The proportion of cleaved anti-Müllerian hormone is higher in serum but not follicular fluid of obese women independently of polycystic ovary syndrome

Maëliss Peigné,Pascal Pigny,Michaël W Pankhurst,Elodie Drumez,Anne Loyens,Didier Dewailly,Sophie Catteau-Jonard,Paolo Giacobini

doi:10.1016/j.rbmo.2020.07.020

Abstract

Research questionDoes the relative distribution of anti-Müllerian hormone (AMH) isoforms differ between patients depending on their body mass index (BMI) and polycystic ovary syndrome (PCOS) status in serum and follicular fluid? DesignObese and normal weight patients (PCOS [n = 70]; non-PCOS [n = 37]) were selected for this case-control study in the serum. Between 2018 and 2019, obese (n = 19) and normal weight (n = 20) women with or without PCOS who were receiving IVF treatment were included in the follicular fluid study. The bio-banked serums and follicular fluid were tested for total AMH (proAMH and AMHN,C combined) and proAMH using an automatic analyzer. The AMH prohormone index (API = [proAMH]/[total AMH]x 100) was calculated as an inverse marker of conversion of proAMH to AMHN,C, with only the latter isoform that could bind to the AMH receptor complex. ResultsThe API was not significantly different between controls and women with PCOS, whereas obese women had a lower API compared with their normal weight counterparts. Grouping PCOS and controls, a lower API was found in obese versus normal weight women, suggesting a greater conversion of proAMH to AMHN,C. The API in the serum was significantly correlated with metabolic parameters. In the follicular fluid, API is not different between obese and normal weight women independently of PCOS and is higher than in the concomitant serum. ConclusionsThe proportion of inactive form of AMH in the serum is higher in normal weight versus obese women but not in the follicular fluid, independently of PCOS. The conversion of proAMH into the cleaved isoform is likely to occur in extra-ovarian tissues and to exacerbate in obese individuals.

Highlights

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine disorder, affecting up to 20% of women of reproductive age and representing the primary cause of anovulatory infertility worldwide (Teede et al, 2018)
Grouping PCOS and controls, a lower AMH prohormone index (API) was found in obese versus normal weight women, suggesting a greater conversion of proAMH to AMHN,C
The proportion of inactive form of anti-Müllerian hormone (AMH) in the serum is higher in normal weight versus obese women but not in the follicular fluid, independently of PCOS

Summary

Introduction

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine disorder, affecting up to 20% of women of reproductive age and representing the primary cause of anovulatory infertility worldwide (Teede et al, 2018). Observed correlations between enhanced basal levels of AMH and PCOS have led to a potential physiological role for AMH in ‘follicular arrest’ in women with PCOS (Dewailly et al, 2014). In this pathology, enhanced numbers of primary and small secondary follicles secrete abnormally high levels of AMH, which associates with excess androgen production or secretion, and leading to arrested follicular maturation (Dewailly et al, 2014)

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