Skip to main content
SpringerLink
Log in
Book cover

Human Gametes and Preimplantation Embryos pp 147–155Cite as

Use of Comparative Genomic Hybridisation (CGH) and Microarray-CGH for Preimplantation Genetic Screening

  • Chapter
  • First Online:

  • 1360 Accesses

Abstract

It has been known for many decades that chromosomal aneuploidies are responsible for more than half of all spontaneous miscarriages and still births (Ann Hum Genet 44:151–178, 1980; Oxf Rev Reprod Biol 6:1–46, 1984; Oxf Rev Reprod Biol 14:47–72, 1992), making aneuploidy one of the most lethal genetic conditions. Most commonly miscarriages are associated with trisomy of chromosomes 16, 21 and 22 (Ann Hum Genet 44:151–178, 1980; Birth Defects Orig Artic Ser 23:153–168, 1987; Am J Med Genet 72:297–301, 1997). Aneuploidy of other chromosomes is rarely seen in prenatal samples or miscarriages possibly because such errors are so lethal that the conceptuses are lost very early in gestation or prior to implantation. The advent of in vitro fertilisation (IVF) technologies and access to early human embryos in the laboratory provided the opportunity to investigate aneuploidy during first few days after conception.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Hassold T, Chen J, Funkhouser J, Jooss T, Manuel B, Matsuura J, et al. A cytogenetic study of 1000 spontaneous abortions. Ann Hum Genet. 1980;44:151–78.

    Article  PubMed  CAS  Google Scholar 

  2. Chandley AC. Infertility and chromosome abnormality. Oxf Rev Reprod Biol. 1984;6:1–46.

    PubMed  CAS  Google Scholar 

  3. Jacobs PA. The chromosome complement of human gametes. Oxf Rev Reprod Biol. 1992;14:47–72.

    PubMed  CAS  Google Scholar 

  4. Kalousek D. Anatomic and chromosome anomalies in specimens of early spontaneous abortion; seven-year experience. Birth Defects Orig Artic Ser. 1987;23:153–68.

    PubMed  CAS  Google Scholar 

  5. Griffin DK, Millie EA, Redline RW, Hassold TJ, Zaragoza MV. Cytogenetic analysis of spontaneous abortions: comparison of techniques and assessment of confined placental mosaicism. Am J Med Genet. 1997;72:297–301.

    Article  PubMed  CAS  Google Scholar 

  6. Wilton L. In vitro culture of biopsied blastomeres and diagnosis of aneuploidy. In Gamete and embryo micromanipulation in human reproduction. London, UK: Edward Arnold; 1993. p. 187–193.

    Google Scholar 

  7. Jamieson ME, Coutts JRT, Connor JM. The chromosome constitution of human preimplantation embryos fertilized in vitro. Hum Reprod. 1994;9:709–15.

    PubMed  CAS  Google Scholar 

  8. Santalo J, Veiga A, Calafell JM, Calderon G, Vidal F, Barri PN, et al. Evaluation of cytogenetic analysis for clinical preimplantation diagnosis. Fertil Steril. 1995;64:44–50.

    PubMed  CAS  Google Scholar 

  9. Clouston HJ, Fenwick J, Webb AL, Herbert M, Murdoch A, Wolstenholme J. Detection of mosaic and non-mosaic chromosome abnormalities in 6- to 8-day old human blastocysts. Hum Genet. 1997;101:30–6.

    Article  PubMed  CAS  Google Scholar 

  10. Griffin DK, Wilton LJ, Handyside AH, Winston RML, Delhanty JDA. Dual fluorescent in situ hybridisation for simultaneous detection of X and Y chromosome-specific probes for the sexing of human preimplantation embryonic nuclei. Hum Genet. 1992;89:18–22.

    Article  PubMed  CAS  Google Scholar 

  11. Benkhalifa M, Janny L, Vye P, Malet P, Boucher D, Menezo Y. Assessment of polyploidy in human morulae and blastocysts using co-culture and fluorescent in-situ hybridization. Hum Reprod. 1993;8:895–902.

    PubMed  CAS  Google Scholar 

  12. Schrurs B, Winston RML, Handyside AH. Preimplantation diagnosis of aneuploidy using fluorescent in-situ hybridization: evaluation using a chromosome 18-specific probe. Hum Reprod. 1993;8:296–301.

    PubMed  CAS  Google Scholar 

  13. Munné S, Alikani M, Tomkin G, Grifo J, Cohen J. Embryo morphology, developmental rates and maternal age are correlated with chromosome abnormalities. Fertil Steril. 1995;64:382–91.

    PubMed  Google Scholar 

  14. Bielanska M, Tan SL, Ao A. Chromosomal mosaicism throughout human preimplantation development in vitro: incidence, type and relevance to embryo outcome. Hum Reprod. 2002;17:413–9.

    Article  PubMed  Google Scholar 

  15. Munné S, Chen S, Colls P, Garrisi J, Zheng X, Cekleniak N, et al. Maternal age, morphology, development and chromosome abnormalities in over 6000 cleavage-stage embryos. Reprod Biomed Online. 2007;14:628–34.

    Article  PubMed  Google Scholar 

  16. Magli MC, Gianaroli L, Ferraretti AP, Lappi M, Ruberti A, Farfalli V. Embryo morphology and development are dependent on the chromosomal complement. Fertil Steril. 2007;87:534–41.

    Article  PubMed  Google Scholar 

  17. Munné S, Lee A, Rosenwaks Z, Grifo J, Cohen J. Diagnosis of major chromosome aneuploidies in human preimplantation embryos. Hum Reprod. 1993;8:2185–91.

    PubMed  Google Scholar 

  18. Staessen C, Platteau P, Van Assche E, Michiels A, Tournaye H, Camus M, et al. Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomised trial. Hum Reprod. 2004;19:2849–58.

    Article  PubMed  Google Scholar 

  19. Mastenbroek S, Twisk M, van-Echten-Arends J, Sikkema-Raddatz B, Korevaar JC, Verhoever HR. In vitro fertilization with preimplantation genetic screening. N Engl J Med. 2007;357:9–17.

    Article  PubMed  CAS  Google Scholar 

  20. Hardarson T, Hanson C, Lundin K, Hillensjö T, Nilsson L, Stevic J, et al. Preimplantation genetic screening in women of advanced maternal age caused a decrease in clinical pregnancy rate: a randomized controlled trial. Hum Reprod. 2008;23:2806–12.

    Article  PubMed  CAS  Google Scholar 

  21. Jansen RP, Bowman MC, de Boer KA, Leigh DA, Lieverman DB, McArthur SJ. What next for preimplantation screening (PGS). Experience with blastocyst biopsy and testing for aneuploidy. Hum Reprod. 2008;23:1476–8.

    Article  PubMed  Google Scholar 

  22. Debrock S, Melotte C, Spiessens C, Peeraer K, Vanneste E, Meeuwis L, et al. Preimplantation genetic screening for aneuploidy of embryos after in vitro fertilization in women aged at least 35 years: a prospective randomised trial. Fertil Steril. 2010;93:364–73.

    Article  PubMed  Google Scholar 

  23. Schoolcraft WB, Katz-Jaffe MG, Stevens J, Rawlins M, Munné S. Preimplantation aneuploidy testing for infertile patients of advanced maternal age: a randomized prospective trial. Fertil Steril. 2009;92:157–62.

    Article  PubMed  Google Scholar 

  24. Weier HU-G, Munné S, Lersch RA, Ben Hsieh H, Smida J, Chen X-N, et al. Towards a full karyotype screening of interphase cells: ‘FISH and chip’ technology. Mol Cell Endocrinol. 2001;183:S41–5.

    Article  PubMed  CAS  Google Scholar 

  25. Kallionemi A, Kallionemi O-P, Sudar D, Rutovitz D, Gray JW, Waldman F, et al. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumours. Science. 1992;258:818–21.

    Article  Google Scholar 

  26. Wells D, Sherlock JK, Handyside AH, Delhanty JDA. Detailed chromosomal and molecular genetic analysis of single cells by whole genome amplification and comparative genomic hybridisation. Nucleic Acids Res. 1999;27:1214–8.

    Article  PubMed  CAS  Google Scholar 

  27. Wells D, Delhanty JD. Comprehensive chromosomal analysis of human preimplantation embryos using whole genome amplification and single cell comparative genomic hybridization. Mol Hum Reprod. 2000;6:1055–62.

    Article  PubMed  CAS  Google Scholar 

  28. Voullaire L, Slater H, Williamson R, Wilton L. Chromosome analysis of blastomeres from human embryos by using comparative genomic hybridization. Hum Genet. 2000;106:210–7.

    Article  PubMed  CAS  Google Scholar 

  29. Wilton L, Williamson R, McBain J, Edgar D, Voullaire L. Birth of a healthy infant after preimplantation confirmation of euploidy by comparative genomic hybridisation. N Engl J Med. 2001;345:1537–41.

    Article  PubMed  CAS  Google Scholar 

  30. Wilton L, Voullaire L, Sargeant P, Williamson R, McBain J. Preimplantation aneuploidy screening using comparative genomic hybridisation or fluorescent in situ hybridisation of embryos from patients with recurrent implantation failure. Fertil Steril. 2003;80:860–8.

    Article  PubMed  Google Scholar 

  31. Wells D, Escudero T, Levy B, Hirschhorn K, Delhanty JDA, Munné S. First clinical application of comparative genomic hybridisation and polar body testing for preimplantation genetic diagnosis of aneuploidy. Fertil Steril. 2002;78:543–9.

    Article  PubMed  Google Scholar 

  32. Rius M, Obradors A, Daina G, Ramos L, Pujol A, Martínez-Passarell O, et al. Detection of unbalanced chromosome segregations in preimplantation genetic diagnosis of translocations by short comparative genomic hybridization. Fertil Steril. 2011;96:134–42.

    Article  PubMed  CAS  Google Scholar 

  33. Obradors A, Fernández E, Oliver-Bonet M, Rius M, de la Fuente A, Wells D, et al. Birth of a healthy boy after a double factor PGD in a couple carrying a genetic disease and at risk for aneuploidy: case report. Hum Reprod. 2008;23:1949–56.

    Article  PubMed  CAS  Google Scholar 

  34. Sher G, Keskintepe L, Keskintepe M, Maassarani G, Tortoriello D, Brody S. Genetic analysis of human embryos by metaphase comparative genomic hybridization (mCGH) improves efficiency of IVF by increasing embryo implantation rate and reducing multiple pregnancies and spontaneous miscarriages. Fertil Steril. 2009;92:1886–94.

    Article  PubMed  CAS  Google Scholar 

  35. Schoolcraft WB, Fragouli E, Stevens J, Munné S, Katz-Jaffe MG, Wells D. Clinical application of comprehensive chromosomal screening at the blastocyst stage. Fertil Steril. 2010;94:1700–6.

    Article  PubMed  Google Scholar 

  36. Hu DG, Webb G, Hussey N. Aneuploidy detection in single cells using DNA array-based comparative genomic hybridization. Mol Hum Reprod. 2004;10:283–9.

    Article  PubMed  CAS  Google Scholar 

  37. Wells D, Bermudez MG, Steuerwald N, Chu L, Weier U, Cohen J, et al. Microarrays for analysis and diagnosis of human embryos. In: Papp Z, Rodeck C, editors. Recent advances in prenatal genetic diagnosis. Italy: Medimond; 2004. p. 9–17.

    Google Scholar 

  38. 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 

  39. Hellani A, Abu-Amero K, Azouri J, El-Akoum S. Successful pregnancies after application of array-comparative genomic hybridization in PGS-aneuploidy screening. Reprod Biomed Online. 2008;17:814–7.

    Article  Google Scholar 

  40. Yang Z, Lui J, Collins GS, Salem SA, Liu X, Lyle SS, et al. Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet. 2012;5:24–9.

    Article  PubMed  Google Scholar 

  41. Fragouli E, Alfarawati S, Daphnis DD, Goodall NN, Mania A, Griffiths T, et al. Cytogenetic analysis of human blastocysts with the use of FISH, CGH and aCGH: scientific data and technical evaluation. Hum Reprod. 2011;26:480–90.

    Article  PubMed  CAS  Google Scholar 

  42. Alfarawati S, Fragouli E, Colls P, Stevens J, Gutiérrez-Mateo C, Schoolcraft WB, et al. The relationship between blastocyst morphology, chromosomal abnormality, and embryo gender. Fertil Steril. 2011;95:520–4.

    Article  PubMed  Google Scholar 

  43. Alfarawati S, Fragouli E, Colls P, Wells D. First births after preimplantation genetic diagnosis of structural chromosome abnormalities using comparative genomic hybridization and microarray analysis. Hum Reprod. 2011;26:1560–74.

    Article  PubMed  CAS  Google Scholar 

  44. Fiorentino F, Spizzichino L, Bono S, Biricik A, Kokkali G, Rienzi L, et al. PGD for reciprocal and Robertsonian translocations using array comparative genomic hybridization. Hum Reprod. 2011;26:1925–35.

    Article  PubMed  CAS  Google Scholar 

  45. Delhanty J, Griffin D, Handyside AH, Harper JC, Atkinson G, Pieters MHEC, et al. Detection of aneuploidy and chromosomal mosaicism in human embryos during preimplantation sex determination by fluorescent in situ hybridisation. Hum Mol Genet. 1993;2:1183–5.

    Article  PubMed  CAS  Google Scholar 

  46. Delhanty JDA, Harper JC, Ao A, Handyside AH, Winston RML. Multicolour FISH detects frequent chromosomal mosaicism and chaotic division in normal preimplantation embryos from fertile patients. Hum Genet. 1997;99:755–60.

    Article  PubMed  CAS  Google Scholar 

  47. Munné S, Weier H-UG, Cohen J. Chromosome mosaicism in human embryos. Biol Reprod. 1994;51:373–9.

    Article  PubMed  Google Scholar 

  48. Munné S, Magli C, Adler A, Wright G, deBoer K, Mortimer D, et al. Treatment-related chromosome abnormalities in human embryos. Hum Reprod. 1997;12:780–4.

    Article  PubMed  Google Scholar 

  49. Benadiva CA, Kligman I, Munné S. Aneuploidy 16 in human embryos increases significantly with maternal age. Fertil Steril. 1996;66:248–55.

    PubMed  CAS  Google Scholar 

  50. Daphnis DD, Delhanty JD, Jerkovic S, Geyer J, Craft I, Harper JC. Detailed FISH analysis of day 5 human embryos reveals the mechanisms leading to mosaic aneuploidy. Hum Reprod. 2005;20:129–37.

    Article  PubMed  CAS  Google Scholar 

  51. Fragouli E, Katz-Jaffe M, Alfarawati S, Stevens J, Colls P, Goodall NN, et al. Comprehensive chromosome screening of polar bodies and blastocysts from couples experiencing repeated implantation failure. Fertil Steril. 2010;94:875–87.

    Article  PubMed  Google Scholar 

  52. 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;26:3173–80.

    Article  PubMed  CAS  Google Scholar 

  53. Fishel S, Gordon A, Lynch C, Dowell K, Ndukwe G, Kelada E, et al. Live birth after polar body array comparative genomic hybridization prediction of embryo ploidy-the future of IVF? Fertil Steril. 2010;93:1006.e7–e10.

    Article  Google Scholar 

  54. Wells D, Alfarawati S, Konstantinidis M, Jaroudi S, Fragouli E. Characterisation of mechanisms causing oocyte aneuploidy reveals a flaw in embryo selection strategies based upon polar body chromosome screening. Hum Reprod. 2012;27 Suppl 2:ii106–8.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Preimplantation Genetics, Melbourne IVF, East Melbourne, VIC, Australia

    Leeanda Wilton

  2. Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Institute of Reproductive Sciences, Oxford, UK

    Dagan Wells

Authors
  1. Leeanda Wilton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dagan Wells
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leeanda Wilton .

Editor information

Editors and Affiliations

  1. University of Melbourne, Department of Zoology, Royal Parade, Melbourne, 3010, Victoria, Australia

    David K. Gardner

  2. Boston IVF, Second Ave. 130, Waltham, 02451, Massachusetts, USA

    Denny Sakkas

  3. Yale School of Medicine, Dept. of Ob/Gyn & Reproductive Sciences, Cedar St. 333, New Haven, 06510, Connecticut, USA

    Emre Seli

  4. Obstetrics & Gynaecology, University of Oxford, Nuffield Department of, Garsington Road, Oxford, OX4 2HW, Oxfordshire, United Kingdom

    Dagan Wells

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Wilton, L., Wells, D. (2013). Use of Comparative Genomic Hybridisation (CGH) and Microarray-CGH for Preimplantation Genetic 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_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6651-2_13

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-6650-5

  • Online ISBN: 978-1-4614-6651-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation