Gonadotropins induce higher active renin levels in the follicular fluid of normal and hyperstimulated cycles

The objective of this study was to analyze follicular fluid active renin and its relationship to steroid hormones throughout the normal and gonadotropin-stimulated menstrual cycle. Active renin was measured in the follicular fluid of patients undergoing tubal sterilization (n = 16) and in vitro fertilization (IVF) (n = 25); IVF patients were either in a natural cycle (n = 7) or undergoing controlled ovarian hyperstimulation (n = 18). The largest visible follicle was aspirated at the time of laparoscopic tubal sterilization; ultrasound guided transvaginal follicular aspiration was used in the IVF group. Follicular fluid active renin, estradiol and progesterone levels were measured with immunoradiometric and fluoroimmunoassays. The cycle day was correlated with the spontaneous luteinizing hormone (LH) surge or human chorionic gonadotropin (hCG) administration, as well as active renin, estradiol, progesterone levels and the estradiol/progesterone ratio using simple and multiple regression and analysis of variance (ANOVA). Cycle day independently influenced active renin, progesterone and the estradiol/progesterone ratio in a statistically significant manner (p < 0.0001). The active renin and progesterone levels were highest during the periovulatory period (p < 0.0001 and p < 0.002, respectively) and the estradiol/progesterone ratio correlated inversely with cycle day (p < 0.003). Although the follicular fluid active renin, estradiol and progesterone levels were higher after controlled ovarian hyperstimulation when compared to natural cycles, this difference did not reach statistical significance. Our findings suggest that active renin levels in follicular fluid increase in the follicular phase of the menstrual cycle, reaching peak levels in the periovulatory period following the LH surge or hCG administration, providing indirect support for the hypothesis that the ovarian renin-angiotensin system (RAS) is under gonadotropin control.