Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-76c49bb84f-vcmr7 Total loading time: 0 Render date: 2025-07-01T10:39:18.678Z Has data issue: false hasContentIssue false

Chapter 17 - Preimplantation Genetic Testing (PGT)

from Section 3 - Genetics and Preimplantation Genetic Testing

Published online by Cambridge University Press:  05 March 2021

By
Eliezer Girsh  and
Mira Malcov
Edited by
Eliezer Girsh
Eliezer Girsh
Affiliation:
Barzilai Medical Center, Ashkelon
Get access

Summary

The risk for transmission of genetic disorders to offspring has been a critical obstacle for couples known to be carriers for severe genetic disorders. To prevent the birth of an affected child, prenatal testing by amniocentesis or chorionic villus sampling (CVS) is offered. An alternative approach, available with assisted reproductive technology (ART), is preimplantation genetic testing – PGT – enabling testing of the embryo for the familial disorder before the corresponding embryo is transferred to the uterus of the mother.

Information

Type
Chapter
Information
A Textbook of Clinical Embryology , pp. 207 - 225
Publisher: Cambridge University Press
Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Gardner, RL, Edwards, RG. Control of the sex ratio at full term in the rabbit by transferring sexed blastocyst. Nature 1968; 218:346–348.Google Scholar
Handyside, AH, Kontogianni, EH, Hardy, K, Winston, RM. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 1990; 344:768–770.Google Scholar
International Working Group on Preimplantation Genetics. 10th anniversary of preimplantation genetic diagnosis. J. Assist. Reprod. Genet. 2001; 18:66–72.Google Scholar
Hasson, J, Limoni, D, Malcov, M, et al. Obstetric and neonatal outcomes of pregnancies conceived after preimplantation genetic diagnosis: cohort study and meta-analysis. RBM Online 2017; 35:208–218.Google ScholarPubMed
Heijligers, M, Verheijden, LMM, Jonkman, LM, et al. The cognitive and socio-emotional development of 5-year-old children born after PGD. Hum. Reprod. 2018; 33:2150–2157.CrossRefGoogle ScholarPubMed
Sermon, K, Van Steirteghem, A, Liebaers, I. Preimplantation genetic diagnosis. Lancet 2004; 363:1633–1641.CrossRefGoogle ScholarPubMed
Dreesen, JC, Jacobs, LJ, Bras, M, et al. Multiplex PCR of polymorphic markers flanking the CFTR gene; a general approach for preimplantation genetic diagnosis of cystic fibrosis. Mol. Hum. Reprod. 2000; 6:391–396.CrossRefGoogle ScholarPubMed
Harper, JC, Harton, G. The use of arrays in preimplantation genetic diagnosis and screening. Fertil. Steril. 2010; 94:1173–1177.CrossRefGoogle ScholarPubMed
Sermon, K, Capalbo, A, Cohen, J, et al. The why, the how and the when of PGS 2.0: current practices and expert opinions of fertility specialists, molecular biologists, and embryologists. Mol. Hum. Reprod. 2016; 22:845–857.CrossRefGoogle ScholarPubMed
Frumkin, T, Peleg, S, Gold, V, et al. Complex chromosomal rearrangement—a lesson learned from PGS. J. Assist. Reprod. Genet. 2017; 34:1095–1100.CrossRefGoogle ScholarPubMed
Munné, S. Status of preimplantation genetic testing and embryo selection. RBM Online 2018; 37:393–396.Google ScholarPubMed
Malcov, M, Schwartz, T, Mei-Raz, N, et al. Multiplex nested PCR for preimplantation genetic diagnosis of spinal muscular atrophy. Fetal. Diagn. Ther. 2004; 19:199–206.CrossRefGoogle ScholarPubMed
Tadir, Y, Wright, WH, Vafa, O, et al. Review: micromanipulation of gametes using laser microbeams. Hum. Reprod. 1991; 6:1011–1016.Google Scholar
Rink, K, Delacrétaz, G, Salathé, RP, et al. Non-contact microdrilling of mouse zona pellucida with an objective-delivered 1.48-μm diode laser. Lasers Surg. Med. 1996; 18:52–62.Google Scholar
Kalma, Y, Bar-El, L, Asaf-Tisser, S, et al. Optimal timing for blastomere biopsy of 8-cell embryos for preimplantation genetic diagnosis. Hum. Reprod. 2018; 33:32–38.Google Scholar
Harton, GL, Magli, MC, Lundin, K, et al. 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; 26:41–46.Google Scholar
Verlinsky, Y, Kuliev, A. An Atlas of Preimplantation Genetic Diagnosis. London: The Parthenon Publishing Group. 2000.Google Scholar
De Vos, A, Van Steirteghem, A. Aspects of biopsy procedures prior to preimplantation genetic diagnosis. Prenat. Diagn. 2001; 21:767–780.Google Scholar
Feichtinger, W, Strohmer, H, Fuhrberg, P, et al. Photoablation of oocyte zona pellucida by erbium-YAG laser for in-vitro fertilisation in severe male infertility. Lancet 1992; 339:811.Google Scholar
Neev, J, Schiewe, M, Sung, V, et al. Assisted hatching in mouse embryos using a noncontact Ho:YSGG laser system. J. Assist. Reprod. Genet. 1995; 12:288–293.Google Scholar
MacLennan, M, Crichton, JH, Playfoot, CJ, Adams, IR. Oocyte development, meiosis and aneuploidy. Semin. Cell Dev. Biol. 2015; 45:68–76.Google Scholar
Capalbo, A, Hoffmann, ER, Cimadomo, D, Ubaldi, FM, Rienzi, L. Human female meiosis revised: new insights into the mechanisms of chromosome segregation and aneuploidies from advanced genomics and time-lapse imaging. Hum. Reprod. Update 2017; 23:706–722.CrossRefGoogle ScholarPubMed
Montag, M, van der Ven, K, Rösing, B, van der Ven, H. Polar body biopsy: a viable alternative to preimplantation genetic diagnosis and screening. RBM Online 2009; 18(Suppl. 1):6–11.Google Scholar
Verlinsky, Y, Kuliev, A. Preimplantation polar body diagnosis. Biochem. Mol. Med. 1996; 58:13–17.CrossRefGoogle ScholarPubMed
Levin, I, Almog, B, Shwartz, T, et al. Effects of laser polar-body biopsy on embryo quality. Fertil. Steril. 2012; 97:1085–1088.Google Scholar
Dumoulin, JC, Bras, M, Coonen, E, et al. Effect of Ca2+/Mg2+-free medium on the biopsy procedure for preimplantation genetic diagnosis and further development of human embryos. Hum. Reprod. 1998; 13:2880–2883.Google Scholar
McCoy, RC, Demko, ZP, Ryan, A, et al. Evidence of selection against complex mitotic-origin aneuploidy during preimplantation development. PLoS Genet. 2015; 11:e1005601.Google Scholar
Adler, A, Lee, HL, McCulloh, DH, et al. Blastocyst culture selects for euploid embryos: comparison of blastomere and trophectoderm biopsies. RBM Online 2014; 28:485–491.Google Scholar
Weissman, A, Shoham, G, Shoham, Z, et al. Chromosomal mosaicism detected during preimplantation genetic screening: results of a worldwide web-based survey. Fertil. Steril. 2017; 107:1092–1097.Google Scholar
Liñán, A, Lawrenz, B, El Khatib, I, et al. Clinical reassessment of human embryo ploidy status between cleavage and blastocyst stage by next generation sequencing. PLoS One 2018; 13:e0201652.CrossRefGoogle ScholarPubMed
Del Rey, J, Vidal, F, Ramírez, L, et al. Novel double factor PGT strategy analyzing blastocyst stage embryos in a single NGS procedure. PLoS One 2018; 13:e0205692.CrossRefGoogle Scholar
Fragouli, E, Alfarawati, S, Daphnis, DD, et al. Cytogenetic analysis of human blastocysts with the use of FISH, CGH and aCGH: scientific data and technical evaluation. Hum. Reprod. 2011; 26:480–490.Google Scholar
Ventura-Juncá, P, Irarrázaval, I, Rolle, AJ, et al. In vitro fertilization (IVF) in mammals: epigenetic and developmental alterations. Scientific and bioethical implications for IVF in humans. Biol. Res. 2015; 48:68.Google Scholar
Laskowski, D, Humblot, P, Sirard, MA, et al. DNA methylation pattern of bovine blastocysts associated with hyperinsulinemia in vitro. Mol. Reprod. Dev. 2018; 85:599–611.CrossRefGoogle ScholarPubMed
De Rycke, M, Goossens, V, Kokkali, G, et al. ESHRE PGD Consortium data collection XIV-XV: cycles from January 2011 to December 2012 with pregnancy follow-up to October 2013. Hum. Reprod. 2017; 32:1974–1994.Google Scholar
Yaron, Y, Schwartz, T, Mey-Raz, N, et al. Preimplantation genetic diagnosis of Canavan disease. Fetal Diagn. Ther. 2005; 20:465–468.CrossRefGoogle ScholarPubMed
Rechitsky, S, Pakhalchuk, T, San Ramos, G, et al. First systematic experience of preimplantation genetic diagnosis for single-gene disorder, and/or preimplantation human leukocyte antigen typing, combined with 24-chromosome aneuploidy testing. Fertil. Steril. 2015; 103:503–512.Google Scholar
Harper, JC, Wells, D. Recent advances and future developments in PGD. Prenat. Diagn. 1999; 19:1193–1199.3.0.CO;2-5>CrossRefGoogle ScholarPubMed
Malcov, M, Naiman, T, Yosef, DB, et al. Preimplantation genetic diagnosis for fragile X syndrome using multiplex nested PCR. RBM Online 2007; 14:515–521.Google Scholar
Zhao, M, Lian, M, Cheah, FSH, et al. Identification of novel microsatellite markers flanking the SMN1 and SMN2 duplicated region and inclusion into a single-tube tridecaplex panel for haplotype-based preimplantation genetic testing of spinal muscular atrophy. Front. Genet. 2019; 10:1105.Google Scholar
Ray, PF, Handyside, AH. Increasing the denaturation temperature during the first cycles of amplification reduces allele dropout from single cells for preimplantation genetic diagnosis. Mol. Hum. Reprod. 1996; 2:213–218.CrossRefGoogle ScholarPubMed
Rechitsky, S, Verlinsky, O, Amet, T, et al. Reliability of preimplantation diagnosis for single gene disorder. Mol. Cell Endocrinol. 2001; 183 (Suppl. 1):S65–S68.Google Scholar
Jovanovich, S, Bogdan, G, Belcinski, R, et al. Developmental validation of a fully integrated sample-to-profile rapid human identification system for processing single-source reference buccal samples. Forensic Sci. Int. Genet. 2015; 16:181–194.Google Scholar
He, G, Zou, X, Wang, M, et al. Population genetics, diversity, forensic characteristics of four Chinese populations inferred from X-chromosomal short tandem repeats. Leg. Med. (Tokyo) 2020; 43:101677.Google Scholar
Liu, Y, Sun, Y, Wu, J, et al. Polymorphisms in IL-1A are associated with endometrial cancer susceptibility among Chinese Han population: a case-control study. Int. J. Immunogenet. 2020; 47:169–174. doi:10.1111/iji.12463.CrossRefGoogle ScholarPubMed
Malcov, M, Ben-Yosef, D, Schwartz, T, et al. Preimplantation genetic diagnosis (PGD) for Duchenne muscular dystrophy (DMD) by triplex-nested PCR. Prenat. Diagn. 2005; 25:1200–1205.Google Scholar
Sciorio, R, Tramontano, L, Catt, J. Preimplantation genetic diagnosis (PGD) and genetic testing for aneuploidy (PGT-A): status and future challenges. Gynecol. Endocrinol. 2020; 36:6–11.Google Scholar
Frumkin, T, Malcov, M, Yaron, Y, Ben-Yosef, D. Elucidating the origin of chromosomal aberrations in IVF embryos by preimplantation genetic analysis. Mol. Cell Endocrinol. 2008; 282:112–119.Google Scholar
Coonen, E, Dumoulin, JC, Ramaekers, FC, Hopman, AH. Optimal preparation of preimplantation embryo interphase nuclei for analysis by fluorescence in-situ hybridization. Hum. Reprod. 1994; 9:533–537.Google Scholar
Barbash-Hazan, S, Frumkin, T, Malcov, M, et al. Preimplantation aneuploid embryos undergo self-correction in correlation with their developmental potential. Fertil. Steril. 2009; 92:890–896.Google Scholar
Harton, GL, Harper, JC, Coonen, E, et al. ESHRE PGD consortium best practice guidelines for fluorescence in situ hybridization-based PGD. Hum. Reprod. 2011; 26:25–32.Google Scholar
Borgstrom, E, Paterlini, M, Mold, JE, Frisen, J, Lundeberg, J. Comparison of whole genome amplification techniques for human single cell exome sequencing. PloS One 2017; 12:e0171566.Google Scholar
Deleye, L, Gansemans, Y, De Coninck, D, Van Nieuwerburgh, F, Deforce, D. Massively parallel sequencing of micro-manipulated cells targeting a comprehensive panel of disease-causing genes: $ comparative evaluation of upstream whole-genome amplification methods. PLoS One 2018; 13:e0196334.Google Scholar
França, LT, Carrilho, E, Kist, TB. A review of DNA sequencing techniques. Q. Rev. Biophys. 2002; 35:169–200.Google Scholar
Anderson, MW, Schrijver, I. Next generation DNA sequencing and the future of genomic medicine. Genes 2010; 1:38–69.Google Scholar
Muzzey, D, Kash, S, Johnson, JI, et al. Software-assisted manual review of clinical next-generation sequencing data: an alternative to routine Sanger sequencing confirmation with equivalent results in >15,000 germline DNA screens. J. Mol. Diagn. 2019; 21:296–306.CrossRefGoogle Scholar
Fiorentino, F, Biricik, A, Bono, S, et al. Development and validation of a next-generation sequencing-based protocol for 24-chromosome aneuploidy screening of embryos. Fertil. Steril. 2014; 101:1375–1382.Google Scholar
Friedenthal, J, Maxwell, SM, Munné, S, et al. Next generation sequencing for preimplantation genetic screening improves pregnancy outcomes compared with array comparative genomic hybridization in single thawed euploid embryo transfer cycles. Fertil. Steril. 2018; 109:627–632.Google Scholar
Popovic, M, Dhaenens, L, Taelman, J, et al. Extended in vitro culture of human embryos demonstrates the complex nature of diagnosing chromosomal mosaicism from a single trophectoderm biopsy. Hum. Reprod. 2019; 34:758–769.Google Scholar
Victor, AR, Tyndall, JC, Brake, AJ, et al. One hundred mosaic embryos transferred prospectively in a single clinic: exploring when and why they result in healthy pregnancies. Fertil. Steril. 2019; 111:280–293.Google Scholar
Munné, S, Spinella, F, Grifo, J, et al. Clinical outcomes after the transfer of blastocysts characterized as mosaic by high resolution next generation sequencing – further insights. Eur. J. Med. Genet. 2020; 63:103741.Google Scholar
Orvieto, R, Gleicher, N. Preimplantation genetic testing for aneuploidy (PGT-A)-finally revealed. J. Assist. Reprod. Genet. 2020; 37:669–672. doi:10.1007/s10815-020-01705-w.Google Scholar
Magli, MC, Jones, GM, Gras, L, et al. Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro. Hum. Reprod. 2000; 15:1781–1786.Google Scholar
Orvieto, R, Gleicher, N. Should preimplantation genetic screening (PGS) be implemented to routine IVF practice? J. Assist. Reprod. Genet. 2016; 33:1445–1448.Google Scholar
Practice Committee of the American Society for Reproductive Medicine, Practice Committee of the Society for Assisted Reproductive Technology. Blastocyst culture and transfer in clinically assisted reproduction: a committee opinion. Fertil. Steril. 2018; 110:1246–1252.Google Scholar
Lawrenz, B, El Khatib, I, Liñán, A, et al. The clinicians’ dilemma with mosaicism-an insight from inner cell mass biopsies. Hum. Reprod. 2019; 34:998–1010.CrossRefGoogle ScholarPubMed
Escribà, MJ, Vendrell, X, Peinado, V. Segmental aneuploidy in human blastocysts: a qualitative and quantitative overview. Reprod. Biol. Endocrinol. 2019; 17:76.Google Scholar
Banker, JM, Arora, P, Khajuria, R, Banker, M. India’s first child using PGT-M, PGT-A and HLA matching for helping a sibling having β-thalassemia major. J. Hum. Reprod. Sci. 2019; 12:341–344.Google Scholar
Backenroth, D, Zahdeh, F, Kling, Y, et al. Haploseek: a 24-hour all-in-one method for preimplantation genetic diagnosis (PGD) of monogenic disease and aneuploidy. Genet. Med. 2019; 21:1390–1399.CrossRefGoogle ScholarPubMed
Natesan, SA, Bladon, AJ, Coskun, S, et al. Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro. Genet. Med. 2014; 16:838–845.CrossRefGoogle ScholarPubMed
Prates, R, Konstantinidis, M, Goodall, NN, et al. Clinical experience with karyomapping for preimplantation genetic diagnosis (PGD) of single gene disorders. Fertil. Steril. 2014; 102:e25–e26.CrossRefGoogle Scholar
Treff, NR, Zimmerman, R, Bechor, E, et al. Validation of concurrent preimplantation genetic testing for polygenic and monogenic disorders, structural rearrangements, and whole and segmental chromosome aneuploidy with a single universal platform. Eur. J. Med. Genet. 2019; 62:103647.Google Scholar
Van Rij, MC, De Rademaeker, M, Moutou, C, et al. BruMaStra PGD working group preimplantation genetic diagnosis (PGD) for Huntington’s disease: the experience of three European centers. Eur. J. Hum. Genet. 2012; 20:368–375.CrossRefGoogle Scholar
Rechitsky, S, Pomerantseva, E, Pakhalchuk, T, et al. First systematic experience of preimplantation genetic diagnosis for de-novo mutations. RBM Online 2011; 22:350–361.Google ScholarPubMed
Altarescu, G, Brooks, B, Kaplan, Y, et al. Single-sperm analysis for haplotype construction of de-novo paternal mutations: application to PGD for neurofibromatosis type 1. Hum. Reprod. 2006; 21:2047–2051.Google Scholar
Hellebrekers, DM, Wolfe, R, Hendrickx, AT, et al. PGD and heteroplasmic mitochondrial DNA point mutations: a systematic review estimating the chance of healthy offspring. Hum. Reprod. Update 2012; 18:341–349.CrossRefGoogle ScholarPubMed
Johnston, IG, Burgstaller, JP, Havlicek, V, et al. Stochastic modelling, bayesian inference, and new in vivo measurements elucidate the debated mtDNA bottleneck mechanism. eLife 2015; 4:e07464.Google Scholar
Sallevelt, SC, Dreesen, JC, Coonen, E, et al. Preimplantation genetic diagnosis for mitochondrial DNA mutations: analysis of one blastomere suffices. J. Med. Genet. 2017; 54:693–697.Google Scholar
Sallevelt, SC, Dreesen, JC, Drüsedau, M, et al. PGD for the m.14487 T>C mitochondrial DNA mutation resulted in the birth of a healthy boy. Hum. Reprod. 2017; 32:698–703.Google Scholar
Treff, NR, Campos, J, Tao, X, et al. Blastocyst preimplantation genetic diagnosis (PGD) of a mitochondrial DNA disorder. Fertil. Steril. 2012; 98:1236–1240.Google Scholar
Wolf, DP, Mitalipov, N, Mitalipov, S. Mitochondrial replacement therapy in reproductive medicine. Trends Mol. Med. 2015; 21:68–76.CrossRefGoogle ScholarPubMed
Tang, M, Guggilla, RR, Gansemans, Y, et al. Comparative analysis of different nuclear transfer techniques to prevent the transmission of mitochondrial DNA variants. Mol. Hum. Reprod. 2019; 25:797–810.Google Scholar
Scott, KL, Hong, KH, Scott, RT. Selecting the optimal time to perform biopsy for preimplantation genetic testing. Fertil. Steril. 2013; 100:608–614.Google Scholar
Leaver, M, Wells, D. Non-invasive preimplantation genetic testing (niPGT): the next revolution in reproductive genetics? Hum. Reprod. Update 2020; 26:16–42.Google Scholar
Heijligers, M, van Montfoort, A, Meijer-Hoogeveen, M, et al. Perinatal follow-up of children born after preimplantation genetic diagnosis between 1995 and 2014. J. Assist. Reprod. Genet. 2018; 35:1995–2002.Google Scholar
Heijligers, M, Verheijden, LMM, Jonkman, LM, et al. The cognitive and socio-emotional development of 5-year-old children born after PGD. Hum. Reprod. 2018; 33:2150–2157.CrossRefGoogle ScholarPubMed
Kuiper, D, Bennema, A, Bastide-van Gemert, S, et al. Developmental outcome of 9-year-old children born after PGS: follow-up of a randomized trial. Hum. Reprod. 2018; 33:147–155.CrossRefGoogle ScholarPubMed
Thornhill, AR, deDie-Smulders, CE, Geraedts, JP, et al. ESHRE PGD Consortium. ‘Best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS)’. Hum. Reprod. 2005; 20:35–48.CrossRefGoogle ScholarPubMed
Harton, GL, De Rycke, M, Fiorentino, F, et al. ESHRE PGD consortium best practice guidelines for amplification-based PGD. Hum. Reprod. 2011; 26:33–40.Google Scholar

Accessibility standard: Unknown

Accessibility compliance for the PDF of this book is currently unknown and may be updated in the future.

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×