GONADOTROPIN-RELEASING-HORMONE ANTAGONIST VERSUS AGONIST ADMINISTRATION IN WOMEN UNDERGOING CONTROLLED OVARIAN HYPERSTIMULATION - CYCLE PERFORMANCE AND IN-VITRO STEROIDOGENESIS OF GRANULOSA-LUTEIN CELLS

OBJECTIVES: We sought to determine the effectiveness of a gonadotropin -releasing hormone antagonist compared with an agonist in suppressing a spontaneous luteinizing hormone surge in women undergoing controlled ovarian hyperstimulation for in vitro fertilization and gamete intraf allopian transfer and to examine whether in vivo administration of the se analogs effects granulosa-lutein cells steroidogenesis in vitro. ST UDY DESIGN: This prospective case-control study included 30 healthy wo men undergoing ovarian hyperstimulation with human menopausal gonadotr opins. Fifteen women received the Nal-Glu antagonist, 5 mg intramuscul arly daily, when the lead follicle was greater than or equal to 15 mm or serum estradiol level was greater than or equal to 500 pg/ml. The c ontrol group included 15 women who underwent oocyte retrieval on the s ame day as the study subjects and were given the agonist leuprolide ac etate, 250 mu g subcutaneously daily, starting on cycle day 1. Granulo sa-lutein cells were purified from follicular aspirates from six subje cts and six controls and cultured in parallel, evaluating basal proges terone production, progesterone response to follicle-stimulating hormo ne or luteinizing hormone and aromatase activity. RESULTS: No differen ce was demonstrated in the total amount of gonadotropins received by t he two groups. Overall, the gonadotropin-releasing hormone antagonist was given for only 2.5 +/- 0.2 (mean +/- SEM) days before human chorio nic gonadotropin administration. The antagonist group showed significa ntly lower levels of serum luteinizing hormone than did the agonist gr oup, 1.0 +/- 0.2 versus 4.2 +/- 0.5 mlU/ml (p = 0.0001) on the day of human chorionic gonadotropin administration. Serum estradiol levels we re significantly lower in the antagonist than the agonist group, 820 /- 120 versus 1361 +/- 110 pg/ml (p = 0.003) on the day of human chori onic gonadotropin administration, There was no difference in the numbe r of retrieved oocytes, but the antagonist group had a higher proporti on of mature oocytes, 82% +/- 4% versus 62.4% (p = 0.02), and a higher proportion of embryos of good quality, 69.8% +/- 9.8% versus 44.3% +/ - 7.2% (p = 0.03) in the agonist group. Granulosa-lutein cells from an tagonist-treated women showed significantly lower aromatase activity t he first 6 hours after retrieval, 17.6 +/- 1.6 versus 31.3 +/- 7.4 ng/ ml per 6 hours estradiol (p = 0.03), whereas basal and gonadotropin-st imulated with progesterone responses were similar. CONCLUSION: Gonadot ropin-releasing hormone antagonist administration during the late foll icular phase resulted in lower serum luteinizing hormone and estradiol levels and more mature oocytes and embryos of better quality compared with gonadotropin-releasing hormone agonist administration. These res ults suggest that gonadotropin-releasing hormone antagonist administra tion in ovarian hyperstimulation has practical advantages over the ago nist regimen. Gonadotropin-releasing hormone analogs may have direct a ction on ovarian function with differential effects on granulosa-lutei n cell aromatase activity. This could explain the lower serum estradio l levels routinely observed in women given gonadotropin-releasing horm one antagonist.