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

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.

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 of twins conceived by IVF or IVF/ICSI, compared with spontaneously twins, that matched or controlled for at least maternal age.

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.

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).

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.