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Physicist, Startup Founder, Blogger, Dad

Saturday, December 13, 2014

Preimplantation genetic diagnosis and screening using next generation sequencing

This BGI study reports pre-implantation sequencing of hundreds of blastocysts. 42 ongoing pregnancies were achieved, with 24 babies born thus far.
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 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.

4 comments:

FuturePundit said...

I do not understand the relationship between the 60 and the 80 here:

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.

60 out of 114 women got implanted? But 49 out of 80 women got a pregnancy started? How can the 80 number be higher than the 60 number?

steve hsu said...

Not sure -- implantation rate might refer to individuals (60 women had an implantation cycle) whereas pregnancy refers to transferred eggs (80 eggs transferred)? I think there are more details in the paper itself.

Ch said...

What's next after the IQ puzzle has been solved? Will BGI be working on other traits?

gwern said...

Well, first they need to solve IQ! Since the results from their genome-sequencing still haven't been announced and that was a small sample, cracking that puzzle is clearly not going to happen overnight.

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