Hum. Reprod. Advance Access originally published online on July 24, 2009
Human Reproduction 2009 24(11):2679-2682; doi:10.1093/humrep/dep266
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What next for preimplantation genetic screening? High mitotic chromosome instability rate provides the biological basis for the low success rate


1 Center for Human Genetics, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium 2 Leuven University Fertility Center, University Hospital Gasthuisberg, Leuven, Belgium 3 Center for Medical Genetics, University Hospital and Medical School, Dutch-speaking Brussels Free University, Brussels, Belgium
4 Correspondence address. Center for Human Genetics, University Hospital Gasthuisberg, Herestraat 49, Box 602, 3000 Leuven, Belgium. E-mail: joris.vermeesch{at}uz.kuleuven.be
Preimplantation genetic screening is being scrutinized, as recent randomized clinical trials failed to observe the expected significant increase in live birth rates following fluorescence in situ hybridization (FISH)-based screening. Although these randomized clinical trials are criticized on their design, skills or premature stop, it is generally believed that well-designed and well-executed randomized clinical trials would resolve the debate about the potential benefit of preimplantation genetic screening. Since FISH can analyze only a limited number of chromosomal loci, some of the embryos transferred might be diagnosed as normal but in fact be aneuploid for one or more chromosomes not tested. Hence, genome-wide array comparative genome hybridization screening enabling aneuploidy detection of all chromosomes was thought to be a first step toward a better design. We recently showed array screening indeed enables accurate determination of the copy number state of all chromosomes in a single cell. Surprisingly, however, this genome-wide array screening revealed a much higher frequency and complexity of chromosomal aberrations in early embryos than anticipated, with imbalances in a staggering 90% of all embryos. The mitotic error rate in cleavage stage embryos was proven to be higher than the meiotic aneuploidy rate and as a consequence, the genome of a single blastomere is not representative for the genome of the other cells of the embryo. Hence, potentially viable embryos will be discarded upon screening a single blastomere. This observation provides a biological basis for the failure of the randomized clinical trials to increase baby-take-home rates using FISH on cleavage stage embroys.
These authors contributed equally to this work.
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