Nuclear error phenotypes in the two-cell embryo are correlated to blastocyst formation rate after assisted reproduction

Purpose: Map the nuclear error phenotypes in the two-cell embryo after assisted reproduction using time lapse images and the effect on good quality blastocyst formation.

Methods: Retrospective cohort study using time lapse images, categorizing 2331 two-cell embryos from 392 patient couples and 504 ART cycles categorizing each embryo as mononucleated, multinucleated, micronucleated, binucleated, split nucleation or mixed error. Correlating nuclear error phenotype with good quality blastocyst formation rate (BFR) using contingency tables and unadjusted odds ratio.

Results: An overall nuclear error rate of 47.1% was observed in two-cell embryos. The most frequent error was multi-nucleation (14.2%) followed by mixed error (11%), micro-nucleation (8.6%), bi-nucleation (7.4%) and split nucleation (5.8%). Blastocyst formation rate (BFR) was reduced in embryos with nuclear errors, 46.2% for embryos with one cell affected, 27.6% for embryos with both cells affected, compared to 58.6% for mononucleated cells, p < 0.001 for both. Binucleated embryos were as likely as mononucleated embryos to become clinically useful blastocysts (56.8% vs 58.6%, n.s., unadjusted OR 0.94), whereas all the other phenotypes were less likely to develop into good quality blastocysts. The worst outcome was noted for embryos with split nucleation, with just 12.4% BFR, OR 0.12 (0-08-0.21), p < 0.001.

Conclusion: Nuclear errors are common at the two-cell stage. Overall, presence of nuclear errors reduces the likelihood of becoming good quality blastocysts. Both the number of affected cells and the different nuclear error phenotypes have impact on blastocyst formation rate, except binucleated embryos.