A randomized, prospective study of microdose leuprolide vs. ganirelix in IVF cycles for poor response patients

Abstract

Objective: Various stimulation protocols have emerged in attempts to improve the IVF outcomes for the poor responding patient during controlled ovarian hyperstimulation. This current investigation compares a GnRH antagonist protocol with a microdose GnRH agonist protocol in the treatment of “poor responders” undergoing IVF. Design: A randomized prospective study with clinical IVF outcome measures and laboratory assessment of embryo quality. Materials/Methods: Thirty-seven patients with a poor response during previous gonadotropin stimulated cycles were randomized to treatment with 300 IU r-FSH and 150 IU hMG in combination with either ganirelix acetate, 250 ug (Group A, 19 patients) or microdose leuprolide acetate (Group B, 18 patients). A poor response was defined as a peak estradiol (E2) ≤ 850 pg/ml and/or ≤ 4 preovulatory follicles ≥ 15 mm on the day of hCG administration while undergoing stimulation with 300 IU of gonadotropins with or without leuprolide acetate down regulation. Demographics of the two groups were analyzed for age, height, weight, body mass index, months of infertility, cycle day 3 FSH, LH and E2, diagnosis and previous number of cycles. In group A, ganirelix was administered when an E2 ≥ 250 pg/ml and follicles ≥ 12 mm were observed. The microdose protocol in group B was utilized as originally described by Schoolcraft. Analyzed cycle data included: cycle cancellation rates, peak E2, number of follicles ≥ 16 mm, number of stimulation days, ampules of FSH, ampules of hMG, number of oocytes, fertilization rates, number of embryos transferred and ongoing clinical pregnancy rates. Statistical analysis was done using t-test, rank sum, Chi-square or Fischer’s exact tests where appropriate. Results: No significant differences were noted in the demographic parameters between groups A and B. Cancellation rates for groups A and B for inadequate follicular development (≤3 follicles ≥16 mm) were 47.4% and 55.6% (p >0.05). Cancelled patients had a higher day 3 FSH than non-cancelled patients (9.5 ± 0.7 vs. 7.0 ± 0.5 IU/L, p = 0.007). For completed cycles in groups A vs. B, no statistically significant differences were noted in peak E2 (1380 ± 289 vs. 1810 ± 365 pg/ml), mean number of follicles >16 mm (4.0 vs. 3.5), mean number of stimulation days (9.8 ± 0.4 vs. 10.0 ± 0.8), mean number of ampules of FSH (35.9 ± 2.6 vs. 35.1 ± 3.5), mean number of ampules hMG (15.2 ± 1.9 vs. 17.8 ± 1.6), mean number of oocytes (8.8 ± 1.1 vs. 8.8 ± 1.6), fertilization rates (64.5% vs. 64.7%), mean number of embryos transferred (2.8 ± 0.3 vs. 3.1 ± 0.3) and ongoing pregnancy rate per embryo transfer (33.3% vs. 42.9%). Conclusions: GnRH antagonist utilization in poor responders appears to be as effective as the conventional microdose protocol in the treatment of poor responders. Unfortunately, cycle cancellation rates remain high in both treatment protocols. Supported by: An Unrestricted Educational Grant from Organon Pharmaceuticals, Inc. and in part by Ferring Pharmaceuticals.