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Evidence Library · Risks

Birth defects after IVF, and after ICSI

A real but modest increase. The IVF signal mostly disappears after adjustment. The ICSI signal does not.

The cleanest study linked 308,974 South Australian births to a defects register, with diagnoses counted up to the child's fifth birthday:

GroupAny birth defectAdjusted odds ratio
No assisted conception5.8%reference
IVF7.2%1.07 (0.90 to 1.26), not significant
ICSI9.9%1.57 (1.30 to 1.90), remains significant
Any assisted conception8.3%1.28 (1.16 to 1.41)

Put in plain numbers: about 5 to 6 babies in every 100 conceived without help are born with a birth defect. After IVF that is around 7 in 100, and after ICSI around 10 in 100.

The adjustment column is the interesting part. Once the parents' age, health and the infertility itself were accounted for, the IVF excess was no longer statistically significant. The ICSI excess remained. The authors add that residual confounding cannot be excluded, which is the correct caution: couples needing ICSI differ from couples who do not.

A separate pooling of 45 cohort studies covering 92,671 assisted reproduction infants found any birth defect at relative risk 1.32 (95% CI 1.24 to 1.42), and 1.36 (95% CI 1.30 to 1.43) when restricted to single babies, so this is not an artefact of twins.

What follows from thisThe absolute increase is a few babies per hundred, and most defects in that count are minor. It is not a reason to avoid IVF, and it is not something to be reassured out of either. It is one more reason to ask why ICSI is being used if there is no sperm reason for it, since ICSI is where the signal that survives adjustment sits.
Where this comes from:
64. Davies MJ, Moore VM, Willson KJ, Van Essen P, Priest K, Scott H, et al. Reproductive technologies and the risk of birth defects. N Engl J Med. 2012;366(19):1803-1813.
65. Hansen M, Kurinczuk JJ, Milne E, de Klerk N, Bower C. Assisted reproductive technology and birth defects: a systematic review and meta-analysis. Hum Reprod Update. 2013;19(4):330-353.
61. Qin J, Liu X, Sheng X, Wang H, Gao S. Assisted reproductive technology and the risk of pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a meta-analysis of cohort studies. Fertil Steril. 2016;105(1):73-85.e1-6.

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