Comprehensive chromosomal analysis of human preimplantation embryos using whole genome amplification and single cell comparative genomic hybridization

Analysis of small numbers of chromosomes using interphase fluorescent in-si tu hybridization (FISH) probes has revealed that 50% of human preimplantati on embryos contain abnormal cells. Detection of high levels of mosaicism wi th so few probes has led same researchers to extrapolate that a full analys is of all 23 pairs of chromosomes would reveal that all human embryos conta in a proportion of abnormal cells. However, existing cytogenetic protocols cannot achieve such an analysis due to technical limitations. We have devel oped a novel technique based on whole genome amplification and comparative genomic hybridization (CGH), which for the first time allows the copy numbe r of every chromosome to be assessed in almost every cell of a cleavage-sta ge embryo. We have successfully analysed 64 cells (blastomeres) derived fro m 12 embryos and have detected unusual forms of aneuploidy, high levels of chromosomal mosaicism, non-mosaic aneuploidy and chromosome breakage. This is the first report of a comprehensive assessment of chromosome copy number in human embryos and indicates that, despite high levels of mosaicism, som e embryos do have normal chromosome numbers in every cell. Such embryos may have a superior developmental potential, and their low frequency may expla in correspondingly low success rates of natural and assisted conception in humans.