Differential secretion of dimeric inhibin in cultured luteinized granulosa cells as a function of ovarian reserve

Day 3 serum FSH is an indirect assessment of ovarian reserve and has been shown to be prognostic of outcome in ovulation induction and assisted reproductive technology programs. The precise physiologic basis for day 3 serum FSH screening is unknown. We tested the hypothesis that dimeric inhibin is differentially secreted from luteinized granulosa cells collected from women in preparation for in vitro fertilization with low vs. high day 3 serum FSH levels. This prospective study consisted of luteinized granulosa cells harvested from 7 women with low day 3 serum FSH levels (less than or equal to 6 IU/L) and from 8 women with high FSH levels (greater than or equal to 10 IU/L) in preparation for in vitro fertilization-embryo transfer. Following retrieval, cells were isolated and then pooled within each individual patient and plated at 50,000 cells per well. Media was removed at 24 and 48 h and analyzed for dimeric and total inhibin concentrations by immunoassay as well as estradiol and progesterone concentrations by RIA. Dimeric inhibin was secreted at 2-fold higher concentrations in the low FSH group 43.2 pg/ml (30.8-60.6) (geometric mean and 95% confidence interval) compared with the high FSH group, 21.0 pg/ml (15.0-29.6), P < 0.004. Total inhibin was secreted at 1.8-fold higher concentrations in the low FSH group, 1148.2 pg/ml (931.1-1415.8) compared with the high FSH group, 639.7 pg/ml (428.5-955.0), P < 0.013. No significant differences in either estradiol or progesterone concentrations were noted. These data suggest that day 3 serum FSH is an indirect bioassay of dimeric inhibin production at the granulosa cell level. Thus, these data provide a potential physiological basis for day 3 serum FSH screening in ovulation induction and ART programs.