Preterm birth and low birth weight among in vitro fertilization singletons: a systematic review and meta-analyses

Our objective was to determine the risks of preterm birth (PTB) and low birth weight (LBW) in singletons conceived through in vitro fertilization (IVF)+/-intracytoplasmic sperm injection (ICSI) compared to spontaneously conceived singletons after matching or controlling for at least maternal age. The MOOSE guidelines for meta-analysis of observational studies were followed. Medline and Embase were searched using comprehensive search strategies. Bibliographies of identified articles were reviewed. English language studies examining LBW or PTB in singletons conceived by IVF or IVF/intracytoplasmic sperm injection, compared with spontaneously conceived singletons, that matched or controlled for at least maternal age. Two reviewers independently assessed titles, abstracts, full articles and study quality and extracted data. Dichotomous data were meta-analyzed using relative risks (RR) as measures of effect size with a random effects model and for continuous data weighted mean difference was calculated. Seventeen studies were included with 31,032 singletons conceived through IVF (+/-ICSI) and 81,119 spontaneously conceived singletons. After matching or controlling for maternal age and often other factors, compared to spontaneously conceived singletons, IVF singletons had increased risks of our two primary outcomes, PTB (RR 1.84, 95% CI 1.54, 2.21) and LBW (<2500 g, RR 1.60, 95% CI 1.29, 1.98). Singletons conceived through IVF or IVF/ICSI were at increased risk for late PTB (32-36 weeks, RR 1.52, 95% CI 1.01, 2.30), moderate PTB <32-33 weeks (RR 2.27, 95% CI 1.73, 2.97), very LBW (<1500 g, RR 2.65, 95% CI 1.83, 3.84), and intrauterine growth restriction (RR 1.45, 95% CI 1.04, 2.00), lower birth weights (-97 g, 95% CI -161 g, -33 g) and shorter mean gestations (-0.6 weeks, 95% CI -0.9 weeks, -0.4 weeks). In conclusion, IVF singletons have significantly increased risks of PTB, LBW and other adverse perinatal outcomes compared to spontaneously conceived singletons after matching or controlling for maternal age at least.