PCOS ESHRE GuidelinesDr. Asha S Vijay

Polycystic ovary syndrome (PCOS) is a significant 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 various 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).

❖ In adolescents (<20 years of age) who are more than two years after her onset of menarche, 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

❖ There are exclusion categories, including thyroid disease stimulating thyroid hormone hyperprolactinemia (prolactin level) and non-classic congenital adrenal hyperplasia (serum 17-OHP) in all women with further assessment guided by clinical judgment. 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

Screening, diagnostic assessment regular cycles a, 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 dysfunctions. 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 determine 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 helpful in establishing the diagnosis of PCOS, and the phenotype where clinical signs of hyperandrogenism are unclear or absent, in particular, hirsutism

❖ A comprehensive history and physical examination should be completed for symptoms and signs of clinical hyperandrogenism, including acne, female pattern h, an ir 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, except 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 ensure no corpora lutea, cysts, or dominant follicles are present in one or both ovaries

❖ In patients with irregular menstrual cycles and hyperandrogenism, and 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 ≥ and an ovarian volume ≥ 10ml

❖ Clear protocols are recommended for ultrasound reporting antral follicle count and ovarian volume. 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 layers assessment may be unhelpful can exclude endometrial pathology

• Other ovarian and uterine pathology, including ovarian cysts, corpus luteum, dominant follicles > equal 10mm

❖ 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 PCO.S 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 the 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 improve symptoms adequately

❖ Inositol (in any form) should currently be considered an experimental therapy in women with PCOS, with the evidence on efficacy too uncertain about advocating this therapy

❖ Letrozole should be considers-line 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 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 a first-line treatment, in the presence of ultrasound monitoring, following counseling on cost and potential risk of multiple pregnancies, 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 ovarian surgery could be a second-line therapy for women with PCOS, who are clomiphene citrate resistant, with anovulatory infertile, ty and no other infertility factors

❖ Laparoscopic ovarian surgery could potentially be the first-line treatment if laparoscopy is indicated for another reason in women with PCOS with anovulatory infertility and no other infertility factors

❖ 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, IVF is effective, and when elective single embryo transfer is used, multiple pregnancies can be minimized.

❖The urinary or follicle-stimulate hormone can be used in women with PCOS undergoing controlled ovarian hyperstimulation for IVF ± ICSI, with insufficient evidence to recommend specific FSH preparations

❖ Luteinizing 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

❖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 during follicle-stimulating hormone ovarian stimulation in women with PCOS undergoing an 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.