Validation of concurrent preimplantation genetic testing for polygenic and monogenic disorders, structural rearrangements, and whole and segmental chromosome aneuploidy with a single universal platform

Treff, Nathan R.; Zimmerman, Ray A.; Bechor, Elan; Hsu, Jeff; Rana, Bhavini; Jensen, J.; Li, Jeremy; Самойленко, А. В.; Mowrey, W.; Alstine, James Van; Leondires, M.P.; Miller, Kathy Ann; Paganetti, E.L.; Lello, Louis; Avery, S.; Hsu, Stephen; Tellier, Laurent

doi:10.1016/j.ejmg.2019.04.004

Cited by 72 publications

(62 citation statements)

References 17 publications

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“…In addition, 147 embryos were from patients who had an abnormal karyotype were used for analysis of positive controls. 36 2018 May 24 NGS Whole blastocyst NGS Tsuiko 37 2018 June 14 NGS ICM NGS Popovic 38 2018 July 58 NGS TE/ICM NGS Chuang 39 2018 December 29 NGS TE/ICM NGS Victor 16 2019 January 100 NGS TE/ICM NGS Victor 40 2019 February 8 NGS TE/ICM NGS Popovic 41 2019 April 45 NGS Blastocyst outgrowth NGS Lawrenz 42 2019 June 84 NGS TE/ICM NGS Huang 43 2019 July 50 NGS Whole blastocyst NGS Treff 44 2019 August 14 NGS TE SNP array Munne 45 2020 January 57 NGS TE NGS Ou 46 2020 January 63 NGS Whole blastocyst NGS Sachdev 47 2020 February 32 NGS TE/ICM NGS Girardi 9 2020 March 88 NGS TE/ICM NGS Navratil 48 2020 April 75 NGS TE/Whole blastocyst NGS Rubio 49 2020 May 64 NGS ICM NGS Lin 50 2020 June 41 NGS ICM NGS Abbreviations: aCGH, array comparative hybridization; CGH, comparative genomic hybridization; ICM, inner cell mass; NGS, next-generation sequencing; qPCR, quantitative real-time PCR; PGT-A, preimplantation genetic testing for aneuploidy; SNP, single nucleotide polymorphism; TE, trophectoderm.…”

Section: Resultsmentioning

confidence: 99%

Preimplantation genetic testing for aneuploidy: A review of published blastocyst reanalysis concordance data

Marín

Treff

2020

Prenatal Diagnosis

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Preimplantation genetic testing for aneuploidy (PGT-A) reduces miscarriage risk, increases the success of IVF, shortens time to pregnancy, and reduces multiple gestation rates without compromising outcomes. The progression of PGT-A has included common application of next-generation sequencing (NGS) from single nucleotide polymorphism microarray, quantitative real-time PCR, and array comparative hybridization platforms of analysis. Additional putative advances in PGT-A capability include classifying embryos as mosaic and predicting the presence of segmental imbalance. A critical component in the process of technical validation of these advancements involves evaluation of concordance between reanalysis results and initial testing results. While many independent studies have investigated the concordance of results obtained from the remaining embryo with the original PGT-A diagnosis, compilation and systematic analysis of published data has not been performed. Here, we review results from 26 primary research articles describing concordance in 1271 human blastocysts from 2260 pairwise comparisons. Results illustrate significantly higher discordance from PGT-A methods which utilize NGS and include prediction of mosaicism or segmental imbalance. These results suggest caution when considering new iterations PGT-A.

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Section: Resultsmentioning

confidence: 99%

Preimplantation genetic testing for aneuploidy: A review of published blastocyst reanalysis concordance data

Marín

Treff

2020

Prenatal Diagnosis

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“…The first step in making such testing (PGT-P) possible, is demonstrating the ability to accurately obtain genome-wide genotypes from an embryo biopsy. This step has been completed, with >99% concordance between limited quantities of DNA when compared to large quantities of DNA (9). As a result of this advance, it is now possible to equate performance of polygenic risk scoring in adult populations to performance on embryos produced during IVF.…”

Section: Introductionmentioning

confidence: 99%

Utility and First Clinical Application of Screening Embryos for Polygenic Disease Risk Reduction

et al. 2019

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For over 2 decades preimplantation genetic testing (PGT) has been in clinical use to reduce the risk of miscarriage and genetic disease in patients with advanced maternal age and risk of transmitting disease. Recently developed methods of genome-wide genotyping and machine learning algorithms now offer the ability to genotype embryos for polygenic disease risk with accuracy equivalent to adults. In addition, contemporary studies on adults indicate the ability to predict polygenic disorders with risk equivalent to monogenic disorders. Existing biobanks provide opportunities to model the clinical utility of polygenic disease risk reduction among sibling adults. Here, we provide a mathematical model for the use of embryo screening to reduce the risk of type 1 diabetes. Results indicate a 45-72% reduced risk with blinded genetic selection of one sibling. The first clinical case of polygenic risk scoring in human preimplantation embryos from patients with a family history of complex disease is reported. In addition to these data, several common and accepted practices place PGT for polygenic disease risk in the applicable context of contemporary reproductive medicine. In addition, prediction of risk for PCOS, endometriosis, and aneuploidy are of particular interest and relevance to patients with infertility and represent an important focus of future research on polygenic risk scoring in embryos.

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“…Reproduction (2020) 160 A13-A17 human trait (Lello et al 2018); third, the capability to obtain embryonic genome-wide genotypes with accuracy equivalent to adults (Treff et al 2019b); and fourth, the capability to achieve significant reduction in polygenic disease risk following genetic selection of a sibling (Treff et al 2019a). The latter of these developments, demonstrating clinical utility in genetic selection across >2000 siblings, is an important outcome to highlight.…”

Section: Pgt-p A15mentioning

confidence: 99%

PREIMPLANTATION GENETIC TESTING: Preimplantation genetic testing for polygenic disease risk

et al. 2020

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Since its introduction to clinical practice, preimplantation genetic testing (PGT) has become a standard of care for couples at risk of having children with monogenic disease, and for chromosomal aneuploidy to improve outcomes for patients with infertility. The primary objective of PGT is to reduce the risk of miscarriage and genetic disease and to improve the success of infertility treatment with the delivery of a healthy child. Until recently, the application of PGT to more common but complex polygenic disease was not possible, as the genetic contribution to polygenic disease has been difficult to determine, and the concept of embryo selection across multiple genetic loci has been difficult to comprehend. Several achievements, including the ability to obtain accurate, genome-wide genotypes of the human embryo, and the development of population level biobanks have now made PGT for polygenic disease risk applicable in clinical practice. With the rapid advances in embryonic polygenic risk scoring, diverse considerations beyond technical capability have been introduced.

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Validation of concurrent preimplantation genetic testing for polygenic and monogenic disorders, structural rearrangements, and whole and segmental chromosome aneuploidy with a single universal platform

Cited by 72 publications

References 17 publications

Preimplantation genetic testing for aneuploidy: A review of published blastocyst reanalysis concordance data

Preimplantation genetic testing for aneuploidy: A review of published blastocyst reanalysis concordance data

Utility and First Clinical Application of Screening Embryos for Polygenic Disease Risk Reduction

PREIMPLANTATION GENETIC TESTING: Preimplantation genetic testing for polygenic disease risk

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