Synchronization of ovarian stimulation with follicle wave emergence in patients undergoing in vitro fertilization with a prior suboptimal response: a randomized, controlled trial

Objective: To test the hypothesis that synchronizing initiation of ovarian stimulation with follicle wave emergence would optimize IVF/intracytoplasmic sperm injection (ICSI) outcomes in patients with a prior suboptimal response. Design: Prospective, randomized, controlled trial. Setting: Academic and private reproductive endocrinology and infertility centers. Patient(s): Eighty women <= 43 years of age with a history of a suboptimal response. Intervention(s): Initiation of recombinant FSH/GnRH antagonist/recombinant LH/hCG on day 1 (n = 39) or day 4 (n = 41). Main Outcome Measure(s): Numbers of clinical and biochemical pregnancies, follicles >= 10 and >= 15 mm, oocytes collected, fertilized oocytes, cleavage stage embryos, and blastocysts; serum E-2 concentrations. Outcomes were compared between treatment groups. Result(s): The numbers of follicles that developed to >= 10 and >= 15 mm and serum E-2 were greater when recombinant FSH was initiated on day 1 (5.4, 4.3, 5,827.2 pmol/L) versus day 4 (3.6, 2.5, 4,230.1 pmol/L). The numbers of collected, metaphase II, and fertilized oocytes; cleavage stage embryos; and blastocysts were not different between groups. When we evaluated only those cycles that proceeded to oocyte pick-up, a lower implantation rate (16.1%, 56.0%), biochemical pregnancy rate (PR) (16.1%, 48.0%), and clinical PR (12.9% vs. 36.0%) were detected in the day 1 group versus day 4 group. Conclusion(s): Synchronizing initiation of ovarian stimulation with follicle wave emergence in patients with a prior suboptimal response resulted in an increase in the number of dominant follicles and serum E-2 concentrations; however, improvements in oocyte, embryo, or pregnancy outcomes did not occur. Clinical Trial Registration Number: NCT00439829. (Fertil Steril (R) 2012;98:881-7. (C) 2012 by American Society for Reproductive Medicine.)