lunes, 23 de febrero de 2015

Genomics|Update|Non Communicable Diseases ► Reproductive Health

Genomics|Update|Non Communicable Diseases

Non Communicable Diseases wiith DNA

Volume 34  Number 7  February 19-26, 2015

Reproductive Health

 2014 Dec 4;3(1):30. doi: 10.1186/2047-217X-3-30. eCollection 2014.

Clinical outcome of preimplantation genetic diagnosis and screening using next generation sequencing.

Tan Y1Yin X2Zhang S3Jiang H4Tan K5Li J6Xiong B7Gong F8Zhang C9Pan X10Chen F11Chen S12Gong C6Lu C8Luo K8Gu Y8Zhang X13,Wang W14Xu X6Vajta G15Bolund L16Yang H17Lu G18Du Y19Lin G18.



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.


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.


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.


Blastocyst; Clinical outcome; Cryopreserved embryo transfer; Next generation sequencing; Preimplantation genetic diagnosis/screening

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