Polycystic ovary syndrome (PCOS) is a significant public health issue with reproductive, metabolic and psychological features. PCOS is one of the most common conditions in women affecting 8-13% of reproductive-aged women with up to 70% of affected women remaining undiagnosed. Women with PCOS present with diverse features including psychological (anxiety, depression), reproductive (irregular menstrual cycles, hirsutism, infertility and pregnancy complications) and metabolic features (insulin resistance (IR), metabolic syndrome, prediabetes, type 2 diabetes (DM2) and cardiovascular risk factors).

ESHRE recommends that PCOS be diagnosed:
❖ In adolescents (<20 years of age) who are more than two years after onset of menarche, where both androgen excess and ovulatory dysfunction are present. Ultrasound is not recommended for diagnosis in this age group ❖ In adult women if two of the three of androgen excess, ovulatory dysfunction, or polycystic ovarian morphology are present, with ultrasound required where either androgen excess or ovulatory dysfunction are not present ❖ Where disorders of exclusion are ruled out including thyroid disease (thyroid stimulating hormone), hyperprolactinemia (prolactin level), and non-classic congenital adrenal hyperplasia (serum 17-OHP) in all women with further assessment guided by clinical judgement.. ESHRE also endorses the recommendation of the NIH evidence-based methodology workshop in PCOS, that specific phenotypes should be reported explicitly in all research and ideally identified in practice across:
A) Androgen Excess + Ovulatory Dysfunction + Polycystic Ovarian Morphology
B) Androgen Excess + Ovulatory Dysfunction
C) Androgen Excess + Polycystic Ovarian Morphology
D) Ovulatory Dysfunction + Polycystic Ovarian Morphology

ESHRE RECOMMENDATIONS ON PCOS
Screening, diagnostic assessment
Irregular cycles and ovulatory dysfunction
❖ In adolescents (<20 years), two years after the onset of menarche, if a patient reports irregular menstrual cycles (>35 or <21 days) a diagnosis of PCOS should be considered and assessed according to the guidelines ❖ Irregular menstrual cycles (>35 days of <21 days) in adult women clinically reflect ovulatory dysfunction. However ovulatory dysfunction can still occur with regular cycles and biochemical progesterone levels can be assessed when PCOS is clinically suspected and cycles are regular Biochemical hyperandrogenism

❖ Calculated bioavailable testosterone, calculated free testosterone or free androgen index should be used to assess biochemical hyperandrogenism in the diagnosis of PCOS
❖ Androstenedione and dehydroepiandrosterone sulfate (DHEAS) could be considered if total or free testosterone are not elevated; however these provide limited additional information in the diagnosis of PCOS
❖ Assessment of biochemical hyperandrogenism is most useful in establishing the diagnosis of PCOS, and the phenotype where clinical signs of hyperandrogenism are unclear or absent, in particular hirsutism

Clinical hyperandrogenism
❖ A comprehensive history and physical examination should be completed for symptoms and signs of clinical hyperandrogenism, including acne, female pattern hair loss and hirsutism

Ultrasound and polycystic ovarian morphology (PCOM)

❖ Ultrasound should not be used for the diagnosis of PCOS in adolescence, due to the high incidence of multi-follicular ovaries in this life stage
❖ The transvaginal ultrasound approach should be used in the diagnosis of PCOS if acceptable to the patient, with the exception of those not yet sexually active
❖ Using ultrasound transducers with a frequency > 8MHz, the threshold for PCOM should be a follicle number per ovary of ≥ 18 and/or an ovarian volume > 10 ml, ensuring no corpora lutea, cysts or dominant follicles are present in one or both ovaries
❖ In patients with irregular menstrual cycles and hyperandrogenism, an ovarian ultrasound is not necessary for PCOS diagnosis; however ultrasound will identify the complete PCOS phenotype
❖ Transabdominal ultrasound should primarily report ovarian volume with a threshold of ≥ 10ml, given the difficulty of accurately assessing follicle number with this approach
❖ If using lower resolution ultrasound transducers with a frequency < 8MHz, the threshold for PCOM should be a follicle number per ovary of ≥ 12 and/or an ovarian volume ≥ 10ml ❖ Clear protocols are recommended for reporting antral follicle count and ovarian volume on ultrasound. Minimum reporting standards should include: • Last menstrual period • Approach/route assessed, transducer frequency • Total follicle number per ovary measuring 2-9mm • Three dimensions of each ovary and the volume • Reporting of endometrial thickness and appearance is preferred – 3 layer endometrial assessment may be useful and can exclude endometrial pathology • Other ovarian and uterine pathology, including ovarian cysts, corpus luteum, dominant follicles > equal 10mm

Anti- Müllerian Hormone (AMH)
❖ Serum AMH levels should not yet be used as an alternative for the detection of PCOM or as a single test for the diagnosis of PCOS Pharmacological treatment for non-fertility indications

Combined Oral Contraceptive Pills (COCPs)/ Metformin/ Antiandrogen
❖ The COCP alone should be recommended in adult women with PCOS for management of hyperandrogenism and irregular menstrual cycles
❖ The COCP alone should be considered in adolescents with a clear diagnosis of PCOS for management of clinical hyperandrogenism and irregular menstrual cycles
❖ Metformin should be considered for management of metabolic features and weight
❖ Antiandrogens should only be added in PCOS to treat hirsutism, after six months or more of COCP and cosmetic therapy have failed to adequately improve symptoms
❖ Inositol (in any form) should currently be considered an experimental therapy in women with PCOS, with the evidence on efficacy too uncertain to advocate this therapy

Ovulation Induction Principles
Letrozole
Letrozole should be considered first line pharmacological treatment for ovulation induction in women with PCOS with anovulatory infertility and no other infertility factors to improve ovulation, pregnancy and live birth rates
Clomiphene citrate and Metformin
❖ Clomiphene citrate or metformin could be used alone or in combination ( in CC resistant) in women with PCOS with anovulatory infertility and no other infertility factors to improve ovulation, pregnancy and live birth rate
Gonadotrophins
❖Gonadotrophins could be used as second line pharmacological agents in women with PCOS who have failed first line oral ovulation induction therapy and are anovulatory and infertile, with no other infertility factors
❖ Gonadotrophins could be considered as first line treatment, in the presence of ultrasound monitoring, following counselling on cost and potential risk of multiple pregnancy, in women with PCOS with anovulatory infertility and no other infertility factors
❖ Gonadotrophins (with or without metformin), where available and affordable, should be used in preference to clomiphene citrate combined with metformin therapy for ovulation induction, in women with PCOS with anovulatory infertility, clomiphene citrate-resistance and no other infertility factors, to improve ovulation, pregnancy and live birth rates
Laparoscopic surgery
❖ Laparoscopic ovarian surgery could be second line therapy for women with PCOS, who are clomiphene citrate resistant, with anovulatory infertility and no other infertility factors
❖ Laparoscopic ovarian surgery could potentially be first line treatment if laparoscopy is indicated for another reason in women with PCOS with anovulatory infertility and no other infertility factors

In-vitro fertilisation (IVF)
❖ In the absence of an absolute indication for IVF ± ICSI, women with PCOS and anovulatory infertility could be offered IVF if first or second line ovulation induction therapies have failed.
❖ In women with anovulatory PCOS, the use of IVF is effective and when elective single embryo transfer is used multiple pregnancies can be minimised.
❖Urinary or recombinant follicle stimulation hormone can be used in women with PCOS undergoing controlled ovarian hyperstimulation for IVF ± ICSI, with insufficient evidence to recommend specific FSH preparations
❖ Exogenous recombinant luteinising hormone treatment should not be routinely used in combination with follicle stimulating hormone therapy in women with PCOS undergoing controlled ovarian hyperstimulation for IVF ±ICSI
❖ A gonadotrophin releasing hormone antagonist protocol is preferred in women with PCOS undergoing an IVF ± ICSI cycle, over a gonadotrophin releasing hormone agonist long protocol, to reduce the duration of stimulation, total gonadotrophin dose and incidence of ovarian hyperstimulation syndrome (OHSS)
❖ Human chorionic gonadotrophins should be used at the lowest doses to trigger final oocyte maturation in women with PCOS undergoing an IVF ± ICSI cycle to reduce the incidence of OHSS
❖ Triggering final oocyte maturation with a GnRH agonist and freezing all suitable embryos could be considered in women with PCOS having an IVF/ICSI cycle with a GnRH antagonist protocol and at an increased risk of developing OHSS or where fresh embryo transfer is not planned
❖ In IVF ± ICSI cycles using the gonadotrophin releasing hormone antagonist protocol in women with PCOS, consideration should be given to an elective freeze of all embryos
❖ Adjunct metformin therapy could be used before and/or during follicle stimulating hormone ovarian stimulation in women with PCOS undergoing a IVF ± ICSI therapy with a gonadotrophin releasing hormone agonist protocol and antagonist protocol, to improve the clinical pregnancy rate and reduce the risk of OHSS
❖ In units with sufficient expertise, IVM could be offered to achieve pregnancy and livebirth rates approaching those of standard IVF ± ICSI treatment without the risk of OHSS for women with PCOS, where an embryo is generated, then vitrified and thawed and transferred in a subsequent cycle.