Assisted Reproduction · Safety and Risks

Congenital anomalies observed in children conceived through assisted reproductive technology-a systematic review and meta-analysis

Bhat P, Dhyani VS, Lakshmi V, Uppangala S, Adiga SK, Adiga P, Kumar P, Gupta A

Published May 2025 Journal of assisted reproduction and genetics
DOI 10.1007/s10815-025-03454-0 PMID 40163274 PMC PMC12167209

RRM Academy Synopsis

Birth defects are slightly more common after ART conception

Birth defects were about 39% more likely after ART than after spontaneous conception, a meta-analysis of 70 studies found. The authors estimate about 2.5 out of 100 children conceived spontaneously and about 3.5 out of 100 conceived with ART had a birth defect.

Key Findings

  • Across 70 studies, the pooled log risk ratio for congenital anomalies after ART versus spontaneous conception was 0.327 (95% CI 0.274 to 0.381), a risk ratio of 1.39.
  • The authors estimated anomaly incidence at 2.48% for spontaneously conceived children and 3.45% for ART-conceived children, an absolute difference of 0.97 percentage points.
  • ICSI versus IVF in 29 studies: log risk ratio 0.0877 (95% CI 0.058 to 0.118), with anomalies in 3.34% after ICSI and 3.06% after IVF.
  • Fresh versus frozen embryo transfer in 30 studies: log risk ratio 0.117 (95% CI 0.036 to 0.199), with anomalies in 2.21% after fresh and 1.97% after frozen transfer.
  • Day 5 versus Day 3 transfer in 7 studies: log risk ratio −0.304 (95% CI −0.564 to −0.044), with anomalies in 3.03% after Day 5 and 4.10% after Day 3.

Interpretation

The review pooled published studies with a random-effects model. Results varied widely between studies. Heterogeneity (I-squared) was 92.47% in the main comparison, and the 95% prediction interval for the log risk ratio, −0.027 to 0.682, includes values below zero. The authors name maternal age, infertility itself, parental health conditions, lifestyle and genetics as factors that may add risk apart from ART. The review included English-language published studies only. The Day 5 versus Day 3 result rests on 7 studies. The authors note possible publication bias in the fresh versus frozen comparison.

RRM Context

IVF bypasses infertility and leaves unresolved why conception fails. The review compares ART with spontaneous conception. The authors write that infertility conditions in either partner may raise the risk of birth defects. Restorative reproductive medicine evaluates and treats the cause of infertility in both partners. Conception that follows takes place in vivo.

Abstract

Congenital anomalies (CAs) are a leading cause of perinatal and child mortality. With the increasing use of assisted reproductive technology (ART), there is a growing need for research on the health outcomes of children conceived through ART. This systematic review was performed to assess the incidence of CAs in ART-conceived children compared to those conceived naturally. This review followed the PRISMA 2020 guidelines and was registered with PROSPERO. A total of 113 studies were included in this meta-analysis, comprising 768,929 children in the ART group and 40,709,337 children in the control group which comprised spontaneously conceived (SC) children. The primary findings indicated that ART-conceived children have a marginally higher risk of CAs compared to the control group. Subgroup analyses showed that children conceived via ICSI, Day 3 transfer, and fresh embryo transfer (ET) had a slightly higher risk of CAs than those conceived via IVF, Day 5 transfer, or frozen embryo transfer (FET). The study highlights a slightly increased incidence of CAs among ART-conceived children over SC children, underscoring the importance of improving ART methods and closely monitoring the health of these children to reduce the risk of CAs.

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Assisted Reproduction › Safety and Risks › Birth Defects
Paripoorna Bhat, Vijay Shree Dhyani, Vani Lakshmi, Shubhashree Uppangala, Satish Kumar Adiga, Prashanth Adiga, Pratap Kumar, Aditi Gupta
P Bhat, V Dhyani, V Lakshmi, S Uppangala, S Adiga, P Adiga, P Kumar, A Gupta
PMID 40163274 40163274 DOI 10.1007/s10815-025-03454-0 10.1007/s10815-025-03454-0 Bhat et al. 2025, Bhat 2025