Neonatal outcome in a Danish national cohort of 8602 children born after in vitro fertilization or intracytoplasmic sperm injection: the role of twin pregnancy

Abstract

Background: In Denmark, 4% of all infants are born after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and 40% of these children are twins.

Methods: We investigated neonatal outcome in a complete Danish IVF/ICSI birth cohort including 8602 infants born between 1995 and 2000: 3438 twins (40%) and 5164 singletons (60%). Births conceived after IVF or ICSI were identified by record linkage with the Danish IVF Registry and the National Medical Birth Registry. Data on neonatal outcome were collected from the National Patient Registry.

Results: IVF/ICSI twins had a 10-fold increased age- and parity-adjusted risk of delivery before 37 completed weeks [odds ratio (OR) 9.9, 95% confidence interval (95% CI) 8.7-11.3] and a 7.4-fold increased risk of delivery before 32 completed weeks (OR 7.4, 95% CI 5.6-9.8) compared with singletons. Correspondingly, ORs of birthweight <2500 g and birthweight <1500 g in twins were 11.8 (95% CI 10.3-13.6) and 5.4 (95% CI 4.1-7.0), respectively. The stillbirth rate was doubled in twins (13.1/1000) compared with singletons (6.6/1000) (p = 0.002). The risk of cesarean section and of admittance to a neonatal intensive care unit (NICU) was 4.6- and 1.8-fold higher in IVF/ICSI twins than in singletons. The rate of major malformations was 40.4/1000 in twins and 36.8/1000 in singletons (p = 0.4), whereas the total malformation rate (major + minor) was higher in twins (73.7/1000) than in singletons (55.0/1000) (p = 0.001). After exclusion of patent ductus arteriosus (PDA), which is strongly associated with preterm birth, no significant differences in any malformation rates were observed between twins and singletons. Apart from the frequency of ICSI children with hypospadias, which reached a significance level of p = 0.05, malformation rates in ICSI children were similar to those in IVF children.

Conclusions: This study indicates that neonatal outcome in IVF/ICSI twins is considerably poorer than in singletons. Thus, the impact is to draw the attention of clinicians to the benefit of elective single embryo transfer (eSET).