Human embryos with unevenly sized blastomeres have lower pregnancy and implantation rates: indications for aneuploidy and multinucleation

Uneven blastomere cleavage in human embryos of 'good morphology', i.e. thos e normally used for transfer, is a phenomenon which has been poorly investi gated. The main objective in this study was to probe deeper into the aetiol ogy behind previous findings that embryos with uneven cell cleavage have a lower developmental capacity in comparison with evenly cleaved embryos. Our hypothesis was that uneven cleavage may result in embryos with a higher de gree of aneuploidy and/or multinuclear rate, which in turn might help to ex plain their low implantation rate. In the first part of the study, 378 embr yo transfers performed over a 3-year period were analysed retrospectively, where all the transferred embryos in each cycle were of identical morpholog y score and cleavage stage. In the second part of the study, multicolour fl uorescence in-situ hybridization (FISH) analyses on good quality embryos, r epresenting the uneven (n = 11) and even (n = 13) study groups were perform ed. When comparing day 2 transfers between 4-cell embryos, it was found tha t unevenly cleaved embryos had significantly lower implantation (23.9 and 3 6.4%) and pregnancy rates (37.6 and 52.9%) compared with evenly cleaved emb ryos. A significantly higher degree of aneuploidy (29.4 and 8.5%) and multi nuclear rate (21.1 and 2.1%) in blastomeres from uneven embryos was also fo und. It is concluded that uneven blastomere cleavage has a negative effect on both pregnancy and implantation rates in human IVF, and that this can pa rtly be explained by a higher degree of aneuploidy/multinuclear rate. In th e light of the results obtained, a new approach in the current embryo scori ng system, placing more emphasis on blastomere size, is recommended.