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Induction of Multiple Follicular Development by a Single Dose of Long-Acting Recombinant Follicle-Stimulating Hormone (FSH-CTP, Corifollitropin Alfa) for Controlled Ovarian Stimulation before in Vitro Fertilization

Center for Reproductive Medicine (P.D., P.P.), Dutch-Speaking Brussels Free University, 1090 Brussels, Belgium; Center of Reproductive Medicine (B.C.F., N.G.B.), Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; University Hospital Gent (M.D.), B-9000 Gent, Belgium; and Clinical Development Department (B.M.M.), NV Organon, 5340 BH Oss, The Netherlands

Address all correspondence and requests for reprints to: Bernadette Mannaerts, M.Sc., Clinical Development Department, PO Box 20, 5340 BH Oss, The Netherlands. E-mail: b.mannaerts{at}organon.com.

In a first feasibility study, the efficacy and safety of a single dose of recombinant long-acting FSH (FSH-CTP) were investigated in in vitro fertilization (IVF) patients undergoing controlled ovarian stimulation with a flexible GnRH antagonist protocol. Eligible subjects were randomized to receive a single dose of 120 µg (n = 25), 180 µg (n = 24), or 240 µg (n = 25) corifollitropin alfa (FSH-CTP) or to start daily fixed doses of 150 IU recombinant FSH (rFSH) (n = 24, reference). Subjects who received a single dose of FSH-CTP continued 1 wk after injection (treatment d 8) with fixed daily doses of 150 IU rFSH (Puregon/Follistim) until the day of triggering final oocyte maturation.

The terminal half-life of FSH-CTP was, on average, 65 h and dose independent. Cycle cancellation before human chorionic gonadotropin (hCG) administration occurred in only three subjects treated with FSH-CTP. The median duration of stimulation was 10.0 d in each FSH-CTP group and 9.0 d in the daily rFSH group. The total number of follicles at least 11 mm at stimulation d 8 and at the day of hCG administration tended to increase with dose of FSH-CTP, although a significant dose-response relationship was revealed only for the number of follicles at least 15 mm on the day of hCG (P = 0.03). Serum estradiol levels and inhibin-B levels were not significantly different between the four groups on d 8 and on the day of hCG. In total, 12 subjects (17.6%) in the FSH-CTP groups and two subjects (8.3%) in the rFSH group experienced a premature LH rise (defined as LH 10 IU/liter) before the start of the GnRH antagonist (P value not significant between groups). This relatively high incidence of women demonstrating an early LH rise in the FSH-CTP groups may be related to the higher initial rises of serum estradiol and the use of a flexible GnRH antagonist protocol. The mean number of oocytes recovered per started cycle was higher in FSH-CTP-treated subjects compared with rFSH-treated subjects (significant at P = 0.03 for the 240-µg FSH-CTP group), but no difference could be noted between the number of good quality embryos (range of means, 3.8–4.8 per attempt), and equal numbers of embryos were available for embryo transfer. In summary, FSH-CTP appeared to be a potent inducer of multiple follicular growth; additional research will be needed to select the optimal FSH-CTP dose and treatment time interval.

This work was supported by NV Organon.

Abbreviations: AUC, Area under the serum concentration-time curve; C_max, peak serum concentration; CTP, carboxyl-terminal part; E₂, estradiol; EIA, enzyme immunoassay; ET, embryo transfer; FSH-CTP, long-acting recombinant FSH; hCG, human chorionic gonadotropin; ICSI, intracytoplasmatic sperm injection; IVF, in vitro fertilization; OHSS, ovarian hyperstimulation syndrome; P, progesterone; rFSH, recombinant FSH.

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