Per-follicle measurements indicate that anti-Müllerian hormone secretion is modulated by the extent of follicular development and luteinization and may reflect qualitatively the ovarian follicular status

Abstract

In adult women, anti-Müllerian hormone (AMH) expression in granulosa cells is, at least in part, regulated by the stage of follicular growth, with predominant production by preantral and early antral follicles. Whereas the ability of preovulatory follicles to secrete AMH is reduced (Baarends et al. Endocrinology, 1995), the consequences of follicular luteinization on AMH production are less documented. Also, high peripheral AMH levels reflect increased number of early antral follicles (Fanchin et al. Fertil. Steril., 2003), but whether they also reflect increased per-follicle AMH production remains unclear. Hence, we decided to investigate the possible modulating role of follicular maturation and luteinization on AMH secretion and the possible relationship between per-follicle AMH levels and ovarian follicular status and responsiveness to controlled ovarian hyperstimulation (COH). Prospective study. We studied 37 normo-ovulating IVF-ET candidates undergoing COH. On the day of oocyte retrieval, 36 h after hCG administration, serum samples and follicular fluids (FFs) from 2 large (16–20 mm in diameter) and 2 small (8–12 mm in diameter) follicles were collected for serum and FF AMH, E2, and progesterone (P4) measurements. Sizeable AMH levels were detected both in serum and FFs. Hormonal contents were similar between two small and between two large follicles in the same patient and were averaged. Small follicles secreted approximately 3 times as high AMH levels as large follicles (P < 0.0001), but less P4 (P < 0.0001), and similar E2 levels. FF AMH and P4 levels correlated negatively both in small (r=-0.61; P < 0.0001) and large (r=-0.36; P < 0.03) follicles. In large follicles, FF AMH levels correlated positively with the number of early antral follicles on cycle day 3 before COH (r= 0.58; P < 0.0002), growing follicles (beyond 11 mm; r= 0.45; P < 0.0005) and oocytes retrieved (r= 0.48; P < 0.0003), and negatively with FSH requirement (r= -0.48; P < 0.0003). AMH production by granulosa cells is modulated by the degree of follicular development, with a hefty gradient from small to large follicles, and luteinization, as indicated by the inverse relationship between FF AMH and P4 levels. The remarkable correlation between intra-follicular AMH content, baseline ovarian follicular status, and response to COH indicates that peripheral AMH measurements may reflect not only follicle count but also per-follicle AMH production. Further insights into this sensitive issue may contribute to refine the interpretation of serum AMH levels not only as a quantitative but also as a qualitative marker of ovarian follicular status.