Worth the wait? Day 7 blastocysts have lower euploidy rates but similar sustained implantation rates as Day 5 and Day 6 blastocysts

Abstract

Does the reproductive potential of embryos change when blastocyst development takes longer than the traditionally accepted 5 days when accounting for aneuploidy and endometrial-embryo asynchrony? Aneuploidy increases with increasing duration of blastulation, but if blastocyst morphologic quality and endometrial-embryo asynchrony are controlled for, euploid Day 7 embryos have similar sustained implantation as compared to Days 5 and 6 euploid blastocysts. The relative contributions of diminished embryo quality versus endometrial and embryo asynchrony to poor outcomes associated with embryos cultured past Day 6 are not clear. Asynchrony can be eliminated by embryo vitrification with transfer in a subsequent month after retrieval. Retrospective cohort study of patients from a single center attempting conception through ICSI and utilizing preimplantation genetic testing for aneuploidy screening (PGT-A) from January 2017 to September 2018. Cycles were excluded if they utilized surgical sperm or preimplantation genetic testing for monogenetic/single gene defects. ICSI cycle outcomes from 2586 patients were evaluated for ploidy status of embryos. Only patients undergoing single, euploid frozen embryo transfer were included when analyzing cycle outcomes by day of blastocyst expansion of the transferred embryo (n = 2130). Ploidy rates by the day upon which an embryo was considered to be usable (denoted, 'usable blastulation day') were determined so as to assess the contribution of aneuploidy to slow embryo development. Outcomes of euploid frozen single embryo transfers (SET) of Day 7 embryos were evaluated to assess the reproductive potential associated with embryos that were slowly developing for reasons other than aneuploidy. Analyses were adjusted by maternal age and blastocyst morphology. Overall, 67.7% (n = 3508) of usable Day 5 blastocysts were euploid, 52.1% (n =5560) of usable Day 6 blastocysts were euploid and 43.1% (n =229) of usable Day 7 embryos were euploid (Day 5 versus Day 6: odds ratio (OR) 0.7 (95% CI, 0.64-0.76), P < 0.001; Day 5 versus Day 7: OR 0.56 (95% CI, 0.46-0.69), P < 0.001; Day 6 versus Day 7: OR 0.81 (95% CI, 0.67-0.99), P = 0.036). Stratified by Society for Assisted Reproductive Technology maternal age groups, a reduction in the prevalence of euploidy by increasing time to embryo blastulation was still seen. The sustained implantation rate (SIR) was similar after euploid SET of Days 5 and 6 embryos (overall, 68.9% (95% CI, 66.0-71.6) and 66.8% (95% CI, 63.8-69.7), respectively; P = 0.81). SIR after euploid Day 7 SET appeared slightly lower than that of Days 5 and 6 embryos (52.6% (95% CI, 35.8-69.0); (Day 5 versus Day 7: OR, 0.67 (95% CI, 0.32-1.41), P = 0.29; Day 6 versus Day 7: OR 0.58 (95% CI, 0.28-1.2), P = 0.14)) but did not achieve statistical significance. The primary limitation is the low number of Day 7 blastocyst transfers that limits statistical power. Additionally, the retrospective nature of this study may prevent full elucidation of potential biases with respect to culture, morphologic assessment and selection of Day 7 embryos for transfer. Routine culture through Day 7 may successfully increase the pool of transferrable embryos for patients who would otherwise have no usable embryos if culture terminated on Day 6. This is particularly true for older patients (i.e. greater than 35years of age), whose embryos take longer to blastulate and, therefore, are more susceptible to cycle cancelation. Additionally, as evidenced by an adequate overall SIR of 52.6% after euploid SET of Day 7 blastocysts, embryos developing to a usable blastocyst on Day 7 are likely within the 'window of blastulation.' None.