Preterm birth and low birth weight among in vitro fertilization twins: A systematic review and meta-analyses

Objective: The objective of this systematic review and meta-analyses was to determine the risks of preterm birth (PTB) and low birth weight (LBW) in twins conceived through in vitro fertilization (IVF) or IVF/intracytoplasmic sperm injection (ICSI) compared to spontaneously-conceived twins after matching or controlling for at least maternal age. Study design: The MOOSE guidelines for meta-analysis of observational studies were followed. Search strategy: Medline and Embase were searched using comprehensive search strategies. Bibliographies of identified articles were reviewed. Selection criteria: English language studies of twins conceived by IVF or IVF/ICSI, compared with spontaneously twins, that matched or controlled for at least maternal age. Data collection and analysis: Two reviewers independently assessed titles, abstracts, articles and study quality and extracted data. Statistical analyses were performed using the Review Manager (RevMan 5.0) software using a random effects model. Dichotomous data were meta-analyzed using relative risks (RR) and continuous data with a weighted mean difference. Results: Twelve studies were included which had a total of 4385 twins conceived after IVF or IVF/ICSI (one stillbirth was excluded) and 11,793 spontaneously-conceived twins. After matching or controlling for maternal age and often other factors, compared to spontaneously-conceived twins, IVF twins had increased risks of both our primary outcomes: PTB (RR 1.23, 95% CI 1.09, 1.41) and LBW (<2500 g, RR 1.14, 95% CI 1.06, 1.22). They were at increased risk for PTB <32-33 weeks (RR 1.63, 95% CI 1.17, 2.27) although the risks of late PTB (32-36 weeks, RR 1.12, 95% CI 0.85, 1.47), very LBW (<1500 g, RR 1.28, 95% CI 0.73, 2.24), extremely LBW (<1000 g, RR 0.88, 0.04, 19.40), intrauterine growth restriction (RR 1.06, 95% CI 0.72, 1.55) and the difference in the duration of gestation (-0.5 weeks, 95% CI -1.2 weeks, 0.2 weeks) were not statistically significantly increased compared to spontaneously-conceived twins. IVF twins had significantly lower mean birth weights (-105 g, 95% CI -204 g, -3 g). Conclusions: IVF twins have small but significantly increased risks of PTB, LBW, and lower mean birth weight compared to spontaneously-conceived twins after matching or controlling for at least maternal age.