Abstract: We included 27 RCTs (4031 couples or women). The live birth rate following fresh transfer was higher in the blastocyst transfer group (odds ratio (OR) 1.48, 95% confidence interval (CI) 1.20 to 1.82; 13 RCTs, 1630 women, I2 = 45%, low quality evidence) following fresh transfer. This suggests that if 29% of women achieve live birth after fresh cleavage stage transfer, between 32% and 42% would do so after fresh blastocyst stage transfer. There was no evidence of a difference between the groups in rates per couple of cumulative pregnancy following fresh and frozen-thawed transfer after one oocyte retrieval (OR 0.89, 95% CI 0.64 to 1.22; 5 RCTs, 632 women, I2 = 71%, very low quality evidence). The clinical pregnancy rate was also higher in the blastocyst transfer group, following fresh transfer (OR 1.30, 95% CI 1.14 to 1.47; 27 RCTs, 4031 women, I2 = 56%, moderate quality evidence). This suggests that if 36% of women achieve clinical pregnancy after fresh cleavage stage transfer, between 39% and 46% would do so after fresh blastocyst stage transfer. There was no evidence of a difference between the groups in rates of multiple pregnancy (OR 1.05, 95% CI 0.83 to 1.33; 19 RCTs, 3019 women, I2 = 30%, low quality evidence), or miscarriage (OR 1.15, 95% CI 0.88 to 1.50; 18 RCTs, 2917 women, I2 = 0%, low quality evidence). These data are incomplete as under 70% of studies reported these outcomes. Embryo freezing rates were lower in the blastocyst transfer group (OR 0.48, 95% CI 0.40 to 0.57; 14 RCTs, 2292 women, I2 = 84%, low quality evidence). This suggests that if 60% of women have embryos frozen after cleavage stage transfer, between 37% and 46% would do so after blastocyst stage transfer. Failure to transfer any embryos was higher in the blastocyst transfer group (OR 2.50, 95% CI 1.76 to 3.55; 17 RCTs, 2577 women, I2 = 36%, moderate quality evidence). This suggests that if 1% of women have no embryos transferred in (planned) fresh cleavage stage transfer, between 2% and 4% will have no embryos transferred in (planned) fresh blastocyst stage transfer. The evidence was of low quality for most outcomes. The main limitation was serious risk of bias, associated with failure to describe acceptable methods of randomisation, and unclear or high risk of attrition bias. There is low quality evidence for live birth and moderate quality evidence for clinical pregnancy that fresh blastocyst stage transfer is associated with higher rates than fresh cleavage stage transfer. There was no evidence of a difference between the groups in cumulative pregnancy rates derived from fresh and frozen-thawed cycles following a single oocyte retrieval, but the evidence for this outcome was very low quality. Thus, although there is a benefit favouring blastocyst transfer in fresh cycles, it remains unclear whether the day of transfer impacts on cumulative live birth and pregnancy rates. Future RCTs should report rates of live birth, cumulative live birth, and miscarriage to enable couples or women undergoing assisted reproductive technology (ART) and service providers to make well informed decisions on the best treatment option available.

Plain-language summary: We included 27 randomised controlled trials (RCTs), which included 4031 women. The evidence is current to April 2016. There was low quality evidence for live birth and moderate for clinical pregnancy that fresh blastocyst stage transfer is associated with higher rates than fresh cleavage stage transfer. This suggests that if 29% of women achieve live birth after fresh cleavage stage transfer, between 32% and 42% would do so after fresh blastocyst stage transfer. There was no evidence of a difference between the groups in cumulative pregnancy rates (i.e. pregnancies from both fresh and thawed cycles deriving from a single egg collection procedure), but the evidence for this outcome was very low quality. Thus, although there is a benefit favouring blastocyst transfer in fresh cycles, it remains unclear whether the day of transfer impacts on cumulative rates of live birth and pregnancy. There was no evidence of a difference between the groups in multiple pregnancy and miscarriage rates, but the quality of evIdence was low. Future RCTs should report rates of live birth, cumulative live birth, and miscarriage to enable ART consumers and service providers to make well informed decisions on the best treatment option available. The evidence was of low quality for most outcomes. The main limitation was serious risk of bias, associated with failure to describe acceptable methods of randomisation, and unclear or high risk of attrition bias.