Improved detection of aneuploid blastocysts using a new 12-chromosome FISH test

Abstract

Fluorescence in-situ hybridization (FISH) has been the principal method used for the identification and preferential transfer of chromosomally normal embryos, in the context of both preimplantation genetic diagnosis (PGD) and screening (PGS). Generally, the probe combinations used during PGS have focused on chromosomes frequently identified as abnormal in prenatal samples or material derived from first-trimester spontaneous abortions. Recent data, however, obtained with the use of comparative genomic hybridization (CGH), have suggested that commonly used PGS strategies may fail to detect a large number of aneuploidies affecting preimplantation embryos. Some chromosomes, which have been relatively neglected in PGS protocols thus far, display a disproportionate contribution to embryo aneuploidy and should be prioritized for screening. Using CGH data, it is possible to design new probe combinations that examine between 10 and 12 chromosomes and are capable of accurately diagnosing 89-91% of anomalies seen in embryos. At present, 24-chromosome tests, such as CGH, array CGH or single nucleotide polymorphism arrays, remain relatively costly and, in some cases, are yet to be fully validated. For these reasons, a cost-effective method, capable of accurately detecting almost all aneuploid embryos, represents an attractive alternative to comprehensive chromosome screening approaches.

A review of, and commentary on, the ongoing second clinical introduction of preimplantation genetic screening (PGS) to routine IVF practice

“…Aneuploid embryos often demonstrate multiple chromosomal defects. Linkages between different chromosomes, therefore, were believed to detect most chromosomally abnormal embryos, even when assessing only limited chromosome numbers [25,26].…”

“…While Munné et al suggested that by selecting new probe combinations for 10 to 12 chromosomes, FISH could be improved to an accuracy of 89 to 91 % of aneuploidies [26], assessments of a full chromosome complement have to be assumed more accurate.…”

Mesenchymal Stem Cells: Possibilities of New Treatment Options

“…Using rehybridization cycles (two to three cycles), 10-12 chromosomes (e.g., X, Y, 13, 18, 21, 16, 17, 18, 15, 22) can be tested and nearly 70-90% of aneuploidies can be detected (Griffi n et al 1991 ;Grifo et al 1992 ;Munné et al 1993 ;Colls et al 2007 ;Munné et al 2010 ) .…”

Twenty-four chromosome FISH in human IVF embryos reveals patterns of post-zygotic chromosome segregation and nuclear organisation

“…Array CGH (Colls et al 2009;Munne et al 2010) and/or the use of SNP arrays (Handyside et al 2010) could, in theory, be used to do this with great accuracy on a cell by cell basis however using such an approach would be prohibitively expensive in practice. It is more likely that the whole embryo would be assayed by array CGH or SNP haplotyping, thereby neglecting a cell by cell analysis and making any assessment of mosaicism limited.…”