In vitro fertilization is associated with an increase in major birth defects

OBJECTIVE: To determine the risk of major birth defects in cohorts of children conceived through IVF or through IUI as compared with naturally conceived children. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): Children conceived by IVF or IUI at the University of Iowa from 1989 through 2002, compared with a matched cohort of naturally conceived children. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Outcome data were obtained from Iowa state birth and fetal death certificates and from the Iowa Birth Defects Registry. RESULT(S): Ninety of 1,462 IVF-conceived children (6.2%) and 17 of 343 IUI-conceived children (5.0%) had a major birth defect, compared with 369 of 8,422 naturally conceived children (4.4%). The adjusted odds ratio of a major birth defect in all IVF-conceived children was 1.30 (95% confidence interval [CI] 1.00-1.67) and 1.11 (95% CI 0.67-1.84) for IUI-conceived children. The birth defect rate was increased after IVF when the analysis was limited to term singletons. Cardiovascular and musculoskeletal defects and known birth defect syndromes were increased after IVF. Among IVF-conceived children, there was no difference in birth defect rates after intracytoplasmic sperm injection (ICSI) or after transfer of cryopreserved embryos. CONCLUSION(S): Infants conceived through IVF have a slightly higher rate of major birth defects. More birth defects are noted among children born to infertile couples treated with IUI, although this difference is not statistically significant. Larger studies of infants conceived by infertile couples after all types of infertility treatment are needed to definitively determine whether the increased risk of birth defects is secondary to problems inherent in the infertile couple and/or factors associated with some aspect of the treatment.