Effect of gonadotropin-releasing hormone agonist and antagonist on steroidogenesis of low responders undergoing in vitro fertilization

The aim of the study was to investigate the cause of the lower estradiol (E2) concentration in women treated with gonadotropin-releasing hormone (GnRH) antagonist compared with those treated with agonist protocol in in vitro fertilization (IVF). Thirty patients who were known low responders were prospectively randomized into two equal groups for IVF treatment. Group 1 used GnRH agonist (flare-up) protocol and group 2 used antagonist protocol. The results showed that serum luteinizing hormone (LH) levels were significantly higher in the agonist group during the folliculogenesis stage. Despite this higher LH, serum E2 levels were significantly higher in the agonist group on cycle day 2 only, not on day 5 or day 9. The significantly higher E2 level in the agonist group reappeared on the day of administration of human chorionic gonadotropin (hCG). The rate of folliculogenesis in the antagonist group was faster than in the agonist group; therefore their E2 production should have been higher on hCG day. Furthermore, the rate of decline in E2 after hCG administration was significantly higher in the antagonist group. These findings, along with the fact that both groups received exogenous LH (human menopausal gonadotropin) that should optimize steroidogenesis and make the difference in E2 insignificant, enable us to conclude that GnRH antagonists have a suppressive effect on the production of E2.