Establishing an Anti-Müllerian Hormone (AMH) Cut-off to Determine Polycystic Ovarian Morphology (PCOM) Supporting Diagnosis of Polycystic Ovarian Syndrome (PCOS): the Aphrodite Study

To derive and validate a cut-off for AMH to discriminate PCOM using the Elecsys® AMH Plus immunoassay. APHRODITE is a case-control study of PCOS-positive (cases) and PCOS-negative (controls) women aged 25–45 years. Cases were defined using Rotterdam criteria, showing the full phenotype A (irregular cycles/ovulatory dysfunction, clinical or biochemical hyperandrogenism and PCOM); controls had an antral follicle count (AFC) ≤20, based on the new international guideline for PCOS. The discovery cohort included 290 cases and 575 controls, whereas the validation cohort consisted of 455 cases and 500 controls. Serum levels of AMH were measured using the Elecsys® AMH Plus immunoassay; AFC was determined by transvaginal ultrasound. An AMH cut-off was optimised in the discovery cohort based on concordance analysis. Performance (sensitivity, specificity and area under the curve [AUC]) of the defined cut-off was evaluated in the validation cohort. Exploratory analyses in different sub-cohorts (including age groups) were also performed. Compared with controls, PCOS cases were younger (median age 29.0 vs 34.0 years), with a higher body mass index (median 29.2 vs 23.8 kg/m2) and higher AMH level (median 6.23 vs 2.13 ng/mL). Good correlation was observed between AMH and AFC in the discovery and validation cohorts, with Spearman correlation coefficients of 0.83 and 0.84, respectively. A serum AMH cut-off of 3.5 ng/mL (25 pmol/L) was determined in the discovery cohort, which achieved 85.9% sensitivity and specificity. In the validation cohort, this cut-off achieved 82.4% (95% confidence interval [CI] 78.6–85.8) sensitivity and 89.8% (95% CI 86.8–92.3) specificity, with an AUC of 94.0% (95% CI 92.6–95.5). In women aged ≤35 years, the AMH cut-off of 3.5 ng/mL showed 84.2% (95% CI 81.3–86.9) sensitivity and 83.5% (95% CI 80.0–86.6) specificity; in women aged >35 years, specificity remained high (91.8% [95% CI 89.2–93.9]) but sensitivity was lower (77.4% [95% CI 63.8–87.7]). The Elecsys® AMH Plus immunoassay provides a robust method for identifying PCOM as part of PCOS diagnosis with a cut-off of 3.5 ng/mL (25 pmol/L).