PCOS
INTRODUCTION AND BACKGROUND
Polycystic Ovary Syndrome (PCOS) is a prevalent hormonal condition affecting women of
reproductive age. The Rotterdam criteria, which is widely used for diagnosis, define PCOS as the
presence of two or three of the following: oligo-anovulation, hyperandrogenism, and polycystic
ovaries [1]. Its prevalence varies depending on the diagnostic criteria used, with estimates ranging
from 6% to 20% globally [2,3]. PCOS presents with a wide range of symptoms that can
significantly impact an individual's quality of life. Some of these symptoms include menstrual
irregularities, hirsutism (excessive hair growth on the face or body), acne, infertility, and
metabolic disturbances [4].
The underlying pathophysiology of PCOS is complex and multifactorial, involving genetic
predisposition, insulin resistance, and chronic low-grade inflammation [4].
frequently coexists with obesity and metabolic syndrome, a cluster of interconnected metabolic
abnormalities that collectively increase the risk of cardiovascular issues. Excess adiposity
contributes to insulin resistance, a key underlying mechanism in the pathogenesis of PCOS,
thereby heightening the risk of developing type 2 diabetes and other metabolic complications.
Emphasizing early intervention, personalized management approaches, and comprehensive
cardiovascular risk assessment is essential in promoting optimal health outcomes and improving
the quality of life for individuals living with PCOS [4][5].
Beyond medical interventions, providing holistic support is vital in addressing the psychosocial
aspects of PCOS. Patients with PCOS often face anxiety, depression, and negative body image
issues, with symptoms such as infertility and obesity leading to social stigma. This stigma can
impact their relationships, family dynamics, and community involvement. Increasing awareness
about PCOS can help create a more inclusive and supportive environment for those affected. Once
a diagnosis is made, care plans should be tailored to the individual needs of each patient.
Treatment strategies may include lifestyle modifications, pharmacotherapy, and, in some cases,
surgical interventions. Personalized management approaches that address hormonal imbalances,
manage symptoms, and mitigate long-term health risks can significantly enhance patients' quality
of life.
CHALLENGES ASSOCIATED WITH PCOS
PCOS has emerged as a prevalent cause of female infertility due to anovulation, increasingly
becoming a recognized condition in public discourse. However, managing this clinical entity
presents significant challenges for patients, their families, and healthcare providers [6].
DIAGNOSTIC CHALLENGES
The diagnosis of this condition is established using the Rotterdam criteria, which require the
presence of at least two out of the following three criteria: biochemical and/or clinical features of
hyperandrogenism, oligo- or anovulation, and polycystic morphology on ultrasound, while
excluding other endocrine disorders [7]. A confirmatory diagnosis involves a comprehensive
clinical history, physical examination findings, and a series of laboratory investigations.
Another study done in Canada points out the challenge in the variation in clinical presentation.
Each symptom is treated differently, which can delay diagnosis being made or follow-up care
received [9][10].
PCOS is a diagnosis of exclusion, necessitating the elimination of other conditions with similar
presentations before a definitive diagnosis can be made. This diagnostic challenge is particularly
pronounced in adolescents, where there is a significant overlap between the features of PCOS and
the normal physiological changes of puberty, complicating the diagnostic process in this age group
[8]. A study conducted by ____ highlights the difficulties posed by the variability in clinical
presentation of PCOS. Each symptom often requires individualized treatment, which can delay
both the diagnosis and subsequent follow-up care. The absence of multidisciplinary care in certain
facilities, coupled with a scarcity of information provided by healthcare professionals and delays
or lack of referrals to specialists who can offer diagnostic and therapeutic care, exacerbates these
challenges. These diagnostic delays hinder the implementation of preventive and comprehensive
treatment for presenting symptoms and associated conditions, further negatively impacting overall
quality of life and morbidity [7].
PSYCHOLOGICAL IMPACT.
Diagnostic delays and the complexity of the diagnostic process tends to leave the patient (and their
family) emotionally and financially drained. This creates doubts in their minds concerning the
validity, trustworthiness of the healthcare provider and the healthcare system in its entirety [7]
[10]. This could also create a ripple effect if more people experiencing similar symptoms are
dissuaded from seeking healthcare, as it could be tagged as “a waste of efforts and resources” [7].
Upon diagnosis, there could be a cocktail of possible emotions/feelings, shock, relief, worry,
resilience and even indifference. There are also usually concerns or fear about possible
complications, like infertility and comorbidities, like type 2 DM [6]. A qualitative study done by
Guanpeng Wang shows that women with PCOS generally experience
anxiety, depression, low self-esteem, body image dissatisfaction, eating disorders amongst others.
Also, especially for those of the lower socio-economic cadre, treatment for reproductive issues can
add to the financial burden [30]. Another qualitative study done in Iran by Amiri et al shows that
some women with PCOS feel robbed of their femininity and attractiveness, hence the PCOS tag,
“thief of womanhood” [31]. This is mainly attributed to the features of hyperandrogenism (acne,
hirsutism, male pattern alopecia), and obesity [31].
Patients with PCOS have been shown to have a higher risk of developing anxiety, depression, low
self-esteem, body image dissatisfaction, eating disorders amongst others [6].
FERTILITY ISSUES
Unfortunately, many young people do not receive a diagnosis of PCOS until they start
experiencing infertility [7]. The hormonal imbalances of elevated levels of luteinizing hormone,
follicle stimulating hormone, androgens and insulin (and insulin resistance) contribute to the
menstrual irregularities, anovulation and infertility seen in this condition [32][33]. Even when
ovulation is present, there tends to be issues with oocyte quality and/or compromised endometrial
quality [33]. Women living with PCOS who eventually become pregnant are at a higher risk of
having spontaneous pregnancy losses, gestational diabetes, preterm delivery, small for gestational
age babies [34].
IMPACTS OF PCOS ON WOMEN'S HEALTH
Polycystic Ovary Syndrome (PCOS) is a common endocrine illness that affects women of
reproductive age, it is characterized by hormonal imbalances and various symptoms that extend
beyond the reproductive system. Despite being a common illness, its effects on the health of
women are frequently underappreciated. Women who have PCOS are at higher risk for glucose
intolerance and type 2 diabetes mellitus; hepatic steatosis and metabolic syndrome; hypertension,
dyslipidemia, vascular thrombosis, cerebrovascular accidents, and possibly cardiovascular events;
subfertility and obstetric complications; endometrial atypia or carcinoma, and possibly ovarian
malignancy; and mood and psychosexual disorders[11]. The adverse clinical effects related to
PCOS have been identified as significant contributors to the decline in quality of life in affected
women[12].
HORMONAL IMBALANCE
Hormonal imbalance is a defining feature for many women with polycystic ovarian syndrome
(PCOS)[13]. Hormones like gonadotrophin-releasing hormone (GnRH), insulin, the
leutinizing/follicle-stimulating hormone (LH/FSH) ratio, androgens, estrogens, growth hormones
(GH), cortisol, parathyroid hormone (PTH) and calcitonin are disturbed in women who suffer
from PCOS[13]. The hormonal abnormalities in PCOS women are a reflection of the disruption of
the normal gonadotropin-ovarian axis[14]. There is an elevated release frequency of GnRH in
women with PCOS[15]. Higher frequencies of GnRH release result in higher levels of LH and
lower levels of FSH. Additionally, in certain individuals, the cells responsible for making LH
respond strongly to GnRH, which causes an excess of LH to be produced. The release of high
levels of LH and low levels of FSH prevents the development of ovarian follicles, which prevents
the generation of estrogen[15].
A study on hormonal Imbalance in Polycystic Ovarian Syndrome (PCOS) in Teaching Hospitals
in Ekiti State, Nigeria showed a significant increase in the level of Luteinizing hormone in PCOS
subjects compared with the control subjects and a significant decrease in the concentration of FSH
in the PCOS subjects compared with the control [14]. Another study by Khmil et al showed
elevated levels of luteinizing hormone compared to the control group and at the same time, the
concentration of FSH decreased significantly by 35.9% [16].
Furthermore, Oyebanji et al in a study carried out in Ekiti State, Nigeria found a significant
increase (p < 0.05) in the testosterone concentration of PCOS group when compared with Non-
PCOS control group, higher concentration of Insulin in PCOS patient compared with the control
subject, significant decrease (p < 0.05) in the progesterone level of PCOS subjects and a
significant increase in concentration of Estradiol in PCOS subjects in comparison with the control
subject[14]. Research by Khmil et al also revealed that levels of anti-Müllerian hormone,
estradiol, and testosterone were elevated in patients with PCOS compared to the control
group[16].
METABOLIC SYNDROME
Metabolic syndrome is characterized by a collection of related metabolic disorders, such as insulin
resistance, central obesity, dyslipidemia, and hypertension. There is a great deal of overlap
between the metabolic syndrome and polycystic ovarian syndrome (PCOS). PCOS patients have a
metabolic syndrome prevalence of 43–47%, which is two times higher than the general
population's rate for women with the same conditions[17].
A study done by Kandaraki et al found that compared to their age-matched peers in the general
population, women with PCOS tend to have a much greater prevalence of metabolic syndrome
(MS). It is not just Caucasian women with PCOS that experience the interplay between PCOS and
MS. Although the stated prevalence rates of MS vary between ethnic/racial regions, a high MS
prevalence has been found in Brazilian, Chinese, Korean, Indian, and multiracial PCOS
populations, at least in overweight/obese patients[18].
The most common elements of the metabolic syndrome in PCOS are low blood HDL cholesterol
and a high body mass index. Insulin resistance is probably the pathogenic connection between
metabolic syndrome and PCOS. Consequently, compared to PCOS without the metabolic
syndrome, the existence of the metabolic syndrome in PCOS indicates a higher level of insulin
resistance. Common metabolic abnormalities found in PCOS include obesity, atherogenic
dyslipidemia, hypertension, impaired glucose tolerance/impaired fasting glucose, and vascular
abnormalities[17].
CARDIOVASCULAR DISEASE
Cardiovascular problems are more likely to occur in women with PCOS as a result of the
hormonal and metabolic abnormalities linked to the condition.
Numerous established cardiovascular disease (CVD) risk factors are highly prevalent in women
with PCOS. Among these are modifiable risk factors which include obesity, diabetes,
hypertension, and dyslipidemia. Cardiovascular disease (CVD) is not exclusive to men. Actually,
cardiovascular disease (CVD) claims the lives of one in three women and accounts for more
deaths among women than the next five leading causes of mortality[19]. Comparing women with
PCOS to age-matched controls, there is enough evidence to support the presence of subclinical
atherosclerosis in these women[19].
A metanalysis of cardiovascular disease risk markers in women with polycystic ovary syndrome
showed that women with PCOS have increased serum concentrations of CVD risk markers
compared with controls[20].
LONG TERM HEALTH COMPLICATIONS
A higher chance of acquiring many medical disorders, including dermatologic conditions, non-
alcoholic fatty liver disease, sleep apnea, and endometrial cancer, has been connected to PCOS.
Major comorbidities for women with PCOS include metabolic, psychosocial, and reproductive
issues. However, patients experience problems with obstructive sleep apnea (OSA), dermatology,
and endometrial cancer[21].
Dermatologic- Acne, androgenic alopecia, and hirsutism are the most prevalent dermatological
conditions linked to high androgen[21].
Cancer- Women with PCOS often have unopposed estrogen exposure linked to chronic
hyperandrogenism with aromatization, chronic anovulation, hyperinsulinemia, and obesity, which
are risk factors for cancer. For women with PCOS, the risk of endometrial cancer is increased,
particularly in the event of persistent amenorrhea and irregular vaginal bleeding[21].
OBSTRUCTIVE SLEEP APNEA (OSA)
OSA is linked to upper airway instability that occurs during sleep, which can cause snoring and
repeated upper airway blockages. In OSA, there are changes in oxygen saturation, blood pressure,
sympathetic activity, intrathoracic pressure, and heart rate. Many nocturnal awakenings disturb the
architecture of sleep. Hypertension and cardiovascular illness are linked to OSA[21].
Meta-analysis and systematic reviews revealed that obese women with PCOS had a greater
prevalence of obstructive sleep apnea[21].
TREATMENT PERSPECTIVE FOR PCOS
Polycystic Ovary Syndrome (PCOS) is a complex and multifaceted condition with a variety of
dermatological, reproductive, metabolic, and psychological features, no single therapeutic
intervention can combat the entire spectrum of disorders associated with the condition[22][23].
Therapy is often multi-factorial, combining lifestyle interventions, pharmacological treatment,
reproductive interventions, and potentially surgery[24].
LIFESTYLE INTERVENTIONS
Based on the available evidence, the 2023 international evidence-based guideline for the
assessment and management of PCOS underscores the importance of lifestyle modifications,
highlighting it as a core focus in PCOS management[22]. Although PCOS also occurs in lean
women, studies have found obesity to be more prevalent in women with PCOS than in women
without PCOS[24]. As obese women with PCOS are at an increased risk of metabolic
abnormalities and cardiovascular conditions than their non-PCOS counterparts, a therapeutic
approach targeting weight control (maintaining weight, preventing weight gain, and/or modest
weight loss) is the cornerstone in the treatment of PCOS[23]. Even a small reduction in body
weight (of at least 5%), particularly in overweight or obese women with PCOS can improve
ovulatory function[23] [24]. Lifestyle modification interventions including exercise alone or diet
combined with exercise and behavioral strategies) are therefore recommended as first-line therapy
for all women with PCOS, for improving metabolic health including central adiposity and lipid
profile[22]. Lifestyle interventions were stated to improve ovulation in 40 -50% of women with
PCOS, 30 – 40% of whom were able to achieve a spontaneous pregnancy[24].
DIET
The role of certain dietary modifications has been investigated in the context of PCOS.
A meta-analysis of eight RCTs by Zhang et all in 2019 indicated the beneficial effects of a low
carbohydrate diet in the management of PCOS. According to the study, limiting intake of
carbohydrates to less than 45% of the total daily calorie intake can yield a significant decrease in
BMI, insulin resistance, and blood lipids in women with PCOS[25]. Meanwhile, a meta-analysis
of 10 RCT by Gu et all in 2022 reported that a high-protein diet led to weight loss compared to a
standard protein diet with no significant difference between a vegan diet and a caloric diet, and
between a low-glycemic-index diet and a hypocaloric healthy eating diet[26].
EXERCISE
Exercise plays a crucial role in the management of PCOS.
In line with a 2011 systematic review on the effect of exercise therapy on PCOS, a 2016 review on
the condition stated that physical exercise of at least 30 minutes per day for at least 5 days per
week improved insulin resistance and reduced cardiovascular risk in women with PCOS[24].
Furthermore, a systematic review evaluating exercise intervention in PCOS reported that
moderate-intensity regular aerobic exercise over a short period improved menstrual irregularity
and ovulation and contributed to reduced weight and insulin resistance in obese women with
PCOS[23]. Although current international evidence-based guidelines state that there is a lack of
evidence to support any one type and intensity of exercise being better than another for
anthropometric, metabolic, hormonal, reproductive, or psychological outcomes, they emphasize
that any physical activity (even light-intensity) will have health benefits over none[22]. They go
on to suggest that adults aiming for modest weight loss and prevention of weight gain should aim
for a minimum of 250 min/week of moderate-intensity activities or 150 min/week of vigorous
intensities or an equivalent combination of both, plus muscle-strengthening activities (e.g.,
resistance/flexibility) ideally on 2 non-consecutive days per week[22].
OTHER CONSIDERATIONS
It is important to note that the management of PCOS extends beyond the physical manifestations
of the syndrome.
Psychological factors (such as body image concerns, fear of injury, fear of failure, and mental
health) can serve as barriers to lifestyle management[22]. Current guidelines advise health
professionals to discuss these barriers and facilitators, including personal safety concerns,
environmental factors, physical limitations, socioeconomic factors, sociocultural factors, and
personal motivators for change to optimize adherence to interventions[22]. According to the
guidelines, lifestyle interventions could also include behavioral strategies such as goal setting, and
self-monitoring, to optimize weight management, healthy lifestyle, and emotional well-being in
women with PCOS[22].
In addition, lifestyle programs should include psychological support, social support, and
avoidance of toxic substances (such as smoking, alcohol, and drugs)[24].
PHARMACOLOGICAL INTERVENTIONS
While lifestyle interventions are first-line in the treatment of PCOS, several pharmacological
interventions can be used when lifestyle modifications fail to manage the metabolic dysfunctions
in PCOS[24].
Combined Oral Contraceptive Pills (COCP)
COCP is considered a first-line pharmaceutical treatment for PCOS due to its effectiveness in
reducing androgen levels and restoring normal menstrual cycles[25].
Metformin
Metformin, a biguanide approved for the treatment of T2DM is often used off-label in the
management of the metabolic factors associated with PCOS[24]. Women with PCOS, regardless
of age and BMI, have an increased risk of impaired fasting glucose, impaired glucose, and type 2
diabetes[22]. Many studies have documented the proven benefits of metformin in the context of
women with PCOS.
A review of the therapeutic options for managing the metabolic aspects of PCOS documented a
study comparing metformin and lifestyle interventions in women with PCOS. In the study, a
significant reduction in BMI was observed in both groups however the metformin group also
demonstrated a reduction in androgen levels, emphasizing its many benefits[23]. Many studies
have emphasized that metformin especially in combination with lifestyle modifications improved
glucose levels, adiposity, insulin resistance, and lipid profiles[27]. Thus, current guidelines
recommend that metformin alone can be considered in adults with PCOS and BMI>/ 25 kg/m2 for
anthropometric and metabolic benefits including those earlier described[22]. Metformin may also
be considered in adults with PCOS and BMI <25 despite limited evidence[22]. This is likely
because even lean women with PCOS have insulin resistance and are thus prone to increased CVD
risk[27]. Additionally, a recent review documented studies that suggested a modest improvement
in ovulation and live birth with metformin over placebo[27]. It should however be noted that
though metformin could be used over COCP for metabolic indications in PCOS(1), the effects of
metformin on menstrual irregularity and hyperandrogenism have been reported to be inferior to
those of COCP treatment[22][27].
GLP-1 agonists/analogues
Glucagon-like peptide-1 receptor analogs such as liraglutide are known stimulators of insulin
release following meal ingestion. A review by Abdalla et al describes several studies exploring the
efficacy of GLP-1 agonists in the context of several outcomes. Jensterle et al also mentioned
several studies in their review of the clinical applicability of GLP-1RAs in PCOS patients. One
such study was a meta-analysis that compared the effectiveness of liraglutide, orlistat, and
metformin in promoting weight loss in PCOS women[28]. This study revealed Liraglutide
monotherapy to be superior in reducing body weight and waist circumference with its highest
efficacy being at 3mg daily dose[28]. A study by Yaribeygu et al suggested that GLP-1 agonists
can also enhance insulin sensitivity through 8 different molecular pathways[23][28]. Another
systematic review and meta-analysis that compared the efficacy of GLP-1 agonists and metformin
in women with PCOS demonstrated a significant improvement in insulin sensitivity compared to
metformin in addition to reduced BMI and abdominal girth[23]. In a trial that compared the effects
of liraglutide treatment on atherothrombotic risk in Obese women with PCOS to control, a
significant reduction in both weight and atherothrombotic markers including endothelial function
and clotting was reported[23].
Thiazolidinediones
The effect of Thiazolidinediones, notably Pioglitazone in the context of PCOS has been
investigated. In one RCT investigating the effect of pioglitazone against placebo in PCOS,
pioglitazone resulted in a significant reduction in fasting serum insulin and free androgen index
with increasing SHBG levels [23]. Another meta-analysis comparing metformin and pioglitazone
reported a significant improvement in ovulation and menstrual cycle in the pioglitazone
group[23]. This points to the possible benefits of thiazolidinediones including improvement of
insulin resistance, hyperandrogenemia, ovarian dysfunction, and menstrual cycle[23].
However, certain concerning effects were also found. In the meta-analysis comparing metformin
and pioglitazone, a marked increase in BMI was seen in the pioglitazone compared with
metformin[23].
Inositol
Inositol, particularly myo-inositol, has gained attention for its potential therapeutic effects in
PCOS management.
Inositol is a carbocyclic sugar that in humans, is synthesized in the liver and kidney and has been
shown to have insulin-mimetic properties[24]. It has also been shown to lower post-prandial blood
glucose[23]. As abnormalities in inositol synthesis and metabolism have been reported in type 1
and type 2 diabetes, inositol has been used as a dietary supplement in the treatment of various
conditions such as T2DM, gestational diabetes, and recently, PCOS[23]. A retrospective study
reported a significantly lower risk of gestational diabetes in PCOS women treated with myo-
inositol compared with controls[23].
Currently, the international evidence-based guidelines consider inositol in any form or
combination with other therapies as worthy of consideration for the management of the metabolic
aspects of PCOS, given their limited harm and potential for improvement in metabolic
measures[22]. However, considering the limited data on the benefit of Myo-inositol for improving
ovulation, live birth rates, or clinical pregnancy rates, they should be considered experimental for
the treatment of fertility issues in sub-fertile women with PCOS[22][27].
Anti-androgen medications
Given the negative psychological impact of features of hyperandrogenism such as female pattern
hair loss, one of the targets in the management of PCOS involves addressing the signs of
excessive androgens in women with PCOS[22]. A recent RCT comparing the combination of
bicalutamide, an androgen receptor antagonist, and COCP with placebo, showed only minimal
additional benefit[27].
Currently, the international evidence-based guidelines suggest the consideration of anti-androgens
to treat hirsutism in women with contraindications to COCP therapy, when COCPs are poorly
tolerated or if there is suboptimal response after a minimum of 6 months on COCP[22].
Ovulation induction agents
Women with PCOS are at increased risk of infertility related to anovulation[27]. Therefore,
ovulation induction agents, while off-label in many countries are used where allowed as infertility
therapy[22]. These ovulation induction agents include clomiphene citrate and letrozole.
Clomiphene citrate, a selective estrogen receptor modulator aims at restoring ovulation by
interfering with inappropriate estrogen feedback mechanisms while letrozole, an aromatase
inhibitor aims at affecting estrogen production in adipose tissue[24]. Several studies in the context
of women with PCOS have reported that letrozole is superior to clomiphene citrate in affecting
live births[24][27]. A recent meta-analysis comparing the action of letrozole and clomiphene
citrate concluded that letrozole improves live birth and clinical pregnancy rates in women with
PCOS and infertility when compared to clomiphene citrate[27]. Interestingly, when used in
combination with metformin, clomiphene citrate may be superior to treatment with clomiphene
alone[27].Therefore, clomiphene citrate combinations with metformin could be used rather than
clomiphene citrate alone in anovulatory women with PCOS to improve ovulation and clinical
pregnancy[22]. However, given the increased risk of multiple pregnancies with clomiphene
citrate, women on clomiphene (alone or in combination with metformin) may require ultrasound
monitoring[22].
Surgical interventions
Surgical interventions can sometimes relieve PCOS-related symptoms[27]. Particularly for those
women who fail to control their weight on diet and medications alone, bariatric surgery is an
important option[24]. Although various procedures can be used, the most common surgeries are
sleeve gastrectomy, Roux-en-Y gastric bypass (RYGB), and adjustable gastric binding[23]. The
effect of bariatric surgery on body weight, blood pressure, reproductive function, and the risk of
cardiovascular diseases in the context of women with PCOS has been demonstrated[23][25]. For
example, a meta-analysis of 13 studies showed that bariatric surgery decreased the incidence of
PCOS symptoms from 45.6% to 7.1% and resulted in a weight loss of 57.2%[24]. A prospective
study following 17 PCOS women for 26 months following bariatric surgery, reported an average
weight loss of 41 kg. In addition, normalization of menstruation, and improvement of insulin
resistance, hirsutism, and androgen profile were observed[23].Click or tap here to enter
[Link] retrospective study of 24 morbidly obese women with PCOS who were followed for
2 years after RYGB reported a weight loss of about 56.7%, reduced HBA1c, and resumption of
their menstrual cycle[23].
Reproductive surgeries
In the management of PCOS, when other treatment modalities have not been successful in
inducing ovulation or regulating the menstrual cycle, for example in clomiphene-resistant women,
surgical options such as ovarian surgery can be considered[24].
The surgery commonly preferred is laparoscopic ovarian drilling[24]. This is a minimally invasive
procedure in which a laser beam or surgical needle is used to destroy ovarian tissue to improve
ovarian function[27]. Therefore, in current guidelines, laparoscopic ovarian surgery is considered
second-line therapy for women with PCOS and anovulatory infertility who are clomiphene citrate
resistant and when letrozole is not an option[22][27]. However, healthcare professionals and
patients should be aware of both the intra-operative and post-operative risks associated with
surgery, many of which are higher in overweight or obese women[22].
Furthermore, studies have found that with IVF, women with PCOS can have similar or better
pregnancy rates than women with other indications[24].
However, the procedure is associated with an increased risk of ovarian hyperstimulation syndrome
(OHSS) and multiple pregnancies[22]. With IVF, when elective single-embryo transfer is used,
multiple pregnancies can be minimized[22].
In PCOS women undergoing IVF/ICSI, GnRH antagonist protocol is recommended as it enables
the use of an agonist trigger with the freezing of all embryos generated if required[22].
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