Delays in the final stages of fertilization are strongly associated with trichotomous cytokinesis and cleavage arrest

Purpose: Recent evidence showed that the phase between pronuclear fading and the first cleavage is a perilous bridge connecting the zygote and the embryo. Indeed, delay in the short interval between pronuclear breakdown (PNBD) and the first cytokinesis may result in chromosome segregation errors. We tested the hypothesis that delays in this final phase of fertilization are associated with a detrimental impact on embryo development.

Methods: This is a retrospective study of 1315 zygotes cultured using time lapse technologies generated in 205 first ICSI-cycles.

Results: We observed an association between increasing times of the pronuclear fading-first cleavage interval (t2-tPNf) and the rates of trichotomous/direct unequal cleavage at the first (DUC-1) and second (DUC-2) mitotic cycle. Moreover, we observed a reduced blastulation rate. No significant associations were observed between rates of direct unequal cleavage at the third mitotic cycle (DUC-3) and top-quality blastocysts, euploidy, and live births. To evaluate whether the interval t2-tPNf could have a predictive value for the onset of DUC-1 and DUC-2, ROC curve analyses were performed. The area under the curve values obtained for DUC-1 showed a significant prediction accuracy. The best cut-offs to identify zygotes with a high risk of DUC-1 and DUC-2 occurrence were t2-tPNf > 2.78 (hours) and t2-tPNf > 2.50 (hours), respectively.

Conclusion: Delay in the short interval between PNBD and the first cytokinesis result in trichotomous cleavage and early developmental arrest. However, if the embryos reach the blastocyst stage, rates of euploidy and live birth do not appear to be compromised.