Polycystic ovary syndrome (PCOS): diagnosis, treatment and fertility
Key Takeaways
Polycystic ovary syndrome (PCOS) affects about 8 to 13 % of women of reproductive age. Diagnosis follows the revised Rotterdam criteria (two of three: oligo/anovulation, clinical or biochemical hyperandrogenism, polycystic ovarian morphology) — the 2023 International Evidence-based Guideline updated the ultrasound thresholds (≥ 20 follicles or volume ≥ 10 mL with high-frequency probes) and allowed AMH as a substitute. Letrozole is now the first-line treatment for ovulation induction, ahead of clomiphene. Weight and insulin-resistance management are central. For IVF, an antagonist protocol with a GnRH-agonist trigger drastically reduces the risk of ovarian hyperstimulation.
PCOS: what the 2023 guidelines say
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, with a worldwide prevalence estimated between 8 and 13 % depending on diagnostic criteria. It is also the leading cause of anovulatory infertility.
The 2023 International Evidence-based Guideline for the Assessment and Management of PCOS (Teede et al., Fertility & Sterility), developed jointly by ESHRE, ASRM, the Endocrine Society and 39 partner societies, substantially updated management. Three key changes:
- The Rotterdam diagnostic criteria are retained but thresholds are clarified: the antral follicle count required is now ≥ 20 per ovary (high-frequency probe ≥ 8 MHz), and AMH may substitute for ultrasound when high-quality imaging is unavailable.
- Letrozole is recommended as first-line for ovulation induction, ahead of clomiphene citrate.
- Weight and metabolic health management are central at every age, regardless of fertility intentions.
These changes aim to standardise diagnosis internationally, improve fertility outcomes, and reduce complications.
PCOS in numbers
- Overall prevalence: 8 to 13 % of women of reproductive age (roughly 1 in 10 to 1 in 8).
- Among infertile women: PCOS accounts for about 70 to 80 % of anovulatory infertility.
- Diagnostic delay: international median of about 2 years, with consultation across 3 clinicians on average before diagnosis.
- Metabolic risk: relative risk of type 2 diabetes 3 to 4× higher in the long term, independent of weight.
- Obstetric risk: increased rates of early miscarriage, gestational diabetes, pre-eclampsia and prematurity — pregnancy warrants adapted surveillance.
Pathophysiology: three interconnected axes
No single cause explains PCOS. Three mechanisms coexist and reinforce one another:
- Hypothalamic-pituitary dysfunction: increased GnRH pulsatility raises the LH/FSH ratio, which stimulates ovarian androgen production and blocks normal follicle maturation.
- Ovarian hyperandrogenism: excess testosterone and androstenedione from theca cells, driven by LH and hyperinsulinism.
- Insulin resistance: present in 65 to 70 % of women with PCOS, independent of weight. High insulin stimulates ovarian steroidogenesis and suppresses hepatic SHBG, raising the free fraction of circulating androgens.
Add to this a genetic component (heritability around 70 %, over 30 risk loci identified to date), environmental factors (insulin resistance, endocrine disruptors, intrauterine environment), and a chronic low-grade inflammation documented in multiple studies.
Diagnostic criteria: Rotterdam 2003, updated 2023
Diagnosis follows the revised Rotterdam criteria: two of three features are needed, after excluding other causes of hyperandrogenism or anovulation.
The three criteria
- Oligo- or anovulation: fewer than 8 cycles per year, intervals over 35 days, or amenorrhoea.
- Clinical or biochemical hyperandrogenism:
- clinical: hirsutism (Ferriman-Gallwey score ≥ 4–6 depending on population), moderate-to-severe acne, androgenic alopecia;
- biochemical: elevated total or free testosterone, or elevated free androgen index.
- Polycystic ovarian morphology on ultrasound OR elevated AMH:
- ultrasound: ≥ 20 antral follicles per ovary (high-frequency probe) or ovarian volume ≥ 10 mL;
- AMH ≥ 3.2 ng/mL (≈ 23 pmol/L) may replace ultrasound in adults per the 2023 guideline.
Exclusions to rule out
- Hyperprolactinaemia (see hyperprolactinaemia).
- Thyroid dysfunction.
- Non-classic congenital adrenal hyperplasia (17-OH-progesterone).
- Cushing’s syndrome if clinically suspected.
- Androgen- or cortisol-secreting tumours.
The four PCOS phenotypes
Applying the Rotterdam criteria defines four phenotypes, which guide metabolic and reproductive prognosis:
- Phenotype A (complete) — anovulation + hyperandrogenism + polycystic morphology: most severe form, worst metabolic profile.
- Phenotype B — anovulation + hyperandrogenism: metabolic profile similar to A.
- Phenotype C (ovulatory) — hyperandrogenism + polycystic morphology, preserved cycles: intermediate phenotype.
- Phenotype D (non-hyperandrogenic) — anovulation + polycystic morphology without hyperandrogenism: mildest metabolic profile but infertility possible.
This classification guides cardiometabolic risk stratification and surveillance frequency.
Symptoms
- Cycle disturbance: widely spaced periods, amenorrhoea, or markedly irregular cycles since puberty.
- Cutaneous hyperandrogenism: hirsutism (face, midline, chest, back), persistent inflammatory acne, androgenic alopecia in a crown or midline pattern.
- Infertility: chronic anovulation — the most frequent driver.
- Acanthosis nigricans: dark velvety patches on the neck, axillae, and skin folds — a sign of marked insulin resistance.
- Weight gain or resistant overweight: present in 40 to 80 % of patients depending on population.
- Sleep disturbance: obstructive sleep apnoea is more common, independent of weight.
- Psychological impact: anxiety, depression, body image and quality-of-life burden.
Clinical examination assesses Ferriman-Gallwey score, blood pressure, waist circumference, BMI, and looks for acanthosis nigricans.
Biochemical workup
The recommended diagnostic workup includes:
- Total and free testosterone, SHBG (with free androgen index calculation if needed);
- 17-OH-progesterone (early follicular or random) to rule out non-classic CAH;
- DHEAS (to assess adrenal contribution);
- AMH (for alternative morphological diagnosis);
- TSH;
- Prolactin;
- Fasting glucose + HbA1c (or 75 g OGTT if BMI ≥ 25 or risk factors);
- Complete lipid profile;
- Vitamin D.
An OGTT is advised every 1 to 3 years per risk profile, and routinely before any planned pregnancy.
Metabolic and cardiovascular risks
PCOS carries an increased cardiometabolic risk independent of weight:
- Type 2 diabetes: 3–4× risk, screen every 1–3 years (OGTT).
- Gestational diabetes: 2–3× risk; early-pregnancy screening.
- Dyslipidaemia: high triglycerides, low HDL.
- Metabolic syndrome: in 30–40 % of adult patients.
- NAFLD (non-alcoholic fatty liver disease): increased prevalence, evaluate at least with ALT/AST.
- Sleep apnoea: screen when symptoms suggestive.
- Long-term cardiovascular risk: signal in multiple studies, to confirm in prospective cohorts.
Metabolic surveillance is lifelong: annual at minimum for blood pressure, weight, waist circumference, lipids and glucose.
Managing symptoms beyond fertility
Lifestyle
Lifestyle modification (nutrition, physical activity, sleep, stress) is the universal first line, regardless of weight. A 5 to 10 % weight loss in women with overweight significantly improves cycles, spontaneous fertility and metabolic markers.
No specific diet has been shown superior — Mediterranean, low-glycaemic-index and DASH are all reasonable approaches. Aerobic exercise and strength training (at least 150 min/week moderate, or 75 min vigorous) are recommended.
Treating hyperandrogenism and cycles
- Combined hormonal contraceptives: first-line for cycle regulation, acne, hirsutism and alopecia. Anti-androgenic progestins (drospirenone, cyproterone, dienogest) are preferred, with individualised thromboembolic risk/benefit assessment.
- Topical and cosmetic treatments: laser hair removal, electrolysis, topical eflornithine.
- Anti-androgens (spironolactone, cyproterone): second-line, always with effective contraception (teratogenic risk).
Metformin
- Indicated for documented insulin resistance, prediabetes/type 2 diabetes, or to support weight loss and cycle regulation in selected patients.
- Usual dose 1500–2000 mg/day in 2–3 divided doses, progressively titrated. Common gastrointestinal side effects at initiation.
- Modest but real benefit on cycles, BMI, glucose profile and pregnancy outcomes, independent of ovulation induction.
Inositols
Inositols (myo-inositol alone or with D-chiro-inositol, often at a 40:1 ratio) are sometimes offered. Evidence remains mixed and the 2023 guideline classifies them as experimental rather than validated first-line therapy. No significant safety concerns at usual doses.
Ovulation induction for fertility
Letrozole: first line
Letrozole (aromatase inhibitor, 2.5–7.5 mg/day for 5 days early in the cycle) is now the first-line treatment for ovulation induction in women with PCOS and anovulation.
The PPCOS II trial (Legro et al., 2014, N Engl J Med) directly compared letrozole and clomiphene in 750 women:
- Live birth rate: 27.5 % with letrozole vs 19.1 % with clomiphene — significant difference.
- Cumulative ovulation rate: 61.7 % vs 48.3 %.
- Tolerance: comparable profile, no increase in major risks.
- Endometrial effect: less than with clomiphene, more favourable for implantation.
Clomiphene citrate: second line
Still used as second line or when letrozole is unavailable. Dose 50–150 mg/day for 5 days, with ultrasound monitoring.
Gonadotrophins
If letrozole and clomiphene fail, low-dose FSH or hMG stimulation with close ultrasound monitoring. Multiple-pregnancy risk and hyperstimulation should be closely watched.
Ovarian drilling
Reserved for patients resistant to oral therapy or requiring surgery for another indication. No longer part of routine care per the 2023 guideline.
PCOS and IVF: an adapted protocol
PCOS carries a high risk of ovarian hyperstimulation syndrome (OHSS) due to high antral follicle counts and increased ovarian sensitivity. IVF strategy must limit this risk.
Recommended protocol
- GnRH-antagonist protocol rather than long agonist.
- Adapted initial FSH dose (often 100–150 IU/day in young patients with high AMH), titrated to response.
- GnRH-agonist trigger (instead of hCG) when OHSS risk is significant — drastically reduces moderate-to-severe OHSS.
- Freeze-all strategy (vitrification of all embryos, deferred transfer in a later cycle) often preferred when OHSS risk is real.
- Pre-cycle metabolic optimisation: weight, glucose, blood pressure before stimulation.
IVF pregnancy rates are comparable, even slightly higher, in PCOS patients vs other infertile women when the strategy is well executed, thanks to high ovarian reserve.
Ovarian hyperstimulation syndrome (OHSS)
OHSS is a potentially severe complication (third-space fluid, thrombosis, renal or hepatic injury). Prevention in PCOS patients relies on:
- dose adjustment;
- GnRH-agonist trigger instead of hCG;
- freeze-all if E2 is too high or ≥ 20 follicles;
- dopamine agonists (cabergoline) post-retrieval in moderate risk.
Pregnancy and PCOS
Pregnancy needs adapted surveillance:
- Early gestational diabetes screening in the first trimester (HbA1c, fasting glucose, or early OGTT if high risk), with repeat at 24–28 weeks.
- Pre-eclampsia surveillance: blood pressure, proteinuria.
- Pre-pregnancy metabolic optimisation: weight, glucose control, folic acid, vitamin D, iodine supplementation.
- Metformin in pregnancy: may be continued depending on clinical context where indicated, no formal contraindication at usual doses.
Adolescent PCOS
Diagnosis in adolescents is challenging because some features (irregular post-menarche cycles, comedones, ovarian morphology) are physiological early in adolescence. The 2023 guideline restricts firm diagnosis to situations with:
- both criteria of oligo/anovulation and clinical or biochemical hyperandrogenism present simultaneously;
- at least 2 to 3 years after menarche (outside clearly early-onset cases);
- ultrasound is not required for adolescent diagnosis.
A “at risk of PCOS” category is introduced: single criterion + follow-up to 8 years or until clarification.
Turkish context
Turkish regulations prohibit oocyte, sperm and embryo donation, and surrogacy. This constraint rarely affects PCOS patients with preserved ovarian reserve: the vast majority conceive with their own oocytes after simple induction or optimised IVF. The rare cases of PCOS combined with secondary ovarian insufficiency (post-surgery, post-gonadotoxic treatment) are limited to own-oocyte strategies in Turkey.
In practice
- Diagnosis by Rotterdam criteria (2 of 3) with 2023 thresholds (AFC ≥ 20 or AMH ≥ 3.2 ng/mL).
- Systematic exclusion of hyperprolactinaemia, thyroid dysfunction, congenital adrenal hyperplasia and other endocrine causes.
- Four distinct phenotypes that guide metabolic risk and management.
- Lifestyle as the universal first line; 5–10 % weight loss in overweight women significantly improves cycles and fertility.
- Combined contraceptives for cycle regulation and hyperandrogenism.
- Letrozole as first-line ovulation induction (superior to clomiphene, PPCOS II trial).
- IVF on antagonist protocol with GnRH-agonist trigger and freeze-all to minimise OHSS.
- Lifelong metabolic surveillance: annual blood pressure, weight, glucose, lipids.
FAQ
Can PCOS be cured?
No, PCOS is a chronic condition. But its manifestations (cycles, hyperandrogenism, metabolism) are well controllable by treatment and lifestyle. Many women see their cycles normalise over time, particularly after their forties as ovarian function naturally declines.
Does PCOS make infertility inevitable?
No. Most women with PCOS conceive — naturally (with preserved cycles or regulated by weight loss), with ovulation induction, or with IVF. Ovarian reserve is generally preserved, often higher than average.
Why letrozole rather than clomiphene?
The PPCOS II trial (Legro et al., 2014) showed a 27.5 % live birth rate with letrozole vs 19.1 % with clomiphene. Letrozole is also better tolerated by the endometrium. The 2023 international guideline now ranks it first-line.
Should metformin always be prescribed in PCOS?
No. It is indicated for documented insulin resistance, prediabetes/type 2 diabetes, or to support weight loss and cycles in selected patients. Not an automatic treatment for everyone.
Are inositols effective?
Evidence is mixed. The 2023 guideline classifies them as experimental rather than reference therapy. No significant safety concerns at usual doses, but efficacy needs confirmation in high-quality trials.
What is the OHSS risk in IVF with PCOS?
Real but largely controlled by the antagonist protocol, GnRH-agonist trigger (instead of hCG), and freeze-all strategy. With these measures, moderate-to-severe OHSS becomes rare. The centre should be experienced with this profile.
What weight target should I aim for?
There is no universal target weight. A 5 to 10 % weight loss in women with overweight significantly improves cycles, insulin sensitivity and spontaneous fertility. The goal is progressive and sustainable, not a precise BMI.
My teenager has irregular cycles and acne. Could this be PCOS?
Irregular cycles and acne are physiological early in adolescence (2–3 years post-menarche). Firm diagnosis requires oligo/anovulation + hyperandrogenism simultaneously and at least 2–3 years post-menarche. A paediatric gynaecology consultation can set up “at-risk” follow-up without prematurely labelling a diagnosis.
What should I bring to the consultation?
Bring recent blood test results (testosterone, AMH, TSH, prolactin, glucose, lipid profile), pelvic ultrasound reports, a cycle diary for the past few months, your weight history, family history of diabetes, and a list of current medications.
Sources
- Teede HJ, Tay CT, Laven JJE, et al. Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Fertil Steril 2023;120(4):767–793.
- Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med 2014;371(2):119–129.
- Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Hum Reprod 2004;19(1):41–47.
- Azziz R, Carmina E, Chen Z, et al. Polycystic ovary syndrome. Nat Rev Dis Primers 2016;2:16057.
- Norman RJ, Teede HJ. A new evidence-based guideline for assessment and management of polycystic ovary syndrome. Med J Aust 2018;209(7):299–300.
- WHO. Polycystic Ovary Syndrome Fact Sheet, 2023.
The content has been created by Dr. Senai Aksoy and medically approved.