Prospective follow-up of 838 fetuses conceived after ovarian stimulation with corifollitropin alfa: comparative and overall neonatal outcome.

Is treatment with corifollitropin alfa, a new recombinant gonadotrophin with sustained follicle-stimulating activity, safe in terms of perinatal complications and birth defects in infants conceived following corifollitropin alfa treatment for contolled ovarian stimulation (COS)? In terms of neonatal outcome and risk of malformations, treatment with a single dose of corifollitropin alfa during COS is as safe as treatment with daily recombinant FSH (rFSH). This is the first pooled analysis of individual safety data in terms of neonatal outcome and major and minor congenital malformations collected following intervention trials of corifollitropin alfa. Pregnancy and follow-up studies were conducted prospectively and data were collected from all Phase II and III trials with corifollitropin alfa intervention, including two comparative randomized controlled trials (RCTs) in which patients received either a single dose of corifollitropin alfa or daily rFSH for the first 7 days of COS. Patients with ongoing pregnancies at 10 weeks after embryo transfer were followed up to labour and the health of the offspring was assessed up to 412 weeks after birth. Following corifollitropin alfa treatment prior to IVF or ICSI, the health of 677 pregnant women, 838 fetuses and 806 live born infants was evaluated. Among 440 fetuses in the corifollitropin alfa arm and 381 fetuses in the rFSH arm of the two RCTs, there were 424 (96.4) and 370 (98.7) live births, respectively. Neonatal characteristics, the frequency of premature births and the incidence of infant adverse events were similar in both treatment arms. The overall incidence of any 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 (OR) for major malformations, 0.71; 95 confidence interval, 0.361.38]. From 838 fetuses assessed in all corifollitropin alfa intervention trials, there were 806 (96.2) live births with a major malformation rate of 4.5 in live born infants. Both RCTs had a double-blind and active-controlled design and the adjudication of congenital malformations was also performed in a blinded fashion. As the total number of major malformations was limited (37), the confidence interval around the OR was rather wide. The similarity of corifollitropin alfa and rFSH with respect to the incidence of congenital malformations was consistent across the RCTs and pregnancy type (singleton, multiple). This suggests that this similarity could hold in general. Overall incidences, however, may depend on the definitions of malformations and rules to adjudicate these events as major or minor. Financial support for this study was provided by Merck, Sharp Dohme Corp. (a subsidiary of Merck Co. Inc., Whitehouse Station, NJ, USA). NCT00703014, NCT00702624, NCT 00702195, NCT 00702195, NCT 00702988, NCT 00702520, NCT 00702338and NCT 00702234.