REVISITING GONADOTROPIN-RELEASING-HORMONE AGONIST PROTOCOLS AND MANAGEMENT OF POOR OVARIAN RESPONSES TO GONADOTROPINS

Within the past decade, gonadotrophin-releasing hormone (GnRH) agonist s have contributed greatly to the success of cycles programmed for in- vitro fertilization and embryo transfer, However, apart from a prevent ive effect on the luteinizing hormone (LH) surge, most of the benefici al effects of these molecules are still only partly known, A precise a nalysis of regimens using GnRH agonists for ovarian stimulation shows that many parameters may interfere with the outcome of long-term and s hort-term protocols, The great variability between these protocols ham pers our comprehension of the mechanisms involved in the overall clini cal improvement seen with this therapy, The hypophyseal desensitizatio n induced by GnRH agonists is greatly dependent on the dose and durati on of their administration, but the residual gonadotrophin secretion i s imperfectly estimated by hormonal measurements using radioimmunometr ic assays, Moreover, the specific role of GnRH agonist-induced ovarian quiescence on subsequent ovarian responsiveness to gonadotrophins and on endometrial receptivity deserves further investigation. Finally a direct ovarian action of GnRH agonists on steroidogenesis, folliculoge nesis and embryo quality is still controversial in humans, These putat ive deleterious effects of GnRH agonists have led some authors to reco mmend a reduction of both dose and duration of GnRH agonist administra tion for women identified by a poor response to gonadotrophins. Using this approach, a few reports have recently shown some clinical advanta ges for ovarian responsiveness but no convincing evidence for any impr ovement in pregnancy rate, It thus appears that the overall impact of GnRH agonists on reproductive function is still partly misunderstood.