Preimplantation genetic diagnosis
- Glenn L Schattman, MD
Glenn L Schattman, MD
- Associate Professor of Reproductive Medicine
- The Ronald O Perelman and Claudia Cohen Center for Reproductive Medicine
- The Weill Medical College of Cornell University
There are two types of preimplantation genetic testing:
●Preimplantation genetic diagnosis (PGD) is performed on cell(s) removed from a preimplantation embryo or a polar body from an oocyte. The goal is to establish a pregnancy that is unaffected by specific genetic characteristics, such as a known heritable genetic mutation or chromosomal abnormality (eg, translocations) carried by one or both biological parents. It is also used to select embryos for transfer that have specific characteristics, such as a particular gender or compatible HLA type.
●Preimplantation genetic screening (PGS) is performed on cell(s) removed from a preimplantation embryo or a polar body from an oocyte. The goal is to identify de-novo aneuploidy in embryo(s) of couples presumed to be chromosomally normal. Theoretically, avoiding transfer of aneuploid embryos will reduce the risk of pregnancy failure and improve the probability of conceiving a viable pregnancy .
When preimplantation genetic testing is planned, assisted reproductive technology (ART) must be used for conception even if infertility is not an issue for the couple. ART is expensive, intrusive, and associated with risks, such as ovarian hyperstimulation syndrome, multiple gestations and risks to singleton gestations, that occur less frequently in natural conceptions. (See "In vitro fertilization" and "Intracytoplasmic sperm injection".)
This topic will discuss issues related to PGD. PGS is reviewed separately. (See "Preimplantation genetic screening".)
Subscribers log in hereLiterature review current through: Jul 2017. | This topic last updated: Nov 18, 2016.References
- Practice Committee of the Society for Assisted Reproductive Technology, Practice Committee of the American Society for Reproductive Medicine. Preimplantation genetic testing: a Practice Committee opinion. Fertil Steril 2007; 88:1497.
- Cieslak-Janzen J, Tur-Kaspa I, Ilkevitch Y, et al. Multiple micromanipulations for preimplantation genetic diagnosis do not affect embryo development to the blastocyst stage. Fertil Steril 2006; 85:1826.
- Handyside AH, Pattinson JK, Penketh RJ, et al. Biopsy of human preimplantation embryos and sexing by DNA amplification. Lancet 1989; 1:347.
- Handyside AH, Kontogianni EH, Hardy K, Winston RM. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 1990; 344:768.
- Boada M, Carrera M, De La Iglesia C, et al. Successful use of a laser for human embryo biopsy in preimplantation genetic diagnosis: report of two cases. J Assist Reprod Genet 1998; 15:302.
- Clement-Sengewald A, Buchholz T, Schütze K, et al. Noncontact, laser-mediated extraction of polar bodies for prefertilization genetic diagnosis. J Assist Reprod Genet 2002; 19:183.
- Verlinsky Y, Rechitsky S, Verlinsky O, et al. Prepregnancy testing for single-gene disorders by polar body analysis. Genet Test 1999; 3:185.
- Verlinsky Y, Rechitsky S, Verlinsky O, et al. Preimplantation diagnosis for sonic hedgehog mutation causing familial holoprosencephaly. N Engl J Med 2003; 348:1449.
- Verlinsky Y, Rechitsky S, Cieslak J, et al. Preimplantation diagnosis of single gene disorders by two-step oocyte genetic analysis using first and second polar body. Biochem Mol Med 1997; 62:182.
- Goossens V, De Rycke M, De Vos A, et al. Diagnostic efficiency, embryonic development and clinical outcome after the biopsy of one or two blastomeres for preimplantation genetic diagnosis. Hum Reprod 2008; 23:481.
- Scott RT Jr, Upham KM, Forman EJ, et al. Cleavage-stage biopsy significantly impairs human embryonic implantation potential while blastocyst biopsy does not: a randomized and paired clinical trial. Fertil Steril 2013; 100:624.
- Carson SA, Gentry WL, Smith AL, Buster JE. Trophectoderm microbiopsy in murine blastocysts: comparison of four methods. J Assist Reprod Genet 1993; 10:427.
- Sermon K, Van Steirteghem A, Liebaers I. Preimplantation genetic diagnosis. Lancet 2004; 363:1633.
- Veiga A, Sandalinas M, Benkhalifa M, et al. Laser blastocyst biopsy for preimplantation diagnosis in the human. Zygote 1997; 5:351.
- Yan L, Huang L, Xu L, et al. Live births after simultaneous avoidance of monogenic diseases and chromosome abnormality by next-generation sequencing with linkage analyses. Proc Natl Acad Sci U S A 2015; 112:15964.
- Rechitsky S, Pakhalchuk T, San Ramos G, et al. First systematic experience of preimplantation genetic diagnosis for single-gene disorders, and/or preimplantation human leukocyte antigen typing, combined with 24-chromosome aneuploidy testing. Fertil Steril 2015; 103:503.
- Musters AM, Twisk M, Leschot NJ, et al. Perspectives of couples with high risk of transmitting genetic disorders. Fertil Steril 2010; 94:1239.
- Ethics Committee of American Society for Reproductive Medicine. Use of preimplantation genetic diagnosis for serious adult onset conditions: a committee opinion. Fertil Steril 2013; 100:54.
- Munné S, Sandalinas M, Escudero T, et al. Outcome of preimplantation genetic diagnosis of translocations. Fertil Steril 2000; 73:1209.
- Verlinsky Y, Tur-Kaspa I, Cieslak J, et al. Preimplantation testing for chromosomal disorders improves reproductive outcome of poor-prognosis patients. Reprod Biomed Online 2005; 11:219.
- Fischer J, Colls P, Escudero T, Munné S. Preimplantation genetic diagnosis (PGD) improves pregnancy outcome for translocation carriers with a history of recurrent losses. Fertil Steril 2010; 94:283.
- Stephenson MD, Sierra S. Reproductive outcomes in recurrent pregnancy loss associated with a parental carrier of a structural chromosome rearrangement. Hum Reprod 2006; 21:1076.
- Verlinsky Y, Rechitsky S, Schoolcraft W, et al. Preimplantation diagnosis for Fanconi anemia combined with HLA matching. JAMA 2001; 285:3130.
- Amor DJ, Cameron C. PGD gender selection for non-Mendelian disorders with unequal sex incidence. Hum Reprod 2008; 23:729.
- Goossens V, Harton G, Moutou C, et al. ESHRE PGD Consortium data collection IX: cycles from January to December 2006 with pregnancy follow-up to October 2007. Hum Reprod 2009; 24:1786.
- Committee on Ethics, American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 360: Sex selection. Obstet Gynecol 2007; 109:475.
- Sex selection and preimplantation genetic diagnosis. The Ethics Committee of the American Society of Reproductive Medicine. Fertil Steril 1999; 72:595.
- Wilton L, Thornhill A, Traeger-Synodinos J, et al. The causes of misdiagnosis and adverse outcomes in PGD. Hum Reprod 2009; 24:1221.
- Navidi W, Arnheim N. Using PCR in preimplantation genetic disease diagnosis. Hum Reprod 1991; 6:836.
- Rechitsky S, Verlinsky O, Amet T, et al. Reliability of preimplantation diagnosis for single gene disorders. Mol Cell Endocrinol 2001; 183 Suppl 1:S65.
- Hussey ND, Davis T, Hall JR, et al. Preimplantation genetic diagnosis for beta-thalassaemia using sequencing of single cell PCR products to detect mutations and polymorphic loci. Mol Hum Reprod 2002; 8:1136.
- Lewis CM, Pinêl T, Whittaker JC, Handyside AH. Controlling misdiagnosis errors in preimplantation genetic diagnosis: a comprehensive model encompassing extrinsic and intrinsic sources of error. Hum Reprod 2001; 16:43.
- Strom CM, Levin R, Strom S, et al. Neonatal outcome of preimplantation genetic diagnosis by polar body removal: the first 109 infants. Pediatrics 2000; 106:650.
- Harper JC, de Die-Smulders C, Goossens V, et al. ESHRE PGD consortium data collection VII: cycles from January to December 2004 with pregnancy follow-up to October 2005. Hum Reprod 2008; 23:741.
- Verlinsky Y, Kuliev A. An Illustration Textbook and Reference for Clinicians: An Atlas of Preimplantation Genetic Diagnosis, Parthenon Publishing, New York 2000.
- International Working Group on Preimplantation Genetics. Tenth anniversary of preimplantation genetic diagnosis. J Assist Reprod Genet 2001; 18:64.
- Ginsberg N, Cieslak J, Rechitsky S, et al. Clinical outcome following PGD in one large center. Reprod BioMed Online 2002; 4 (suppl 2, abs O-47):31.
- Verlinsky Y, Cohen J, Munne S, et al. Over a decade of experience with preimplantation genetic diagnosis: a multicenter report. Fertil Steril 2004; 82:292.
- Fischer J, Escudero T, Chen S, et al. Obstetric outcome of 100 cycles of PGD of translocations and other structural abnormalities. Reprod Biomed Online 2002; 4 (suppl 2, abs O-37):26.
- Desmyttere S, De Schepper J, Nekkebroeck J, et al. Two-year auxological and medical outcome of singletons born after embryo biopsy applied in preimplantation genetic diagnosis or preimplantation genetic screening. Hum Reprod 2009; 24:470.
- Desmyttere S, De Rycke M, Staessen C, et al. Neonatal follow-up of 995 consecutively born children after embryo biopsy for PGD. Hum Reprod 2012; 27:288.
- Eldar-Geva T, Srebnik N, Altarescu G, et al. Neonatal outcome after preimplantation genetic diagnosis. Fertil Steril 2014; 102:1016.
- Nekkebroeck J, Bonduelle M, Desmyttere S, et al. Mental and psychomotor development of 2-year-old children born after preimplantation genetic diagnosis/screening. Hum Reprod 2008; 23:1560.
- Schendelaar P, Middelburg KJ, Bos AF, et al. The effect of preimplantation genetic screening on neurological, cognitive and behavioural development in 4-year-old children: follow-up of a RCT. Hum Reprod 2013; 28:1508.
- Winter C, Van Acker F, Bonduelle M, et al. Cognitive and psychomotor development of 5- to 6-year-old singletons born after PGD: a prospective case-controlled matched study. Hum Reprod 2014; 29:1968.
- OBTAINING DNA FOR ANALYSIS
- Polar body biopsy (PBB)
- Blastomere biopsy
- Blastocyst biopsy
- GENETIC EVALUATION
- REASONS COUPLES CHOOSE TO UNDERGO PGD
- Unable or unwilling to undergo pregnancy termination of an affected fetus
- Reduce high risk of recurrent pregnancy loss
- Increase chances of giving birth to a child with a compatible HLA type for stem cell therapy
- Preimplantation sex selection to avoid sex-linked disorders in offspring
- Avoid passing a suspected but unconfirmed autosomal dominant disease to offspring
- SUMMARY AND RECOMMENDATIONS