Investigation of chromosomal imbalance in human embryos using comparative genomic hybridization

Studies of cleavage-stage human embryos using fluorescence in-situ hybridization (FISH) to identify sub-sets of chromosomes have indicated that the incidence of chromosomal abnormalities is high. Whole genome amplification (WGA) and comparative genomic hybridization (CGH) to investigate the full chromosome complement applied to a small number of human embryos suggested an even higher rate of abnormality. WGA and CGH were used to identify genomic imbalance in individual blastomeres from human embryos, and the results were correlated with FISH analysis of sibling blastomeres. Forty embryos were analysed; 17 (42.5%) had a normal diploid karyotype and 23 (57.5%) were abnormal, with a chromosome imbalance in one or more cells including three (7.5%) that had a chaotic chromosome complement. Of the abnormal embryos, only three showed consistent aneuploidy. FISH results obtained from sibling blastomeres were in agreement with the CGH results in all 22 of the embryos where both tests were informative. It is concluded that rates of meiotic aneuploidy in human embryos may be lower than previous estimates. The results indicate that chromosomally abnormal embryos were more likely to have arisen as a result of cultural artefact or inadequate cell cycle surveillance, rather than meiotic error.