Obstetrical and perinatal outcomes following blastocyst transfer compared to cleavage transfer: a systematic review and meta-analysis.

STUDY QUESTION: Is blastocyst transfer safe when compared to cleavage stage embryo transfer regarding obstetric and perinatal outcomes?

SUMMARY ANSWER: The clinical equipoise between blastocyst and cleavage stage embryo transfer remains as the evidence associating blastocyst transfer with some adverse perinatal outcomes is of low/very low quality.

WHAT IS KNOWN ALREADY: Extended embryo culture to the blastocyst stage provides some theoretical advantages and disadvantages. While it permits embryo self-selection, it also exposes those embryos to possible harm due to the in vitro environment. Both effectiveness and safety should be weighed to permit evidence-based decisions in clinical practice.

STUDY DESIGN, SIZE, DURATION: This is a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies reporting perinatal outcomes for singletons comparing the deliveries resulting from blastocyst and cleavage stage embryo transfer. Observational studies were included because the primary outcomes, perinatal mortality and birth defects, are rare and require a large number of participants (>50 000) to be properly assessed. The last electronic searches were last run on 11 March 2016.

PARTICIPANTS/MATERIALS, SETTING, METHOD: There were 12 observational studies encompassing 195 325 singleton pregnancies included in the study. No RCT reported the studied outcomes. The quality of the included studies was evaluated according to the Newcastle-Ottawa Scale and the quality of the evidence was evaluated according to GRADE criteria.

MAIN RESULTS AND THE ROLE OF CHANCE: Blastocyst stage transfer was associated with increased risks of preterm birth (<37 weeks), very preterm birth (<32 weeks), large for gestational age and perinatal mortality, although the latter was only identified from one study. Conversely, blastocyst stage transfer was associated with a decrease in the risks of small for gestational age and vanishing twins, although the latter was reported by only one study.

LIMITATIONS, REASONS FOR CAUTION: The observational nature of the included studies and some inconsistency and imprecision in the analysis contributed to decreasing our confidence in the estimates.

WIDER IMPLICATIONS OF THE FINDINGS: Due to the overall low quality of available evidence, the clinical equipoise between cleavage stage and blastocyst transfer remains. More large well-conducted studies are needed to clarify the potential risks and benefits of blastocyst transfer. As this review was initiated to support global recommendations on best practice, and in light of the challenges in lower resource settings to offer extended culture to blastocyst stage, it is critical to take into consideration these obstetric and neonatal outcomes in order to ensure any recommendation will not result in the overburdening of existing maternal and child health care systems and services.

STUDY FUNDING/COMPETING INTERESTS: No external funding was either sought or obtained for this study. The authors have no competing interests to declare.

PROSPERO REGISTRATION NUMBER: CRD42015023910.