A meta-analysis of the impact of IVF and ICSI on major malformations after adjusting for the effect of subfertility

J Assist Reprod Genet. 2011 Aug;28(8):699-705. doi: 10.1007/s10815-011-9583-z. Epub 2011 May 31.


Objective: To estimate the effect of assisted reproductive technology (ART) on major malformation (MM) rate in ART offspring independent of the effect of subfertility on MM.

Design: Meta-analysis.

Methods: This meta-analysis is based on our previously published meta-analysis of observational studies evaluating the relationship between ART treatment and MM rates, as well as recent research by Zhu et al. to estimate the impact of subfertility alone on MM in subfertile couples conceiving spontaneously.

Results: The overall odds ratio for MM in our original meta-analysis, in which all studies used apparently inappropriate control groups of "normal" populations, was 1.29 (95% CI 1.01-1.67). Here we attempted to estimate the risk of subfertility and used this estimate to perform an adjusted meta-analysis. Zhu et al. found that about 40% of the odds of MM was due to subfertility. When we took Zhu's finding into account, the adjusted odds ratio in the meta-analysis was 1.01 (95% CI 0.82-1.23).

Conclusions: Our study suggests ART does not increase the risk of MM as much as previously reported. More research is needed to quantify the underlying risk of subfertility and separate it from the risk associated with ART. Physicians who counsel subfertile couples should recognize that previous studies of MM rates in ART patients probably overestimated the risk.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Congenital Abnormalities / etiology*
  • Fertilization in Vitro / adverse effects*
  • Humans
  • Infertility / therapy*
  • Odds Ratio
  • Sperm Injections, Intracytoplasmic / adverse effects
  • Sperm Injections, Intracytoplasmic / methods