Current and Novel Methods for Chromosome Testing
More than 50% cleavage and blastocyst stage embryos produced in-vitro are found to be chromosomally abnormal, increasing up to 80% in women over 42 years of age. While some abnormal embryos arrest during culture, most do not. Embryos with numerical chromo
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Current and Novel Methods for Chromosome Testing Sarthak Sawarkar and Santiago Munné 49.1
PGS Version 1 and Its Limitations – 604
49.2
Biopsy Techniques – 604
49.3
Polar Body Biopsy – 604
49.4
Cleavage-Stage Biopsy – 605
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Blastocyst Biopsy – 605
49.6
Screening Techniques Used in PGS v2 – 606
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GH – 606 C aCGH – 606 SNP Arrays – 606 qPCR – 608 High-Resolution NGS – 608 Targeted NGS – 608 Validation of PGD V2 Techniques – 608 Clinical Results – 609 Mosaicism – 610 Chromosome Abnormalities Are Center-Dependent – 610
Review Questions – 610 References – 610
© Springer Nature Switzerland AG 2019 Z. P. Nagy et al. (eds.), In Vitro Fertilization, https://doi.org/10.1007/978-3-319-43011-9_49
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S. Sawarkar and S. Munné
More than 50% cleavage and blastocyst stage embryos produced in vitro are found to be chromosomally abnormal, increasing up to 80% in women over 42 years of age [1]. While some abnormal embryos arrest during culture, most do not. Embryos with numerical chromosomal abnormalities are usually not compatible with either implantation or birth, with and up to 70% of spontaneous abortions being chromosomally abnormal, clearly highlighting the detrimental effects of aneuploidy. Thus, we hypothesized that the selection of normal (euploid) embryos for transfer should improve the success rate of IVF [2]. This process of selection against aneuploidy is known as preimplantation genetic diagnosis (PGD) of aneuploidy (PGD-A) or preimplantation genetic screening (PGS). 49.1
PGS Version 1 and Its Limitations
Early strategies for PGS involved using fluorescent in situ hybridization (FISH) to analyze day-3 blastomere biopsy or polar bodies biopsied from oocytes and/or zygotes [3]. FISH allowed the analysis of anywhere between 5 and 12 chromosomes per sample but a complete evaluation of the chromosome complement. Even with this limited coverage, FISH detected more than 80% of chromosomally abnormal embryos. Another limitation of FISH was the need of fixing the cells, which required dexterity, and some methods were better than others [4] but not used widely. More importantly, cleavage-stage biopsy required as much skills, and although experienced centers showed improved results in clinical randomized trials (CRTs) [5], on the other hand, it could reduce implantation potential by half [6–8]. Thus, while some studies showed an improvement in implantation rates, reduction in spontaneous abortions, and take-home-baby rates [9–18], others showed no improvement or even a detrimental effect of PGS [6, 19–21]. The most likely cause explaining the inter-center differences in PGD outcomes are variations in biopsy and genetic techniques employed. For example, one of the studies showing detrimental effects of PGD used a two-cell biopsy [22]. However, the same group later reported a detrimental effect of a two-celled biopsy compared to the one-celled biopsy from cleavage-stage embryos [23]. Biopsying even a sing
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