Women with polycystic ovary syndrome (PCOS) undergoing IVF-embryo transfer based-assisted reproductive technology (ART) treatment show variable ovarian responses to exogenous FSH administration. For better understanding and control of PCOS ovarian responses in ART, the present study was carried out to compare the follicular hormones and the expression of granulosa cell genes between PCOS and non-PCOS women during ART treatment as well as their IVF outcomes. Overall, 138 PCOS and 78 non-PCOS women were recruited for the present study. Follicular fluid collected from PCOS women showed high levels of testosterone. The expression of aromatase was found significantly reduced in luteinized granulosa cells from PCOS women. In cultured luteinized granulosa cells isolated from non-PCOS women, their exposure to testosterone at a level that was observed in PCOS follicles could decrease both mRNA and protein levels of aromatase in vitro. The inhibitory effect of testosterone was abolished by androgen receptor antagonist, flutamide. These results suggest that the hyperandrogenic follicular environment may be a key hazardous factor leading to the down-regulation of aromatase in PCOS.Reproduction (2015) 150 289-296

Objective: To measure blood and follicular antim€ ullerian 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 ¼ 86) and without (n ¼ 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 insulinpromoted aromatase expression in granulosa cells. (Fertil Steril Ò 2019;111:157-67. Ó2018 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.