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The Origins of Aneuploidy in Human Embryos

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Human Gametes and Preimplantation Embryos

Abstract

One of the main causes of the relatively low reproductive success rates seen in humans is numerical chromosome abnormalities (aneuploidy). The advent of in vitro fertilisation (IVF) and associated diagnostic methods such as preimplantation genetic diagnosis and screening enabled a detailed investigation of the chromosome content of human gametes and embryos. Such investigations clearly showed that the incidence of numerical chromosome abnormalities was high and as would be expected had an adverse impact on the progress of embryo development and viability.

Embryonic aneuploidy can have a meiotic origin with chromosome malsegregation taking place during gametogenesis, and a post-zygotic origin with abnormalities occurring after fertilisation. Direct analysis of the human female gamete using a variety of cytogenetic methods has shown that the majority of meiotically derived aneuploidies arise during oogenesis. The close relationship between advancing female age and increasing aneuploidy rates was also confirmed, as more than 50 % of oocytes generated by women over the age of 40 years were demonstrated to be chromosomally abnormal. Graphs illustrating the changing oocyte aneuploidy rate with advancing maternal age are a mirror image of those showing the declining implantation rate of IVF embryos with age, suggesting that the increase in meiotic errors might explain the reduced success rate of IVF treatments for women in their late 30s and 40s.

The contribution of aneuploidy of male meiotic origin to the embryo is not as clear. Several studies have been carried out, and it was concluded that the incidence of chromosome anomalies ranged between 3 and 5 % in the sperm of fertile men, but significantly (approximately threefold) increased in the sperm obtained by infertile men.

Studies investigating two different preimplantation development stages, namely the cleavage stage and blastocyst stage, have suggested that post-zygotic chromosome anomalies take place even more frequently compared to the meiotic ones, especially at the cleavage stage. A result of post-zygotic anomalies is chromosome mosaicism, the presence of two or more karyotypically distinct cell lines within the same embryo.

During this chapter, the data obtained from cytogenetic investigations of human oocytes, sperm and also embryos at the cleavage and blastocyst stage of preimplantation development will be summarised. In addition, the different mechanisms leading to aneuploidy of meiotic and post-zygotic origin will be described and their frequencies and impact on embryonic survival will be discussed.

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Additional Reading

  • Jones KT. Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age. Hum Reprod Update. 2008;14:143–58.

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Authors and Affiliations

  1. Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK

    Elpida Fragouli

  2. Reprogenetics UK, Oxford, UK

    Elpida Fragouli

  3. Fetal and Maternal Medicine, Institute for Women’s Health, University College, 86-96 Chenies Mews, London, UK

    Joy Delhanty

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  1. Elpida Fragouli
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Correspondence to Elpida Fragouli .

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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

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Fragouli, E., Delhanty, J. (2013). The Origins of Aneuploidy in Human Embryos. 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_10

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