Objective: To determine pregnancy course and major malformation rate after intracytoplasmic sperm injection (ICSI).
Design: Prospective, controlled, multicenter, nationwide German cohort study.
Setting: Tertiary infertility centers in Germany.
Patient(s): Three thousand three hundred seventy-two children and fetuses and 8,016 children and fetuses after the 16th week of gestation in pregnancies after ICSI and natural conception, respectively.
Intervention(s): Standardized prospective follow-up.
Main outcome measure(s): Major malformation rate.
Result(s): The major malformation rate was 8.7% (295/3,372) for the ICSI cohort and 6.1% (488/8,016) for the population-based control cohort (relative risk, 1.44 [1.25-1.65]). After adjustment for risk factors, the risk declined (adjusted odds ratio, 1.24 [95% CI, 1.02-1.50]). Regarding singletons, there was a significant difference for birth weight and gestational age, with a higher number of preterm and low birth weight children in pregnancies achieved after ICSI.
Conclusion(s): Children who are born after intracytoplasmic sperm injection have an increased risk of a major congenital malformation compared with those born after spontaneous conception. This risk is mainly due to paternal and maternal risk factors, which are more prevalent in couples who use ICSI for reproduction. An infertility-linked risk is highly probable for the observed findings. A technique-related risk, however, cannot be ruled out.