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Clinical outcome of preimplantation genetic diagnosis and screening using next generation sequencing
BACKGROUND: Next generation sequencing (NGS) is now being used for detecting chromosomal abnormalities in blastocyst trophectoderm (TE) cells from in vitro fertilized embryos. However, few data are available regarding the clinical outcome, which provides vital reference for further application of th...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326468/ https://www.ncbi.nlm.nih.gov/pubmed/25685330 http://dx.doi.org/10.1186/2047-217X-3-30 |
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author | Tan, Yueqiu Yin, Xuyang Zhang, Shuoping Jiang, Hui Tan, Ke Li, Jian Xiong, Bo Gong, Fei Zhang, Chunlei Pan, Xiaoyu Chen, Fang Chen, Shengpei Gong, Chun Lu, Changfu Luo, Keli Gu, Yifan Zhang, Xiuqing Wang, Wei Xu, Xun Vajta, Gábor Bolund, Lars Yang, Huanming Lu, Guangxiu Du, Yutao Lin, Ge |
author_facet | Tan, Yueqiu Yin, Xuyang Zhang, Shuoping Jiang, Hui Tan, Ke Li, Jian Xiong, Bo Gong, Fei Zhang, Chunlei Pan, Xiaoyu Chen, Fang Chen, Shengpei Gong, Chun Lu, Changfu Luo, Keli Gu, Yifan Zhang, Xiuqing Wang, Wei Xu, Xun Vajta, Gábor Bolund, Lars Yang, Huanming Lu, Guangxiu Du, Yutao Lin, Ge |
author_sort | Tan, Yueqiu |
collection | PubMed |
description | BACKGROUND: Next generation sequencing (NGS) is now being used for detecting chromosomal abnormalities in blastocyst trophectoderm (TE) cells from in vitro fertilized embryos. However, few data are available regarding the clinical outcome, which provides vital reference for further application of the methodology. Here, we present a clinical evaluation of NGS-based preimplantation genetic diagnosis/screening (PGD/PGS) compared with single nucleotide polymorphism (SNP) array-based PGD/PGS as a control. RESULTS: A total of 395 couples participated. They were carriers of either translocation or inversion mutations, or were patients with recurrent miscarriage and/or advanced maternal age. A total of 1,512 blastocysts were biopsied on D5 after fertilization, with 1,058 blastocysts set aside for SNP array testing and 454 blastocysts for NGS testing. In the NGS cycles group, the implantation, clinical pregnancy and miscarriage rates were 52.6% (60/114), 61.3% (49/80) and 14.3% (7/49), respectively. In the SNP array cycles group, the implantation, clinical pregnancy and miscarriage rates were 47.6% (139/292), 56.7% (115/203) and 14.8% (17/115), respectively. The outcome measures of both the NGS and SNP array cycles were the same with insignificant differences. There were 150 blastocysts that underwent both NGS and SNP array analysis, of which seven blastocysts were found with inconsistent signals. All other signals obtained from NGS analysis were confirmed to be accurate by validation with qPCR. The relative copy number of mitochondrial DNA (mtDNA) for each blastocyst that underwent NGS testing was evaluated, and a significant difference was found between the copy number of mtDNA for the euploid and the chromosomally abnormal blastocysts. So far, out of 42 ongoing pregnancies, 24 babies were born in NGS cycles; all of these babies are healthy and free of any developmental problems. CONCLUSIONS: This study provides the first evaluation of the clinical outcomes of NGS-based pre-implantation genetic diagnosis/screening, and shows the reliability of this method in a clinical and array-based laboratory setting. NGS provides an accurate approach to detect embryonic imbalanced segmental rearrangements, to avoid the potential risks of false signals from SNP array in this study. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2047-217X-3-30) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4326468 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43264682015-02-14 Clinical outcome of preimplantation genetic diagnosis and screening using next generation sequencing Tan, Yueqiu Yin, Xuyang Zhang, Shuoping Jiang, Hui Tan, Ke Li, Jian Xiong, Bo Gong, Fei Zhang, Chunlei Pan, Xiaoyu Chen, Fang Chen, Shengpei Gong, Chun Lu, Changfu Luo, Keli Gu, Yifan Zhang, Xiuqing Wang, Wei Xu, Xun Vajta, Gábor Bolund, Lars Yang, Huanming Lu, Guangxiu Du, Yutao Lin, Ge Gigascience Research BACKGROUND: Next generation sequencing (NGS) is now being used for detecting chromosomal abnormalities in blastocyst trophectoderm (TE) cells from in vitro fertilized embryos. However, few data are available regarding the clinical outcome, which provides vital reference for further application of the methodology. Here, we present a clinical evaluation of NGS-based preimplantation genetic diagnosis/screening (PGD/PGS) compared with single nucleotide polymorphism (SNP) array-based PGD/PGS as a control. RESULTS: A total of 395 couples participated. They were carriers of either translocation or inversion mutations, or were patients with recurrent miscarriage and/or advanced maternal age. A total of 1,512 blastocysts were biopsied on D5 after fertilization, with 1,058 blastocysts set aside for SNP array testing and 454 blastocysts for NGS testing. In the NGS cycles group, the implantation, clinical pregnancy and miscarriage rates were 52.6% (60/114), 61.3% (49/80) and 14.3% (7/49), respectively. In the SNP array cycles group, the implantation, clinical pregnancy and miscarriage rates were 47.6% (139/292), 56.7% (115/203) and 14.8% (17/115), respectively. The outcome measures of both the NGS and SNP array cycles were the same with insignificant differences. There were 150 blastocysts that underwent both NGS and SNP array analysis, of which seven blastocysts were found with inconsistent signals. All other signals obtained from NGS analysis were confirmed to be accurate by validation with qPCR. The relative copy number of mitochondrial DNA (mtDNA) for each blastocyst that underwent NGS testing was evaluated, and a significant difference was found between the copy number of mtDNA for the euploid and the chromosomally abnormal blastocysts. So far, out of 42 ongoing pregnancies, 24 babies were born in NGS cycles; all of these babies are healthy and free of any developmental problems. CONCLUSIONS: This study provides the first evaluation of the clinical outcomes of NGS-based pre-implantation genetic diagnosis/screening, and shows the reliability of this method in a clinical and array-based laboratory setting. NGS provides an accurate approach to detect embryonic imbalanced segmental rearrangements, to avoid the potential risks of false signals from SNP array in this study. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2047-217X-3-30) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-04 /pmc/articles/PMC4326468/ /pubmed/25685330 http://dx.doi.org/10.1186/2047-217X-3-30 Text en © Tan et al.; licensee BioMed Central. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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 Tan, Yueqiu Yin, Xuyang Zhang, Shuoping Jiang, Hui Tan, Ke Li, Jian Xiong, Bo Gong, Fei Zhang, Chunlei Pan, Xiaoyu Chen, Fang Chen, Shengpei Gong, Chun Lu, Changfu Luo, Keli Gu, Yifan Zhang, Xiuqing Wang, Wei Xu, Xun Vajta, Gábor Bolund, Lars Yang, Huanming Lu, Guangxiu Du, Yutao Lin, Ge Clinical outcome of preimplantation genetic diagnosis and screening using next generation sequencing |
title | Clinical outcome of preimplantation genetic diagnosis and screening using next generation sequencing |
title_full | Clinical outcome of preimplantation genetic diagnosis and screening using next generation sequencing |
title_fullStr | Clinical outcome of preimplantation genetic diagnosis and screening using next generation sequencing |
title_full_unstemmed | Clinical outcome of preimplantation genetic diagnosis and screening using next generation sequencing |
title_short | Clinical outcome of preimplantation genetic diagnosis and screening using next generation sequencing |
title_sort | clinical outcome of preimplantation genetic diagnosis and screening using next generation sequencing |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326468/ https://www.ncbi.nlm.nih.gov/pubmed/25685330 http://dx.doi.org/10.1186/2047-217X-3-30 |
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