A large double-blind efficacy and safety trial of corifollitropin alfa versus daily recombinant FSH in women 35 to 42 years of age undergoing ovarian stimulation prior to IVF or ICSI (pursue trial)

ObjectiveTo examine the efficacy and safety of a single injection of corifollitropin alfa (CFA) vs daily rFSH for ovarian stimulation in women aged 35–42 years.DesignPhase 3 randomized, double-blind, double-dummy, active-controlled, noninferiority trial.Materials and methods1390 women were randomized and treated at 33 IVF centers in the USA (NCT01144416). During the first 7 days of ovarian stimulation, 694 women received a single injection of 150 μg CFA and 696 were treated with daily 300 IU rFSH. When required, they continued the cycle with daily rFSH (maximally 300 IU) until 3 follicles reached ≥17 mm. Ganirelix acetate (0.25 mg) was started on stimulation day 5 and recombinant human chorionic gonadotropin was given to trigger oocyte maturation. Three days after oocyte pick-up 2 embryos were transferred. The primary end point was vital pregnancy (≥1 fetus with heart activity ≥35 days after embryo transfer) and the predefined noninferiority margin was –8%. Secondary end points included number of oocytes retrieved, ongoing pregnancy rate (≥70 days after embryo transfer), and safety evaluations.ResultsVital pregnancy and ongoing pregnancy rates per started cycle were 23.9% and 22.2% in the CFA group and 26.9% and 24.0% in the rFSH group. The estimated differences and 95% confidence intervals were –3.0% [–7.4 to 1.4] for the vital pregnancy rate and –1.9% [-6.1 to 2.3] for the ongoing pregnancy rate. The mean (standard deviation) number of recovered oocytes was 10.7 (7.2) and 10.3 (6.8) in the CFA and rFSH groups, respectively, with an estimated difference of +0.5 [–0.2 to 1.2] oocytes. The incidence of serious adverse events (SAEs) was 0.4% vs 2.6% in the CFA and rFSH groups, respectively. The incidence of AEs (SAEs) of moderate/severe ovarian hyperstimulation syndrome (OHSS) was 0.7% (0%) vs 1.4% (0.7%), respectively.ConclusionCFA was proven noninferior to rFSH in terms of efficacy and was well tolerated in women aged 35–42 years. ObjectiveTo examine the efficacy and safety of a single injection of corifollitropin alfa (CFA) vs daily rFSH for ovarian stimulation in women aged 35–42 years. To examine the efficacy and safety of a single injection of corifollitropin alfa (CFA) vs daily rFSH for ovarian stimulation in women aged 35–42 years. DesignPhase 3 randomized, double-blind, double-dummy, active-controlled, noninferiority trial. Phase 3 randomized, double-blind, double-dummy, active-controlled, noninferiority trial. Materials and methods1390 women were randomized and treated at 33 IVF centers in the USA (NCT01144416). During the first 7 days of ovarian stimulation, 694 women received a single injection of 150 μg CFA and 696 were treated with daily 300 IU rFSH. When required, they continued the cycle with daily rFSH (maximally 300 IU) until 3 follicles reached ≥17 mm. Ganirelix acetate (0.25 mg) was started on stimulation day 5 and recombinant human chorionic gonadotropin was given to trigger oocyte maturation. Three days after oocyte pick-up 2 embryos were transferred. The primary end point was vital pregnancy (≥1 fetus with heart activity ≥35 days after embryo transfer) and the predefined noninferiority margin was –8%. Secondary end points included number of oocytes retrieved, ongoing pregnancy rate (≥70 days after embryo transfer), and safety evaluations. 1390 women were randomized and treated at 33 IVF centers in the USA (NCT01144416). During the first 7 days of ovarian stimulation, 694 women received a single injection of 150 μg CFA and 696 were treated with daily 300 IU rFSH. When required, they continued the cycle with daily rFSH (maximally 300 IU) until 3 follicles reached ≥17 mm. Ganirelix acetate (0.25 mg) was started on stimulation day 5 and recombinant human chorionic gonadotropin was given to trigger oocyte maturation. Three days after oocyte pick-up 2 embryos were transferred. The primary end point was vital pregnancy (≥1 fetus with heart activity ≥35 days after embryo transfer) and the predefined noninferiority margin was –8%. Secondary end points included number of oocytes retrieved, ongoing pregnancy rate (≥70 days after embryo transfer), and safety evaluations. ResultsVital pregnancy and ongoing pregnancy rates per started cycle were 23.9% and 22.2% in the CFA group and 26.9% and 24.0% in the rFSH group. The estimated differences and 95% confidence intervals were –3.0% [–7.4 to 1.4] for the vital pregnancy rate and –1.9% [-6.1 to 2.3] for the ongoing pregnancy rate. The mean (standard deviation) number of recovered oocytes was 10.7 (7.2) and 10.3 (6.8) in the CFA and rFSH groups, respectively, with an estimated difference of +0.5 [–0.2 to 1.2] oocytes. The incidence of serious adverse events (SAEs) was 0.4% vs 2.6% in the CFA and rFSH groups, respectively. The incidence of AEs (SAEs) of moderate/severe ovarian hyperstimulation syndrome (OHSS) was 0.7% (0%) vs 1.4% (0.7%), respectively. Vital pregnancy and ongoing pregnancy rates per started cycle were 23.9% and 22.2% in the CFA group and 26.9% and 24.0% in the rFSH group. The estimated differences and 95% confidence intervals were –3.0% [–7.4 to 1.4] for the vital pregnancy rate and –1.9% [-6.1 to 2.3] for the ongoing pregnancy rate. The mean (standard deviation) number of recovered oocytes was 10.7 (7.2) and 10.3 (6.8) in the CFA and rFSH groups, respectively, with an estimated difference of +0.5 [–0.2 to 1.2] oocytes. The incidence of serious adverse events (SAEs) was 0.4% vs 2.6% in the CFA and rFSH groups, respectively. The incidence of AEs (SAEs) of moderate/severe ovarian hyperstimulation syndrome (OHSS) was 0.7% (0%) vs 1.4% (0.7%), respectively. ConclusionCFA was proven noninferior to rFSH in terms of efficacy and was well tolerated in women aged 35–42 years. CFA was proven noninferior to rFSH in terms of efficacy and was well tolerated in women aged 35–42 years.