What next for preimplantation genetic screening? High mitotic chromosome instability rate provides the biological basis for the low success rate  

Oleh:

Vanneste, Evelyne ; Voet, Thierry ; Melotte, Cindy

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Human Reproduction vol. 24 no. 11 (Nov. 2009), page 2679-2682.
Topik: fluorescence in situ hybridization

Ketersediaan

Perpustakaan FK Nomor Panggil: H07.K.2009.04 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

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.

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