Do the children born after assisted reproductive technology have an increased risk of birth defects? A systematic review and meta-analysis.

Background: Assisted reproductive technologies (ARTs) have made great progress. However, whether tube baby born after ART were at an increased risk of birth defects is not clear.Objective: To assess whether the ART increases the risk of birth defects in children born after ART.Search strategy: Medline, Google Scholar, and the Cochrane Library were searched.Selection criteria: Clinical trials that evaluate the risk of birth defect in children born after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) and natural conceptions (NC) were included. The primary outcome was the prevalence of birth defects.Data collection and analysis: The relative risk was used as the summary measure with random effects model. We assessed heterogeneity between studies using the I2 index.Main results: Totally 46 studies were included. The pooled relative risk (RR) estimated suggested there was an increased risk of birth defects in ART compared with the NC group (RR: 1.40; 95% CI 1.31-1.49). Twenty and fifteen studies were included to compare the risk of birth defects between NC and IVF/ICSI, respectively. The results indicated that both IVF and ICSI increase the risk of birth defects (IVF: RR 1.25; 95% CI 1.12-1.40; ICSI: RR 1.29; 95% CI 1.14-1.45). When subgroup according to plurality, 22 studies assessed the risk of birth defects after ART or NC in singletons and 15 studies evaluated the risk of birth defects in twins. The pooled RRs were 1.41 (95% CI 1.30-1.52) and 1.18 (95% CI 0.98-1.42), respectively.Conclusions: Children born after ART were at an increased risk of birth defects compared with NC. There was no difference in birth defects risk between ART twins and NC twins.