Anovulation & ovulation induction: WHO classification (FIGO HyPO-P 2023), letrozole first-line, gonadotropins, and OHSS prevention

A 28-year-old with PCOS, a BMI of 32, and irregular cycles every 40 to 60 days has been trying to conceive for 9 months. Her day-21 progesterone is 1.2 ng/mL (below the ovulatory threshold), her FSH and oestradiol are normal, and her AMH is 8.4 ng/mL (high). Your job is to apply the WHO classification, recognise her as Group II, and walk the evidence-based ladder — lifestyle, letrozole first-line, gonadotropins if resistant, and an OHSS-aware IVF protocol if needed — while never forgetting that this woman's high AMH marks her as a high OHSS responder. The PPCOS II trial and the 2023 International Guideline exist to stop doctors reaching for clomiphene first.^[2][12]

Overview and definition

Anovulation is the failure to release an oocyte in a menstrual cycle. Clinically it presents as oligomenorrhoea (cycles over 35 days or fewer than 8 per year) or amenorrhoea (no cycle for over 3 months). It accounts for roughly 25% of female-factor infertility, of which PCOS (WHO Group II) is around 80% — which is why the letrozole-first evidence, built almost entirely in PCOS, dominates this topic.^[1][4]

The single most important diagnostic act is the biochemical sorting into WHO groups, because the first-line treatment is determined by which group the woman sits in. The 2023 FIGO HyPO-P update reorganises the half-century-old WHO system into four axes — Hypothalamic, Pituitary, Ovarian, and PCOS — but the gonadotropin-and-oestrogen logic that drives treatment choice is unchanged.^[1]

^{[1] [2] [4]}

References14ShowHide

1. [1]Balen AH, Tamblyn J, Skorupskaite K, Munro MG. A comprehensive review of the new FIGO classification of ovulatory disorders. Hum Reprod Update, 2024.PMID 38412452
2. [2]Legro RS, Brzyski RG, Diamond MP, Coutifaris C, Schlaff WD, Casson P, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med, 2014.PMID 25006718
3. [3]Franik S, Le QK, Kremer JA, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome. Cochrane Database Syst Rev, 2022.PMID 36165742
4. [4]Joham AE, Norman RJ, Stener-Victorin E, Legro RS. Polycystic ovary syndrome. Lancet Diabetes Endocrinol, 2022.PMID 35934017
5. [5]ESHRE Capri Workshop Group. Health and fertility in World Health Organization group 2 anovulatory women. Hum Reprod Update, 2012.PMID 22611175
6. [6]Morley LC, Tang T, Yasmin E, Norman RJ. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev, 2017.PMID 29183107
7. [7]Costello MF, Misso ML, Balen A, Boyle J, Garad R. A brief update on the evidence supporting the treatment of infertility in polycystic ovary syndrome. Aust N Z J Obstet Gynaecol, 2019.PMID 31514246
8. [8]Ovarian Stimulation TEGGO, Bosch E, Broer S, Griesinger G, Grynberg M, Humaidan P, et al. ESHRE guideline: ovarian stimulation for IVF/ICSI. Hum Reprod Open, 2020.PMID 32395637
9. [9]Practice Committee of the American Society for Reproductive Medicine. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertil Steril, 2016.PMID 27678032
10. [10]Humaidan P, Papanikolaou EG, Kyrou D, Alsbjerg B, Polyzos NP, Fatemi HM, et al. The luteal phase after GnRH-agonist triggering of ovulation: present and future perspectives. Reprod Biomed Online, 2012.PMID 22197130
11. [11]Romualdi D, Ata B, Bhattacharya S, Bosch E, Costello M, Gersak K, Homburg R, Mincheva M, Norman RJ, et al. Evidence-based guideline: unexplained infertility. Hum Reprod, 2023.PMID 37599566
12. [12]Teede HJ, Tay CT, Laven JJE, Dokras A, Moran LJ, Piltonen TT, et al. Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Fertil Steril, 2023.PMID 37589624
13. [13]Broer SL, van Disseldorp J, Broeze KA, Dolleman M, Opmeer BC, Bossuyt P, et al. Added value of ovarian reserve testing on patient characteristics in the prediction of ovarian response and ongoing pregnancy: an individual patient data approach. Hum Reprod Update, 2013.PMID 23188168
14. [14]Li HJ, Seifer DB, Tal R. AMH independently predicts aneuploidy but not live birth per transfer in IVF PGT-A cycles. Reprod Biol Endocrinol, 2023.PMID 36739415