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Quantitative SNP Array and Real-Time PCR-Based Human Preimplantation Embryo Aneuploidy Screening

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Human Gametes and Preimplantation Embryos
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Abstract

Chromosome imbalance (aneuploidy) is the most common genetic abnormality found in human embryos, and the leading genetic cause of implantation failure and miscarriage. Screening embryos for aneuploidy prior to their transfer during IVF should therefore provide a substantial benefit to many patients with infertility. Indeed, preimplantation genetic screening (PGS) is currently the subject of exciting advancements that may result in finally realizing the potential to improve the success of IVF and revolutionize the standard of care in reproductive medicine. The ideal of routine elective single embryo transfer may soon become a reality with the incorporation of valid comprehensive chromosome screening (CCS) technology. Furthermore, selective transfer of embryos predicted to possess a normal complement of 23 pairs of chromosomes not only represents an important clinical application, but also a unique opportunity to conduct more well-controlled research to develop additional prognostic markers of embryonic reproductive potential. While there are a large number of unique methodologies for CCS, this chapter will focus on results of research and development of two specific technologies.

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References

  1. Treff NR, Su J, Bergh EP, Levy B, Miller KA, Scott J. Single-blastomere whole-genome DNA fingerprinting results in unequivocal embryo identification – a powerful new clinical and diagnostic tool. Fertil Steril. 2007;88:S3–4.

    Article  Google Scholar 

  2. Treff NR, Su J, Mavrianos J, Bergh PA, Miller KA, Scott J. Accurate 23 chromosome aneuploidy screening in human blastomeres using single nucleotide polymorphism (SNP) microarrays. Fertil Steril. 2007;88:S1.

    Article  Google Scholar 

  3. Treff NR, Su J, Tao X, Levy B, Scott Jr RT. Accurate single cell 24 chromosome aneuploidy screening using whole genome amplification and single nucleotide polymorphism microarrays. Fertil Steril. 2010;94:2017–21.

    Article  PubMed  CAS  Google Scholar 

  4. Treff NR, Su J, Tao X, Northrop LE, Scott Jr RT. Single-cell whole-genome amplification technique impacts the accuracy of SNP microarray-based genotyping and copy number analyses. Mol Hum Reprod. 2011;17:335–43.

    Article  PubMed  CAS  Google Scholar 

  5. Fiegler H, Geigl JB, Langer S, Rigler D, Porter K, Unger K, et al. High resolution array-CGH analysis of single cells. Nucleic Acids Res. 2007;35:1–10.

    Article  Google Scholar 

  6. Handyside AH, Robinson MD, Simpson RJ, Omar MB, Shaw MA, Grudzinskas JG, et al. Isothermal whole genome amplification from single and small numbers of cells: a new era for preimplantation genetic diagnosis of inherited disease. Mol Hum Reprod. 2004;10:767–72.

    Article  PubMed  CAS  Google Scholar 

  7. Le Caignec C, Spits C, Sermon K, De Rycke M, Thienpont B, Debrock S, et al. Single-cell chromosomal imbalances detection by array CGH. Nucleic Acids Res. 2006;34:e68.

    Article  PubMed  Google Scholar 

  8. Treff NR, Scott Jr RT. Genome-wide chromosome aneuploidy assessment on single cells using two types of arrays – SNP based arrays are more accurate and less variable than BAC arrays. Fertil Steril. 2007;88:S87–8.

    Article  Google Scholar 

  9. Treff NR, Levy B, Su J, Northrop LE, Tao X, Scott Jr RT. SNP microarray-based 24 chromosome aneuploidy screening is significantly more consistent than FISH. Mol Hum Reprod. 2010;16:583–9.

    Article  PubMed  CAS  Google Scholar 

  10. Northrop LE, Treff NR, Levy B, Scott Jr RT. SNP microarray-based 24 chromosome aneuploidy screening demonstrates that cleavage-stage FISH poorly predicts aneuploidy in embryos that develop to morphologically normal blastocysts. Mol Hum Reprod. 2010;16:590–600.

    Article  PubMed  CAS  Google Scholar 

  11. Scott Jr RT, Ferry K, Su J, Tao X, Scott K, Treff NR. Comprehensive chromosome screening is highly predictive of the reproductive potential of human embryos: a prospective, blinded, nonselection study. Fertil Steril. 2012;97(4):870–5.

    Article  PubMed  Google Scholar 

  12. Treff NR, Ferry KM, Zhao T, Su J, Forman EJ, Scott RT. Cleavage stage embryo biopsy significantly impairs embryonic reproductive potential while blastocyst biopsy does not: a novel paired analysis of cotransferred biopsied and non-biopsied sibling embryos. Fertil Steril. 2011;96:S2.

    Article  Google Scholar 

  13. Schoolcraft WB, Treff NR, Stevens JM, Ferry K, Katz-Jaffe M, Scott Jr RT. Live birth outcome with trophectoderm biopsy, blastocyst vitrification, and single-nucleotide polymorphism microarray-based comprehensive chromosome screening in infertile patients. Fertil Steril. 2011;96:638–40.

    Article  PubMed  Google Scholar 

  14. Treff NR, Northrop LE, Kasabwala K, Su J, Levy B, Scott Jr RT. Single nucleotide polymorphism microarray-based concurrent screening of 24 chromosome aneuploidy and unbalanced translocations in preimplantation human embryos. Fertil Steril. 2010;95:1606–12. e1–2.

    Article  PubMed  Google Scholar 

  15. Treff N, Su J, Tao X, Miller K, Scott Jr RT. First IVF babies born after rapid 24 chromosome embryo aneuploidy screening and fresh embryo transfer. Fertil Steril. 2009;92:S49.

    Google Scholar 

  16. Geraedts J, Montag M, Magli MC, Repping S, Handyside A, Staessen C, et al. Polar body array CGH for prediction of the status of the corresponding oocyte. Part I: clinical results. Hum Reprod. 2011;26(11):3173–80.

    Article  PubMed  CAS  Google Scholar 

  17. Gabriel AS, Thornhill AR, Ottolini CS, Gordon A, Brown AP, Taylor J, et al. Array comparative genomic hybridisation on first polar bodies suggests that non-disjunction is not the predominant mechanism leading to aneuploidy in humans. J Med Genet. 2011;48(7):433–7.

    Article  PubMed  CAS  Google Scholar 

  18. Treff NR, Su J, Tao X, Katz-Jaffe M, Schoolcraft WB, Scott Jr RT. Characterizing the nature of meiotic errors: PSSC is the principal meiotic error in human oocytes and may correct during the 2nd meiotic division and result in the birth of a healthy infant. Fertil Steril. 2009;92:S25.

    Article  Google Scholar 

  19. Treff NR, Tao X, Lonczak A, Su J, Taylor D, Scott Jr RT. Four hour 24 chromosome aneuploidy screening using high throughput PCR SNP allele ratio analyses. Fertil Steril. 2009;92:S49–50.

    Google Scholar 

  20. Treff NR, Tao X, Ferry KM, Su J, Taylor D, Scott Jr RT. Development and validation of an accurate quantitative real-time PCR based assay for human blastocyst comprehensive chromosomal aneuploidy screening. Fertil Steril. 2012;97(4):819–24.

    Article  PubMed  CAS  Google Scholar 

  21. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc. 2008;3:1101–8.

    Article  PubMed  CAS  Google Scholar 

  22. Scott Jr RT, Tao X, Taylor D, Ferry K, Treff N. A prospective randomized controlled trial demonstrating significantly increased clinical pregnancy rates following 24 chromosome aneuploidy screening: biopsy and analysis on day 5 with fresh transfer. Fertil Steril. 2010;94:S2.

    Article  Google Scholar 

  23. Forman EJ, Tao X, Ferry KM, Taylor D, Treff NR, Scott Jr RT. Single embryo transfer with comprehensive chromosome screening results in improved ongoing pregnancy rates and decreased miscarriage rates. Hum Reprod. 2012;27(4):1217–22.

    Article  PubMed  CAS  Google Scholar 

  24. Treff NR, Su J, Taylor D, Scott Jr RT. Telomere DNA deficiency is associated with development of human embryonic aneuploidy. PLoS Genet. 2011;7:e1002161.

    Article  PubMed  CAS  Google Scholar 

  25. Treff NR, Su J, Lonczak A, Taylor D, Scott Jr RT. A subset of the cumulus cell transcriptome is predictive of euploid human oocyte reproductive potential. Fertil Steril. 2010;94:S34–5.

    Article  Google Scholar 

  26. Su J, Tao X, Baglione G, Treff NR, Scott RT. Mitochondrial DNA is significantly increased in aneuploid human embryos. Fertil Steril. 2010;94:S88–9.

    Article  Google Scholar 

  27. Treff NR, Su J, Tao X, Frattarelli JL, Miller KA, Scott RT. Characterization of the source of human embryonic aneuploidy using microarray-based 24 chromosome preimplantation genetic diagnosis (mPGD) and aneuploid chromosome fingerprinting. Fertil Steril. 2008;90:S37.

    Article  Google Scholar 

  28. Treff NR, Scott Jr RT, Su J, Campos J, Stevens J, Schoolcraft W, et al. Polar body morphology is not predictive of its cell division origin. J Assist Reprod Genet. 2012;29(2):137–9.

    Article  PubMed  Google Scholar 

  29. Fragouli E, Alfarawati S, Goodall NN, Sanchez-Garcia JF, Colls P, Wells D. The cytogenetics of polar bodies: insights into female meiosis and the diagnosis of aneuploidy. Mol Hum Reprod. 2011;17:286–95.

    Google Scholar 

  30. Handyside AH, Montag M, Magli MC, Repping S, Harper J, Schmutzler A, et al. Multiple meiotic errors caused by predivision of chromatids in women of advanced maternal age undergoing in vitro fertilisation. Eur J Hum Genet. 2012;20:1–6.

    Article  Google Scholar 

  31. Taylor D, Pike JW, Kasabwala K, Northrop LE, Treff NR, Scott RT. A genome-wide association scan identifies several maternal susceptibility loci for embryo aneuploidy. Fertil Steril. 2010;94:S183.

    Article  Google Scholar 

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Correspondence to Nathan R. Treff .

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Treff, N.R. (2013). Quantitative SNP Array and Real-Time PCR-Based Human Preimplantation Embryo Aneuploidy Screening. In: Gardner, D., Sakkas, D., Seli, E., Wells, D. (eds) Human Gametes and Preimplantation Embryos. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6651-2_14

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  • DOI: https://doi.org/10.1007/978-1-4614-6651-2_14

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  • Publisher Name: Springer, New York, NY

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