Neonatal outcomes among singleton births after blastocyst versus cleavage stage embryo transfer: a systematic review and meta-analysis.

BACKGROUND Several studies have evaluated outcomes of singleton pregnancies after blastocyst versus cleavage stage embryo transfer. Higher incidences of preterm birth (PTB), very preterm birth (VPTB), low birthweight (LBW) and congenital malformations were identified in a few of them. The objective of our study was to systematically review and meta-analyze pregnancy and neonatal outcomes among singleton births following blastocyst versus cleavage stage embryo transfer. METHODS EMBASE, MEDLINE, EBM Reviews and bibliographies of included studies were searched from their inception until March 2013. Observational studies or clinical trials comparing blastocyst with cleavage stage embryo transfer and reporting on outcomes of PTB (<37 weeks), VPTB (<32 weeks), LBW (<2500 g), very low birthweight (VLBW) (<1500 g) and/or congenital anomalies in singleton neonates were included. Data on the outcomes were extracted by two reviewers. Statistical heterogeneity among studies was evaluated by calculating I(2) values and χ(2) statistics. Meta-analyses were conducted to estimate the pooled unadjusted odds ratio (OR) and the adjusted OR (AOR) with a 95% confidence interval (CI) using the random effect model. RESULTS Six observational studies, of low to moderate risk of bias, were included in this review. There were significantly higher odds of PTB (four studies, 54 792 cleavage stage and 20 724 blastocyst stage births; AOR 1.32, 95% CI 1.19-1.46) and congenital anomalies (two studies, 22 068 cleavage stage and 4517 blastocyst stage births; AOR 1.29, 95% CI 1.03-1.62) among births after blastocyst transfer compared with cleavage stage transfer. There was no difference in the adjusted odds of VPTB (four studies, 54 792 cleavage stage and 20 724 blastocyst stage births; AOR 1.18, 95% CI 0.93-1.49), LBW (four studies, 54 109 cleavage stage and 20 392 blastocyst stage births; AOR 1.06, 95% CI 0.99-1.15) or VLBW (three studies, 22 088 cleavage stage and 5772 blastocyst stage births; AOR 1.01, 95% CI 0.73-1.38). CONCLUSIONS Risk of PTB in IVF singleton pregnancies is significantly higher following blastocyst transfer compared with cleavage stage transfer. Risk of congenital anomalies may also be higher but further studies are needed to confirm this finding and to identify reasons for such outcomes.