A Patient Friendly Corifollitropin Alfa Protocol without Routine Pituitary Suppression in Normal Responders

Abstract

The release of corifollitropin alfa simplifies daily injections of short-acting recombinant follicular stimulating hormone (rFSH), and its widely-used protocol involves short-acting gonadotropins supplements and a fixed GnRH antagonist regimen, largely based on follicle size. In this study, the feasibility of corifollitropin alfa without routine pituitary suppression was evaluated. A total of 288 patients were stimulated by corifollitropin alfa on cycle day 3 following with routine serum hormone monitoring and follicle scanning every other day after 5 days of initial stimulation, and a GnRH antagonist (0.25 mg) was only used prophylactically when the luteinizing hormone (LH) was ≧ 6 IU/L (over half of the definitive LH surge). The incidence of premature LH surge (≧ 10 IU/L) was 2.4% (7/288) before the timely injection of a single GnRH antagonist, and the elevated LH level was dropped down from 11.9 IU/L to 2.2 IU/L after the suppression. Two hundred fifty-one patients did not need any antagonist (87.2% [251/288]) throughout the whole stimulation. No adverse effects were observed regarding oocyte competency (fertilization rate: 78%; blastocyst formation rate: 64%). The live birth rate per OPU cycle after the first cryotransfer was 56.3% (161/286), and the cumulative live birth rate per OPU cycle after cyrotransfers was 69.6% (199/286). Of patients who did and did not receive GnRH antagonist during stimulation, no significant difference existed in the cumulative live birth rates (78.4% vs. 68.3%, p = 0.25). The results demonstrated that the routine GnRH antagonist administration is not required in the corifollitropin-alfa cycles using a flexible and hormone-depended antagonist regimen, while the clinical outcome is not compromised. This finding reveals that the use of a GnRH antagonist only occasionally may be needed.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. The serum hormone profiles of the patients with and without GnRH antagonist administration.

L-rFSH w/ GnRH antagonist, the individuals who received GnRH antagonist in the follicular phase; L-rFSH w/o GnRH antagonist, the individuals who did not receive GnRH antagonist in the follicular phase. (A) Serum LH levels of the two groups; the LH levels on day 8 and day 12 were significantly higher in the L-rFSH with GnRH antagonist group [LH on day 8 = 6.2±3.8 IU/L vs. 2.0±1.7 IU/L, p<0.0001; LH on day 12 = 2.5±1.9 IU/L vs. 1.6±1.5 IU/L, p = 0.0047]. (B) Serum E2 levels of the two groups; the E2 level on day 12 was significantly higher in the L-rFSH with GnRH antagonist group [3450±276 pg/mL vs. 2528±183 pg/mL, p = 0.02]. (C) Serum P4 levels of the two groups; the P4 levels on day 8 and day 10 were significantly higher in the L-rFSH with GnRH antagonist group [P4 on day 8 = 1.8±0.5 ng/mL vs. 1.3±0.6 ng/mL, p<0.0001; P4 on day 10 = 1.9±0.9 ng/mL vs. 1.6±0.8 ng/mL, p = 0.02]. All the comparisons were using Mann-Whitney U test.