Nuclear error phenotypes at the first mitosis predict cleavage-stage outcomes but not blastocyst competence

Nuclear errors (NE) observed at the two-cell stage reflect early mitotic disturbances, but their clinical relevance for embryo implantation and live birth remains un-clear. We investigated whether nuclear status at the two-cell stage predicts pregnancy and live birth outcomes following cleavage-stage and blastocyst transfer.

This retrospective cohort study included 3,793 single embryo transfers with clinical outcomes performed at a university-affiliated reproductive medicine centre. Embryos were retrospectively assessed at the two-cell stage and classified as normal or exhibiting nuclear errors, further stratified by the number of affected blastomeres and by phenotype (multinucleation, micronucleation, split nuclei, or mixed errors). Live birth rate (LBR) was the primary outcome; pregnancy and clinical pregnancy rates were secondary outcomes. Associations were evaluated using contingency analyses, regression models of nuclear error occurrence, and mixed-effects logistic regression analyses of clinical outcomes adjusted for maternal age, paternal age, fertilisation method, and patient-level clustering.

NE occurred in 24% of transferred embryos and were more frequent after ICSI than IVF (adjusted OR 1.74). In cleavage-stage transfers, NE were associated with reduced LBR compared with embryos without NE (23.2% vs. 34.8%). The clinical outcomes decreased with increased numbers of affected blastomeres. Micronucleation and split nuclei showed the poorest outcomes and remained adversely associated with reproductive outcomes after adjustment, whereas multinucleation was not detrimental. No association between NE and outcomes was observed after blastocyst transfers.

Nuclear error phenotypes at the two-cell stage provided prognostic information relevant for cleavage-stage embryo transfer but had limited influence for blastocyst selection. Outcome differences associated with early nuclear abnormalities were no longer detectable among transferred blastocysts.