A Comparison of 3-Day and Daily FSH Injections (Days 1–6) in Women Undergoing Ovarian Stimulation

Abstract

Objectives: Daily injections of FSH is the standard regimen for follicular growth stimulation. FSH injected on alternate days has proven effective, as has an alternate-day, step-down FSH regimen. This study examined the efficacy of further spacing of FSH injections in women undergoing ovarian stimulation prior to IVF-ET. Design: A pilot, open, randomized, parallel group study conducted at a single German center (1998–2000), involving infertile women who failed to conceive after at least 1 year of unprotected coitus, and whose infertility justified IVF-ET. Materials and Methods: Following pituitary downregulation, patients were randomized to receive either 450 IU FSH at 3-day intervals or 150 IU FSH daily for the first 6 days of follicular stimulation. From day 7, dose titration of r-hFSH was based on ovarian response for all patients; treatment was continued until follicular development was considered adequate (one follicle ≥18 mm, two or more follicles ≥16 mm, E2 within an acceptable range). A single dose of 5000 IU urinary-hCG was administered to promote final follicular maturation. Results: 48 patients in the 3-day dose group and 50 in the daily dose group received hCG. Patients in the 3-day dose group had, by the end of the study, received significantly fewer injections than those who had received daily r-hFSH from day 1; 7.7 and 10.6, respectively (p<0.001, ANOVA). A significantly higher mean number of oocytes was retrieved in the daily dose group (11.0 compared with 8.5 in the 3-day dose group; p = 0.028, ANOVA), but there were no significant differences between the groups in mean values for: total cumulative r-hFSH dose, number of follicles ≥11 mm and ≥14 mm, number of oocytes inseminated (7.0 and 8.3 in the 3-day and daily dose groups, respectively) and number of transferred embryos (2.1 in both groups). Analysis of the implantation and pregnancy rates revealed a clear trend favoring the 3-day dose regimen. Implantation rates were 17% and 10% in the 3-day and daily dose groups, respectively (p = 0.264, ANOVA), while biochemical and clinical pregnancy rates were 29.2% and 14% (p = 0.086, Fisher’s exact test) and 25% and 14% (p = 0.206; Fisher’s exact test), respectively. Conclusions: In patients undergoing ovarian stimulation prior to IVF-ET, administration of r-hFSH at 3-day intervals for the first 6 days of follicular stimulation significantly reduces the total number of r-hFSH injections compared with a conventional FSH regimen (7.7 vs. 10.6, respectively, p<0.001). Pregnancy rates, while in favor of the 3-day dose group, did not achieve statistical significance difference. A reduction in injection frequency would be expected to further increase patient acceptability. This study was sponsored by Ares-Serona International SA, Geneva, Switzerland.