Journal of Assisted Reproduction and Genetics

, Volume 28, Issue 8, pp 699–705

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

  • Alfred A. Rimm
  • Alyce C. Katayama
  • K. Paul Katayama
Assisted Reproduction Technologies

DOI: 10.1007/s10815-011-9583-z

Cite this article as:
Rimm, A.A., Katayama, A.C. & Katayama, K.P. J Assist Reprod Genet (2011) 28: 699. doi:10.1007/s10815-011-9583-z



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.




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.


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).


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.


Subfertility and major malformationsART outcomesMeta-analysisIVF/ICSI outcomes

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Alfred A. Rimm
    • 1
  • Alyce C. Katayama
    • 2
  • K. Paul Katayama
    • 3
  1. 1.Department of Epidemiology and BiostatisticsCase Western Reserve University School of MedicineClevelandUSA
  2. 2.Health Law Group, Quarles & Brady LLPMilwaukeeUSA
  3. 3.Department of Obstetrics and GynecologyUniversity of Wisconsin School of Medicine and Advanced Institute of FertilityMilwaukeeUSA