Genetic Abnormalities in the Human Preimplantation Embryo

  • Alan H. Handyside
Conference paper
Part of the Serono Symposia, USA book series (SERONOSYMP)


In the human, gross genetic abnormalities, mainly involving chromosome number, are a major cause of pregnancy failure. The incidence of chromosomal abnormalities at birth in the normal population is about 0.5% (1). However, a high proportion of fetuses examined after induced or spontaneous abortions are karyotypically abnormal, with numerical chromosome anomalies indicating that the incidence at conception is much higher (2). The development of methods associated with in vitro fertilization (IVF) for the treatment of infertility over the last ten years has facilitated direct study of the incidence of genetic abnormalities in gametogenesis, at fertilization, and during preimplantation development.


Duchenne Muscular Dystrophy Preimplantation Embryo Cystic Fibrosis Transmembrane Regulator Preimplantation Development Hypoxanthine Phospho Ribosyl Transferase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Nielsen J. Chromosome examination of new-born children. Purpose and ethical aspects. Humangenetik 1975;26:215–222.Google Scholar
  2. 2.
    Burgoyne PS, Holland K, Stevens R. Incidence of numerical chromosome anomalies in human pregnancy: estimation from induced and spontaneous abortion data. Hum Reprod 1991;6:555–565.PubMedGoogle Scholar
  3. 3.
    Martin RH, Balkan W, Burns K, Rademaker AW, Lin CC, Rudd NL. The chromosome constitution of 1000 human spermatozoa. Hum Genet 1983;63:305–309.PubMedCrossRefGoogle Scholar
  4. 4.
    Van Blerkom J, Henry G. Cytogenetic analysis of living human oocytes: cellular basis and developmental consequences of perturbations in chromosomal organization and complement. Hum Reprod 1988;3:777–790.PubMedGoogle Scholar
  5. 5.
    Wramsby H, Fredga K. Chromosome analysis of human oocytes failing to cleave after insemination in vitro. Hum Reprod 1987;2:137–142.PubMedGoogle Scholar
  6. 6.
    Hassold T, Jacobs P, Kline J, Stein Z, Warburton D. Effect of maternal age on autosomal trisomies. Ann Hum Genet 1980;44:29–36.PubMedCrossRefGoogle Scholar
  7. 7.
    Angell RR. Predivision in human oocytes at meiosis I: a mechanism for trisomy formation in man. Hum Genet 1991;86:383–387.PubMedCrossRefGoogle Scholar
  8. 8.
    Jacobs PA, Angell RR, Buchanan IM, Hassold TJ, Matsuyama A, Manuel B. The origin of triploids. Ann Hum Genet 1978;44:49–57.CrossRefGoogle Scholar
  9. 9.
    Hardy K, Handyside AH, Winston RML. The human blastocyst: cell number, death and allocation during late preimplantation development in vitro. Development 1989;107:597–604.PubMedGoogle Scholar
  10. 10.
    Van Blerkom J, Bell H, Henry GH. The occurrence, recognition and developmental fate of pseudomultipronuclear eggs after in vitro fertilization of human oocytes. Hum Reprod 1987;2:217–225.PubMedGoogle Scholar
  11. 11.
    Kola I, Trounson A, Dawson G, Rogers P. Tripronuclear human oocytes: altered cleavage patterns and subsequent karyotype analysis of embryos. Biol Reprod 1987;37:395–401.PubMedCrossRefGoogle Scholar
  12. 12.
    Sathananthan AH, Kola I, Osbourne J, et al. Centrioles in the beginning of human development. Proc Natl Acad Sci USA 1991;88:4806–4810.PubMedCrossRefGoogle Scholar
  13. 13.
    Angell RR. Chromosome abnormalities in human preimplantation embryos. In: Yoshinaga K, Mori T, eds. Development of preimplantation embryos and their environment. Prog Clin Biol Res 1989;294:181–187.Google Scholar
  14. 14.
    Papadopoulos G, Templeton AA, Fisk N, Randall J. The frequency of chromosome anomalies in human preimplantation embryos after in vitro fertilization. Hum Reprod 1989;4:91–98.PubMedGoogle Scholar
  15. 15.
    Plachot M, de Grouchy J, Junca A-M, et al. From oocyte to embryo: a model, deduced from in vitro fertilization for natural selection against chromosome abnormalities. Ann Genet 1987;30:22–32.PubMedGoogle Scholar
  16. 16.
    Bongso A, Fong C-Y, Ng S-C, Ratnam S, Lim J. Preimplantation genetics: chromosomes of fragmented human embryos. Fertil Steril 1991;56:66–70.PubMedGoogle Scholar
  17. 17.
    Schrurs B, Winston RML, Handyside AH. Preimplantation diagnosis of aneuploidy by fluorescent in situ hybridization: evaluation using a chromosome 18 specific probe. Hum Reprod 1992.Google Scholar
  18. 18.
    Angell RR, Sumner AT, West JD, Thatcher SS, Glasier AF, Baird DT. Post-fertilization polyploidy in human preimplantation embryos fertilized in vitro. Hum Reprod 1987;2:721–727.PubMedGoogle Scholar
  19. 19.
    Handyside AH. Preimplantation diagnosis. Curr Obstet Gynaecol 1992;2:85–90.CrossRefGoogle Scholar
  20. 20.
    Hardy K. Development of the human blastocysts in vitro. In: Bavister B, ed. Preimplantation embryo development. New York: Springer-Verlag, 1992.Google Scholar
  21. 21.
    Dokras A, Sargent IL, Ross C, et al. Trophectoderm biopsy in human blastocysts. Hum Reprod 1990;5:821–825.PubMedGoogle Scholar
  22. 22.
    Dawson KJ, Rutherford AJ, Winston NJ, et al. Hum blastocyst transfer, is it a feasible proposition? Hum Reprod 1988;suppl 145:44–45.Google Scholar
  23. 23.
    Bolton VN, Wren ME, Parsons JH. Pregnancies following in vitro fertilization and transfer of human blastocysts. Fertil Steril 1991;55:830–832.PubMedGoogle Scholar
  24. 24.
    Hardy K, Martin KL, Leese HJ, et al. Human preimplantation development in vitro is not adversely affected by biopsy at the 8-cell stage. Hum Reprod 1990;5:708–714.PubMedGoogle Scholar
  25. 25.
    Handyside AH, Kontogianni EH, Hardy K, Winston RML. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 1990;344:768–770.PubMedCrossRefGoogle Scholar
  26. 26.
    Trask BJ. Fluorescence in situ hybridisation: applications in cytogenetics and gene mapping. Trends Genet 1991;7:149–154.PubMedGoogle Scholar
  27. 27.
    White TJ, Arnheim N, Erlich HA. The polymerase chain reaction. Trends Genet 1989;5:185–189.PubMedCrossRefGoogle Scholar
  28. 28.
    Griffin DK, Handyside AH, Penketh RJA, et al. Fluorescent in situ hybridisation to interphase nuclei of human preimplantation embryos with X and Y chromosome specific probes. Hum Reprod 1991;6:101–105.PubMedGoogle Scholar
  29. 29.
    Feldberg D, Farhi J, Dicker D, Ashkenazi J, Shelef M, Goldman JA. The impact of embryo quality on pregnancy outcome in older women undergoing in vitro fertilization-embryo transfer (IVF-ET). J In Vitro Fertil Embryo Transfer 1990;7:257–261.CrossRefGoogle Scholar
  30. 30.
    Boué A, Boué J, Gropp A. Cytogenetics of pregnancy wastage. Adv Hum Genet 1985;14:1–58.PubMedGoogle Scholar
  31. 31.
    McKusick VA. Mendelian inheritance in man. 9th ed. Baltimore, MD: Johns Hopkins University Press, 1991.Google Scholar
  32. 32.
    Koenig M, Hoffman EP, Bertelson CJ, et al. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 1987;50:509–517.PubMedCrossRefGoogle Scholar
  33. 33.
    Handyside AH, Delhanty JDA. Cleavage stage biopsy and diagnosis of X-linked disease. In: Edwards RG, ed. Preimplantation diagnosis of human genetic disease. Cambridge, UK: Cambridge University Press, 1992.Google Scholar
  34. 34.
    Handyside AH, Pattinson JK, Penketh RJA, et al. Biopsy of human preimplantation embryos and sexing by DNA amplification. Lancet 1989;1:347–349.PubMedCrossRefGoogle Scholar
  35. 35.
    Rutherford AJ, Subak-Sharpe RJ, Dawson KJ, et al. Improvement of in vitro fertilisation after treatment with Buserelin, an agonist of luteinising hormone releasing hormone. Br Med J 1988;296:1765–1768.CrossRefGoogle Scholar
  36. 36.
    Griffin DK, Wilton L, Handyside AH, et al. Dual fluorescent in situ hybridization for simultaneous detection of X and Y chromosome-specific probes for the sexing of human preimplantation embryonic nuclei. Hum Genet 1992;89:18–22.PubMedCrossRefGoogle Scholar
  37. 37.
    Riordan J, Rommen JM, Kerem B-S, et al. Identification of the cystic fibrosis gene: cloning and characterisation of complementary DNA. Science 1989;245:1066–1073.PubMedCrossRefGoogle Scholar
  38. 38.
    Lesko J, Snabes M, Handyside A, Hughes M. Amplification of the cystic fibrosis ΔF508 mutation from single cells: applications toward genetic diagnosis of the preimplantation embryo. Am J Hum Gen 1991;49(4)suppl:223. Google Scholar
  39. 39.
    Handyside AH, Lesko J, Tarin J, Winston RML, Hughes M. Birth of a normal girl following preimplantation diagnosis for cystic fibrosis. New Engl J Med 1992.Google Scholar

Copyright information

© Springer-Verlag New York, Inc 1993

Authors and Affiliations

  • Alan H. Handyside

There are no affiliations available

Personalised recommendations