MANIBA BHULA NURSING COLLEGE

Subject: Obstetrics & Gynaecology

Topic: An assignment on Assisted Reproductive Techniques

Submitted To: Submitted By:

Ms. Kinjal Mistry Ms. Hiral Mistry
Assistant Professor, Ist Year [Link] Nursing,
MBNC MBNC

Submitted on:
 ASSISTED REPRODUCTIVE TECHNOLOGY
 Introduction:
Assisted Reproductive Technology (ART) includes in vitro fertilization-embryo transfer (IVF-
ET), gamete intrafallopian transfer (GIFT), zygote intrafallopian transfer (ZIFT), and frozen
embryo transfer (FET). These techniques also apply to oocyte donation and gestational carriers.
Approximately 99 percent of ART cycles performed are IVF-ET. IVF-ET has helped many
couples conceive successfully. ART may be recommended when other treatments (such as
intrauterine insemination) have not been successful or when there is severe male factor
infertility, severe endometriosis or tubal obstruction.
Fertility therapy generates a wide range of emotions. Waiting, uncertainty, and the demands of
treatment can lead to feelings of frustration, confusion, and resentment. We believe that the more
you know about the tests and treatments, the less anxiety and concern you will feel about your
condition. If you are going through this process with a partner, please review this information
together.
Most centers utilize a multi-disciplinary professional team. During your treatment cycle, many
team members, in addition to your individual physician, will participate in your care. Advanced
infertility procedures require time and energy, as well as an emotional and financial
commitment. The entire staff should make every effort to provide you with personal and
compassionate care in order to make this difficult time as comfortable and manageable as
possible.
Success rates:
Success varies with many factors. The age of the woman is the most important factor, when
women are using their own eggs. Success rates decline as women age, specifically after the mid-
30’s. Part of this decline is due to a lower chance of getting pregnant from ART, and part is due
to a higher risk of miscarriage with increasing age, especially over age 40.
Success rates vary with the number of embryos transferred. However, transferring more and
more embryos at one time does not increase the chance of live birth significantly, but may only
increase the risk of a multiple pregnancy, and its associated risks. The impact of the number of
embryos that are transferred also varies with the age of the woman.
SART, in conjunction with, The American Society for Reproductive Medicine (ASRM), has
published guidelines for the recommended number of embryos to transfer (add to link). These
guidelines are based on SART-sponsored research which continually evaluates success rates
around the country. This helps to determine the optimal number of embryos to transfer, based on
specific patient characteristics, like age and history of prior IVF. Patients may require several
cycles of treatment to have a baby. Success rates remain fairly constant over several cycles, but
may vary greatly between individuals. It is important to note that patient characteristics vary
among programs; therefore, success rates should not be used to compare treatment centers.
Types of ART:
Following are different Assisted Reproductive Technologies:
A) Intra uterine insemination
B) In vitro fertilization (IVF)
C) GIFT
D) ZIFT
E) Intra cytoplasmic injection (ICSI)
 F) Assisted hatching
G) Gestational carriers
H) Freezing of embryos and frozen embryo transfer
I) Donor eggs

A) INTRA UTERINE INSEMINATION:

 Introduction:
Intrauterine insemination (IUI) is a fertility treatment that involves placing sperm inside a
woman’s uterus to facilitate fertilization. The goal of IUI is to increase the number of sperm that
reach the fallopian tubes and subsequently increase the chance of fertilization.
IUI provides the sperm an advantage by giving it a head start, but still requires a sperm to reach
and fertilize the egg on its own. It is a less invasive and less expensive option compared to in
vitro fertilization.
 Indications for IUI:
The most common reasons for IUI are a low sperm count or decreased sperm mobility.
However, IUI may be selected as a fertility treatment for any of the following conditions as
well:

 Unexplained infertility
 A hostile cervical condition, including cervical mucus problems
 Cervical scar tissue from past procedures which may hinder the sperms’ ability to enter
the uterus
 Ejaculation dysfunction
IUI is not recommended for the following patients:

 Women who have severe disease of the fallopian tubes

 Women with a history of pelvic infections
 Women with moderate to severe endometriosis

 Procedure:
1. Ovulation stimulation:
Before intrauterine insemination, ovulation stimulating medications may be used, in which case
careful monitoring will be necessary to determine when the eggs are mature. The IUI procedure
will then be performed around the time of ovulation, typically about 24-36 hours after the surge
in LH hormone that indicates ovulation will occur soon.
2. Semen collection:
In order to obtain sperm of optimal quality, it is important that patients follow clinic instructions
for semen collection. (Be aware that clinics may have different protocols for sperm collection for
intrauterine insemination and in vitro fertilization. Also, some programs may have men take an
antibiotic prior to collection for IVF cases.) Common instructions include:
Do not ejaculation for at least two days but not more than five days before obtaining the semen
sample.
Semen should be collected in a sterile, non-toxic plastic jar provided by the laboratory. Other
containers are not [Link] clinics prefer that the specimen be collected in the office, if
possible. Private collection rooms are usually available.
Wash and dry your hands prior to collecting the specimen. Some programs also recommended
cleansing the penis followed with rinsing and drying to remove any soap or water.
Your physician should be notified if there are any problems in collecting. An alternative
collection method could be provided, including the use of a special nontoxic condom for
collection by sexual intercourse or the use of a vibrator. Commercial condoms cannot be used
because they kill the sperm.
Lubricants should not be used unless directed by a physician.
Follow the clinic instructions for labeling and transporting the specimen. It is critical to follow
these instructions carefully. Keep the jar closed tightly to prevent leakage. Let the lab know if
any of the specimen was lost or spilled and whether you have been taking any medications,
including herbal remedies.
Masturbation is the most frequent method used to produce a sperm sample on the day of oocyte
retrieval. Occasionally, intercourse using a special condom or electroejaculation is required for
successful collection. Some men are unable to ejaculate or have no sperm in their semen. In these
special cases, urologists can often obtain usable sperm from the testicle or the epididymis
utilizing a minor surgical procedure.
Some physicians recommend freezing a sample as a “back-up” if problems arise in the
production or quality of the sperm on the day of egg retrieval.
If a patient is using donor sperm, it will be thawed at the time of the egg retrieval. The donor
sperm must be collected and used in accordance with regulatory guidelines.
3. Wash out of semen:
A semen sample will be washed by the lab to separate the semen from the seminal fluid.
Different culture medias are available for the process of wash out. The different machines like
incubator, warmer & filters are used for the same process.
4. Insemination of sperms into uterus:
A catheter will then be used to insert the sperm directly into the uterus. This process maximizes
the number of sperm cells that are placed in the uterus, thus increasing the possibility of
conception.
The IUI procedure takes only a few minutes and involves minimal discomfort. The next step is to
watch for signs and symptoms of pregnancy.

 Risks of IUI:
The chances of becoming pregnant with multiples is increased if take fertility medication when
having IUI. There is also a small risk of infection after IUI.
B) INVITRO FERTILIZATION:

 Evaluation before IVF

Before starting ART, each patient is evaluated to help maximize her chances for success and a
healthy pregnancy. Good preconception health is essential to achieving pregnancy with IVF.
Chronic medical conditions such as diabetes, hypertension and asthma should be well controlled
before attempting to conceive. In addition, women planning an IVF cycle should optimize their
weight. Obesity has been associated with infertility, a reduced chance of success with IVF, and
an increase in the risk of miscarriage and preterm birth. Your physician can help you determine
your ideal weight and refer you to appropriate resources for weight management.
 Blood Tests
General
Prior to starting IVF, the woman's blood type should be verified, and she should be screened for
conditions that could affect the health of a pregnancy. Documentation of immunity to rubella
(German measles) and varicella (chicken pox) may also require a blood test. The patient and her
partner will also be tested for hepatitis B and C, HIV and syphilis. Other genetic tests may be
requested depending on the patient’s genetic background, such as cystic fibrosis and sickle cell
trait.
 Ovarian Reserve Testing
As women age they have a decreased ability to conceive and an increased risk of miscarriage.
Ovarian reserve testing tries to measure egg quality, quantity and reproductive potential. The
following tests may be used to measure ovarian reserve:
1. Day 3 Levels of FSH, LH, and Estradiol. The determination follicle stimulating
hormone (FSH), luteinizing (LH) and estradiol levels on menstrual cycle day 3 has been
used to estimate fertility potential. Women with elevated levels of FSH and/or estradiol
measurements may have reduced pregnancy rates with IVF or may require more
medications during IVF.

2. Clomiphene Citrate Challenge Test. This test requires patient to take 100 mg of
clomiphene citrate on menstrual cycle days 5-9. Blood levels of FSH are measured on
cycle day 3 and again on cycle day 10. Elevated blood levels of FSH on cycle day 3 or
cycle day 10 are associated with reduced pregnancy rates.

3. Anti-Mullerian Hormone Test (AMH). Anti-Mullerian hormone levels are thought to

reflect the remaining number of eggs. This test can be performed on any day of the cycle.
 Semen analysis
A semen analysis should be reviewed. Changes in sperm quality may occur over time that could
affect IVF success.
 Uterus
The uterus is usually evaluated prior to an IVF. Three methods can be used: a
hysterosalpingogram, a saline infusion sonohysterography or a hysteroscopy.
Prior to IVF, a trial or “mock” transfer may be done. The purpose of this procedure is to
determine the length and direction of the uterus. This enables the physician to anticipate any
difficulties with the embryo transfer.
 Other assessment:
o Weight and Fertility
o Smoking and Infertility
o Reproductive Aging in Women
o Diagnostic Testing for Female Infertility
o Diagnostic Testing for Male Factor Infertility

 Procedure:
Step 1 – Pre stimulation Treatment:

Initiation of Oral Contraceptives:

Some patients will receive oral contraceptives in the cycle prior to the ART cycle. This ensures
that GnRH analog therapy will start at the proper time if you have irregular cycles. There is
also evidence that oral contraceptives can help prevent ovarian cysts, which sometimes develop
during GnRH analog therapy. Progesterone may be prescribed for patients who ovulate
irregularly or not at all.

Suppression of Ovulation:
There are two principle ways that physicians ensure ovulation does not occur before egg
retrieval. One involves pre-treatment of a patient with a GnRH agonist. The other involves
treatment after six or so days of stimulation with a GnRH antagonist.

GnRH Agonist Administration:

GnRH agonist (Lupron): This medication is taken by injection. There are two forms of the
medication: A short acting medication requiring daily injections and a long-acting preparation
lasting for 1-3 months. The primary role of this medication is to prevent a premature LH surge,
which could result in the release of eggs before they are ready to be retrieved. Since GnRH-
agonists initially cause a release of FSH and LH from the pituitary, they can also be used to
start the growth of the follicles or initiate the final stages of egg maturation.

A GnRH agonist might be prescribed sometime after taking oral contraceptive pills. This dose
may be reduced when ovarian stimulation is begun. Agonist is often discontinued on the day of
hCG (human chorionic gonadotropin) administration.

Some protocols also might begin GnRH agonist sometime after ovulation in the cycle
preceding stimulation in the "mid-luteal" protocol, after the start of menses in the "flare" or
"micro-flare" protocol.

GnRH-antagonists (ganirelix acetate or cetrorelix acetate) (Antagon, Cetrotide):

These are other classes of medications used to prevent premature ovulation. They are typically
administered several days after stimulation and require fewer injections.

Baseline Pelvic Ultrasound

Around the time of your expected period, your physician will perform an ultrasound scan to
examine the ovaries. If your physician detects a cyst, they may withhold further therapy until
the cysts resolve spontaneously (usually in about a week). Occasionally, cyst aspiration
(drainage) is recommended. This is a procedure in which your doctor inserts a fine needle
connected to a syringe, guided by ultrasound, into the cyst. They may also perform a blood test
(serum estradiol measurement) to confirm that the ovaries are properly suppressed.

Step 2 - Ovarian Stimulation:

In general, ovarian stimulation begins after menstrual bleeding starts. Several similar
medications may be used to stimulate follicle development: Lupron, Gonal-F, GnRH-
antagonists are another class of medications used to prevent premature ovulation and, in
combination with an antagonist trigger, they may offer protection from severe ovarian
hyperstimulation syndrome. They tend to be used for short periods of time in the late stages of
ovarian stimulation. There are several different types of stimulation protocols. Although all
protocols more-or-less employ the same types of medications, specific protocols may help
certain types of patients to have a better response than other types. It is, however, unrealistic to
think that switching from one protocol to another will dramatically change a poorly responding
patient to a highly responding patient.

Step 3 - Monitoring of Follicle Development:

Follicuar development is monitored with a combination of vaginal ultrasound and hormone

measurements (blood tests). These tests are performed frequently during the ART cycle, and
the dose of medication might be adjusted in an effort to improve follicular development. The
amount of medication prescribed also depends upon the results of the blood tests and
ultrasound exams.

Step 4 - Final Oocyte Maturation and hCG Administration:

Human chorionic gonadotropin (hCG) is a hormonal drug that stimulates the final maturation
of the oocytes. Determining the proper day for hCG administration is critical. The time of the
injection determines when the egg retrieval will be scheduled. Some protocols using GnRH
antagonists use GnRH agonists to trigger the final maturation of oocytes.

Step 5 - Transvaginal Oocyte Retrieval:

Eggs are removed from the ovary with a needle under ultrasound guidance.

Anesthesia is provided to make this comfortable. Injury and infection are rare.

Oocyte retrieval is performed about 34-36 hours after hCG has been administered. An
anesthesiologist usually administers intravenous medications (sedatives and pain relievers) in
order to minimize the discomfort that may occur during the procedure. Most patients sleep
through the procedure. A transvaginal ultrasound probe is used to visualize the ovaries and the
egg-containing follicles within the ovaries. A long needle, which can be seen on ultrasound, can
be guided into each follicle and the contents aspirated. The aspirated material includes
follicular fluid, oocytes (eggs) and granulosa (egg-supporting) cells. The physician will collect
the oocytes and follicular fluid into a test tube and the embryologist will search the follicular
fluid and locate the oocytes using a microscope.

After the retrieval, patients recover from anesthesia where they will be observed while the
intravenous medications wear off. It is not uncommon to have some vaginal spotting and lower
abdominal discomfort for several days following this procedure. Generally, patients feel
completely recovered within 1 to 2 days.

The number of oocytes retrieved is related to the number of ovaries, their accessibility, and the
number of follicles that develop in response to stimulation. Ultrasound provides only an
approximation of the number of oocytes that one can expect to recover. On the average, 8 to 15
oocytes are retrieved per patient.

Step 6 - Semen collection:

In order to obtain sperm of optimal quality, it is important that patients follow clinic
instructions for semen collection. (Be aware that clinics may have different protocols for sperm
collection for intrauterine insemination and in vitro fertilization. Also, some programs may
have men take an antibiotic prior to collection for IVF cases.) Common instructions include:

Do not ejaculation for at least two days but not more than five days before obtaining the semen
sample.

Semen should be collected in a sterile, non-toxic plastic jar provided by the laboratory. Other
containers are not acceptable.

Most clinics prefer that the specimen be collected in the office, if possible. Private collection
rooms are usually available. Wash and dry your hands prior to collecting the specimen. Some
programs also recommended cleansing the penis followed with rinsing and drying to remove
any soap or water.

Your physician should be notified if there are any problems in collecting. An alternative
collection method could be provided, including the use of a special nontoxic condom for
collection by sexual intercourse or the use of a vibrator. Commercial condoms cannot be used
because they kill the sperm. Lubricants should not be used unless directed by a physician.

Follow the clinic instructions for labeling and transporting the specimen. It is critical to follow
these instructions carefully. Keep the jar closed tightly to prevent leakage. Let the lab know if
any of the specimen was lost or spilled and whether you have been taking any medications,
including herbal remedies.

Masturbation is the most frequent method used to produce a sperm sample on the day of oocyte
retrieval. Occasionally, intercourse using a special condom or electroejaculation is required for
successful collection. Some men are unable to ejaculate or have no sperm in their semen. In
these special cases, urologists can often obtain usable sperm from the testicle or the epididymis
utilizing a minor surgical procedure.

Some physicians recommend freezing a sample as a “back-up” if problems arise in the

production or quality of the sperm on the day of egg retrieval.

If a patient is using donor sperm, it will be thawed at the time of the egg retrieval. The donor
sperm must be collected and used in accordance with regulatory guidelines.

Step 7- Embryology Lab Procedures:

After eggs are retrieved, they are transferred to the embryology laboratory where they are kept
in conditions that support their needs and growth. The embryos are placed in small dishes or
tubes containing "culture medium," which is special fluid developed to support development of
the embryos made to resemble that found in the fallopian tube or uterus. The dishes containing
the embryos are then placed into incubators, which control the temperature and atmospheric
gasses the embryos experience.

A few hours after eggs are retrieved, sperm are placed in the culture medium with the eggs, or
individual sperm are injected into each mature egg in a technique called intracytoplasmic sperm
injection (ICSI).

The ICSI technique has been developed to treat cases of severe male factor infertility. The ICSI
technique attempts to achieve fertilization by the injection of a single sperm into the cytoplasm
(interior) of the egg. Mature eggs are freed of surrounding cells by a combination of enzyme
treatment and microdissection. Using special micromanipulation equipment (joystick-
controlled robotics), the eggs are individually injected with a single sperm. Injected eggs are
returned to the laboratory incubator and are treated as in conventional IVF-ET.

The eggs are then returned to the incubator, where they remain to develop. Periodically, over
the next few days, the dishes are inspected so the development of the embryos can be assessed.

The following day after eggs have been inseminated or injected with a single sperm (ICSI),
they are examined for signs that the process of fertilization is underway. At this stage, normal
development is evident by the still single cell having two nuclei; this stage is called a zygote.
Two days after insemination or ICSI, normal embryos have divided into about four cells. Three
days after insemination or ICSI, normally developing embryos contain about eight cells. Five
days after insemination or ICSI, normally developing embryos have developed to the blastocyst
stage, which is typified by an embryo that now has 80 or more cells, an inner fluid-filled cavity,
and a small cluster of cells called the inner cell mass.

It is important to note that since many eggs and embryos are abnormal, it is expected that not
all eggs will fertilize and not all embryos will divide at a normal rate. The chance that a
developing embryo will produce a pregnancy is related to whether its development in the lab is
normal, but this correlation is not perfect. This means that not all embryos developing at the
normal rate are in fact also genetically normal, and not all poorly developing embryos are
genetically abnormal. Nonetheless, their visual appearance is the most common and useful
guide in the selection of the best embryo(s) for transfer.

In spite of reasonable precautions, any of the following may occur in the lab that would prevent
the establishment of a pregnancy:

Fertilization of the egg(s) may fail to occur.

One or more eggs may be fertilized abnormally, resulting in an abnormal number of

chromosomes in the embryo; these abnormal embryos will not be transferred.

The fertilized eggs may degenerate before dividing into embryos, or adequate embryonic
development may fail to occur.

Bacterial contamination or a laboratory accident may result in loss or damage to some or all of
the eggs or embryos.

Laboratory equipment may fail, and/or extended power losses can occur which could lead to
the destruction of eggs, sperm and embryos.

Other unforeseen circumstances may prevent any step of the procedure to be performed or
prevent the establishment of a pregnancy.

Embryos are often transferred to the uterus three to six days after retrieval. Sometimes assisted
hatching is used on day 3 embryos, which may consist of six to eight cells. After transfer of a
day 3 embryo, the embryo must continue to develop to the blastocyst stage (a hollow ball of
about 100 cells) before implantation can occur. This development takes several days.
Immediately before implantation, the blastocyst must "'hatch" from the zona coating which
originally enveloped the egg. To assist the hatching process, a hole is made into the sac (zona
pellucida) that surrounds the developing embryos just prior to embryo transfer. This involves
dissolving part of the zona coating with an acid solution or cutting it with a fine needle or laser.
Trained personnel, using specialized micromanipulation tools, must perform this under the
microscope. There is a small risk of damage to the embryos from the procedure.

Preimplantation Genetic Diagnosis (PGD) and Preimplantation Genetic Screening (PGS) are
two techniques that can be used during in vitro fertilization (IVF) procedures to test embryos
for genetic disorders prior to their transfer to the uterus. PGD and PGS make it possible for
couples or individuals with serious inherited disorders to decrease the risk of having a child
who is affected by the same problem. Both of these techniques involve the use of the
micromanipulator to remove a cell from an embryo. This cell is then sent to a diagnostic lab to
determine the embryo’s normalcy. Acceptable embryos can then be transferred into the patient,
decreasing her odds of having an affected child. PGS has also been reported to increase the
pregnancy rates of some women with chromosomal disorders that result in either lower
implantation rates of embryos or higher miscarriage rates.
Step 8 - Embryo Transfer:

After a few days of development, the best appearing embryos are selected for transfer.

The number chosen influences the pregnancy rate and the multiple pregnancy rate.

A woman’s age and the appearance of the developing embryo have the greatest influences on
pregnancy outcome.

Embryos are placed in the uterine cavity with a thin tube. Excess embryos of sufficient quality
that are not transferred can be frozen.

The embryo transfer procedure is usually performed three to five days after oocyte retrieval.
The physician will pass a catheter gently through the cervix into the uterus and deposit the
embryos into the uterine cavity along with an extremely small amount of fluid. This procedure
usually does not require anesthesia, and the patient usually leaves the office after a brief
recovery period. SART has specific guidelines on the number of embryos to transfer – see
below. Remaining embryos can be frozen for a future frozen embryo transfer cycle.

Step 9 - Cryopreservation of Embryos:

Embryo freezing is an important part of the IVF process. Patients who have additional good
quality embryos can freeze them for future use. These embryos provide a second or even third
opportunity for pregnancy without undergoing another ovarian stimulation and retrieval.

Embryos that meet developmental criteria for appearance and rate of growth can be frozen at
any of several stages of development. There are 2 ways to freeze embryos. One is called slow
cooling. With this method embryos are placed into special freezing solutions, and using a
computer, the temperature of the embryos is slowly decreased. Frozen embryos are then stored
in liquid nitrogen (at -196°C or approximately -400°F), or sometimes, in liquid nitrogen vapor.

Another technique for freezing embryos is called vitrification. In this ultra-rapid freezing
method, embryos are placed into special solutions and then placed immediately into liquid
nitrogen. Embryos are stored as for slow cooling. The method used to freeze embryos dictates
how the embryos must be warmed or thawed. Not all embryos survive the freezing/thawing
 procedure and sometimes an embryo cannot be found after freezing.

Embryos can be transferred into patients whose cycle has been synchronized with that of the
stage of the frozen embryo. Alternatively, embryos can be transferred during a “natural” cycle.
Embryos can be stored indefinitely without a compromise in their quality.

Step 10 – Hormonal Support of the Uterine Lining (Progesterone Supplements):

Successful attachment of embryo(s) to the uterine lining depends on adequate hormonal

support.

Progesterone, given by the intramuscular or vaginal route, is routinely given for this purpose.

Progesterone supplementation can occur using vaginal, oral or injectable progestreone, and in
some cases, a combination of methods. Supplementation usually begins on the day of or the day
after oocyte retrieval. Usually, cells in the follicle will produce progesterone following
aspiration. During oocyte retrieval, some of these cells may be removed along with the oocyte.
Supplemental progesterone helps prepare the uterine lining for implantation.

This daily medication will continue until your pregnancy test. If the test is positive, you may be
advised to continue to take progesterone for several more weeks.

Step 11 - Pregnancy Test:

A pregnancy test is necessary regardless of vaginal spotting or bleeding. It determines if

pregnancy has occurred and is done 9-12 days after the embryo transfer. This test is usually
repeated 2 days later if positive. If the test is negative, the doctor may instruct you to stop the
progesterone.

 Side effects of IVF:

Although you may need to take it easy after the procedure, most women can resume normal
activities the following day.
Some side effects after IVF may include:
 Passing a small amount of fluid (may be clear or blood-tinged) after the procedure
 Mild cramping
 Mild bloating
 Constipation
 Breast tenderness

Some side effects of fertility medications may include:

 Headaches
 Mood swings
 Abdominal pain
 Hot flashes
 Abdominal bloating
 RARE: Ovarian hyper-stimulation syndrome (OHSS)
Consult the doctor immediately in case of following complaints:
 Heavy vaginal bleeding
 Pelvic pain
 Blood in the urine
 A fever over 100.5 °F (38 °C)

 Risks associated with IVF:

As with most medical procedures, there are potential risks. More severe symptoms, typically
from OHSS, include the following:

 Nausea or vomiting
 Decreased urinary frequency
 Shortness of breath
 Faintness
 Severe stomach pains and bloating
 Ten-pound weight gain within three to five days

 Additional risks of IVF include the following:

 Egg retrieval carries risks of bleeding, infection, and damage to the bowel or bladder.

 The chance of a multiples pregnancy is increased with the use of fertility treatment. There
are additional risks and concerns related to multiples during pregnancy including the
increased risk of premature delivery and low birth weight.

 Though the rates of miscarriage are similar to unassisted conception, the risk does
increase with maternal age.

 The risk of ectopic pregnancy with IVF is 2-5%. An ectopic pregnancy is when a
fertilized egg implants anywhere outside the uterus and is not viable.

 Assisted reproductive technology (ART) involves a significant physical, financial, and

emotional commitment on the part of a couple. Psychological stress and emotional
problems are common, especially if in vitro fertilization (IVF) is unsuccessful.

C) GIFT (GAMETE INTRA FALLOPIAN TRANSFER):

 Introduction:

GIFT is an assisted reproductive procedure which involves removing a woman’s eggs, mixing
30
them with sperm, and immediately placing them into a fallopian tube.
infertility-specialis

 How is GIFT performed?

GIFT is an assisted reproductive procedure that involves the following:

1. Patients must first have an x-ray to determine the presence of at least one healthy
fallopian tube. The doctor will also use a laparoscope to ensure that there is not any scar
tissue on the outside of the fallopian tube.
2. Using a laparoscope, eggs are then retrieved from the ovaries.
 3. The male provides a sperm sample the same day that the eggs are retrieved.
4. The eggs are then mixed with the sperm in a catheter.
5. The egg and sperm mixture is inserted into the fallopian tubes with a catheter.
6. The woman is then provided with medication to build up the uterine lining to support
implantation of a fertilized egg.

If any additional eggs are left over, you may use them for IVF and save any viable embryos to
use in the future.

 Who can be treated with GIFT?

GIFT has been used with the following patients:

 Couples with unexplainable infertility

 Couples who have not had success with IVF
 Couples who have a religious or moral reluctance to use IVF
 Women who have at least one healthy fallopian tube
 Couples in which the husband has a low sperm count or other problems with his sperm

However, according to the National Institute for Health and Care Excellence, “There is
insufficient evidence to recommend the use of gamete intrafallopian transfer or zygote
intrafallopian transfer in preference to IVF in couples with unexplained fertility problems or
male factor fertility problems.”

 What are the differences between GIFT and in vitro fertilization (IVF)?

 With IVF, the eggs are fertilized in a laboratory rather than in the fallopian tubes as with
GIFT.
 IVF can be used with couples in which the female does not have fallopian tubes or has
blocked fallopian tubes.
 IVF allows for fertilization confirmation and assessment of embryo quality.
 GIFT does not involve fertilization outside of the body, so couples do not have to deal
with the ethical concerns with choosing which embryos to transfer.

 Advantages and Disadvantages:

 The good news is that GIFT does not require to be hospitalized. After the procedure,
patients typically stay in recovery for about eight hours.
 Doctors cannot visibly confirm fertilization or determine embryo quality with GIFT.
 GIFT cannot be used in patients who have damaged or blocked fallopian tubes.

D) ZIFT (ZYGOTE INTRA FALLOPIAN TRANSFER):

Gamete intra fallopian transfer (GIFT) uses multiple eggs collected from the ovaries. The eggs
are placed into a thin flexible tube (catheter) along with the sperm to be used. The gametes (both
eggs and sperm) are then injected into the fallopian tubes using a surgical procedure called
laparoscopy. The doctor will use general anesthesia.

Zygote intra fallopian transfer (ZIFT) combines in vitro fertilization (IVF) and GIFT. Eggs are
stimulated and collected using IVF methods. Then the eggs are mixed with sperm in the lab.
Fertilized eggs (zygotes) are then laparoscopically returned to the fallopian tubes where they will be
carried into the uterus. The goal is for the zygote to implant in the uterus and develop into a fetus.

Pronuclear stage tubal transfer (PROST), similar to ZIFT, uses in vitro fertilization. But it
transfers the fertilized egg to the fallopian tube before cell division occurs.

These procedures have higher costs and risks related to laparoscopy. And they do not provide as
much useful information about embryo development as IVF does. For these reasons, these
procedures are rarely used.

 What to Expect After Treatment

Overall, having the assisted reproductive technology (ART)-related injections, monitoring, and
procedures is emotionally and physically demanding. Superovulation with hormones requires
regular blood tests and frequent monitoring by your doctor. It also requires daily shots. (Some of the
shots are quite painful.) You can expect to return to daily activities after a routine laparoscopic
procedure in less than a week.

 Why It Is Done

GIFT may be appropriate when:

 A couple has religious objections to fertilization taking place outside the body.
 A couple with unexplained infertility only has insurance benefits for GIFT.

For GIFT or ZIFT, a woman must have at least one functional fallopian tube.

 How Well It Works

ZIFT and GIFT are used rarely enough that specific success rates aren't nationally available. But
what is known about assisted reproductive technology (ART) includes the use of ZIFT and GIFT.

 Risks

Risks from laparoscopy (which may be used to collect eggs) include pelvic infection, puncture of
internal organs, and side effects from general anesthesia.

 What Types of Infertility Can GIFT and ZIFT Treat?

GIFT and ZIFT can be used to treat many types of infertility, except in cases where there is damage
to or abnormalities of the fallopian tubes. These techniques can also be used in cases of mild male
infertility, as long as the sperm is capable of fertilizing an egg.

If the woman is not capable of producing eggs that can be used in GIFT, but her partner's sperm is
capable of fertilization, they might consider getting eggs from a donor. One reason for using an egg
donor is age. Women over age 35 are less likely to have viable eggs and more likely to have
children with birth defects than younger women. A woman with premature ovarian failure, a
condition in which menopause has begun early, might also consider a donor if she wants to carry a
child. Most egg donation is anonymous, but some couples prefer to know their egg donor and take
legal steps to contract for the donation of the eggs.
  GIFT: What You Can Expect

The initial process for GIFT is the same as it would be for in vitro fertilization: treatment with
injectable hormones to start superovulation, followed by further injections of a medication that
ripens the developing eggs. The facility where the procedure will be done will provide you with
special instructions to prepare you for the procedure.

The eggs and sperm are collected just as they would be in an IVF procedure, but after that, the two
techniques differ. In IVF, the embryo is placed into the uterus at 3-5 days with a catheter inserted
into the vagina in a quick and simple procedure. In GIFT, an incision has to be made in the
abdomen and the eggs and sperm are immediately placed in the fallopian tubes using a laparoscope,
a small telescope-like instrument. A laparoscopy requires general anesthesia, although it can still
usually be performed as an outpatient procedure.

If all goes well, once the eggs are in the fallopian tubes, at least one will become fertilized by the
sperm and move on to the uterus, where it will mature. But, because the eggs and sperm are placed
into the fallopian tubes before conception, there's no way to know if fertilization has taken place.
Typically, more eggs are used in GIFT to ensure pregnancy, which also increases the risk of
multiple births.

The American Society of Reproductive Medicine recommends that GIFT only be performed in a
facility that is prepared to carry out IVF as an alternative or in addition to GIFT.

 ZIFT: What You Can Expect

This procedure is similar to GIFT in that the assisted reproduction is done in the fallopian tubes. The
difference is that with ZIFT the sperm and egg are mixed together in the laboratory, and given time
to fertilize before being placed in the fallopian tubes. In this sense, ZIFT is closer to traditional in
vitro fertilization. ZIFT, like GIFT, requires treatment with hormones, and the procedure is
performed by laparoscopy. Because ZIFT allows for fertilization to be confirmed before the eggs
are inserted into the fallopian tubes, fewer eggs are usually used, lowering the risk of multiple
pregnancy.

 Success Rates:

The Centers for Disease Control groups together all procedures that constitute assisted reproduction
technology (ART), including in vitro fertilization, GIFT, and ZIFT. So there's no way to know the
success rates of each technique. Combined, however, the most recent report, from 2011, found:

 Successful pregnancy was achieved in 36% of all cycles.

 About 64% of the cycles carried out did not produce a pregnancy.
 Less than 1% of all cycles resulted in an ectopic pregnancy (the embryo implants outside of
the uterus).
 About 30% of these pregnancies involved multiple fetuses.
 About 82% of pregnancies resulted in a live birth.
 About 18% of pregnancies resulted in miscarriage, induced abortion, or a stillbirth.

E) INTRA CYTOPLASMIC SPERM INJECTION:

Introduction:
The ICSI technique has been developed to treat cases of severe male factor infertility. The ICSI
technique attempts to achieve fertilization by the injection of a single sperm into the cytoplasm
(interior) of the egg. Mature eggs are freed of surrounding cells by a combination of enzyme
treatment and micro dissection. Using special micromanipulation equipment (joystick-controlled
robotics), the eggs are individually injected with a single sperm. Injected eggs are returned to the
laboratory incubator and are treated as in conventional IVF-ET.
Indications:
In cases of severe male factor infertility
Benefit:
The benefit of ICSI is that it provides a way to treat extreme cases of male factor infertility
which otherwise would remain untreatable. Experience shows that fertilization in vitro requires a
minimum number of motile, normal-shaped sperm. The chance for fertilization in vitro becomes
very low when this minimum number of sperm is not available. Theoretically, only a few sperm
are necessary to perform ICSI. The alternatives to ICSI for treatment of severe male factor
infertility are limited. One option is donor sperm. Use of donor sperm normalizes the success of
conventional IVF-ET in couples with severe male factor infertility. In cases where male factor is
the only diagnosis, pregnancies with donor sperm can be achieved through timed insemination, a
treatment far less expensive and complicated than IVF-ET.
Side effects:
The potential consequences of injecting a normal appearing sperm, which is in fact genetically
abnormal, include the development of a genetically abnormal embryo.
The incidence of congenital abnormalities (birth defects) following ICSI appears to be no higher
than that of the general ART population. There has been some evidence that ICSI may increase
the probability of abnormal sex chromosomes or imprinting disorders.
Recent evidence suggests that some forms of severe male factor infertility are genetic and may
be passed on to male offspring through the ICSI procedure.
In addition, within the normal human population, a certain percentage (approximately 4%) of
children are born with physical or mental defects (congenital abnormalities) and the occurrence
of such defects is beyond the control of physicians.
F) ASSISTED HATCHING:
Embryos are often transferred to the uterus three to six days after retrieval. Sometimes assisted
hatching is used on day 3 embryos, which may consist of six to eight cells. After transfer of a
day 3 embryo, the embryo must continue to develop to the blastocyst stage (a hollow ball of
about 100 cells) before implantation can occur. This development takes several days.
Immediately before implantation, the blastocyst must "'hatch" from the zona coating which
originally enveloped the egg. To assist the hatching process, a hole is made into the sac (zona
pellucida) that surrounds the developing embryos just prior to embryo transfer. This involves
dissolving part of the zona coating with an acid solution or cutting it with a fine needle or laser.
Trained personnel, using specialized micromanipulation tools, must perform this under the
microscope. There is a small risk of damage to the embryos from the procedure. Fragment
removal may occur at this time.
G) GESTATIONAL CARRIERS:
In some instances, a couple may require the assistance of a gestational carrier to achieve a
successful pregnancy. Gestational carriers differ from true surrogates in that they have no genetic
link to the baby they will carry. The commissioning couple (future parents) will provide the
embryo through IVF. As with egg donation, the best statistics occur when the embryos are
transferred during a fresh cycle, requiring that the woman and her gestational surrogate be
synchronized as with egg donation. Some states have laws that address surrogacy and you should
seek legal advice about this. For example, Florida law requires that a woman have a medical
indication for a gestational carrier to be utilized. The most common indications include a woman
who has congenital absence of the uterus, prior surgery to remove her uterus, severe scarring of
the uterine cavity, or a medical history that precludes pregnancy. In addition to meeting the
medical requirement, a separate legal contract is required before treatment can begin. In Texas,
in order for the carrier not to be identified as the legal mother, the surrogacy arrangement must
be reviewed and approved by a judge before treatment begins. Programs may or may not have
ready access to a group of potential gestational carriers. Generally, however, they can provide
resources for investigation. Once a gestational carrier has been identified and the medical,
psychological, and legal prerequisites completed, treatment can proceed. Because gestational
carriers will receive an embryo from a donor couple, the donors (future parents) must be treated
as egg and sperm donors and follow all of the requirements of the FDA for screening and testing
as indicated by the FDA.
H) FREEZING OF EMBRYOS AND FROZEN EMBRYO TRANSFER:
Embryo freezing is an important part of successful ART programs. Freezing affords patients
several advantages. Couples can freeze embryos in excess of the ones that are transferred during
an IVF cycle. These embryos provide a second or even third opportunity for pregnancy without
undergoing another ovarian stimulation and retrieval. Freezing can also increase the safety of an
IVF cycle and help decrease the probability of multiples, as fewer embryos can be transferred in
the fresh cycle when frozen embryos can be relied upon for subsequent pregnancy attempts.
Embryos that meet developmental criteria for appearance and rate of growth can be frozen at any
of several stages of development. The most common method of freezing is called slow cooling.
With this method embryos are placed into special freezing solutions, and using a computer, the
temperature of the embryos is slowly decreased. Frozen embryos are then stored in liquid
nitrogen (at -196°C or approximately -400°F), or sometimes, in liquid nitrogen vapor.
Another technique for freezing embryos is called vitrification. In this ultrarapid freezing method,
embryos are placed into special solutions and then placed immediately into liquid nitrogen.
Embryos are stored as for slow cooling. The method used to freeze embryos dictates how the
embryos must be warmed or thawed. Not all embryos survive the freezing/thawing procedure
and sometimes an embryo cannot be found after freezing.
Embryos can be transferred into patients whose cycle has been synchronized with that of the
stage of the frozen embryo. This is similar to the method used for recipients of donor eggs where
a GnRH agonist, estrogen and progesterone are used to synchronize the cycle. Alternatively,
embryos can be transferred during a “natural” cycle. Embryos can be stored indefinitely in liquid
nitrogen without a loss of viability.
I) DONOR EGGS:
One of the most important factors in predicting the success of IVF-ET is the age of the female
partner. For patients under 30, success rates of 30-50 percent per egg retrieval can legitimately
be expected; for patients over 40, realistic success rates are only 5 percent to at most 20 percent.
Eggs from younger women possess greater fertility potential, and this potential is utilized in
donor egg treatment. In this situation, eggs from another woman (the donor) are fertilized with
the patient’s (the recipient) husband’s sperm, and the resultant embryos are placed in the
recipient’s uterus. Follicles are stimulated and eggs are retrieved from the donor using routine
IVF-ET techniques. The donor may be known to and recruited by the recipient (non-anonymous
or known donation), or instead may be unknown to the recipient, having been recruited by a
second party (anonymous donation). Anonymous egg donation usually occurs when a young,
fertile woman donates her eggs to a recipient(s) during a particular cycle. The egg donor is
usually reimbursed for her time and effort. Pregnancy rates using young donors are high,
comparable to those achieved in women of similar age using their own eggs.
Candidates for Donor Egg
There are four main indications for treatment using donor eggs: 1) Ovarian failure. This can be
due to a wide variety of different causes, including radiation, chemotherapy, surgical removal of
the ovaries and a variety of disease states which cause or are associated with ovarian failure; 2)
Women who carry a serious genetic disease who wish to diminish the chance that the disease
will be passed on to their offspring; 3) Women whose age is sufficiently advanced so that their
fertility potential is impaired significantly; and 4) Women who have had poor quality embryos
during prior IVF cycles.
Laboratory Testing, Genetic Screening, and Psychological Assessment
A short time before initiating a treatment cycle, the egg donor undergoes a very thorough battery
of tests for sexually transmitted diseases. Donors are screened for sexually transmitted diseases
to minimize the chances that such a disease will be passed from the donor to the recipient (and
possible fetus) by the egg donation process. Despite these thorough precautions, a very small risk
of transmission of disease from donor to recipient remains. All donors must meet strict donor
criteria as determined by the FDA. This includes proscribed tests for diseases, disease screening
through a questionnaire, and a physical exam.
Donors have a very thorough evaluation of their medical, psychological and family history. The
donor is required to fill out a multi-page form detailing her family history. The IVF personnel
review this form and other aspects of the donor’s genetic and medical history prior to acceptance
of the donor into the program. Even with this intensive screening, there remains a small risk that
a baby resulting from the egg donation process will suffer from a genetic disease. Overall, a baby
conceived through egg donation will have the same risk of birth defect, trivial or catastrophic,
genetic or non-genetic, as the human population as a whole, namely 3-5 percent. The donor and
recipient may also receive psychological screening and counseling with a mental health
professional to assess their motivations and acceptance of the process. This evaluation serves as
an additional opportunity to learn about family and medical history.
Matching Donor and Recipient
One requirement of most anonymous donation programs is that anonymity be maintained. In
order to accomplish this, the amount of information given a recipient about the donor is limited.
This information usually includes the donor’s height and weight, hair color, eye color, race,
blood type, age, duration of formal education and family medical history.
Treatment of the Egg Donor
In general, stimulation of the egg donor’s cycle is similar to that of a woman using her own eggs
for in vitro fertilization-embryo transfer. Birth control pills are often used in the cycle preceding
stimulation. Late in the cycle which precedes ovarian stimulation, the donor may be started on
daily treatment with one of two drugs, Lupron® or Synarel®, usually the former. Daily
injections of Lupron® will continue until oocyte retrieval. Alternatively, a GnRH antagonist
such as Antagon® or Cetrotide® may be given after stimulation has begun to prevent ovulation.
After the donor’s period has started, daily intramuscular injections of a pharmaceutical
gonadotropin preparation, such as FSH and HMG, will be added to the daily Lupron® injections.
Various brands of these hormones can be used. Generally, the donor will receive daily
gonadotropin injections for a total of seven to 12 days. During the time that the donor is
receiving the gonadotropin injections, she will have frequent vaginal ultrasound examinations
and blood drawing for determination of estradiol (E2) level. When ultrasound and blood testing
indicate that development of the follicles (follicles are the ovarian structures that contain the
eggs) is optimum, the donor receives an injection of a different pharmaceutical medication called
human chorionic gonadotropin (hCG). Two days (35-36 hours) after hCG injection, egg retrieval
is performed. A sperm specimen is collected from the recipient’s partner on the day of the
retrieval because the eggs are inseminated on this day. Transfer of fertilized eggs (embryos) to
the recipient’s uterus is generally performed three to five days after egg retrieval.
Treatment Regimen for Recipients
The recipient’s cycle must be manipulated to synchronize her with the donor. A combination of
two or three hormonal medications is used to modify the recipient’s cycle.
Recipients who have regular menstrual cycles and bleeding on their own will be given a
medication which suppresses their own cycle. Sometimes oral contraceptives will be used. A
short time after her period starts, the recipient will begin taking estrogen. Estrogen comes in
several forms including patches, oral tablets and vaginal suppositories. The recipient will take
estrogen while waiting for the donor’s cycle to come into synchrony with hers. When the donor’s
cycle has “caught up” with the recipient’s, a simulated (artificial) menstrual cycle will be created
in the recipient with the hormonal medications. To do this, the recipient takes an increased dose
of estrogen as the donor stimulates. Sometimes blood tests and/or ultrasounds are done to ensure
an appropriate response. On the morning after egg retrieval, progesterone treatment is begun.
Daily progesterone can be in the form of an intramuscular injection or a suppository. The
recipient will continue taking estrogen and progesterone at least until the day her pregnancy test
is performed. Fresh embryo transfer is usually done 3-5 days after egg retrieval. A sensitive
blood pregnancy test will be performed 10 to 14 days after embryo transfer. If the recipient is
pregnant, estrogen and progesterone treatment may be continued through about the 12th week of
pregnancy.
 Summary:
I have discussed about assisted reproductive techniques. There are various ARTs which are used
for the treatment of infertility. I have explained about different ARTs like IUI, IVF, GIFT, ZIFT,
Intra cytoplasmic sperm injection, assisted hatching, surrogacy & freezing of eggs & use of
frozen embryo with its meaning, procedure, advantages, disadvantages & risks as well as success
rates.
 Conclusion:
Infertility is the major problem identified in a worldwide. There are various assisted reproductive
techniques which helps the couple to overcome the problem & stress of infertility. IUI & IVF is
the common ARTs which are in great demand in a treatment modalities of infertility. There are
various factors which affect on that & decide the success rate of it.
 Bibliography:

Books:
 1. D.C Dutta. “TEXTBOOK OF GYNECLOGY", 6th edi; 2001, New central book agency
publication, Kolkata, Pp-251-255.
2. Kamini Rao. “TEXTBOOK OF MIDWIFERY & OBSTETRICS FOR NURSES”; 1st edi;
2011, Elsevier publication, New Delhi, Pp-281.
3. Myles, “TEXTBOOK FOR MIDWIVES”, 15th edi: 2009, Elsevier publication, China,
pp-182-186.

Web references:

1. In vitro fertilization: overview Mayo clinic, available from-

[Link]
2. Intra uterine insemination: Uses, risks, benefits, available from-
[Link]
3. GIFT and ZIFT: treatment for infertility, available from-
[Link]
4. GIFT: fertility treatment, available from- [Link]
treatment-gamete-intrafallopian-transfer-gift_4095.bc
5. Surrogacy-How does surrogacy work, available from- [Link]
[Link]#6
6. Intracytoplasmic sperm injection for fertility, available from-
[Link]
for-infertility
7. Fertility treatment: ICSI, available from- [Link]
treatment-intracytoplasmic-sperm-injection-icsi

Journals:

1. Varada Jayant Madge, Ethical Issues in Assisted Reproductive Technologies, Social

medicine, vol-3, issue-3, march 2012,pp-162-170, available from-
[Link]
2. Farnaz Soharabvand, Knowledge and attitudes of infertile couples about assisted
reproductive technology, International journal of reproductive biomedicine, vol- 3,
issue-2, pp-90-94, January 2005, available from-
[Link]
nfertile_couples_about_assisted_reproductive_technology
3. Kerry D, A study: fertility-awareness knowledge, attitudes, and practices of women
seeking fertility assistance, Journal of advanced nursing, vol-69, issue-5, pp-985-
1220, may 2013, available from-
[Link]
4. Paul C, Effect of acupuncture on improvement of IVF, Westlake complementary
medicine, available from-
[Link]