Rate of post-fertilization mitotic activity predicts embryonic competence via next generation sequencing: An analysis of 39,301 cleavage stage embryos

Objective: To investigate the association between cleavage stage development, embryonic competence, and euploidy in patients undergoing in vitro fertilization (IVF) with subsequent next generation sequencing. Methods: The retrospective cohort study included patients at an academic fertility center who underwent IVF with at least one cleavage stage embryo from 2016 to 2019. Embryos were analyzed as slow (<6 cells), intermediate (6-8 cells), or fast (>8 cells); day 3 cell count was also analyzed as a continuous variable. Primary outcomes were blastulation rate, biopsied blastocyst rate, and euploid rate. Odds of blastulation, biopsy, and euploidy were also calculated. Additionally, we modeled the predicted probability of an embryo reaching blastulation, biopsy, and euploidy based on cleavage stage development. Results: When compared with intermediate and slow cohorts, fast cleaving embryos had significantly higher rates of blastulation (82.70% vs. 75.13 vs. 42.48%), biopsy (55.04% vs. 44.00% vs. 14.98%), and euploidy (50.65% vs. 47.93% vs. 48.05%). After adjustment for covariates, there was a significant association between cleavage stage development and odds of blastulation (OR 1.38, 95% CI 1.29-1.48), biopsy (OR 1.42, 95% CI 1.34-1.51), and euploidy (OR 1.08, 95% CI 1.01-1.17). Finally, we observed significant associations between cleavage stage development and predicted probability of reaching blastulation (OR 1.29, 95% CI 1.27-1.32), biopsy (OR 1.24, 95% CI 1.22-1.26), and euploidy (OR 1.02, 95% CI 1.01-1.04). Conclusions: Cleavage stage embryos with greater mitotic activity perform as well as or better than intermediate or slower cleaving embryos. Rapidly cleaving embryos have high rates of euploidy and significant clinical potential.