Incidence, Origin, and Predictive Model for the Detection and Clinical Management of Segmental Aneuploidies in Human Embryos

Despite next-generation sequencing, which now allows for the accurate detection of segmental aneuploidies from in vitro fertilization embryo biopsies, the origin and characteristics of these aneuploidies are still relatively unknown. Using a multifocal biopsy approach (four trophectoderms [TEs] and...

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Autores: Girardi, L, Serdarogullari, M, Patassini, C, Poli, M, Fabiani, M, Caroselli, S, Coban, O, Findikli, N, Boynukalin, FK, Bahceci, M, Chopra, R, Canipari, R, Cimadomo, D, Rienzi, L, Ubaldi, F, Hoffmann, E, Rubio, C, Simon, C, Capalbo, A
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p4215
Acesso em linha:https://incliva.portalinvestigacion.com/publicaciones/4215
Access Level:acceso abierto
Palavra-chave:IVF
PGT
aneuploidies
meiosis
mitotic aneuploidies
mosaicism
preimplantation embryo
preimplantation genetic testing
preimplnatation genetic screening
segmental abnormalities
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spelling Incidence, Origin, and Predictive Model for the Detection and Clinical Management of Segmental Aneuploidies in Human EmbryosGirardi, LSerdarogullari, MPatassini, CPoli, MFabiani, MCaroselli, SCoban, OFindikli, NBoynukalin, FKBahceci, MChopra, RCanipari, RCimadomo, DRienzi, LUbaldi, FHoffmann, ERubio, CSimon, CCapalbo, AIVFPGTaneuploidiesmeiosismitotic aneuploidiesmosaicismpreimplantation embryopreimplantation genetic testingpreimplnatation genetic screeningsegmental abnormalitiesDespite next-generation sequencing, which now allows for the accurate detection of segmental aneuploidies from in vitro fertilization embryo biopsies, the origin and characteristics of these aneuploidies are still relatively unknown. Using a multifocal biopsy approach (four trophectoderms [TEs] and one inner cell mass [ICM] analyzed per blastocyst; n = 390), we determine the origin of the aneuploidy and the diagnostic predictive value of segmental aneuploidy detection in TE biopsies toward the ICM's chromosomal constitution. Contrary to the prevalent meiotic origin of whole-chromosome aneuploidies, we show that sub-chromosomal abnormalities in human blastocysts arise from mitotic errors in around 70% of cases. As a consequence, the positive-predictive value toward ICM configuration was significantly lower for segmental as compared to whole-chromosome aneuploidies (70.8% versus 97.18%, respectively). In order to enhance the clinical utility of reporting segmental findings in clinical TE biopsies, we have developed and clinically verified a risk stratification model based on a second TE biopsy confirmation and segmental length; this model can significantly improve the prediction of aneuploidy risk in the ICM in over 86% of clinical cases enrolled. In conclusion, we provide evidence of the predominant mitotic origin of segmental aneuploidies in preimplantation embryos and develop a risk stratification model that can help post-test genetic counseling and that facilitates the decision-making process on clinical utilization of these embryos.CELL PRESS2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/4215AMERICAN JOURNAL OF HUMAN GENETICSISSN: 00029297ISSNe: 15376605reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p42152026-06-07T16:35:31Z
dc.title.none.fl_str_mv Incidence, Origin, and Predictive Model for the Detection and Clinical Management of Segmental Aneuploidies in Human Embryos
title Incidence, Origin, and Predictive Model for the Detection and Clinical Management of Segmental Aneuploidies in Human Embryos
spellingShingle Incidence, Origin, and Predictive Model for the Detection and Clinical Management of Segmental Aneuploidies in Human Embryos
Girardi, L
IVF
PGT
aneuploidies
meiosis
mitotic aneuploidies
mosaicism
preimplantation embryo
preimplantation genetic testing
preimplnatation genetic screening
segmental abnormalities
title_short Incidence, Origin, and Predictive Model for the Detection and Clinical Management of Segmental Aneuploidies in Human Embryos
title_full Incidence, Origin, and Predictive Model for the Detection and Clinical Management of Segmental Aneuploidies in Human Embryos
title_fullStr Incidence, Origin, and Predictive Model for the Detection and Clinical Management of Segmental Aneuploidies in Human Embryos
title_full_unstemmed Incidence, Origin, and Predictive Model for the Detection and Clinical Management of Segmental Aneuploidies in Human Embryos
title_sort Incidence, Origin, and Predictive Model for the Detection and Clinical Management of Segmental Aneuploidies in Human Embryos
dc.creator.none.fl_str_mv Girardi, L
Serdarogullari, M
Patassini, C
Poli, M
Fabiani, M
Caroselli, S
Coban, O
Findikli, N
Boynukalin, FK
Bahceci, M
Chopra, R
Canipari, R
Cimadomo, D
Rienzi, L
Ubaldi, F
Hoffmann, E
Rubio, C
Simon, C
Capalbo, A
author Girardi, L
author_facet Girardi, L
Serdarogullari, M
Patassini, C
Poli, M
Fabiani, M
Caroselli, S
Coban, O
Findikli, N
Boynukalin, FK
Bahceci, M
Chopra, R
Canipari, R
Cimadomo, D
Rienzi, L
Ubaldi, F
Hoffmann, E
Rubio, C
Simon, C
Capalbo, A
author_role author
author2 Serdarogullari, M
Patassini, C
Poli, M
Fabiani, M
Caroselli, S
Coban, O
Findikli, N
Boynukalin, FK
Bahceci, M
Chopra, R
Canipari, R
Cimadomo, D
Rienzi, L
Ubaldi, F
Hoffmann, E
Rubio, C
Simon, C
Capalbo, A
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv IVF
PGT
aneuploidies
meiosis
mitotic aneuploidies
mosaicism
preimplantation embryo
preimplantation genetic testing
preimplnatation genetic screening
segmental abnormalities
topic IVF
PGT
aneuploidies
meiosis
mitotic aneuploidies
mosaicism
preimplantation embryo
preimplantation genetic testing
preimplnatation genetic screening
segmental abnormalities
description Despite next-generation sequencing, which now allows for the accurate detection of segmental aneuploidies from in vitro fertilization embryo biopsies, the origin and characteristics of these aneuploidies are still relatively unknown. Using a multifocal biopsy approach (four trophectoderms [TEs] and one inner cell mass [ICM] analyzed per blastocyst; n = 390), we determine the origin of the aneuploidy and the diagnostic predictive value of segmental aneuploidy detection in TE biopsies toward the ICM's chromosomal constitution. Contrary to the prevalent meiotic origin of whole-chromosome aneuploidies, we show that sub-chromosomal abnormalities in human blastocysts arise from mitotic errors in around 70% of cases. As a consequence, the positive-predictive value toward ICM configuration was significantly lower for segmental as compared to whole-chromosome aneuploidies (70.8% versus 97.18%, respectively). In order to enhance the clinical utility of reporting segmental findings in clinical TE biopsies, we have developed and clinically verified a risk stratification model based on a second TE biopsy confirmation and segmental length; this model can significantly improve the prediction of aneuploidy risk in the ICM in over 86% of clinical cases enrolled. In conclusion, we provide evidence of the predominant mitotic origin of segmental aneuploidies in preimplantation embryos and develop a risk stratification model that can help post-test genetic counseling and that facilitates the decision-making process on clinical utilization of these embryos.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/4215
url https://incliva.portalinvestigacion.com/publicaciones/4215
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv CELL PRESS
publisher.none.fl_str_mv CELL PRESS
dc.source.none.fl_str_mv AMERICAN JOURNAL OF HUMAN GENETICS
ISSN: 00029297
ISSNe: 15376605
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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