Assessing the Relationship Between Traditional In Vitro Fertilization and Birth Defects: A Systematic Review and Meta-Analysis

Abstract

Background Previously published meta-analyses revealed that IVF combined with intracytoplasmic sperm injection (ICSI) had an increased risk of birth defects in children. ICSI is more invasive, expensive, and time-consuming than IVF, but both result in comparable live birth rates. Currently, despite traditional IVF being used less frequently nationally and internationally than combined IVF/ICSI, it is important to understand the relationship between traditional IVF and birth defects due to a paucity of literature. Objective This systematic review and meta-analysis focused on whether traditional IVF techniques increase the risk for “all” birth defects and “major” birth defects in singletons compared to naturally conceived children. Search Strategy PubMed and EMBASE databases adhered to PRISMA guidelines. Selection Criteria Study selection consisted of original publications in English reporting birth defects for IVF singletons vs. naturally conceived children. Data Collection and Analysis Nine selected items from STROBE criteria were employed to rate study quality. Random effect models were used to calculate pooled odds ratios. Results From 916 publications, fifteen studies met eligibility criteria. Eight studies were rated as high quality, while the remaining 7 were rated as medium. A higher rate of “all” birth defects (pooled OR= 1.44 (95% CI:1.15-1.80) as well as a higher risk for “major” birth defects (pooled OR= 1.64; 95% CI: 1.24-2.18) were observed among traditional IVF-conceived singletons compared to naturally conceived children. Conclusions This is the first systematic review and meta-analysis to date to provide the highest available evidence that IVF is associated with “all” and “major” birth defects among IVF singletons compared to naturally conceived infants. Future large prospective studies should employ standardized reporting and uniform protocols for identifying birth defects with consistent diagnostic criteria for both minor and major birth defects, and comparable durations of follow-up in order to obtain an accurate estimate of birth defects after IVF.