Modelling a risk classification of aneuploidy in human embryos using non-invasive morphokinetics

Abstract

This study determined whether morphokinetic variables between aneuploid and euploid embryos differ as a potential aid to select euploid embryos for transfer. Following insemination, EmbryoScope time-lapse images from 98 blastocysts were collected and analysed blinded to ploidy. The morphokinetic variables were retrospectively compared with ploidy, which was determined following trophectoderm biopsy and analysis by array comparative genomic hybridization or single-nucleotide polymorphic array. Multiple aneuploid embryos were delayed at the initiation of compaction ( t SC ; median 85.1 hours post insemination (hpi); P =0.02) and the time to reach full blastocyst stage ( t B ; median 110.9hpi, P =0.01) compared with euploid embryos ( t SC median 79.7 hpi, t B median 105.9 hpi). Embryos having single or multiple aneuploidy (median 103.4 hpi, P =0.004 and 101.9 hpi, P =0.006, respectively) had delayed initiation of blastulation compared with euploid embryos (median 95.1hpi). No significant differences were observed in first or second cell-cycle length, synchrony of the second or third cell cycles, duration of blastulation, multinucleation at the 2-cell stage and irregular division patterns between euploid and aneuploid embryos. This non-invasive model for ploidy classification may be used to avoid selecting embryos with high risk of aneuploidy while selecting those with reduced risk. Chromosome anomalies (aneuploidy) are prevalent in human embryos and result in either IVF failure, miscarriage or the birth of children with chromosome disorders. After IVF, it is imperative to try to detect aneuploid embryos in order to transfer an embryo with a normal chromosome copy number (euploid) to maximize the chances of a successful and healthy live birth. Currently, the only option is to biopsy a cell (or cells) from the embryo and analyse these using complex and expensive genetic technology. Novel uninterrupted culturing methods using the EmbryoScope now enables detailed observation of the each embryo via time-lapse photography during the whole culture period, for up to 6days. This new technology has permitted us to observe the development of human embryos in detail after IVF, providing analysis of complex patterns of cell division and cell movement (morphokinetics). As far as is known for the first time, we have demonstrated differences between aneuploid and euploid embryos based on their morphokinetic patterns, whereby aneuploid embryos are significantly delayed in reaching the later stages of development, during days 4 and 5 in culture. We postulate that, by using the unique, non-invasive and specifically designed models or algorithms developed in this study, embryologists can make more informed choices on the most viable embryo to select for transfer and reduce the risk of selecting an aneuploid embryo.