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

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Abstract

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.

Introduction

In vitro fertilization (IVF) provides an opportunity for an increasing proportion of couples who were unable to conceive spontaneously to become parents. Following the first successful IVF birth in 1978, the proportion of infants born as a result of this procedure has steadily increased to approximately 1 in 30 in Finland [1] and 1 in 80 in the USA [2].

The last meta-analysis (with the literature search ending in 2003) was published by our group and identified that singletons born after IVF had increased perinatal risks compared to spontaneously conceived singletons after accounting for maternal age [3]. However, there have been a number of studies published since that time, and a current, unbiased, systematic review of the literature is required. Our previous study reported only pooled crude data, whereas we now wanted to also examine data which accounted for confounders. We have focused on singletons given that they make up the largest proportion of IVF infants. This review will concentrate on the two most important determinants of neonatal morbidity and mortality, namely preterm birth (PTB) and low birth weight (LBW) births [4].

Section snippets

Materials and methods

We followed the MOOSE consensus statement on the conduct of meta-analysis of observational studies [5].

Results

Three hundred and sixty-one non-duplicate titles and abstracts were identified, 117 full articles were reviewed and 17 articles met inclusion criteria [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24] with 31,032 singletons conceived through IVF and IVF/ICSI and 81,119 spontaneously conceived singletons (Fig. 1). Although many studies were labeled as case–control studies and others as retrospective cohort studies, all 17 studies involved

Comment

In this systematic review and meta-analyses, we determined that IVF singletons have higher rates of our primary outcomes, PTB and LBW, the two most important determinants of neonatal morbidity and mortality [4]. In addition, IVF singletons have increased risks of moderate and late PTB, VLBW, IUGR, lower mean birth weights and shorter mean gestations. The risks of the most extreme preterm birth cannot be assessed due to the inclusion criteria of the original studies. Two studies included births

Acknowledgement

We thank Elizabeth Uleryk, Chief Librarian, Hospital for Sick Children, Toronto, for developing the search strategy.

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