Accumulating evidence has linked the use of assisted reproductive techniques (ARTs) with increased risk of birth defects. Both in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are associated with increased risk of birth defects. A proportion of the excess birth defects after IVF or ICSI may result from patient characteristics related to infertility. The extent of the contribution of parental factors is unknown. It is also unknown whether the risk of birth defects is similar after IVF or ICSI.
The aim of this study was to compare the risk of birth defects among pregnancies of women who conceived with ART to those who had spontaneous pregnancies (without assisted conception). This latter group was then subdivided into women who had a previous birth with aid of ART, a history of infertility but no treatment with ART, or no history of infertility. Data were obtained by linkage of a census of treatment with ART in South Australia to both a registry of births and terminations that had a gestation period of at least 20 weeks or a birth weight of at least 400 g and to registries of birth defects (including cerebral palsy [CP] and terminations for defects at any gestational period). Two clinics in South Australia provided data on all patients treated for infertility from 1986 to 2002.
A total of 6163 of the 308,974 births available for analysis resulted from use of ART. In univariate analysis, there was a significantly increased risk of any birth defect after any assisted conception (513 defects, 8.3%), compared with risk after spontaneous births among fertile women (17,546 defects, 5.8%); the unadjusted odds ratio (OR) was 1.47, with a 95% confidence interval (CI) of 1.33 to 1.62. This risk remained significant after multivariate adjustment (adjusted OR [aOR], 1.28; 95% CI, 1.16–1.41). There was a significantly increased risk of birth defects associated with IVF (165 defects, 7.2%) in unadjusted analyses (OR, 1.26; 95% CI, 1.07–1.48), but the risk did not persist after adjustment (aOR, 1.07; 95% CI, 0.90–1.26). In the unadjusted data, the risk for birth defects was also increased with ICSI (139 defects, 9.9%); the OR was 1.77, with a 95% CI of 1.47 to 2.12. Unlike IVF, the risk remained significant after adjustment with ICSI (aOR, 1.57; 95% CI, 1.30–1.90). There was a significant increased risk of a birth defect among women with a history of infertility, with or without assisted conception.
These findings show that use of either IVF or ICSI is associated with a significant increase in risk of birth defects in unadjusted analyses. However, the increased risk of birth defects persists only after use of ICSI, but not IVF, after adjustment for parental factors and several other risk factors.
From the Robinson Institute (M.J.D., V.M.M., K.J.W.), Research Centre in the Early Origins of Health and Disease (M.J.D., V.M.M., K.J.W.), Discipline of Public Health (V.M.M., K.J.W.), and Discipline of Paediatrics and Reproductive Health (M.J.D., E.A.H.), University of Adelaide, the South Australian Birth Defects Register, Women’s and Children’s Hospital (P.V.E., H.S., E.A.H., A.C.), the Epidemiology Branch, South Australian Department of Health (K.P., A.C.), and the South Australian Clinical Genetics Service, SA Pathology (E.A.H.), Adelaide, South Australia, Australia.