Perinatal Outcomes of Singleton Pregnancies Achieved by In Vitro Fertilization: A Systematic Review and Meta-Analysis

OBJECTIVE: To determine whether the incidence of adverse obstetric outcomes is higher in singleton pregnancies achieved by in vitro fertilization (IVF) than in spontaneously conceived singletons matched for maternal age. METHODS: We used comprehensive search strategies to search MEDLINE and EMBASE databases. We selected case-control and cohort studies that compared singleton pregnancies conceived by IVF or intracytoplasmic sperm injection (ICSI) with spontaneously conceived singletons (matched for maternal age [case-control studies] or controlled for maternal age [cohort studies]). Two reviewers independently assessed titles, abstracts, and study quality and extracted data. Statistical analysis was performed with Review Manager for Windows (Version 4.2, Oxford, UK). We performed meta-analysis of dichotomous data, using odds ratios (ORs) as measures of effect size, with a random effects model. We followed the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines for meta-analysis of observational studies. RESULTS: Singleton pregnancies resulting from IVF have increased rates of poor obstetric outcome, compared with spontaneously conceived singletons matched for maternal age, with increases in perinatal mortality (OR 2.40; 95% confidence interval [CI] 1.59-3.63), preterm birth at < 33 weeks' gestation (OR 2.99; 95% CI 1.54-5.80), preterm birth at < 37 weeks' gestation (OR 1.93; 95% CI 1.36-2.74), very low birth weight (< 1500 g) (OR 3.78; 95% CI 4.29-5.75), small for gestational age (OR 1.59; 95% CI 1.20-2.11), and congenital malformations (OR 1.41; CI 1.06-1.88). CONCLUSIONS: IVF singleton pregnancies have increased rates of poor obstetric outcome, compared with spontaneously conceived singletons matched for maternal age.