FISH for Aneuploidy Screening

Cytogenetic studies have shown that up to 60% of the early spontaneous abortions in humans are caused by numerical chromosomal abnormalities and that as many as 70% of all human preimplantation embryos may contain aneuploid cells.[5] This prompted the development of PGD for aneuploidy screening of oocytes and preimplantation embryos (PGD-AS). Fluorescent in situ hybridization is

Fig. 2 Polar body biopsy. Removal of the first and second polar body.

Fig. 3 Preimplantation genetic diagnosis for a Robertsonian translocation. Upper row: Blastomeres, obtained by biopsy of eight different embryos, analyzed by FISH using locus-specific probes (green for chromosome 13 and red for chromosome 14). The embryos were the result of fertilization of gametes from a carrier of a Robertsonian translocation, der(13;14)(q10;q10). Bottom row: Corresponding, and also all possible gametes in a der(13;14)(q10;q10) carrier, only chromosomes 13, 14, and der(13;14)(q10;q10) being depicted. Only embryos whose blastomere demonstrates two signals of each probe will result in an unaffected child. These embryos will be either noncarrier (a) or balanced carrier (b); the remaining embryos are unbalanced (c-h). (View this art in color at www.dekker.com.)

Fig. 3 Preimplantation genetic diagnosis for a Robertsonian translocation. Upper row: Blastomeres, obtained by biopsy of eight different embryos, analyzed by FISH using locus-specific probes (green for chromosome 13 and red for chromosome 14). The embryos were the result of fertilization of gametes from a carrier of a Robertsonian translocation, der(13;14)(q10;q10). Bottom row: Corresponding, and also all possible gametes in a der(13;14)(q10;q10) carrier, only chromosomes 13, 14, and der(13;14)(q10;q10) being depicted. Only embryos whose blastomere demonstrates two signals of each probe will result in an unaffected child. These embryos will be either noncarrier (a) or balanced carrier (b); the remaining embryos are unbalanced (c-h). (View this art in color at www.dekker.com.)

performed with enumerating probes for an increasing number of different chromosomes to select embryos that are more likely to implant and thereby enhance IVF success. However, there are limits to the number of probes used simultaneously in interphase FISH as this may result in signal overlapping. New technologies, such as comparative genomic hybridization (CGH), which enable full karyotyping of single cells, may solve these problems.[6]

Several reports have suggested an increased pregnancy rate using PGD-AS for patient groups with poor prognosis including those with increased maternal age, recurrent pregnancy losses, or IVF failures.[5] For this reason, PGD-AS is already practiced and is the most common reason for embryo diagnosis.[7] However, the first randomized, prospective study evaluating PGD-AS in these three high-risk groups could not find proof for an added benefit for any of them.[8] Thus there is an urgent need for further evaluation of this technology with additional large, controlled, randomized studies.

The presence of mosaicism shown in human preim-plantation embryos can result in diagnostic difficulties as the biopsied blastomere may not be representative of the embryo. The risk of misdiagnosis could be assessed by reanalysis of nontransferred embryos. Data from PGD-AS indicate a misdiagnosis rate of 7.2%, of which 5.6% was attributable to mosaicism.[9] The estimated risk for false negative diagnosis was 4.3%. However, this may be reduced if two cells are analyzed.

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