New Study is First to Demonstrate Whole Genome Sequencing of Biopsied Embryos During In Vitro Fertilization (IVF) Can Detect De Novo Mutations Responsible for Most Genetic Diseases

Livingston, NJ, February 12, 2015 – Reprogenetics, the largest U.S. genetics laboratory specializing in Preimplantation Genetic Preimplantation Genetic Diagnosis (PGD), announced today the publication of new clinical data in the February issue of Genome Research demonstrating that de novo single base mutations can be detected in embryos after in vitro fertilization (IVF).  Small biopsies containing just a few cells from the embryos prior to transfer back to the mother showed clinically relevant sensitivity and specificity using a novel advanced whole-genome sequencing (WGS) screening process. The study is the first to show that a large majority of single base de novo mutations, which cause a disproportionately high percentage of genetic diseases, can be detected by PGD. De novo mutations only occur in reproductive cells and in embryos after fertilization. These mutations are not present in the blood of the parents. Standard PGD cannot detect the mutations because the tests are not sensitive.

In addition to Reprogenetics, researchers from Complete Genomics, a leader in accurate whole human genomic sequencing, BGI-Shenzhen ("BGI"), a leading international genomics organization based in Shenzhen, China, and the New York University (NYU) Fertility Center at the NYU Langone Medical Center collaborated on the study.

"These findings are a significant step in developing advanced whole-genome sequencing as the 'ultimate' screen to find the healthiest embryos through PGD," says Santiago Munné, Ph.D., Founder and Director of Reprogenetics and Founder of Recombine. "This new approach can detect almost all genome variation, which may eliminate the need for further genetic testing during pregnancy or after birth while ensuring selection of the healthiest embryo for transfer to the future mother."

In the study, advanced massively parallel WGS was performed on three 5-10 cell biopsies from  embryos cultured for five days in the laboratory. Experimentally derived haplotypes and barcoded read data were used to detect and phase de novo single base mutations in the embryos, achieving a false positive rate of approximately one error per Giga base, that is calling erroneously a mutation in one out of one Giga of letters, and resulting in fewer than 10 errors per embryo. The data show an approximately 100-fold lower error rate than previously published from 10 cells, and is the first demonstration that advanced WGS can accurately identify de novo mutations despite numerous false positives associated with the extensive DNA amplification required for deep sequencing.

"That de novo mutations can be detected with such high sensitivity and an exceptionally low error rate using so few embryonic cells is remarkable," says Brock Peters, Ph.D., Director, Research at Complete Genomics and the study's lead investigator. "Combining massively parallel DNA sequencing with barcoded sequence analysis obtained through our long fragment read technology provides an extremely efficient and cost-effective solution for clinically accurate WGS, and we look forward to continuing further research in this area."

De novo mutations, including single nucleotide and short indel mutations, may cause severe intellectual disability, autism, epileptic encephalopathies and other serious congenital diseases.  Since these mutations are unique to the specific sperm and egg that create an embryo, whole genome analysis of the parents is unable to detect them.

"Up to five percent of newborns are affected by diseases caused by a genetic defect," says Alan Berkeley, M.D., Professor and Director, Department of Obstetrics and Gynecology at the New York University Fertility Center. "Our WGS approach is both comprehensive and targeted in identifying healthy embryos. This may alleviate some of the emotional and physical stress of IVF, especially for those couples at risk of transmitting a genetic disorder."

Additional Study Information

In the study, entitled "Complete and Accurate WGS on IVF Embryos," both parents and paternal grandparents were also analyzed to allow for accurate measurements of false positive and false negative error rates. Overall, more than 95 percent of each embryonic genome was called, starting with approximately 10 cells (as few as approximately 50pg of DNA). Data also demonstrated how small de novo deletions could be detected. These results suggest that WGS using barcoded DNA has high potential as part of the PGD process to maximize comprehensiveness in detecting disease-causing mutations and may ultimately reduce the incidence of genetic diseases detected via PGD. In addition, the data open possibilities for clinical analysis of circulating fetal cells (CFC), circulating tumor cells (CTC) and other micro-biopsies in addition to IVF embryo biopsies. This may have application in non-invasive cancer screening.

To demonstrate the potential of WGS to analyze embryo biopsies, three sequencing libraries were made from biopsies of up to 10 cells from two individual 5-day-old blastocyst stage embryos from the same couple.  For the purpose of de novo mutation validation, two separate biopsies were removed and two separate libraries were made from a single embryo.  As a control, three additional libraries were made from approximately 10 blood cells from unrelated anonymous donors.

The full Genome Research article may be accessed at

About Reprogenetics

Reprogenetics is the largest genetics laboratory in the US specializing in preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD), with over 50,000 performed procedures, >300,000 tested embryos, and hundreds of publications. Dr. Santiago Munné and Dr. Jacques Cohen founded Reprogenetics in 2000 after extensive experience in PGD and IVF. Reprogenetics offers a comprehensive and personalized service to its referring Fertility centers and their patients. Genetic counselors are intricately involved in the process and interact routinely with patients pursuing all diagnostic tests and services to improve pregnancy outcomes. Reprogenetics has locations all over the world including locations in the USA, Spain, Europe, Asia, UK, Japan, Peru and South America. For more information please visit

About Complete Genomics

Complete Genomics is a leader in whole human genome sequencing based in Mountain View, California. Using its proprietary sequencing instruments, chemistry, and software, the company has sequenced more than 20,000 whole human genomes over the past three years. The company's mission is to improve human health by providing researchers and clinicians with the core technology and commercial systems to understand, prevent, diagnose, and treat diseases and conditions. Additional information can be found at