Fifty-six studies were included in the review. At least 124,468 women underwent IVF or ICSI; the number of control participants was not reported. One study had a case control design; details on the others were not reported.
IVF and/or ICSI versus spontaneous conception: There were 46 studies and 24,468 participants underwent IVF or ICSI. Compared with spontaneous conception, IVF and/or ICSI were associated with a statistically significant increased risk of birth defects (RR 1.37, 95% CI 1.26 to 1.48; Ι²=74.6%). In subgroup analyses, the risk of birth defects was significantly larger in clinic-based studies and studies with fewer than 1,000 participants. Sensitivity analysis (exclusion of an outlier study) did not markedly change the estimate and a comparison of analyses using crude or adjusted estimates was not significantly different. Substantial heterogeneity was reported for most subgroup analyses.
IVF versus ICSI: There were 24 studies and 74,644 participants underwent IVF or ICSI. There was no evidence of significant differences in the overall risk of birth defects between IVF and ICSI (RR 1.05, 95% CI 0.91 to 1.20; Ι²=50.6%) or in any of the subgroup analyses.
There was no evidence of publication bias from the funnel plots for IVF and/or ICSI compared to spontaneous conception or for IVF compared to ICSI.