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Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos
BACKGROUND: To preclude transfer of aneuploid embryos, current preimplantation genetic screening (PGS) usually involves one trophectoderm biopsy at blastocyst stage, assumed to represent embryo ploidy. Whether one such biopsy can correctly assess embryo ploidy has recently, however, been questioned....
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011996/ https://www.ncbi.nlm.nih.gov/pubmed/27595768 http://dx.doi.org/10.1186/s12958-016-0193-6 |
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author | Gleicher, Norbert Vidali, Andrea Braverman, Jeffrey Kushnir, Vitaly A. Barad, David H. Hudson, Cynthia Wu, Yang-Guan Wang, Qi Zhang, Lin Albertini, David F. |
author_facet | Gleicher, Norbert Vidali, Andrea Braverman, Jeffrey Kushnir, Vitaly A. Barad, David H. Hudson, Cynthia Wu, Yang-Guan Wang, Qi Zhang, Lin Albertini, David F. |
author_sort | Gleicher, Norbert |
collection | PubMed |
description | BACKGROUND: To preclude transfer of aneuploid embryos, current preimplantation genetic screening (PGS) usually involves one trophectoderm biopsy at blastocyst stage, assumed to represent embryo ploidy. Whether one such biopsy can correctly assess embryo ploidy has recently, however, been questioned. METHODS: This descriptive study investigated accuracy of PGS in two ways. Part I: Two infertile couples donated 11 embryos, previously diagnosed as aneuploid and, therefore, destined to be discarded. They were dissected into 37 anonymized specimens, and sent to another national laboratory for repeat analyses to assess (i) inter-laboratory congruity and (ii) intra-embryo congruity of multiple embryo biopsies in a single laboratory. Part II: Reports on human IVF cycle outcomes after transfer of allegedly aneuploid embryos into 8 infertile patients. RESULTS: Only 2/11 (18.2 %) embryos were identically assessed at two PGS laboratories; 4/11 (36.4 %), on repeat analysis were chromosomally normal, 2 mosaic normal/abnormal, and 5/11 (45.5 %) completely differed in reported aneuploidies. In intra-embryo analyses, 5/10 (50 %) differed between biopsy sites. Eight transfers of previously reported aneuploid embryos resulted in 5 chromosomally normal pregnancies, 4 delivered and 1 ongoing. Three patients did not conceive, though 1 among them experienced a chemical pregnancy. CONCLUSIONS: Though populations of both study parts are too small to draw statistically adequately powered conclusions on specific degrees of inaccuracy of PGS, here presented results do raise concerns especially about false-positive diagnoses. While inter-laboratory variations may at least partially be explained by different diagnostic platforms utilized, they cannot explain observed intra-embryo variations, suggesting more frequent trophectoderm mosiaicsm than previously reported. Together with recentl published mouse studies of lineages-specific degrees of survival of aneuploid cells in early stage embryos, these results call into question the biological basis of PGS, based on the assumption that a single trophectoderm biopsy can reliably determine embryo ploidy. |
format | Online Article Text |
id | pubmed-5011996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50119962016-09-07 Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos Gleicher, Norbert Vidali, Andrea Braverman, Jeffrey Kushnir, Vitaly A. Barad, David H. Hudson, Cynthia Wu, Yang-Guan Wang, Qi Zhang, Lin Albertini, David F. Reprod Biol Endocrinol Research BACKGROUND: To preclude transfer of aneuploid embryos, current preimplantation genetic screening (PGS) usually involves one trophectoderm biopsy at blastocyst stage, assumed to represent embryo ploidy. Whether one such biopsy can correctly assess embryo ploidy has recently, however, been questioned. METHODS: This descriptive study investigated accuracy of PGS in two ways. Part I: Two infertile couples donated 11 embryos, previously diagnosed as aneuploid and, therefore, destined to be discarded. They were dissected into 37 anonymized specimens, and sent to another national laboratory for repeat analyses to assess (i) inter-laboratory congruity and (ii) intra-embryo congruity of multiple embryo biopsies in a single laboratory. Part II: Reports on human IVF cycle outcomes after transfer of allegedly aneuploid embryos into 8 infertile patients. RESULTS: Only 2/11 (18.2 %) embryos were identically assessed at two PGS laboratories; 4/11 (36.4 %), on repeat analysis were chromosomally normal, 2 mosaic normal/abnormal, and 5/11 (45.5 %) completely differed in reported aneuploidies. In intra-embryo analyses, 5/10 (50 %) differed between biopsy sites. Eight transfers of previously reported aneuploid embryos resulted in 5 chromosomally normal pregnancies, 4 delivered and 1 ongoing. Three patients did not conceive, though 1 among them experienced a chemical pregnancy. CONCLUSIONS: Though populations of both study parts are too small to draw statistically adequately powered conclusions on specific degrees of inaccuracy of PGS, here presented results do raise concerns especially about false-positive diagnoses. While inter-laboratory variations may at least partially be explained by different diagnostic platforms utilized, they cannot explain observed intra-embryo variations, suggesting more frequent trophectoderm mosiaicsm than previously reported. Together with recentl published mouse studies of lineages-specific degrees of survival of aneuploid cells in early stage embryos, these results call into question the biological basis of PGS, based on the assumption that a single trophectoderm biopsy can reliably determine embryo ploidy. BioMed Central 2016-09-05 /pmc/articles/PMC5011996/ /pubmed/27595768 http://dx.doi.org/10.1186/s12958-016-0193-6 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Gleicher, Norbert Vidali, Andrea Braverman, Jeffrey Kushnir, Vitaly A. Barad, David H. Hudson, Cynthia Wu, Yang-Guan Wang, Qi Zhang, Lin Albertini, David F. Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos |
title | Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos |
title_full | Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos |
title_fullStr | Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos |
title_full_unstemmed | Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos |
title_short | Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos |
title_sort | accuracy of preimplantation genetic screening (pgs) is compromised by degree of mosaicism of human embryos |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011996/ https://www.ncbi.nlm.nih.gov/pubmed/27595768 http://dx.doi.org/10.1186/s12958-016-0193-6 |
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