Safety of corifollitropin alfa in controlled ovarian stimulation for assisted reproductive technology: pregnancy and infant follow-up data

Introduction:

Corifollitropin alfa is a new recombinant gonadotropin with sustained follicle stimulating activity that has been proven safe and efficacious in achieving ongoing pregnancies after controlled ovarian stimulation (COS) for assisted reproductive technology (ART). To further ensure that the treatment is safe in terms of perinatal complications and birth defects in infants conceived by protocols that include corifollitropin alfa, pregnancy and infant follow-up trials were conducted.

Material and Methods:

Pregnancy and infant follow-up data (Care program) were collected from 2 large, controlled phase 3 trials, Engage (women weighing >60 kg) and Ensure (women weighing 60 kg). Included patients with ongoing pregnancies were previously treated during the first week of stimulation with either a single dose of corifollitropin alfa (Elonva, N.V. Organon) or with daily recombinant follicle-stimulating hormone (rFSH) (follitropin beta, Puregon Pen, N.V. Organon). Information on pregnancy and delivery complications, mode of delivery and neonatal characteristics was prospectively collected through routine assessments. Safety in the offspring was assessed from medical examinations at birth and within 3 months thereafter. Any abnormalities were recorded as adverse events and adjudicated externally by an independent medical expert as either major or minor congenital malformations (a major malformation was defined as any that causes functional impairment or requires surgical correction).

Results:

Follow-up data on 440 fetuses from 342 women who became pregnant after corifollitropin alfa treatment and 381 fetuses from 312 women who became pregnant after rFSH treatment were assessed. The corifollitropin alfa group and rFSH group included 247 and 243 singleton and 95 (27.8%) and 69 (22.1%) multiple pregnancies, respectively. There were 3 triplet pregnancies in the corifollitropin alfa group. In the corifollitropin alfa group, for 2 fetuses the outcome was unknown, 6 fetuses were lost before 20 weeks' gestation and 8 afterward, resulting in a total of 424 live-born infants (96.4%). Correspondingly, in the rFSH group the outcome was unknown for 5 fetuses, 4 fetuses were lost prior to 20 weeks' gestation and 2 afterward, resulting in a total of 370 live-born infants (97.1%). There were no relevant differences between the groups in type and incidence of pregnancy complications. The overall mean gestational age was 37.8 weeks in the corifollitropin alfa group and 38.2 weeks in the rFSH group. For both the singleton and multiple pregnancies, similar birth weights in the corifollitropin alfa and rFSH groups, respectively were reported, with a mean ( ± SD) birth weight of 3297 ( ± 534) g in the singletons born after corifollitropin alfa treatment. Apgar scores reported 1 and 5 minutes after birth were similar between groups. The incidence of infant adverse events was similar and the overall incidence of congenital malformations in live-born infants was 16.3% and 17.0%, with major malformation rates of 4.0% and 5.4% in the corifollitropin alfa and rFSH groups, respectively (odds ratio, 0.73; 95% confidence interval, 0.38-1.42).

Conclusions:

The health of 424 live-born infants conceived after treatment with corifollitropin alfa indicates that there are no differences in neonatal characteristics or in major or minor malformation rates when compared with 370 live-born infants conceived after treatment with daily rFSH. Together with the similar pregnancy progress and pregnancy complications, these data support the new corifollitropin alfa regimen as a safe treatment option for IVF patients and their off-spring.