Revisiting gonadotrophin-releasing hormone agonist protocols and management of poor ovarian responses to gonadotrophins

Within the past decade, gonadotrophin-releasing hormone (GnRH) agonists have contributed greatly to the success of cycles programmed for in-vitro fertilization and embryo transfer, However, apart from a preventive effect on the luteinizing hormone (LH) surge, most of the beneficial effects of these molecules are still only partly known, A precise analysis of regimens using GnRH agonists for ovarian stimulation shows that many parameters may interfere with the outcome of long-term and short-term protocols, The great variability between these protocols hampers our comprehension of the mechanisms involved in the overall clinical improvement seen with this therapy, The hypophyseal desensitization induced by GnRH agonists is greatly dependent on the dose and duration of their administration, but the residual gonadotrophin secretion is imperfectly estimated by hormonal measurements using radioimmunometric 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, folliculogenesis and embryo quality is still controversial in humans, These putative deleterious effects of GnRH agonists have led some authors to recommend a reduction of both dose and duration of GnRH agonist administration for women identified by a poor response to gonadotrophins. Using this approach, a few reports have recently shown some clinical advantages for ovarian responsiveness but no convincing evidence for any improvement in pregnancy rate, It thus appears that the overall impact of GnRH agonists on reproductive function is still partly misunderstood.