Abstract

Abstract Study question Are there differences in perinatal outcomes in singleton live births following transfer of fresh embryos at blastocyst versus cleavage-stage? Summary answer In singleton live births arising from fresh embryos, blastocyst transfer is not associated with higher perinatal risks than cleavage-stage transfer. What is known already Extended culture involves prolonged exposure to culture media. Although blastocyst transfer is currently the default strategy for many fertility clinics, there is a paucity of perinatal data from randomised trials. Previous observational research, including an earlier analysis of United Kingdom (UK) national data (up to 2012) by our group, has been suggestive of increased perinatal risks following blastocyst transfer. As laboratory practices have continued to evolve over time, we felt it was important to address this question again using more contemporary data (up to 2018) which have been recently made available by the UK Human Fertilisation and Embryology Authority (HFEA). Study design, size, duration A retrospective cohort study was undertaken using anonymised HFEA data on all fresh in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) cycles resulting in a singleton live birth (127,632) between 1999 and 2018. Perinatal outcomes were compared in babies conceived from the transfer of fresh embryos which were either at cleavage-stage (2-3 days of culture) or blastocyst-stage (5-6 days). Participants/materials, setting, methods All IVF/ICSI cycles resulting in singleton live births following the transfer of fresh blastocysts or cleavage-stage embryos were included. Logistic regression was used to calculate adjusted risk ratios (aRRs) with 95% confidence intervals (CIs) for perinatal outcomes including a healthy baby (term delivery, normal birth weight, no congenital anomalies) following either blastocyst or cleavage-stage transfer. Outcomes were separately compared in women who had a singleton live birth after their first fresh cycle of IVF/ICSI. Main results and the role of chance Of 127,632 singleton live births, 54,688 occurred after blastocyst transfer while 72,944 resulted from cleavage-stage transfer. The corresponding numbers in 64,812 women who underwent their first cycle of IVF/ICSI were 25,452 (blastocyst) and 39,360 (cleavage-stage). Outcomes following blastocyst and cleavage-stage transfer were comparable in terms of low birth weight (7.2% vs. 7.5%, aRR 0.98, 95% CI 0.93-1.05), very low birth weight (1.7% vs. 1.8%, aRR 0.95, 95% CI 0.82-1.10), high birth weight (6.4% vs. 7.3%, aRR 0.98, 95% CI 0.92-1.04), very high birth weight (1.2% vs. 1.4%, aRR 0.99, 95% CI 0.87-1.14), very preterm birth (1.7% vs. 1.7%, aRR 1.04, 95% CI 0.92-1.17) and congenital anomalies (0.6% vs. 2.5%, aRR 0.93, 95% CI 0.80-1.08). These findings were confirmed in the sensitivity analysis involving women undergoing their first fresh embryo transfer. In the general population, the risk of preterm birth was higher following blastocyst transfer (7.7% vs. 7.3%, aRR 1.07, 95% CI 1.01-1.13) but this difference was not maintained in the sensitivity analysis (aRR 1.05, 95% CI 0.96-1.14). The chance to deliver a healthy singleton was similar across both groups in both primary cycle-based analysis (aRR 1.00, 95% CI 0.98-1.02) and sensitivity analysis (aRR 1.00, 95% CI 0.97-1.02). Limitations, reasons for caution The primary analysis was unable to discriminate between cycles and women or to adjust for clustering of women within cycles. Data were unavailable for some key confounders (body mass index, smoking status, previous medical history and complications during pregnancy). Wider implications of the findings While our findings provide some reassurance to patients undergoing blastocyst transfer, the limitations of the current study mean that further research is needed using women based rather than cycle based data. Trial registration number not applicable

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