Meta-Analyses of Studies Evaluating the Impact of Assisted Reproductive Technology on Malformation in Offspring and Protocol Recommendations for Future Assisted Reproductive Technology Outcome Studies

OBJECTIVE: To update the estimate of the relationship between assisted reproductive technology (ART) and malformation in the offspring, to make recommendations about procedures for future research, and to estimate how much of the observed outcome might be attributable to ART procedures as opposed to subfertility. STUDY DESIGN: Meta-analysis of clinical studies that each had more than 500 in vitro fertilization (IVF) or IVF with intracytoplasmic sperm injection (ICSI) patients and which presented adjusted odds ratios (AORs) for the risk of malformation (major or all) in the offspring. RESULTS: Our meta-analysis found an AOR of 1.28, suggesting that ART increases risk of malformation by 28%. Subgroup analyses showed that studies with longer follow-up found about 30% higher incidence of malformation. ICSI posed a higher malformation risk than did IVF (AOR 1.35 vs. 1.14, respectively). CONCLUSION: Assuming about 350,000 ART infants are born each year, there is less than a 1% chance, over the background rate of 3%, of having an infant with a malformation. Whether subfertility or ART is the cause of the malformation risk observed remains unsettled and further research is needed.