Mind the gap: deciphering the role of anti-Müllerian hormone in follicular development—from animal studies toward clinical application

Anti-Müllerian hormone (AMH) is produced by granulosa cells during follicular development where it inhibits the transition from primordial to primary follicles. It also regulates the FSH sensitivity of early antral stages during dominant follicle selection (Broer et al., 2014). The inhibitory effect of AMH on primordial follicle activation has been described in several mammals (Durlinger et al., 2002; Nilsson et al., 2007; Yang et al., 2017) and has been considered the main mechanism maintaining the pool of primordial follicles from early exhaustion (Moolhuijsen and Visser, 2020). Other than the established role of AMH as an inhibitory molecule on follicle activation and the regulation of FSH sensitivity, it is important to decipher if AMH has any other functions. The December edition of the ESHRE Journal Club discussed a basic science research paper by Zhou et al. (2022), in which an additional role of AMH was suggested, as the results showed experimental evidence of AMH-induced atresia in murine preantral follicles. Zhou et al. used transgenic mice to determine the number of follicles in mice lacking the AMH gene (Amh−/−) and observed that these animals had less primordial follicles but more primary, secondary and small antral follicles compared to wild type mice. The authors observed that this difference was due to a higher survival ratio of primordial follicles transitioning into primary follicles. Mice that overexpress AMH had higher rates of follicle atresia as evidenced by apoptosis markers and empty primordial follicles, thus leading the authors to conclude that the role of AMH is not to maintain the ovarian reserve but rather to prevent the antral follicle pool becoming too large through AMH-induced atresia of preantral follicles. If these findings can be generalized to humans, they would represent a paradigm shift on the role of AMH and possibly affect clinical practice. The Journal Club discussion focused on the different implications of AMH-induced atresia both in biological and clinical contexts. These included the importance of AMH concentration levels, the role of FSH in rescuing follicles from AMH-induced atresia, the variation of AMH levels during ovarian suppression in humans, and the translation of the findings into clinical practice.