First clinical application of comparative genomic hybridization and polar body testing for preimplantation genetic diagnosis of aneuploidy.

OBJECTIVE To develop a preimplantation genetic diagnosis (PGD) protocol that allows any form of chromosome imbalance to be detected. DESIGN Case report employing a method based on whole-genome amplification and comparative genomic hybridization (CGH). SETTING Clinical IVF laboratory. PATIENT(S) A 40-year-old IVF patient. INTERVENTION(S) Polar body and blastomere biopsy. MAIN OUTCOME MEASURE(S) Detection of aneuploidy. RESULT(S) Chromosome imbalance was detected in 9 of 10 polar bodies. A variety of chromosomes were aneuploid, but chromosomal size was found to be an important predisposing factor. In three cases, the resulting embryos could be tested using fluorescence in situ hybridization, and in each case the CGH diagnosis was confirmed. A single embryo could be recommended for transfer on the basis of the CGH data, but no pregnancy ensued. CONCLUSION(S) Evidence suggests that preferential transfer of chromosomally normal embryos can improve IVF outcomes. However, current PGD protocols do not allow analysis of every chromosome, and therefore a proportion of abnormal embryos remains undetected. We describe a method that allows every chromosome to be assessed in polar bodies and oocytes. The technique was accurate and allowed identification of aneuploid embryos that would have been diagnosed as normal by standard PGD techniques. As well as comprehensive cytogenetic analysis, this protocol permits simultaneous testing for multiple single-gene disorders.