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

Hum Reprod. 2009 Nov;24(11):2679-82. doi: 10.1093/humrep/dep266. Epub 2009 Jul 24.


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 embryos.

MeSH terms

  • Aneuploidy
  • Birth Rate
  • Blastocyst
  • Chromosomes, Human*
  • Female
  • Genetic Testing
  • Genomic Instability*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Mitosis
  • Pregnancy
  • Preimplantation Diagnosis*
  • Randomized Controlled Trials as Topic