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  • Print publication year: 2020
  • Online publication date: December 2019

Chapter 14 - Preimplantation Genetic Diagnosis

Summary

Preimplantation genetic diagnosis (PGD) was developed in the late 1980s to help couples who are at risk of transmitting an inherited disease to their offspring, as an alternative to prenatal diagnosis during pregnancy. Prenatal diagnosis has the disadvantage that if the diagnosis shows the fetus to be affected, the couple must decide whether they wish to terminate the pregnancy or continue with the knowledge that their child is going to be affected by the genetic disease. PGD offers some of these couples an alternative, as the diagnosis is performed on the preimplantation embryo, and only embryos assessed as being unaffected by the genetic disease are transferred to the patient. The pregnancy is therefore initiated with the knowledge that the fetus is free from the disease, at that moment in time.

Elder, K, Cohen, J (eds.) (2007) Human Preimplantation Embryo Evaluation and Selection. Informa Press, London.
Dale, B, Ménézo, Y, Coppola, G (2015) Trends, Fads and Art. Journal of Assisted Reproduction and Genetics 32: 489493.
Dale, B, Ménézo, Y, Elder, K (2016) Who benefits from PGS? Austin Journal of IVF 3: 1026.
Dahdouh, EM, Balayla, J, Audibert, F, Genetics Committee (2015) Technical update: preimplantation genetic diagnosis and screening. Journal of Obstetrics and Gynaecology Canada 37(5): 451463.
De Ryck, M, Goossens, V, Kokkali, G, et al. (2017) ESHRE PGD Consortium data collection XIV–XV: cycles from January 2011 to December 2012 with pregnancy follow-up to October 2013. Human Reproduction 32(10): 19741994.
Fauser, B (2006) Pre-implantation genetic screening: the end of an affair? Human Reproduction 23: 26222625.
Geraedts, J, Sermon, K (2016) Preimplantation genetic screening 2.0: the theory. Molecular Human Reproduction 22(8): 539544.
Gleicher, N, Orvieto, R (2017) Is the hypothesis of pre-implantation genetic screening (PGS) still supportable? A review. Journal of Ovarian Research 10: 17.
Harper, J, Delhanty, JDA, Handyside, AH (2001) Preimplantation Genetic Diagnosis. Cambridge University Press, Cambridge, UK.
Harper, J (2009) Preimplantation Genetic Diagnosis, 2nd edn. Cambridge University Press, Cambridge, UK.
Hayward, J, Chitty, L (2018) Beyond screening for chromosomal abnormalities: advances in non-invasive diagnosis of single gene disorders and fetal exome sequencing. Seminars in Fetal and Neonatal Medicine 23(2): 94101.
Mastenbroek, S, Repping, S (2014) Preimplantation genetic screening: back to the future. Human Reproduction 29: 18461850.
Meaney, C, Norbury, G (2011) Non-invasive prenatal diagnosis. In: Theophilus, B, Rapley, R (eds.) PCR Mutation Detection Protocols. Methods in Molecular Biology (Methods and Protocols), vol 688. Humana Press, Springer Science + Business Media, London, pp. 155172.
Munné, S (2018) Status of preimplantation genetic testing and embryo selection. Reproductive BioMedicine Online 28(4): 393396.
Sanders, KD, Griffin, KD (2017) Chromosomal preimplantation genetic diagnosis: 25 years and counting. Journal of Fetal Medicine 4(2): 5156.
Sermon, K, Capalbo, A, Cohen, J, et al. (2016) The why, the how and the when of PGS 2.0: current practices and expert opinions of fertility specialists, molecular biologists and embryologists. Molecular Human Reproduction 22(8): 545557.
Bolton, H, Graham, S, Van de Aa, N (2016) Mouse model of a chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential. Nature Communications 7: 11165.
Coonen, E, Harper, JC, Ramaekers, FCS, et al. (1994) Presence of chromosomal mosaicism in abnormal preimplantation embryos detected by fluorescent in situ hybridisation. Human Genetics 54: 609615.
Delhanty, JDA, Griffin, DK, Handyside, AH, et al. (1993) Detection of aneuploidy and chromosomal mosaicism in human embryos during preimplantation sex determination by fluorescent in situ hybridization (FISH). Human Molecular Genetics 2(8): 11831185.
Delhanty, JDA, Harper, JC, Ao, A, Handyside, AH, Winston, RML (1997) Multicolour FISH detects frequent chromosomal mosaicism and chaotic division in normal preimplantation embryos from fertile patients. Human Genetics 99: 755760.
Gardner, RL, Edwards, RG (1968) Control of the sex ratio at full term in the rabbit by transferring sexed blastocysts. Nature 218: 346349.
Gianaroli, L, Magli, MC, Ferraretti, AP, Munné, S (1999) Preimplantation diagnosis for aneuploidies in patients undergoing in-vitro fertilization with a poor prognosis: identification of the categories for which it should be proposed. Fertility and Sterility 72(5): 837844.
Handyside, AH, Kontogianni, EH, Hardy, K, Winston, RM (1990) Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 344(6268): 768770.
Harper, JC, Coonan, E, Handyside, AH, et al. (1995) Mosaicism of autosomes and sex chromosomes in morphologically normal, monospermic preimplantation human embryos. Prenatal Diagnosis 15: 4149.
Harper, J, Jackson, E, Sermon, K, et al. (2017) Adjuncts in the IVF laboratory: where is the evidence for add-on interventions. Human Reproduction 32(3): 485449.
Hertig, AT, Rock, J, Adams, EC (1956) A description of 34 human ova within the first 17 days of development. American Journal of Anatomy 98: 435.
James, RM, West, JD (1994) A chimaeric animal model for confined placental mosaicism. Human Genetics 93: 603604.
Heyman, Y, Chesné, P, Chupin, D, Ménézo, Y (1987) Improvement of survival rate of frozen cattle blastocysts after transfer with trophoblastic vesicles. Theriogenology 27: 477484.
Kallioniemi, A, Kallioniemi, OP, Sudar, D, et al. (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258: 818821.
Lagalla, C, Tarozzi, N, Sciajno, R, et al. (2017) Embryos with morphokinetic abnormalities may develop into euploid blastocysts. Reproductive BioMedicine Online 34(2): 137146.
Liss, J, Chromik, I, Szczyglinska, J, Jagiello, M, Lukaszuk, A, Lukaszuk, K (2016) Current methods for pre-implantation genetic diagnosis. Ginekologia Polska 87: 522526.
Mackie, FL, Hemming, K, Allen, S, Morris, RK, Kilby, MD (2017) The accuracy of cell-free fetal DNA-based non-invasive prenatal testing in singleton pregnancies: a systematic review and bivariate meta-analysis. British Journal of Obstetrics and Gynaecology 124: 3246.
Mastenbroek, S, Twisk, M, van Echten-Arends, J, et al. (2007) In vitro fertilization with preimplantation genetic screening. New England Journal of Medicine 357: 917.
Munné, S, Scott, R, Sable, D, Cohen, J(1998) First pregnancies after preconception diagnosis of translocations of maternal origin. Fertility and Sterility 69(4): 675681.
Munné, S, Wells, D (2003) Questions concerning the suitability of comparative genomic hybridization for preimplantation genetic diagnosis. Fertility and Sterility 80(4): 871872; discussion 875.
Munné, S, Grifo, J, Wells, D (2016) Mosaicism: survival of the fittest vs no embryo left behind. Fertility and Sterility 105: 11461149.
Platteau, P, Staessen, C, Michiels, A, et al. (2006) Which patients with recurrent implantation failure after IVF benefit from PGD for aneuploidy screening? Reproductive BioMedicine Online 12(3): 334339.
Sagawa, T, Kuroda, T, Kato, K, et al. (2017) Cytogenetic analysis of the retained products of conception after missed abortion following blastocyst transfer: a retrospective, large-scale, single-centre study. Reproductive BioMedicine Online 34(2): 203210.
Schattman, G (2018) Chromosomal mosaicism in human pre-implantation embryos: another fact that cannot be ignored. Fertility and Sterility 109: 5455.
Schrurs, BM, Winston, RM, Handyside, AH (1993) Preimplantation diagnosis of aneuploidy using fluorescent in-situ hybridization: evaluation using a chromosome 18-specific probe. Human Reproduction 8: 296301.
Sermondade, N, Mandelbaum, J (2009) Mastenbroek controversy or how much ink is spilled on preimplantation genetic screening subject? Gynécologie Obstétrique & Fertilité 37(3): 252256.
Swain, J (2019) Controversies in ART: can the IVF laboratory influence preimplantation embryo aneuploidy? Reproductive BioMedicine Online 39(4), published online September 2019.
Tesarik, J (2018) Is blastomere multinucleation a safeguard against embryo aneuploidy? Back to the future. Reproductive BioMedicine Online 37(4): 506507.
Treff, NR, Su, J, Tao, X, et al. (2010) Accurate single cell 24 chromosome aneuploidy screening using whole genome amplification and single nucleotide polymorphism microarrays. Fertility and Sterility 94: 20172021.
Vanneste, E, Voet, T, Melotte, C, et al.(2009) What next for pre-implantation genetic screening: high mitotic chromosome instability rate provides the biological basis for the low success rate. Human Reproduction 24: 26792682.
Verlinsky, Y, Cieslak, J, Freidine, M, et al. (1995) Pregnancies following pre-conception diagnosis of common aneuploidies by fluorescent in situ hybridisation. Molecular Human Reproduction 10: 19271934.
Verlinsky, Y, Strom, C, Cieslak, J, et al. (1996) Birth of healthy children after preimplantation diagnosis of common aneuploidies by polar body fluorescent in situ hybridisation analysis. Fertility and Sterility 66: 126129.
Wells, D (2007) Future genetic and other technologies for assessing embryos. In: Elder, K, Cohen, J (eds.) Human Preimplantation Embryo Evaluation and Selection. Informa Press, London, pp. 287300.
Zhang, WY, von Versen-Höynck, F, Kapphahn, KL, et al., (2019) Maternal and neonatal outcomes associated with trophectoderm biopsy. Fertility and Sterility. 112(2): 283290.e2.
Elder, K, Cohen, J (eds.) (2007) Human Preimplantation Embryo Evaluation and Selection. Informa Press, London.
Dale, B, Ménézo, Y, Coppola, G (2015) Trends, Fads and Art. Journal of Assisted Reproduction and Genetics 32: 489493.
Dale, B, Ménézo, Y, Elder, K (2016) Who benefits from PGS? Austin Journal of IVF 3: 1026.
Dahdouh, EM, Balayla, J, Audibert, F, Genetics Committee (2015) Technical update: preimplantation genetic diagnosis and screening. Journal of Obstetrics and Gynaecology Canada 37(5): 451463.
De Ryck, M, Goossens, V, Kokkali, G, et al. (2017) ESHRE PGD Consortium data collection XIV–XV: cycles from January 2011 to December 2012 with pregnancy follow-up to October 2013. Human Reproduction 32(10): 19741994.
Fauser, B (2006) Pre-implantation genetic screening: the end of an affair? Human Reproduction 23: 26222625.
Geraedts, J, Sermon, K (2016) Preimplantation genetic screening 2.0: the theory. Molecular Human Reproduction 22(8): 539544.
Gleicher, N, Orvieto, R (2017) Is the hypothesis of pre-implantation genetic screening (PGS) still supportable? A review. Journal of Ovarian Research 10: 17.
Harper, J, Delhanty, JDA, Handyside, AH (2001) Preimplantation Genetic Diagnosis. Cambridge University Press, Cambridge, UK.
Harper, J (2009) Preimplantation Genetic Diagnosis, 2nd edn. Cambridge University Press, Cambridge, UK.
Hayward, J, Chitty, L (2018) Beyond screening for chromosomal abnormalities: advances in non-invasive diagnosis of single gene disorders and fetal exome sequencing. Seminars in Fetal and Neonatal Medicine 23(2): 94101.
Mastenbroek, S, Repping, S (2014) Preimplantation genetic screening: back to the future. Human Reproduction 29: 18461850.
Meaney, C, Norbury, G (2011) Non-invasive prenatal diagnosis. In: Theophilus, B, Rapley, R (eds.) PCR Mutation Detection Protocols. Methods in Molecular Biology (Methods and Protocols), vol 688. Humana Press, Springer Science + Business Media, London, pp. 155172.
Munné, S (2018) Status of preimplantation genetic testing and embryo selection. Reproductive BioMedicine Online 28(4): 393396.
Sanders, KD, Griffin, KD (2017) Chromosomal preimplantation genetic diagnosis: 25 years and counting. Journal of Fetal Medicine 4(2): 5156.
Sermon, K, Capalbo, A, Cohen, J, et al. (2016) The why, the how and the when of PGS 2.0: current practices and expert opinions of fertility specialists, molecular biologists and embryologists. Molecular Human Reproduction 22(8): 545557.
Bolton, H, Graham, S, Van de Aa, N (2016) Mouse model of a chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential. Nature Communications 7: 11165.
Coonen, E, Harper, JC, Ramaekers, FCS, et al. (1994) Presence of chromosomal mosaicism in abnormal preimplantation embryos detected by fluorescent in situ hybridisation. Human Genetics 54: 609615.
Delhanty, JDA, Griffin, DK, Handyside, AH, et al. (1993) Detection of aneuploidy and chromosomal mosaicism in human embryos during preimplantation sex determination by fluorescent in situ hybridization (FISH). Human Molecular Genetics 2(8): 11831185.
Delhanty, JDA, Harper, JC, Ao, A, Handyside, AH, Winston, RML (1997) Multicolour FISH detects frequent chromosomal mosaicism and chaotic division in normal preimplantation embryos from fertile patients. Human Genetics 99: 755760.
Gardner, RL, Edwards, RG (1968) Control of the sex ratio at full term in the rabbit by transferring sexed blastocysts. Nature 218: 346349.
Gianaroli, L, Magli, MC, Ferraretti, AP, Munné, S (1999) Preimplantation diagnosis for aneuploidies in patients undergoing in-vitro fertilization with a poor prognosis: identification of the categories for which it should be proposed. Fertility and Sterility 72(5): 837844.
Handyside, AH, Kontogianni, EH, Hardy, K, Winston, RM (1990) Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 344(6268): 768770.
Harper, JC, Coonan, E, Handyside, AH, et al. (1995) Mosaicism of autosomes and sex chromosomes in morphologically normal, monospermic preimplantation human embryos. Prenatal Diagnosis 15: 4149.
Harper, J, Jackson, E, Sermon, K, et al. (2017) Adjuncts in the IVF laboratory: where is the evidence for add-on interventions. Human Reproduction 32(3): 485449.
Hertig, AT, Rock, J, Adams, EC (1956) A description of 34 human ova within the first 17 days of development. American Journal of Anatomy 98: 435.
James, RM, West, JD (1994) A chimaeric animal model for confined placental mosaicism. Human Genetics 93: 603604.
Heyman, Y, Chesné, P, Chupin, D, Ménézo, Y (1987) Improvement of survival rate of frozen cattle blastocysts after transfer with trophoblastic vesicles. Theriogenology 27: 477484.
Kallioniemi, A, Kallioniemi, OP, Sudar, D, et al. (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258: 818821.
Lagalla, C, Tarozzi, N, Sciajno, R, et al. (2017) Embryos with morphokinetic abnormalities may develop into euploid blastocysts. Reproductive BioMedicine Online 34(2): 137146.
Liss, J, Chromik, I, Szczyglinska, J, Jagiello, M, Lukaszuk, A, Lukaszuk, K (2016) Current methods for pre-implantation genetic diagnosis. Ginekologia Polska 87: 522526.
Mackie, FL, Hemming, K, Allen, S, Morris, RK, Kilby, MD (2017) The accuracy of cell-free fetal DNA-based non-invasive prenatal testing in singleton pregnancies: a systematic review and bivariate meta-analysis. British Journal of Obstetrics and Gynaecology 124: 3246.
Mastenbroek, S, Twisk, M, van Echten-Arends, J, et al. (2007) In vitro fertilization with preimplantation genetic screening. New England Journal of Medicine 357: 917.
Munné, S, Scott, R, Sable, D, Cohen, J(1998) First pregnancies after preconception diagnosis of translocations of maternal origin. Fertility and Sterility 69(4): 675681.
Munné, S, Wells, D (2003) Questions concerning the suitability of comparative genomic hybridization for preimplantation genetic diagnosis. Fertility and Sterility 80(4): 871872; discussion 875.
Munné, S, Grifo, J, Wells, D (2016) Mosaicism: survival of the fittest vs no embryo left behind. Fertility and Sterility 105: 11461149.
Platteau, P, Staessen, C, Michiels, A, et al. (2006) Which patients with recurrent implantation failure after IVF benefit from PGD for aneuploidy screening? Reproductive BioMedicine Online 12(3): 334339.
Sagawa, T, Kuroda, T, Kato, K, et al. (2017) Cytogenetic analysis of the retained products of conception after missed abortion following blastocyst transfer: a retrospective, large-scale, single-centre study. Reproductive BioMedicine Online 34(2): 203210.
Schattman, G (2018) Chromosomal mosaicism in human pre-implantation embryos: another fact that cannot be ignored. Fertility and Sterility 109: 5455.
Schrurs, BM, Winston, RM, Handyside, AH (1993) Preimplantation diagnosis of aneuploidy using fluorescent in-situ hybridization: evaluation using a chromosome 18-specific probe. Human Reproduction 8: 296301.
Sermondade, N, Mandelbaum, J (2009) Mastenbroek controversy or how much ink is spilled on preimplantation genetic screening subject? Gynécologie Obstétrique & Fertilité 37(3): 252256.
Swain, J (2019) Controversies in ART: can the IVF laboratory influence preimplantation embryo aneuploidy? Reproductive BioMedicine Online 39(4), published online September 2019.
Tesarik, J (2018) Is blastomere multinucleation a safeguard against embryo aneuploidy? Back to the future. Reproductive BioMedicine Online 37(4): 506507.
Treff, NR, Su, J, Tao, X, et al. (2010) Accurate single cell 24 chromosome aneuploidy screening using whole genome amplification and single nucleotide polymorphism microarrays. Fertility and Sterility 94: 20172021.
Vanneste, E, Voet, T, Melotte, C, et al.(2009) What next for pre-implantation genetic screening: high mitotic chromosome instability rate provides the biological basis for the low success rate. Human Reproduction 24: 26792682.
Verlinsky, Y, Cieslak, J, Freidine, M, et al. (1995) Pregnancies following pre-conception diagnosis of common aneuploidies by fluorescent in situ hybridisation. Molecular Human Reproduction 10: 19271934.
Verlinsky, Y, Strom, C, Cieslak, J, et al. (1996) Birth of healthy children after preimplantation diagnosis of common aneuploidies by polar body fluorescent in situ hybridisation analysis. Fertility and Sterility 66: 126129.
Wells, D (2007) Future genetic and other technologies for assessing embryos. In: Elder, K, Cohen, J (eds.) Human Preimplantation Embryo Evaluation and Selection. Informa Press, London, pp. 287300.
Zhang, WY, von Versen-Höynck, F, Kapphahn, KL, et al., (2019) Maternal and neonatal outcomes associated with trophectoderm biopsy. Fertility and Sterility. 112(2): 283290.e2.