Changes in serum anti-mullerian hormone level during low-dose recombinant follicular-stimulating hormone therapy for anovulation in polycystic ovary syndrome

Context: We previously hypothesized that the excess of anti-mullerian hormone (AMH) at the level of selectable follicles could be involved in the follicular arrest of polycystic ovary syndrome ( PCOS), mainly through inhibition of FSH effect on aromatase expression. Objective: In this study, we investigated whether a decrease in the serum AMH level was concomitant to the appearance of a dominant follicle induced by administration of mild amounts of exogenous FSH in women with PCOS. Design: A total of 30 women with PCOS in whom anovulation was resistant to clomiphene citrate received recombinant FSH using the low-dose step-up protocol during only one cycle. Serum levels of estradiol, AMH, LH, FSH, inhibin B, and ultrasound parameters were assessed twice a week until 3 d after the appearance of one or more dominant follicle(s). Results: The day of dominance ( d 0) was defined by the appearance of at least one follicle more than 10 mm growing 2 mm/d. From d - 14 before dominance to d - 3, the mean serum AMH level and the 2- to 5-mm follicle number at ultrasound declined steadily, although not significantly by ANOVA. Mean AMH relative values (100% being the value at d 0) declined significantly ( P = 0.04), from 125 +/- 32% at d - 14 to 105 +/- 15% at d - 4. Within the same time lag, the mean FSH relative values increased from 91 +/- 17% to 107 +/- 19% ( P = 0.013). In the 87 samples obtained from d - 14 to -4, absolute values of AMH were positively and negatively associated with those of LH and FSH, respectively, in an independent manner ( P = 0.009 and P = 0.03, respectively). In the 55 samples collected at d 0 and +3, they were negatively correlated to those of estradiol ( r = -0.272; P < 0.05). Conclusions: These data suggest that in anovulatory women with PCOS, gently increasing the serum FSH level reduces the AMH excess, thus relieving the inhibition from the latter on aromatase expression by selectable follicles and allowing the emergence of a dominant follicle.