Steroid reduction during ovarian stimulation impairs oocyte fertilization, but not folliculogenesis, in rhesus monkeys

Objective: To test the hypothesis that steroids locally modulate and may be required for normal follicular function and gametogenesis in primates, the effects of steroid reduction during gonadotropin-stimulated folliculogenesis was studied in rhesus monkeys. Design: Animals received human FSH (hFSH; days 1 to 6) and hFSH + human LH (hLH; day 7) to promote multiple follicular growth, and then received hCG (day 8) for ovulatory maturation. Four animals received trilostane (3β-hydroxysteroid dehydrogenase inhibitor) on days 1 to 8 or no inhibitor (controls; n = 4). Follicles were aspirated 34 hours after hCG. Main Outcome Measures: Follicular growth, serum E₂, P, and pregnenolone, oocyte nuclear maturity, and IVF. Results: Trilostane markedly reduced E₂ to levels as low as 7% of controls throughout the follicular phase. Pregnenolone was 66 fold greater during trilostane treatment relative to controls. In both groups, P was at baseline during follicular stimulation but was reduced for 72 hours after hCG in trilostane-treated animals. Despite E₂ suppression, follicular growth and oocyte nuclear maturity were unaltered by trilostane. Trilostane hindered the fertilizability of metaphase II oocytes (15%) in three of four animals compared with controls (65%). Metaphase I oocytes that required >8 hours to complete meiosis in vitro failed to fertilize in the same three of four receiving trilostane relative to controls (31%). Conclusions: Follicular growth and oocyte meiosis did not require high or increasing E₂ levels. Levels of follicular products other than E₂ may be of value in determining the progress of ovarian stimulation protocols. However, the acquisition of oocyte competence for fertilization may require steroids.