Does Intracytoplasmic Sperm Injection Pose an Increased Risk of Genitourinary Congenital Malformations in Offspring Compared to In Vitro Fertilization? A Systematic Review and Meta-Analysis

PurposeWe systematically reviewed and performed a meta-analysis of the genitourinary congenital malformation rate after conception by intracytoplasmic sperm injection compared to in vitro fertilization.Materials and MethodsWe systematically reviewed studies to compare perinatal outcomes between children conceived by intracytoplasmic sperm injection vs in vitro fertilization. Studies showing genitourinary congenital malformation rates were included. We assessed the risk of bias, focusing on the quality of genitourinary congenital malformation reporting and analysis targeted at singletons. Meta-analysis was done using a random effects model for 3 outcomes, including overall genitourinary congenital malformation, hypospadias and cryptorchidism. Sensitivity analysis was also performed in only studies at low risk for bias.ResultsThe initial search yielded 1,482 articles. We performed a full text review of 111 of these studies, of which 22 met inclusion criteria for systematic review. Meta-analysis of intracytoplasmic sperm injection and in vitro fertilization in 12,270 and 24,240 cases, respectively, revealed that intracytoplasmic sperm injection was associated with a significantly higher rate of overall genitourinary congenital malformation compared to in vitro fertilization (OR 1.27, 95% CI 1.02–1.59, p = 0.04). However, when including only 4 studies at low risk for bias with a total of 7,727 and 14,308 intracytoplasmic sperm injection and in vitro fertilization cases, respectively, the difference was not significant (OR 1.28, 95% CI 1.00–1.64, p = 0.05). There was no statistically significant difference in the rate of hypospadias (OR 1.21, 95% CI 0.87–1.69) or cryptorchidism (OR 1.39, 95% CI 0.97–2.00) between males conceived by intracytoplasmic sperm injection vs in vitro fertilization. On all analyses there was no significant statistical heterogeneity between studies (I2 = 0).ConclusionsIntracytoplasmic sperm injection is associated with a slightly higher risk of genitourinary malformation in offspring than in vitro fertilization. However, when only higher quality studies were analyzed, the difference was not significant. The hypospadias and cryptorchidism rates in offspring are similar for the 2 conception methods.