Until recently, gonadotropin-releasing hormone (GnRH) agonists were the only choice available to physicians for prevention of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian stimulation. The recent FDA approval of GnRH antagonists for this indication gives clinicians some new options. Results of clinical trials to date suggest that, with GnRH antagonists, much shorter treatment regimens with fewer injections and possibly less gonadotropin can achieve good clinical results. In most of the trials performed to date, however, the GnRH antagonist regimens have been associated with a slightly lower pregnancy and implantation rate than the established GnRH agonist protocols. This remains the biggest hurdle to their more general acceptance. Herein, the possible contributing factors are discussed, and the proposal made that differences in serum estradiol patterns preceding oocyte retrieval are the most likely contributing factor.