Semin Reprod Med 2014; 32(02): 107-113
DOI: 10.1055/s-0033-1363552
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Preimplantation Diagnosis for Single Gene Disorders

Victoria K. Berger
1   Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California
,
Valerie L. Baker
1   Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California
› Author Affiliations
Further Information

Publication History

Publication Date:
10 February 2014 (online)

Abstract

Preimplantation genetic diagnosis (PGD) allows patients who are carriers or who are affected by genetic diseases to select unaffected embryos for transfer before becoming pregnant. The practice of PGD is evolving with rapid advances in technology and biopsy methods. Testing for a specific gene mutation can be performed in combination with 24-chromosome aneuploidy screening. Several unique applications of PGD are reviewed, including exclusion diagnosis for couples from Huntington disease families, testing for fragile X premutations, and human leukocyte antigen matching for stem cell donor siblings. Although PGD for single gene mutations allows patients to gain information about their embryos and perhaps avoid a difficult decision about whether or not to terminate an ongoing pregnancy, this technique also provides for much ethical debate encompassing the well-being of the prospective couple, embryo, child, and people in the community affected by the diseases being screened.

 
  • References

  • 1 Handyside AH, Kontogianni EH, Hardy K, Winston RM. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 1990; 344 (6268) 768-770
  • 2 Ginsburg ES, Baker VL, Racowsky C, Wantman E, Goldfarb J, Stern JE. Use of preimplantation genetic diagnosis and preimplantation genetic screening in the United States: a Society for Assisted Reproductive Technology Writing Group paper. Fertil Steril 2011; 96 (4) 865-868
  • 3 Goossens V, Traeger-Synodinos J, Coonen E , et al. ESHRE PGD Consortium data collection XI: cycles from January to December 2008 with pregnancy follow-up to October 2009. Hum Reprod 2012; 27 (7) 1887-1911
  • 4 Klitzman R, Chung W, Marder K , et al. Views of internists towards uses of PGD. Reprod Biomed Online 2013; 26 (2) 142-147
  • 5 Brandt AC, Tschirgi ML, Ready KJ , et al. Knowledge, attitudes, and clinical experience of physicians regarding preimplantation genetic diagnosis for hereditary cancer predisposition syndromes. Fam Cancer 2010; 9 (3) 479-487
  • 6 Benöhr-Laqueur S. Fighting in the legal grey area: an analysis of the German Federal Court of Justice decision in case preimplantation genetic diagnosis. Poiesis Prax 2011; 8 (1) 3-8
  • 7 Turone F. European court overturns preimplantation testing ban. BMJ 2012; 345: e5996
  • 8 Basille C, Frydman R, El Aly A , et al. Preimplantation genetic diagnosis: state of the art. Eur J Obstet Gynecol Reprod Biol 2009; 145 (1) 9-13
  • 9 Harper JC, Coonen E, De Rycke M , et al. ESHRE PGD Consortium data collection X: cycles from January to December 2007 with pregnancy follow-up to October 2008. Hum Reprod 2010; 25 (11) 2685-2707
  • 10 Harper JC, Wilton L, Traeger-Synodinos J , et al; The ESHRE PGD Consortium. The ESHRE PGD Consortium: 10 years of data collection. Hum Reprod Update 2012; 18 (3) 234-247
  • 11 Harton GL, Magli MC, Lundin K, Montag M, Lemmen J, Harper JC ; European Society for Human Reproduction and Embryology (ESHRE) PGD Consortium/Embryology Special Interest Group. ESHRE PGD Consortium/Embryology Special Interest Group—best practice guidelines for polar body and embryo biopsy for preimplantation genetic diagnosis/screening (PGD/PGS). Hum Reprod 2011; 26 (1) 41-46
  • 12 Chang LJ, Huang CC, Tsai YY , et al. Blastocyst biopsy and vitrification are effective for preimplantation genetic diagnosis of monogenic diseases. Hum Reprod 2013; 28 (5) 1435-1444
  • 13 Cohen J, Alikani M, Grudzinskas G, Johnson MH. Blastocyst biopsy and preimplantation genetic diagnosis for single gene diseases: a turnaround on the horizon?. Reprod Biomed Online 2012; 25 (5) 441-442
  • 14 Hanson C, Hardarson T, Lundin K , et al. Re-analysis of 166 embryos not transferred after PGS with advanced reproductive maternal age as indication. Hum Reprod 2009; 24 (11) 2960-2964
  • 15 Lathi RB, Massie JA, Gilani M , et al. Outcomes of trophectoderm biopsy on cryopreserved blastocysts: a case series. Reprod Biomed Online 2012; 25 (5) 504-507
  • 16 Brezina PR, Benner A, Rechitsky S , et al. Single-gene testing combined with single nucleotide polymorphism microarray preimplantation genetic diagnosis for aneuploidy: a novel approach in optimizing pregnancy outcome. Fertil Steril 2011; 95 (5) e5-e8
  • 17 Rabinowitz M, Hill M, Potter D, Wemmer N, Keller J, Gemelos G. Report on first 54 patients undergoing preimplantation genetic diagnosis for genetic disorders together with 24 chromosome aneuploidy screening using microarrays. Fertil Steril 2011; 96: S23
  • 18 Rechitsky S, Verlinsky O, Kuliev A. PGD for cystic fibrosis patients and couples at risk of an additional genetic disorder combined with 24-chromosome aneuploidy testing. Reprod Biomed Online 2013; 26 (5) 420-430
  • 19 Treff NR, Fedick A, Tao X, Devkota B, Taylor D, Scott Jr RT. Evaluation of targeted next-generation sequencing-based preimplantation genetic diagnosis of monogenic disease. Fertil Steril 2013; 99 (5) 1377-1384 , e6
  • 20 Martín J, Cervero A, Mir P, Martinez-Conejero JA, Pellicer A, Simón C. The impact of next-generation sequencing technology on preimplantation genetic diagnosis and screening. Fertil Steril 2013; 99 (4) 1054-1061 , e3
  • 21 Tsafrir A, Altarescu G, Margalioth E , et al. PGD for fragile X syndrome: ovarian function is the main determinant of success. Hum Reprod 2010; 25 (10) 2629-2636
  • 22 Treff NR, Zhao T, Su J, Forman EJ, Scott RT. Cleavage stage embryo biopsy significantly impairs embryonic reproductive potential while blastocyst biopsy does not: a novel paired analysis of cotransferred biopsied and nonbiopsied sibling embryos. Fertil Steril 2011; 96: S2
  • 23 Wilton L, Thornhill A, Traeger-Synodinos J, Sermon KD, Harper JC. The causes of misdiagnosis and adverse outcomes in PGD. Hum Reprod 2009; 24 (5) 1221-1228
  • 24 Sermon K, Van Steirteghem A, Liebaers I. Preimplantation genetic diagnosis. Lancet 2004; 363 (9421) 1633-1641
  • 25 Ethics Committee of American Society for Reproductive Medicine. Use of preimplantation genetic diagnosis for serious adult onset conditions: a committee opinion. Fertil Steril 2013; 100 (1) 54-57
  • 26 Shenfield F, Pennings G, Devroey P, Sureau C, Tarlatzis B, Cohen J ; ESHRE Ethics Task Force. Taskforce 5: preimplantation genetic diagnosis. Hum Reprod 2003; 18 (3) 649-651
  • 27 The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993; 72 (6) 971-983
  • 28 Novak MJ, Tabrizi SJ. Huntington's disease. BMJ 2010; 340: c3109
  • 29 de Die-Smulders CE, de Wert GM, Liebaers I, Tibben A, Evers-Kiebooms G. Reproductive options for prospective parents in families with Huntington's disease: clinical, psychological and ethical reflections. Hum Reprod Update 2013; 19 (3) 304-315
  • 30 van Rij M, de Koning Gans P, van Belzen M , et al. The uptake and outcome of prenatal and preimplantation genetic diagnosis for Huntington's disease in the Netherlands (1998–2008). Clin Genet 2014; 85: 187-195
  • 31 van Rij MC, de Die-Smulders CE, Bijlsma EK , et al. Evaluation of exclusion prenatal and exclusion preimplantation genetic diagnosis for Huntington's disease in the Netherlands. Clin Genet 2013; 83 (2) 118-124
  • 32 Sermon K, De Rijcke M, Lissens W , et al. Preimplantation genetic diagnosis for Huntington's disease with exclusion testing. Eur J Hum Genet 2002; 10 (10) 591-598
  • 33 SenGupta SB, Vadaparampil ST, Menon U. Preimplantation genetic diagnosis for hereditary cancers. Adv Exp Med Biol 2012; 732: 103-113
  • 34 Daina G, Ramos L, Obradors A , et al. First successful double-factor PGD for Lynch syndrome: monogenic analysis and comprehensive aneuploidy screening. Clin Genet 2012; 84 (1) 70-73
  • 35 Spits C, De Rycke M, Van Ranst N , et al. Preimplantation genetic diagnosis for neurofibromatosis type 1. Mol Hum Reprod 2005; 11 (5) 381-387
  • 36 Verlinsky Y, Rechitsky S, Verlinsky O , et al. Preimplantation diagnosis for neurofibromatosis. Reprod Biomed Online 2002; 4 (3) 218-222
  • 37 Vanneste E, Melotte C, Debrock S , et al. Preimplantation genetic diagnosis using fluorescent in situ hybridization for cancer predisposition syndromes caused by microdeletions. Hum Reprod 2009; 24 (6) 1522-1528
  • 38 Wilkinson E. Preimplantation genetic diagnosis for mutated BRCA genes. Lancet Oncol 2012; 13 (8) e331
  • 39 Sagi M, Weinberg N, Eilat A , et al. Preimplantation genetic diagnosis for BRCA1/2—a novel clinical experience. Prenat Diagn 2009; 29 (5) 508-513
  • 40 Ormondroyd E, Donnelly L, Moynihan C , et al. Attitudes to reproductive genetic testing in women who had a positive BRCA test before having children: a qualitative analysis. Eur J Hum Genet 2012; 20 (1) 4-10
  • 41 Wittenberger MD, Hagerman RJ, Sherman SL , et al. The FMR1 premutation and reproduction. Fertil Steril 2007; 87 (3) 456-465
  • 42 Stark Z, Massie J, McClaren B , et al. Current practice and attitudes of Australian obstetricians toward population-based carrier screening for inherited conditions. Twin Res Hum Genet 2013; 16 (2) 601-607
  • 43 American College of Obstetricians and Gynecologists Committee on Genetics. ACOG Committee Opinion No. 469: carrier screening for fragile X syndrome. Obstet Gynecol 2010; 116 (4) 1008-1010
  • 44 Sullivan AK, Marcus M, Epstein MP , et al. Association of FMR1 repeat size with ovarian dysfunction. Hum Reprod 2005; 20 (2) 402-412
  • 45 Bibi G, Malcov M, Yuval Y , et al. The effect of CGG repeat number on ovarian response among fragile X premutation carriers undergoing preimplantation genetic diagnosis. Fertil Steril 2010; 94 (3) 869-874
  • 46 Lee HS, Kim MJ, Lim CK, Cho JW, Song IO, Kang IS. Multiple displacement amplification for preimplantation genetic diagnosis of fragile X syndrome. Genet Mol Res 2011; 10 (4) 2851-2859
  • 47 Verlinsky Y, Rechitsky S, Schoolcraft W, Strom C, Kuliev A. Preimplantation diagnosis for Fanconi anemia combined with HLA matching. JAMA 2001; 285 (24) 3130-3133
  • 48 Figueira RC, Setti AS, Cortezzi SS , et al. Preimplantation diagnosis for β-thalassemia combined with HLA matching: first “savior sibling” is born after embryo selection in Brazil. J Assist Reprod Genet 2012; 29 (11) 1305-1309
  • 49 Verlinsky Y, Rechitsky S, Sharapova T, Morris R, Taranissi M, Kuliev A. Preimplantation HLA testing. JAMA 2004; 291 (17) 2079-2085
  • 50 Sparrow R, Cram D. Saviour embryos? Preimplantation genetic diagnosis as a therapeutic technology. Reprod Biomed Online 2010; 20 (5) 667-674
  • 51 Kahraman S, Beyazyurek C, Ekmekci CG. Seven years of experience of preimplantation HLA typing: a clinical overview of 327 cycles. Reprod Biomed Online 2011; 23 (3) 363-371
  • 52 Van de Velde H, De Rycke M, De Man C , et al. The experience of two European preimplantation genetic diagnosis centres on human leukocyte antigen typing. Hum Reprod 2009; 24 (3) 732-740
  • 53 Verpoest W. PGD and HLA matching: not a quick fix. Reprod Biomed Online 2011; 23 (3) 271-273
  • 54 Harton G, Braude P, Lashwood A , et al; European Society for Human Reproduction and Embryology (ESHRE) PGD Consortium. ESHRE PGD consortium best practice guidelines for organization of a PGD centre for PGD/preimplantation genetic screening. Hum Reprod 2011; 26 (1) 14-24
  • 55 Baetens P, Van de Velde H, Camus M , et al. HLA-matched embryos selected for siblings requiring haematopoietic stem cell transplantation: a psychological perspective. Reprod Biomed Online 2005; 10 (2) 154-163
  • 56 Grosse SD, Boyle CA, Botkin JR , et al; CDC. Newborn screening for cystic fibrosis: evaluation of benefits and risks and recommendations for state newborn screening programs. MMWR Recomm Rep 2004; 53 (RR-13): 1-36
  • 57 Asch DA, Hershey JC, Dekay ML , et al. Carrier screening for cystic fibrosis: costs and clinical outcomes. Med Decis Making 1998; 18 (2) 202-212
  • 58 Committee on Genetics, American College of Obstetricians and Gynecologists. ACOG Committee Opinion. Number 325, December 2005. Update on carrier screening for cystic fibrosis. Obstet Gynecol 2005; 106 (6) 1465-1468
  • 59 Davis LB, Champion SJ, Fair SO, Baker VL, Garber AM. A cost-benefit analysis of preimplantation genetic diagnosis for carrier couples of cystic fibrosis. Fertil Steril 2010; 93 (6) 1793-1804
  • 60 Tur-Kaspa I, Aljadeff G, Rechitsky S, Grotjan HE, Verlinsky Y. PGD for all cystic fibrosis carrier couples: novel strategy for preventive medicine and cost analysis. Reprod Biomed Online 2010; 21 (2) 186-195
  • 61 The President's Council on Bioethics. Reproduction and Responsibility: The Regulation of New Biotechnologies. 2004 Available at: http://bioethics.georgetown.edu/pcbe/reports/reproductionandresponsibility/chapter3.html
  • 62 Coron F, Rousseau T, Jondeau G , et al. What do French patients and geneticists think about prenatal and preimplantation diagnoses in Marfan syndrome?. Prenat Diagn 2012; 32 (13) 1318-1323
  • 63 Hershberger PE, Pierce PF. Conceptualizing couples' decision making in PGD: emerging cognitive, emotional, and moral dimensions. Patient Educ Couns 2010; 81 (1) 53-62
  • 64 Hens K, Dondorp W, Geraedts J, de Wert G. Comprehensive pre-implantation genetic screening: ethical reflection urgently needed. Nat Rev Genet 2012; 13 (10) 676-677
  • 65 Hens K, Dondorp W, de Wert G. Embryos without secrets: an expert panel study on comprehensive embryo testing and the responsibility of the clinician. Eur J Med Genet 2013; 56 (2) 67-71
  • 66 Desmyttere S, Bonduelle M, Nekkebroeck J, Roelants M, Liebaers I, De Schepper J. Growth and health outcome of 102 2-year-old children conceived after preimplantation genetic diagnosis or screening. Early Hum Dev 2009; 85 (12) 755-759
  • 67 Thomaidis L, Kitsiou-Tzeli S, Critselis E , et al. Psychomotor development of children born after preimplantation genetic diagnosis and parental stress evaluation. World J Pediatr 2012; 8 (4) 309-316