Luteal Estradiol Pre-treatment Coordinates Follicular Growth During Controlled Ovarian Hyperstimulation with GnRH Antagonists

Background: The purpose of this study was to investigate whether luteal estradiol (E(2)) administration reduces follicular size discrepancies and enhances ovarian response in recombinant FSH (r-FSH)/GnRH antagonist protocols.

Methods: We studied prospectively 90 IVF-embryo transfer (ET) candidates who were randomly pre-treated with 17beta-E(2) (4 mg/day) from day 20 until next cycle day 2 (E(2) group, n = 47) or served as controls (control group, n = 43). On day 3, all women started r-FSH treatment. A single 3 mg dose of GnRH antagonist was administered eventually according to follicular maturation. Outcome measures were magnitude of size discrepancy of growing follicles on day 8 of r-FSH treatment and number of follicles >or=16 mm in diameter on the day of HCG.

Results: On day 8, follicles were smaller (9.9 +/- 2.5 versus 10.9 +/- 3.4 mm, P < 0.001) and their size discrepancies attenuated (P < 0.001) in the E(2) group compared with the control group. This was associated with more >or=16 mm follicles, mature oocytes and embryos in the E(2) group.

Conclusions: Luteal E(2) administration reduces the pace of growth, improves size homogeneity of antral follicles on day 8 of r-FSH treatment and increases the number of follicles reaching maturation at once. Coordination of follicular development optimizes ovarian response to r-FSH/GnRH antagonist protocols and may constitute an attractive approach to improving their outcome.