Elevation of antimullerian hormone in women with polycystic ovary syndrome undergoing assisted reproduction : effect of insulin

Abstract

Objective: To measure blood and follicular antimüllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) undergoing assisted reproductive technologies (ART) and to examine the direct action of insulin on AMH expression in human granulosa cells. Design: Prospective clinical and experimental study. Setting: University Hospital-based laboratory. Patient(s): Women with (n = 86) and without (n = 172) PCOS in ART. Intervention(s): Blood, follicular fluid, and luteinized granulosa cells were collected from PCOS and non-PCOS women in ART. Main Outcome Measure(s): Hormone levels in blood and fluid, and gene expression in granulosa cells. Result(s): Serum levels of AMH were elevated and inversely correlated with embryo cleavage rate in PCOS women in ART. Significant higher levels of AMH were also found in small and large follicles collected from PCOS women compared with non-PCOS women. Luteinized granulosa cells from PCOS women showed higher expression of AMH and its receptor AMHR2. Direct effect of insulin in increasing the expression of AMH in the isolated luteinized granulosa cells was observed, with the PCOS granulosa cells responding to a high dose of insulin. Cotreatment with AMH attenuated insulin-induced aromatase expression in the luteinized granulosa cells. Conclusion(s): These results suggest that insulin may contribute to AMH elevation in PCOS and that AMH counteracts insulin-promoted aromatase expression in granulosa cells.