A randomized controlled trial of increasing recombinant follicle-stimulating hormone after initiating a gonadotropin-releasing hormone antagonist for in vitro fertilization-embryo transfer

Objective: Pituitary suppression with a GnRH antagonist before IVF may result in a plateau or decrease in estradiol levels. We sought to investigate the effect of increasing recombinant FSH (rFSH) after starting a GnRH antagonist on estradiol levels implantation rates, and pregnancy rates. Design: Prospective, randomized multicenter study. Setting: Medical center and private practice. Patient(s): Sixty infertile women undergoing IVF who met the appropriate inclusion criteria. Intervention(s): Participants were pretreated with combined oral contraceptives (COCs) and received a dose 150-300 IU of rFSH 5 days after taking their last COC. They were randomly assigned to receive their current dose of rFSH (control group) or an additional 75 IU of rFSH (step-up group) after starting a GnRH antagonist. Daily GnRH antagonist injections were started when the lead follicles were 13-14 mm in diameter and continued until hCG was given when two follicles were >= 18 mm. One to three embryos were transferred 3 or 5 days following oocyte retrieval. Women with PCOS, a body mass index > 33, a day 3 FSH > 14.1 mIU/ml, or prior poor stimulation were excluded. Main Outcome Measure(s): The primary endpoints of this pilot study were embryo implantation, pregnancy, and livebirth rates. Secondary endpoints included the amount and days of rFSH; number of days of GnRH antagonist use; estradiol levels on the day of GnRH antagonist initiation, day 1 and day 2 after initiation, and on the day of hCG, endometrial stripe thickness; number of follicles; and number of oocytes. Result(s): No differences were reported were reported within the groups with respect to age, BMI, baseline FSH, use of intracytoplasmic sperm injection, vials of rFSH, number of GnRH antagonist, changes in estradiol patterns, or peak estradiol level. The control and step-up groups had similar pregnancies (73.3% vs. 63.3%, P=.41), clinical pregnancies (70.0% vs. 60.0%, P=.42), live births (56.7% vs. 60.0%, P=.8), and implantation rates (50.0% and 39.1%, P=.22). Conclusion(s): The use of rFSH and a GnRH antagonist in good candidates for IVF resulted in outstanding implantation and pregnancy rates. Increasing the dose of rFSH after starting a GnRH antagonist does not alter the estradiol response or improve the implantation and pregnancy rates.