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BACKGROUND: It has been 10 years since we carried out a systematic search of the literature on birth defect risk in infants born following assisted reproductive technology (ART) compared with non-ART infants. Because of changes to ART practice since that review and the publication of more studies the objective of this review was to include these more recent studies to estimate birth defect risk after ART and to examine birth defect risk separately in ART singletons and multiples. METHODS: We searched Medline, Embase and Current Contents databases (1978-2012). We used the same data extraction sheet and questionnaire we had used previously with the addition of a quality score to the questionnaire. Pooled relative risk (RR) estimates were calculated using a random effects model. All data were analysed using Comprehensive Meta-Analysis V2. RESULTS: There were 45 cohort studies included in this review. ART infants (n = 92 671) had a higher risk of birth defects [RR 1.32, 95% confidence interval (CI) 1.24-1.42] compared with naturally conceived infants (n = 3 870 760). The risk further increased when data were restricted to major birth defects (RR 1.42, 95% CI 1.29-1.56) or singletons only (RR 1.36, 95% CI 1.30-1.43). The results for ART multiples were less clear. When all data for multiples were pooled the RR estimate was 1.11 (95% CI 0.98-1.26) but this increased to 1.26 (0.99-1.60) when the analysis was restricted to studies of ART twins where some adjustment was made for differences in zygosity distribution between ART and non-ART multiples. CONCLUSIONS: Birth defects remain more common in ART infants. Further research is required to examine risks for important subgroups of ART exposure.

Original publication




Journal article


Hum Reprod Update

Publication Date





330 - 353


IVF, assisted reproductive technology, congenital malformations, meta-analysis, systematic review, Congenital Abnormalities, Humans, Infant, Reproductive Techniques, Assisted, Risk Factors, Twins