Pretreatment with estrogen does not affect IVF-ICSI cycle outcome compared with no pretreatment in GnRH antagonist protocol: a prospective randomized trial

Objective: To assess effects of estrogen pretreatment in GnRH antagonist protocol. Design: Prospective, randomized multicenter study. Setting: Ten private or university-based centers. Patient(s): A total of 472 patients undergoing IVF/ICSI. Intervention(s): Randomization by sealed envelopes to receive 17 beta-estradiol (4 mg/d) or no pretreatment before daily recombinant FSH administration started on the first day of estrogen discontinuation or on cycle day 2 in nonpretreated women. Main Outcome Measure(s): The primary outcome measure was the number of retrieved oocytes. Secondary efficacy variables included total FSH dose, cycle duration, and outcome. Result(s): The mean numbers of retrieved oocytes (10.9 +/- 5.7 vs. 10.2 +/- 5.6) and obtained embryos (5.5 +/- 3.7 vs. 4.8 +/- 3.7) were not significantly different between women allocated to estrogen pretreatment (n = 238) and no pretreatment (n = 234). Total FSH amount (1,557 +/- 408 vs. 1,389 +/- 347 IU) and stimulation duration (10.8 +/- 1.4 vs. 10.0 +/- 1.5 days) were slightly but significantly increased in pretreated patients. Positive pregnancy tests, ultrasound pregnancy rate, and delivery rate per cycle were similar (36%, 33%, and 26.6%, respectively, vs. 38.2%, 35.4%, and 30%). Conclusion(s): These data confirm that estrogen pretreatment is associated with requirement of higher FSH doses and longer duration of stimulation without any significant increase in the number of retrieved oocytes. However, estrogen does not affect cycle outcome and therefore might be used in clinical practice for programming IVF retrievals during working days. Clinical Trials Registration Number: NCT01489852. (Fertil Steril (R) 2012;97:1359-64. (C) 2012 by American Society for Reproductive Medicine.)