Key Points
-
Preimplantation genetic diagnosis (PGD) is an evolving technique that provides a practical alternative to prenatal diagnosis and termination of pregnancy for couples who are at substantial risk of transmitting serious genetic disorder to their offspring.
-
For PGD, assisted conception techniques are used to generate embryos in vitro and a polar body or a cell is removed as a biopsy either before fertilization or later in preimplantation embryo development (at cleavage or blastocyst stage). This biopsy is used as a tissue representative of the whole embryo and is analysed for the presence of a specific genetic abnormality. Embryos found to be unaffected are replaced into the uterus.
-
PGD provides an alternative way forward, not only for couples at risk of having a child with a severe or life threatening abnormality, but also for couples who are unable to establish a viable pregnancy due to miscarriage caused by chromosome rearrangements.
-
PGD for inherited genetic diseases in fertile couples should be distinguished from PGD for the detection of sporadic chromosomal abnormality to enhance in vitro fertilization success in infertile couples who seek assisted conception treatment. The latter procedure has been designated as PGD-AS (aneuploidy screening) by the ESHRE consortium and PGS (preimplantation genetic screening) by the Human Fertilisation and Embryology Authority, although it tends to be included in the definition of PGD in the United States.
-
The increasing availability of PGD raises many new ethical issues such as sexing for non-medical reasons, selection of affected embryos so they will be the same as their parents for a specific characteristic (such as deafness) and HLA typing to save the life of an affected living sibling.
-
Regulation of PGD varies around the world, with some countries having strict legislation to prevent it, as is the case in Germany, and some having permissive but highly regulated legislation, as in the United Kingdom. However, many countries, including the United States do not have any specific legislation that regulates the use of PGD.
Abstract
Preimplantation genetic diagnosis (PGD) is an evolving technique that provides a practical alternative to prenatal diagnosis and termination of pregnancy for couples who are at substantial risk of transmitting a serious genetic disorder to their offspring. Samples for genetic testing are obtained from oocytes or cleaving embryos after in vitro fertilization. Only embryos that are shown to be free of the genetic disorders are made available for replacement in the uterus, in the hope of establishing a pregnancy. PGD has provided unique insights into aspects of reproductive genetics and early human development, but has also raised important new ethical issues about assisted human reproduction.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Handyside, A. H., Kontogianni, E. H., Hardy, K. & Winston, R. M. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 344, 768–770 (1990). The first pregnancies that resulted from the transfer of embryos that had been genotyped as female were reported here. Embryos from couples who were at risk of transmitting two different X-linked disorders were subjected to biopsy and the cell removed was sexed by the PCR of a Y-chromosome specific repeat sequence.
Handyside, A. H., Lesko, J. G., Tarin, J. J., Winston, R. M. & Hughes, M. R. Birth of a normal girl after in vitro fertilization and preimplantation diagnostic testing for cystic fibrosis. N. Engl. J. Med. 327, 905–909 (1992).
Edwards, R. G. Diagnostic methods for human gametes and embryos. Hum. Reprod. 2, 415–420 (1987).
Gardner, R. L. & Edwards, R. G. Control of the sex ratio at full term in the rabbit by transferring sexed blastocysts. Nature 218, 346–349 (1968).
Johnson, L. Gender preselection in mammals: an overview. Dtsch Tierarztl Wochenschr. 103, 288–291 (1996).
Benson, C. & Monk, M. Microassay for adenosine deaminase, the enzyme lacking in some forms of immunodeficiency, in mouse preimplantation embryos. Hum. Reprod. 3, 1004–1009 (1988).
Monk, M., Handyside, A., Hardy, K. & Whittingham, D. Preimplantation diagnosis of deficiency of hypoxanthine phosphoribosyl transferase in a mouse model for Lesch–Nyhan syndrome. Lancet 2, 423–425 (1987).
Sermon, K. et al. β N-acetylhexosaminidase activity in human oocytes and preimplantation embryos. Hum. Reprod. 7, 1278–1280 (1992).
Saiki, R. K. et al. Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230, 1350–1354 (1985).
Li, H. H. et al. Amplification and analysis of DNA sequences in single human sperm and diploid cells. Nature 335, 414–417 (1988). The successful PCR amplification of DNA sequences from individual diploid cells and from human sperm not only enabled the analysis of DNA sequence variation at the single-cell level, but also opened up the possibility of applying this technology clinically in PGD, to identify the presence of genetic mutations in embryos from carrier patients.
West, J. D. et al. Sexing the human pre-embryo by DNA–DNA in-situ hybridisation. Lancet 1, 1345–1347 (1987).
Griffin, D. K., Handyside, A. H., Penketh, R. J., Winston, R. M. & Delhanty, J. D. Fluorescent in-situ hybridization to interphase nuclei of human preimplantation embryos with X and Y chromosome specific probes. Hum. Reprod. 6, 101–105 (1991).
Beernink, F. J., Dmowski, W. P. & Ericsson, R. J. Sex preselection through albumin separation of sperm. Fertil. Steril. 59, 382–386 (1993).
Vidal, F. et al. Efficiency of MicroSort flow cytometry for producing sperm populations enriched in X- or Y-chromosome haplotypes: a blind trial assessed by double and triple colour fluorescent in-situ hybridization. Hum. Reprod. 13, 308–312 (1998).
HFEA. Code of Practice, 5th edn [online] <http://www.hfea.gov.uk/forclinics/archived/chair_letters/00005.htm> (1999).
Khalaf, Y., Taylor, A. & Braude, P. R. Low estradiol concentrations after five days of controlled ovarian hyperstimulation for IVF are associated with poor outcome. Fertil. Steril. 74, 63–66 (2000).
Palermo, G., Joris, H., Devroey, P. & Van Steirteghem, A. C. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 340, 17–18 (1992).
Vandervorst, M. et al. The Brussels' experience of more than 5 years of clinical preimplantation genetic diagnosis. Hum. Reprod. Update 6, 364–373 (2000).
ESHRE Preimplantation Genetic Diagnosis Consortium. Data collection III. Hum. Reprod. 17, 233–246 (2002).
Verlinsky, Y. et al. Analysis of the first polar body: preconception genetic diagnosis. Hum. Reprod. 5, 826–829 (1990).
Verlinsky, Y. & Kuliev, A. Preimplantation diagnosis of common aneuploidies in infertile couples of advanced maternal age. Hum. Reprod. 11, 2076–2077 (1996).
Munne, S., Bahce, M., Schimmel, T., Sadowy, S. & Cohen, J. Case report: chromatid exchange and predivision of chromatids as other sources of abnormal oocytes detected by preimplantation genetic diagnosis of translocations. Prenat. Diagn. 18, 1450–1458 (1998).
Rechitsky, S. et al. Accuracy of preimplantation diagnosis of single-gene disorders by polar body analysis of oocytes. J. Assist. Reprod. Genet. 16, 192–198 (1999).
Fleming, T. P., McConnell, J., Johnson, M. H. & Stevenson, B. R. Development of tight junctions de novo in the mouse early embryo: control of assembly of the tight junction-specific protein, ZO-1. J. Cell Biol. 108, 1407–1418 (1989).
Liu, J., Van de Abeel, E. & Van Steirteghem, A. The in vitro and in vivo developmental potential of frozen and non frozen biopsied 8-cell mouse embryos. Hum. Reprod. 8, 1481–1486 (1993).
Hardy, K., Martin, K. L., Leese, H. J., Winston, R. M. & Handyside, A. H. Human preimplantation development in vitro is not adversely affected by biopsy at the 8-cell stage. Hum. Reprod. 5, 708–714 (1990). Showed that the removal of 1–2 cells from an 8-cell human embryo did not significantly affect its chances of subsequent in vitro development to the blastocyst stage. After substantial investigations into the safety of biopsy procedures in mouse embryos, this study underlined the efficacy of such techniques and endorsed their clinical application in PGD.
De Vos, A. & Van Steirteghem, A. Aspects of biopsy procedures prior to preimplantation genetic diagnosis. Prenat. Diagn. 21, 767–780 (2001).
Lewis, C. M., Pinel, T., Whittaker, J. C. & Handyside, A. H. Controlling misdiagnosis errors in preimplantation genetic diagnosis: a comprehensive model encompassing extrinsic and intrinsic sources of error. Hum. Reprod. 16, 43–50 (2001).
Van de Velde, H. et al. Embryo implantation after biopsy of one or two cells from cleavage-stage embryos with a view to preimplantation genetic diagnosis. Prenat. Diag. 20, 1030–1037 (2000).
Grifo, J. A., Giatras, K., Tang, Y. X. & Krey, L. C. Successful outcome with day 4 embryo transfer after preimplantation diagnosis for genetically transmitted diseases. Hum. Reprod. 13, 1656–1659 (1998).
Dokras, A., Sargent, I. L., Ross, C., Gardner, R. L. & Barlow, D. H. Trophectoderm biopsy in human blastocysts. Hum. Reprod. 5, 821–825 (1990).
Veiga, A. et al. Laser blastocyst biopsy for preimplantation diagnosis in the human. Zygote 5, 351–354 (1997).
Gentry, W. L. & Critser, E. S. Growth of mouse pups derived from biopsied blastocysts. Obstet. Gynecol. 85, 1003–1006 (1995).
Gardner, D. K. et al. A prospective randomized trial of blastocyst culture and transfer in in-vitro fertilization. Hum. Reprod. 13, 3434–3440 (1998).
De Boer, K., McArthur, S., Murray, C. & Jansen, R. First live birth following blastocyst biopsy and PGD analysis. Reprod. BioMed. Online 4, 35 (2002). <http://www.rbmonline.com>
Edgar, D. H., Bourne, H., Speirs, A. L. & McBain, J. C. A quantitative analysis of the impact of cryopreservation on the implantation potential of human cleavage stage embryos. Hum. Reprod. 15, 175–179 (2000).
Joris, H., Van den Abbeel, E., Vos, A. D. & Van Steirteghem, A. Reduced survival after human embryo biopsy and subsequent cryopreservation. Hum. Reprod. 14, 2833–2837 (1999).
Lee, M. & Munne, S. Pregnancy after polar body biopsy and freezing and thawing of human embryos. Fertil. Steril. 73, 645–647 (2000).
Wilton, L. J., 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. 345, 1537–1541 (2001).
Lalic, I., Catt, J. & McArthur, S. Pregnancies after cryopreservation of embryos biopsied for PGD. Hum. Reprod. 16, 32 (2001).
Sermon, K. Current concepts in preimplantation genetic diagnosis (PGD): a molecular biologist's view. Hum. Reprod. Update 8, 11–20 (2002).
Verlinsky, Y. et al. Preimplantation genetic diagnosis: experience of 3000 clinical cycles- Conference Report. Reprod. BioMed. Online 3, 49–53 (2001). <http://www.rbmonline.com>
Handyside, A. H. et al. Biopsy of human preimplantation embryos and sexing by DNA amplification. Lancet 1, 347–349 (1989).
Pickering, S. J., McConnell, J. M., Johnson, M. H. & Braude, P. R. Use of a polymorphic dinucleotide repeat sequence to detect non-blastomeric contamination of the polymerase chain reaction in biopsy samples for preimplantation diagnosis. Hum. Reprod. 9, 1539–1545 (1994).
Hardy, K. & Handyside, A. H. Biopsy of cleavage stage human embryos and diagnosis of single gene defects by DNA amplification. Arch. Pathol. Lab. Med. 116, 388–392 (1992).
Grifo, J. A. et al. Pregnancy after embryo biopsy and co-amplification of DNA from X and Y chromosomes. JAMA 12, 727–729 (1992).
Monk, M. & Holding, C. Amplification of a β-haemoglobin sequence in individual human oocytes and polar bodies. Lancet 335, 985–988 (1990).
Findlay, I., Ray, P., Quirke, P., Rutherford, A. & Lilford, R. Allelic drop-out and preferential amplification in single cells and human blastomeres: implications for preimplantation diagnosis of sex and cystic fibrosis. Hum. Reprod. 10, 1609–1618 (1995).
Ray, P. F., Ao, A., Taylor, D. M., Winston, R. M. & Handyside, A. H. Assessment of the reliability of single blastomere analysis for preimplantation diagnosis of the δ F508 deletion causing cystic fibrosis in clinical practice. Prenat. Diagn. 18, 1402–1412 (1998).
Findlay, I., Quirke, P., Hall, J. & Rutherford, A. Fluorescent PCR: a new technique for PGD of sex and single-gene defects. J. Assist. Reprod. Genet. 13, 96–103 (1996). Describes the application of fluorescent PCR (FPCR) to the genetic analysis of single cells. With FPCR, several primer sets can be used in the same reaction (multiplexing) with enhanced sensitivity, which overcomes many of the problems that are encountered during conventional PCR, such as allele drop-out and contamination.
Sermon, K. et al. Fluorescent PCR and automated fragment analysis for the clinical application of preimplantation genetic diagnosis of myotonic dystrophy (Steinert's disease). Mol. Hum. Reprod. 4, 791–796 (1998).
Rechitsky, S. et al. Reliability of preimplantation diagnosis for single gene disorders. Mol. Cell. Endocrinol. 183, S65–S68 (2001).
Findlay, I. et al. Simultaneous DNA 'fingerprinting', diagnosis of sex and single-gene defect status from single cells. Hum. Reprod. 10, 1005–1013 (1995).
Dreesen, J. C. et al. Multiplex PCR of polymorphic markers flanking the CFTR gene; a general approach for preimplantation genetic diagnosis of cystic fibrosis. Mol. Hum. Reprod. 6, 391–396 (2000).
Vandervorst, M. et al. Successful preimplantation genetic diagnosis is related to the number of available cumulus–oocyte complexes. Hum. Reprod. 13, 3169–3176 (1998).
Griffin, D. K. et al. Clinical experience with preimplantation diagnosis of sex by dual fluorescent in situ hybridization. J. Assist. Reprod. Genet. 11, 132–143 (1994). Demonstration of the use of in situ hybridization techniques for the preimplantation diagnosis of embryo sex in a clinical setting. Over a 2-year period, 9 pregnancies were achieved after 27 treatment cycles, with no misdiagnoses. This work established the advantages of FISH over PCR amplification for single-cell diagnosis of sex chromosome status.
Munne, S., Dailey, T., Finkelstein, M. & Weier, H. U. Reduction in signal overlap results in increased FISH efficiency: implications for preimplantation genetic diagnosis. J. Assist. Reprod. Genet. 13, 149–156 (1996).
Munne, S., Marquez, C., Magli, C., Morton, P. & Morrison, L. Scoring criteria for preimplantation genetic diagnosis of numerical abnormalities for chromosomes X, Y, 13, 16, 18 and 21. Mol. Hum. Reprod. 4, 863–870 (1998).
Harper, J. C. & Delhanty, J. D. Detection of chromosomal abnormalities in human preimplantation embryos using FISH. J. Assist. Reprod. Genet. 13, 137–139 (1996).
Munne, S. & Cohen, J. Chromosome abnormalities in human embryos. Hum. Reprod. Update 4, 842–855 (1998).
Kuo, H. C., Ogilvie, C. M. & Handyside, A. H. Chromosomal mosaicism in cleavage-stage human embryos and the accuracy of single-cell genetic analysis. J. Assist. Reprod. Genet. 15, 276–280 (1998).
Scriven, P. N., Handyside, A. H. & Ogilvie, C. M. Chromosome translocations: segregation modes and strategies for preimplantation genetic diagnosis. Prenat. Diagn. 18, 1437–1449 (1998).
Scriven, P. N., Flinter, F., Bickerstaff, H., Braude, P. & Mackie Ogilvie, C. Robertsonian translocations–reproductive risks and indications for preimplantation genetic diagnosis. Hum. Reprod. 16, 2267–2273 (2001).
Munne, S., Fung, J., Cassel, M. J., Marquez, C. & Weier, H. U. Preimplantation genetic analysis of translocations: case-specific probes for interphase cell analysis. Hum. Genet. 102, 663–674 (1998).
Munne, S., Scott, R., Sable, D. & Cohen, J. First pregnancies after preconception diagnosis of translocations of maternal origin. Fertil. Steril. 69, 675–681 (1998).
Conn, C. M., Harper, J. C., Winston, R. M. & Delhanty, J. D. Infertile couples with Robertsonian translocations: preimplantation genetic analysis of embryos reveals chaotic cleavage divisions. Hum. Genet. 102, 117–123 (1998).
Munne, S. et al. Spontaneous abortions are reduced after preconception diagnosis of translocations. J. Assist. Reprod. Genet. 15, 290–296 (1998).
Handyside, A. H., Scriven, P. N. & Ogilvie, C. M. The future of preimplantation genetic diagnosis. Hum. Reprod. 13, 249–255 (1998).
Gardner, R. & Sutherland, G. in Chromosome Abnormalities and Genetic Counseling, (Oxford Univ. Press, Oxford, UK, 1996).
Jalbert, P., Sele, B. & Jalbert, H. Reciprocal translocations: a way to predict the mode of imbalanced segregation by pachytene-diagram drawing. Hum. Genet. 55, 209–222 (1980).
Knight, S. et al. An optimized set of human telomere clones for studying Telomere Integrity and Architecture. Am. J. Hum. Genet. 67, 320–332 (2000).
Scriven, P. N. et al. Clinical pregnancy following blastomere biopsy and PGD for a reciprocal translocation carrier: analysis of meiotic outcomes and embryo quality in two IVF cycles. Prenat. Diagn. 20, 587–592 (2000).
Mackie Ogilvie, C. M., Braude, P. & Scriven, P. N. Successful pregnancy outcomes after preimplantation genetic diagnosis (PGD) for carriers of chromosome translocations. Hum. Fertil. 4, 168–171 (2001).
Warburton, D. et al. Does the karyotype of a spontaneous abortion predict the karyotype of a subsequent abortion? Evidence from 273 women with two karyotyped spontaneous abortions. Am. J. Hum. Genet. 41, 465–483 (1987).
Conn, C. M., Cozzi, J., Harper, J. C., Winston, R. M. & Delhanty, J. D. Preimplantation genetic diagnosis for couples at high risk of Down syndrome pregnancy owing to parental translocation or mosaicism. J. Med. Genet. 36, 45–50 (1999).
Ryan, A. K. et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J. Med. Genet. 34, 798–804 (1997).
Vincent, M. C. et al. 22q11 deletion in DGS/VCFS monozygotic twins with discordant phenotypes. Genet. Counsel. 10, 43–49 (1999).
ASRM. Preimplantation genetic diagnosis. A practice committee report. 1–4 (American Society for Reproductive Medicine, June 2001). (cited 06-11-02), <http://www.asrm.org/Media/Practice/practice.html.>
Templeton, A. Infertility and the establishment of pregnancy — / overview. Br. Med. Bull. 56, 577–587 (2000).
Munne, S. et al. Positive outcome after preimplantation diagnosis of aneuploidy in human embryos. Hum. Reprod. 14, 2191–2199 (1999). A three centre study on the effect of aneuploidy screening of preimplantation embryos from women of 35 years or older. Statistical analysis showed a small, but significant, decrease in miscarriage rate and an increase in ongoing pregnancy rate.
Verlinsky, Y. et al. Polar body based preimplantation diagnosis for X–linked disorders. Reprod. Biomed. Online 4, 38–42 (2002). <http://www.rbmonline.com>
Ozbekhan, H. in Man-Made Futures: Readings in Society, Technology and Design (eds Cross, N., Elliott, D. & Roy, R.) (Hutchinson, London, 1968).
Munne, S. & Weier, H. U. Simultaneous enumeration of chromosomes 13, 18, 21, X, and Y in interphase cells for preimplantation genetic diagnosis of aneuploidy. Cytogenet. Cell Genet. 75, 263–270 (1996).
Angell, R. R., Aitken, R. J., van Look, P. F., Lumsden, M. A. & Templeton, A. A. Chromosome abnormalities in human embryos after in vitro fertilization. Nature 303, 336–338 (1983). The first evidence to suggest that some human embryos might harbour aneuploid cells. These findings provoked a plethora of further studies into the chromosomal constitution of human embryos, eventually resulting in the development of PGD for the detection of aneuploidy in 'at risk' groups.
Plachot, M. et al. Chromosome investigations in early life. II. Human preimplantation embryos. Hum. Reprod. 2, 29–35 (1987).
Evsikov, S. & Verlinsky, Y. Visualization of chromosomes in single human blastomeres. J. Assist. Reprod. Genet. 16, 133–137 (1999).
Willadsen, S. et al. Rapid visualization of metaphase chromosomes in single human blastomeres after fusion with in-vitro matured bovine eggs. Hum. Reprod. 14, 470–475 (1999).
Voullaire, L., Slater, H., Williamson, R. & Wilton, L. Chromosome analysis of blastomeres from human embryos by using comparative genomic hybridisation. Hum. Genet. 106, 210–217 (2000).
Wells, D. & Delhanty, J. D. A. Comprehensive chromosomal analysis of human preimplantation embryos using whole genome amplification. Mol. Hum. Reprod. 6, 1055–1062 (2000). The first demonstration that comparative genomic hybridization can be used to test for genomic imbalance in single human embryo cells after whole-genome amplification.
Harper, J. C. & Wells, D. Recent advances and future developments in PGD. Prenat. Diagn. 19, 1193–1199 (1999).
Wilton, L., Williamson, R., McBain, J., Edgar, D. & Voullaire, L. Preimplantation of anueploidy using comparative genomic hybridisation. Reprod. BioMed. Online 4, 13 (2002). <http://www.rbmonline.com>
Maughan, N., Lewis, F. & Smith, V. An introduction to arrays. J. Pathol. 195, 3–6 (2001).
Clarke, P. A., te Poele, R., Wooster, R. & Workman, P. Gene expression microarray analysis in cancer biology, pharmacology, and drug development: progress and potential. Biochem. Pharmacol. 62, 1311–1336 (2001).
Braude, P. R., De Wert, G. M., Evers-Kiebooms, G., Pettigrew, R. A. & Geraedts, J. P. Non-disclosure preimplantation genetic diagnosis for Huntington's disease: practical and ethical dilemmas. Prenat. Diagn. 18, 1422–1426 (1998).
Braude, P. Preimplantation genetic diagnosis and embryo research–human developmental biology in clinical practice. Int. J. Dev. Biol. 45, 607–611 (2001).
Savulescu, J. Deaf lesbian, 'designer disability', and the future of medicine. Br. Med. J. 325, 771–773 (2002).
Santalo, J. et al. The decision to cancel a preimplantation genetic diagnosis cycle. Prenat. Diagn. 20, 564–566 (2000).
Pettigrew, R. et al. A pregnancy following PGD for X-linked dominant incontinetia Pimenti (Bloch–Sulzberger syndrome). Hum. Reprod. 15, 2650–2652 (2000).
Savulescu, J. Sex selection: the case for. Med. J. Aust. 171, 373–375 (1999).
Savulescu, J. & Dahl, E. Sex selection and preimplantation diagnosis: a response to the Ethics Committee of the American Society of Reproductive Medicine. Hum. Reprod. 15, 1879–1880 (2000).
Malpani, A. & Modi, D. Preimplantation sex selection for family balancing in India. Hum. Reprod. 17, 11–12 (2002).
Gottlieb, S. US doctors say sex selection acceptable for non-medical reasons. Br. Med. J. 323, 828 (2001).
ASRM. Preconception gender selection for nonmedical reasons. Fertil. Steril. 75, 861–864 (2001). Provides a useful overview of the ethical issues that surround gender selection for non-medical reasons.
Gleicher, N. & Karande, V. Gender selection for non-medical reasons. Fertil. Stertil. 78, 460–462 (2002).
Robertson, J. Sex selection for gender variety by preimplantation genetic diagnosis. Fertil. Stertil. 78, 463 (2002).
Kilani, Z. & Hassan, L. Sex selection and preimplantation genetic diagnosis at The Farah Hospital Reprod. BioMed. Online 4, 68–70 (2002). <http://www.rbmonline.com>
Kumar, A. Does preimplantation genetic diagnosis for gender selection really offer a solution for family balancing? A response to the article by Malpani and Malpani. Reprod. BioMed. Online 4, 10–11 (2002). <http://www.rbmonline.com>
Verlinsky, Y., Rechitsky, S., Schoolcraft, W., Strom, C. & Kuliev, A. Preimplantation diagnosis for Fanconi anemia combined with HLA matching. JAMA 285, 3130–3133 (2001). Describes the application of PGD to preselect a potential donor for an affected sibling who required stem cell donation. An HLA-matched, unaffected child was born after four attempts of PGD, and cord blood was used to successfully treat the affected sibling.
Meek, J. Baby with selected gene born in Britain. Guardian 7 (London, 2002).
Boyle, R. J. & Savulescu, J. Ethics of using preimplantation genetic diagnosis to select a stem cell donor for an existing person. Br. Med. J. 323, 1240–1243 (2001).
Gunning, J. Regulating assisted reproduction technologies. Med. Law 20, 425–433 (2001).
Viville, S. Preimplantation genetic diagnosis, finally a reality in France. Gynecol. Obstet. Fertil. 28, 873–874 (2000).
Jones, H. W. & Cohen, J. IFFS surveillance 01. Fertil. Steril. 76, S24–S25 (2001).
Gardner, R. L. in Implantation of the Human Embryo (eds Edwards, R. G., Purdy, J. M. & Steptoe, P. C.) 155–178 (Academic, London, 1985).
Acknowledgements
The authors thank the other members of the Centre for Preimplantation Genetic Diagnosis for helpful and regular discussion about the issues raised in this review.
Author information
Authors and Affiliations
Corresponding author
Related links
Related links
DATABASES
LocusLink
OMIM
severe combined immunodeficiency disorder
FURTHER INFORMATION
American Society for Reproductive Medicine (ASRM)
European Society of Human Reproduction and Embryology (ESHRE)
Glossary
- REPRODUCTIVE RISK
-
The risk of establishing a pregnancy in which a fetus miscarries or has a phenotypic abnormality as a consequence of the familial genetic condition.
- ANEUPLOIDY
-
The presence of extra copies, or fewer copies, of some chromosomes.
- BLASTOCYST
-
A preimplantation embryo that contains a fluid-filled cavity called a blastocoel.
- AMNIOCENTESIS
-
A procedure in which a small sample of amniotic fluid is drawn out of the uterus through a needle that is inserted into the abdomen. The fluid is then analysed to detect genetic abnormalities in the fetus or to determine the sex of the fetus.
- CHORIONIC VILLUS SAMPLING
-
(CUS). Sampling of the placental tissue of the conceptus for laboratory analysis.
- TRIMESTER
-
One of the ∼12-week stages into which pregnancy is divided for clinical purposes.
- FLUORESCENCE ACTIVATED CELL SORTING
-
(FACS). A method whereby dissociated and individual living cells are sorted, in a liquid stream, according to the intensity of fluorescence that they emit as they pass through a laser beam.
- GONADOTROPHINS
-
Hormones that are produced by the pituitary gland, which act on the gonads to control endocrine functions. Examples include follicle stimulating hormone and luteinizing hormone.
- FOLLICLES
-
Structures in the ovary in which primary oocytes develop into mature oocytes before ovulation.
- ULTRASONOGRAPHY
-
A technique in which sound waves are bounced off tissues and the echoes are converted into a picture (a sonogram).
- ZONA PELLUCIDA
-
The glycoprotein coat that surrounds the oocytes and the early embryos of mammals.
- PRONUCLEUS
-
The haploid nucleus of an egg or sperm.
- BLASTOMERE
-
A cell that results from embryonic cleavage.
- POLAR BODY
-
A small haploid cell that is produced during oogenesis and that does not develop into a functional ovum.
- BIVALENT
-
A chromosome that has undergone replication. The two identical sister chromatids remain joined at the centromere.
- PREDIVISION OF CHROMATIDS
-
The abnormal separation of chromatids during meiosis I (normally, sister chromatids separate during meiosis II) usually gives rise to gametes with a genetic imbalance.
- TIGHT JUNCTION
-
A connection between individual cells in an epithelium that forms a diffusion barrier between the two surfaces of an epithelium.
- TOTIPOTENTIALITY
-
The capacity of an undifferentiated cell to develop into any type of cell.
- TROPHECTODERM
-
The outer layer of the blastocyst-stage embryo.
- FRAGMENT LENGTH POLYMORPHISMS
-
The individual variation in the length of a particular region of DNA (such as a dinucleotide repeat), which, if the DNA is cut with a restriction enzyme or amplified using PCR, gives rise to the generation of differently sized fragments.
- NESTED PCR
-
A technique for improving the sensitivity and specificity of PCR by the sequential use of two sets of oligonucleotide primers in two rounds of PCR. The second pair (known as 'nested primers') are located in the segment of DNA that is amplified by the first pair.
- ALLELE DROP-OUT
-
(ADO). The failure to detect an allele in a sample or the failure to amplify an allele during PCR.
- PENETRANCE
-
The proportion of affected individuals among the carriers of a particular genotype. If all individuals with a disease genotype show the disease phenotype, then the disease is said to be 'completely penetrant'.
- ACROCENTRIC CHROMOSOME
-
A chromosome with the centromere located at one end.
- α-SATELLITE DNA
-
Repetitive DNA sequences arranged in tandem arrays that usually lie near the centromere.
- NICK TRANSLATION
-
A method for in vitro DNA labelling. Nicks are introduced into the DNA by an endonuclease and are subsequently repaired using labelled residues.
- KARYOTYPE ANALYSIS
-
The ascertainment of chromosome constitution by the light microscopy analysis of stained metaphase chromosomes.
- METAPHASE SPREADS
-
The result of a cytogenetic method in which dividing cells are artificially arrested at metaphase, when chromosomes are shortened and condensed. The fixed material from such preparations is dropped onto microscope slides, where the chromosomes from individual cells form clusters or spreads, which can be stained and analysed.
- PLOIDY
-
The number of sets of chromosomes in a cell (n). Normal human somatic cells are diploid (2n), with 2 sets of 23 chromosomes.
Rights and permissions
About this article
Cite this article
Braude, P., Pickering, S., Flinter, F. et al. Preimplantation genetic diagnosis. Nat Rev Genet 3, 941–953 (2002). https://doi.org/10.1038/nrg953
Issue Date:
DOI: https://doi.org/10.1038/nrg953
This article is cited by
-
Analysis of Preimplantation and Clinical Outcomes of Two Cases by Oxford Nanopore Sequencing
Reproductive Sciences (2024)
-
Combining PGT-A with PGT-M risks trying to do too much
Journal of Assisted Reproduction and Genetics (2022)
-
Application of improved single blastomere fixation technique in preimplantation genetic diagnosis
Cytotechnology (2020)
-
Preimplantation genetic testing for a family with usher syndrome through targeted sequencing and haplotype analysis
BMC Medical Genomics (2019)
-
Design and control of a piezoactuated microfeed mechanism for cell injection
The International Journal of Advanced Manufacturing Technology (2019)