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The phenotypic diversity in per-follicle anti-Müllerian hormone production in polycystic ovary syndrome

STUDY QUESTION Is intrinsic dysregulation of granulosa cells (GC) and consequent increases in the per-follicle production of anti-Müllerian hormone (AMH), correlated with the phenotypic presentation of women with polycystic ovaries? SUMMARY ANSWER Involvement of intrinsic GC dysregulation in oligo-anovulation associated with polycystic ovary syndrome (PCOS) is likely because among women with PCOS, those with oligo-amenorrhea have higher per-follicle AMH production than those who ovulate normally, irrespective of their androgen and/or metabolic status. WHAT IS KNOWN ALREADY Women with PCOS have higher serum AMH level than non-PCOS women due to an increased follicle number and excessive AMH production per follicle, the latter reflecting a putative GC dysfunction that may vary between PCOS phenotypes. STUDY DESIGN, SIZE, DURATION This is a retrospective analysis of data collected from 1021 women undergoing infertility evaluation from March 2011 to October 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS The study included women with polycystic ovarian morphology (PCOM) who met the Rotterdam criteria for PCOS (n = 272), women with PCOM only (n = 168) and controls (n = 581). MAIN RESULTS AND THE ROLE OF CHANCE We used serum AMH to antral follicle count (AFC) ratio (AMH/AFC) as a marker of per-follicle AMH production and checked whether this ratio was associated with the PCOS phenotype and to the menstrual, androgen and metabolic status in women with PCOS, women with PCOM only and in controls. AMH/AFC was significantly higher in oligo-amenorrheic women with PCOS than in eumenorrheic women with PCOS or PCOM (P < 0.001) but also in the latter group compared with controls (P < 0.001) regardless of androgen status. Stepwise discriminant analysis yielded a significant score for the menstrual status with a discriminant power of 26.5% (P < 0.001). This score included AFC, AMH/AFC, waist circumference and LH with partial R2 of 0.172, 0.042, 0.024 and 0.023, respectively. LIMITATIONS, REASONS FOR CAUTION The AMH to AFC ratio as a surrogate marker for average AMH may be subject to error because follicles below the sensitivity limit of the ultrasonography used may also contribute to serum AMH concentration and secondly, AFC can be subjective. WIDER IMPLICATIONS OF THE FINDINGS The higher AMH/AFC in women with PCOM only than in controls suggests that isolated PCOM may represent a PCOS-like phenotype in which an inherent dysfunction of GC exists but is too mild to affect the ovulatory process. STUDY FUNDING/COMPETING INTEREST(S) No funding was obtained for this study. There are no conflicts of interest to be declared. TRIAL REGISTRATION NUMBER Non-applicable.

anovulation; anti-Müllerian hormone; hyperandrogenism; polycystic ovary; PCOS

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