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J Assist Reprod Genet. 2004 December; 21(12): 437–443.
PMCID: PMC3455612

A Meta-Analysis of Controlled Studies Comparing Major Malformation Rates in IVF and ICSI Infants with Naturally Conceived Children

Abstract

Purpose: To estimate the risk of major malformations in IVF and ICSI infants.

Methods: Forty-four studies published in English since 1990 where the major malformation rate for IVF or ICSI cases was compared to an appropriate control group were reviewed. Nineteen studies met all selection criteria. In addition, a quality score was developed to assess each study based on sample size, timing of diagnosis, appropriateness of control group and other factors.

Results: In 19 studies, the major malformation rates ranged from 0–9.5% for IVF; 1.1–9.7 for ICSI; and 0–6.9% in the control groups. When ICSI was compared to IVF, and multiple births compared to singleton, there were no statistically significant differences. When data from 16 studies involving 28,524 IVF infants and 2,520,988 spontaneously conceived controls and 7 studies involving 7234 ICSI infants and 978,078 controls were pooled, we found an overall odds ratio for the 19 studies of 1.29 (95% CI 1.01–1.67).

Conclusions: The overall odds ratio of 1.29 was statistically significant at the 5% level. These results may be useful for counseling ART patients and properly designing the consent forms used for ART procedures. It is not clear whether this risk is due to the procedures used in ART. We found that some of these studies have design flaws. All of them lacked an appropriate control group, i.e. infertile patients conceiving spontaneously. These flaws may create biases that would in almost all instances increase the risk of major malformations in the study group. Further research with better designed studies will likely result in a better estimate of the risk of major malformations associated with IVF and ICSI.

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Selected References

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