Worldwide prevalence of adverse pregnancy outcomes associated with in vitro fertilization/intracytoplasmic sperm injection among multiple births: a systematic review and meta-analysis based on cohort studies

Purpose

To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among multiple births conceived with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).

Methods

PubMed, Google Scholar, Cochrane Libraries and Chinese databases were searched through May 2016 for cohort studies assessing adverse pregnancy outcomes associated with IVF/ICSI multiple births. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses.

Results

Sixty-four studies, with 60,210 IVF/ICSI multiple births and 146,737 spontaneously conceived multiple births, were selected for analysis. Among IVF/ICSI multiple births, the pooled estimates were 51.5% 95% confidence interval (CI): 48.7–54.3] for preterm birth, 12.1% (95% CI: 10.4–14.1) for very preterm birth, 49.8% (95% CI: 47.6–52.0) for low birth weight, 8.4% (95% CI: 7.1–9.9) for very low birth weight, 16.2% (95% CI: 12.9–20.1) for small for gestational age, 3.0% (95% CI: 2.5–3.7) for perinatal mortality and 4.7% (95% CI: 4.0–5.6) for congenital malformations. When the data were restricted to twins, the pooled estimates also showed a high prevalence of adverse outcomes. There was a similar prevalence of poor outcomes among multiple births conceived with IVF/ICSI and naturally (all P?≥?0.0792). Significant differences in different continents, countries, and income groups were found.

Conclusions

The IVF/ICSI multiple pregnancies have a high prevalence of adverse pregnancy outcomes. However, population-wide prospective adverse outcomes registries covering the entire world population for IVF/ICSI pregnancies are needed to determine the exact perinatal prevalence.