nausea. An alternative treatment is secnidazole (a 5-nitroimidozole)e.g.
Flagentyl given as a single 2g dose. The male partner should be similarly treated even if
asymptomatic, and the couple should refrain from sexual intercourse until they become
symptom free. The treatment is effective in 90% of cases.
Resistant cases should receive the high dose oral therapy for 3 to 5 days or repeat the
treatment at the time of menstruation for 3 months. Intravaginal metronidazole can be
combined to oral treatment in resistant cases to cover the possibility of inadequate absorption
of the drug from the intestines.
Trichomoniasis has been implicated as a risk factor for cuff cellulitis after
hysterectomy, cuff abscess and adverse outcomes of pregnancy, particularly premature
rupture of membranes and preterm labor. However, these associations have not yet been
confirmed by reliable evidence.

Other types of vaginitis

A. Allergic vaginitis - drug sensitivity: This is not uncommon. The conditions present with
sudden onset of discharge and pruritus. This may not be associated with allergy
elsewhere. The condition results from topical contacts with antiseptics frequently used by
some women (to clean themselves), soaps, deodorants, underwear, contraceptives like
condom.
B. The treatment is normal saline douches and antihistaminics. Care should be made to
identify and avoid the involved allergen.

C. Mechanical vaginitis: may result from the long-term use of a mechanical pessary, e.g.
ring pessary in prolapse.
D. Urinary encrustation: may form in cases with urinary vaginal fistulae.
E. STD related lesion, e.g. Herpes, syphilis.

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Cervicitis
A. Acute cervicitis
This refers to acute infection of the endocervix. It usually represents part of the
gonorrheal, chlamydial, postabortion or puerperal infection, usually associated with acute
infection at other sites. The clinical picture is frequently overshadowed by the manifestation
of infection of these other sites. In itself acute cervicitis causes excess of purulent discharge.
The cervix is congested and edematous and pus is seen coming down the external os. The
mucous membrane may be pouting from the external os. It can be tender or palpation due to
associated parametritis.
Acute cervicitis usually disappears spontaneously, but may result in PID or lead to
chronic cervicitis. Its treatment is that for the condition of which the cervicitis is a component.

B. Chronic cervicitis
Chronic cervicitis is a common gynecological condition, estimated to be present in 30
to 80% of multiparae and some nulliparae. The diagnosis is frequently overmade; (of each 10
gynecological consultations, 12 will end by the diagnosis of chronic cervicitis and
cautarization of the poor cervix!!).
Etiology
The condition is a sequela of infection and traumatic lacerations. It can follow an
acute infection, but usually this is not the case. The normal vaginal flora may become
pathogenic infecting the endocervix. This can be determined by lacerations resulting from
childbirth and abortion. Exposure of the thinner columnar epithelium in cervical ectopy may
predispose to infection.
Pathology
The varied clinical picture depends upon various combinations of chronic
inflammatory infiltration, chronic congestion, fibrous hypertrophy, pouting of the endocervix
down the external os, obstruction of glandular crypts and their distension with mucus or pus,
and the usually associated parametritis.

Clinical picture
The possible symptoms include:
- Increased discharge, which can be mucoid or purulent.
- Vague pelvic pain and lower back pain, which is not completely relieved by rest.
- Dyspareunia, occasionally contact bleeding.

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- Congestive dysmenorrhea, and rarely menorrhagia or polymenorrhagia may be

associated.
- Urinary tract symptom may result from associated cystitis.
- Infertility has been ascribed to interfering with sperm penetration and ascent in the
infected cervical mucus. Pregnancy has, however, been frequently observed to occur
in spite of markedly pathological cervix.
- Other distant manifestations like arthritis, tenosinovitis, iritis, dyspepsia, have been
ascribed to chronic cervicitis but without any real evidence.
The possible physical signs include:
- Enlargement and congestion leading to hypertrophic portio vaginalis.
- Cervical laceration and ectropion. The latter condition results from bilateral cervical
tears cutting of the circular muscle fibers, and the contracture of the longitudinal
fibers. This results in evertion of the anterior and posterior lips of the cervix and
exposure and infection of the endocervix.
- Induration of the parametrium above the site of an old tear
- Nabothian follicles: These are follicular or shotty cysts on the surface or in the
substance of the cervix varying in size from a pin’s head to a bean. They are either
bluish or yellowish. They result from blockage of the mouths of the cervical crypt by
fibrosis and their distention with mucus or pus.
- Pouting out of the red endocervical epithelium. It appears congested red.
- Mucous polyps. These are small (rarely as big as a bean), soft polyps. They are deep
red in color and soft, may bleed on touch. These cervical polyps have a long pedicle
arising from high up in the endocervix. They can be multiple.
- Cervical ectopy (erosion) may be associated. This represents creeping out of the
endocervical columnar epithelium to replace the stratified squamous epithelium on the
ectocervix. The thinner columnar epithelium shows the color of blood in the
underlying vessels, therefore appears red. The name erosion is in fact a misnomer
since there is no breach in the epithelial covering. The ectopy is characterized by its
continuity with the endocervix, red color and distinct demarcation from surrounding
epithelium. Cervical ectopy is not a manifestation of infection or inflammation. It is
part of a continuous ebb and tide of the two types of epithelium at the mucosquamous
junction on the area of the external os. This junction is called the transformation zone
(see under cervical cancer) and is not static but dynamic. Cervical ectopy in itself does
not require any treatment. It is frequently seen in young women and shortly after the
end of pregnancy.

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Treatment
Local antiseptics and systemic antibiotics are quite useless.
1. Cautarization
This is the most frequently done gynecological procedure, frequently unnecessarily. It
is usually done by electrically heated loop, but it can be done by diathermy, cryoprobe or
by CO2 laser (see also under CIN). Cervical cautarization is usually an office procedure
and no anesthesia is required since the cervix is devoid of pain-sensitive nerve endings.
However, for marked chronic cervix, it is better to carry out the procedure under
anaesthesia, which allows prior dilatation of the cervix.
Linear cauterization cuts are made at 12, 2, 4, 6, 8, 10 o’clock of the cervix, extending
from the endocervical canal down to the edge of any lesion on the ectocervix. The 6 and 9
o’clock should be avoided in order not to get near to the cervical vessels on the sides.
These cuts should open up crypts harboring infection. In addition, any nabothian follicle in
between should be opened and its lining vaporized.
No postoperative antibiotics are routinely required. The patient should expect an
increase in the purulent discharge and bleeding 7 to 10 days after the procedure, at the time
of sloughing of the necrotic tissue resulting from cautarization. This sort of secondary
hemorrhage can sometimes be severe. It is managed by warm antiseptic vaginal washes
(douches), and rarely requires packing. The discharge will gradually disappear over 4 to 6
weeks when the raw area left behind gets a stratified squamous covering. Sexual
intercourse should be avoided for 10 to 15 days after cautarization.
Complications
This simple operation is not free from complications:
1. Secondary hemorrhage (see above).
2. Ascending infection causing PID or parametritis.
3. Stenosis of the external os, and destruction of endocervical epithelium. These
result in cervical factor infertility.
4. Rarely cervical dystocia.

2. Trachelorrhaphy may be needed to repair deep cervix tears. This operation is done
mainly to remove the tender scar at the apex of the old tear. Some apprehensive women
dislike having a disfigured cervix (our clientele are usually of the habit of carefully
washing their vagina!).
3. Cone excision is done when the endocervix and external os are badly affected. The
procedure, however, is commonly done as part of the diagnostic workup and treatment of

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CIN (see under this section). The crater left behind after conization is covered by the
Sturmdorf’s operation.

4. Hysterctomy: This is rarely indicated for severe cases that can be corrected by the above
measure, when childbearing is no more required, particularly where there is another
supporting indication like persistent uterine bleeding. The operation can be done vaginally
if the pelvic floor is lax, otherwise AH is needed.

Endometritis
• Acute endometritis
It is a temporary fleeting condition. This is with the exception of puerperal and
postabortive infection when the uterine cavity has big wounds (mainly the placental site) and
necrotic infected remnants of pregnancy.
• Chronic endometritis
It is a rare clinical entity during childbearing period because of the monthly renewal of
the endometrium. However, this is a frequent finding in pathological reports on endometrial
biopsy. This latter diagnosis is frequently based on observations of large collections of plasma
cells and lymphocytes in the stroma. It needs to be mentioned, however, that the presence of
lymphocytes is normally found in the endometrial stroma. When the endometrium shows
marked evidence of chronic infection, a careful search should be made for endometrial
tuberculosis.
• Tuberculosis and bilharziasis of the endometrium (see above)
• Senile Endometritis
Pathology
After the menopause, the endometrium is thinned out and has poor resistance to
pathogenic bacteria that ascend to it from the vaginal flora. The endometrium is infiltrated by
inflammatory reaction and may get replaced by granulation tissue, which oozes pus. The pus
may collect in the uterus causing its distension, thus forming a pyometra. This is determined
by fibrotic stenosis of the cervix and weakness of the tone of the myometrium. The latter gets
thinned out to form a sac filled with pus. Formation of a pyometra may be determined by
presence of endometrial or cervical carcinoma. There is a possibility of senile endometritis
predisposing to endometrial cancer, but this relationship is not completely established.

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Clinical picture
The presenting symptom is excessive purulent, very offensive discharge that can be
blood-tinged. When pyometra has developed, the discharge becomes intermittent occurring
every some days or weeks and may be associated with lower abdominal colicky pain. The
uterus in senile endometritis is small and atrophic, but it can get enlarged and cystic if
pyometra has developed. Senile vaginitis may be associated.
Diagnosis
The diagnosis should aim at excluding an associated endometrial or cervical cancer.
Fractional curettage is required. Great care should be exercised not to perforate the uterus,
which is thinned out. If dilatation of the cervix reveals pyometra, the operation is better
stopped at drainage and curettage is deferred for two weeks. This is done under antibiotic
cover in order to prevent the spread of infection to the peritoneal cavity.
Treatment
Drainage of pyometra is sometimes enough. It may be followed by giving cyclic
postmenopausal hormone therapy for 3 months. However, the patient should be kept under
close observation. Hysterectomy is a good option in significantly fit cases because of possible
association with endometrial cancer.
Pyometra
Causes:
- Senile endometritis.
- Endometrial and cervical carcinoma.
- Following radiological brachytherapy.
- Surgical stenosis of the cervix - resulting from amputation.
- Tuberculous endometritis.
- Rarely benign polyps.
- Rarely puerperal and postabortal infection.

Salpingo-oophoritis
Salpingo-oophoritis is a common infection that can have serious consequences. The
infection of the fallopian tube is usually bilateral and frequently, but not invariably, involves
the ovaries. The infection usually spreads to the peritoneum. Infection of these upper genital
organs is frequently ascending from infection of the lower genital tract. The term pelvic
inflammatory disease (PID) is being frequently used to describe salpingo-oophoritis. This
recent trend has been in attempt to diagnose this serious infection at any early stage
depending on an algorism of symptoms and signs (see above). This trend has become

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necessary after it was realized that some cases of mild salpingo-oophoritis may escape early
detection by waiting for typical conclusive clinical picture of acute salpingooophoritis. Such
mild cases frequently end in serious consequences including sterility. This particularly applies
to Chlamydia trachomatis infection, which is the commonest cause of PID in some Western
countries.
Etiology
- Gonococcal
In gonorrhea, the infection spreads along lumens to the upper genital tract. The main
brunt of affection is on the endosalpinx resulting in serious damage to the tube.
- Chlamydial
Chlamydia trachomatis is a venereal infection that spreads to the upper genital tract
along lumens, but the pathology is usually milder than in cases of gonococcal infection.
- Puerperal and postabortal
The infection results from nonspecific pyogenic organisms like streptococci,
staphylococci, E. coli and occasionally anaerobes, which infect the placental site and other
wounds, and any retained remnant of pregnancy. The infection spreads along lymphatics and
veins to the upper genital tract. The affection is initially and mainly a perisalpingitis affecting
the tube from the outside. The consequent damage to the tube, particularly on the endosalpinx
is usually not serious. Therefore, these types carry better prognosis upon corrective
microsurgery.
- Spread from inflamed intraperitoneum structures as in appendicitis and divertculitis.
The infection is by coliform organisms. The affection is more marked on the right adnexal
structures or limited to this side.
- Introduction of pathogen during procedures like salpingography and insertion of an
IUD.
- Tuberculosis (see above).
- Schistosomiasis (see above).
Pathology
In the acute phase, the tubes are reddened, swollen and edematous. Fibrinous
adhesions to the surface of the tubes and ovary may form. They may discharge pus from their
abdominal ends. Thereafter, the following consequences are possible:
1. Resolution.
2. Abscess formation: This may result in pyosalpinx or ovarian abscess. Pyosalpinx is
frequently retort-shaped (i.e. the lateral part is more distended), has thick walls and is
surrounded by adhesions. Its size may reach that of a big orange and is usually

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bilateral. Pus may collect in the uterorectal pouch and gets roofed by intestinal and
omental adhesions giving rise to pelvic abscess.
3. Hydrosalpinx: When the inflammation subsides leaving behind sealed fimbrial end
but a mostly intact endosalpinx, the tube gets distended with clear serous tubal fluid.
The fimbriae as a result of fibrosis fall inside the lumen and their outer walls adhere
together, resulting in a clubbed lateral end. Careful inspection of this end usually
reveals a dimple at the site of adhesion of the fimbriae. The hydrosalpinx is usually
retort-shaped and rarely exceeds the size of an orange. Its wall is thin and usually free
from adhesion. The fluid content is serous and clear. The hydrosalpinx is flaccid and is
not palpable on gynecological examination. The uterine end of the tube remains patent
allowing visualization of the hydrosalpinx during hysterosalpingography. The
hydrosalpinx may periodically discharge its content in the uterine cavity. This has been
suggested by the relatively poorer results of embryo transfer after IVF in cases with
hydrosalpinx; the embryos may be flushed away by discharged tubal fluid. The results
of ET can be improved by salpingectomy in these cases.

4. Chronic interstitial salpingitis: The tubal wall gets thickened and fibrosed as a whole
or in parts; in the latter condition the tube becoming nodular. The lumen is usually
blocked at the lateral, medial or both ends. Beading and thickening of the isthmical
portion of the tube is called salpingitis isthmica nodusa (SIN). The SIN is bilateral, and
the rest of the tube is usually normal. The tubal lumen is blocked. The condition was
thought to be indicative of tuberculous salpingitis. However, SIN can be a
manifestation of old nonspecific infection. SIN may represent an isolated adenomyosis
of the intestinal and isthmical portions of the tube. This latter pathogenesis is frequently
suggested by absence of any evidence of infection in the rest of the tubes or
peritoneum.
5. Fibrocystic disease of the ovaries: Fibrosis around the ovary leaves behind thickening
of its capsule and adhesions to the surrounding structures including the pelvic
peritoneum, omentum and intestines. Multiple small follicular retention cyst form
under the capsule. Cystic collections of clear fluid may also occur between the capsule
and the adherent structures.

6. Tuboovarian cyst (mass): when a hydrosalpinx is adherent to an ovary containing

multiple retention follicular cysts, the two conditions give the appearance of a single
multilocular structure. Tuboovarian cysts usually do not exceed the size of an orange.

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Clinical picture
A. Acute salpingo-oophoritis: Pelvic inflammatory disease
The clinical features mainly reflect pelvic peritonitis. The onset is sudden with acute
lower abdominal or pelvic pain, which is usually bilateral. This is associated with pyrexia,
malaise and sometimes vomiting. The patient looks toxic and has tacchycardia. An attack of
untimely vaginal bleeding may be associated., and can be heavy and/or prolonged. There may
be a history of lower genital tract infection in the weeks preceding the illness or some
predisposing event e.g. recent marriage, abortion or IUD insertion or hystrosalpingography.
There can be associated symptoms of lower urinary tract infection.
The lower abdomen is tender with some muscle guarding. Pelvic examination reveals
tenderness in the whole pelvis and pain results from manipulating the uterus. If a pyosalpinx
has developed there will be ill-defined tender swellings above the lateral or posterior fornices.
Purulent discharge may be present on the cervix.
With development of spreading peritonitis there will be intestinal distension,
vomiting, constipation. Formation of pelvic abscess results in rectal pain, diarrhea and
tenesmus and sometimes retention of urine. A very serious complication is rupture of a
pyosalpinx, which causes severe acute abdominal emergency resulting in rapidly spreading
[Link] condition is associated with marked leucocytosis and rise in ESR.
The clinical picture of salpingo-oophoritis is not always as acute as described above.
In subacute or milder forms not all the features are present and are not marked i.e. less pain,
less tenderness, and slight pyrexia. This is particularly common with chlamydial infection, the
commonest cause of upper genital tract infection in some western countries. This has been the
basis of evolution of the concept of the clinical syndrome of PID, which entails high level of
clinical suspicion (see above under PID) in order to institute antibiotic treatment at an early
stage. This can help to avoid the serious consequence of pelvic infection particularly as
regards fertility. Laparoscopy should be utilized to confirm a suspected diagnosis of subacute
PID.
Diagnosis
The salient clinical features of acute and subacute salpingo-oophoritis that help to
differentiate it from other causes of acute abdomen include bilaterality of the manifestations,
tenderness on moving the cervix, history of a cause, presence of manifestations of lower
genitourinary infection and leucocytosis. Laparoscopy is indicated to confirm a doubtful
diagnosis. However, if the diagnosis is certain, the risk of spreading the infection as a result of
laparoscopy outweigh the benefit.
The differential diagnosis includes consideration of the following conditions:
- Acute appendicitis.

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- Cystitis.
- Ectopic pregnancy.
- Spastic colilitis.
- Diverticulitis.
- Torsion of a predicted subserous myoma or ovarian cyst.
- Rupture of an ovarian cyst or hemorrhage in an ovarian cyst.
( See under PID )
- Ovulation pain.
- Intestinal obstruction.
- Other causes of acute abdomen.

B. Chronic salpingo-oophoritis
- This condition is frequently asymptomatic and discovered during investigation of
infertility.
- There may or may not be a history suggestive of acute salpingitis.
- The condition may cause chronic lower abdominal or pelvic pain, heaviness,
dystpareunia, or vague lower back pain. The pain is worst during the premenstrual
days and is relieved by menstrual flow. Increased mucoid or mucopurulent discharge
may be present. The condition may be associated with polymenorrhea or
polymenorrhagia when the ovaries are involved.
- There can be no physical signs. In other cases, the uterus may be fixed in retroversion
and tender. The adnexa can be tender and there can be ill-defined induration above the
lateral or the posterior fornices. Definite adnexal masses may be palpable in cases of
old pyosalpinx. They are bilateral and usually ill defined.
- Chronic salping-oophoritis is liable to acute exacerbations usually through a
secondary infection reaching the pathological tubes from the adherent intestines.
These take the form of acute salpingints.

Diagnosis of chronic salpingo-oophoritis

The manifestations, if present, can be nonspecific: The condition has to be
distinguished from: chronic disturbed ectopic, appendicitis, colitis, ovarian tumors, fibroids
and pelvic endometriosis and other causes of chronic pelvic pain. Laparoscopy is a valuable
tool for the diagnosis.

Treatment
Severe cases of acute salpingo-oophoritis need be admitted to hospital for institution
of parenteral antibiotic administration and observation for progress. Due to the possible
seriousness of consequences on fertility, the condition should be energetically treated with

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broad spectrum antibiotics. Cervical swabs should be obtained for culture and sensitivity
before initiated therapy but the initiation of treatment should not await the result.
The major emphasis has been on using combinations agents to cover the multitude of
microbes involved. Two or three antibiotics should be given in full therapeutic doses. These
include a cephalosporin plus doxycycline, or clindamycin plus gentamycin. Metronidazole
may be added in serious infections and particularly if there is evidence of traumalization of
genital tract as in cases of suspected induction of abortion done under unfavorable conditions.
Antibiotics should be administered parenterally at the beginning in severe cases, and after
subsidence of the acute manifestations, oral therapy (of the same drugs) should be continued
for 14 days. If there is no immediate response, shift should be made to fourth generation
cephalosporine or third generation quinolones.

Surgical treatment
With availability of several effective antibiotics, resort to surgery in acute salpingo-
oophoritis should be rare. Indications including: 1) spreading peritonitis in spite of intensive
antibiotic treatment, 2) rupture of pyosalpinx, 3) ovarian abscess, 4) pelvic abscess, and 5) if
the diagnosis is in doubt. In the latter situation, laparotomy is preferred to laparoscopy, which
carries the risk of injuries or spreading the intraperitoneal infection. If acute salpingitis is
diagnosed, the best treatment is to leave pelvic organs untouched, obtain bacteriological
samples and close. This unless there is a large pyosalpinx when it can be removed. Drainage
of pelvic pus can be made via the posterior vaginal fornix.
Treatment of chronic salpingo-oophoritis is usually unsatisfactory. Antibiotics are
only indicated if there is active infection. Relief of pain can be achieved by short-wave
therapy to the pelvic and hot vaginal douches. Bleeding complications can be diminished by
use of combination oral contraceptives; these result in regular and lighter menstruations.
Surgical treatment of chronic salpingo-oophoritis: Indications include: 1) persistence
of pelvic pain or menorrhagia, 2) recurrent attacks of acute salpingo-oophoritis, 3) persistence
of big adnexal mass, 4) uncertain diagnosis, 5) microsurgical correction of tuboperitoneal
infertility (see under Infertility), and 6) salpingectomy before attempt of IVF/ET, this has
been shown to improve the success rates in cases with hydrosalpinx (see above).

Nature of the operation

- If the patient is young, excision of the hopelessly diseased tubes together with the
cornu of the uterus. The infected intramural part of the tubes if left behind can result
in persistence of symptoms.
- If the desired family size has been achieved resort is to by total hysterectomy plus
salpinectomy. The ovaries are better conserved.

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- Surgical correction of tuboperitoneal-factor infertility (see under Infertility).

- Treatment of chronic pelvic pain.
- Prostaglandin synthetase inhibitor and other analgesic.
- Short wave therapy.
- Laparoscopic therapy ablation of sacral nerve plexuses under the uterosacral
ligament utilizing cutting and diathermy coagulation.
- Hysterectomy – is rarely needed in intractable cases.
Prevention of salpingo-oophoritis
1. Prevention measures directed to STDs, like safe sexual practice, use of condom
and education about early manifestation.
2. High index of suspicion of PID.
3. Energetic treatment should be instituted.

Oophoritis without salpingitis:

Oophoritis may result from blood - or lymph - borne infection from elsewhere. This
may be complicated mumps and rarely influenza as well as other viral infections or enterica.
This is equivalent to orchitis that may occur in males having such infections. Chronic
insidious oophoritis may develop as a part of autoimmune disease and has been alleged to be
a cause for premature ovarian failure.
Acute inflammatory reaction involves the ovaries, but it frequently resolves
spontaneously without causing any ill effect. Mumps rarely has any sterilizing effects in
females because of elasticity of the ovarian capsule, so ischemic necrosis of ovarian follicular
structures rarely occur, in contrast to what occurs in the testes, which have a rigid capsule.
All that may result from this fleeting oophoritis is pelvic pain and untimely or
prolonged bleeding.

Pelvic peritonitis
Etiology
- Any infection of the upper genital tract.
- Appendicitis or diverticulitis.
- Perforating intestinal ulcer as in typhoid fever.
- As part of generalized peritonitis including tuberculous peritonitis.
- Perforation or rupture of infected uterus.
- Infection of the pelvic hematocele. This is usually due to subacute or chronic disturbed
ectopic, but may result from imperfect hemostasis in operations like myomectomy,

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ovarian cystectomy and operative laparoscopic procedures and rarely after cesarean
section.
- Chemical irritation: This is rarely seen after hystrosalpingography. This can be a sort of
chemical irritation but may result from imperfect asepsis. It may result from sebaceous
material spillage from dermoid cyst during cystectomy.

Pathology
The infection may resolve spontaneously or under antibiotic therapy. However, a
pelvic abscess may develop behind the uterus and gets roofed by intestines and omentum. It
can point into the rectum or the bladder and rarely in the vagina, which has a thicker fascial
covering. The condition may spread to cause generalized peritonitis.

Clinical picture
The same as with salpingo-oophoritis. When the abscess forms the patient develops
rectal pain, tenderness, diarrhea and mucoid discharge from the rectum, bladder irritability
associated with abdominal and vaginal tenderness.

Treatment
Combination antibiotic two or three-drug therapy. If an abscess forms it should be
drained preferably through the posterior vaginal fornix.

Pelvic cellulitis or Parametritis

Pelvic cellulites or parametritis is an infection of the pelvic cellular tissue above the
levator ani and below the pelvic peritoneum on the sides of the uterus and vagina. This loose
connective tissue has a weak resistance to infection and is continuous with other
retroperitoneal cellular tissue.
Etiology
The infection may spread by lymphatic channel from adjacent pelvic organs but a
direct access of infection can be caused by perforation of the vagina, cervix or the uterine
body. These injuries are usually obstetrical following traumatic or operative labor. Attempt at
surgical induction or abortion is an important cause of injuries. Surgical injuries may occur
during cervical dilation or curettage and may result in parametritis, Other types of pelvic
surgery may leave behind a hematoma that gets infected. The sources of infection may be
spread from inflamed adjacent organs or may follow pelvic operations.
Adjacent organs infections comprise:
- Cervicitis - may be associated or result in parametritis, particularly as a
complication of cauterization.

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- Salpingo-oophoritis.
- Diverticulitis or carcinoma of the rectum.
- Severe cystitis or ulcer or carcinoma in the bladder.
- Carcinoma of the cervix or endometrium.

Pelvic operations that can result in parametritis include:

- Imperfect hemostasis during repair of an episiotomy or perineal tear.
- Cervical cauterization.
- Dilatation and curettage in presence of infected uterine content.
- Evacuation of pregnancy.
- Hysterectomy - imperfect hemostasis.
- Myomectomy - imperfect hemostasis.
- Other obstetrical operations.
- Other gynecological surgery.
- The insertion of IUD - imperfect asepsis or perforation of the uterus.

Radiotherapy: brachytherapy or external beam radiotherapy may result in flaring up of pelvic

cellulitis resulting in excessive infiltration and induration of pelvic cellular tissue. This may
amount to a “frozen pelvis”.

Pathology
The looseness, and weakness of tissue resistance and wide communications with
retroperitoneal spaces allow spread of acute infection and inflammatory infiltration. The
infiltration is frequently unilateral. The consequences include: (1) complete resolution, (2)
Abscess formation, the pus may track and point into the rectum, bladder, vagina, lower
anterior abdominal wall, inguinal regions via the external inguinal foramen, the thigh via the
obturator foramen or in the buttock via the sacrosciatic notch; (3) Healing by fibrosis may
occur causing chronic parametritis. One complication is suppurative thrombophelebitis of the
veins in the broad ligament and this may result in septicemia and repeated embolization.

Clinical picture:
Symptoms and signs do not usually make their appearance until 7 - 14 days after the
original infection or trauma. Pyrexia and pelvic pain are the main symptoms. Frequency of
micturition, rectal pain and diarrhea may be present. Pelvic examination reveals extensive
induration resulting in a hard mass extending to the pelvic wall and confluent with uterus. It is
usually unilateral and may be overlying a wound in the genital tract. The induration may
extend in the iliac or lumbar regions. Involvement of the uterosacral ligament results in a
horseshoe mass, which is better felt per rectum. The mass is tender, woody hard and fixed and
may push the uterus to one side or high in the abdomen to get out of reach.

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The formation of an abscess results in swinging temperature, rigor and toxic

appearance. The abscess may spread to iliac or lumbar regions. It may point mainly through
the rectum, bladder, vagina or abdominal wall.

The development of suppurative thrombophlebitis is associated with fluctuant

pyrexia, tacchycardia and profound toxemia. Pyemic embolization may result in fainting
attacks, and as a result of pulmonary embolism, pleural pain and dyspnea. Pyemic abscess
may occur elsewhere like in the brains or bones. One or both legs are usually swollen with
edema. Doppler ultrasonography can locate the site of venous block.
Chronic fibrotic cellulitis may or may not be preceded by acute cellulites. It results in
chronic pelvic pain, lower back pain, dyspareunia and may be rectal pain. Menorrhagia and
discharge may be associated due to congestion of pelvic organs.

Treatment:
- Multiple agent antibiotic treatment like acute salpingitis.
- Drainage of an abscess, best through the posterior fornix. An extraperitoneal inguinal
drainage is also possible if the abscess is reaching anteriorly.
- In case of suppurative thrombophebitis requires in addition to paranetral antibiotics,
administration of anticoagulant or ligation of the ovarian vein or common iliac vein
proximal to the clot to prevent repeated embolization.
- The treatment of chronic cellulitis is similar to that of chronic salingo-oophoritis.
Trachelorrhaphy with excision of the overlying fibrous tissue may improve pelvic pain
and dyspareunia.
- Resistant pain and menorrhagia in a multipara with completed family size may indicate
total hysterectomy.

Urinary tract infection

Urinary tract infection (UTI) is quite common in all stages of the woman’s life.
Although UTI is not a gynecologic condition, urinary symptoms are associated with many
gynecologic disorders, certain STDs, notably gonorrhea and chlamydia infection, with
pregnancy, puerperium, and postmenopausal genitourinary atrophy.

Etiology
More than 80% of UTI are caused by E. coli; and 10% Staphylococcus saprophyticus.
There are two mechanisms of infection: It can be descending from colonic organism reaching
the urinary system via the rich lymphatic connections between the colon and the urinary tract.
The second mechanism is an ascending one from bacteria, mainly coliforms, colonizing the
vaginal introitus and lower urethra. Bacteria in urine are readily washed out by the ongoing

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stream or urine. Invasion of the urinary tract is predisposed to by a number of factors

including:
- Stasis of urine as during pregnancy (see under pyelitis of pregnancy).
- Abnormalities of the urinary tract e.g. reflux, obstructions, stones, or cystocele.
- Abnormality in host defense e.g. diabetes or immunosuppression.
- Postmenopausal atrophy of the mucosa of the urethra and bladder.
- Introduction of virulent organism by catheterization.
- Poor natural defenses against the bacterial adherence to and the ascent into the urinary
tract may be genetically determined.
Clinical picture
The following forms are possible:
1. Asymptomatic bacteriuria, as defined by the presence > 100,000/ml of a single pathogen
found on 2 or more midstream (clean catch) specimen of urine, can be found in 2 to 10%
of women. Asymptomatic bacteriuria can be transient or intermittent. In nonpregnant,
nonimmunocomprised women, with morphologically normal urinary tracts, asymptomatic
bacteriuria is not associated with UTI or with long-term morbidity and does not require
treatment. Among pregnant women and women with morphological abnormalities in the
urinary tract eradication is warranted, because it can result in pyelonephritis or predispose
to preterm labor.
2. Lower urinary tract infection in the form of cystitis is the commonest form and causes
scalding micturition (dysuria), frequency and urgency of acute onset. There can be gross
pyuria, hematuria, suprapubic pain in the flanks. Urine culture may reveal a bacterial
count of > 100,000/ml mainly E. coli, S. saprophylicus.
3. Pyelonephritis: The onset is usually subacute and may follow upon lower UTI.
Pyelonephritis causes flank or back (costovertebral angle) pain and tenderness. Symptoms
of lower UTI (dysuria, frequency, urgency or gross pyuria) are present in 50%. In
addition, fever, chills, malaise can be present. Urinalysis shows pyuria, hematuria and
casts. Urine culture may show counts of > 100,000/ml. The infecting organism can be E.
coli, or other gram-negative enterics, enterococci. Pyelonephritis causes more morbidity
than lower UTI; it may cause long-term sequelae and the need for prolonged treatment.
4. Urethritis can be caused by sexually transmitted infection by C. trachomatis, N.
gonorrheae, T. vaginalis and Herpes simplex virus. These infections can have acute or
subacute symptoms of frequency, dysuria and urgency. Pyuria is present, urine culture
may be negative.
5. Vaginitis and vulvitis may cause dysuria and urgency. Although in these cases the dysuria
is external in contrast to internal dysuria associated with lower UTI, this distinction may
be difficult to make by many patients. In vaginitis unassociated with cystitis a clean catch

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specimen of urine will show no pyuria or bacteriuria. Other symptoms and signs of
vaginitis are present.
Diagnosis
1. Clinical picture.
2. Urinalysis - clean catch specimen showing more than 8 to 10 WBCs per ml in unspun
urine. This allows diagnosis of pyuria and indicats the need for urine culture and colony
count.
3. Although a bacterial count of > 100,000 of a single pathogen per ml is required for the
diagnosis of asymptomatic bacteruria, this population may not present in cases with lower
UTI. Levels much lower than this should not rule out diagnosis of cystitis if symptoms are
present.
4. Recurrent cystitis or persistence in spite of adequate treatment indicate presence of
urinary tract abnormality or pyelonephritis and needs referral to a urologist.

Treatment
Single agent treatment if given for 3 - 7 days is usually adequate for the majority of
cases of cystitis. The first line of antimicrobial agents includes nitrofurantoin, trimethoprim -
sulfamethoxazole, ampicillin and cephalosporin. The use of more expensive fluoroquinolones
should be reserved for treatment failure, recurrent cases or infections with resistant gram-
negative organisms. Pyelonephritis should be treated with standard antibiotics for 10 days.

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Carcinoma of the cervix

Chapter 16
CARCINOMA OF THE CERVIX

Contents
• Etiological considerations
- Epidemiological findings
- Natural history of cervical neoplasia: Pathogenesis
- Molecular biological considerations
• Pathology
- Dysplasia, cervical intraepithelial neoplasia (CIN) and Carcinoma in situ
- Microinvasive carcinoma (superficial carcinoma)
- Invasive carcinoma
- Spread of cervical carcinoma
- Complications
- Staging
• Symptoms and physical signs
• Diagnosis of CIN
- Cytological screening
- Colposcopy
- Biopsy: colposcopically guided
- Auxiliary investigations
• Treatment of CIN
• Treatment of Invasive carcinoma
- Pretreatment evaluation
- Treatment plans
- Surgery
- Main steps
- Radiotherapy
- Brachytherapy: various approaches (Stockholm, Paris, Manchester,
afterloading)
- External beam irradiation
- Complications of radiotherapy: immediate and late

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- Combined radiotherapy and surgery

- Chemotherapy
• Stump carcinoma
• Carcinoma of the cervix in pregnancy
• Recurrent and advanced cancer

Etiological considerations
1. Epidemiological findings
- Incidence: In the first half of the 20th century invasive cervical cancer was the
commonest female genital cancer after breast cancer. It used to be said that for every case
of endometrial carcinoma there are three or four cases of invasive cervical carcinoma.
Over the last 30 years, there has been a decline in the absolute and relative incidence of
invasive cervical cancer in most western countries. This has been due, at least in part, to
early diagnosis and management of preinvasive cervical cancer, and partly due to the
increasing rate of hysterectomies for benign uterine conditions. In these countries, the
ratio between cervical and corporeal cancer is now 1:1. However, the incidence of
cervical cancer is still high in Subsaharran Africa and Latin America. In Egypt, the
impression (no reliable data are available) is that the three major cancers of the female
genital system, cervical, corporeal and ovarian have almost equal incidence rate. Death
rate from cervical cancer has been estimated to be 0.3 per 100,000 in Egypt (the data are
not completely reliable), while it can be as high as 16 per 100,000 in parts of the world,
like Latin America.
- Age: Although invasive cancer of the cervix is reported in all ages, it has now two peaks,
one, the smaller at about the age of 35 years and another at about 50-55 years which is a
bigger peak. Following the latter age there is reduced incidence.
- Cervical intraepithelial neoplasia (carcinoma in situ - CIS) occurs at a much lower age;
the peak incidence is 10 years earlier than invasive cancer (i.e. 45 years).
- Sexual activity: The sexually active woman is two to four times more likely to develop
cancer cervix than the sexually inactive women. The disease is almost unseen in nuns.
The early beginning of active sexual life before the age of 20 seems to be predisposing to
cervical carcinoma. Equally important are the diversity of sexual partners and the
diversity of partners of sexual partners. These observations suggest an underlying
etiological contribution of sexually transmitted diseases.
- Parity: Ninety-five percent of invasive cancers occur in multiparae, but there is no clear
association with increasing parity.

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Carcinoma of the cervix

- Socioeconomic factors: The disease is more prevalent amongst women living in poor
conditions. This can be due to higher frequency of reproductive tract infections, including
STDs, early marriage, early pregnancy, poor hygienic condition, like poor penile and
vaginal hygiene, frequency of sexual intercourse and promiscuity of sexual relations.
- Race: Orthodox Jewesses are rarely affected by cervical cancer. This has been attributed
to the practice of male circumcision. Smegma under the male prepuce was incriminated as
an etiological carcinogenic factor but this has not been definitely proven. Genetic factors
can be contributing. Muslim women may be similarly less likely to develop cervical
cancer due to similar factors, but one should not ignore the type of sexual practice and the
less likelihood of diversity of sexual partners.
- Viral infection: Two types of viral infections transmitted through sexual relations have
been incriminated in the etiology of cervical cancer: Herpes simplex and Human
papilloma virus. These associations have been supported by epidemiological finding and
the more frequent presence of the viral antigens in specimens of cancer (preinvasive and
invasive) and of antibodies in the serum of affected patients. Particular associations have
been found for HV-type 2, and HPV-16 and HPV-18. These two types of viral infections
are sexually transmitted and cause lesions in the lower genital tract, and there is a growing
body of evidence that cervical cancer is a sexually transmitted disease. Lesions of HPV
infection show basal cell hyperplasia that is sometimes difficult to differentiate from CIN.
- Hormonal contraceptives: Recent data indicate that there is no definite overall
association between past or current use of combined oral contraceptives and invasive
cancer. Any association can be accounted for by the predisposing influence of sexual
activity and promiscuity of either or both partners. Nevertheless, there may be an
association of the use of COCs and a slightly increased risk CIN. Again, there is a
likelihood of bias or confounding effect of other factors other than the use of the pill,
notably increased effort of screening in the users (diagnostic bias), and sexual life
variables (confounding variables).

2. Pathogenesis of cervical carcinoma:

Cervical carcinoma usually begins in the squamocolumnuar junction near the external
os. This is called the transformation zone, because it is not a static line but tends to move out
and in the site of the external os of the cervix. In children and adolescents, columnar
epithelium tends to be spreading out, and in older age the squamocolumnuar junction tends to
move inwards. The junction moves outwards to cover a good part of the cervix, during
pregnancy particularly in the first pregnancy. Squamous epithelium tends thereafter to spread
inwards to replace the columnar epithelium. This replacement occurs by a process of

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Carcinoma of the cervix

metaplasia. Proliferation of the reserve cells beneath the columnar epithelium is followed by
progressive transformation to stratified squamous epithelium. The metaplastic epithelium
does not only cover the external surface but may be seen spreading down the glandular crypts
of the columnar epithelium (Figure 1). The exposure of columnar epithelium to the low pH of
the vagina during postpubertal years and the highly acid vagina during pregnancy is
enhancing this process of metaplasia. It seems that the early, young metaplastic cells are
particularly vulnerable to mutogenic effect of environmental factors like exposure to viral
infections or even the frequent exposure to sperms. The viral DNA can insert itself in the
chromosomal material of these young actively dividing metaplastic cells. This leads to
atypical metaplastic epithelium resulting in atypical transformation zone.

Carcinoma of the cervix; Figure 1: Squamous metaplasia.

Adequate host response can eradicate this atypical epithelium. The body usually gets
rid of these atypical cells. Inadequate host response allows perpetuation of the epithelial
dysplasia, which can lead to CIN, carcinoma in situ and invasive cancer. Therefore, the
abnormal transformation zone begins early in the life history of the woman shortly after
beginning of active sexual intercourses and after the first pregnancy. The transition from one
stage to another usually takes a number of years and this depends upon the host tissue
response. Invasive cancer occurs once host resistance is completely overcome, and thereafter
the progression becomes rapid. Some preinvasive lesions can remain as such for several
years, and may revert to normal. The chance of normalization depends upon the extent of
progression along the pathway of dysplasia.

3. Molecular biological considerations:

These are mainly pertaining to HPV types 16, 18 and 31. HPV DNA has been found
incorporated in 93% of cervical invasive cancer specimens, and 94% of CIN lesions, whilst in
normal tissue (cytology material) a 43% detection rate has been observed. Two regions on the
viral DNA, the E6 and E7 have been found to be particularly important. These encode for
oncoproteins E6 and E7, respectively, which are critical for viral replication as well as for

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host cell immortalization and transformation. The E6 protein alters growth through its
negative effect on the p53 protein of the host cell, which is an endogenous tumor-suppressor
protein. E7 protein has high oncogenic activity and, by itself immortalizes human
keratinocytes. This can also be achieved through its negative interaction of E7 protein with
retinoblastoma protein (pRb). Both p53 and pRb act as negative regulators or checkpoints, to
prevent abnormal cell division. Loss of these regulatory pathways probably contributes to the
development of cancer. Other molecular pathways may be elucidated in the future.
The clinical implications of these informations are greatly valuable. The detection of
HPV DNA in cytology screening programs can greatly enhance prediction rates.
Immunization by HPV antigenic material can be utilized for cancer prophylaxis.

[Link] of cervical cancer

§ Preinvasive carcinoma of the cervix: Cervical Intraepithelial neoplasia (CIN)
This is a histological diagnosis comprising a range of intraepithelial abnormalities of
varying degrees, which have been described in cervical epithelium and are now collectively
referred to as cervical intraepithelial neoplasia (CIN). The spectrum comprises the following:
a. CIN I = mild dysplasia = basal cell hyperplasia: Abnormal dysplastic cells involve the
lower one- third of the epithelial thickness. Normally the basal cell layer is one to two
cell-thickness; in CIN I basal cells are several-layers thick and comprise dysplastic
cells. The dysplastic cells are atypical (not columnar) in shape, have bigger
hyperchromatic nuclei and loss of polarity (polarity = flatter cells are nearer to the
surface). Mild dysplasia includes HPV changes. These mainly take the form of
Koilocytosis. Koilocytes are large cells with perinuclear halos well defined cell
borders, and irregular, big hyperchromatic nuclei. Some cells are multinucleated.
b. CIN II = moderate dysplasia: dysplastic cells form about half the thickness of the
epithelium.
c. CIN III = severe dysplasia: Dysplastic cells form almost the full thickness of the
epithelium, but there are few flat cells on the surface.
d. Carcinoma in situ: Like the CIN III, but no such flat cells are on the surface.
However, there is no invasion of the underlying stroma. Presently, carcinoma in situ
is included in severe dysplasia. (Figure 2)

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Carcinoma of the cervix

Carcinoma of the cervix; Figure 2: Diagrammatic representation of changes in cellular

morphology from mild dysplasia to CIS.

The present concept is that these conditions are a spectrum in one disease: CIN. The
progression from one stage to the severer one usually takes some years to occur. They may
return to normal particularly in the case of CIN I, but the chance of this is less likely to occur
in severer dysplasia. It has been estimated that between 60 to 70% of untreated CIN III will
eventually progress to invasive carcinoma, whilst about 25% of CIN I will progress to more
severe lesions. Progression however may, not need to go in all the stages in this order; CIN II
may proceed directly to invasive cancer.
Preinvasive carcinoma is usually asymptomatic. Recognition of the lesions depends
upon cervical cytological screening followed by colposcopy and biopsy. However there may
be contact bleeding, erosion or area of white epithelium (see Diagnosis).
Cytological examination may suggest the degree of dysplasia, but this usually requires
histopathological confirmation.
- Microinvasive minimal invasion carcinoma: Stage Ia 1 carcinoma cervix: Superficial
carcinoma:
This is also a microscopic diagnosis which has no gross pathological picture. It is
suspected through cytological and colposcopic screening; but a subsequent biopsy is needed
and this shows minimal invasion. The following requirements should be fulfilled before such
critical diagnosis is made: (1) The whole pathological area should be contained in the biopsy
specimen, (2) tongues of invasion should not be wider than 7 mm diameter, and not extending
in the stroma for more than 3 mm measured from the lower border of the surface epithelium
or glandular crypts, (3) no confluent tongues of invasion and (4) no invasion seen in
lymphatic spaces. In this stage of carcinoma, a 100% cure rate is expected after total
hysterectomy without pelvic lymph-adenectomy. This type of diagnosis should be made by an

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Carcinoma of the cervix

experienced pathologist. The type of management can be similar to that of carcinoma, in situ
i.e. even conization can be used in case of need to preserve reproductive capability or else
simple hysterectomy can be done. When the invasive is more than 3 mm but less than 5 mm
in depth the condition is classified as stage Ia2. When any of the above conditions is not
fulfilled, the condition is managed as invasive carcinoma of Stage Ib.
The term “occult” invasive cancer is used to describe the rare case in which no gross
picture exists, but the invasion exceeds the above limits.

§ Invasive carcinoma of the cervix

a. Gross appearance: The lesion shows the cardinal manifestations of malignancy:
ulceration, friability, contact bleeding and spread to surrounding structures. In 90%
cases, the lesion is on the ectocervix beginning at the squamocolumnuar junction. It is
either cauliflower in appearance, an ulcer, or a combination of the two forms. In 10%
of cases, the lesion is endocervical resulting in barrel-shaped enlargement of the
cervix, which is filled with friable tissue. In advanced cases, the vaginal vault is filled
with necrotic tissue or excavated by a big ulcer crater.
b. Histopathology
1. In 90% of cases of carcinoma cervix are of epidermoid or squamous cell type.
Uncommonly it is well differentiated with formation of cell nests or pearls which
differentiate towards their center with formation of a core of keratin. Most cases,
however, are moderately undifferentiated i.e. there is no differentiation towards
the centers; the epithelial clumps are composed of large nonkeratinizing cells. The
least common is the poorly differentiated type, Grade 3 formed of small basal
cells. The histological grading has not been proven useful in predicting the
prognosis; usually there is variable differentiation in different parts of the tumor.
2. Adenocarcinoma forms about 5% of cervical carcinoma. Recent series tend to
show increasing proportion of adenocarcinoma. Adenocarcinoma tends to be of
endocervical gross type, but it can be ectocervical. In adenocarcinoma the glands
are increased in number, and present all degrees of atypical patterns. The
glandular formations are lined by several layers of active atypical epithelium
different from the regular picket-type of cells within the normal glandular crypts
of the cervix.
3. Mixed adenocarcinoma and epidermoid carcinoma are occasionally seen; i.e.
malignant features are seen in the two components of the tumor. Rare types
include adenoacanthoma and mesonephric carcinoma. The latter may be seen in
younger patients and develop from mesonephric vestiges and can be multifocal
affecting more than one site in the genital system.

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Carcinoma of the cervix

Spread
Direct extension occurs to the corpus uteri, the vaginal wall, parametrium (in the base
of the broad ligament), the uterosacral ligaments, and the bladder. Extension to the rectum is
late due to the intervention of the pouch of Douglas. In the parametrium the growth surrounds
the ureter, constricting it and causing hydronephrosis. However, the ureteric wall is rarely
invaded. Similarly, when the spread reaches the pelvic wall it compresses the sacral plexus
causing sciatic pains but the nerve tissues are not penetrated.
Lymphatic permeation and embolism is an early occurrence in carcinoma of cervix.
It involves the parametrial and paracervical small nodes in the broad ligaments (not always
present), the obturator, the hypogastric (internal iliac), the external iliac nodes. At a later stage
the sacral, common iliac, inguinal and periaortic nodes are involved. Lymph node
involvement does not always correspond to direct spread or clinical stages and this is the basis
for the need for lymph node dissection in apparently localized cervical cancer.
Bloodstream spread is much less frequently seen; the patient usually dies before there
are significant distant metastases. These occur in the ovary, brain, bones and lungs. The
occurrence of distant metastases without prior involvement of the lungs is explainable by
transfer malignant cells via vertebral venous plexuses.

Complications
- Parametritis
- Pyometra
- Vesicovaginal fistula
- Rectovaginal fistula
- Hydro - and pyonephroses,
- Severe hemorrhage
- Cachexia.
- Complications of treatment

Staging
The FIGO staging of cancer cervix (Figure 3) is a clinical approach supplemented by
examination under anesthesia, rectal cystoscopic, proctoscopy examination, and intravenous
pylography. It is intended to choose the plan of management and to compare the results of
different approaches whether radiological or surgical and compare the results of different
institutions. Therefore, it should not be changed later if the findings at operations reveal more
advancement of the disease.

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Carcinoma of the cervix

FIGO (Federation International of Gynecology and Obstetrics) 1982

Classification Description
Stage 0 Carcinoma in situ (cases of Stage 0 should not be included in any
statistics about therapy of invasive cancer).

Stage I The carcinoma is confined to the uterus (Extension to the corpus should
be disregarded).
Stage Ia Preclinical carcinoma of the cervix i.e., those diagnosed by microscopy.
Minimal microscopically evident abnormal invasion: tongues of
Stage Ia1 invasion should not extend in the stroma for more than 3 mm depth, and
7 mm width, and they are not horizontally confluent or involve
lymphatic or venous spaces.
Measured invasion of stroma greater than 3 mm but not greater than 5
Stage Ia2 mm in depth and not more than 7 mm in width.

Clinically evident lesion confined to the cervix.

Stage Ib Clinical lesion not grater than 4 cm in size.
Stage Ib1 Clinical lesion greater than 4 cm in size.
Stage Ib2
The carcinoma extends beyond the cervix but has not extended on to
Stage II the pelvic wall and/or the carcinoma involves the vagina but not as far
as the lower third.
No obvious parametrial involvement.
Stage IIa Obvious parametrial involvement.
Stage IIb
The carcinoma has extended on to the pelvic wall. On rectal
Stage III examination there is no cancer-free space between the tumor and the
pelvic wall and/or the tumor involves the lower third of the vagina.
All cases with hydronephrosis or nonfunctioning kidney should be
included unless they are known to be due to other causes.
No extension reaching to the pelvic wall, but involvement of the lower
Stage IIIa third of the vagina.
Extension on to the pelvic wall and/or hydronephrosis or
Stage IIIb nonfunctioning kidney.

The carcinoma has extended beyond the true pelvis or has clinically
Stage IV involved the mucosa of the bladder or rectum.
Spread of the growth to the adjacent organs.
Stage IVa Spread to distant organs.
Stage IVb

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Carcinoma of the cervix; Figure 3: FIGO staging and classification of cancer cervix.

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Carcinoma of the cervix

Diagnosis of carcinoma of the cervix

A. Diagnosis of cervical intraepithelial cancer or CIN: Early diagnosis
of cervical cancer
1. Clinical picture: CIN is usually asymptomatic, and on examination, the lesion is
frequently not observed. The mucous membrane sometimes bleeds easily on contact, and
an ectropion or erosion may be observed. The diagnosis is made by cytological screening,
followed by evaluation of cases with abnormal cervical smear by colposcopy and
microscopic diagnosis of the biopsy.
Where screening programs have become widely available deaths from cervical
cancer are considerably reduced. However, in most developing countries, such wide-
scale screening programs are not existent. Therefore, attention has been recently focused
on alternative means of providing cervical screening. Prominent among these is visual
inspection, performed after washing the cervix with acetic acid (VIA), either without or
with a simple device to magnify the cervix e.g. a hand lens. Suspicious areas include
white patches, raised areas, areas bleeding on contact and areas of superficial ulceration;
these indicate colposcopic examination and biopsy. Results so far, indicate reasonable
sensitivity as compared to cervical cytology, but wide scale application is still in needs
further verification.
2. Cytological screening: Cytology was introduced in gynecological practice in the forties
by Papanicolaou (American). Screening of nonsymptomatic women by cytology (Pap
smear) resulted in increased detection of preinvasive cervical cancer, decreased incidence
of invasive carcinoma and decrease in the mortality rate of the disease.
Techniques: of collecting samples:
a. Vaginal cytology: In the original method of Papanicolaou a specimen is obtained
from the pool of the vaginal fluid collecting in the posterior fornix after visualization
by a dry (nonlubricated) bivalve spectrum. A suction pipette with a fitted rubber bulb
is used. The obtained drop is evenly smeared on to a grease-free microscopic slide
and immediately (while still wet) fixed by spraying with 90% alcohol to which a
small amount of carbowax and glacial acetic acid is added. The slide dries in 5 - 10
minutes to leave the smear with protective covering wax. Alternatively, the slide is
immersed for one hour in 95% alcohol, dried in air and transferred to the lab. There,
the smear is stained by the Papanicolaou’s or Shor’s methods.
This method of sampling is easy, may occasionally contain endometrial cells
as well as cervical cells, and hence can give a lead to the presence of cancer in both
sites. However, its detection rate of cervical or endometrial cancer is less than the

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Carcinoma of the cervix

alternative methods of cervical scraps and endometrial brush respectively, therefore,

this method is rarely used in present practice.
b. Cervical scrape: This method involves two components: (1) light scraping of the
superficial cells of the external os by a special wooden spatula. The fishtail ended:
Ayre’s spatula is used (Figure 4). The longer side of the fishtail is firmly applied to
the os and the spatula is rotated 360 degrees to scrape the whole of the circumference
of the squamocolumnar epithelial function. The scrap is smeared on a slide. The
specimen is supplemented by (2) a swab taken from the cervical canal obtained by a
cotton-wool-topped swab. The two specimens are spread on the same slide and
handled as previously described. This technique yields a higher detection rate of CIN
than vaginal smear and hence it is the preferred method.

Carcinoma of the cervix; Figure 4: Cervical smear by Ayre’s spatula.

Scheduling of screening:
The first cytological screening should be initiated shortly after beginning of
sexual activity, and if negative, it should be repeated after one year. Thereafter, it
needs to be repeated every three years. Women at high risk of developing cervical
carcinoma like those indulging in frequent intercourse with multiple partners or
whose partner(s) have multiple sexual consorts need more frequent screening e.g. at
yearly intervals. Women who have repeatedly given negative cervical smears up to
the age of 55 or 60 years do not require further screening; the transformation zone
has by this age, becomes inactive and moved into the cervical canal.
Positive smears: The exfoliated cells in the smear when properly stained
show criteria of dysplasia reflecting the changes in the tissue from which they have
shed (Figure 5). As the epithelial lesions become more dysplastic, the cells exfoliated
from the surface tend to show: (a) more severe nuclear (dyskaryotic) abnormalities,

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Carcinoma of the cervix

including large size, hyperchromatosis, irregular course chromatin granules, wavy

nuclear membrane and may show normal or abnormal mitosis; (b) a decrease in
cytoplasmic maturation i.e. loss of squamification or columnar maturation and
decrease in amount of cytoplasm. The presences of such cellular abnormalities
suggest CIN, carcinoma in situ or invasive carcinoma. The extent of nuclear and
cytoplasmic abnormalities and the number of dysplastic cells in the smear is
proportional to the degree of epithelial abnormality, but since the relationship is not
always linear it is imperative to subject patients with evident and suspicious
cytological abnormality to the same verification routine. When cervical cytology
shows low grade of atypia or suggests a possible inflammatory nature, cytology is
repeated 3-6 months later. Persistence of abnormality indicates colposcopic
verification.

Carcinoma of the cervix; Figure 5: Cervical smears. Four categories:

1. Negative smear; 2. Possibly inflammatory with koilocytes: note that the nuclei are
hyperchromatic with prenuclear halos and mulli nucleation; 3. Positive smear with some
grossly abnormal cells; 4. All cells are abnormal large nuclei and coarse chromatin.

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Carcinoma of the cervix

Detection rates:
In women aged 25 years and above in whom there are no clinical grounds for
suspecting the presence of cervical cancer, cytodiagnosis leads to the recognition of
carcinoma in seven out of every 1000 cases. In four of these, the lesion is preinvasive
i.e. severe dysplasia, in one, it is invasive. There are two or three additional cases in
which CIN of mild or moderate degrees are found. The peak age incidence for
positive smear is 30 - 40 years. These figures apply in developed countries, the
corresponding figures in Egypt are needed in order to estimate the workload entailed
in screening of the population and the cost-effectiveness of well-women screening.
During pregnancy, the findings are approximately the same, but at least 50% of such
lesions undergo reversal after pregnancy.
Attempst to diminish the workload of population screening has included the
following measures:
1. Diminishing the frequency of screening of the population as described above,
instead of the more frequent (yearly) screening utilized some 20 years ago.
2. Concentration on high-risk groups. This still needs to be demonstrated as a safe
strategy.
3. Utilization of nurses and midwives in taking the smear (or the woman herself) and
of technicians in staining and reading of the smears. However, the incidence of
false positive and negative diagnosis is higher than when the smears are taken by
gynocologists or examined by cytologists/pathologists.
4. Automation of scanning of the smears, which react to the intensity of nuclear
staining, and fluorescent microscopy of smears stained with acridine orange to
show up a large amount of nucleic acids in the nuclei. The results of this
approach, so far, have not been satisfactory.
For a satisfactory smear, squamous cells and at least two of the following:
metaplastic cells, endocervical cells, or endocervical mucus must be present.
The false negative rate of cytology is difficult to estimate but it has been estimated
that in routine population screening it can be as high as 20% in the single screening.
The reasons for false-negative Pap smear are numerous, for example:
1. Improper cell collection.
2. Smear too thin or too thick or bloody.
3. Improper fixation or staining.
4. Absence of endocervical cells.

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Carcinoma of the cervix

5. Mistakes in interpretation. It is to be remembered that false negative

cytodiagnosis is commoner in invasive cancer than preinvasive lesion due to
necrotic changes affecting the surface layers.
It is also to be remembered that false positive cytodiagnosis is as serious because
it unnecessarily exposes the woman to the hazards of the diagnostic workup, not to
mention the worry. An important source of false positive results is mainly the
confusing changes due to infections like with trichomonas vaginalis and human
papilloma virus.

3. Diagnostic workup of abnormal smear

The cervical cytological smear is not a diagnostic tool but a screening mechanism.
Diagnosis rests with a tissue biopsy. Colposcopy is an additional tool for directing to the site
of taking the biopsy. This is the ideal approach. If colposcopic examination is not available,
Schiller’s iodine staining test of the vagina coupled with endocervical scrapping is done. If
these are unsatisfactory, cone biopsy is needed.
a. Schiller’s iodine test: The vagina and portiovaginalis of the cervix are stained by pouring
into the vagina of Gram’s iodine solution, consisting of one part of iodine and two parts
of potassium iodide in 300 parts of water. Normally, the squamous epithelium on the
cervix takes a homogenous deep mahogany brown stain due to formation of glycogen
iodine complex. The parts covered by columnar, metaplastic, dysplastic epithelium or
uncovered due to ulceration will be much lighter and appear dirty yellow. These areas are
the target sites of taking biopsies. The test does not exclusively delineate abnormal areas
covered by abnormal epithelium, therefore it cannot reliably indicate the site of taking the
biopsy as achieved by using the colposcope, and; the result is usually taking multiple
biopsies or cone biopsy. In all cases (other than those in whom a cone is taken)
endocervical curettage (ECC) is needed to cover for the possibility of the presence of
endocervical lesion.
b. Colposcopy
The colposcope is a stereoscopic binocular microscope by which the surface
epithelium of the cervix is visualized under bright light under 6x to 40x magnification.
Concentration is made on the transformation zone around the external os with the aim of
diagnosis of atypical metaplasia or dysplasia. Colposcopy is not a screening tool, and again it
does not give a final diagnosis. It points to the site from which a biopsy can be taken in cases
with abnormal cervical smear. Colposcopy mainly evaluates the terminal vascular network of
the surface epithelium, which closely corresponds to histological changes.
In routine colposcopy a magnification of 16x is used and a green filter allows
better color differentiation and visualization of vascular pattern. The cervix is visualized

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Carcinoma of the cervix

and inspected after being moistened with normal saline. Then, a generous amount of 5%
acetic acid is applied to the cervix. Acetic acid helps to coagulate mucus that can be
easily mobbed away. Acetic acid temporarily removes the water from the cells, and in
areas where there is high nuclear density (immature squamo-epithelium, dysplasia or
carcinoma in situ) the epithelium becomes white over a demarcated area. The abnormal
colpscopic findings include:
A. Atypical transformation zone
1. Leukoplakia: heavy thick white lesion that can usually be seen by the naked
eye.
2. Aceto-white epithelium.
3. Punctation pattern.
4. Mosaicism.
5. Atypical vessels
(Refer to picture in colposcopic atlas).
B. Suspect or frank invasive cancer.
C. Unsatisfactory colposcopic findings, meaning that the squamocolumnar function is
not visible; a condition that occurs more often in postmenopausal women.
D. Other colposcopic findings including inflammatory changes, atrophic epithelium,
true erosion, condylomata or papillomata.
Colposcopic examination is frequently followed by endocervical curettage
(ECC), especially in cases of unsatisfactory colposcopic findings. This is done in the
office without anesthesia. A sharp narrow curret is inserted to the level of the internal os,
and then with firm circumferential strokes, the endocervical is curetted two times,
making sure not to pull the curette out through the external os. All the obtained mucus,
blood and tissue debris are received on a piece of paper towel, which is folded over the
specimen, put in the fixative, and sent for pathological examination.
c. Biopsy: After ECC, a punch biopsy is taken under colposcopic guide using Kevorkian pin
and punch biopsy forceps. This takes a 2 - 3 mm deep specimen, which involves the
underlying stroma. The punch should involve the edge of the abnormal area. More than
one punch may be needed if the colposcopically abnormal area is wide. The bleeding is
usually minimal and stops by pressure.
A cone biopsy is needed if the colposcopic examination is unsatisfactory or if the
ECC proves positive in malignant material. Conization is done under anesthesia as an
inpatient procedure. The cervix needs dilatation up to 6 - 8 hegar. With the dilator in the
cervical canal, the cone is excised using a cold fine knife. Diathermy knife is not suitable
because it will destroy a good part of the specimen. The apex of the cone should be high
in the cervical canal as near to the internal os (Figure 6). The base of the cone should be

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Carcinoma of the cervix

outside the Schiller-light-colored area around the external os. A stitch can be put at 12
o’clock point of the circumference of the cone as a landmark to orientate the site of
pathology. Serial slices, usually 20 in number, are needed to evaluate the cone. Each
slice is separately embedded, and multiple e.g. 5 sections are examined from each. A
cold knife cone may leave bleeding points. These can then be touched by a diathermy
point. Occasionally, a big crater will need to be covered by folding-in of the vaginal
epithelium by anterior and posterior suture of Sturmdorf’s type. The suture initially picks
up the posterior flap of mucosa in the midline near the edge and long ends are left. Each
of the long threads is directed high into the cervical canal, passing through the wall of
cervical canal and out through posterior lip near the fornix, about 2 cm from the site of
the initial suture. The other end of the suture is similarly treated. Tying the two ends will
invert the mucosal flap and control the bleeding. The procedure is repeated for the
anterior lip. The lateral parts of the wound may need to be approximated by one or more
interrupted sutures.
Conization is not without risks. It may result in a) cervical stenosis and infertility
or b) cervical incompetence. Therefore, it is resorted to in young patients, only when
necessary i.e. in cases of unsatisfactory colposcopy and cases with positive ECC.

Carcinoma of the cervix: Figure 6: Cone biopsy of the cervix.

Large Loop Excision of the transformation zone (LLE)

Instead of cone biopsy, an electrified thin wire loop is used to remove the
transformation zone under colposcopic guide (or after iodine staining). The procedure
combines the diagnosis and treatment. It can be done as an outpatient procedure under
local anesthesia. A wire loop large enough to remove at least the abnormal area on a
single strip of the cervix is used. The strip removed is sent for histopathology. The
problem with this approach is difficulty in assessing the margin of the pathology and in
positive cases a closer follow up is more needed than with cone biopsy procedure.

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Carcinoma of the cervix

Diagnosis of the invasive carcinoma of the cervix

The clinical picture usually suggests the diagnosis:
Symptoms:
1. Irregular bleeding: usually the acyclic bleeding begins, as contact bleeding following
coitus or douching, and then will be spontaneous. It can be so heavy to be life-
threatening.
2. Increased vaginal discharge is at first mucoid then it gets purulent and later becomes thin
dirty brown with shreads of hanging tissue. It has a foul penetrating smell.
3. All other symptoms occur late in the disease and indicate involvement of other pelvic
structures. These can include frequency, and burning micturition. Strangury (painful
desire to micturate) can be severe and this precedes incontinence, which can be urgency
incontinence and later becomes continuous dribbling due to fistulation. Rectal pain, deep
pelvic pain, low back pain. Rectal fistulation occurs latter. Later on, sciatica-like root pain
shoot down the lower limbs and these can get very severe. Loss of weight and anorexia
and cachexia develops. There is no more miserable way of dying than dying from
carcinoma of the cervix.
A remarkable feature of carcinoma of the cervix in our practice is that the patients
present late in spite of all the emphasis put on the importance or irregular uterine bleeding
in the perimenopausal age in medical teaching.
Physical signs
The combination of induration, friability, contact bleeding and fixation due to spread
to surrounding structures are highly suggestive of the disease. The diagnosis is usually made
later if the growth is entirely endocervical; the external os looks normal, while the cervix feels
enlarged and barrel-shaped.
Rectal examination can assess the extent of spread of the disease better than vaginal
examination.
Investigations:
Pretreatment evaluation should comprise the following:
1. Examination under anesthesia (EUA).
2. Biopsy by punch biopsy forceps.
3. Cystoscopy.
4. Proctoscopy.
5. Intravenous pyelography.
6. Ultrasonography.

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Carcinoma of the cervix

7. CT scan does not offer much help in assessing the extent of parametric spread and
lymph node involvement. MRI is a valuable tool for assessing spread in the
parametrium and of nodal involvement.
8. Lymphoangrography: is not of much help in assessing involvement of pelvic
lymph nodes. However, it may indicate the involvement of the periaartic lymph
nodes. Due to limitation of methodology, this radiography is rarely used.
9. Tumor markers such as CA125, CA 19 - 9, CEA, and squamous cell carcinoma
antigen (SCCA) are rarely used because of lack of sensitivity and specificity.
10. CT scan of the lungs.
11. General assessment of general fitness.

Management of carcinoma of the cervix

Treatment of CIN:
Management of the various grades of CIN involves a number of options; the choice
between them depends upon: 1) the degree of dysplasia, 2) the age of the patient and her
further desire of pregnancy, 3) prior conization for diagnosis, 4) the expected reliability of
follow-up, 5) the patient’s personal preference. The pros and cones of the various treatments
should be explained to the patient, and she should be involved in the decision about
management plan.
Treatment options for CIN
1. Observation.
2. Electrocautary.
3. Cryosurgery.
4. Laser.
5. Conization: see above.
6. Large loop excision (LLE): see above.
7. Hysterectomy.
1. Observation alone is rarely used, and only if the diagnosis of CIN I is made in a young
patient who can be kept under close observation.
2. Electrocautary: when properly done (deep), it can eradicate early CIN with a success rate
of about 90%. Cytological and colposcopic follow-up is required. The procedure can
cause secondary hemorrhage and may result in cervical stenosis and infertility.
3. Cryosurgery: It is an outpatient treatment. It is less painful than electrocautary and less
likely to cause secondary hemorrhage. The refrigerant used in cryosurgery includes freon,
carbon dioxide or better liquid nitrogen. In experienced hands, it can entail a recurrence

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Carcinoma of the cervix

rate of only about 1%. The probe chosen should cover the entire lesion, and a 4 to 5 mm
ice ball around the probe is required for adequate freeze. A double-freeze technique is
used; the cervix is allowed to thaw for 4 to 5 minutes and is then frozen again using the
same technique.
4. Laser surgery: This is a most promising approach. The term laser is an abbreviation for
light amplification by stimulated emission of radiation. Carbon dioxide laser is the type,
which has been mostly used for this purpose. The energy of the laser is absorbed by the
water in the tissue, which is destroyed by vaporization. Due to focusing of energy, the
laser beam acts like a knife. Since the tissue is destroyed by vaporization, the bleeding is
limited and the base of destruction is clean, with little necrotic tissue and rapid healing.
The depth of destruction should be 5 to 7 mm. This depth diminishes the recurrence rate.
The procedure is more painful than cryosurgery and may need anesthesia.
5. Conization of the cervix: This approach is utilized if the dysplasia is marked and the
limits of the lesion could not be defined by colposcopy, but there is a need to preserve the
uterus. The technique has been described under diagnosis.
6. LLE of the transformation zone: see above
7. Total hysterectomy: It is the most appropriate treatment of major grades of CIN in
patients who have completed childbearing. There is no need to remove the vaginal cuff
with the uterus unless colposcopy has indicated spread of the lesion beyond the portio
vaginalis. Hysterectomy can be done by the abdominal or vaginal route; the latter
approach is attended with less morbidity. In all cases, however, frequent cytological
follow-up is still required.
Follow-up: A follow up colposcopy and smear at 6-month post treatment. If normal, cervical
cytology is then repeated after 6 months and thereafter annually. If the cytology is negative
for 3 years, the patient is returned to the normal screening program.

Treatment of invasive carcinoma of the cervix

The treatment of invasive carcinoma of the cervix utilizes surgery, radiotherapy or a
combination of them. Surgery usually involves mainly radical hysterectomy in the form of
Wertheim’s/Meigs’ operation, but may involve total hysterectomy or pelvic exenteration
under specific indications. Radiotherapy usually involves mainly intracavitary radiation by
radium or cesium (brachytherapy) and external irradiation. Chemotherapy is having a limited
role in carcinoma of the cervix. Advanced cases need palliative measures to diminish terminal
suffering. The plan of management should depend upon 1) the availability of treatment
facilities and expertise, 2) surgical fitness of the patients, 3) the stage of the disease, 4) the
risk of lymph node involvement, 5) presence of complicating conditions. The risk of lymph

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Carcinoma of the cervix

node involvement increases with a) increasing tumor stage, b) large sized tumor, c)
lymphovascular space involvement, and c) poorly differentiated histology.

Treatment plans:
1. Stage Ia1 (superficial carcinoma) are treated with total hysterectomy without
lymphadenectomy. This can be done by vaginal or abdominal route. When
colposcopic examination demonstrates no evidence of extension of the tumor onto the
portio or adjacent vaginal fornices, partial vaginectomy i.e. removal of a wide vaginal
cuff need not be done, since vaginal lymphatics are not involved. The hysterectomy
specimen must be subjected to the most careful examination to confirm the minimal
stromal invasion. If deeper than expected invasion is found, additional treatment will
be needed in the form of external radiation. The expected 5-year survival is 100%.
Exceptionally, if the patient is unfit for surgery, intracavitary radiation is used.
In a patient keen to preserve her fertility, a good conization followed by close
observation is resorted to. The cone should contain the entire lesion with all the
criteria of minimal invasion being reconfirmed.
2. Stage Ia2 and Stage Ib are treated by radical hysterectomy. One can expect that 8% of
these patients will have positive lymph nodes. Lateral pelvic wall irradiation is not
needed in these cases if there is no risk factor of lymph node involvement (tumor <4
cm in diameter, no lymph vascular space involvement, and well differentiated
squamous carcinoma). Patients who are not good surgical risks can be treated with
intracavitary radiation. The expected 5-year survival rate for Stage Ib is around 78%.
3. Stage IIa is treated by radical hysterectomy followed by external radiation. The latter
covers the lateral pelvic wall - lymph nodes which may be left behind. The surgically
unfit patient can be primarily managed by intracavitary radiation plus external
radiation. However, radiotherapy is always an equally effective to surgery and can be
safely used when expertise in the latter is not available. The expected 5-year survival
rate is in the region of 60%.
4. Stage IIb and Stage III are primarily treated by a combination of intracavitary and
external radiation. Certain cases with Stage IIIa may be treated by radical
hysterectomy plus vaginectomy followed by external radiation. This approach is
required in cases with complicating conditions, which contraindicate primary
radiation therapy.
Contraindication for radiotherapy include: (1) chronic salpingoophoritis, (2)
pyometra, (3) fibroid uterus distorting the uterine cavity, (4) associated ovarian tumor
(these can however, be removed before radiotherapy), (5) chronic pyelonephritis
(may be flared up) and (6) certain types of cervical carcinoma: In the past there was a

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Carcinoma of the cervix

feeling that adenocarcinoma, endocervical carcinoma and well differentiated

squamous cell carcinoma may be more resistant to radiation therapy, but the present
attitude indicates that these ideas are not correct.
Treatment of Stage III carcinoma of the cervix gives a 5-year survival rate of
about 30%.
5. Stage IV cases are treated by various types of pelvic exenteration (if the patient is fit
for that), followed by external radiation. Sometimes, all that can be done are
palliative measures. The survival rate in such cases is between 10 to 20%.

Surgical management:
Radical hysterectomy as originally performed by Wertheim of Vienna involved
abdominal extended hysterectomy and partial lymphadenectomy. Schauta of Vienna
introduced the vaginal extended hysterectomy with the aim of improving the mortality of
Wertheim’s operation. Meigs of Boston, USA developed Wertheim’s operation by
incorporating extensive parametrial dissection and extensive pelvic lymphadenectomy. In this
latter operation the following structures are removed either in mass or piecemeal:
- The uterus
- Tubes and ovaries – the ovaries may be conserved in young women with stage Ib, thus
avoiding early menopausal symptoms
- Broad ligament
- The parametrium including most of the uterosacral ligament and Mackenrodt’s ligaments
- The upper one half or three-fourth of the vagina
- The external iliac, obturator, internal iliac (hypogastric) and common iliac lymph nodes

Operative hints:
1. Adequate midline incision extending 5 cm above the umbilicus. Exploration of the
abdomen and testing the mobility of the uterus will indicate the task ahead.
2. Dissection of the bladder from the cervix: The two round ligaments are cut,
transfixed and sutured. The peritoneum of the uterovesical pouch is incised in
between, and the bladder is separated from the front of the cervix with blunt
dissection with occasional scissor snips of the bladder pillars on the sides. If the
base of the bladder is infiltrated, the surgeon is left with either desisting the
operation or proceeding to partial excision of the base of the bladder and
reimplantation of the ureters in the bladder pouch. Parametric dissection is expected
to be difficult as well in such cases.

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Carcinoma of the cervix

3. Opening the broad ligament after severing the infundibulopelvic ligament. Its
posterior leaf is incised down on the medial side of the ureter (which is recognized
at the point of crossing upon the bifurcation of the common iliac artery).
4. Removal of the lymph nodes around the external and common iliac vessels: The
nodes on both sides of the vessels, and underneath them should be removed. The
dissection of the vessels should start from the point of origin of the inferior
epigastric and deep circumference iliac arteries below (behind the inguinal
ligament), and reach to the origin of the common iliac artery. Care should be
exercised not to cut the small branch from the common iliac artery to the ureter.
Occasionally the inferior epigastric vessels give an aberrant branch to the obturator
fossa which if cut will cause bleeding. There is no need to injure the iliofemoral
nerve, which is lateral to the external iliac artery.
5. Development and dissection of the pararectal fascial space (Figure 7): This
potential space is having the ureter crossing its top in its way from the posterolateral
pelvic wall towards the bladder. It is bound anteriorly by Mackenrodt’s ligament,
postrolaterally by the pelvic wall muscles carrying on them the internal iliac
(hypogastric) vessels and their branches and medially by the uterosacral ligament
and the rectal pillar underneath, and the rectum. The lymph nodes on the internal
iliac arteries (hypogastric) are dissected. The internal iliac artery should be followed
down to its anterior division from which arises the obliterated hypogastric, uterine,
superior, middle and inferior vesical and vaginal, together with the obturator and
inferior gluteal before it leaves the pelvis as the internal pudendal (Figure 8). It is
advisable to exercise great care not to injure the internal iliac vein and its tributaries.
These tributaries of the internal iliac vein form a flattened plexus of veins; some of
the branches (the parietals) leave the pelvis immediately after their origin (end). If
these are torn, they can cause considerable bleeding which is difficult to control,
blood wells up into the pelvis. Trial to secure bleeding points (areas) by clamps will
further tear other veins. The best method of control of such venous bleeding is a
firmly applied pack for 3 to 5 minutes. It is sometimes advisable to leave the pack
and shift to dissection of the other side.

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Carcinoma of the cervix

Carcinoma of the cervix; Figure 7: Potential spaces in the endopelvic fascia.

1. Mackenrodt ligament; 2. Uterosacral ligament; 3. Pubocervical faschia; 4. Paravesical
space; 5. Pararectal space; 6. Ureter; 7. vesicovaginal space; 8. Rectovaginal space.

Carcinoma of the cervix;Figure 8: Wertheim’s Meigs Operation. The left pararectal and
paravesical spaces opened. 1. Common iliac artery; 2. External iliac artery (lymph nodes
removed); 3. External iliac vein; 4. Internal iliac artery; 5. Uterine artery crossing on the
ureter at the side of the uterus; 6. The pelvic part of ureter completely dissected but left
adherent to the posterior leaf of the broad ligament; 7. The bladder retracted downward; 8.
Obturator nerve and vessels.

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Carcinoma of the cervix

6. Development and dissection of the paravesical fascial space: The fatty connective
tissue roofing this space is crossed over by the obliterated hypogastric, which is
secured anteriorly and lifted backward, to its origin from the anterior division of the
internal iliac artery. It frequently has a common origin with the uterine artery, and
this procedure of dissection will direct the surgeon to the origin of the uterine artery.
The space is bound anteriorly by pelvic wall muscle (the obturator and the levator
ani), posteriorly by the Mackenrodt’s ligament and medially by the bladder. The
obturator lymph nodes are dissected from the lateral side, avoiding injury to the
obturator nerve and vessels. Injury of obturator nerve results in loss of motor supply
to the adductors of thigh and sensation on the inner side of the thigh.
7. Ligation of the uterine vessels and completing dissection of the ureter: The uterine
vessels are ligated at the origin in the lateral pelvic wall. When the medial stump of
the artery is lifted inward, the uterine artery is found to be actually forming the roof
of the ureteric canal. A curved artery passed in the ureteric canal from behind will
allow dissection of the ureter by lifting the roof of the canal. The bladder pillars,
(between the lateral angles of the bladder and the cervix) are then cut, and this
allows pushing down the bladder base at the sides and completing the dissection of
the part of the ureter between the bladder base and the anterior vaginal wall. The
branch from the superior vesical to the lower part of the ureter can usually be
preserved.
8. The above procedures are then completed on the other side.
9. Posterior dissection: The uterosacral ligaments are cut near the rectum and secured
by ligatures. The peritoneum of the Douglas pouch is incised and the posterior
vaginal wall is dissected from the rectum. By pulling on the uterine specimen, the
vagina can be further dissected both on its anterior and posterior aspects. The
Mackenrodt’s ligament can then be seen stretching from the vagina to the lateral
pelvic wall above the levator ani.
10. Securing and cutting the Mckenrodt’s ligaments: This is best done by an aneurysm
needle carrying the ligating string (No 1) silk a vicryl ligature (Figure 9).
11. Cutting the vagina: This is done between two pairs of right-angled curved clamps,
and is done as near as possible to the pelvic floor. The vaginal stump is closed by
two or three stitches. The ureters are inspected; they are hanging to the lateral leaves
of pelvic peritoneum.
12. The periaortic glands are examined and can be biopsed if enlarged; care should be
exercised not to injure the short vertebral branches.
13. The pelvic peritoneum is approximated, usually above the tip of a suction drain.

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Carcinoma of the cervix; Figure 9: Wertheim’s/Meig’s operation. 1. Tying the Mackenrodt

ligament by underrunning by aneurysm suture carrier; 2. The paravesical space; 3. Bladder;
4. Vagina; 5. Ureters; 6. Uterine vessel stump.

Complications of the radical hysterectomy:

The primary mortality of the operation is 1 - 2 percent except in skilled hands.
1. Hemorrhage: Wertheim / Meigs hysterectomy requires on the average two units of
blood transfusion; two more units should be ready.
2. Injury of important structures including vessels, nerves, urinary bladder, ureter or
rectum can occur during operation. These should be appropriately repaired.
3. Retention of urine due to denervation of bladder is common, and continuous
drainage by Foley’s catheter is required for 7 days. This is followed by periodic
drill by clamping and releasing the catheters for 3 more days before final removal.
4. Necrotic uretrovaginal fistula can result from devascularization of the pelvic
ureter. The blood supply of ureter from the common iliac and supervesical arteries
should be preserved. The ureter does not need to be lifted from the posterior leaf
of the broad ligament; since this increases the chance of devascularization of the
ureter.

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Carcinoma of the cervix

5. Infection and pelvic cellulitis.

6. Lymphocele: Due to extensive dissection and removal of lymph nodes. Collection
of serous fluid occurs in the space left behind by the operation can result in
formation of a big lymphocyst or lymphocele, which can persist for a long time.
Closed suction drainage should decrease the chance of its formation. It can be
aspirated under ultrasonic guide if small or marsupialized into the peritoneal
cavity if big. Secondary infection requires drainage.
7. Venous thrombosis and pulmonary embolism is a real threat after major pelvic
surgery that is usually followed by prolonged immobilization (unnecessary, and
better avoided).

Radiotherapy:
This is the treatment of choice in the majority of cases and is applicable at all stages
of the disease. It carries lower primary mortality (< 0.5%). It aims at giving a carcenocidal
dose of ionizing radiation to all areas where there is a growth or where there is likely to be a
growth. The tissue of the cervix and in its near vicinity are aimed to receive 7000–8000 rads
(r) (equivalent to 70–80 gray or gy in the presently used System International Unites), the
parametrium and the lateral pelvic walls are aimed to receive 5000 r (50 gy). These sites are
usually designated respectively as points A and B. Point A is situated 2 cm above the vaginal
vault and 2 cm to the side of the cervix, while point B is 3 cm lateral to point A. The first aim
is achieved by intracavitary radium. The dose declines rapidly at a short distance from point
A. The required dose at point B requires supplementation by external beam radiotherapy
delivered by cobalt units or linear acceleration high voltage X-ray machine.
Mechanism of effect of radiotherapy: Ionizing irradiation (whether it is gamma rays
of radium or cesium or X-rays of the linear accelerator) have two effects: The first or direct
effect includes injury to nuclear material of the rapidly dividing cells of the tumor. This injury
results in death of the tumor cells, its degeneration, but most importantly their differentiation
that means loss of ability to multiply i.e. their sterilization. The second, indirect effect is a
host tissue reaction including devascularization and fibrosis, and thus rendered the tumor bed
an infertile soil for the growth of any cancer cells, which escape destruction or differentiation.
A balance between these two effects, direct and indirect, is the aim of therapy. Overdosage
not only causes adverse reactions and permanent ill effects but is less likely to cure the
carcinoma because of burning the host tissue and interfering with the growth - limiting host
tissue response. This is the basis of administering the required dose piecemeal. Successful
radiation therapy depends on greater sensitivity of cancer cells as compared with the cells in
adjacent normal tissues and the greater ability of the latter tissue to recuperate after radiation.

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Carcinoma of the cervix

Intracavitary radiation; Brachytherapy: In spite of the great advance in external

beam radiotherapy systems and their ability to focus the beam upon the required depth in the
body, intracavitary radiation has remained the primary, first step, approach in the treatment of
carcinoma of the cervix. Radium is the isotope that has traditionally been used for this
purpose. It has a long half-life of some 160 years. It is available in the form of short rods
covered in lead containers. In recent years, radium has been almost completely replaced by
the cheaper and more readily available artificially produced isotopes such as cesium, cobalt
60 and irridium.
The traditional method of treatment is to place the isotope in the uterine cavity and in
the two lateral vaginal fornices (Figure 10). The cervical canal itself is usually left empty to
avoid excessive irradiation to the bladder base and rectal ampulla. The vaginal sources are put
in cork ovoids, which are kept apart by a steel spring spacer. Moreover, the vagina is tightly
packed by gauze to displace the bladder and rectum away from the source. The radium is
applied for 24–48 hours and then removed and the treatment is repeated on three occasions
with an interval of one or two weeks (Stockholm technique); or alternatively two applications
are made, each for 48-hour duration separated by 10 days (Manchester technique). A third
technique is to apply a smaller dose divided equally between the vagina and the uterus and
left for 12 to 14 hours every day for 5 to 7 consecutive days (Paris technique).
In all the approaches the dose delivered at the lateral pelvic wall needs to be built up
to 5000 r by external beam radiation; this is called total pelvic irradiation.

Carcinoma of the cervix; Figure 10: Loading of brachytherapy. Intrauterine source and
vaginal source in vaginal ovoids and spacer.

The use of radioactive sources in brachytherapy involves exposure to radiation of the

medical and nursing staff whilst the sources are in the theatre and/or in situ in the patient,
hence the development of the after-loading technique. In the latter, the more rigid applicators

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Carcinoma of the cervix

are inserted under general anesthesia and left in the patient. The source is thereafter filled in
with the staff well protected. Much higher doses of cesium or cobalt 60 is used in each
application but they are left for a much shorter time: 15 - 30 minutes in contrast to 24 - 48
hours in the traditional techniques. There are manual and automated system for after-loading.
The latter is more expensive and needs expertise but it yields more protection of personnel,
and allows more patients to be treated in a short time.
Teletherapy: External irradiation: The linear accelerator is the preferred approach
used to allow proper focusing of the effect to the required depth without irradiation of the
tissue on the way. Alternatively, gamma rays are delivered from a cobalt beam. The treatment
is delivered in small daily doses over a period of 3-6 weeks. This fractionation of the dose
ensures a balanced effect on the tumor and the host tissue and carries less risk to the
surrounding normal structures. If there is a big tumor mass and distorted anatomy, the
external irradiation can be delivered in advance to brachytherapy to reduce the mass of the
tumor and make the subsequent intracavitary treatment less risky.
Extended field irradiation aiming at covering the periaortic lymph nodes is used in
advanced cases of carcinoma of the cervix. The field irradiated involves the pelvis and
extends to reach the dome of the diaphragm. The total dose given to the extended treatment is
4000 - 5000, with an extra dose of 1000 r to the pelvis.

Complications of radiotherapy
The morbidities resulting from properly conducted radiotherapy should be low and
much lower than surgery. These comprise:
1. Immediate effects include malaise, anorexia, and wasting, loose stools and may be
diarrhea. Symptomatic treatment is usually helpful, but diarrhea can be really
distressing.
2. Flaring up of pelvic infections in cases of salpingoopheritis can result in pelvic or
general peritoritis.
3. Flaring up of urinary tract infection can also occur causing pyelonephritis.
4. Late effects: These result from overirradiation of the rectum and the bladder; the
rectum is more vulnerable because of the infected contents. The symptoms include
rectal pain, tenismus, bleeding, frequency, and urgency of micturition. Later on
fistulation may occur. The radiological fistulae are the worst fistulae, because of the
fibrosis and poor vasculation of the edges.
5. Frozen pelvis may result from excessive fibrosis in the pelvic cellular tissue and can
result in severe pelvic pain and heaviness, and may occasionally result in intestinal
obstruction.

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6. Severe menopausal symptom can occur in premenopausal women but can be safely
treated by hormone replacement. The vagina may be obstructed as a result of
treatment and can become atrophic. This can cause dyspareunia or frequently
apareunia.

Combinations of surgery and radiotherapy

Combination of radiotherapy and surgery is planned from the start in Stage 1b2, stage
II and some Stage III carcinoma. This is the routine followed in 80% of cases in some clinics.
They are complimentary and usually radiotherapy is done after surgery. Sometimes the order
is reversed, and this is particularly valuable if the cervical lesion is bulky e.g. in barrel-shaped
endocervical growth. This cannot be generalized because the subsequent radical operation can
be rendered more difficult because of radiation reaction. This approach will expose tissues
e.g. the ureter, to the two risks with increased incidence of fistula formation. Healing of the
vaginal vault will be delayed. These disadvantages can be diminished by giving a reduced
dose of radiotherapy e.g. two-thirds of the usual dose; but this carries the disadvantage of
losing the chance of cure if the first treatment is not successful due to under-dosing since the
chance of effective treatment by radiation is less in cases which recur after having received
the prior incomplete radiation.
External beam - radiotherapy is to be used in cases of occult carcinoma (Stage Ia2) in
which marked invasion of the stroma is discovered after a simple hysterectomy done on the
assumption of preinvasive or minimal invasion carcinoma cervix.

Chemotherapy in cervical carcinoma

Chemotherapy is much less commonly used in cervical carcinoma. This has been
because: 1) 95% of cases of squamous cell carcinoma comprise types which are less sensitive
to chemotherapeutic agents. 2) Chemotherapy is usually resorted to after failure of
radiotherapy, which renders the tumor less vascular and less amenable to chemotherapy. 3)
The chemotherapeutic agents are usually nephrotoxic and may not be suitable for cases where
kidney functions are already compromised by ureter stricture and infection.
Chemotherapy has been recently used in treating advanced and recurrent cases of
carcinoma of the cervix with a small to moderate success. A number of agents have been
utilized including bleomycin, vincristine, methotrexate (combined with leucoverin rescue) but
the most promising modality is cisplatinum based treatment. Intraarterial infusion of
chemotherapeutic agents has been tried with occasional success. The chemotherapy is
continuously infused for some 10 weeks into an intraarterial catheter introduced

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percutaneously into the femoral artery and pushed up the abdominal aorta to a point below the
origin of the inferior mesenteric artery. These approaches are still in trial phase.
Another possibility, which is still under trial, is utilizing chemotherapy prior to
intracavitary radiation therapy in Stage II and Stage III carcinoma cervix. The systemic
effects of such approach may be severe.

Cervical stump carcinoma

The possible development of carcinoma in the cervical stump is the reason for
advocating total rather than subtotal hysterectomy; the technical difficulty is rarely enough
reason for avoiding the total operation. The total hysterectomy is particularly required in
parous women. Stump carcinoma can arise de novo in the stump and can represent a
recurrence of endometrial carcinoma after subtotal hysterectomy done for improperly
diagnosed cases of uterine bleeding. Consequently, there is a higher proportion of
adenocarcinoma in stump cancer than in the usual cases with the body present.
It is expected that the diagnosis of stump cancer should be made earlier because of the
unexpected occurrence of the symptoms (bleeding) in a patient whose uterus has been
removed. However, the prognosis of stump carcinoma is generally worse (an overall survival
of 20 to 30%) because of the following reasons:
1. The close proximity to bladder, ureter and pelvic peritoneum caused by the prior
surgery. These structures are more readily infiltrated in stump carcinoma.
2. Difficulty and high morbidity of radical surgery.
3. Inapplicability of intracavity radiotherapy. Delivery of the usual dose by external
beam radiotherapy carries increased risk of bladder, rectal and ureteric over-
irradiation.
The best approach for management is radial surgery if applicable which can involve
removal of the bladder base and reimplantation of the ureters in the remaining part of the
bladder. This is followed by external radiation. In advanced cases pelvic exenteration may be
done.

Carcinoma of the cervix in pregnancy

The presence of pregnancy should not delay the diagnosis of cervical carcinoma. This
is achieved when bleeding during pregnancy is not always presumed to be caused by
separation of the placenta. The pregnancy does not influence the progression of the
carcinoma. Sometimes the management of the case presents a personal and ethical dilemma
because of considerations related to the fetus. However, one cannot wait long to get a viable
fetus before beginning a definite treatment. If the condition is diagnosed before the 24th week

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the interest of the fetus is usually disregarded, unless the cancer is too advanced beyond
reasonable cure. During the first weeks of the pregnancy, radical surgery can be carried out, if
applicable. The planes of the pelvis are more easily developed but troublesome bleeding from
congested veins is expected; this requires a skilled surgeon. In later pregnancy, one may wait
for some weeks to get a viable fetus after counseling with the patient. In these cases, the
uterus can be evacuated by upper segment cesarean section (vaginal delivery is out of place).
After 10 - 14 days, one can start radiotherapy or perform radical surgery as seems appropriate
by the stage of the disease. If radiotherapy is the treatment chosen, it is better to begin by
whole pelvis external irradiation followed by brachytherapy.

Advanced and Recurrent Carcinoma of the Cervix

Late presentation of carcinoma of the cervix is quite common in our practice. It can
present with bleeding that can be so heavy to be life threatening. Due to tissue necrosis and
saprophyte bacterial action, a thin sero-sanguineous discharge is present; this has a very foul
permeating odor. Pain results from extrauterine extension to important pelvic structure. It can
be very severe and contributes to cachexia (wasting + appearance of ill health).
Two types of pain can be present: Visceral pain, which results from spread to
important viscera. It is a dull diffuse pelvic and back pain and heaviness which is exacerbated
by the function of the involved viscus i.e. severely painful urination or defecation. Somatic
pain results from involvement of the nerve sheaths of the sacral or lumber nerves or roots.
This causes a sharp lower back and lower limb pain, which has a defined course, which
shoots down the lower limbs. Fistulation partially relieves the visceral pain but the misery of
incontinence of urine or stools makes life unbearable; carcinoma of the cervix is one of the
worst ways to die.
Recurrence of carcinoma following initial therapy occurs within the first or second
year, rarely it occurs after this. It results in weight loss, leg edema (excessive and often
bilateral), visceral or somatic pain, serosanguineous discharge, progressive uretral
obstruction, left supracalvicular lymph node enlargement, cough, chest pain and hemoptysis
or combinations of them.
The diagnosis usually requires a biopsy from local recurrence. Cytological changes
are caused by prior radiation, and smear examination results in detection of suspicious cell for
several months after completion of therapy and may erroneously lead to supposition of
persistence of the disease. A fine needle biopsy under ultrasonic or CT scan guide may be
used to obtain biopsy. Repeated IVP is needed to follow any progression of ureteric stricture.
CT lung and abdominal scan and bone scan are helpful. Lymphoangiography can detect
periaortic lymph node involvement. After the advent of monoclonal technology, tumor

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markers particularly squamous cell carcinoma (SCC) antigen have been used to follow-up
patients of treated cervical carcinoma and for detection of recurrence of the disease.
Adenocarcinoma can be followed up by CA-125 assay (see under endometrial carcinoma).
The management of advanced and recurrent cervical carcinoma is to be done in
special cancer institutes and can involve the following lines:
1. Radiotherapy: There are indications that reirradiation of sites previously treated by
radiotherapy is poorly effective. For sites not previously irradiated e.g. periaortic lymph
node radium can be occasionally effective. Radiotherapy can give reasonable palliation in
some cases.
2. Chemotherapy (see above) can be occasionally effective.
3. Pelvic exenteration: Brunschwig introduced pelvic exenteration operation some 40 years
ago. With improvement of supportive care during major surgery, these types of seemingly
mutilating surgery is more commonly accepted by patients and practiced by experienced
surgeons. Anterior pelvic exenteration means concurrent removal of the urinary bladder;
posterior exenteration means removal of the rectum; while total exenteration involves
removal of the two structures. In the past, the ureters were implanted in the colon.
However, this was followed by severe electrolyte imbalance and ascending
pyclonephritis. Nowadays the ureters are implanted in a separated segment of the bowel,
either ilial or colonic. Its blood supply is maintained and its distal end is made to open in
the abdominal wall (conduct formation). This diminishes the incidence of the above
complications.
4. Defunctioning of involved viscera like colostomy, and anastmosing ureters to a conduct.
5. Measures for relief of distressing somatic pain: Several approaches can be used, including
drugs (which should be generously supplied), intrathecal absolute alcohol injection
(relieves pain for several weeks) or resection of spinothalamic tract of the spinal cord.

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Chapter 17
TUMORS OF THE CORPUS UTERI

Contents
• Myoma including discussions of Myomectomy and Hysterectomy
- Etiology
- Pathology
- Secondary changes
- Clinical picture
- Management
Of asymptomatic myomata
Of symptomatic myomata:
§ Medical
§ Surgical (Myomectomy/hysterectomy)
§ Of cases presented with infertility
§ Myoma with pregnancy
• Rare benign tumors: as hemangioma, cysts
• Adenomyosis
• Endometrial carcinoma
- Epidemiology - and possible etiological factors
- Pathology - spread
- Clinical picture
- Diagnosis
- Staging
- Prognostic factors
- Treatment
Surgery
Radiotherapy
Hormonal therapy
Results
• Sarcoma

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Myoma
A myoma is a benign tumor of the uterus composed mainly of smooth muscle cells but
containing varying amounts of fibrous connective tissue. It is also known as leiomyoma to
emphasize the smooth muscle origin, fibromyoma to emphasize the fibrous connective tissue
element and also fibroid. The latter is the commonest name used though being least correct.
Myomata (also myomas) arise from the smooth muscles of the myometrium and are usually
multiple. Myoma is a very common tumor and may be the commonest tumor in the body but
is frequently asymptomatic. Careful postmortem studies indicated a prevalence of 50% in
women 40 years old or more. The condition is increasingly diagnosed after the frequent use of
pelvic sonography. Myomata grow slowly and malignant transformation is quite rare.

Etiology
The exact etiology of myoma is unknown. However the following factor are
predisposing:

§ Age
Myomata are usually diagnosed in women between the age of 35 and 45 years.
However, they start their existence long time before that. Myomata are rarely diagnosed
before the age of 20. After menopause myoma cease to grow but some growth may occur
particularly in obese women.
§ Parity
Myomata are more common in nulliparous or relatively infertile women, but are not
known whether infertility causes myomata or vice versa, or whether both conditions have a
common cause. It seems that deferment or infrequent pregnancy as a consequence of late
marriage or divorce predispose to myomata, the pregnancy seems to be protective against the
development of myoma, i.e. both voluntary and involuntary infertility predispose to myomas.
§ Race
Myomata are commoner in black women. It is quite a public health problem in sub-
saharran African countries.
§ Family history: is frequently positive.
§ Hormonal influences
A. Estrogens: seem to stimulate the growth as indicated by:
- postmenopausal regression,
- growth during pregnancy; but this can be an effect of increased vascularity.

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- the relation to infertility suggests that a continuous exposure to long estrogen

stimulation uninterrupted by pregnancy and /or lactation enhances the
development or the growth of myomata.
- The commonly associated anovulation, follicular cysts, endometrial
hyperplasia, endometrial carcinoma and endometriosis.
- The old notion that the prolonged use of combined oral contraception
predispose to myomata has been contradicted by recent epidemiological
studies indicating the opposite i.e. diminished risk results from ever use of
COCs.
- long-term treatment with progestogens e.g. by DMPA may arrest the growth
of myomata.
- regression of myomata under the effect of long-term treatment with GnRH
agonists which produces a state of temporary menopause. After the cessation
of such treatment, the tumor grows back to its original size.
- demonstration of the presence of estrogen receptor in the cells of the myomata
and in a higher concentration than in surrounding myometrium.
- Investigations suggested relatively less conversion of estradiol to the less
active estrone in patient with fibroid.
B. Other endocrine influences that have been associated with myomata include 1) high
prolactin, 2) low FSH, 3) increased production of ovarian growth factors like insulin-like
growth factor-I, epidermal growth factor and growth factor-alpha.

Pathology
- Myomata may be single but mostly multiple. As many as a hundred or more myomata can
be present in the uterus. They can reach huge dimensions filling the abdominal cavity.
Sometimes the uterus is studded by many small myomata.
- Myomata usually develop in the corpus uteri, cervical fibroid account for 1-2%
of cases.
- Myomata can be subserous, interstitial, or submucous according to their
relation to the peritoneal coat and the endometrium (figure 1). A subserous
myoma can become pedunculated. It can also grow between the two leaves of
the broad ligament. A submucous myoma may become polypoidal (when it
projects in the uterine cavity by more than half of its circumference). This
fibroid polyp can as a result of uterine contraction dilates the cervix and
protrudes in the vagina. This can be associated with partial or complete uterine
inversion. Myoma can rarely develop in the round ligament.

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Tumors of the corpus uteri

Tumors of the corpus uteri (Figure 1): Location of Myomata. 1. Interstitial; 2. Subserous; 3.
Submucous; 4. Pedunculated Subserous; 5. Pedunculated submucous; 6. Cervical; 7 Broad
ligament; 8. Round ligament myoma.

- Cervical myoma is usually single and may reach huge dimensions; the body of
the uterus sitting on top as a monkey sitting on top of a big rock. The cervical
myoma is either interstitial or subserous and can be in the anterior or posterior
walls or is central. Because of the frequent absence of menstrual disturbance,
the cervical myoma can grow slowly filling the pelvis and pressing on the
surrounding structures. Rarely a cervical fibroid gets polypoidal; most of
fibroid polyps seen at the cervix are coming from the corpus. A myoma
developing in the cervical stump is rare but can constitute a surgical difficulty
because of distorted anatomy.
- The myomas are rounded or lobulated.
- The cut section of myoma is quite characteristic. It protrudes slightly above the
level of the surrounding compressed myometrium. The distinction between the
myoma and the surrounding myometrium is usually clear since the myoma is
pinkish and shows whorl like arrangement of muscle and fibrous tissue. In
contrast, the surrounding myometrium is paler and aligned in a compressed
capsule. This capsule is in fact, a pseudocapsule belonging to the normal
myometrium, which have been pushed aside and compressed by the growing

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Tumors of the corpus uteri

myoma, i.e. the myoma is not a capsulated tumor. The myoma is joined to its
pseudocapsule by loose areolar tissue crossed by the blood vessels feeding the
tumor. This pathological anatomy makes "enucleation: of the myoma possible.
With careful dissection the major feeding vessels can be identified, secured and
cauterized by diathermy.
The presence of myomata is frequently associated with hypertrophy of the
normal surrounding myometrium and the uterine cavity may be markedly
enlarged and distorted.
- Microscopically, the myoma shows interlacing bundle of smooth muscle
(short and plump) and fibrous tissue cell (longer and spindle shaped). The
proportion of the two types of cells varies, older tumors tend to contain more
fibrous tissue. The extracellular matrix is composed mostly of collagen but
also contains fibronictin and proteoglycans.
Secondary changes in myoma
A. Degenerations are commoner in big and old myomata.

§ Hyaline degeneration is the commonest degeneration. The myomatous tissue is replaced

by a homogeneous, structureless hyaline substance that stains red with eosin. The hyaline
change first affects the fibrous tissue element before the muscle tissue component. The
hyalinized areas are to start with scattered in the tumor and then coalesce and get
liquefied resulting in cystic change. Due to different rates of degenerated the cut section
of the tumor is formed of ragged septa separating irregular cystic spaces filled with
colorless or blood stained fluid.
§ Fatty degeneration can occur as a result of diminished blood supply and fat is seen in the
substance of the myoma. Consequent upon fatty changes is the deposition of calcium i.e.
calcification. The calcification may be diffused throughout the tumor, a change, which
form what is described as a womb stone in x-ray examination. The calcium deposition
may be peripheral giving an eggshell appearance. Calcification is a feature in old
myomas particularly subserous myoma poor in their blood supply. The subserous
pedunculated myoma may get adherent to the omentum and receive blood supply from
the latter origin. It may get weaned off the uterus forming a parasitic myoma.
§ Red degeneration is an acute or rapid degeneration. It is mostly seen during pregnancy
and the puerperium, but can occur apart from these occasions. It causes acute abdominal
pain and can be mistaken with other types of acute abdomen. The tumor may slightly
enlarge, is soft and homogeneous or may show central necrosis. It is diffusely stained red

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Tumors of the corpus uteri

or salmon-pink. Histologically the degenerated area appears structureless and poorly

stained and there is evidence of thrombosis in some blood vessels.
The pathogenesis of red degeneration is not clear, but the initial change may be a
subacute necrosis that is presumed to result from an interference of the blood supply or
venous drainage, probably secondary to thrombosis. The coloration is due to hemoglobin
that results from hemolysis of blood in blocked vessels.
§ Sarcomatous change in myoma is very rare and is in the region of one per 1000 (0.1%).
This takes the form of leiomyosarcoma. The malignant changes usually start in the center
of large tumors. It is associated with rapid enlargement of the tumor and development of
pain. Postmenopausal growth of myoma should raise suspicion of malignancy. The tumor
is vascular and soft and its enucleation from the capsule may be difficult. These naked-
eye appearances are only suggestive; the diagnosis should depend upon histopathology.
Even with histopathology the differentiation is sometimes not certain between a cellular
myoma and myosarcoma. The differentiation can depend upon 1) the counting of mitotic
figures per 10 high-power fields – tumors with less than 5 mitotic figures are considered
benign, tumors with more than 10 mitotic figures are malignant, and those in between are
of uncertain malignant potential. 2) Other features that may be relied upon are the
presence of nuclear hyperchromatism, nuclear pleomorplism, or giant or bizarre cells.
§ Atrophy After menopause the tumor may show regression in size but this is not always or
commonly observed. Because of associated atrophy of the myometrium an interstitial
myoma may become submucous and polypoidal and therefore symptomatizes for the first
time after the menopause.
B. Torsion of the pedicle of a subserous pedunculated myoma interrupt first the veins causing
acute congestion of the tumor and then the arteries causing gangrene. Chronic torsion may
result in adhesion of the myoma to the omentum or other peritoneal sites from which the
tumor gets new blood supply. Eventually the myoma may get weaned from the uterus
resulting in parasitic myoma. Torsion of big myoma may cause torsion of the whole uterus
(See under Displacents)
C. Incarceration of a pedicled subserous myoma in the cul-de-sac can occur and cause
pressure manifestations.
D. Hemorrhage due to rupture of surface vein results in acute internal hemorrhage.
Hemorrhage in the substance of the myoma is rare and causes sudden enlargement and pain,
and the hematoma may be infected, resulting in abscess formation
E. Infection: a submucous myoma may be infected through ulceration of the stretched
devascularized endometrium. This results in excessive purulent discharge. In other sites,
infection follows necrosis or hemorrhage. It is common after abortion or delivery. It causes
acute pain and bad toxemia because the pus is held under pressure in a confined space.

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F. Ascites: very mobile pedicled subserous myoma may rarely be associated with mild or
moderate ascites. This may be due to mechanical irritation of the peritoneum. Hydrotharax
might be associated i.e. simulating Meig's syndrome.
Leiomyotosis peritonealis dissminata
This is a rare condition where there are widespread small fibromyomatous tumors in
the pelvic peritoneum and less densely in the general peritoneum. This is usually associated
with myomatous uterus and is mainly reported during pregnancy and the puerperium. The
condition simulated disseminated malignancy but the histopathology reveal benign
fibromyomatous tissue. The lesions may regress after the end of pregnancy.

Clinical Picture
There are three possible clinical presentations of uterine myomata, which greatly
influence the management:
- Asymptomatic myomata
- Symptomatic myomata
- Myomata associated with infertility
A. Asymptomatic myomata
Most myomata are asymptomatic. The majority of these asymptomatic myomata
require no treatment. This is based in very low likelihood of malignant transformation (<0.1).
This is definitely different from other lesions in the genital system particularly ovarian
neoplasm, which should never be treated conservatively. Asymptomatic myomata need to be
observed annually. Rapid growth, particularly after menopause and the occurrence of
symptoms should indicate removal of the tumor by the appropriate approach. Asymptomatic
myomata may be removed under special circumstances.
B. Symptomatic myomata
Less than 50% of uterine myomata are associated with symptoms, and these are
mainly in the form of abnormal uterine bleeding.
• Abnormal uterine bleeding
The nearer the myoma to the uterine cavity the higher the incidence of bleeding. This
abnormality can take any form:
- Menorrhagia
This is the commonest menstrual abnormality and is taking the form of excessive
and/or prolonged menstrual bleeding. One or more of the following mechanism can cause
menorrhagia.

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Tumors of the corpus uteri

1. Ovarian dysfunction in the form of anovulation; anovulatory menstruation is heavier

than ovulatory menstruation. The persistence of ovarian dysfunction is one of the
possible explanations of persistence of menorrhagia after myomectomy.
2. Associated endometrial hyperplasia and polyposis.
3. Enlargement of the bleeding surface, the endometrial cavity. The surface area of the

normal endometrial cavity is 15 cm2 and this can be increased to 2002 in a

myomatous uterus. The nearer the myoma to the uterine cavity, like with interstitial
and submucous myomata, the greater the abnormality in bleeding.
4. Increased vascularity of the uterus due to the presence of the tumor. Tumor may be
strategically located in the myometrium so that it cause obstruction and proximal
congestion of veins in the inner myometrium and endometrium.
5. The presence of the myoma may interfere with contractility of the myometrium and
the spiral arterioles in the basal part of the endometrium.
- Polymenorrhea and polymenorrhagia:
The associated ovarian dysfunction and ovarian congestion may cause short cycles.
- Metrorrhagia:
This may take the form of intermenstrual bleeding or blood stained discharge,
episodes of amenorrhea of 6-8 weeks alternating with prolonged bleeding episodes, or
continuous bleeding to an extent that the patient does not recognized her menstrual period.
This abnormality can be contributed to by:
- ovarian dysfunction.
- thinning, ulceration and infection of the endometrium covering a
submucous myoma or a myomatous polyp.
- complication of unsuspected pregnancy.
- associated endometrial polyps
- an associated endometrial carcinoma. This cancer is rare relative to
myoma, but both conditions tend to occur in relatively infertile women
with ovarian dysfunction.
- Postmenopausal bleeding may result when an originally interstitial myoma projects in the
uterine cavity and become polypoidal. However, if myomatous uterus is palpated in a
patient with postmenopausal bleeding, other causes for bleeding like endometrial
carcinoma need be urgently investigated. D&C and better hysteroscopy should be done in
order to diagnose or rule out the presence of associated endometrial cancer.
Abnormal bleeding associated with myomata is progressive and ultimately leads to
depletion of iron stores and then anemia. The former state is detectable by measurement
of serum ferritin sometime before the drop in the hematocrit and hemoglobin

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Tumors of the corpus uteri

concentration. Women in our culture tend delay seeking gynecological consultation or

accepting surgical treatment until they are severely anemic.
• Pain
Pain is not a common feature of myomata:
- A chronic aching pelvic pain or pelvic weight may be associated with big or
degenerated (hyaline, cystic or calcareous) myoma.
- Colicky lower abdominal can result from attempt of the myometrium to expel a
submucous myoma.
- Congestive dysmenorrhea developing de novo in the fourth or fifth decade of
life can be a feature of myomata.
- Associated adenomyosis or endometriosis causes dysmenorrhea.
- Associated chronic PID. The association of myomas with chronic salpingo-
oophoritis is a frequent clinical observation ( cause and effect relationship has
not been proved)
- Acute abdominal pain this may result from red degeneration, torsion,
hemorrhage from or within the myoma, or infection.
• Vaginal discharge
Increased mucoid discharge may result from pelvic congestion. Purulent or fowl
smelling sanguineous discharge can result from infected submucous myoma, particularly
when it gets polypoidal.
• Abdominal mass
Abdominal mass may be the presenting symptom of an otherwise asymptomatic
myomata.
• Pressure on pelvic structures
Pressure symptoms particularly occur with myomata kept in the pelvis like cervical
and broad ligamentary myomata.
1. Pressure on the urinary bladder causes frequency, urgency or urgency
incontinence. Stress incontinence can be associated and may be caused by
protrusion of bladder base through the urogenital diaphragm.
2. Pressure or stretching elongation of the urethra may cause retention of urine. This
can also result from a big myomatous polyp protruding from the cervix and filling
the vagina.
3. Silent compression of the ureters by displacement and compression by a cervical
or broad-ligamentary myoma may cause hydronephrosis. This can also result
from pressure of a big myoma on the ureter(s) at the pelvic brim. When urinary

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Tumors of the corpus uteri

infection occurs (as a result of stasis) the destruction of renal substance can be
marked.
4. Pressure on the rectum is less likely but this can sometimes result in constipation
and sense of rectal heaviness.
• Pregnancy complications
In spite of common association between myomata and infertility pregnancy may
occur. The chances are higher the further the myoma from the uterine cavity. The pregnancy
can proceed uneventually but there is increased chance of the following complications of
pregnancy:
1. Abortions: these can be caused by
- Abnormal vascular arranged of the myometrium and endometrium.
- Implantation of the pregnancy in a thinned out endometrium over a
submucous myoma.
- Irritability and increased contractility of myometrium.
- This may be related to disturbance of prostaglandin induced
contractions.
- Failure of a myomatous uterus to grow to accommodate the growing
fetus.
- Relatively older age of affected subject.
- Persistent anovulation and PCOS that is commonly associated.
2. Premature labor, due to some of the above reasons.
3. Increase of the stillbirth rate, due to defective placentation
4. Abnormal lie and presentation.
5. Placental abruption.
6. Uterine inertia.
7. Postpartum hemorrhage: a severe hemorrhage can result from extrusion of a
submucous myoma into the uterine cavity.
8. Retained placenta and placenta acreta.
9. On the other hand, at the same time pregnancy may result in enlargement of the
myoma. Red degeneration is commoner during pregnancy. Torsion of subserous
pedunculated myoma can occur.
10. Anemia, is an important complication of neglected long-term bleeding
abnormalities.
Symptoms caused by complications, like torsion and hemorrhage present with acute
abdominal pain

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Tumors of the corpus uteri

C. Infertility
Myoma is commonly associated with infertility but the three possibilities are equally
possible one causing the other or the two conditions have a common denominator. The
possible causes of infertility assocated with myomata
- associated Persistent anovulation and PCO.
- Interference of sperm transport due to: 1) enlargement of the uterine cavity, 2)
impingement of the myomata on the endocervical canal or the interstitial
portion of the fallopian tube or 3) interference with prostaglandin-induced
uterine contraction which are thought to influence sperm transport.
- Endometrial abnormalities including its thinning out over a submucous
myoma, the associated endometrial hyperplasia, vascular changes and
enlargement of uterine cavity can interfere with implantation of the fertilized
ovum. These effects are greater when the myoma encroaches on the uterine
cavity.
- Other associated conditions including.
- Relatively older age.
- Endometriosis.
- Dyspareunia.
- Tuboperitoneal factor. An association of myomata with chronic
salpingoophoritis has been observed, but whether chronic pelvic
inflammatory disease is commoner in patients with myomata has not
been based on strong evidence.
The above considerations make it imperative to submit the infertile couple with
presence of myomas to the whole of the diagnostic work-up of infertility.

Physical signs and diagnosis

The uterine enlargement is commonly irregular due to the multiplicity of the
myomata, but a single myoma can result into symmetrical enlargement of the utreus.
Subserous or broad ligamentary myomata can simulate adnexal mass particularly ovarian
tumor. The differentiation between myoma and ovarian tumor is highly important because of
different attitudes in the management of the two conditions. Myomata are confluent in the
uterus, in this case, the angle between the lower pole of any para-uterine mass and the cervix
is a wide one, and the movement of the mass is conducted to the cervix. A pedunculated
subserous myoma may however feel separate from the uterus. Soundings of the uterus usually
demonstrate its elongation in case of myomata.

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Tumors of the corpus uteri

The myoma usually feels firm, but can be hard when calcified and soft if affected by
hyaline or cystic degeneration. In the latter case, it simulates pregnancy.
Diagnostic imaging
Diagnostic imaging are definitely helpful particularly sonography. Transvaginal
sonography can diagnose a myoma as small as 2 cm in diameter. The nearness of the myoma
to the uterine cavity can be assessed. Hydrohystrosonagraphy i.e. injection of saline in the
uterine cavity can help visualizing small tumor. The focus of sonographic evaluation is the
differentiating a myoma from ovarian tumor. It can also visualize an associated pregnancy.
With big myoma, examination of the kidneys can reveal a backpressure effect.
Sonography may not be able to differentiate localized adenomyosis from a
leiomyoma. Extensive hyaline degeneration can be rarely mistaken for vesicular molar
pregnancy.
CT scan and MRI may be needed to differentiate and ovarian tumor from a subserous
myoma.
Plain x-ray can show a calcified fibroid. Hysterosalpingography (HSG) shows the
distortion and enlargement of the uterine cavity by a submucous myoma, and is needed to
demonstrate tubal patency when infertility is a problem. HSG can also help in planning the
type of surgery required and may indicate the need for opening the uterine cavity during
myomectomy, if a polyp is seen.
If the diagnosis of pelvic tumor remains in doubt laparoscopy is indicated.

Management
The management is discussed under 4 headings covering asymptomatic and
symptomatic myomas, and the special management of patients presenting with infertility and
during pregnancy.
A. Asymptomatic:
Asymptomatic myomata should receive no treatment other than reassurance and
periodic examinations with, may be sonographic measurements. One can be affirmative about
the extreme rarity of malignant change in the tumors. However, some women find it difficult
to keep a "tumor" in their body. Indications for surgical treatment of asymptomatic
myomata include:

1. Large tumor >12 weeks gestational size, but this not a fixed rule. One may be more
conservative in a woman approaching the menopause, and less so for a young patient
with many years to go before cessation of ovarian function.

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Tumors of the corpus uteri

2. Cervical and broad ligamentary myomata likely to compress important viscera when
they enlarge.
3. Subserous pedicle myoma for fear of torsion.
4. If laparotomy has been done for an uncertain diagnosis. Finding a myoma in such
situation indicates its removal.
5. Growth of the myoma after menopause suggests malignancy, or the occurrence of
postmenopausal bleeding.
6. Rapid growth of the myoma is another indication of possible malignancy and points
to the need for surgical management.
7. When conservation is unacceptable by the patient.
The surgery can be a myomectomy or hysterectomy depending upon the need, the feasibility
and safety of conserving the uterus.
B. Symptomatic Myomata
When significant symptoms are present myomata can be treated by one of the
following options: 1) medical treatment; 2) vaginal myomectomy; 3) hysteroscopic resection
of submucous myoma; 4) laparoscopic myomectomy or myolysis, 5) Abdominal
myomectomy, 6) Hysterectomy abdominal, vaginal or laparoscopically assisted.
The patient may need important preoperative treatment to improve her anemia.
• Medical treatment of myomata
This is not usually the final line of management. It is used, as a temporary line giving
time to improve the general condition of severely anemic patient or for the one whom is
temporarily surgically unfit. Medical treatment can result in reduction of the size of the
tumor.
- GnRH analogues are the most effective treatment presently used for temporary treatment
of myoma. A depot subcutaneous biodegradable GnRH agonist implant (e.g. Goserelin =
Zoladex, Zineca), or depo-decapeptyl as intramuscular injection is frequently given at
monthly intervals for 6 months. Other modalities of administration like daily nasal spray
(Buserline) or subcutaneous daily injections( Decapeptyl) are not practical for the
required time. The treatment results in an initial "flare" effect of GnRH on gonadotrophin
secretion, and this is followed by down regulation of the gonadotrophin secretion. This
results in a state of temporary hypoestrogenism equal to that seen after the menopause.
This temporary menopause usually results in a reduction of the size of the myomata. This
can amount to 40 to 50% reduction after 3 to 6 months of treatment. Amenorrhea usually
results, and usually with all manifestations of menopause including hot flushes, sweating
insomnia, mood liability, headache vaginal dryness. The treatment can result in

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Tumors of the corpus uteri

diminution of trabicular bone density predisposing to osteoporosis. Such changes may not
be completely replenished after discontinuation of treatment.
The effect of GnRH treatment has been found to comprise both diminution of the
amount of collagen in the myomatous stroma and reduction in cell size of the tumor. The
vascularity of the tumor diminishes. This can diminish intraoperative bleeding in
subsequent surgery. This however does not always result in making the subsequent
myomectomy easier, since the medical treatment may make the enucleation of the tumor
from its pseudocapsule more difficult. These changes are reversed after discontinuation of
treatment; the tumor regrows back to the original size.(More information on GnRH
treatment is given under endometriosis).
Disadvantage of GnRH treatment: (In spite of the merits given above)
- Expensive,
- Temporary,
- may make subsequent myomectomy more difficult due to difficulty in
enucleation of myoma from the capsule,
- small myomata can become invisible and escape removal during the
subsequent myomectomy to regrow thereafter resulting in early
recurrence.
Other alternative medical treatment:
These include:
1. Danazol: not always effective and has side-effects (see under endometrosis).
2. Progestogens e.g. MPA given orally or as depot injections (depo-provera): not
always effective and may give rise to unacceptable bleeding.
3. Gestrinone: a synthetic derivative of ethinyl nor-testosterone with antiestrogen
and antiprogesterone properties. It is effective in reducing the size of the myoma. It
is not widely available.
4. Antiprogesterones like mifepristone (RU486) given orally for 3 to 6 month can
be effective. It results in amenorrhea. The effect can be a direct effect of the
antiprogestin or an effect of antagonizing an estrogen stimulation.
5. Combination oral contraceptives (OCs): Low dose COCs containing 30 or 35 µg
of ethinyl estradiol can be used to produce regular and less heavy menstruation in a
patient with a small sized myoma. It seems that the small dose of estrogen contained
is balanced by the contained progestogen. The tumor does not grow and the
endometrium gets thinner and less vascular.
6. Low dose COC treatment is an inexpensive treatment in management of
myomatous uterus in women approaching the menopause. Besides offering reliable

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Tumors of the corpus uteri

contraception the blood loss gets regular and lighter. The treatment can tide the
patient over until her menopause is established.

• Vaginal myomectomy:
Vaginal removal is indicated for myomatous polyps. These can be still within the
uterine cavity or have protruded in the cervical canal or into the vagina. They are presenting
with acyclic bleeding which can be severe and cause severe anemia. The polyp is frequently
infected and partially necrotic due to interference of blood supply of and ulceration of the
covering endometrium. This results in foul smelling discharge. With big polyps in the vagina,
the patient can be really anemic and toxic. Abdominal surgery (myomectomy or
hysterectomy) can carry the risk of spreading the infection to the peritoneum and may prove
unnecessary.
The general condition of the patient needs to be first corrected and blood transfusion
can be needed. However complete correction of the anemia and toxemia may be unattainable
until the infected bleeding tumor has been removed.
Techniques for vaginal myomectomy varies from:
1. Grasping a small polyp by a ring forceps introduced after dilating the cervix, and
twisting the tumor off. Diagnostic curettage in cases of bleeding should always begin
with ring forceps exploration of uterine cavity; this may reveal a previously
unsuspected polyp.
2. For big polyps, protruding into the vagina an associated inversion of the uterus should
first be excluded by sounding the uterine cavity on the side of the polyp. The polyp
can be twisted off. With big myomatous polyps morcellation may be needed. The
pedicle, if it is identified after twisting can be snared and tied. However, if this is not
possible the bleeding is usually minimal and stops by the retraction of the pedicle. If
bleeding persists, the uterine cavity can be temporarily tampoonaded by the balloon of
a Folley's catheter. The cervix may be tightened by sutures around the stem of the
catheter. If this is difficult, a curved clamp can be applied to the broad pedicle and left
in situ for 48 hours. All the time, care should be taken not to invert the fundus. After
removal the uterine wall should be explored between a finger inside the cavity and the
other hand on the lower abdomen. Frequently the removed submucous polyp is the
only myoma and the patient is, this obviated a hazardous abdominal operation.
3. For removal of a big fibroid polyp that is still inside the cavity, a vaginal trachelotomy
may be needed. The cervix may be already dilated by the myoma, or may need
surgical dilatation. A transverse incision is done in the anterior fornix and the bladder
is mobilized upward. Then a middle line incision in the anterior cervical wall, which
allows admittance to the uterine cavity. The myomatous polyp is removed either en

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Tumors of the corpus uteri

mass or by morecellation. The pedicle is snared and ligated. The anterior cervical wall
is then repaired in two layers by slowly absorbable sutures. The vaginal incision is
then closed. Occasionally the operation described is less time consuming than the
alternative of hysteroscopic myomectomy.
• Hysteroscopic myomectomy:
This operation is now increasingly used for treatment of symptomatizing submucous
myoma. The better case is a small or moderate sized tumor, solitary (or few tumors), with
no other myomata in the wall, and when the myoma is seen by pelvic sonography to
protrude in the uterine cavity by 50% or more of its circumference.
Preoperative preparation of the patient by 3 to 6 month treatment with GnRH agonist,
or if not affordable by cyclic use of COC, is usually required, along with correction of
anemia.
Operating hysteroscope is used with continuous irrigation system and continuous
monitoring of the amount of fluid retrieved to avoid circulatory overload. (See also under
infertility). The myoma is removed piecemeal with diathermy/ resectoscope or by
neodymium: Yttrium-alminium-garnet (Nd: YAG) laser. The two types of energy are not
markedly different. Destruction of a big myoma can take some time. The operation can be
monitored from above by simultaneous laparoscopy; when the laparoscopic light is dimmed
down the extent of thinning of the myometrium can be judged. This is in attempt to reduce the
possibility of perforating the uterus. The operation can also be monitored by abdominal
sonography.
The operation can be done in two stages: In the first stage the part of the myoma
projecting in the cavity is removed down to the level of the endometrium. After 6-8 weeks
(under further GnRH therapy) the part in the wall will be extruded in the uterine cavity and its
hysteroscopic resection will be easy without endangering perforation of the uterus( Figure 2).
Endometrial ablation can be also done in women not interested in pregnancy. The
amount of menstrual bleeding is thus markedly reduced or amenorrhea is induced. Otherwise,
pregnancy is possible after hysteroscopic resection.

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Tumors of the corpus uteri

Tumors of the corpus uteri (Figure 2): Hysteroscopic myomectomy in two stages. A. At the
first stage half of the myoma is shaved down to the endometrial level; B. Two month latter,
the remaining part of the myoma is now protruding in the cavity and can be resected without
risking perforation of the uterus.

• Laparoscopic myomectomy and myolysis:

This is an alternative to abdominal myomectomy, which should have a limited
application. It is possible for small subserous myomata for which surgical removal is rarely
needed. The approach is better avoided in cases with infertility problem, since peritoneal
closure of the uterine wound left after laparoscopic myomectomy is less than optimal.
The advocates of laparoscopic myomectomy have devised a number of equipment to
make the operation feasible. Both monopolar and bipolar diathermy are used, or alternatively
Nd:YAG laser. The capsule is incised. A corkscrew myomectomy manipulator is pierced in
the myoma to fix it while the capsule is peeled off the tumor by blunt and hydrodissection.
Bleeding points are coagulated. The bed is closed by extracarporeal sutures. The tumor is
morcellated and sucked out utilizing an automatic morecellator. Alternatively, the myoma can
be retrieved through a posterior colpotomy or minilaparotomy.
The ideal candidate for this procedure is a perimenopausal woman with symptomatic
myoma measuring less than 7 cm.
The disadvantages of laparoscopic myomectomy are:
1. not suitable for deep interstitial myomata.
2. not optimal for big tumors.
3. not suitable for strategically located myoma e.g. cornual or cervical.
4. The bed of the tumor is difficult to close securely, predisposing to hematoma
formation.

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Tumors of the corpus uteri

5. The peritoneal surface cannot be neatly coapted like in open myomectomy.

Adhesion formations may be more likely making the procedure less favorable in
infertility cases.
6. Needs special expertise. It can take longer time than open surgery prolonging the
anesthesia and the pneumoperitoneum.
7. Rupture uterus can occur due to poorly repaired suture.

Laparoscopic myolysis:
The myoma is drilled at several points either by bipolar diathermy or Nd:YAG laser
needle. This results in subsequent atrophy of the myoma. The procedure though simpler than
laparoscopic myomectomy is open to the same complications described above. It is only
suitable for small symptomatizing myoma in an elderly patient not interested in any future
childbearing. It may be followed by regrowth of the myoma.

• Abdominal myomectomy:
This is one of the most commonly performed gynecological operations.
Myomectomy-involves enucleation of the myoma from its pseudocapsule, which is then
obliterated. It aims at leaving behind a functional uterus. For symptomatizing myomata the
choice is usually between myomectomy and hysterectomy. This choice depends upon whether
preserving the uterus is needed, possible, and safe.
The uterus is needed for childbearing. However, women who are not interested in
further childbearing should not be pressed to have the uterus removed unless when necessary;
women usually prefer to preserve the capability of childbearing. Monthly menstruation may
reassure her of her femininity. Even if the tubes are blocked the uterus can carry a pregnancy
achieved through IVF (see under hysterectomy).
The number and the location of the myomas determine the feasibility of
myomectomy. These are not absolute determinants. One can remove a big number of
myomata from a uterus. Although myomectomy for cervical myoma has its special
difficulties, (particularly, the obliteration of the dead space without closure of the cervical
canal), it is still possible with exercise of extra care.
Myomectomy can be or prove unsafe when bleeding becomes severe, when
sarcomatous change is suspected, and when associated with endometrial carcinoma.
During preoperative counseling surgeon should ensure to himself the option of
resorting to hysterectomy if a real need arises.
• Preoperative preparations:

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Tumors of the corpus uteri

- Anemia should be corrected. Administration of hematenics is usually better accepted

than giving homologous blood transfusion. There can be some blood loss during
myomectomy and blood should be reserved in case of need.
- Preoperative medical treatment (see above) gives time for correction of anemia or any
general condition.
- Planning of the myomectomy should start before the operation by diagnostic imaging
which determine the number size and sites of the myoma (see above).
- Prophylactic antibiotic are usually required in myomectomy and can be initiated at the
time of surgery.
• Principles of myomectomy:
1. adequate exposure.
2. measures to control intraoperative bleeding.
3. planning the best site of incision(s).
4. enucleation of the myomata.
5. trimming of hypertrophied myomatrium.
6. opening the uterine cavity---------only when necessary.
7. closure of the bed of the tumor(s).
8. careful approximation of the serosal wound.
9. Throughout the operation of myomectomy two principal rules should be kept
in mind:
a. The anatomy of the uterus should be always kept in mind; preserving the
integrity of 1) the endometrial cavity, 2) the interstitial portions of the tubes
and 3) the cervical canal.
b. All the principals of microsurgery should be observed in order to minimize the
formation of postoperative adhesions.
• Steps of myomectomy:
- Spinal anesthesia is preferred if acceptable by the patient. It ensures less intraoperative
bleeding. Controlled hypotensive anesthesia is useful if a major myomectomy is
anticipated.
- After catheterizing the patient she is usually put in dorsal position with a trendelenberg
tilt. If a need for testing for tubal patency during the operation is anticipated the patient is
put in Allen universal stirrups, this will allow fixing a canula to the uterus.
- Pfannestiel incision is adequate for small to moderate sized myoma. Enucleation of an
anterior wall myoma can allow delivery of the uterus in the incision. For larger tumor a
Maylard incision (which cut all the layer of anterior abdominal wall transversely); or
middle line incision is used.

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Tumors of the corpus uteri

- A four-way retractor and packing the intestines in the upper abdomen allows good
exposure. The laparotomy packs that are used to hold the intestines in the upper abdomen
may be placed in plastic bags in order to reduce microscopic traumatization of the
peritoneal surfaces. Rough-surfaced gauze packs can cause fine abrasion; fibrin deposits
will form atop, and these can be the starting point of adhesion formation. The operative
field should be kept moist and free of clots by a continuous irrigation with a solution of
Ringer lactate containing heparin. Suction is used to remove blood rather than mobbing
with towels. Fine instruments should be used and these are never applied on the peritoneal
surfaces.
- Adhesions to intestines, omentum, if present are broken and ligated. Exposure of the
cornue will allow decision about the pathological anatomy, and where the incision should
be.
- Temporary hemostasis: Some surgeons prefer to temporary occlude the blood supply
during myomectomy. Both the uterine and ovarian arteries need be occluded, inadequate
pressure occludes the veins rather the arteries and results in actual congestion of the uterus
with increased bleeding. Bonney occluded the uterine vessels on the sides of the waist of
the uterus by a special clamp carrying his name. The ovarian vessels in the
infundibulopelvic ligament were temporarily occluded by applying ring forceps.
An alternative method is to make small windows in avascular points in the two broad
ligament near the cervix, lateral to the uterine vessels. Through these two holes a plastic
tourniquet, like 5 F pediatric tube, is looped around the isthmus uteri, tightened, and held
tight by a clamp. Through the same wholes in the broad ligaments two other tourniquets
loop around the infundibulopelvic ligament (figure 3). These two methods can reduce the
bleedings during the operation.
Alternatively, vasopressin is injected around the tumor to produce temporary spasm of
the feeding blood vessels.
There is, however, a fear that this temporary ischemia can injure the peritoneal
surfaces of the tubes and uterus and can, after being eased off, result in fibrinous
adhesions. Moreover, a sizable blood vessel in the bed of the tumor can escape
recognition and suturing during obliteration of the bed of the tumor. This can result in
oozing from the uterine wound or in the formation of a hematoma. The author rarely uses
this temporary hemostasis and depends upon identifying any significant bleeding vessel
and either transfixing and ligating it or cauterizing it with diathermy. Each tire of suture
should control the bleeding underneath it. Suction irrigation allows identifying bleeders.
Tourniquets are used only if there are many myomata.

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Tumors of the corpus uteri

Tumors of the corpus uteri (Figure 3): Myomectomy. Tourniquets around the blood supply
of the myomatous uterus. Passed through holes in the base of the broad ligaments. 1. Uterine
vessels; 2. Ovarian Vessels.

Tumors of the corpus uteri (Figure 4): Abdominal myomectomy. Enucleating two myomata
through one anterior wall incision. The lateral-wall myoma is being approached through a
secondary tunneling incision.

- The site of the incision should be planned with care to fulfill as far as possible the
following 4 needs: 1) the least possible incisions, 2) being intermediate between the
myomata, 3) being in the middle line, the least vascular area (the blood vessels come from

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Tumors of the corpus uteri

the sides, 4) in the anterior wall; fundal and posterior wall incision are better avoided
because they are more exposed to omental and intestinal adhesions. The incision over a
big projecting myoma can be elliptical. The incision cuts until it reaches and cuts through
the myoma, thus defining the pseudocapsule. A multiloothed volsellum or Alis forceps
hold upon the myoma; or better traction is mad by strong silk suture passed by a big bite
into the myoma.
- Enucleation of the myoma makes use of the areolar connective tissue space between the
myoma and pseudocapsule. Significant blood vessels crossing this space should be
secured. The completion of enucleation of certain myoma deferred for sometime and
pulled upon until the enucleation of less accessible myoma (s) is completed (Figure 4).
- Secondary tunneling incisions are made in the sides of the anterior wall incision (Figure
4). Myomata on the side of the original incision are pushed "moved" towards and
enucleated through these secondary incisions, thus avoiding leaving multiple incision on
the surface. The surgeon should keep in mind the anatomy of the uterus, particularly
where are the tubes and the cervix.
- Posterior wall myomata are dealt with by one of the following methods:
a. Direct longitudinal incision upon them. This is inevitable if a sizable subserous
myoma in the lower posterior wall is present. Careful hemostasis is needed because
this site is exposed to the tubes, ovaries, omentum and intestines and there is a
possibility of adhesion.
b. Posterior wall, interstitial or submucous myoma can be removed by transcavitary
enucleation. Careful obliteration of the bed is done before approximation the
endometrium by plain catgut (Figure 5). Care should be exercised not to obliterate
the endometrial cavity.
c. Bonney's hood operation: This is needed for high posterior wall or fundal myoma.
A transverse or an anteriorly convex incision is made at the fundus. The incision is
deepened backward rasing a hood formed of the part of the capsule with its
peritoneal covering. After enucleation of the myoma from under the hood, several
tiers of suture advancing the hood forward upon the top and front of the uterus
(Figure 6) obliterate the dead space. This brings the final sutural line well down the
anterior uterine wall away from the omentum and intestines (Figure 7). The
operation can be elegant but it carries a serious disadvantage of compressing the
isthmical portions of the tubes underneath the hood, and is better not used if
infertility is a problem.

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Tumors of the corpus uteri

Tumors of the corpus uteri (Figure 5): Myomectomy: Obliteration of the cavity left behind
enucleation of multiple myomata. 1. Anterior wall myoma; 2. Lateral wall myoma that has
been removed by tunneling incision; 3. Endometrial cavity; 4. Cavity left after removal of
posterior wall myoma, which has been removed through a transcavitary incision. The
obliteration of the cavities is as made from behind forewords. The edges of the edges of the
anterior cavity are trimmed (dotted parts) to alloy near approximation by vertical mattress
sutures.

Tumors of the corpus uteri (Figure 6): Myomectomy. Bonney’s hood operation for
enucleation of a posterior wall myoma.

Tumors of the corpus uteri (Figure 7): Myomectomy. The final suturing of the Bonney’s
hood to the front of the uterus. The arrow points to the possible constriction of the tube by the
hood. B= Bladder.

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Tumors of the corpus uteri

- Opening the uterine cavity allows detection of a submucous myoma, or associated

pathology. The myometrium can be effectively palpated between a finger inside the cavity
and another on the surface of the uterus to detect any small missed interstitial myoma.
Opening the uterine cavity is particularly needed in cases presenting with irregular uterine
bleeding. The endometrium is curetted by the handle of the scalpel and sent for
histopathological evaluation. The endometrial cavity is then closed by interrupted fine
suture 3-0 absorbable catgut picking on the subendometrial myometrium rather than on
the endometrium itself.
Opening the endometrial cavity is not always needed in myomectomy. It can result in
the formation of intrauterine adhesion. It is better avoided in infertility cases. The
information gained through exploring the uterine cavity can be got through pre-
myomectomy sonography or hydrosonogography and D&C.
- Trimming of hypertrophic myometrium: The uterus harboring myomas hypertrophies like
the one carrying a pregnancy. After enucleation of the myomata the uterus can remain big
and it cavity enlarged. There is expected diminution in size during a postmyomectomy
"involution”. However, the hypertrophic myometrium may need to be trimmed by
removing slices of the sides of the incision (Figure 8). This should bring the uterus to a
size slightly larger than the normal size of the uterus, allowing for the expected
involution.

Tumors of the corpus uteri (Figure 8): Myomectomy. Trimming of hypertrophic

myometrium. 1. Slices of hypertrophic myometrium excised in both sides of the incision; 2.
Opened endometrial cavity; 3. Lateral tunneling incision, which have been used to remove a
lateral wall myoma.

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Tumors of the corpus uteri

- Obliteration of the beds of the myomata and the incision(s). This is achieved by a number
of tiers of suture; no dead space should be left unobliterated (Figure 5). The sutures are
interrupted, through and through. Occasionally figure of eight or transverse mattress
sutures are used to include the mouths of oozing vessels. Fine 2-0 delayed absorbable
suture material is used. In reconstructing the uterus, the surgeon should always refer to
certain landmark points; the tubal attachment and the cervical canal in order not to block
these channels. The last layer should be burried continuous suture of 4-0 dexon or vicryl
using "baseball stitching, i.e. one edge is bitten from the deep to the superficial part and
the other edge is bitten from the superficial to the deep part, when the thread is pulled
together, the edges will fall coapted without leaving rough sutural knots on the surface.
No surface ooze should be left behind.
- The round ligaments need be shortened by plicating them with unabsorbable sutures to
bring the uterus to good anteflexion leaving a smooth fundus and posterior wall. The
round ligament may be bent over and fixed in front of an anterior wall incision.

C. Myomata in patients presenting with infertility:

When infertility is a problem for the patient a full investigation of the couple is
needed before embarking on treatment of myomata. The appropriate management of the
infertility problem should be attempted first and given full trial, usually disregarding the
presence of the myoma. This should be the attitude when the myomata are small, not causing
other symptoms and not likely to contribute to infertility.
• Indications of myomectomy for patients presenting with infertility:
1. The myoma is causing bleeding.
2. The myoma is strategically placed at sites that interfere with ascent of sperms
or fertilization, e.g. near the interstitial portion of the tube.
3. The myoma is encroaching on the uterine cavity.
4. The myomata are causing marked enlargement of the uterus (>12 week
gestational size).
5. There is another indication for laparotomy, e.g., for correction of a tubal or
peritoneal factor contributing to infertility.
6. Failure of reasonable trial of medical treatment of infertility to achieve the
goal, and in presence of no other etiological factor contributing to infertility.
7. Before attempts at IVF or other ART it is reasonable to remove any significant
myoma. A small subserous myoma does not warrant removal before attempts
of ART.

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Tumors of the corpus uteri

§ Technique
For technical details, the reader is referred to section on infertility, particularly for the
approaches that can be used for adhesion prevention.

§ Postoperative care
- Prophylactic antibiotics are better given.
- Patients should be kept under observation for internal bleeding and ileus.
- Postoperatively: The patient should avoid pregnancy for 3 month until the
repair of uterine wound has become secure. The use of low dose COCs is
possible in patients with present or past myomata. It seems that the estrogen
effect is well balanced by the contained progestogen. Rupture of myomectomy
scar is rare during subsequent pregnancy; a straightforward uncomplicated
delivery is possible.

• Results and Complications of Myomectomy:

A- Immediate complications
1. Intraoperative bleeding is more likely in myomectomy than in hysterectomy.
2. Postoperative reactionary hemorrhage is possible, if perfect hemostasis has not
been achieved during the operation. The patient should be under close
observation for 12 to 24 hours. A change in pulse rate, blood pressure and
hematocrite should indicate careful clinical and sonographic evaluation to
detect blood in the peritoneal cavity. Aspiration of blood under sonographic
guide is conclusive. The patient should be immediately reopened and the
bleeding is appropriately dealt with.
3. Postoperative rise of temperature and ileus can occur after extensive
myomectomy due to tissue trauma, hematoma formation, oozing from the
peritoneal surface, and actual infection. Prophylactic antibiotic is usually
started preoperatively. Perfect hemostasis in layers is essential not leaving any
dead spaces that fill with blood.
B- Late sequelae
1. Persistence of menorrhagia
This is possible in about 20% of cases and may continue for 2 or 3 months after the
operation. The possible causes comprise:
- persistence of ovarian dysfunction.

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Tumors of the corpus uteri

- postoperative reaction and congestion resulting from presence of many

sutures. These disappear with time.

- enlarged uterine cavity. This involute with time.

- missing of a submucous myoma.
- missing of an associated pathology.
- The condition is usually managed medically along the lines given under DUB.
2. Persistence of pelvic pain and dysmenorrhea can be caused by associated
conditions like endometriosis a chronic salpingo-oophoritis. Nevertheless,
clinical improvement is expected in more than 80% of cases after subsidence of
tissue reaction caused by the presence plenty of sutural material.
3. Persistence of infertility
Pregnancy rate after myomectomy done for infertility varies between 40 and 60% in
different studies. It is expected within 2 years after the operation. The deficit can be
accounted to by:
- relatively elderly patient.
- presence of other etiological factors in the couple.
- persistence of ovarian dysfunction.
- de novo developments resulting from the operation including blocking
of the interstitial part of the tubes, intrauterine adhesion, pelvic
adhesion distorting the normal anatomy. These are greatly avoidable
by observing certain improvements in the technique of myomectomy
and application of microsurgical measures for prevention of peritoneal
adhesion.
4. Rupture of myomectomy scar during subsequent pregnancy is rare and
definitely much less expected than rupture of a classical cesarean section scar.
5. Recurrence of myomata is expected in about 10% of cases, usually after the
lapse of more than 2 years. It is due to missing of seedling myomata and the
basal predisposition of the patient to grow myomata in her uterus. Recurrence
is definitely commoner when the first operation was done in young age. Cases
with recurrent myomata should be reevaluated according to their clinical
presentation, age, and the pathological anatomy present. The gynecologist
should respects the wishes of the patient and is better to secure for himself the
option to remove the uterus.
These possible complications should be described to the patient during the
preoperative counseling to help her to make an informed consent.

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Tumors of the corpus uteri

• Hysterectomy:
Uterine myomas are the most common reason for hysterectomy accounting for 30% of
the indications of this operation in the USA. Hysterectomy is indicated in myoma giving rise
to significant symptoms and when the alternative of preserving the uterus is not needed, not
possible, and unsafe. Hysterectomy is usually the safer and easier of the two alternatives.
Therefore, the indications include:
- elderly patient above the age of 45 year.
- for younger patient not needing to preserve her uterus and if the desired family
size has been completed; the ovaries should be preserved in these cases.
- The presence of other causes of infertility like blocked tubes or markedly
defective semen quality are not any more reason for removing a uterus
harboring myomata. IVF and ET, and ICSI have given a new hope for such
couples to have children of their own.
- Too many myomas or myomas in certain sites e.g. cervical may make
myomectomy difficult and rarely impossible. This depends upon the
experience of the surgeon. The desire of the patient should be respected as for
as possible. There are cases however, when this is quite impossible, like in
diffuse leiomyomatosis uteri where the uterus is studded with hundreds of
small myomata. The price of preserving the uterus is the continuation of the
symptoms and the future need for another surgery to remove the uterus.
- In case of big cervical myoma it is sometimes quite difficult to obliterate the
big and deep dead space left behind after removal of the myoma. There is
always the risk of obliterating the cervical canal. A number-8 Foley's catheter
in the cervical canal can serve as landmark to repair a cervical canal around. To
allow for reaching the depth of the bed, the myoma should not be completely
detached and used for traction until some of the first tire of obliterating sutures
is placed. There is a definite risk of injury of bladder or its inclusion or ureteric
inclusion in the sutures. Hysterectomy should be a safer alternative in such a
case.
- If there is suspicion of sarcomatous change in the myoma (see above)
hysterectomy is the safer alternative. However, it needs to remember that
sarcomatous change of myoma is exceedingly rare. Degenerative changes and
necrosis may simulate malignant change. Histopathological confirmation is
required before removing a needed uterus. If frozen section service is not
available, one should risk another laparotomy in such a case, rather than
removing the uterus (Technique of AH is discussed in a separate section).

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D. Myomas associated with pregnancy:

Such a combination is better to be managed conservatively as Pregnancy is not a
suitable time for myomectomy. The uterus and the tumor are very vascular, and myomectomy
in this circumstance is hazardous unless the myoma is subserous and pedunculated. Attempt
at removal of the myoma usually results in opening the uterine cavity and evacuating the
pregnancy. Severe bleeding can end in hysterectomy. Even if such events did not occur
postoperative abortion is likely.
Consequently, the management of myomas diagnosed during pregnancy should be
conservative. This should be the attitude unless removal of the uterus is contemplated upon
and there is indication for cesarean delivery when Cesarean/hysterectomy is done.
Complicating red degeneration is managed conservatively by giving analgesics and antibiotic.
Even if the abdomen has been opened for other possibilities of acute abdomen, the tumor
should not be removed.

Contraception with present and past myomata:

- Low dose combined oral contraception can be used in presence of
myomata. The progestogen contained can effectively balance any trophic
effect of estrogen on growth of the myoma.
- When there is contraindication of receiving estrogen, progestogen only
contraceptives (minipill, injectables, and Norplant) can be used. They
however cause menstrual irregularities that might be considered caused by
myomata.
- IUDs are usually not suitable because of the enlargement and distortion of
the uterine cavity. This is unless the myoma has been demonstrated to be
far from the uterine cavity. Levonorgestroel IUD have the merit of
diminishing blood loss.
- Sterilization: When this required abdominal hysterectomy is a better
alternative,

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Tumors of the corpus uteri

Adenomyosis Uteri
Pathology:
Adenomyosis refers to the presence of endometrial glandular tissue in the substance of
the myometrium. These glandular islets are surrounded by hypertrophy of the muscle and
fibrous elements of the myometrium. These hypertrophy results in an enlargement of the
uterus which is usually diffusely symmetrical, but may be localized to either wall, more
frequently the posterior one. The enlargement rarely exceeds 12-week pregnancy size. The
cut section shows striated appearance resulting from admixture of muscular and fibrous
elements and frequently shows whorled appearance like that of a myoma. However
adenomyosis differ from myoma in the absence of the pseudocapsule surrounding the
myoma, therefore it is not dissectable from the uterine wall.
The glandular element of adenomyosis may not be apparent to the naked-eye
inspection. It is mainly formed of basal type of endometrial glands. Therefore, the glands are
usually not responsive to cyclic hormonal changes like in the case of enometriosis. Rarely, the
glandular rests menstruate and cause few brown or black specks in the myometrium. These
are usually small not larger than pinheads.
Pathogenesis:
The condition is essentially similar to endometriosis. However, the two conditions are
rarely associated. Endometriosis may however affect the serosa of the uterus and this is
considered as part of pelvic endometriosis.
The most probable mechanism of pathogenesis is that adenomyosis represents an
outward growth from the basal layer of the endometrium. The glandular crypts in the
endometrium may show continuity with the uterine cavity. The connection may however be
cut by overgrowth of surrounding myofibrosis tissue. Branching tubules can rarely be
demonstrated during hystrosalpingography in a case of adenomyosis uteri. Another possible
mechanism is in situ metaplastic changes in the myometrium. This is understandable because
of the common origin of all elements of the upper genital tract from the Mullerian duct.
The condition is commoner in cases with anovulatory infertility.
Clinical picture:
Menorrhagia is the commonest symptom and is explained by enlargement of the
bleeding surface, the uterine cavity, and by the increased pelvic and uterine congestion.

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Tumors of the corpus uteri

Pelvic pain and heaviness. This can be continuous but increases premenstrually and is
worst during menstruation to subside gradually after its end. Bladder irritation may result
from pressure of the enlarged uterus.
On bimanual examination, the uterus is felt enlarged but mobile. The size rarely
exceeds 12-week - pregnancy size. The enlargement is usually symmetrical, but less
commonly affecting one of the walls more than the other. Differentiation from myomatous
uterus is sometimes difficult if the latter condition is not resulting in bossy enlargement of the
uterus. Vaginal sonography may indicate the diffuseness of the lesion and the absence of the
pseudocapsule, but this is more readily seen in magnetic resonance imaging. However, the
condition is frequently an unexpected finding at laparotomy done for treatment of myoma.
Management:
The management of adenomyosis depends on the patient's age, desire of future
fertility and severity of symptoms. In the one desiring to preserve her uterus, nonsteroidal
antiinflamnmatory drugs are helpful. The use of low-dose COCs can diminish the
menorrhagia. Alternatively, continuous use of progestogen-only contraceptive can relieve
most of the symptoms. GnRH agonists can be helpful, like with myomatous uterus.
Patient desiring pregnancy should be encouraged and helped by treatment of any
associated cause like anovulation.
Wedge resection from the affected wall can reduce the brunt of the pathology and may
improve persistent menorrhagia. It can be done when the diagnosis of adenomyosis is done
after incision of the uterus on assumption of presence of myoma.
Women with completed family size who have failed to respond to conservative
treatment are counseled to have hysterectomy.

Adenoma of the Endometrium

A true adenoma occurs with or without associated endometrium hyperplasia. It is
always polypoidal and may be multiple. The tumor is usually small and rarely exceeds the
size of a grape and is soft. Microscopically is shows endometrial glands and stroma and these
may show cyclic response to ovarian hormone. Sometimes the stroma is dense and contains
smooth muscle fiber, and then it deserves the name of adenomyoma. The tip of the polyp may
get necrotic and infected and thus causing irregular bleeding and foul smelling discharge.
Clinical picture:
- The condition can be asymptomatic.
- It frequently causes abnormal uterine bleeding. This may take the form of
menorrhagia but is frequently acyclic in the form of intermenstrual or post-

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coital bleeding or continuous bleeding. Adenomatous polyp can be a cause of

postmenopausal bleeding.
- Vaginal discharge is increased and can be purulent or blood tinged. Colicky
pain may result from attempts of the uterus to expel the polyp. The uterus may
succeed in dilating the cervix and extruding the polyp into the vagina when it
feels as a soft polyp that readily bleeds on touch.
- The diagnosis can be made by vaginal sonography or hydrosonography. The
condition can be an unexpected finding an hysterosalpingography or
hysteroscopy. The latter is now increasingly used for the diagnosis of acyclic
uterine bleeding. The presence of the polyp can be also diagnosed by
exploration of the uterine cavity by a ring forceps, which should be done in
conjunction of D&C.
Treatment:
- curettage, plus ring forceps removal.
- hysteroscopic polypectomy is the better treatment since it gives opportunity
for inspection of the uterine cavity and removal of multiple polyps.
Polyps presenting at the cervix
A- Polyps arising from the cervix:
1. mucous polyp.
2. myomatous polyp.
3. hanging tags from lacerated cervix.
4. bilharzial polyp.
5. carcinoma.
B- Polyps arising from the corpus uteri:
1. Myomatous polyp.
2. Adenomatous polyp.
3. Adenomyomatous polyp.
4. Placental polyp (remnants of pregnancy which get organized and maintain
blood supply from the uterus).
5. endometrial carcinoma.
6. Choriocarcinoma.
7. Chronic inversion of the uterus.

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Other Benign Uterine Tumors

Hemangioma:
This is rare benign tumor. It is usually localized to part of the endometrium and spread
to involve the overlying myometrium. It is formed of an admixture of capillaries, spaces,
veins, and arteries.
The condition cause bleeding that can be alarmingly heavy and resistant to medical
treatment and is not controlled by curettage. The condition may be diagnosed by transvaginal
sonography, CT or MRI. However, the case is usually diagnosed after hysterectomy.

Glioma, chondroma or osteoma in the uterus are very rare.

Endometrial Carcinoma
Contents:
- Epidemiology - and possible etiological factors
- Pathology - spread
- Clinical picture
- Diagnosis
- Staging
- Prognostic factors
- Treatment
Surgery
Radiotherapy
Hormonal therapy
Results

Epidemiology:
Cancer of the uterine corpus is the second common cancer of the genital organ in the
UK being preceded by ovarian cancer. It is however, the commonest type in North America.
Endometrial cancer has a lower incidence in Asian countries. The situation for Egypt is
unknown, but the impression is that it comes second to ovarian cancer. The overall mortality
from endometrial cancer is much less than that of cervical cancer and ovarian cancer being
30%, 50% and 75% in the three types of cancer respectively. This reflects pathological

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differences, but mainly results from earlier diagnosis of endometrial cancer and late diagnosis
of ovarian cancer.
Endometrial cancer is a disease of mainly postmenopausal women; more than 80% of
cases occur after the menopause. The median age for endometrial cancer is 61 years.
Postmenopausal bleeding usually results in seeking medical consultation at an early stage.

Etiological factors:
Most of the etiological predisposition relates to exposure to excess of or unopposed
estrogens. Risk factors for endometrial cancer include the following; some of these factors
are interdependent:
1. Early menarche, < 12 years.
2. Late menopause > 52 years.
3. Infertility,
4. Anovulation and PCOS.
5. Obesity, particularly trunckal obesity. The biological basis is that in
postmenopausal obese women there is increased peripheral conversion of
androgens to estrogens. There are also lower levels of sex-hormone binding
globulin. This can be resulting in higher estrogens particularly the free
estrogens.
6. History of endometrial hyperplasia particularly when the hyperplasia affects
the glandular element rather than the stroma. While simple hyperplasia has a
low malignant, potential (2%), atypical glandular hyperplasia has a 23% risk
of developing endometrial carcinoma. The latter condition is presently
considered carcinoma in situ of the endometrium and is usually an indication
for hysterectomy. The uterus is only conserved if it is really needed and if the
pathology reverts to normal under progestional drugs.
7. Diabetes mellitus.
8. Hypertension.
9. Granulosa/theca tumors.
10. Unopposed postmenopause estrogen therapy. The administration of a low
dose of a progestogen during at least 10-12 days each month will counteract
this predisposition (see under Menopause).
11. Tamoxifen an antiestrogen widely used in the treatment of breast cancer has a
weak estrogen effect and has been found to increases the risk of endometrial
hyperplasia and carcinoma. Prolonged use of tamoxifen for more than 5 years
may result in a twofold increase in the incidence of endometrial cancer, and

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such patients should be kept under surveillance aiming at early detection of the
endometrial changes. Recently selective estrogen receptor modulators (SERMs)
have been introduced to cover for the need of postmenopausal prophylactic
hormone therapy. Raloxfen is a SERM which selectively acts as estrogen in
protection against osteoporosis without increasing the chance of development
of endometrial cancer, and possiblly breast cancer as well.
12. The use of combined oral contraceptive (COCs) has a strong protective effect
against endometrial cancer. Women, who have used COCs for 12 month or
more, have an effect of 50% reduction of the risk of developing endometrial
cancer, and this protection extends for at least 10 years after discontinuation.
13. Race: endometrial cancer is commoner in white American than in African
Americans. It is also commoner in Jews.
14. Senile endometritis and pyometria may predispose to endometrial cancer, but
the relationship is not strongly evidence - based.
15. Myomas are common tumor, which are associated with many of the above risk
factors of endometrial cancer. These explain an association of the two
conditions but do not prove any cause and effect relationship.

Pathology:
Gross picture: Endometrial cancer can be predominantly polypoidal into the cavity or
invasive. Sometimes it is found only in a polyp. It may occupy a small area of the
endometrium and might thus be missed during curettage. It may involve a wide area or
multiple foci. Most endometrial carcinoma arise in the upper region of the uterus, the internal
os is not usually involved until the disease has become extensive within the uterus.
Histologically more than 90% of endometrial cancers are endometrioid
adenocarcinomas, which show glandular pattern, but invades both the stroma and
myometrium. The majority of cases are well differentiated. Benign squamous changes are
present in 20-25 percent of such tumors. These latter tumors are known as adenoacanthomas,
but their behavior and prognosis is not different from that of a pure endometrioid
adenocarcinoma. Rarely, the squamous element is malignant (adenosquamous carcinoma).
The prognosis in the latter condition depends upon the degree of differentiation of the adeno
component, and is usually worse than adenocarcinoma.
Other histological types of endometrial cancer are rare and include:
- Papillary serous carcinoma, which looks under the microscope, behaves like a
papillary serous carcinoma of the ovary, and has an aggressive course and a poor
prognosis.

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Tumors of the corpus uteri

- Clear cell carcinoma resembling clear cell carcinoma of the kidney and has a poor
prognosis.
- Squamous carcinoma is extremely rare and may represent an extension from the
cervix.
- Secretory adenocarcinoma is a very rare histological type in which the cells show
progestational secretory changes. The prognosis is favorable in such cases.

Spread:
1. Direct invasion:
The tumor usually grows slowly, especially when it is well differentiated. It spreads
down to the endocervix producing the condition of carcinoma corporis et cervices. The tumor
can spread along the fallopian tubes to the ovaries and peritoneal cavity. It gradually
infiltrates the myometrium and can reach the peritoneal covering or infiltrate the
parametrium. Very advanced cases of endometrial carcinoma may simulate advanced ovarian
cancer, with wide spread intraperitoneal metastases.
2. Lymphatic spread:
Permeation of lymphatic may in part account to direct invasion of the tubes ovaries or
vault of the vagina. Spread can occur to both pelvic and para-aortic lymph nodes, the former
being more common. Pelvic wall lymph node involvement increases when the endocervix is
involved or when there is deep invasion of myometrium. The para-aortic lymph nodes may
occur secondary to involvement of pelvic nodes or directly via lymphatics accompanying
ovarian vessels to the upper para-aortic nodes. Very rarely the inguinal lymph nodes are
involved along lymphatics accompanying the round ligaments.
3. Blood stream spread:
Embolism accounts for remote metastases in the lungs or to local metastases in the
ovaries or to the lower anterior vaginal wall. There is most probably, a portal type-vascular
connection between the uterus and the lower anterior vaginal wall that may account for the
latter type of metastases.

Clinical picture:
The main symptom of endometrial carcinoma is abnormal uterine bleeding. Since the
majority of cases occur after the age of fifty, the bleeding is usually postmenopausal or
perimenopausal. Care should be exercised in excluding endometrial cancer in women
presenting for acyclic bleeding during the fifth decade or beyond. Among the many causes of
postmenopausal bleeding endometrial cancer form about 20%, the probability is higher the

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older the patient. Endometrial carcinoma affecting women in their reproductive years causes
intermenstrual or continuous bleeding, but may rarely cause menorrhagia.
Vaginal discharge may be complained of, usually in addition to bleeding and is
usually purulent, blood tinged and foul smelling. Occasionally an abnormal discharge is the
only symptom in a postmenopausal woman and this should not ascribed to senile vaginitis
(which can be concomitantly present) until endometrial cancer is excluded. Intermittent
profuse discharge can occur with pyometra. The presence of latter condition should alert the
clinician to a possible underlying malignancy, which can be either in the endometrium or the
cervix. Hematometra may rarely develop due to cervical obstruction by the tumor.
Pelvic pain is not a common symptom and suggests extrauterine spread. However,
recurrent colicky pain may result from attempts of the uterus to expel the intrauterine
swelling.
On bimanual examination, the uterus feels small since the patient is usually
postmenopausal. It can however be enlarged by the growth or hematopyometra and in
advanced cases can be irregular and fixed.
Diagnosis:
1. High index of suspicion must be maintained if endometrial carcinoma will be
diagnosed at an early stage. The more irregular the bleeding and the older the
patient the more the need to exclude organic causes. Postmenopausal bleeding
should be taken to mean endometrial carcinoma until proved otherwise. The
exceptions to this are the patients under postmenopausal hormonal therapy; a
bleeding episode is expected at the end of use of the added progestogen. However, if
such bleeding occurs at "unexpected times" or develops de novo after bleeding-free
months of treatment, investigation is required.
2. Transvaginal sonography (TVS) is used to assess the endometrial thickness. A cut-
off thickness (myometrium to myometrium) of £5 mm is expected in
postmenopausal women. This has been used as screening method combined with
outpatient suction endometrial sampling (e.g. using a pipette). In symptomatic
postmenopausal women if TVS shows normal ovaries and thin endometrium (5 mm
or less) and the suction endometrial biopsy is benign, then no further action is
required unless the bleeding recurs. If, however, the endometrium is thickened or
insufficient material is obtained by biopsy for diagnosis, or the bleeding recurs more
invasive procedure is needed. This ideally comprises hysteroscopy accompanied or
followed by D&C biopsy.
TVS has the added advantage of detecting any ovarian lesion and assessing the
extent of myometrial involvement of endometrial cancer.

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Tumors of the corpus uteri

3. Hystroscopy is increasingly used in the diagnosis of abnormal uterine bleeding. It

allows inspecting the endometrial cavity and indicating the site from which
endometrial biopsy is to be taken.
4. Dilatation and curettage (D&C) has been the standard means for the diagnosis of
endometrial pathology. If endometrial suction instrument is not available, D&C is
the primary method of diagnosis. If methodologically performed, covering all the
walls of the uterus, D&C rarely misses the site of the lesion. However, for this latter
possibility hysteroscopy has been added. Care should be exercised in performing
D&C in an old woman with a small thinned out uterus to avoid perforating the
uterus by the uterine sound or the curette. The naked-eye picture can be suggestive
of malignancy if the curettings are profuse, in the form cheesy lumps rather than
strips and if they are dark in color. Failure of the uterine wall to "grate" with
curetting is suggestive. However, histopathological confirmation should be awaited.
There is little added advantage in performing a fractional curettage (samples taken
from the cervix and then from the body of the uterus) as this can rarely reliably diagnose
or exclude cervical involvement. Considering this difficulty, the new surgical staging of
FIGO uses the inspection of the opened uterine specimen as the final determination of
endocervical involvement.
Routine investigations include chest x-ray, IVP, blood picture, and liver and renal
function test.
In addition, preoperative staging can utilize MRI to determine the depth of myometrial
invasion. However, this can be equally achieved by TVS.
Staging:
The recent FIGO staging of endometrial cancer is surgico-pathological classification.
This "posthysterctomy staging" allows more complete identification of the staging and proper
planning of adjuvant treatment required, and better assessing the prognosis of the case in
comparison to the clinical staging used before.

FIGO* staging for carcinoma of the endometrium (1988)

Stage Features
I Confined to the corpus uteri
Ia Carcinoma confirmed to the endometrium
Ib Invasion of less than half of the myometrial thickness
Ic Invasion of more than half of the myometrial thickness.
II

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IIa Cervix involved.

IIb Endocervical gland involvement only
Cervical stromal involvement but does not extend beyond the uterus.
III
IIIa Carcinoma involves the serosa of the uterus or adnexae, or positive ascites/or
positive peritoneal washings.
IIIb Vaginal involvement either direct or metastatic.
IIIc Para-aortic or pelvic node involvement.
IV
IVa Carcinoma involving the mucosa of the bladder or rectum.
IVc Distant metastases and involvement of other abdominal or inguinal lymph
nodes.
* FIGO, International Federation of Gynecology and Obstetrics.
Note: Preinvasive or histologically suspicious pathology (atypical endometrial
hyperplasia) is not included in this recent classification; previously it was listed as
stage 0.
Prognostic factors: Multiple factors have been identified which significantly
influence the prognosis in carcinoma in endometrial carcinoma; some of these factors are
interdependent:
Prognostic factors in endometrial carcinoma
1. Age and body morphology
2. Stage
3. Histopathologic type
4. Histologic differentiation.
5. Depth of myometrial invasion.
6. Lymph node involvement.
7. Peritoneal cytology.
8. Adnexal metastasis.
9. Molecular indices.

1. Age and body morphology:

Older patients do worse. Obese patients do better than lean ones. It seems that the
obese, hyperlipidemic women, with evidence of hyperesterogenism like anovulatory uterine
bleeding, infertility, late menopause, and hyperplasia of ovarian stroma tend to have more
differentiated endometrial carcinoma with better prognosis.
2. Stage:

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Involvement of the cervix definitely worsens the prognosis; cervical stromal invasion
is worse than involvement of the endocervix only. Even the situation of the cancer low in the
corpus is associated with poorer prognosis. Involvement of the cervix increases the rate of
finding of lymph node involvement.
The survival rates for different stages of endometrial cancer are shown in the box:
Stage 5 years survival
I 82%
II 56%
III 32%
IV 10%
The overall survival rate for endometrial cancer is high as there is a preponderance of
women diagnosed with stage I disease.
3. Histological type:
The rare tumor types of endometrial carcinoma like the serous papillary, clear cell,
and squamous carcinoma have a definitely poorer prognosis than usual endometrioid
adenocarcinoma. The frequent presence of squamous metaplasia not showing malignant
feature i.e. adenoacanthoma, does not change the prognosis.
4. Histological differentiation: Tumor grade
Cases of endometrial carcinoma are grouped under the following three grades:
- Grade 1 or G1 = well differentiated = < 5% is formed of nonsquamous solid
growth pattern i.e. areas with no glands present.
- Grade 2 or G2 = moderately differentiated = 6-50% formed of a nonsquamous
solid growth pattern.
- Grade 3 or G3 = poorly differentiated = >50% formed of nonsquamous solid
growth pattern.
As the tumor gets less differentiated, the risk of deep myometrial invasion increases.
Within each stage the prognosis is therefore, influenced by the tumor grade.
5. Depth of myometrial invasion:
The depth of myometrial involvement is incorporated in the FIGO substaging of stage
I endometrial cancer (Figure 9). Deep invasion is associated with higher rates of lymph node
involvement and is usually associated with lesser degrees of differentiation. Reaching the
serosa will shift the disease to stage III and is associated with poor prognoses.

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Tumors of the corpus uteri (Figure 9): Diagram of a section showing endometrial
carcinoma in some of the FIGO stages.

6. Lymph node involvement:

There is a good deal of correlation between lymph node involvement and other
prognostic factors, but multivariate statistical analysis has identified nodal involvement as a
significant variable. In stage I disease the incidence of pelvic lymph node involvement is
about 10% and the 5-years survival in these subset of is only 30% as compared with more
than 70% for the whole of stage I cases.
Histologically demonstrated lymph space involvement may be an important
unfavourable prognostic indicator.
7. Peritoneal cytology:
Obtaining peritoneal washings for cytology examination is an easy procedure for
assessment of prognosis. However its value independent of other prognostic indicators is not
fully established.
8. Adnexal metastases:
Adnexal metastases are present in about 10% apparantly stage I disease. This should
shift the case to stage III since it is associated with high incidence lymph node involvement
and higher recurrence rates.
9. Molecular indices:
The subjectivity of the traditional histopathological features has led to development of
rapid more precise quantitative measures to assess cellular characteristics. Flow cytometry
has been used in assessment of the ploidy of the tumor. This determines cellular nuclear DNA

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content and measures the fraction of the tumor cells in proliferative phase (S-phase). Flow
cytometry will determine DNA histogram, which reflects the cell cycle phase. G0 and G1
cells contain diploid nuclear DNA content. In a well-differentiated tumor, a smaller number
of cells enter the S-phase and begin DNA replication (S-phase fraction). DNA ploidy can be
denoted as the DNA index (DI), which is the numerical ratio of DNA content of the tumor
cells to the DNA content of G0/G1 peak of normal control population. A diploid tumor has a
DI range of 0.95% to 1.1 and a tetraploid tumor has a DI range of 1.9 to 2%; peaks outside
these ranges e.g. 1.5 or 2.6 are defined as aneuploid.
Most endometrial cancers are diploid but aneuploidy indicates advanced disease and a
poor prognosis. A raised fraction of cells in the S-phase (with DI around 2) also indicates a
poor prognosis.
Amplification of certain oncogenes in the tumor (c-erb B2 or c-myc) has been
associated with aggressive course of endometrial cancer.

Treatment:
In summery, the majority of cases of endometrial carcinoma are primarily treated by
surgery in the form of total abdominal hysterectomy (TH) plus bilateral salpingo-
oopherectomy (BSO). The uterus should be opened after removal. If the cervix is found,
involved radical hysterectomy will be completed if the patient is fit. This can be followed by
adjuvant radiotherapy. Preoperative radiotherapy is nowadays rarely used; it does not
improve results. Advanced case of endometrial carcinoma of stage III and IV are treated by
radiotherapy, with or without hormonal treatment and chemotherapy. Rarely, radiotherapy is
used as a palliative procedure, which may comprise also limited surgery to remove the central
tumor.
Suggested treatment plain(detailed):
1. Stage I endometrial carcinoma with grade 1cancer is treated by TAH and BSO -
peritoneal washing for cytology and examination of pelvic and paraortic lymph
nodes. The hysterectomy is of the extrafacial type. No further treatment is required in
this case (i,e when the glands are not evidently involved and the peritoneal cytology
is negative).
If only positive peritoneal cytology is found intraperitoneal radioactive phosphorus is used

(32P), or alternatively the patient is treated by abdominal and pelvic irradiation,

2. Stage Ia, Ib with G2 or G3 carcinoma are usually treated with TAH plus BSO
followed by vaginal irradiation. The dose of radiotherapy is 6000 cGy delivered by
either vaginal ovoids or vaginal obturator.

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3. Stage Ia, Ib with G2 and G3 are alternatively treated by TAH, BSO, and pelvic
and paraortic lymph adenectomy to be followed by pelvic irradiation.
For pelvic lymph adenectomy the retroperitoneal pelvic spaces are developed in the
usual way as described for Wertheim's operation. The external iliac and common iliac
groups, are removed plus those on the obturator fossa anterior to the obutarator nerve,
and on the internal iliac artery. No attempt is made to remove and lymph nodes on the
internal iliac vein.
The periaortic nodes are approached by retracting the small intestines into the upper
abdomen and incising the peritoneum over the right common iliac artery and lower
aorta. The main blood vessels arising from the abdominal aorta are outlined, and the
ureter is retracted laterally. The tissues overlying the inferior vena cava and aorta are
removed en block. The upper limit of dissection is usually the second and third portions
of the duodenum as it crosses the main vessels retroperitoneally. Usually about 20-30
lymph nodes are available in such cases for histopathological evaluation.
The choice between these two alternatives for stage Ia, Ib, G2, G3 depends upon
available expertise, and fitness of the patient. Many patients with endometrial cancer
would not tolerate the more extensive surgery in view of old age, obesity, and
hypertension.
4. If grade 3 disease, associated with deep myometrial invasion i.e. >half the thickness of
myometrium (stage Ic) but the disease is still limited to the uterus, a postoperative local
vaginal plus external beam whole pelvis irradiation are given. Chemotherapy may be tried.
5. Women with clinical stage II cancer of the endometrium (diagnosed preoperatively) are
treated as if they are having stage I cancer of the cervix, i.e. with radical hysterectomy
followed by pelvic irradiation. If the patient is unfit for this surgery radical radiotherapy is
given again as described for carcinoma of the cervix.
However the majority of cases with stage II disease are pathological stage II i,e
diagnosed postoperatively. These cases are treated with post-operative radiotherapy to the
pelvis and vaginal vault.
6. Cases of endometrial carcinoma not fit for TH=BSO are treated by radical radiotherapy.
Stage III and IV disease is treated with radiotherapy with or without hormonal
treatment and chemotherapy. The radiotherapy consists of both external beam pelvic and
vaginal irradiation.
Radical radiotherapy:
There are two types of treatment of cancer of the endometrium by radiotherapy, one
is by intracavitary radiotherapy alone, and the second is by external radiotherapy to the pelvis
followed by an intracavitary insertion.

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Intracavitary therapy can be carried out by either Heyman's technique in which the
uterus is packed with radium 226 or presently by cesium-137. A dose of 70-80 Gy to point A
is given in two insertions, one week apart, for a low dose rate system. Intracavitary irradiation
can be done by the after-loading system, which allows for individualizing the treatment and
giving a high dose rate system.

Hormonal therapy:
Progestogens: are the most frequently used form of hormone therapy. They are used in
treatment of advanced and recurrent disease. Their role as adjuvant in early cases is most
doubtful. Medroxyprogesteroneacetate (MPA) is the most commonly used progestogen in the
oral doses of 200-400 mg daily and continued for several months. An overall response rate of
15-30 percent has been reported. These the treatment is continued indefinitely. It can produce
water retention and mood changes. Alternatively, the contraceptive injectable depo-provera
150 mg is given twice weekly. The response is more expected in patient with well
differentiated endometrial cancer and those who have experienced late recurrence after initial
treatment. Such tumors are more likely to have progesterone and estrogen receptors. The
response is however, usually partial and lasts for short duration.
Tamoxifen: can increase intracellular progesterone receptors (PR) content, and had been used
in advanced and recurrent disease refractory to progestogen therapy with occasional response.
It can be combined to or given prior to progestogen therapy.
GnRH agonist e.g. goserelin (zoladex) can be given in monthly depot injection. It has
produced some improvement in few cases who failed to respond to progesterone.
Chemotherapy:
Adjuvant chemotherapy is seldom given in endometrial cancer and is prescribed to
patients with advanced or recurrent disease. The anthracyclines like doxorubicin and platinum
drugs like cisplastin and carboplatin can be given alone or in combination. A response is
expected in 20-35% of patients. Response tends to be partial and short-lived.

Results:
Endometrial cancer is considered to have good prognosis. This is due to
preponderance of early stage disease: A 5-year survival of 80-90% is expected in stage I
disease. When lymph nodes are positive this falls to 60%. In advanced disease, which affects
less than 10% of women (USA statistics), the prognosis is poor as it is for any other form of
gynecological cancer.
CA-125 can be used to detect recurrence; but false negative results are common.

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SARCOMA OF THE UTERUS

Sarcoma of the uterus is rare representing 4% of all uterine malignant tumors. This is
fortunate because the prognosis is poor. They comprise the following types:
- Leiomyosarcoma.
- Endometrial stromal sarcoma.
low grade endometrial sarcoma.
high grade endometrial sarcoma.
- Mixed or mixed mullerian tumors (the commonest sarcoma).
Mixed homologous (mullerian) sarcoma.
Mixed heterologous (mullerian) sarcoma.
Rhabdomyosarcoma.
- Other rare sarcomas.
Hemangiopericytoma.
Lymphomas.
Melanoma.

Leismyosarcoma (LMS):
Leiomyosarcoma account for 30% of uterine sarcomas. Only 10% are associated with
myoma and may represent a malignant change in a myoma; i.e. the majority of cases develop
de novo. The gross appearance may simulate a myoma. The tumors are usually solitary and
grows either towards the uterine cavity or infiltrate the myometrium. The tumor is specially
vascular and softer than and the myoma and lacks any pseudocapsule formation.
The microscopic picture of LMS may be difficult to differentiate from an
exceptionally cellular myoma. The differentiation depends upon the frequency of mitotic
figures and nuclear atypia. If more than 10 mitotic figures are present in 10 high power fields
(HPF), malignancy should be assumed. If less than 5 mitotic figures are present in 10 HPFs
the tumor is benign. Between figures 5 and 10 the prognosis is guarded and depends upon the
presence of nuclear atypia and infiltrating features. Spread occurs by lymphatics and blood.
Staging follows the same system of staging of endometrial carcinoma but without substages.
Clinically the condition presents in the sixth decade with irregular postmenopausal
bleeding. The uterus is enlarged either irregularly or symmetrically and is soft. Frequently the
condition is diagnosed as myoma and histopathology reveals the nature of the disease.
Treatment is by AH + BSO. Adjuvant pelvic radiotherapy giving 50-60 Gy is
commonly advocated in attempt to reduce local of recurrence. However there is a high

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incidence of recurrence. Chemotherapy with doxorubicin is the treatment of choice for

advanced and recurrent LMS.
The results of treatment of LMS are poor, and definitely poorer than that of mixed
mesodermal tumor.

Endometrial stromal sarcomas (ESS):

These tumors tend to occur in a younger age group than other types of sarcoma;
usually in the fifth decade. The tumors mainly grow in the myometrium, but are composed of
endometrial stroma. Two forms of ESS are recognized, low-grade and high-grade stroma
sarcoma.
Low-grade stromal sarcoma:
Grossly the tumor causes diffuse infiltrating non-capsulated tumor in the
myomaterium and sends finger like processes in the uterine wall, which may reach the
parametrium. It shows a peculiar tendency to permeate veins and lymphatics so, when the
uterus is removed, these extensions pull out from the broad ligament as warm-like processes.
The tumor may grow polyps into the myometrial cavity. The tumor may be associated with
adenomyosis or endomoteriosis but does not essentially represent a malignant change in these
lesions.
Microscopically the tumor consists of masses of round and oval stromal cells with
only mild nuclear atypia.
Although distant metastases are not common local, extension beyond the uterus is
common. Local recurrence is common after removal of the tumor and occurs as late as after
10-20 years. Ultimately 5 to 25% of the patients die from the disease.
Clinically the condition presents with irregular uterine bleeding. However, the lesion
is occasionally incidentally found at the time of hysterectomy. The uterus is enlarged either
diffusely or irregularly.
The treatment is AH + BSO. Those patient with extrauterine spread should be given
adjuvant pelvic irradiation and/or high-dosed progesterone treatment. The use of the latter
may be based upon finding of progesterone receptors in the tumor cells. Recurrent and
advanced cases are treated by radiotherapy, progesterone therapy, and chemotherapy.
High-grade endometrial stromal sarcoma:
High grade ESS is a highly malignant tumor with a poor prognosis. These tumors tend
to have soft fleshy fungating masses protruding into the uterine cavity or in the vagina and
produce severe alarming bleeding. Histologically the tumor is highly cellular and grows as
cords or sheets of endometrial stroma-like cell that extensively infiltrate the myometrium.

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In addition to local spread, the sarcoma gives early blood metastases, mainly in the
lungs.
Clinically profuse bleeding may be associated with colicky pain. The tumor is bulky
and friable and pieces of the tumor may detach during examination. Cachexia may be
profund.
The treatment is surgery followed by pelvic irradiation. Additionally multiagent
chemotherapy is better given including doxorubicin, cisplatin and ifosfamide.

Mixed mesodermal tumors (MMT):

This tumor is also called mixed mullerian tumors because they are thought to arise
from mullerian mesenchymal rests which differential into both stromal or epithelial elements
in varying proportions.
Mixed mesodermal tumors are the most common uterine sarcoma, and usually occur
in women aged between 60 and 70 years.
The epithelial element is usually an endometrioid carcinoma that is usually poorly
differentiated. Rarely the epithelial element looks benign i.e. adenomatous. The stromal
element may be homologous, that is, composed of malignant cells derived from types
normally present in the uterus, such as leiomyosarcoma, fibrosarcoma, and endometrial
stromal sarcoma, or they may be undifferentiated. Such tumors can be described
carcinosarcoma, or rarely adenosarcoma.
If the stromal elements are not related to the expected uterine tissue, as with
rhabdomyosarcoma, osteosarcoma, and chondrosarcoma, the tumor is described as
heterologous mixed mesodermal sarcoma.
- Clinically, the patients present with postmenopausal bleeding and discharge. Colicky
pain is common. Pieces of necrotic tissue may be passed.
- The uterus is enlarged, fleshy, and soft. Polypoidal tumor may fill the uterus and
protrude into the vagina. The tumor contains foci of hemorrhage and necrosis.
- Spread of the tumor is early and aggressive and can be local or by lymphatics or blood
vessels. The prognosis is much better for homologous mixed mesodermal tumor e.g.
adenosarcoma; than heterologous tumor.
- Treatment is primarily surgical by AH + BSO. Postoperative radiotherapy reduces the
tendency to local recurrence. For advanced and recurrent sarcomas the anthracyclines
(e.g. doxorubicin), cisplatin and ifosfamide have all been shown to be effective either
singly or in combinations.

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Rhabdomyosarcomas:
These are very rare tumors that may arise from the uterine corpus or from the cervix
or vagina. Vaginal rhabdomyosarcomas of young girls are usually referred to as sarcoma
botryoides (grape-like). It usually presents as a mass in or projecting from the vagina or with
vaginal bleeding. Other symptoms are caused by local spread or lung metastases.
Sarcoma botryoides is an embryonal rhabdomyosarcoma originating in subepithelial
tissue of the vagina or cervix. As the polyps grow into the vaginal cavity they retain the
vaginal squamous epithelial covering.
The typical sarcoma botryoides seen in children is often fatal.
Results of treatment of uterine sarcomas:
With the exception of low grade ESS, the polypoidal mixed mesodermal tumor with
no myometrial invasion and the rare leiomyosarcoma occurring within a myoma, the overall
prognosis for uterine sarcoma, regardless of the type, is very poor indeed and for practical
purposes there are no survivors at five years. Even for stage I, the two year survival is only 45
percent. Recurrences are common in the pelvis, pelvic nodes, abdomen, or lungs. Pelvic
irradiation reduces the pelvic recurrence but does not improve the five-year survival.
Adjuvant chemotherapy has no proven role in increasing survival. For low grade ESS,
progestogens are an effective treatment for recurrent disease, resulting in long-term remission.

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Chapter 18
OVARIAN TUMORS

Contents

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Ovarian Tumors

- Treatment of borderline ovarian carcinoma

- Treatment of invasive ovarian carcinoma
* Surgery
* Chemotherapy: single agents and combined therapy
* Hormone therapy and immunotherapy
* Radiotherapy: external beam and intraperitoneal agents
* Salvage therapy
• Prognostic factors and results
• Treatment of germ cell tumors
• Treatment of sex-chord stromal tumors
• Carcinoma of the Fallopian tube

Introduction
- The ovary is a common site for both benign and malignant neoplasias. The
latter includes both primary and secondary tumors. In addition, the ovary is a
common site of nonneoplastic tumors including a variety of retention cyst,
inflammatory cystic formations, and endometriotic cysts.
- The pathology of ovarian tumors is most diverse, reflecting the multiple
embryological origins of the cellular constituents of the gonad.
- The etiology of ovarian neoplasia remains most obscure.
- In spite of the addition of a number of diagnostic aids (imaging and chemical
tests), and various attempts at screening for ovarian neoplasia, the diagnosis
of ovarian malignancy still tends to be late. This results from lack of specific
alerting symptoms, and the growth of ovarian neoplasm in a capacious
space, the peritoneal cavity.
- In spite of more aggressive surgical attack and great advances in
chemotherapy, the salvage rate remains low relative to other types of
gynecological malignancies.
- A group of ovarian epithelial neoplasias has now been characterized as
having borderline malignant features or low malignant potential (LMP).
They have suggestive naked-eye appearance, certain histopathological
features, and less aggressive clinical course. They can receive less radical
management in young women keen to preserve their childbearing function.
- Nonepithelial malignancies of the ovary have a distinctive position, both in
their clinical manifestations and management.

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Ovarian Tumors

Classification of ovarian tumors

Most of the pathological classification of ovarian tumors is based on the embryological
origin of the predominant cell type. Embryologically the ovary is formed of the following cell
types:
1. Epithelial element, which belongs to the mesothelial, cells which
cover the genital ridge, and belongs to the lining of the embryonic
celomic cavity (the forerunner of the peritoneum). These mesothelial cells
are having the potential to differentiate into cells similar to the
endosalpinx, endometrium, and endocervix.
2. Specialized mesodermal (mesenchymal) element, which can result in
hormone producing cells. These are the sex cords that mainly give rise to
granulosa and theca cells of the ovary, and medullary structures of the
testis.
3. Nonspecialized mesodermal (stromal) elements.
4. Germ cells that migrate to the gonad from the dorsum of the yolk sac.
The pathogenesis of ovarian tumors can represent a development from
vestigeal nests or a metaplasia of already developed ovarian tissue elements.
The following is a logic classification, which is most acceptable (but
cannot be claimed to be completely comprehensive):

1. Nonneoplastic cysts
1.1. Functional cysts.
- Follicular cysts.
- Lutein (luteinized) cysts.
- Theca-lutein cyst.
- Polycystic ovary syndrome.
[Link] cyst.
1.3. Pregnancy luteoma.

2. Neoplastic tumors
[Link] tumors
2.1.1. Benign
[Link]. Serous; including:

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Ovarian Tumors

- Simple serous cyst

- Papillary cystadenoma.
- Surface papilloma.
[Link]. Mucinous: Mucinous cystademoma.
[Link]. Pseudomyxoma pritonei.
[Link]. Endometriod cyst.
[Link]. Brenner tumor.

2.1.2. Borderline: ovarian neoplasia

[Link]. Serous cystadenocarcinoma of LMP.
[Link]. Mucinous cystadenocarcinoma of LMP
[Link]. Endometriod tumor of LMP.

2.1.3. Malignant
[Link]. Serous, including:
- Cystadenocarcinoma.
- Adenocarcinoma.
- Surface papillary carcinoma.
[Link]. Mucinous, including:
- Cystadenocarcinoma.
- Adenocarcinoma.
[Link]. Endometriod, including:
- Adenocarcinoma.
- Adenoacanthoma.
[Link]. Clear cell (mesonephroid) carcinom:
(These can be benign, borderline or malignant)
[Link]. Malignant Brenner tumor.
[Link]. Mixed malignant carcinoma.
[Link]. Undifferentiated adenocarcinoma.
[Link]. Unclassified adenocarcinoma.

2.2. Sex cord stromal tumors

2.2.1. Ganulosa – theca cell tumors.
2.2.2. Androblastoma: Sertali cell or Leydig cell tumors.
2.2.3. Gynandroblastoma.
The above three subtypes can be well differentiated, of
intermediate differentiation and poorly differentiated.
2.2.4. Lipoid cell tumors.

2.3. Nonspecific Stromal tumors (connective tissue

tumors):

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Ovarian Tumors

2.3.1. Fibroma.
2.3.2. Lymphoma.
2.3.3. Sacroma.

2.4. Germ cell tumors

2.4.1. Tumors of germ cells origin
-Dysgerminoma.
2.4.2. Tumors of embryonic origin; including either
[Link]. Tumors of embryonic cells
- Teratoma
- Benign cystic teratoma (dermoid
cyst).
- Malignant teratoma.
- Embryonal carcinoma
[Link]. Tumors of extra-embryonic cells, including:
- Endodermal sinus tumor.
- Struma ovarii.
- Choriocarcinoma.
- Mixed tumors.
2.5. Unclassified tumors
2.6. Metastatic (secondary) tumors

Pathology of the important ovarian masses including tumors

* Functional cysts
• the most frequent cysts in the ovary.
• result from fluid distention and/or hemorrhage into one of the natural constituents
of the ovarian cortex.
• occur during reproductive years.
• nowadays increasingly diagnosed as a result of frequent use of pelvic sonography.
• small sized - rarely reach a diameter of 10 cm.
• resolve spontaneously over few weeks.
• usually asymptomatic but rarely disturb menstrual function.
• rarely cause pelvic pain (when complicated by hemorrhage or rupture)which
may be mistaken for other causes of acute abdomen.
• Managed conservatively.
• They comprise the following subtypes:
1. Follicular cysts

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Ovarian Tumors

- lined by granulosa cells

- Usually represent a follicle in the process of atresia, i.e. not
active in hormone production.
- rarely functioning resulting in a short-term delay in
menstruation or an episode of abnormal bleeding.
- more commonly found during ovulation induction ; and in
ovarian hyperstimulation syndrome, they can be multiple and
reach huge dimensions.
- They are commonly noticed during the use of certain
progestogen - only contraceptives like Norplant and
progestogen - only pills.
2. Lutein (luteinized) cyst
- frequently represents a cystic corpus luteum.
- lined by granulosa-lutein and/or theca lutein cyst.
- may delay menses.
- may rapture causing acute pelvic pain associated with a
bleeding episode. This picture may be mistaken for disturbed
ectopic.
3. Theca-lutein cysts
- Commonly seen in association with vesicular molar
pregnancy, choriocarcinoma or rarely in normal pregnancy.
They can be present in ovarian hyperstimulation syndrome
after the HCG administration.
- Multiple, can reach huge dimensions (can reach the size of a
man’s head).
- Lined by luteinized theca cells.
- Result from excessive HCG stimulation.
- Spontaneously regress (usually slowly) over the course of
months after cessation of the HCG stimulation.
4. Polycystic ovary syndrome
- represent a functional disturbance of the hypothalamo-pituitary
ovarian axis associated with chronic anovulation.
- The ovary may be slightly enlarged.
- It has many small subcapsular cysts not exceeding the 8 mm
diameter, hence the necklace appearance on pelvic
sonography.

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Ovarian Tumors

- Commonly associated with chronic anovulation, amenorrhea,

oligomenorrhea, dysfunctional uterine bleeding, acne and
hirsutism.
* Endometriomas
• The ovary is the most frequent site of endometriosis that can result in
endometriotic cyst.
• rarely exceed the diameter of 10 cm, but can be multiple.
• frequently bilateral and associated with pelvic adhesion and
endometriotic deposits on other pelvic structures.
• Filled with thick, brown fluid - similar to liquid chocolate.
• Lined by endometrial epithelium; this in longstanding cases can
become atrophic leaving only a lining of hemosidren-laden connective
tissue. This may make the histological differentiation difficult from old
hemorrhage in another retention cysts.
• Usually rupture during attempt at removal.

* Pregnancy luteoma
• rare
• solid small-to-moderate sized (8 - 15 cm), may be bilateral.
• separate from the corpus luteum.
• cut section may be yellow or gray.
• Formed of luteinized benign cells usually theca-lutein cells.
• It is usually asymptomatic discovered accidentally during
sonography or cesarean section.
• It is not a true neoplasm and regress after delivery.
• Rarely result in virilization of the mother or her female fetus.
* Benign ovarian tumors
Benign ovarian tumors form the majority of ovarian neoplasms (about
80%). They may replace the whole ovary, but sometimes-normal ovarian tissue can
be present on the surface. However, since the differentiation from tumors of low
malignant potential (LMP), and frankly malignant tumors is occasionally difficult on
naked-eye inspection (or even on microscopial assessment), it is wiser to consider
most ovarian neoplasm as malignant until proved otherwise. It is not totally agreed
upon whether progress can occur from benign to borderline or to frank malignant
nature. This change may occasionally occur, but there are evidence that ovarian

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Ovarian Tumors

neoplasm inherently belong to one of the three subtypes. The following are the
common benign ovarian tumors.

Serous cystademona
• The commonest type.
• so called because the fluid contained resembles the serum in being thin
and contain albumin and glubulin ; it can be hemorrhagic.
• small to moderate dimension (20 -30 cm).
• May be bilateral.
• Usually unilocular or comprises a small number of locules.
• Serous cysts can be nonpapillary-called simple serous cyst or cystoma
simplex; in the form of a thin-walled cyst which may be difficult to
differentiate from functional follicular cyst.
• They can be papillary containing intracystic papillae or occasionally
papillae on the external surface (Figure 1). The papillae can be in the form
of cauliflower growths, which may fill the pelvis in however,
histologically benign lesion.
• The cystadenoma is lined, and the papillae are covered by a layer of
cuboidal epithelium similar to that of the endosalpinx. Usually the cells
comprise both cilliated and secretory epithelium (Figure 2). In the frankly
benign growths, the epithelium is one-cell thickness, however tangential
sectioning can suggest stratification.
• Serous adenofibroma may occur without any cyst formation.
• Psamoma bodies can be present in the stromal of the papillae. These are
calcified granules that can be dense resulting in gritty sensation of the
papillae. They are most specific to this tumor, and are not indicative of
malignancy.

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Ovarian Tumors

Ovarian Tumors (Figure 1): Papillery serous cystadenoma of the ovary. Interacystic and
surface papillas. This histologicaly can be benign, borderline, or frankly malignant.

Ovarian Tumors (Figure 2): Benign serous Papillery cystadenoma of the ovary. The
papillae are covered by low cubical partially ciliated epithelium.

Mucinous cystadenoma
• a common type.
• rarely bilateral.
• smooth surfaced.
• may reach a huge dimensions, filling and distending the abdominal cavity (to an
extent similar to massive ascites).
• thin walled.
• usually multilocular ; part of the cyst can be in the form form a honeycomb of
small compartments (Figure 3).
• filled with mucin-like, thick, clear, bluish or colorless fluid; but differs from
mucin in the glycoprotein content and in deficient reaction with acetic acid, hence
the occasional designation as pseudomucinous.

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Ovarian Tumors

• Usually having no papillae

• Lined by tall columnar cells (picket fence cells) with clear cytoplasm, similar to
the epithelium of the endocervix or the intestinal mucosa. Goblet cells may be
present (Figure 4).
• The cell lining is a single layered.
• rarely show active cells suggesting malignant potential. Malignant version are less
common than with serous tumors.
• may perforate resulting in pseudomyxoma peritonei.

Ovarian Tumors (Figure 3): Mucinous cystadenoma, showing multilocular apperance on

section

Ovarian Tumors (Figure 4): Mucinous cystadenoma, cystic space are lined by tall
columnar secretory epithelium

Pseudomyxoma peritonii
• a rare condition, commonly associated with benign, rarely malignant mucinous
ovarian tumor. Rarely secondary to a mucocele of the appendix.

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• The peritoneal cavity is filled with a huge amount of mucinous material, and
this causes extensive adhesions.
• The condition commonly recurs after laparotomy evacuation and excision of
the ovarian tumor. They may need radiotherapy or interperitoneal instillation of
radioactive isotope.

Endometriod cystadenomas
• rare.
• May rarely arise on top of endometriosis.
• Small or moderate size.
• Frequently endometriod tumors are malignant but usually with LMP, and their
prognosis is in general better than the serous cystoacdenoma.
• The epithelial element is similar to the endometrium.

Brenner tumor
• uncommon.
• usually benign, but occasionally shows malignant epithelial element.
• usually solid.
• Grossly similar to fibroma, but may have a yellowish tint of the cut section.
• Microscopically, the tumor is formed of hyperplastic fibrous tissue with islands
of epithelioid cells. These epithelioid cells under high power magnification show a
coffee-bean appearance caused by longitudinal grooving of the nuclei (Figure 5).
The cell nests may show a central cystic degeneration producing a resemblance to
an ovarian follicle.
• Usually endocrinologically inert, but rarely produce estrogen, resulting in post-
menopausal bleeding.
• It can be part of the wall of a mucinous cystodenom.

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Ovarian Tumors (Figure 5): Brenner Tumor, fibrous tissue with islands of clear epithelioid
cells. Note, the characteristic longitudinal grooving, that produces the “ café-been” pattern.

Fibroma
• not uncommon, representing 3 - 5 % of ovarian tumors.
• small to moderate size.
• round or lobulated.
• firm solid tumor, rarely shows central degeneration.
• The cut surface is homogenously fibrous, white, or grayish.
• Formed of fusiform fibrous cells, with fibrous matrix, (no muscle element is
present). It is occasionally hyalinized. In fact, it is liable to all types of
degenerative changes that occur in uterine fibromyoma, with the exception of red
degeneration.
• a benign tumor.
• may be associated with Meigs’ syndrome comprising ascites and hydrothorax.
These characteristically spontaneously disappear after removal of the ovarian
fibroma. The pathophysiology of Meigs’ syndrome is not clear. It may be
resulting from lymphatic irritation due to presence of the tumor, the hydrothorax
resulting from rich lymphatic connections across the diaphragm. Meigs’
syndrome may also be associated with Brenner tumor or Krubenberg secondaries.

Dermoid Cyst (Benign Cystic Teratoma)

• Common: 10% - 15% of ovarian tumors.
• tends to occur in young women, therefore may complicate pregnancy.
• may acquire a long pedicle, hence specifically liable to torsion.

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• may be bilateral.
• Small to moderate sized.
• uniocular.
• thick, opaque yellowish wall.
• The content is greasy sebaceous fluid, and usually there is a tuft of hair.
• The inner wall usually shows a nodule or mammilla to which hair is attached,
and which contains tissue elements belonging to a variety of embryological
origins. These include skin, skin appendages, teeth, bone, castilalge, thyroid tissue,
gastrointestinal epithelium, and neural tissue (indeed all tissue elements normally
seen in fetal life).
• Elsewhere the cyst is generally lined by stratified squamous epithelium.
• Dermoid cyst may coexist with mucinous cyst in the same ovary.
• Essentially benign, when a very rare malignant change occurs it is an
epidermoid carcinoma. The latter malignancy is distinctive from malignant
teratoma, which is essentially malignant from the start and comprises malignant
components of multiple tissue origins.
• Dermoid cysts are frequently removed by cystectomy, Complete removal is
essential to avoid recurrence from part of the wall. The other ovary must be
carefully examined (usually by vaginal sonography)and may require bisection if a
deeply seated dermoid is suspected.

* Borderline Malignant Epithelial Ovarian Tumors

There is an increasing tendency to consider these tumors as a separate category,
which shows little tendency to recurrence, and the recurrences have the same
histopathological features like the original tumor. They tend to occur in younger patients with
a mean age around 45 years while the mean age of frankly invasive epithelial cancer being
about 53 years. These borderline malignancies account for approximately 15% of ovarian
cancer. There is a 5-year salvage rate of 95 % for stage I lesions of this low malignant
potential.
Most borderline tumors remain confined to the ovaries, but rarely give rise to
metastases. However, these tend to remain stationary or even regress after removal of the
ovarian primary.
The diagnosis of borderline malignant ovarian neoplasia may be suggested by the
young age of the patient, and a certain naked-eye feature, but finally depends on expert
histopathological assessment. Cytogenetic assessment of ploidy may be helpful.

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Ovarian Tumors

The majority of borderline malignancy belongs to the serous type, less commonly the
mucinous type. Other types of borderline tumors are rare.

Borderline serous epithelial Tumors

Borderline serous epithelial tumors occupy an intermediate position between the benign
serous cystademona and the frankly malignant serous cystadenocarcinoma in their gross
appearance, histologic feature and prognosis.
1. Grossly the borderline tumors have more abundant internal and external
papillae than the benign type, and are more likely to be bilateral.
2. Histologically the borderline tumors show the following features:
- stratification of the epithelial covering papillae.
- formation of microscopic tufts projecting from the surface epithelium.
- cellular pleomorphim, hyperchromatic nuclei and frequent typical and
atypical mitotic division.
- However, there is no stromal invasion.
3. Genetic assessment of the ploidy can be helpful, with aneuploid tumors being
frankly malignant and diploid tumor being of the borderline with low malignant
potential; the formers having about 20-fold increased death risk relative to the
latter.

Borderline mucinous tumors

Borderline mucinous tumors are less common and more difficult to ascertain.
1. Grossly: the borderline mucinous tumors do not differ from the benign type, but may
show intrcystic papillary and solid parts.
2. Microscopically: borderline tumors show stratification of the epithelium with atypia,
hyperchromatosis and frequent mitotic figures, but no invesions into the stroma.
3. Stage I borderline mucinous tumor shows a high 10-year salvage rate of 95%.

* Malignant ovarian tumors

Ovarian cancer is the most common gynecological cancer in the United States and
United Kingdom. Due to the relatively lower salvage rate of ovarian cancer, it causes more
deaths per annum than those do from cancer of the cervix and endometrium combined.

1. Epithelial ovarian cancer

The majority (85 - 90%) of malignant ovarian cancer is epithelial. These can be
further grouped into histological types as follows:

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Ovarian Tumors

- Serous adenocarcinoma 42%.

- Mucinous adenocarcinoma 12%.
- Endometriod adenocarcinoma 15%.
- Undifferentiated carcinoma 6%.
- Other types of malignant ovarian tumors are much less common.

Serous adenocarcinom
• can be partially cystic: cystadenocarcinoma, or solid.
• Bilateral in 30% of stage I disease.
• Papillary patterns intracystic and on the external surface can be seen in the better-
differentiated tumor.
• Psammoma bodies can be present.
• Multiple dense papillary structure (Figure 6).
• Stromal invasion and cellular atypia are abundant.

Ovarian Tumors (Figure 6): Papillary serous cystadenocarcinoma, breaking through the
basement membrane

Mucinous adenocarcinoma
• Mutilocular cysts containing mucinous fluid.
• can be huge filling the peritoneal cavity.
• can have solid parts or intrcystic papillae.
• can be associated with pseudomyxoma peritonii.
• epithelial lining can show in parts the picket fence cells.
• Stratification, cellular atypia and invasion of stroma are present (Figure 7).

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Ovarian Tumors

Ovarian Tumors (Figure 7): Mucinous cystadenocarcinoma of the ovary, Some cells shows
picket cell arrangement.

Ovarian Tumors (Figure 8): Endometrtrioid carcinoma Attempts at glandular formation.

Endometriod adenocarcinoma
• Can be partially cystic containing brown fluid or totally solid.
• The lining of the cyst usually has round polypoidal projections and solid areas.
• Microscopically there is resemblance to endometrial carcinoma with attempt at
glandular formations. These are usually present in only part of the tumor (Figure
8).
• Concomitant ovarian endometriosis may be noted.

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Ovarian Tumors

• Relative to serous cancer, the endometriod cancer has better prognosis.

• About 15% of the ovarian endometriod carcinomas have concurrent cancer of
the endometrium. Some of these tumors may be secondaries from one site to the
other, but usually they appear to be two separate primary tumors.

Clear cell carcinoma (Mesonephroid carcinoma)

• Uncommon type.
• Resembling the clear cell carcinoma of the kidney.
• They may be associated with endometroid carcinoma in the same tumor, and
may considered as a subtype of the latter.
• Microscopically there are cystic or tubular formations with papillary enfolding
which are lined by clear cells with apical dark nuclei, hence the description
hobnail cells (Figure 9).
• Greatly simulate endodermal sinus tumors.
• Similar tumors may arise at any point in the pelvis at which the primitive
mesonephric duct was once present e.g. in the vaginal wall. These tumors can be
part of diethyl stilbosteral (DES) syndrome resulting from intrauterine exposure to
this steroid hormone by maternal intake.

Ovarian Tumors (Figure 9): Clear cell carcinoma of the ovary: Note cystic spaces with
papilleray infoldings and clear cells with apical dark nuclei (Hobnail cells)

Undifferentiated carcinoma

• Different patterns may coexist in different areas of the same tumor.

• Sometimes specific features of any of the above types may be lacking in the
epithelial cancer.

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Histological grading of epithelial cancer

Any of the above types of epithelial carcinoma can be histologically graded
according to collateral atypia and activity into one of three categories:
Grade 1: well differentiated.
Grade 2: moderately differentiated.
Grade 3: poorly differentiated.
These grades may not correspond to grading cancer as borderline or frankly
malignant tumor. Well-differentiated epithelial tumors of the ovary tend to be more
often associated with early stage disease.

2. Sex cord stromal tumors

These tumors represent those derived from specialized mesenchymal cells. This
group of tumors includes all those that contain granulosa cells, theca cells, Sertolie cells, or
Leydig cells, either separately or in combinations. These tumors are usually hormonally
active. Moreover, certain epithelial ovarian tumors may contain foci of hormonally active
stroma. This is notably possible with Brenner tumor and cystadenomafibroma. The sex cord
stromal tumors are generally rare and include the following types:

Granulosa cell / theca cell tumors

• The commonest sex cord stromal tumor (1.5% of all malignant ovarian tumors).
• Functioning tumors producing estrogen.
• Can occur at any age but most frequent in postmenopausal women when they
produce postmenopausal bleeding. They rarely occur in prepupertal girls when
they produce precocious puberty.
• May produce endometrial hyperplasia or endometrial carcinoma.
• Most tumors contain a mixture of granulosa cell and theca cell elements.
• Pure theca tumors are usually benign. Most tumors are a mixture of benign theca
and malignant granulosa elements. Generally, granulosa cell tumors are malignant
but of low-grade malignancy; recurrences are late.
• Generally small, rarely larger than an orange.
• smooth surface and yellowish cut section.
• Usually solid, but large tumors can have cystic degeneration and hemorrhage in
the cavity.
• Histologically: the granulosa cell element consists of cuboidal cells with deeply
staining nuclei These are arranged either diffusely, in columns, or cords
(cylinderomatous) or rounded (folliculoid pattern) or tubular masses separated by

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hyaline stroma. The cells may be arranged around small cavity forming rosettes of
cells which create the appearance of Call-Exner bodies (Figure 10). The cavities
may represent collected secretion or degeneration.
• Microscopically the theca element is formed of thick spindle cells distributed in an
irregular pattern. They may simulate a fibroms.
• High inhibin level may be associated which can be used as a tumor marker.

Ovarian Tumors (Figure 10): Granuolosa cell tumor of the ovary, - Follicular pattern with
numerous cystic spaces simulating call-Exiner bodies. The basic cells are cuboidal similar to
granuolosa cells with abundant cytoplasm but with deeply stained nuclei.

Androblastomas
• These rare tumors were previously called “ arrhenoblastoma”. They are thought to
originate from certain male directed stromal elements. However, they are not
always virilizing; may be endocrinologically inert, or even feminizing.
Androblastoma comprises tumor of Sertoli cells, Leyig cells, or the precursors of
either, alone or in combinations.
• Androblastoma can occur at any age but the majority occurs in women aged
between 10 and 35 years.
• They may cause defeminization (amenorrhea, breast atrophy) then viriliztion
(hirsutism)
• They are usually benign but can occasionally be malignant.

Sertoli cell tumor

• Rare, usually small, often solid and cut section is yellowish.

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Ovarian Tumors

• Histologically, the tumor is well differentiated, shows uniform tubules lined by a

single layer of radially arranged cell with clear cytoplasm and basal nuclei. The
cells usually contain lipoid droplets. These cells become fainter towards the
lumen. The cell boundaries may be so faint to give a syncytium-like appearance.

Leyig cell tumor

• Rare, small, clearly defined, fleshy or soft, the cut section is yellow or brown.
• Microscopically, there are sheets or cords of cells similar to the Leydig cells: The
cytoplasm is markedly esonophilic and contains lipoid granules; the nuclei are
central and large.
• Leydig cell tumors tend to occur in older women and are usually virilizing.

Sertoli- Leydig cell tumors

• Contain a mixture of sertoli and Leydig elements.
• usually small.
• Histologically can show variable grade of differentiation.

Gynandroblastoma
• Very rare tumors, which contain a mixture of granulosa and Sertoli-Leyig, cell
types.
• Benign.
• Can be either androgenic or estrogenic.

3. Connective tissue tumors (tumors of nonspecialized ovarian stroma)

These are thought to arise from the nonspecialized ovarian stroma. The main
representative of this group is the fibroma (discussed above), but include the rare
adenofibroma, myoma, lipoma, chondroma, hemamangioma, and lymphangroma. Sarcomas
of the ovary are rare. They are the malignant counterpart of fibroma. The spindle cell
histology is the main type.
4. Germ cell tumors
• Germ cell tumors represent a relatively small proportion of all ovarian malignant
tumors.
• The most commonly occurring germ cell tumor is the dysgerminoma. This is
supposed to arise from the germ cells, which migrate, to the gonadal site from the
hindgut. The male can develop an exactly similar tumor but is called seminoma.
Each of these two has the same karyotype as the host i.e. dysgerminomas have XX
chromosomal complement.

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Ovarian Tumors

• Tumors can arise from vestigial rests left behind in the ovary from the various
steps of development of germ cells; tumors can arise from stem totipotents - cells -
embryonal carcinoma. Tumors can arise from extraembryonic cells are
represented by endodermal sinus tumor and choriocarcinoma. Tumors arising
from embryonic cell rests are represented by tertomas ; the benign cystic tertoma
(discussed above), and the malignant tertomas (Figure 11).

Ovarian Tumors (Figure 11); Derivation of germ cell tumors, (From Teilum 1965).

• They occur in young women.

• Germ cell tumors have a much better prognosis.
• They are sensitive to radiotherapy and chemotherapy, which are the main lines of
their treatment. Radical surgery, such as bilateral oophorectomy, does not improve
cure rate.
• Therefore it is important to recognize them preoperatively or during surgery so
that conservative management is carried out to retain fertility of those usually
young women.
• The diagnostic workup should include, in addition to the usual measures, chemical
tests for certain tumor markers including alpha-fetoprotein (AFP) produced by
yolk sac cells and beta-subunit of human charionic gonadotrophin (BHCG)
produced by syncytiotrophoblastic element of the tumor. Lactate dehydrogenase
(LDH) and placenta alkaline phosphatase (PLAP) should be estimated.

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Ovarian Tumors

Dysgerminonoma
• Dysgerminonoma is a malignant ovarian tumor.
• Dysgermina accounts for 2 – 5 % of all primary malignant ovarian cancer and
form about 40 % of germ cell tumors.
• They usually occur in women less than 30 years old, but can occur at any age.
• A small proportion of dysgerminomas (or seminoma) occur in mixed ovarian
dysgenesis or androgen insensitivity syndrome where it may be associated with
gonadoblastoma.
• Grossly, they are moderate in size but may reach large dimensions.
• Solid, soft or rubbery with smooth or nodular outer surface.
• Bilateral in 10 % of cases.
• Microscopically, the picture is characteristic, composed of nests of large round
cells with abundant cytoplasm separated by fibrous stromal septa infiltrated by
lymphocytes (Figure 12).
• Occasionally, the tumor contains an element of embryonal carcinoma, endodermal
sinus tumor, or giant syncytotrophoblastic cells.
• Like the seminoma dysgerminoma spread by lymphatic to paraaortic, mediastinal
and supraclavicular lymph nodes.
• Dysgerminoma is endocirnologically inert, rarely results in elevation of b-HCG
(when the tumor comprise a choriocarcinomatous element) .
• Because of occurrence in young women, it can complicate pregnancy or cause
obstructed labor.
• Dysgerminoma is highly sensitive to radiotherapy.
• It is also highly sensitive to chemotherapy.
• The majority of patients have Stage I disease at the time of surgery; conservative
surgery by unilateral salpingo-oopharectomy is usually possible.

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Ovarian Tumors

Ovarian Tumors (Figure 12): Dysgerminoma, Showing nests of large round cells with
connective tissue septa and lymphocytic infiltration.

Endodermal sinus tumor

• is the second common form of malignant germ cell tumor (20 % of these tumors).
• cccurs in young women; always unilateral.
• Characterized by rapid growth and extensive intraabdominal spread.
• Usually solid with areas of necrosis or hemorrhage.
• Microscopically, the tumor consists of a loose vacuolated network of microcysts
lined by flat or cuboidal cells. The stroma is loose reticular. Some of the cystic
spaces have a characteristic papillary structure with central blood vessel, (Schiller-
Doval body).
• Alpha-fetoprotein is characteristically elevated.
• Not sensitive to radiotherapy.
• Usually treated by surgical removal that can be unilateral in a young patient
followed by combination chemotherapy.

Embryonal carcinoma
• A very rare germ cell tumor that is highly malignant.
• It grows rapidly. It is exclusively unilateral.
• Histologically, it consists of large primitive highly active cells with occasional
glandlike formation.
• May produce both aFP and bHCG.
• It may produce precocious puberty, uterine bleeding or virilization.

Choriocarcinoma of the ovary

• A very rare, highly malignant tumor.

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Ovarian Tumors

• Can be primarily ovarian or a secondary from gestational trophoblastic tumor.

• Can contain components of other germ cell tumor.
• Secretes HCG.
• May be associated with precocious puberty or abnormal uterine bleeding.

Teratomas
• Composed of a mixture of tissues derived from the three germ layers:
ectoderm, mesoderm and endoderm.
• Benign cystic teratoma is common accounting for 15% of all ovarian tumors
(see above).
• Mature solid teratoma is very rare.
• Immature teratoma or malignant teratoma is a rare tumor that occurs in young
women.
• Struma ovarii is a teratoma in which thyroid tissue predominate and may be
associated with hyperthyroidism.
• Carcinoid tumor is a teratoma in which intestinal or respiratory epithelium
predominates.

Gonadblastoma
• A rare malignant tumor composed of both germ cells resembling
dysgerminoma and gonadal stromal cells resembling granulosa or sertoli tumor.
• Seen in young patients with primary amenorrhea associated with mixed
gonadal dysgenesis or rarely androgen insensitivity syndrome (see under primary
amenorrhea).
• They carry good prognosis if the tumor and the other ovary (gonad) are
removed.

Spread of ovarian cancer:

Malignant ovarian tumors are disseminated as follows:
1. Direct spread: cancer of the ovary invades the ovarian capsule and spreads
directly to involve the pelvic peritoneum and other pelvic organs. Involvement of
the other ovary (and occasionally the endometrium)) can represent multifocal
cancer.
2. Transcelomic spread: The peritoneal fluid carries the malignant cells through
the peritoneal cavity, to the omentum, to the peritoneal surfaces of the large and

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Ovarian Tumors

small gut, and liver, and to the undersurface of the diaphragm. Metastases on the
latter site are found in over 40 % of cases with disease confined to pelvis (Stage I
and II) i.e. should be looked for. Intraperitoneal metastases from ovarian cancer
are characteristically superficial and seldom involve the substance of the under-
lying organ and even when the surface of the bowel is extensively involved, the
muscle layer is seldom infiltrated. Hemorrhagic ascites is usually present:
3. Woodruff suggested another mechanism for this transcelomic spread. He
suggested that the entire celomic epithelium can give rise to these numerous
widely spread “miliary” lesions under the influence of carcinogenic agents that
gain access to the peritoneal cavity from the vagina via the fallopian tubes, i.e.
the peritoneal lesion represents multifocal origin of malignancy with the initial
involvement of the ovary. This explains the widely spread miliary metastases
(simulated to miliary tuberculosis) in association with a small involvement (or
rarely no involvement altogether) of the overies.

4. Lymphatic spread: Lymphatic spread is mainly along the lymphatics that

accompany the ovarian vessels to the upper aortic (celiac) lymph nodes. These
nodes may be involved in 15% of cases where the cancer is still within the pelvis
but the involvement rises to 50% when the cancer has spread beyond the pelvis.
Pelvic lymph nodes on the same side of the tumor may be also involved, rarely
the inguinal lymph nodes. The left supracalvicular lymph nodes may be involved
by lymph carried in the thoracic ducts. Malignant deposit present on the
undersurface of the diaphragm may represent a spread by lymphatics. These can
also spread to the pleura causing hydrothorax.
5. Blood spread: This usually occurs late with most women dying while the disease
is still restricted to the peritoneal cavity. The hematological spread occurs mainly
to the liver and the lungs, although bone or brain metastases may occur.
Metastatic (secondary) ovarian neoplasia
These account for 10% of malignant ovarian tumors. The ovary is an exception to the
old “Virchow rule” indicating that the organ, which is a common site of primary malignancy,
is a rare site for secondary malignancy. This special case may be related to the rich lymphatic
connections or a special attraction of ovarian tissue to cancerous cells originating from certain
specific sites. Ovarian secondary malignancy arises from the following malignancies:
1. Carcinoma of the other ovary or the endometrium (rarely the cervix). Some
of these represent multifocal malignant diseases. These secondaries are
usually small and may be microscopic.

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2. Carcinoma of breast: About 25 % of women dying from breast cancer have

ovarian secondaries. These can develop several years after removal of the
primary. Ovarian secondaries are most likely in relatively young patients.
The secondaries are of small to moderate size commonly bilateral, solid and
bossy, freely mobile. The histology may simulate that of the original tumor,
and is rarely Krukenberg tumor with signet cells.
3. Gastrointestinal (GIT) primary: The primary site can be the stomach, colon,
goal bladder, or small intestines.
The ovarian metastases are commonly of Krukenberg type which are largely solid,
bilateral, lobulated and free. They may attain a large size overshadowing the primary
gastrointestinal tumor. Large secondaries may be cystic.
Microscopically, the picture is variable. It may simulate the histology of the
primary, which may create difficulty in differentiating the secondary from a primary
mucinous ovarian carcinoma.

Krukenberg tumor
• It is a special type of ovarian secondaries particularly arising from a
gastrointestinal primary. However, not all ovarian secondary from GIT
primary is of Krukenberg type.
• Grossly: Krukenberg tumors are firm, solid growth, kidney shaped, of
moderate size usually bilateral. They have a thick intact capsule and are
freely mobile. The cut section shows firm, cystic, degenerated and
hemorrhagic areas (Figure 13).
• Microscopically: the epithelial element consists of clusters of vaculated
cells (mucoid cytoplasm) with peripheral nuclei, hence the signet ring
description. The stroma may be firm richly cellular in areas and loose
edematous in others (Figure 14).

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Ovarian Tumors

Ovarian Tumors (Figure 13): Bilateral Krukenberg tumors, moderate sized, bilateral kidney
shaped, lobulated, solid, thick capsule with areas of hemorrhage and cystic degeneration.

Ovarian Tumors (Figure 14): Krukenberg tumor, the characteristic signet ring-cells

Epidemiology of ovarian cancer and etiological factors

Approximately 25% of gynecological cancers are ovarian and 50% of all deaths from
cancer of the female genital occur in women with ovarian malignancy. Thus, it may not be the
commonest but it is the most lethal gynecological (excluding breast) cancer.
Ovarian cancer can occur at all ages; the mean age of frankly malignant epithelial
ovarian cancer is 53 years while that of borderline ovarian cancer is 45 years. The malignant
germ cell tumors occur in young women. The etiology of ovarian cancer is far from being
understood: There are, however, the following associations:
• Familial ovarian cancer

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Inheritance plays a significant role in only 5 % of ovarian epithelial

cancers usually of the serous type. The majority of ovarian cancer is sporadic.
Families with predisposition to this familial ovarian cancer include families
with multiple cases of certain types of familial cancer syndrome in multiple
female members of the family. These syndromes comprise in order of
importance:
- Breast / ovarian cancer syndrome.
- Organ specific ovarian cancer.
- Lynch II syndrome: comprising history of breast,
colorectal (nonpolypoidal) or endometrial cancer.
The more the number of previously affected members and the closer the kinship,
the higher the risk. However, for an individual woman in these families the lifetime risk
does not exceed 10% on the whole. Genetic screening is indicated in these families for
presence of Breast cancer genene 1 (BRCA 1). This is particularly needed if a member
of this family has developed breast or ovarian cancer at a young age. The presence of
mutation of BRCA 1 gene indicates a lifetime risk of either breast or ovarian cancer
amounting to 30 % to 50%. Screening the general population is of little significance
because there is no firm evidence to show that BRCA 1 gene mutation contributes to
sporadic cancer of the ovary. A second gene mutation has been discovered in some of
the breast and ovarian cancer patients and is designated as BRCA 2. The significance
of the latter gene has not yet been clearly worked out.
• Effect of parity: The odds of developing invasive epithelial cancer
decreases with increased parity.
• Effect of use of combined oral contraceptives (COC): The risk of
developing ovarian cancer is markedly diminished by ever or past use of
COCs. This has been explained by the theory of incessant ovulation
(repetitive uninterrupted ovulation predisposing to ovarian epithelial
cancer with COC use preventing this effect).
• Effect of clomiphene and similar drugs: There is suggestion, which
needs more confirmation, that prior use of fertility drugs particularly
clomid may increase the risk of borderline and invasive ovarian
neoplasia.
Effect of certain environmental influences: Woodruff et al., suggested
the hypothesis that migration of certain chemical carcinogens from the
vagina via the tubes to the pelvic peritoneum including the ovaries. These
may include talc powder.

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Ovarian Tumors

• Effect of tubal sterilization: There are epidemiological evidence,

which still require more confirmation that tubal sterilization results in 40
% reduction of the incidence of ovarian cancer. This may be explained by
decrease of likelihood of certain environmental carcinogen to reach the
peritoneal cavity.

Clinical picture of ovarian tumors:

A. Symptoms:
Ovarian tumors do not produce specific symptoms. They grow in the wide peritoneal
cavity and are late in producing pressure on certain abdominal structure. They rarely disturb
the menstrual function. Therefore, they remain asymptomatic for a long time. They are
frequently discovered during abdominal examinations done for other purposes, or a routine
ultrasonographic examination.
The presence of an abdominal swelling is usually the first manifestation. Cases may
present for vague abdominal pain or dyspeptic manifestations, bladder irritation or pelvic
heaviness. They may not be discovered until they have undergone certain mechanical
complications like impaction in the pelvis, torsion, hemorrhage or rupture. Edema of the
lower limbs or vulva is a rare presenting manifestation of malignant ovarian tumors. Cachexia
(a combination of general illness and weight loss) occurs with big ovarian tumors, not
essentially the malignant ones only.
Therefore, the presence of asymptomatic abdominal or pelviabdominal mass should
suggest an ovarian tumor.
Sudden development of ascites should suggest an ovarian tumor.
Uterine bleeding, usually in the form of postmenopausal uterine bleeding, may rarely
result from some ovarian tumors. This bleeding results from the rare functioning ovarian
tumors or from some epithelial tumors with functioning elements in their stroma. Mechanical
complications like torsion may precipitate an episode of bleeding due to sudden pelvic
congestion. Malignant ovarian tumors may cause uterine secondaries. Rarely the malignancy
is primarily multifocal involving both the ovary and the endometrium.
In metastatic ovarian tumors, there can be history of the primary diseases (e.g. breast
cancer) or manifestation of their presence, e.g. gastrointestinal symptoms.
B. Signs:
Small ovarian tumors lie in the pelvis behind the uterus; usually the side of origin cannot
be determined. If a small ovarian cyst is found in the uterovesical pouch, this suggests a long-
pedicled one, or one which has undergone an element of torsion, e.g. dermoid cyst.

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Ovarian Tumors

When an ovarian tumor enlarges, it grows out of the pelvis to come behind the
abdominal wall, usually in the middle line, (Figure 15) which, results in central dullness of
the abdomen, usually with resonance on the flanks due to lateral displacement of the
intestines. This is unless there is an associated ascites when both flanks should be dull and
there is shifting of the resonance. Huge ovarian cysts filling the abdominal cavity may
simulate ascites. These can be easily differentiated by abdominal percussion; a patch of
resonance in one of the flanks should exclude the presence of free fluid in the peritoneal
cavity.
Small or moderate sized ovarian tumors may demonstrate some more side-to-side and
upward mobility relative to other abdominal tumors; this mobility is not conducted to the
cervix. The uterus can be occasionally felt separate from the tumor. If this cannot be
achieved, an acute angle between the lower pole of the tumor and the uterus suggests an
ovarian tumor. This is in difference from uterine tumors where there is a wide or obtuse angle
between the lower pole of the tumor and the uterus (Figure 16).

Ovarian Tumors (Figure 15): The common position of ovarian tumors in relation to the
uterus, (A) a small tumor lying to the side of the uterus; (B) a medium sized tumor lying
behind; (C) a small to medium sized tumor lying in front, and it is likely to have its pedicle
twisted;.(D) a large tumor lying above and in front of the uterus, directly behind the anterior
abdominal wall. (after Jeffcoate’s 1987)

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Ovarian Tumors

Ovarian Tumors (Figure 16): Distinguishing between uterine and extrauterine tumors by not
feeling and feeling notch on vaginal examination (after Jeffcoate’s 1987)

C. The diagnosis of ovarian tumor goes in 4 steps:

a. Is the tumor a functional ovarian cyst?
b. Is this an ovarian tumor?
c. Is it a secondary (metastatic) ovarian tumor?
d. Is it a benign or a malignant ovarian tumor?

a. Functional ovarian cyst is suspected when a small cystic tumor is felt behind or to one
side of the uterus. The diameter should not exceed 10 cm. A functional nature of this cyst
is proved by disappearance or marked reduction over few weeks. Functional cysts in the
ovaries are now frequently diagnosed due to the frequent use of pelvic sonography; and
they may be felt clinically. This is particularly so in patients receiving treatment for
induction of ovulation. The menstruation is rarely changed by the presence of these cysts,
because they represent a cystic distention of an atretic follicle. However, the menstrual
period may be few-days delayed or there is an episode of uterine bleeding or vague
abdominal pain. It needs to be widely appreciated in the medical profession that these
functional cysts are quite common. This will save the ovary from unnecessary
“cystectomies” done by general surgeons during appendectomy laparotomies. This may
unnecessarily compromise the future fertility of the patient through resulting in pelvic
adhesions or removal of valuable ovarian tissue. Rupture of a corpus luteum cyst may
simulate disturbed ectopic or other types of acute abdomen.

b. The second step of ascertaining an ovarian nature of a tumor should take in consideration
the big list of possible differential diagnosis. The common mistakes include the
following:
1. A full bladder may be mistaken for an ovarian cyst. The patient should evacuate her
bladder (particularly during the winter) before being submitted to pelvic examination.
This may be neglected in a busy clinic, and results in the examination being painful
and inaccurate. One may need to pass a catheter if urinary retention is suspected.

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Ovarian Tumors

2. A rare but equally unnecessary mistake is when a pelvic colon laden with fecal are
mistaken for ovarian tumor in the Douglas pouch. These fecal masses are, however,
indentable, a feature which differentiates them from tumors.
3. A pregnant uterus may be acutely tilted to one side to an extent suggesting an ovarian
tumor. History may suggest pregnancy. The pregnant uterus has a certain characteristic
sensation (plastic) resulting from the presence of the amniotic sac, and
characteristically contracts (hardens up) and relaxes (softens) if observed over a short
period of time (Palmer’s sign). The gynecologist should not forget the possibility of
pregnancy in a woman presenting for any reason during childbearing period.
4. Fibroids are commonly mistaken for ovarian tumors. Fibroids are, however,
commonly associated with uterine bleeding, a rare occurrence with ovarian tumors.
With fibroids the uterus is usually not felt separate from the mass, and the angle
between the lower pole of the mass and the cervix is obtuse or absent. Pelvic
sonography can usually differentiate between these two possibilities.
5. A fatty lower abdominal wall may superficially simulate an ovarian tumor. Percussion
of the abdomen easily avoids this mistake.
6. Free fluid-ascites can be mistaken, as indicated above, with tense ovarian cyst.
7. Colonic distention with gases(flatus).
The above seven possibilities can be remembered by the famous 7 Fs-full bladder, fecal
mass, fetus, fibroid, peritoneal fluid, fatty abdomen, and flatus.

8. Adnexal masses - mainly inflammatory or endometriotic - may be mistaken for

ovarian tumors or vice versa. However, anamnestic data suggest these possibilities,
and the masses are usually bilateral and fixed. Serous fluid can collect between pelvic
adhesions in a patient who has undergone previous laporotomies, resulting in mass that
simulates ovarian cysts.
9. Other pelvic masses like pelvic kidney, bladder, or rectal tumor should also be not
overseen.
10. Other abdominal masses like encystic tuberculous ascites or retroperitoneal or
mesenteric cysts or tumor can be differentiated from ovarian tumors by the
demonstration of patches of resonance on the surface of the swelling.

c. When an ovarian neoplasm is diagnosed, it is next necessary to determine whether it is

primary or metastatic. A full history and examination concentrating on possible sites of
primary malignancies, which metastasize to the ovaries, should be done. Metastases from
breast cancer can develop several years after treatment of the primary. The diagnosis may

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Ovarian Tumors

need certain radiological examination to exclude GIT tumors (barium meal or barium
enema, as well as endoscopic examinations).

d. When the lesion appears to be primary in the ovary, it needs to be decided whether it is
benign or malignant. Features suggesting a malignant nature include the following:
1. Age: The older the patient the higher the chance of the tumor being malignant;
more than 50% of ovarian tumors above the age of fifty are malignant. On the
other extreme of life ovarian tumor in children or adolescents are usually
malignant, frequently of the germ cell type.
2. Rate of growth: rapidly growing tumors are usually malignant. However, a
sudden enlargement of an ovarian tumor can result from hemorrhage in the tumor.
3. A dull aching pain: (as distinct from acute abdomen that can result from
mechanical complications) is suggestive of malignancy.
4. Bilaterality of the tumor is suggestive of malignancy. However, benign tumor like
dermoid cyst or benign serous cystadenoma can be bilateral.
5. Solidity of the tumor or presence of solid parts in otherwise cystic tumor suggests
a malignant nature.
6. Fixation of the tumor suggests malignant nature. Exception can result with benign
ovarian tumors from impaction of the tumor in the pelvis, development of
adhesion after torsion, and an associated endometriosis.
7. Ascites: The presence of ascites suggests transcelomic spread, or at least that the
tumor has broken through the ovarian capsule. Meigs’ syndrome is an exception.
Tapping of the ascites may get a hemorrhagic fluid, a finding highly suggestive
of malignancy. The ascetic fluid should always be subjected to cytological
examination.
8. Edema of the lower limbs and vulva and/or varcosities suggests venous or
lymphatic obstruction, which result from malignant growth.
9. Root pains suggest advanced malignant disease involving the roots of sacral
plexus.
10. Presence of metastases: These may comprise a cacked-up omental mass (usually
demonstrated by sonography), shotty masses in the Douglas pouch, and/or a mass
in umbilicus. The upper aortic lymph nodes may be felt enlarged-in the
epigastrium. The left supraclvicular nodes may be palpabally enlarged (Virchow
nodes) Blood spread to a distant site is rarely seen in late disease - the patient
usually expires with the disease still within the peritoneal cavity. Bone or brain
metastases are not seen until the primary tumor is large enough to be palpable, i.e.

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an ovarian origin of metastases in bones or brain is highly improbable in the

absence of a pelvic tumor.

D. Complications of ovarian tumors

1. Torsion of the pedicle
Predisposing factors: small size, long pedicle (as with dermoid cyst),
fixation of the tumor at one point initiates tilting around a fulcrum, and pregnancy
and puerperium because of rapid change the position of the tumor which initiates the
tilting. The condition may be precipitated by straining during defection, labor, by
turning over in bed, or sexual intercourse.
The process is initiated by a sudden twist around the pedicle, which rapidly
accentuates itself by the hydrodynamic effect of the blood flow in the pedicle;
resulting in several-fold torsion precipitated all of a sudden. At the beginning the
venous flow is impeded resulting in sudden congestion which may precipitate
intracystic hemorrhage. Later, the arterial flow is impeded which will result in tissue
necrosis and gangrene. The tube is usually involved with torsion of ovarian tumor.
Minimal torsion may result in adhesion of the tumor to the abdominal wall or
intestines.
Clinically: there is acute pain associated with feeling a tender mass in the
lower abdomen. The condition needs to be differentiated from the many causes of
acute abdomen; sonography is helpful. There is usually fluid in the peritoneal cavity.
Treatment: Immediate laparotomy is needed. If the tumor looks gangrenous
and there is several-fold torsion, salpingooopherectomy is done. If the ovary looks
viable there can occasionally be a place for cystectomy conserving viable ovarian
tissue.
2. Hemorrhage into or from a cyst
This is predisposed to by torsion, trauma to the abdomen, infection,
degeneration, or malignant nature. The condition results in acute, intraperitoneal
hemorrhage, collapse, and peritonitis. If the tumor had been previously diagnosed
the mass suddenly enlarges. Immediate laparotomy is needed.
3. Rupture
Predisposing factors include torsion, or hemorrhage. The condition may be
precipitated by external trauma. Papillary cystadenoma or malignant lesions may
undergo spontaneous perforation through the capsule. The acute pain is associated
with spreading peritonitis and presence of free fluid in the peritoneal cavity. A
severe peritoneal reaction may result from rupture of a dermoid cyst. A previously

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Ovarian Tumors

known cyst may undergo a sudden reduction in size or disappearance. A possible

late sequel of rupture of a mucinous cystadenoma is pseudomyxoma peritonei(see
above)
4. Infection
Infection may result from torsion, hemorrhage, and is commoner during
puerperium. Infection may result from tapping ovarian cyst. The severe pain is
associated with severe systemic toxemia and fever because the pus is held in a
closed space. Omental and intestinal adhesion may make removal of the tumor
difficult.
5. Impaction in the pelvis
This is predisposed to by long pedicle and small size. The tumor may be
impacted in the pelvis because of adhesion or pushed in the pelvis by a growing
pregnancy. Pelvic impaction results in pelvic pain, irritability of the bladder, urinary
retention and rectal pressure or constipation. It can obstruct labor.
6. Degeneration
Most large solid tumors can show evidence of necrosis and hemorrhage in the substance.
Fibroma of the ovary can undergo all types of degeneration that can occur in uterine
fibromyoma with the exception of red degeneration. These degenerations are usually
asymptomatic but may result in a dull aching pain.
7. Intestinal obstruction
This rarely complicates adhesion of benign tumor to the intestine, but is common with
malignant tumors. Intestinal obstruction is the commonest mode of death from ovarian
cancer.
8. Malignant change
Malignant change may occur in some benign ovarian tumors, particularly in serous
cystadenoma. However, there is always the doubt that a malignant component might have
been missed in the initial pathological assessment. Increasing experience with borderline
malignant tumor indicates that this may represent a specific entity that generally carries a
better prognosis, and features of low malignancy potential.

E. Aids to Diagnosis of ovarian tumors

• Diagnostic imaging
1. Ultrasonography: is greatly helpful. It can usually exclude a uterine
origin of the mass. Sonography assesses whether the tumor is cystic or
partially solid, can diagnose intracapsular or extracapsular papillae and
the nature of the fluid inside the cyst, with either a thin or a thick

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Ovarian Tumors

echogenicity. It can suggest associated adhesions, omental involvement,

ascites, and liver metastases. Doppler ultrasonography may indicate
increased vascularity of the tumor, and this may suggest a malignant
nature.
2. X-ray: may occasionally show the outline of the tumor by persistent
displacement of intestinal loops. It can show teeth or bone in a dermoid
cyst, irregular faint shadows of psmomma bodies. IVP can indicate
ureteric compression or displacement. Contrast studies are needed for
diagnosis of GIT primary of suspected ovarian secondaries.
3. CT. Screen or MRI can further help the definition of the mass and
indicate involvement of the omentum paraaortic lymph nodes and liver
metastases. The presences of loops of intestines on the front of the tumor
throws serious doubt on an ovarian origin and suggest a retropretonial
tumor.

• Diagnostic laparoscopy:
This is specially needed with small pelvic masses. It can be needed to differentiate
ovarian neoplasm from uterine fibroid or pelvic endometriosis. It is contraindicated in the
presence of big abdominal mass.

• Tumor markers:
Tumor markers are chemical compounds produced by tumors in the patient’s
[Link] detection and levels in the blood indicate the presence,
progression or regression of the neoplasm. The first, and by far the most
successful, tumor marker has been HCG particularly its beta-subunit. The
successful use of HCG as a tumor marker had not only depended upon the
development of highly sensitive immunoassays, but also on the availability of
highly effective chemotherapy.
Other types of neoplasia produce certain antigenic proteins, which can
be used to raise antibodies for them by immunizing other species of animals.
The antibodies can then be utilized in the assay of the tumor antigen in the
blood of the patients, i.e. can be used as a marker for the presence and
progression of neoplasia. Unlike HCG, most of the tumor antigens have no
hormonal functions, i.e. have no physiological significance. By utilization of
newer molecular biology technologies, more specific tumor markers have
been produced.

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Ovarian Tumors

However, the use of these tumor markers have been hampered by

certain difficulties, including:
1. Tumor antigen(s) or marker(s) may not be specific to a certain
type of neoplasia but may be produced by more than one type of
neoplasia.
2. Tumor associated antigens can be produced in small amount by
normal tissue or in certain nonneoplastic diseases, e.g.
inflammatory conditions.
3. Tumor antigens are variably produced by a single tumor type or
even by different parts of one tumor.
4. For an antigen to be present in the circulation and available for
detection by the antibodies, it must not only be produced by the
cancer cells, but also secreted or shed into the circulation i.e. they
can be undetectable in the early stages of neoplasia. Thus are
unsuitable for early diagnosis.
5. Lack of effective curative therapies equal to that of trophoblastic
neoplasia have diminished the utility of certain tumor markers.

• CA – 125:
CA - 125 is a glycoprotein shed from the surface cells of epithelial ovarian
cancer particularly the serous carcinomas. A monoclonal antibody has been raised to
CA - 125 by immunizing mice, and this is used for assay of CA - 125. Using this assay,
only 1- 3 % of healthy nonpregnant women have elevated CA - 125. Levels of more
than 35 u/ml are detected in 80 - 90% of patients with epithelial cancer. Mucinous
tumors are less likely than serous tumors to produce elevated CA - 125. Moreover,
about 50% of patients with Stage I ovarian cancer have normal levels of CA- 125, i.e. it
is not sensitive enough for screening purposes.
CA - 125 lacks specificity. Elevated serum levels have been found in patients
with metastatic endometrial, fallopian tube, endocervical and pancreatic cancers, and in
a minority of patients with breast, lung and colon cancer. A slight to moderate elevation
of this antigen may be associated with acute pelvic inflammatory disease, adenomyosis,
endometrisis, benign ovarian tumor, menstruation, cirrhosis, amongst other conditions.
Despite these limitations, CA - 125 is the most useful new gynecological tumor
marker developed (after HCG) using monoclonal technology. Its clinical application
includes:
1. Distinguishing benign from malignant adnexal masses.

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Ovarian Tumors

2. Monitoring the progression or regression of epithelial ovarian carcinoma

and assessment of effect of therapeutic modalities.
3. Predicting the presence of residual lesions after cytoreductive surgery.
4. detection of recurrence of the disease.
5. It is not cost-effective to use periodic assay of CA - 125 for screening the
population with the aim of early detection of ovarian cancer, even if coupled
with blood tests for other tumor markers such as human milk factor globulin
1 and 2 (HMFG 1/2). placental alkaline phosphates (PLAP), macrophage
colony simulating factor (M - CSF). The effort is however, warranted in
women with possibility of familial ovarian cancer.

• Carcino-embryonic antigen (CEA) may be raised in mucinous

cystadenocarcinoma.

• Inhibin is raised in patients with granulosa-theca tumors, and some cases of

mucinous carcinoma with hormonally active stroma.

• Alpha-fetoprotein (AFP) and bHCG should be measured if the patient with

ovarian tumor is younger than 40, in an effort to diagnose germ cell tumors.
Alpha-fetoprotein is raised with endodermal sinus tumor and may be also raised
with embryonal carcinoma and malignant teratoma (Table 1). b-HCG is raised in
the very rare malignant teratoma. However, the commonest germ cell tumor, the
dysgermina, is not associated with raised levels of A-FP and is rarely associated
with secretion of HCG from a chariocarcinomatous element in the tumor. Lactate
dehydrogenase (LDH) and placental alkaline phosphatase (PLAP) may be raised
with germ cell tumors.
Table 1: Production of aFP and bHCG tumor markers by germ cell tumors

Type of the tumor aFP b-HCG

Dysgerminoma ___ Rarely
Embryonic carcinoma +/- +/-
Endodermal sinus tumor + +
Choriocarcinoma ___ +
Benign cystic teratoma ___ ___
Malignant teratoma +/- ___

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Ovarian Tumors

• Cytokines are peptide growth promoting factors which may be elevated in some
advanced ovarian cancer. Measurement of the cytokine, like interleukin-6 (IL - 6)
and macrophage colony-simulating factor (M - CSF) in the serum of patients with
advanced ovarian malignancy can be used complementary with measurement of
CA - 125 in the follow up of progression of the disease.

Screening for early detection of ovarian cancer

Given the silent nature of early ovarian cancer and the poor salvage of the disease, a
number of screening strategies have been tested for early detection of ovarian neoplasia.
These have included:
1. Periodic pelvic clinical examination.
2. Periodic Pelvic ultrasonography-including vaginal and Doppler
ultrasonography.
3. Measurement of serum CA - 125 alone or complemented by assay of certain
other tumor markers.
4. Cytological examination of cul-de-sac aspirates.
However, experience has, so far, indicated that these efforts are not cost-effective, even
if coupled together for screening the whole population. For example, it has been shown that
10,000 routine pelvic examinations would be required to pick up one early ovarian cancer in
an asymptomatic women population. To date, no one has demonstrated that any screening
technique significantly affects mortality from ovarian cancer.
One strategy to help improving the effectiveness of ovarian cancer screening would be
to target populations at increased risk of the development of the disease, such as individuals
with family predisposition. These women at a high risk of gynecological cancer (5 - 10%
lifetime risk) include:
Women in families with a family history suggestive of one of the three types
of familial ovarian cancer syndrome (i.e. breast/ovarian cancer syndrome, organ
specific ovarian cancer syndrome or Lynch II syndrome), particularly when several
members of the family had been affected.
Several clinical options are available for these high-risk women, including a)
yearly screening by vaginal sonographic examination and b) measurement of CA - 125.
This can be reasonably started at the age of 40 years. However, it should be made clear
that these may not detect all cases at a preclinical stage and may not have a definite
impact on mortality. There is a significant false positive rate associated with screening
which may result in anxiety and unnecessary surgery particularly in premenopausal
women.

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Ovarian Tumors

Genetic analysis is available in certain specialized centers for DNA analysis of

samples from the individual or relatives (including archival pathology material) ; it may
be possible to perform linkage analysis to establish which individual family member
has inherited the disease linked chromosome.
Women at “increased” or high risk of familial ovarian cancer can be kept under
COC use once they have completed the desired family size. This is since it has been
shown that the use of COC reduces the relative risk of development of ovarian cancer
and that this protection can persist for 10 years after discontinuation of COC use.
Now, prophylactic oopherectory as a primary procedure (i.e. not as a part of
laparotomy done for other purposes) is not recommended for women with increased
risk of ovarian cancer. The risk of development of ovarian cancer (2 - 10%) in this
group is considered not high enough to warrant the risk of primary surgery and the
subsequent risk of osteoporosis and the small increase of development of breast cancer
that has been shown after prolonged use of hormone replacement therapy. However,
the possibility of having bilateral salpingooophorectomy in conjunction with
hysterectomy done for another indication should be offered to all such patients. The
discussion should take in consideration the need for long-term HRT and its
implications.
Palpable or enlarged postmenopausal ovary
The postmenopausal ovary atrophies to a size of 1.5 x 1 x 0.5. However, it may take
the ovaries several years to reach these dimensions. It can be slightly larger than this in obese
and multiparous women. A palpable postmenopausal ovary must alert the physician to the
possibility of malignancy. The diagnosis needs certain confirmatory measure like vaginal
sonography (better with use of color Doppler flow, CT scan, MRI and measurement of serum
CA – 125). The presence of ascites, which can be detected clinically or by ultrasonic
markedly increases the possibility of malignancy. Early surgical exploration is indicated in
this high-risk group.
However, women with only slightly enlarged or cystic ovary do not generally require
laparotomy. Oophorectomy in these cases frequently detect no pathology or benign lesion like
a fibroma or a benign Brenner tumor. The possibilities that the lesion represent an old
hydrosaplinx, a follicular cyst, or a fluid-filled pocket of adhesions in patients with a history
of previous pelvic surgery should be considered. Repeated (six-monthly) vaginal sonography
and CA - 125 assay are required in these patients.

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Ovarian Tumors

Staging of ovarian cancer

The FIGO have suggested the following system of staging of ovarian cancer.
This is a surgico-pathological staging, which comprises cytological examination of
ascites or peritoneal washings, and is dependant on the findings at laparotomy in
majority of cases:

Table 2 FIGO staging of ovarian cancer

Stage Description

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Ovarian Tumors

Stage I Growth limited to the ovaries.

Stage Ia Growth limited to one ovary; no ascites present containing malignant cells; no
tumor on the external surfaces; capsule intact.
Stage Ib Growth limited to both ovaries; no ascites present containing malignant cells ; no
tumor on the external surfaces; capsule intact.
Stage Ic Tumor Stage Ia or Stage Ib with tumor on the surface of one or both ovaries; or with
capsule(s) ruptured* ; or with ascites present containing malignant cells or with
positive peritoneal washings.

Stage II Growth involving one or both ovaries with pelvic extension.

Stage IIa Extension and/or metastases to the uterus and/or tubes.

Stage IIb Extension to other pelvic tissue.

Stage IIc Tumor Stage II a or Stage II b but with tumor on the surface of one or both ovaries,
or with capsule(s) ruptured* ; or with ascites present containing malignant cells or
with positive peritoneal washings.
Tumor involving one or both ovaries with peritoneal implants outside the
Stage III
pelvis and/or positive retroperitoneal or inguinal nodes and/or superficial liver
metastases.
Tumor involving one or both ovaries but limited to the true pelvis, negative nodes,
Stage IIIa
but with histologically confirmed microscopic seeding of abdominal and peritoneal
surfaces.
Tumor with histologically confirmed implants on abdominal peritoneal surfaces
Stage IIIb
none exceeding 2 cm diameter. Nodes are negative.
Abdominal implants greater than 2 cm diameter; and/or positive retroperitoneal; or
Stage IIIc
inguinal nodes.
Growth involving one or both ovaries with distant metastases, parenchymal
Stage IV
liver metastases; or pleural effusion containing malignant cells.
In order to evaluate the impact on prognosis of stage Ic, IIc, it would be of value to
indicate if rupture of the capsule was (1) spontaneous) or (2) caused by the surgeon.

Requirements for staging of ovarian cancer:

1. Laparotomy
2. Peritonial cytology
3. Determination of the extent of the disease

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Ovarian Tumors

a. Pelvis
b. peritoneal surfaces
c. Diaphragm
d. Omentum
e. Paraaorrtic and pelvic limn nodes
4. Removal of all tumor possible (total abdominal hysterectomy and bilateral
salpingo-ophrectomy plus omentectomy and node sampling).

Management of ovarian tumors

Treatment of apparently benign ovarian tumor:
Small ovarian cysts not exceeding the diameter of 10 cm and containing thin fluid with
low echogenic density should be first considered functional if seen during the reproductive
years. They are observed both clinically and by vaginal sonography over 4 - 6 weeks. They
usually regress or disappear during this time. If the cyst persists or enlarges, it should be
considered neoplastic and the patient should have a laparotomy.
All ovarian neoplastic tumors should be removed even if small or are causing no
symptoms. This is based on two reasons: First, the nature of the swelling is only known after
exploration of the abdomen and submitting the removed tumor to histopathology. Second, is
the high liability to mechanical complication, like torsion, rupture or hemorrhage.
Adequate laparotomy, usually middle line incision is generally used. This allows full
exploration of the peritoneal cavity. The tumor should be removed intact. Tapping of an
ovarian cyst in order to reduce its size at an early stage of an abdominal operation may be
permissible in young women when the cyst is obviously benign and when there is no
indication that it is dermoid cyst. This is to avoid disfiguring the abdomen by a big incision.
This might be also used in old frail women with huge cyst, which is obviously innocent, to
save her the poor healing of the large incision. The tapping of the cyst is done through a
purse-string suture in the cyst wall that is tightened around the nozzle of the suction cannula.
If the cyst ruptured during removal, the content should be carefully mobbed out of the
peritoneal cavity. With increasing experience with laparoscopic removal of benign ovarian
cysts it is becoming increasingly apparent that the risk of leakage of the content of innocent
cyst has been exaggerated. Suction irrigation can safely remove the contents of even the
dermoid cyst. Tapping of ovarian cyst should be avoided if there is any doubt about the
innocence of the tumor.

Three types of operations can be done for apparently benign ovarian tumors:
1. Ovarian cystectomy

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Ovarian Tumors

Ovarian cystectomy is the dissection of the ovarian cyst out of the ovary. Normal
ovarian tissue is usually spread out over the surface of the tumor and is frequently thickest at
the point of attachment of the ovarian ligament and the mesovarium, and thins out
peripherally. Every part of the stretched ovarian capsule should be conserved. After shelling
out of the cyst wall, preferably without rupturing it, the normal ovarian tissue is remodelled
into a more or less normal ovary by one or two tyres of fine catgut plickating sutures.
Temporary hemostasis may be ensured during the operation by applying a light non-crushing
intestinal clamp across the mesovarium.
Ovarian cystectomy is indicated in a young patient with evidently innocent tumor when
normal ovarian tissue is identifiable over the surface of the tumor. If the tumor is having an
area of suspected malignancy, shelling out of the tumor will be difficult and attended with
bleeding; in this case oophorectomy is usually necessary (or AH+ BSO if the desired family
size completed). If subsequent histopathology indicates a malignant nature the appropriate
treatment should be given including chemotherapy or reopening the abdomen to do the
appropriate surgery.

2. Salpingo oophorectomy
This operation was called in the past ovariotomy, which is evidently a misnomer.
Removal of the ovary, which is the seat of an ovarian tumor, is done to conserve the other
ovary. It is better to remove the tube as well. This operation is indicated in a young patient
keen to preserve her fertility if the tumor is evidently benign; and when there is no
identifiable normal ovarian tissue on the surface of the tumor. Salpingo-oopherectomy is also
indicated with suspicious or malignant ovarian tumor confined to one ovary, Stage Ia; if the
patient is young. It can be also done for old frail high-risk patient with malignant tumor, if
more cytoreductive surgery carries a definite risk to the patient. The other ovary should be
carefully examined and may need be bisected to see if it is harboring another neoplasm.
Peritoneal washing should be obtained for cytology. The subsequent management will depend
upon histopathological examination.

3. Total hysterectomy with bilateral salpingo-oophorectomy

This is indicated in benign tumors when the patient is above the age of 45 years. This
is to cover for the possibilities of presence of a still undetected tumor in the other ovary and
the possibility of a malignant nature being detected on histopathological examination. This
“radical” approach is usually the first part of the treatment of malignant or suspicious tumors.
• Laparoscopic surgery in benign tumors

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Ovarian Tumors

Advances in ultrasonography have provided an opportunity to predict the benign

nature preoperatively. This is better achieved by vaginal sonography together with colored
Doppler. Laparoscopic removal is a possible alternative to laparotomy with the following
provisions:
1. An ovarian cyst. If a significant solid part is present, laparotomy is needed.
2. No doubt about the benign nature or sonography.
3. Unilateral tumor.
4. Young patients.
5. CA - 125 is not elevated.
6. The size of the tumor is less than 10 cm.
7. Some surgeons prefer laparotomy removal if a dermoid cyst is suspected.
8. The surgeon should be experienced in laparoscopic surgery.
9. The patient should give her consent to proceed to laparotomy if need arises.

The operation is done under general anesthesia. It begins with careful examination of
the tumor and the whole peritoneal cavity is also examined, usually before attaching the video
camera, because the eyepiece gives a clearer assessment of the fine details and color
differentiation than most video systems. Cell washings are obtained from the pelvis and upper
abdomen and saved for proper staging if a malignancy will be subsequently found on
histopathological examination.

The laparoscopic management of the benign cystic ovarian tumor comprises the following
steps:
1. Aspiration of the fluid which is sent for cytological examination.
2. Fenestration of the cyst wall.
3. Inspection of the interior under fluid irrigation.
4. Biopsy and frozen section may be required if a suspicious area is detected. It is,
however, preferable to shift to laparotomy in this case.
5. The cyst wall is dissected using a combination of twisting of the cyst wall and
fluid dissection.
6. Bleeding points should be cautarized by bipolar diathermy.
7. The whole of collapsed cyst wall should be removed via a small minlaparotomy
or a posterior colpotomy.
8. If the surgeon is in doubt about complete removal of the cyst wall, laparotomy is
required. Persistence or “ recurrence” is frequently seen after the increasing use of
laparoscopic surgery for ovarian cyst.

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Ovarian Tumors

9. Endometriotic cysts may not be completely dissectable, and their interior should
be completely cautarized. One should however, be careful to not excessively
cautarise ovarian tissues.
10. The ovarian capsule can be left open or better needs approximation by
endosuture.
11. Repeated washing by heparinized ringer is needed.
The above description indicated that it is occasionally wiser and less time consuming
to remove cyst with the above criteria by a minilaporotomy.

• Treatment of ovarian tumors complicating pregnancy

The commonest types of ovarian tumors encountered in pregnancy are benign cystic
teratoma, parovarian cyst, serous cystadenoma, cystic corpus luteum of pregnancy, fibroma
and dysgerminoma. They are more easily discovered in early months for, when the uterus
enlarges in the abdomen, the ovarian mass is pushed behind the uterus or into one of the
flanks. The corpus luteum cyst disappears by the twelfth to the sixteenth week. An ovarian
tumor does not interfere with the progress of pregnancy. However, an ovarian tumor is more
liable during pregnancy and puerperium to mechanical complications like torsion,
hemorrhage, rupture, infection and impaction in the pelvis. The latter occurrence can result in
acute retention of urine or obstruction of labor.

The differential diagnosis of ovarian cyst associated with pregnancy are: 1) uterine
fibroids, 2) non-pregnant horn of a doubled uterus, 3) pelvic kidney, 4) retroperitoneal tumor,
5) an ectopic pregnancy, and 6) polyhydramnios.

The general principle of no conservation with ovarian tumors also applies during
pregnancy. First, because the nature of the tumor is not determinable until laparotomy and
histopathological examination of the removed tumor are done. Moreover, ovarian tumors are
more liable to complications during pregnancy and puerperium. Torsion may be precipitated
by rapid or sudden change of posture of the tumor. Hemorrhage is predisposed to be increased
congestion. Infection can spread from puerperal infections in the genital tract. There are two
exceptions to this general rule:
1. A cystic tumor discovered in early pregnancy can be left until the end of the
first trimester. This is to give time for functional cyst like a cystic corpus luteum to
regress over few weeks. Moreover, an oophorectomy in early pregnancy may
disturb the hormonal support of the pregnancy by removal of the corpus luteum

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before the placenta has fully taken over the function of hormonal support.
Manipulation of early pregnancy ovary may precipitate an abortion.

2. A tumor found after the twenty-eighth week of pregnancy is not readily

assessable and may require a big laparotomy. Its removal at this time may
precipitate a premature labor, or may leave a painful scar that deters the patient
from bearing down during labor. The patient whose pregnancy is far advanced
should, therefore, be kept under observation, and allowed to have vaginal delivery,
but the ovarian tumor needs to be removed during the first week of the
puerperium.
When there are, evidences suggesting malignancy there should be no conservation at
all. Complicated ovarian tumors require immediate surgery irrespective of the period of
pregnancy.
A patient with an ovarian tumor impacted in the pelvis and obstructing labor should be
treated by lower segment cesarean section and the ovarian tumor is removed in the same
session. Trials to disimpact the tumor from the pelvis during pregnancy are usually futile and
may result in rupturing the tumor.

Treatment of Pseudomyxoma peritonei

Surgical evacuation along with removal of the ovarian mucinous cystadenoma and the
appendix is the standard treatment, and because of the recurrent nature of the disease, it may
be repititive. Because of the usually associated cachexia, the patient needs long-term
nutritional support. In addition one or more of the following measures can be added:
1. Intraperitoneal installation of alkylating agents.
2. Total abdominal irridiation (see below).
3. Interperitoneal installation of radioactive material (see below).
4. Systemic chemotherapy has been shown to be of little value.

Treatment of epithelial ovarian cancer

Both surgery and chemotherapy have major roles in the treatment of ovarian cancer.
Surgery is the initial treatment for making the final diagnosis, staging, obtaining peritoneal
washings, and for removal of tumors. Frozen section service is of value under certain
circumstances mainly in differentiating benign from borderline and invasive ovarian cancer.
Laparotomy is always done through a longitudinal incision that is required for proper
exploration. Post-operative (adjuvant) chemotherapy is usually given, except for some early
or borderline cases, where the disease is confined to the ovaries, which may be treated with

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Ovarian Tumors

surgery alone. Radiotherapy has been used for palliation, and has now been mostly replaced
by chemotherapy.
• Surgery
Surgery is presently being utilized in three approaches; the first is the usual:
1. Primary surgery is performed at the time of initial laparotomy with the aim of
removing all tumor masses. It is frequently described as debulking or
cytoreductive surgery.

2. Interval debulking surgery is performed in advanced ovarian cancer, when

primary surgery was incomplete or not feasible. After the patient has received
several courses of chemotherapy, an interval surgery is done. Following this
interval surgery chemotherapy is continued. This approach has been shown to
prolong patient survival when compared with advanced cases treated with
chemotherapy alone. However, this approach has not yet been shown to improve
the 5-year survival rates in big series.

3. Secondary surgery: includes second look surgery and palliative surgery.

- Second look surgery refers to laparoscopy and laparotomy performed
to assess the effect of chemotherapy in patients who appear to have had
complete clinical and radiological cure. A second look-laparotomy is
better than laparoscopy since it allows better assessment and obtaining
specimens. However, this secondary surgery has not been shown to
definitely improve the salvage rates.
- Palliative surgery is most often carried out to relieve bowel
obstruction. It should better be avoided as far as possible when small
bowel obstruction is suspected, because this is usually multiple-site
obstruction or may be due to neuromuscular paralysis of the intestines.

Management of borderline ovarian cancer

When exploration of the abdominal cavity (preferably if supported by histopathological
evidence on a rapid examination of frozen sections) points to the presence of a borderline
ovarian neoplasia the following scheme of management is advisable:
1. The majority of borderline epithelial neoplasms belong to Stage Ia disease. When
future childbearing is desired in a young patient, the usual treatment is removal of
the tumor by oophorectomy. In few selected cases even cystectomy is applicable.

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2. In Stage Ib, Ic, total abdominal hysterectomy plus bilateral salpingooophorectomy

(TAH + BSO) are needed. This also applies to tumors of stage Ia when
childbearing is not required. If histopathology confirms a low-grade malignancy,
the patients can be spared the hazards of chemotherapy. They are, however, kept
under long-term observation by repeated transvaginal sonography and CA - 125
measurement done at + 3 month intervals. A recurrence, though rare, can develop
after several years.
3. Patients with borderline malignancy belonging to Stage II or Stage III (these are
actually rare) are usually treated like those with overtly malignant disease, i.e. with
optimal cytoreductive surgery followed by postoperative chemotherapy and
followed by usual observation.

Management of invasive ovarian cancer

A. Cytoreductive or debulking surgery for ovarian cancer
The debulking procedure has gained considerable attention in management of ovarian
cancer. The concept is based on reducing the residual tumor burden to a point where adjuvant
therapy will be optimally effective. This concept has resulted in resort to aggressive surgical
exercises (maximal surgical effort) in order to achieve the maximal reduction of the tumor
mass. However, it is becoming increasingly clear that this approach can improve the salvage
rates if any remaining residual tumor masses are less than 2 cm in diameter. If this is
considered to be not attainable at the initial exploration, the debulking procedure will be only
palliative; and is only warranted if it is considered not to be putting the patient’s life to a
definite risk. Intestinal resections and partial hepatectomy are definitely not to be attempted in
such cases, because of high intraoperative mortality and severe postoperative morbidity.
There should be a limit to the aggression of the surgeon.

Principal steps of debulking surgery

1. A vertical middle line incision is made.
2. Peritoneal washings are obtained from the pelvis and the right and left paracolic
gutters by instillation and suction of about 100 ml saline into each area.
3. The under surface of the diaphragm should be searched for any tumor mass. If it
feels normal, multiple cytological scrapings of this surface are obtained by
cytobrush as used for the endocervical Pap smears.
4. The entire pelvis and abdomen are carefully explored; and biopsy of any
suspicious nodules is undertaken.
5. Ovarian tumor is resected as intact as possible; and frozen sections are examined.

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6. If malignancy is confirmed, TAH - BSO are performed. In patients with large

pelvic tumors, the pelvic structures - including the ovarian tumor itself, bladder,
uterus, and rectosigmoid colon - are sometimes indistinguishable. In such cases
and in order to avoid injury to the ureter and pelvic blood vessels, a
retroperitoneal approach for the resection is used: The lateral peritoneum is
incised along the psoas muscle to allow identification of the external iliac artery;
and the incision is extended cephalward lateral to the cecum or sigmoid colon.
With this wide exposure, both ureters are identified and the ovarian vessels are
ligated under vision. Thereafter retrograde removal of the large ovarian mass
together with the uterus is easier and safer (i.e. beginning at the uterus and
proceeding upwards)
7. Omentectomy is performed. It is usually infracolic omentectomy. When the
omentum is caked up with tumor, clear spaces usually exist on the side of the
transverse colon whereby the right and left gastroepiploic vessels are ligated; and
the omental cake is excised from above downward.
8. A loop of small intestine may need to be resected, but the colon should rarely be
resected.
9. Pelvic lymphadenectomy is performed on the side of the tumor, including the
common iliac, external iliac and internal iliac vessels and obturator groups.
10. Paraaortic lymphadenectomy is performed by removing the lymph nodes from the
aorta and vena cava from the bifurcation of aorta to just below the renal vessels.

• Second-look laparotomy
Second look laparotomy is defined as exploration in patients with advanced Stage III or IV
ovarian cancer who, after a previous debulking surgery and standard chemotherapy, have no
clinical biochemical (CA - 125), or radiologic evidence of disease. The value of a second-
look therapy, therefore, is (1) to discontinue all chemotherapy if there is no evidence of
disease (2) to remove (if possible) any residual disease. The weight of evidence suggests that
this practice is rarely of benefit in improving the salvage rates.

B. Chemotherapy
Chemotherapy plays a central role in the present time management of ovarian cancer.
Except for patients with FIGO Stage Ia and Ib with well or moderately differentiated
histopathology, adjuvant chemotherapy is always given after surgery. This has resulted in
improvement of the 5-year survival rate. Occasionally chemotherapy is used as a primary
treatment for advanced ovarian cancer before interval debulking surgery. Chemotherapy for

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ovarian cancer is usually a combination of two or more of the following groups of drugs;
single agent therapy is rarely used.
Chemotherapeutic agents used in ovarian epithelial cancer comprise the following groups:

1. Alkylating drugs: They are so called because they have alkyl groups that bond
together the amino and carboxyl groups of nucleic acid bases, cross-linking the DNA
strands; thus preventing replication of DNA, and consequently cellular division. The
most commonly used alkylating agent used for ovarian cancer is cyclophosphamide
(injection), thiotepa (injection), hexamethylmelamine (oral), melphalan and
chlorambucil (oral). These drugs were the first types tried in ovarian cancer as single
agents. Presently, however, they are used in combination regimens which comprise a
platinum drug.

2. Antimetabolites: like 5-flurouracil (5-FU)and methotrexate are also part of

combination regimens (they act mainly by inhibiting essential steps in DNA
synthesis) ; and also cytotoxic antibiotics like doxorubicin. It seems however, that
combinations not involving a platinum drug carry no advantage over single agent
therapy.

3. Platinum drugs: they are the most widely used drugs in the management of ovarian
cancer (and other gynecological malignancies) alone or in combination. They are
heavy metal compounds which cause cross linkage of the DNA strands in a similar
fashion to alkylating drugs. Cisplatin was the first type used and has been shown to
give superior results relative to other alkylating agents. The cis-isomer of the
combound is the active form. Another platinum drug has come to use in recent years,
carboplatin. The platinum drugs when used as a single agent or in combination
therapy give high initial response in approximately 70 % of epithelial ovarian cancer.
However, following an initial response, recurrence frequently occurs. Therefore, the
overall 5-year survival rate has not been markedly improved. Germ cell tumors are
also highly sensitive to platinum drugs.

Cisplatin (e.g. Platamine, Pharmacia & Upjohn ampoules of 50 mg / 50 ml, 100

mg/100ml) is given intravenously at a dose of 70 - 100 mg/meter square body surface area (as
indicated in monograms calculated from the height in feet and weight in kilograms) when
given as a single agent. It is also given in a dose of 50 mg/ m2 in combinations therapy. The
typical dose is 50-100 mg as a single dose by IV infusion every 3-4 weeks. Cisplatin is

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usually given in hospital with pretreatment and posttreatment intravenous hydration to

diminish its toxicity; since it is excreted by the kidney. The most serious side effect is
nephrotoxicity (reducing both glomerular filtration rate and tubular functions). Therefore, the
urine output needs to be monitored after cisplatin treatment; a urinary output of 100 ml per
hour should be maintained. Before repeating the dose normal creatinine or EDTA clearance
test must be ensured. The drug dose must be reduced if renal function is shown to be
impaired. The dose needs be repeated every 3 to 4 weeks. The total dose of cisplatin does not
better exceed 300 mg/m2. Other toxicities include neurotoxicity (in the form of peripheral
neuropathy), ototoxicity (loss of high tone hearing), and nausea and vomiting. The latter side
effects can be reduced by giving dexamethasone (8 mg IV) and 5HT3 receptor antagonists
like granisetron (e.g. Kytril, Beecham) or ondasetron (e.g. Zofran, Glaxo: 8mg/amp.) at the
initiation of therapy. Myelotoxicity and alopecia are not usual features of cisplatin treatment.
The recommended regmin of ciplatin tretment:
• Prehydration
- 1 litter normal saline plus 10 nmol Mg SO4, over 2 hours
- 1 litter normal saline plus 20 nmol KCL, over 2 hours.
- 200 ml manitol 20 % over 20 minutes (for forced diuresis before
cisplatin).
- Dexamethasone 8 mg IV bolus initially.
- Ondasetron 8 mg IV bolus initially (repeat after 8 hours if necessary).
• Cisplatin
50-75 mg/m2 in 1 litter normal saline, over 2 hours
• Posthydration
- 1 litter normal saline plus 10 mmol Mg SO4, over 2 hours
- 1 litter normal saline plus 20 mmol KCl, over 2 hours
- The urine output should be maintained at more than 100 ml/hour

Carboplatin: This is an analogue of cisplatin and acts in the same manner. At the standard
dose it has the advantage of causing minimal nephrotoxicity and neurotoxicity. Nausea and
vomiting are usually less marked than with cisplatin. However, unlike cisplatin, carboplatin is
myelotoxic and a low platelet and granulocyte counts are particular problems. As cisplatin,
carboplatin is excreted by the kidney and myelotoxicity is related to renal function.
Carboplatin is excreted in urine at a constant rate which is linearly related to the creatinine or
EDTA clearance, or the glomerular filtration rate. Each dose of carboplatin is usually
calculated by multiplying the glomerular filtration rate (in ml/min) by a factor of 5 to 9 e.g., if
GFR is 70 ml/min; the dose of carbiplatin is usually 475 mg. The dose is repeated every 3

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Ovarian Tumors

weeks until maximal shrinkage of the tumor is reached. Carboplatin can be given in 60-
minute infusion and can be given as an outpatient procedure without the need for forced
diuresis like with cisplatin.
Carboplatin treatment should, like all other types of chemotherapies for cancer, be
monitored by peripheral hemogram. The nadir of the count is expected 10 to 14 days after the
dose. Myelotoxicity results in severe infections, which need active intravenous antibiotic
treatment. Blood cultures should be also made. Recombinant human granulocyte colony
stimulating factor (h GCSF) can be effectively used to stimulate bone marrow and to improve
tolerance to myelotoxic chemotherapy. If a dangerous depression of the platelet population (<
20 x 10 per ml) is caused by the treatment, transfusion of fresh platelets is required.
In the last decade, high dose chemotherapy combined with autologous bone marrow
transplant (ABMT) has been used for several solid tumors including ovarian cancer, and has
resulted in improvement of the initial response rate, and may be - an improved salvage rate.
Bone marrow is aspirated (under general anesthesia) from the iliac crests before therapy, half
of the cryopreserved bone marrow is thawed and infused intravenously on the fourth day of
the therapy.

Platinum based combination regimens: has been shown to produce better initial response
than single platinum drug therapy. In combination, therapy a lower dose of cisplatin can be
used in order to diminish the toxicity side effects. The combinations tested for this purpose
includes the addition to the platinum drug either of cyclophosphamide (e.g. Endoxan),
doxorubicin or taxane drug (see below). The latter combination (cisplatin+ paclitaxel) has
become the “gold-standard” for combination first-line chemotherapy for epithelial ovarian
cancer.

4. Taxanes
This newer class of compound has been derived from plant origin. They act by a
novel mechanism through stabilization of cytoplasmic microtubules, which are essential
cellular component needed for various cellular activities including mitosis.
The two most commonly used taxanes are paclitaxel and docetaxol. Paclitaxel was first
used in the treatment of platinum resistant ovarian cancer, but it is now commonly used in
combination with cisplatin as a primary chemotherapy. The dose of paclitaxel can be either
175 mg/m2 given in an intravenous infusion over 3 hours or 135 mg/m2 given over 24 hour
period. The drug produces myelosuppression, sensory neuropathy, marked alopecia, and
hypersensitivity (allergic) reaction. Nephrotoxicity, nausea, and vomiting are less marked
than with cisplatin.

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Docetaxol (e.g. Taxoter, Rhone-Poulenc Rover) is semisynthetic taxane and has a

similar activity to paclitaxel but also has an unusual skin (hair less) toxicity and can produce
marked edema.

5. Other new drugs under trial include gemcitabine, a pyrimidine antimetabolite, and
topotecan, a topisomerase-I inhibitor are being tried in platinum-resistant disease.

C. Intraperitoneal therapy
This approach exploits the natural history of ovarian cancer with tendency to extensive
local peritoneal implantation without more widespread metastatic disease. However, the use
of intraperitoneal therapy is only suitable for treating small superficial deposits because the
penetration of the drug is limited. Cisplatin is the drug usually infused into the peritoneal
cavity through an indwelling catheter.

Patients with persistent minimal residual ovarian cancer following initial intravenous
cisplatin-based chemotherapy and who have demonstrated some response to the systemically
diluted regimen are the appropriate candidates for intraperitoneal cisplatin-based programs.
However, this approach has proved inappropriate for pseudomyxoma peritonei.

D. Immunotherapy:
Immunotherapy has been used for ovarian cancer for some years but without a
definite benefit. Non-specific immunotherapy with BCG (Bacille-Calmette-Guerin) or
corynebacterium parvum has been combined with chemotherapy and appeared to prolong
response. Alpha interferon has been also used for the purpose, either as subcutaneous
injection or as intraperitoneal installation in combination with chemotherapy.

E. Hormonal therapy
Cytoplasmic estrogen and progesterone receptors have been demonstrated in ovarian
cancer cells. Progestogens, tamoxifen, and long-acting GnRh analogs have been tried as
adjuvants to chemotherapy but without definite results.

F. Radiotherapy
Radiotherapy has little place left in present time management of ovarian cancer after
the developments in chemotherapy. To be of any value in definitive treatment of the disease
radiotherapy had to be directed to the whole abdominal cavity, which is at risk of occult
metastases. However, the total dose delivered to the whole abdomen by external beam
radiation was limited in order to protect the radiosensitive organs such as the liver and

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kidneys. This limitation of dose resulted in external radiotherapy being ineffective for treating
residual ovarian malignancy. Radiotherapy is, however, useful for palliation, for example, to
relieve pressure symptoms in the pelvis, vaginal bleeding or metastatic deposits in the brain or
bone.

G. Intraperitoneal radiotherapy
Radioactive isotopes, linked to colloidal carriers have been used as intraperitoneal
installations as a postoperative treatment in patients without or with residual lesions, either
alone or in combination with external radiation. The radioactive isotopes act by being
absorbed by the macrophages in the peritoneal surfaces. However, only the superficial 4 - 6
mm of the peritoneal lining receive a sufficiently high dose of radiation and most of the dose
received by intra-abdominal organs is from the isotope absorbed in the circulation.
Radioactive gold [198Au] or phosphorus [32P] has been used. The latter is presently
preferred because 10% of the activity of 198Au is gamma radiation, which is hazardous to both
the patient and staff. Experience with intraperitoneal radiotherapy has not been shown to be of
any advantage over cisplatin-based chemotherapy. Combination of external radiation with
intraperitoneal radioactive phosphorus cause serious bowel injury.
A novel approach using intraperitoneal radioimmunotherapy is with ytterium-90
attached to monoclonal antibodies such as human milk factor globulin 1 (HMFG 1), which
binds to surface antigen present in ovarian epithelial cancer. This approach is under trial as a
“consolidation therapy” in patients who have apparent pathological remission after surgery
followed by adjuvant chemotherapy.

Results of treatment of ovarian cancer and prognostic factors

• Borderline ovarian cancer

Tumors with limited malignant potential have a good prognosis. The overall 5-year
survival of borderline ovarian epithelial cancer is 90 - 95% and 15-year survival is in the
region of 60 - 85%. Most cases of borderline ovarian cancer belong to Stage I, and in these,
100% 5-year survival is expected; cases with more advanced but borderline cancer, like Stage
III disease can expect 65 - 85% survival.
In addition to the stage of the disease at the time of laparotomy, the prognosis of
borderline tumors appears to be related to ploidy; patients with aneuploid tumors (rare)
having 19-fold risk of death from the disease as compared to patients with diploid tumor.
Increasing age and non-serous histology are additional poor prognostic factors.

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• Invasive tumors
The overall 5-year survival of invasive cancer is still low, 25 - 35%. This has been in spite of
advances in treatment of the disease, and mainly reflects the usually late presentation of the
patients.
The prognostic factors include the following:

1. Stage of the disease: This is the most important determinant, the chance of 5-year
survival being 75%, 45%, 20% and < 5% for Stage I, II, III and IV respectively.
2. Stage Ia and Ib tumors have a 5-year survival rate of over 90%, while Stage Ic has
a poorer prognosis particularly if it is poorly differentiated.
3. The size of the original tumor mass: Patients with large volume disease at the
outset have a poor prognosis, even after successful cytoreductive surgery.
4. The extent of residual tumor after cytoreductive surgery appears to be the most
highly significant prognosis factor. Patients with no residual disease have the best
prognosis, while patients having any residual lesion greater than 2 cm have a poor
prognosis.
5. The present-time adjuvant chemotherapy has improved the prognosis particularly
when no residual lesion or lesions no more than 2 cm in diameter have been left
behind the surgery. Cisplatin-based combination therapy gives better results,
particularly when combined with taxane.
6. Histological grading: well-differentiated epithelial ovarian cancers tend to be
more often associated with early disease at the time of detection. However, the
grade of the tumor histology seems to be an independent factor in multivariate
analysis.
7. Ploidy is also an important prognostic factor (see above).
8. Age is less important prognostic factor, but women over 70 years have a poorer
prognosis.
9. Functional performance grading measuring the ability of the patients to carry
out their daily activity has been suggested as a prognostic factor. Women who can
carry out all their normal activity after completion of the initial therapy have better
prognosis, while completely disabled ones have a poor prognosis.
10. Oncogenes have been recently utilized as prognostic indicators. A certain
oncogene (growth promoting gene) coding for an epidermal growth factor (EGF)
receptor protein is overexpressed in about 30% of ovarian cancer. The
overexpression of the EGF receptor was found to be sensitive indicator of a poor

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Ovarian Tumors

prognosis in ovarian cancer. Other gene mutations have also been utilized in
assessment of prognosis of this disease (see under Genetics).
Follow-up practice after definitive treatment:
This can comprise physical examination, serum CA-125, abdominal and vaginal
sonography; to be repeated every 3 months for 2 years and 6-monthly thereafter. MRI or CT
scan examinations can be also used when there is any doubt, particularly when CA-125 starts
to rise again. Routine second look laparotomy is of doubtful value when the other parameters
are reassuring.

Salvage therapy
This term is used to describe the management of advanced cases of ovarian cancer in
whom cytoreductive surgery is not possible at the time of primary laparotomy, and the
management of recurrence after primary surgery/chemotherapy treatment. In these cases cure
is not a realistic goal; palliation is all that can be aimed at. The measures, which can be used,
include:
1. Chemotherapy using cisplatin-based regimen. This can result in reduction of the
size of chemosensitive tumors.
2. Interval or second debulking can then be feasible. However, cure is most unlikely.
3. Trial of other newer chemotherapeutic agents. The success rate should be poor
had the original regimen comprised a platinum drug. Trial of new courses of
chemotherapy is not usually effective particularly when less than 6 months have
elapsed after the end of the first course.
4. High, aggressive doses of platinum drug with special measures to combat the
expected higher complication rates.
5. The late stages of the disease are associated with severe cachexia, gastrointestinal
obstructions, and electrolyte imbalance. It is important to support these patients
with parental alimentation to sustain their tolerance to the usually aggressive
therapies. The placement of Port-O-cath may be needed (a semisynthetic silicon-
rubber catheter inserted subutaneously, and then into the subclavian vein and into
the right atrium). Usually the intestinal obstruction is at multiple sites and with an
element of ilius; therefore, bypass surgery is not always of value.

Treatment of germ cell tumors:

Special features of germ cell tumors that influence their management include:

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Ovarian Tumors

1. Younger ages; 2. The majority of cases are seen in early stage ; 3. with the exception
of 10 % of cases of dysgerminoma, germ-cell tumors tend to be unilateral ; 4. special
predilection for lymphatic spread ; 5. high radiosensitivity ; 6. high chemosensitivity ; 7.
presence of certain tumor markers and, 8. occasional association with gonadal dysgenesis.

Malignant germ cell tumors have been characterized by being highly sensitive to
radiotherapy. However, they have been shown to be highly sensitive to chemotherapy as well.
The latter has therefore become the standard adjuvant therapy after the initial surgery. This
can spare the usually young patients the inevitable ovarian ablation that follows upon
radiotherapy. Chemotherapy can more adequately deal with lymph node involvement, which
is an early feature of germ cell tumor. The availability of multiple tumor markers as A-FP and
bHCG have allowed more frequent resort to conservative attitude with germ cell tumors.

Initial surgery in young women with any tumor affecting only one ovary should be
unilateral oophorectomy, together with the usual attempts to discover any spread of the
disease. The need for any further surgery should await the histopathological assessment.
Further management of young patients with early Stage Ia and Ib germ cell tumors varies
between:
1. Nothing other than frequent observation (clinical, chemical and by imaging
techniques). This is possible in dysgerminoma particularly when the tumor is
small and not containing other elements of germ cell tumors. This has resulted in
preservation of fertility potential in some young patients.
2. Multiple agent chemotherapy is needed for all cases with endodermal sinus
tumor or, embryonal carcinoma or choriocarcinoma because of high malignant
potential. This is also needed in all cases with advanced disease.
3. If the course of the disease suggests recurrence, another surgical debulking will
be necessary, and/or combination chemotherapy.
Radical, cytoreductive surgery is needed in all cases beyond Stage I; and this is
followed by multiple-agent chemotherapy.
Chemotherapy for germ cell tumors is with cisplatin in combination, usually with
bleomycin and etoposide (Etoposide injections Pharmacia & Upjohn) (BEP). This is curative
in the majority of patients with germ cell tumors who do not have adverse prognostic
indicators like very high levels of tumor markers, very bulky disease or involvement of the
liver or the brain. A short but intensive course of chemotherapy given over a short time has
been tried with success. This regimen alternates, cisplatin, vincristine, and methotrexate, and
bleomycin given as a group; with actinomycin- D, cyclophosphamide, and etoposide

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(POMB/ACE) as the other group, every two weeks for three to five courses. This course does
not interfere with fertility, and there have been no congenital abnormalities reported in
children born to mothers who have received the POMP/ACE therapy.
The rare cases of gonadoblastoma (usually associated with gonadal dysgenesis) are
treated by excision of the tumor together with excision of the contralateral gonad, which is
frequently represented by a streak. The latter can harbor a yet undetectable tumor.

Benign cystic teratoma (dermoid cyst) belongs to germ cell tumor, and its
management has been discussed under benign tumors.

Treatment of sex-chord tumors

Five to ten percent of ovarian cancers belong to the sex-chord-stromal group; most of
these are granulosa-theca cell tumors, which have low-grade malignancy. The majority of
granulosa-theca tumors occur postmenopausallly. They may be associated with endometrial
hyperplasia. They may recur after long intervals after primary treatment.
Surgery is the main treatment, usually in the form of bilateral salpingo-oophorectomy,
hysterectomy and infracolic omentectomy. Unilateral oopherectomy is indicated only in
young women (occasionally children) with Stage Ia disease to preserve fertility. No adjuvant
treatment is required for patients with Stage I disease that shows low-grade malignancy. More
advanced cases should receive adjuvant chemotherapy. This is essentially similar to that used
for epithelial ovarian cancer. The overall survival rate is around 80%. However, delayed
recurrence can occur after several years. Inhibin, which is normally secreted by granulosa
cell, may serve as a tumor marker.

Carcinoma of the Fallopian Tubes

Primary carcinoma of the fallopian tubes is very rare. Most tumors of the
tubes are spread from ovarian cancer or secondaries from gastrointestinal or breast
cancer. The disease is usually seen after menopause.

Pathology:
The tumor usually distends the lumen and may simulate a pyo or
hydrosalpinx; but it is solid and unilateral. The tumor is fragile. Microscopically; it
is identical to serous papillary carcinoma of the ovaries. It spreads in the same way
as ovarian cancer.

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Ovarian Tumors

Clinical picture:
The condition is discovered at laparotomy done for uterine bleeding. It is
rarely suspected preoperatively. It is a cause postmenopausal vaginal bleeding,
watery discharge or lower abdominal pain. The condition may be suspected when
the D&C are hysteroscopy done for uterine bleeding are negative, in addition to the
presence of unilateral adnexal swelling.

Treatment:
Treatment is similar to ovarian cancer and comprises AH+BSO followed by multiple
agents chemotherapy.
Results:
The overall 5-year survival rate is in the region of 35%. However, if the disease is
discovered before it has broken through the tubal wall the survival rate can reach 75%. The
progress of the disease can be monitored by measurements of CA-125.

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

Chapter 19
NONNEOPLASTIC EPITHELIAL
DISORDERS OF THE VULVA AND
CARCINOMA OF THE VULVA
Contents:
• Nonneoplastic Epithelial Disorders (Dystrophy) of Vulval Skin and Mucous
Membranes
- Squamous cell hyperplasia
- Lichen sclerosus
- Other dermatosis
• Vulval Intraepithelial Neoplasia (VIN)
• Clinical Picture - Diagnosing and Treatment
• Pruritus Vulvae
• Invasive Cancer of the Vulva
- Epidemiology
- Etiology
- Anatomy
- Pathology
- Clinical picture: symptoms, signs and investigation
- Prognostic factors
- Staging of carcinoma of the vulva
- Treatment
Surgical treatment
Classical radical vulvectomy - technique of radical vulvectomy
Recent modifications: limited skin excision
: Extent of lymphadenectomy
Postoperative radiotherapy
Preoperative radiotherapy
Preoperative chemotherapy
Results
• Uncommon Malignant Tumors of the Vulva

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

• Carcinoma of the Vagina

- Vaginal intraepithelial neoplasia VAIN
- Invasive carcinoma of the vagina
Incidence
Etiology
Pathology
Clinical picture
Treatment
Surgery
Radiation therapy

Nonneoplastic Epithelial Disorders

(Dystrophy) of Vulvar Skin and Mucous
Membrane
The vulval skin is special type of skin. Although it is affected by most skin diseases,
the vulval skin (and scrotal skin) is the seat of special disorders. Some of these disorder can
be described as dystrophies. This is an imprecise word indicating disordered growth and can
comprise both hyperplasia and hypoplasia or a combination of both. The relationship of these
dystrophic lesions to vulval carcinoma has been a matter of debate between dermatologists,
gynecologists and pathologists for some long time.
In 1987, the International Society for the study of Vulvar Diseases (ISSVD) issued the
following classification of these disorders that is still holding up till now. It has replaced a
number of old names like leukoplakia vulvae and Kraurosis vulvae:
Vulvar nonneoplastic epithelial disorders:
Squamous cell hyperplasia
Lichen sclerosus
Other dermatosis; including:
− Seborrheic dermatitis
− Psoriasis
− Tinea
− Lichen simplex chronicus
− Lichen plannus

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

Vulvar intraepithelial neoplasia (VIN):

A. Squamous VIN:
VIN I: Mild dysplasia
VIN II: Moderate dyplasia.
VIN III: Severe dysplasia or carcinoma in situ (IS)
B. Non-squamous VIN:
Paget's disease.

Mixed epithelial disorders can occur but both conditions are to be reported, e.g. lichen
sclerosis with associated squamous cell hyperplasia. (Which was formerly described as mixed
dystrophies). Lesions demonstrating in any part cellular atypia do not belong to nonneoplastic
epithelial disorders and are included in VIN since their natural history is essentially different.

▪ Squamous cell hyperplasia(SCH):

− Old name “leucoplakia” or leukoplakia (from Greek leuco = white and plax = a flat plate.
− A common vulval disease of obscure etiology.
− Age: The condition can occur in the reproductive and postmenopausal years.
− Symptoms: mainly pruritus vulvae, which can be very intense, bleeding and infection can
result from scratching. There can be pain and dyspareunia.
− Sites of affection: most commonly the labia majora, intralabial fold and outer aspects of
labia minora and clitoris. It usually stops at the vaginal introitous; i.e. not involving the
vaginal skin. It can extend, however, to involve the perineum and the crural fold.
− Appearance: The lesion takes the form of areas, which are white, tough (lost elasticity),
slightly raised i.e. like parchment paper. Alternatively or in addition there are raised
dusky red areas. There can be fissures or excoriations or papules. These areas should be
especially biopsied because these areas can be harboring VIN or invasive cancer. The
condition is distinct from leukoderma, which is represented by areas of depigmented skin
without any other manifestation.
− Histologyically: squamous cell hyperplasia reveals a variable increase in the thickness of
the horny layer (hyperkeratosis) and irregular thickening of the epidermis and prominent
distorted rete pegs. An inflammatory reaction is often present in the dermis with varying
numbers of lymphocytes and plasma cells together with hyalinization of collagen layer
and loss of elastic tissue elements.
− Squamous cell hyperplasia may be associated with VIN changes. These are the cases,
which can get invasive carcinoma. Squamous cell hyperplasia is a forerunner of VIN and

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

the rare invasive vulvar cancer, the extent of the risk of the latter cancer in cases SCH has
not be definitely estimated but is roughly 1%.
− Etiological factors
The etiology of squamous cell hyperplasia (leucoplakia) is poorly understood. It is
definitely related to vulvar environment. Skin brought to the area after local vulvectomy is
frequently affected by the same "leucoplacic" changes. It is not definitely determined what
are the factors in this site that are producing these characteristic pathological changes. The
possibilities suggested include the following factors (without any definite proof):
1- poor personal hygiene.
2- chronic mechanical changes resulting from rubbing and scratching.
3- chronic infection by tineas, candidas.
4- allergy to clothing, detergents or depilating agents.
5- autoimmune disorder.
6- metabolic disorders; diabetes mellitus ureamia can cause chronic vulvar itching.
7- deficiency state. A number of micronutrient deficiencies have been implicated
including deficiency vitamin B subfractions (riboflavine, B12, folic acid), or iron
deficiencies. The condition has once been ascribed to achlarhydria or chronic
diarrheas.
However, any gynecologist of experience has seen a number of cases of squamous cell
hyperplasia which can not be ascribed to any of the above factors.
− Treatment
The treatment of squamous cell hyperplasia is most difficult and disappointing. The
following measures may help:
1. General hygienic measures: The vulva should be kept cool and free from sweat by the
wearing loose light cotton underwear. Nylon and similar synthetic fabrics should be
avoided. Cold nonspecific bland creams can help.
2. Sedative at night can diminish scratching. Scratching can easily become a habit.
3. Correction of any associated vulval or perineal infection.
4. Antihistamics.
5. Corticosteroid creams can be helpful. Systemic administrations of corticosteroids are
rarely helpful.
6. Vitamins and micronutrients suspected to be deficient.
7. Topical testosterone has been used for this condition with some success (no personal
experience).
8. Local analgesics: useless in relieving itching.
9. Subcutaneous injection of absolute alcohol may cause temporary relief.

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10. Division of coetaneous nerves by a circular incision around the vulva can help by
interrupting the scratching habit.
11. Biopsy: multiple biopsies from a fissure, an ulcer or popular areas are essential to
exclude an associated VIN or invasive cancer.
12. Local excision: If the lesion is localized the best is to remove it. In resistant extensive
cases local vulvectomy is done. It is disfiguring and may result in dyspareunia.
However it relieves the patient from disabling, diminishing pruritus vulva.
Unfortunately the condition can recur in the skin mobilized to replace the vulval skin.
▪ Lichen sclerosus
− Formally called krauroris vulvae or atrophic leucoplakia.
− Age: Most patients are postmenopausal but young adults are rarely affected.
− Symptoms: vulval pain and tightness and dyspareunia are the leading complaints. The
dyspareunia can amount to apareunia. Pruritus vulvae and scratching can be present.
− Lesion: all vulval structure can be involved in lichen sclerosis. They get atrophic; the
labia minora may disappear. The introitus is narrowed. The vulvar structures are red and
inflamed. Senile vaginitis may be associated. Synechae often develop between inflamed
labia minora. The skin of the vulva is usually red but can be white as in squamous cell
hyperplasia. It can be wrinkled and thin like cigarette – paper, or can be parchment like.
Fissures also develop in the natural folds of the skin and especially in the fourchette. The
urethral introitus may be inflamed. The condition can extend to involve the perianal skin.
On the whole the vulvar structures are atrophic and inflamed.
− Histologically: lichen sclerosis shows not only a thin and inactive epithelium, but also
thickened keratin layer (hyprekeratosis). The dermis shows loss of elastic tissue,
hyalinization of collagen layer, and leucocytic infiltration. This lesion of lichen sclerosis
is most probably not a forerunner of malignant change. This is unless associated with
squamous cell hyperplasia or VIN.
− Etiology: all etiological factor discussed under squamous cell hyperplasia can be involved
in lichen sclerosis. In addition an element of estrogen deficiency is involved. This is
suggested by the age of the patients and the improvement of manifestations that occurs
after estrogen therapy. This can be topical or systemic. Estrogen administration should be
associated with progestogen superaddition for at least part of the time. Medical
surveillance along the line described for HRT needs be instituted.
▪ Other dermatosis
These represent skin general disorders that commonly affect the vulval area and
therefore are a cause of gynecologic consultation. By far, Tinea is the commonest. However
one may meat seborrheic dermatitis and pasoriasis.

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Tinea
− Tinea cruris is a common infection of men and women. Tinea means skin fungus with the
next term describing the location, e.g. tinea capitis (scalp), tinea pedis (foot), tinea cruris
(groin), and tinea corporis (body). The disease is commonly called "ringworm", and this
describes the appearance of the annular lesion of tinea that has cleared center, leaving and
an advancing raised ring of papules that creeps outwards. It has no relation to the parasitic
infection Taenia (tape warm), i.e. it is not caused by a worm but a fungus (dermatophytes)
which colonizes and digests coetaneous keratin, hairs and nails. The three dermatophytes
genera are trichophyton, epidermophyton and microsporon. They infect superficial skin
structures only without deeper involvement. Tinea at multiple sites are commonly
associated, and the husband is frequently also affected somewhere. Environmental factors
are important in tinea infection including humidity, heat, occlusion and proximity. The
condition takes severe forms in immune compromised patients. It has no relation to vulval
neoplasia.
− Tinea cruris starts in as an intertrigo affecting the crural folds and spread to involve the
upper thigh and vulva perineaum and perianal region. It causes itching and soreness of the
area. Some patients (or their husbands) complain from a smell. The affection causes a
ring-shaped red eruption with an an active advancing border and a scaly healing center.
The edge is slightly raised and may contain blisters or small pastules.
− Potassium hydroxide (KOH) test is used to demonstrate the dermatophyte. To a scraping
from the edge of the lesion a drop of warm 20% solution of KOH is added. This dissolves
the keratin after 10 minutes and allows visualization of the glistening hyphae under the
low power of the microscope. They are cylinderic and of uniform thickness and sparsely
branching.
− Treatment:
The condition is difficult to eradicate; improvement are frequently followed by
exacerbations. In contrast to monilial infection, Nystatin is not effective but imidazole
compounds (clotrimazole e.g. Canesten, miconazole e.g. Daktarine, or terconazole) are good.
Twice daily local applications should be rubbed well on the lesion. Other areas in the body
should be similarly treated if affected by tinea. The treatment should be continued for two
weeks after disappearance of the lesion. Hydrocortisone or betamethasone 1% can be added
to the imidazole, topical treatment particularly at the beginning of therapy in order to achieve
a rapid relief. Systemic treatment with griseofulvin or ketaconazole or itraconazol (e.g.
Sporanox) can be given for 4 to 6 weeks in chronic cases.
Seborrheic dermatitis:
This is the common affection of scalp (dandruff) and eyebrows and side of the nose. It
rarely affects the gluteal cleft and groin. The affection when mild produces fine scales, but

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

when severe it produces red or brown sharply defined plaques. Pruritus is its main symptom.
It flares in periods of stress.
The cause of seborrheic dermatitis is not known. It clears with topical agents. Scalp
affection is responding to shampoos. Body involvement clears with use of low potency
topical steroids.
Psoriasis:
Psoriasis is a chronic, relapsing skin disease presenting in certain different ways,
ranging from scaly patches, erruptive guttates (weeping papules), round sharply demarcated
red plaques with thick silvery adherent scales and generalized erythema and edema. It is an
indolent affection. It affects scalp, bent of elbow or knee, sacrum, umbilical region rarely the
groin and vulva.
The etiology is not clear, and it is familial and can be inherited by an autosomal
dominant gene with varying pentrance.
The treatment comprises topical and systemic corticosteroids. It is something that
should be left to dermatologists.
Lichen planus:
This is a rare condition that causes pruritic eruption of shiny, smooth, flat-topped
papules on the kin and white patches or erosions on mucous membranes. The mucous
membrane erosion affects the vagina and mouth.
The cause of lichen planus is not known and can be autoimmune disorder. It may
respond to corticosteroid treatment.
Lichen simples chronicus:
This is a rare condition that cause lichenfied plaques, on the nape of the neck, ankles,
forearms, antecubital or popluteal fossa and may be labia majora. It causes itching.

Pruritus Vulvae
Definition and occurrence: Pruritus = itching
Pruritus vulvae is a common gynecologic complaint. Pruritus is distinct specific
complaint, different from soreness or pain, but such latter complaints may be associated with
pruritus or resulting from repeated scratching: pruritus can be severe causing disabling misery
of the affected patient; it is very embarrassing to the patient. It is sometimes difficult to be
relieved.
Causes:
The causes are varied and are dealt with in different parts of this text a book. The
following is a resume of the possible causes:

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

1. Pruritus associated with vaginal discharge

These account for a good percentage of cases and are mainly caused by:
- Trichormonas vaginalis vaginilis.
- Candida albicans vaginitis, including diabetic candidiasis.
- Some cases of bacterial vaginosis.
2. Pruritus without vaginal discharge
- Part of generalized itching caused by general disease.
Jaundice, uremia, lymphoma.
- Skin diseases not specific to the vulva including
a. allergy skin or drug sensitivity: The allergy may be localized to the vulval
region and is caused by certain allergens brought in contact with the vulva (e.g.
underwear material, douches, depilator, deodorants, drugs ... etc.
b. psoriasis.
c. seborrheic dermatitis.
d. scabies.
e. tinea.
f. lichen planus.
- Specific vulval dystrophies and neoplasias:
a. Squamous cell hyperplasia.
b. Lichen scloresus
c. VIN
d. Paget's disease
3. Invasive carcinoma of the vulva.
4. Disease of the anus and rectum
a. anal fissure
b. hemorhoids
c. thread warm, entrobius (common in children)
d. pruritus ani can be part of tinea affection
5. Disease of the urinary tract
- urinary incontinence.
- glycosuria diabetic vulvitis
6. Deficiency states (see under squamous cell hyperplasia)
7. Psychological factors can accentuate pruritus. A scrtatch habbit can easily developed.

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Vulvar Intraepithelial Neoplasia (VIN)

VIN is being increasingly diagnosed in the American and European practice at the
present time. This may represent and an increased suspicion index. In our local practice this
trend has not occurred. The disease is frequently multifocal in nature.
The chance of VIN to progress to invasive cancer has been variably estimated, but it is
roughly less than 5%. The malignant potential is thus less than that of CIN, with which it may
coexist. The median age of VIN cases is in the forties and the progression to invasive cancer
may take 2 to 8 years.
Clinical features:
1. The condition is asymptomatic in 50% of cases.
2. In the remainder, pruritus vulvae is the presenting symptom. Presence of a distinct mass,
fissure, ulcer or bleeding usually indicates presence of invasive cancer.
3. Good inspection of the vulvar structures in good light is the key to diagnosis. Milder
forms of VIN on the vaginal skin may appear as white areas. More severe forms are seen
as whitish papules or macules. They can be multiple and may be coalescent. By contrast,
lesions on the mucous membrane are usually pink or red macules. Vulval lesions are
hyperpigmented in 10% of cases. Similar lesions may be coexisting in the cervix, vagina
and anal canal.
Diagnosis:
1. High index of suspicion and free resort to biopsy. The area of the vulva in any elderly
patient should receive careful inspection in good light including the perineum and perineal
regions. This should specially be not neglected in patient with history of CIN, or invasive
cervical or rectal cancer.
2. The use of 5% acetic acid paint to suspicious area; this shows white patches.
3. Colposcopic examination help to delineate the areas from which biopsies should be taken.
It is always good practice to combine any procedure done for detection of CIN with
attempt at detection of VIN.
4. Biopsy: multiple biopsies should be taken by a special punch biopsy or a knife. They will
show loss of orderly mosaic pattern of the stratified squamous epithelium, associated with
cellular crowding, nuclear pleomorphism and hyperchromatosis with normal and
abnormal mitosis. The changes involves the basal third, two thirds or the whole thickness
of epidermis in VIN I, VIN II, and VIN IIII respectively. Hair follicles may be involved.
Treatment of VIN:
The treatment for this disease is difficult because of its multifocal nature. It comprises
the following:

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

1. Conservation: asymptotic patients particularly under the age of 50, can, after an excision
biopsy, best be observed regularly and biopsies repeated if there is any suspicious lesion.
2. Surgical excision is the main treatment removing the lesion(s) with 5 mm safety margin.
The main advantage of this approach is making sure that the lesion has been removed and
an invasive lesion in the neighborhood is excluded. If multiple lesions are present local
vulvectomy with mobilization of the surrounding skin is possible and better than using
half-thickness skin graft.
3. Laser vaporization: utilizing carbon dioxide laser, the lesion can be vaporized. The depth
of vaporization required varies from 1 mm in nonhairy areas to 3 mm where hair follicles
are present because hair follicles can be involved to a depth of 2.5 mm. Vaporization by
laser can give of good cosmotic results but only if the lesion is superficial and is not
involving a large area. The patient should be kept under observation and repeat
vaporization may be required.
Paget's disease: see later

Invasive Vulvar Cancer

Epidemiology:
Vulvar cancer is an uncommon malignancy. It accounts for about 5% of the female
genital tract cancer; it follows in the order of frequency the uterine corpus, the ovary and then
the uterine cervix (United State's data). With increasing longevity of women vulvar,
carcinoma will be increasingly encountered. The median age at time of presentation is in the
7th decade. There is no relation to gravidity or race. However, the condition is more
frequently seen in poor women, this may be related to poorer personal hygiene.
Etiology:
The etiology of vulvar cancer is not clear. There is often, but not always, a long
history of vulval irritation leading to scratching and further irritation. Like in cervical cancer
the human papillpma virus (HPV) particularly types 16 and 18 may be involved in the
pathogenesis. The type 2 human herpes simplex virus (HSV), may be a cofactor. However,
the involvement of such viruses in vulvar cancer is less confirmed than in cervical cancer.
Some cases are preceded by squamous cell hyperplasia (leukoplakai). However, it cannot be
reliably estimated which percentage of cases proceeded by leukoplakia or VIN changes.
However, invasive cancer is commonly associated with squamous cell hyperplasia
(leukoplakia).

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

Pathology:
The lesion: is either a nodule or an ulcer. This is usually preceded by a period of intense
pruritus vulvae. The ulcer has raised edges, sloughing floor and firm base. The nodular form
is usually cauliflower in shape. Less frequently a flat plaque is present. The old patients tend
frequently delay seeking consultation until the disease is quite advanced.
Location: the lesion can appear anywhere on the vulva. The disease more commonly occurs
in the labia majora; however, it may appear on labia minora, clitoris, and perineum. Multiple
growths are not uncommon; sometimes there are labial “kiss ulcers” whose appearance
suggests that the lesion spreads from one side to another by direct contact - a most doubtful
mechanism.
Spread: extension of the growth is slow. It occurs by direct spread to involve the vagina,
urethra, perineum, anus and groin. Lymphatic spread mainly occurs by embolization to the
regional lymph nodes rather than by permeation spread. Realizing this point has obviated the
need to remove the skin area intervening between the lesion and the location of lymph nodes
as originally required in the original radical vulectomy operation described by Stanley Way in
the 1960s. The bigger the primary lesion the higher the chance of finding lymph node
involvement. With advanced big tumors with clinically enlarged lymph nodes, complete
obstruction of lymphatic system can lead to involvement of subcutaneous and dermal
lymphatics of the vulva, mons and upper thigh. Consequently, in such advanced cases wide
skin excision is required. Unfortunately most cases we see are quite advanced.
The lymphatics draining the vulva tend to proceed forwards before curving laterally.
The spread primarily to the superficial femoral and superficial inguinal lymph nodes. The
former group is situated around the terminal portion of the long (great) saphenous vein (before
it joins the femoral vein), upon the cribriform fascia (covering the fossa ovalis). Spread to
lower lymph nodes in the thigh is exceptional and these need not be removed. The superficial
inguinal nodes are just below the skin fold along the medial two thirds of the inguinal
ligament and upon the external inguinal ring.
There is a rich lymphatic connection between the two sides of the vulva; spread to the
contralateral lymph nodes occurs in 25%; hence the need for bilateral lymphadenectomy in
radical vulvectomy.
Involvement of deeper lymph nodes in the groin and pelvic (iliac) lymph nodes is not
common, and only occurs when the superficial lymph nodes are involved. Realization of this
point has resulted in modifying the classical management and has allowed two new
therapeutic options. In the first option, the removed superficial nodes are subjected to frozen
section examination and when positive for malignancy, the surgeon proceed to removal of

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

deep lymph nodes. These comprise, the deep femoral, deep inguinal, external iliac and
internal iliac groups of node.
The second option is to give pelvic irradiation to those cases that show malignant
involvement of the superficial lymph nodes. The above-described modifications of the
classical radical vulvectomy have been also substantiated by the fact that women with vulvar
cancer are old and frail and may not stand extensive surgery.
An exception to the above modifications is when the vulvar cancer is involving
middle-line structures, e.g. the clitoris. Cancer in these sites may metastasize directly to the
node of cloqute and pelvic lymph nodes.
Blood spread is late, and usually the patient expires earlier as a result from exhaustive
pain, infection and incontinence.
Histopathology:
The majority (85%), of vulvar cancer is squmous cell carcinoma, which tends to be
more differentiated than cervical cancer. Less than 5% are melanomas and the remainders are
carcinoma of the Bartholin gland (adenocarcinomas), basal cell carcinoma or the very rare
verrucous carcinoma. Sarcomas are very rare, comprising rhabdomyosarcoma, fibrosarcoma,
leiomyosarcoma.
Clinical features:
The patients may suffer from pruritus or discomfort in the vulva, or be aware of
presence of a small tumor. They may disregard the lesion for sometime considering it a
simple wart. The lesion produces some slight bleeding or discharge. Though the appearance
of the lesion is highly suggestive of the diagnosis, this should await histopathological
confirmation; a bilharzial lesion in the vulva could simulate a malignant lesion. The lymph
nodes in both groins should be carefully palpated for.
Other investigations include full blood count, serum biochemistries, chest x-ray, heart
assessment. The patients may look very old and frail but, if medically fit, they should be
persuaded to accept the operation; many of them enjoy some good years of reasonable, pain-
free years of life after the operation. The operation can sometimes be tailored to the general
health of the patient.
Prognostic factors:
There are number of interdependent prognostic factors in carcinoma of the vulva:
1- Involvement of inguinal and femoral nodes: ipsilateral or bilateral.
2- Site and size of the tumor.
3- The tumor free margin in the removed vulva around the lesion.
4- The histopathological grade.
5- The depth of invasion of the stroma.

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

6- The FIGO stage.

Histologically proven involvement of lymph nodes in the groin is the most important
single prognostic factors. The percentage 5-year survival is more than 90% if the lymph
nodes have not been involved. This drops to 75% when only the ipsilateral nodes are
involved, but when bilateral or contralateral lymph nodes are affected by malignancy, the
chance of 5-year survival becomes about 30%. The more the number of the involved lymph
nodes, the worse is prognosis.
Middle-line tumors have a worse prognosis, may be through causing deep pelvic
lymph node involvement.
Tumors 2 cm in diameter have an excellent prognosis while tumor 8 cm in diameter
has a poor prognosis. The prognosis of the intermediate diameters largely depends on lymph
node involvement.
If the width of the removed tumor-free margin in the vulva is less than 8 mm there is a
serious prognosis.
Lesser tumor differentiation carries a worse prognosis; verrucous carcinoma has an
excellent prognosis (see later). Melanoma carries bad prognosis.
When the depth of tumor infiltration in the stroma is more than 1 mm the prognosis
becomes worse. The depth of invasion is measured from the epithelial stromal junction of the
adjacent most superficial dermal papilla to the deepest point of invasion.
Staging:
The FIGO classification take in consideration most of the above prognostic factors. It
is a surgico-pathological classification.
The 5-year percent survival worsen with the increase of stage, being 70%, 50%, 30%
and 13% for stage I, II, III and IV respectively.

FIGO Staging of Invasive Cancer of the Vulva

Stage Features
O Preinvasive carcinoma, or carcinoma in situ (VIN III)
I Tumor confined to the vulva and/or perineum, 2 cm or less in greatest dimension,
and no lymph node metastasis
Ia ---------- with stromal invasion no greater than 1.0 mm
Ib ---------- with stromal invasion greater than 1.0 mm
II Tumor confined to the vulva and/or perineum, more than 2 cm in the greatest
dimension, and no lymph node involvement.
III Tumor of any size arising on the vulva and/or perineum with adjacent spread to the

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

lower urethra and/or vagina or anus.

and/or
IVa unilateral regional (inguinal or femoral) lymph node metastases.
Tumor invading any of the following: upper urethera, bladder mucosa, rectal
mucosa, and pelvic bone.
and/or
IVb bilateral regional lymph (inguinal or femoral) node metastases.
Any distant metastases including pelvic lymph node

Management:
[Link]:
Surgery is the mainstay of treatment for vulvar carcinoma. Radiotherapy is poorly
tolerated by the thin epithelium of the vulva, leading to acute moist desquamation and severe
late normal tissue damage in the form of severe fibrosis with atrophy and necrosis. This
results in vulvar, urethral or rectal strictures and fistula formation. In contrast, skin cancer in
other sites of the body responds favorably to radiation therapy whether interstitial or by
external - beam treatment.
Classical surgical approach:
The classical operation done for carcinoma of the vulva is radical vulvectomy as
described by Way. It comprises removing the following structure en block:
1. Vulvectomy = removal of all vulval structures: skin and subcutaneous tissue with a good
safety margin of at least one cm beyond any tumor induration. The inner incision is at the
past site of the hymen, and just behind the urethral meatus. All the mons veneers is
removed regardless of involvement, on the assumption that lymphatic of the vulva pass
forward to the mons before curving laterally to the inguinal lymph nodes. The lower
urethra and perineum are removed when necessary.
2. Bilateral removal of the skin and subcutaneous tissue overlying the inguinal ligament and
femoral (scarpa's) triangle (Figure 1). This leave behind a huge skin defect, difficult to
cover through mobilization of the skin from around. Usually this is done under tension
and the stitches break and skin edges slough leading to prolonged difficult convalesces
and severe disfigurement. Occasionally, plastic surgical procedures are required either at
the time of primary surgery or at a later stage. This wide skin excision was based on a
belief that the cancer spreads by permeating into skin lymphphatics rather than by
embolization. This assumption has been shown to be not valid, at least in the early cases.
3. Removal of the deep fascia covering the muscles of the lower abdomen and femoral
triangle. This may not be needed excepte in advanced disease.

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

4. Removal of the following groups of lymph nodes on both sides regardless of involvement:
− The superficial inguinal lymph nodes, which lie below, the medial two thirds of the
inguinal ligament and on the external inguinal ring.

Carcinoma of the vulva; Figure 1:The big area of inguinofemoral skin removed in the
classical radical vulvectomy operation.

− Superficial femoral lymph nodes which lie around the terminal part of the great (long)
saphenous vein (Figure 2) before it pierce the cribriform fascia. At the dissection of this
group of lymph node the following tributaries of the femoral veins need be identified and
legated: the long saphenous vein, the lateral accessory saphenous vein, the superficial
circumflex iliac and superficial epigastric veins.
− The deep inguinal nodes in the inguinal canal around the terminal part of the round
ligament. The canal is reached by incising the external oblique aponeurosis above the
inguinal ligament.
− The deep femoral nodes. These lie underneath the cribriform fascia in the femoral canal,
which is on the medial side of the femoral vein. The upper most member of this group is
the node of cloquet. This node may be involved in cancer in around the clitoris without
prior involvement of the superficial node. To reach this gland the femoral vessels are
exposed, skeletonized and the inguinal ligament is usually transversely incised. At the end
of the operation the femoral vessels will need be covered by cutting and transposing the
upper end of the sartorius muscle.

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

Carcinoma of the vulva; Figure 2:The superficial blood vessels in the inguinal region:
GSV= great saphenous vessels, ASV= assessory saphenous vessels, SSI= superficial
circumflex iliac vessels, SEV= superficial epigastric vessels, CF= the cribriform-fascia
(shaded). The femoral vein is shown by interrupted lines. IL= inguinal ligament.

− The iliac lymph nodes: These comprise the external iliac and internal iliac (hypogastric)
groups. To reach these suprainguinal structures, the lateral fibers of the internal oblique
and transvelsalis muscles are transversely cut along their fibers. Underneath, the
transversalis fascia is identified and transversely incised to expose the pelvic peritoneum.
The inferior epigastric vessels are to be safeguarded. The peritoneum is not incised (if
inadvertently incised it should be repaired), but is pushed up with a broad curve of
retractor. Usually this raises the ureter with the peritoneum. Injury of the ureter and the
branches of the internal iliac vessels need be carefully avoided.
− This Way's radical vulvectomy gave excellent results particularly in early cases.
Moreover, it is still the reasonable choice for most of the advanced case seen in our
practice. However, since many of the patients are old and frail and the disfigurement the
operation causes is marked, some of concepts have been challenged, and the following
modifications have been suggested and widely accepted for early cases:
a. The three-incision approach (Figure 3): One is the vulvectomy incision and two
incisions parallel and below the inguinal ligaments. This modification has been
substantiated by failure to demonstrate cancer cells in lymphatics of the big
butterfly of skin removed in the Way's operation. The procedure greatly facilitates
covering the vulval defect and reduces the morbidity of the operation.

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

Carcinoma of the vulva; Figure 3:Three incision techniques in radical vulvectomy. IL=
inguinal ligament (The incisions represented by interrupt line).

b. Removal of the whole of the mons veneres is not necessary. The lymphatics of
the vulva do not reach that far anteriorly and if so this rarely occurs by
permeation. The most formidable task after removal of the whole of the mons is
to bring the abdominal skin to near to the urethral meatus.
c. Lymphadenectomy, confined to the ipsilateral inguinal and femoral (superficial
and deep) is advocated in small lesions of stage Ia. If pathologically positive
nodes are found in such cases (rare) the contralateral nodes will need to be excised
at a later date.
d. Pelvic lymphadenectomy is only done when the superficial nodes are involved.
This can be known through frozen sections, or this deep lymph nodes are dealt
with later by surgery or radiation. It has been realized that when the superficial
nodes are pathologically negative pelvic nodes are not involved. The exception is
when the cancer is involving the region of the clitoris or is crossing the middle
line.
Postoperative complications:
Primary morbidities are common in this operation, including hemorrhage and shock. Late
morbidities include mainly wound infection and wound breakage due to tension. However,
healing ultimately occurs. It can leave excessive scarring with stenosis of the vaginal urethral

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

and rectal orifices. Leg edema is common. Numbness and hypothesis of the front of the thigh
(due to severing of femoral nerves) can occur.
B. Radiotherapy:
External beam or interstitial radiotherapy is poorly tolerated by vulval skin. The
balance between the primary effect on the cancer cells and the secondary effect on the host
tissues, which is required for cure, can not usually achieved in the vulva. Consequently, if a
curative (radical) dose of radiotherapy is given, acute moist necrosis of the skin occurs,
associated with severe damage to the normal host tissue resulting and atrophy or necrosis.
Urethral, anal and vulval fibrosis occurs without the adequate growth-limitation effect
produced by the host tissue. As a result surgery has remained the primary treatment of vulval
cancer. However there has been recently a renewed interest in radiotherapy with a modified
dosage and technique given as an adjuvant to surgery either preoperatively or postoperatively.
Pre-operative radiotherapy:
Pre-operative radiotherapy and/or chemotherapy has been used in trial to reduce the
advanced tumors with bowel and bladder involvement to enable, subsequently the surgery to
be viscera-preserving. Surgery is done after 2-week gap following the end of preoperative
radiation.
Interstitial radiotherapy can be done for small vulval carcinoma, but this is better
followed by radical vulvectomy.
Post-operative radiotherapy:
Up to one third of patients with advanced vulval cancer will have local recurrence, this
incidence can be reduced by post-operative radiation. The criteria for post-operative
radiotherapy to the nodes, both inguinal and pelvic, have been specified as:
− a single clinically involved inguinal node or
− two or more histologically involved nodes or
− extracapsular spread.
− the safety margin excised around the tumor has be less than 1 cm in one side
A typical radiation dose for postoperative radiotherapy dose given to the groin and
pelvic nodes is 45-50 Gy at 1.8-2.0 Gy per fraction. There is no total agreement on the dosage
schedules. Usually a daily fraction of 1.6-1.8 Gy is given. It is important to limit the size of
the treatment field to reduce long-term morbidity. Concomitant chemotherapy may be added,
mainly with a combination of 5-fluorouracil (5FU) and cisplatin.
Radiation is not alternative to excision of the inguinal and femoral lymph node.
However, if these are found involved postoperative radiation is needed. This post-operative
radiation can substitute, the need for dissection of pelvic nodes in each radical vulvectomy.

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

C. Chemotherapy:
Chemotherapy has not played a significant role in treatment of carcinoma of the vulva.
It has been usually given in combination of radiotherapy as a pre-operative adjuvant in
advanced case to make viscera-preserving surgery possible. The old age and the usually poor
health of the patient's have been limiting the use of these agents. The chemotherapeutic agents
have involved cisplatin, 5-FU, bleomycin and methotrexate, given as single-agent or better as
multiple agent treatment.
Conclusion:
The following is a summary of the reasonable approach for management of carcinoma
of the vulva:
1. Lesions of 1 mm depth or less (rarely seen in our practice) are treated by a vulvectmy
removing 1 cm safety margin around the tumor, no lymphadenectomy is done.
2. Lesions of more than 1 mm depth are treated by the usual radical vulvectomy with the two
modifications: (1) “3-incision” approach; (2) pelvic lymph nodes are not removed except
when the superficial nodes are involved. If post-operative histological evaluation reveals
nodal involvement, radiation therapy is given to the site of the groin and pelvic lymph
nodes.
3. Carcinomas of the vulva involving a middle-line structure require bilateral deep inguinal
and femoral node and pelvic node dissection if the general health of the patient can allow.
In high-risk cases, the modified operation is done and is followed by radiation therapy.
4. For advanced carcinoma of the vulva, the original radical (Way's) operation is done if the
general health of the patient can allow. Rotational skin flap may be required to close the
skin defect. Post-operative radiation to the site of inguinal and pelvic nodes is required.
5. An alternative approach possible for these advanced cases is preoperative radiation
chemotherapy followed two weeks later by radical surgery.
Results:
The 1988 FIGO results gave the following 5-year survival rates:
Stage I 69%
Stage II 49%
Stage III 32%
Stage IV 13%

Uncommon Neoplasia in the Vulva

Paget's disease:
Paget's disease is a rare variant of intraepithelial carcinoma of the vulva (VIN). In this
condition, the epidermis contains large cells with clear granular cytoplasm arranged singly or

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

in sheets or groups which are called Paget's cells. Their nuclei are polymorphic,
hyperchromatic and active. The cytoplasm contains a mucopolysaccharide (mucin), which
takes mucin stain. The upper dermis is infiltrated by lymphocytes and plasma cells. The cells
may extend in the hair follicles.
The condition is usually seen in old women. They present for pruritus and tenderness.
The lesion may be localized or diffuse involving the whole of the vulva and extends in the
vagina. The lesion is red and slightly raised and may have areas of leukoplakia due to
thickening of the keratin. It has excoriations and areas of induration and scratching signs.
The lesion is superficial without any underlying indurations.
A similar lesion occurs in the breast nipple area where it is commonly associated with
a duct carcinoma. However, at the vulva Paget's disease is rarely associated with any
underlying adenocarcinoma.
Paget's disease behaves like VIN and its malignant transformation or its association
with adenocarcinoma of the apocrine gland occurs in less than 20% of cases.
The management of Paget's disease of the vulva is similar to VIN. Wide local
excision to include the entire lesion is usually done. Histological assessment is needed to
confirm that the edge of the pathology has been included in the removed skin. This is required
since histological infiltration by Paget's cells may extend beyond the visually identified edge.

Bartholin gland carcinoma:

This is a rare tumor of the vulva. It is usually an adenocarcinoma, rarely
adenosquomous or squamous.
Carcinoma of the Bartholin gland is usually a disease of old women in there sixties or
above. The condition is diagnosed rather late, and present for a painful mass or a malignant
ulcer. A mass developing in the Bartholin gland in postmenopausal woman is to be
considered malignant until proved otherwise. The tumor spread to involve the vagina,
ischiorectal fossa and rectum. Lymphatic spread to the femoral and inguinal lymph nodes is
early, and commonly involves the pelvic lymph nodes.
Treatment is by radical vulvectomy. Adjuvant radiotherapy is needed in cases with
involved lymph nodes.
Adenoid cystic tumor of the Bartholin gland is a rare entity. The tumor behaves like
adenoid cystic tumor of the salivary glands in: (1) slow growth, (2) wide local invasion and
spread along nerve sheathes, making complete excision difficult and (3) great liability to local
recurrences. The treatment is radical vulvectomy including excision of a big safety margin.
Radiotherapy is needed for local recurrences.

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

Malignant melanoma of the vulva and vagina:

Malignant melanoma accounts for about 5% of cases of carcinoma of the vulva. The
median age of the patient is 65 year. Most of the cases arise in the labia minora.
Most lesions arise in the site of a nevus. High risk for this tumor may be familial or
constitutional (high propensity to sunburn) unusual moles (dark, speckled or irregular border
or big mole). These nevi are at increased risk and should be excised. Also, a recent change in
size, shape or color of the mole should prompt excision biopsy.
As elsewhere in the body, malignant mole is a raised pigmented lesion but may be an
ulcerated lesion. The lesion is usually black but some lesions are amelanotic. Histologically
the lesion simulates an undifferentiated squamous carcinoma with melanine pigmentation.
The melanoma presents as an enlargement, itching and bleeding in a nevus. The
growth occurs both in downward and outward direction, necessitating a wide excision.
The prognosis is related to the depth of the tumor and is good for depth less than 0.76
mm. The greater the depth of the lesion from the surface to the point of deepest penetration,
the worse is the prognosis. The prognosis is generally worse than that of squamous
carcinoma, particularly when the regional lymph nodes are involved. Malignant melanoma of
the vagina has a particularly bad prognosis.
Malignant melanoma is treated by radical vulvectomy including inguinal and pelvic
lymph adenectomy along the same guiding rules of other types of vulval cancer.

Basal cell carcinoma:

Basal cell carcinoma in the vulva is similar to the disease elsewhere. It presents as an
indolent ulcer with undermined edges and indurate base. Lymph node spread is most
exceptional, and the tumor is treated by local excision.

Verrucous carcinoma of the vulva:

(Verrucous = covered with warts). This is a rare variant of epithelial cancer of the
vulva, taking the form of a papillary growth, resembling condyloma acuminata.
Histologically, it is difficult to distinguish this tumor from a benign lesion unless a deep
biopsy is taken. Verrucous carcinomas are locally invasive but seldom metastasize to the
inguinal nodes. The usual treatment is either wide local excision for small lesions or
vulvectomy, but there is no indication to remove the regional lymph nodes unless enlarged.

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

Sarcoma:
This is a very rare tumor of the vulva. It occurs in young adults. The tumor forms a
big nodular ulcerating tumor. The histological grade of the tumor greatly decides the
prognosis. A well-differentiated leomyosarcoma carries a good prognosis but late recurrence
may occur. The undifferentiated rhabdomyosarcoma is highly malignant. The clinical picture
and treatment is similar to these of carcinoma.

Carcinoma of the Vagina

Incidence:
Carcinoma of the vagina is very rare accounting for 1-2 percent of all gynecological
malignancy. Primary carcinoma of the vagina is the rarest type of malignant disease in the
human. It is a disease of old women.
The upper third of the vagina is the most common site of primary vaginal cancer. The
lower third is the seat of 25% of cancer while the middle third is least affected.
Most of the cancer seen affecting the vagina represents a direct spread from carcinoma
in the cervix uteri, vulva, bladder or rectum; the first type being the commonest. Indirect,
metastatic spread to the vagina occurs from carcinoma of the endometrium, trophoblastic
neoplasia or carcinoma of the ovaries or tubes. The vaginal secondaries are usually located in
the lower anterior vaginal wall suggesting the existence of some “portal” type of circulation
between the upper genital tract and the lower anterior vaginal wall.
Vaginal intra-epithelial neoplasia (VAIN), is now increasingly seen in countries
utilizing screening PAP smears. It is more common after hysterectomy done for benign
condition. VAIN is usually multifocal; a positive or suspicious smear will necessitate careful
colposcopic evaluation. Like CIN, VAIN can progress to malignant disease.

Etiology:
The etiology of the vaginal carcinoma is obscure. It is possible to be related to a viral
infection, probably the human papilloma virus.
A special rare type of vaginal cancer, the clear cell carcinoma (of mesonephroid
pattern) has been ascribed to intrauterine exposure of the patient (as an embryo or fetus) to
diethylstilbosterol (DES), a non steroidal synthetic estrogen. This drug was given to the
mothers in support, of early pregnancy. The exposed fetuses are affected in later stage of their
life by this rare type of cancer. The offspring developed the cancer either in the cervix or

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

upper vagina while they are children or young adults. The DES received the dimension of a
syndrome, when it was observed that these offspring exposed in utero to DES had a higher
incidence of infertility, repeated abortions, hypoplastic uterus and adenosis in the cervical and
lateral vaginal wall, besides the predisposition to clear cell carcinoma of the vagina and cervix
and increased incidence of CIN.
Serious doubt has, however, been raised against the idea that in utero exposure to
estrogens is carcinogenic. Other hereditary or coincidental environmental factor might have
been involved instated or as well. In utero exposure to combination contraceptive pills
inadvertently taken during pregnancy did not show an association with later development of
any type of cancer.

Pathology:
− Vaginal intra-epithelial neoplasia (VAIN) is classified in a similar manner to CIN, to mild
moderate and severe.
− More than 95% of cases of invasive vaginal cancer are of the squamous type. Other types
include melanoma, clear cell carcinoma and sarcoma.
− Spread:
Local extension is early and involves the parameterium and a number of important
structures like the bladder, urethra and rectum. The lymphatic drainage of the upper two
thirds of the vagina is to the pelvic lymph nodes, similar to the lymphatic drainage of the
cervix. The drainage of the lower third is similar to that of the vulva and involves the inguinal
and femoral lymph nodes. Hematogenous spread is late and rare.

Clinical picture:
VAIN is asymptomatic and have no special appearance. It is diagnosed by screening
vaginal smear; positive or suspicious cases are examined by colposcopy. Suspicious areas are
biopsied. They can be multiple. Post-hysterectomy cases needs special attention to the vault
area around the suture line, but the whole of the vagina should also be examined. The cost-
effectiveness of the screening programs is debatable unless it is part of the screening for CIN.
Symptoms of invasive disease include bleeding and infected discharge. Pain, urinary
and rectal symptoms are late. The majority of cases are advanced at the time of the first
presentation.
Examination under anesthesia is required to assess the extent of the spread of the
disease and comprises rectal and cystoscopic examinations. Methods of imaging like vaginal
sonography, pyelography, CT and MRI are needed to assess the extent of spread of the
disease.

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

Staging:
The FIGO staging is a clinical one:
Stage Features
0 Pre-invasive carcinoma (VAIN)
I Carcinoma limited to the vaginal mucosa
IIa Involvement of subvaginal tissues: not extending to parametrium.
IIb Parametrial involvement not extending to pelvic side wall
III Carcinoma extending to pelvic side wall
IVa Involvement of mucosa of the bladder or rectum
IVb Spread beyond the pelvis

The prognosis mainly depends on the stage of the disease. It also depends upon the
depth of invasion, the histopathological grade and involvement of regional lymph node.

Treatment:
Treatment of VAIN:
Local excision or laser ablation is usually sufficient for a localized lesion.
Intracavitory, radiation is used for multiple vault lesions following hysterectomy. widely
spread multiple lesions may need vaginectomy.
Invasive carcinoma of the vagina should be mainly treated by radiotherapy. This
includes a combination of external radiation and intracavitory and/or interstitial radiation.
Surgery is used in few cases.
Surgery:
Local excision with a wide safety margin can be done for stage I disease. Carcinoma
in the upper third of the vagina can be treated like cervical cancer by radical hysterectomy
including pelvic lymphadenectomy and partial or complete vaginectomy. This can be
accomplished through the abdominal approach, but may require an abdomino-vaginal
approach.
Stage IV a and recurrent disease after radiation can be treated by pelvic exenteration
when the general condition of the patient allows.

Radiotherapy:
This should be the usual treatment of vaginal cancer. It usually starts by external
beam treatment followed by brachytherapy. The field irradiated by external beam depends on

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Nonneoplastic epithelial disorders of the vulva and carcinoma of the vulva

the site of the tumor. In all cases the lateral pelvic wall is included. In tumors in the lower
third of the vagina the inguino-femoral nodes must be also included in the treatment volume.
A total dose of 45-50 Gy, in 25-28 fractions is given over 5-6 weeks.
Brachytherapy:
This can be in the form of either:
1. Intrauterine tube plus vaginal vault ovoids is given for upper third vaginal cancer
in the same way as in cervical cancer. The after-loading technique is better used.
2. For lesions below the vault not deeply invading to the parameterium or the ones,
which have markedly regressed under external beam therapy vaginal intracavitary
treatment, using a vaginal obturator. The total dose given at the vaginal mucosa is
70-75 Gy.
3. Intersteial brachytherapy has been found to be more effective than intracavitary
treatment for lesions below the vault. The interstitial implants are ideally given by
using an after-loading technique with iridium-192 wires. A plastic template is
used to hold rigidly the steel tubes that carry the iridium wires. The template is
fixed under anesthesia to the perineum. The steel holders of iridium are inserted
through the perineum into the paravaginal space. A total dose of 70-80 Gy is
given in two insertions 2 weeks apart. Interstitial brachytherapy can be used as the
sole treatment of carcinoma in the middle or lower vagina.

Complications:
a. chronic ulceration.
b. fistula formation: this should be avoided by proper geometry of the radiation.
c. vaginal stenosis. This can be reduced by vaginal douching during treatment and vaginal
dilators after treatment.
Results:
The prognosis is definitely poorer than with vulval cancer; the 5-year survival ranges
between 77 percent in patients with stage I disease, 45 percent in stage II, 30% in stage III and
18 percent with stage IV disease.

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Common questions