July 8, Dr. Dagan Wells of the NIHR Biomedical Research Centre at the University of Oxford, UK announced the first birth achieved by analyzing embryos using a new genome sequencing technique known as “next generation sequencing”.
A researcher said the advance “provides an unprecedented insight into the biology of embryos.”
NGS is a powerful method capable of decoding entire genomes and is expected to revolutionize embryo selection for in vitro fertilization. Using the new method, scientists are able to produce vast quantities of DNA data each sample tested, revealing detailed information on the inheritance of genetic disorders, chromosome abnormalities and mitochondrial mutations present in the DNA. When applied to the assessment of embryos, the NGS will allow the concurrent analysis of serious inherited disorders and lethal chromosome abnormalities.
According to the Centre’s announcement of findings to the European Society of Human Reproduction and Embryology, “The identification of an embryo destined to implant in the uterus and form a pregnancy remains the holy grail of IVF. On average, only around 30% of embryos currently selected for transfer actually implant. The reason for this high failure rate is unknown, but the prime suspects are unidentified genetic or chromosomal defects. Several genetic screening methods have been introduced over the past decade, but all have been shown to have drawbacks (and have not realized their potential) when tested in randomized clinical trials. This new NGS technique developed by Wells and colleagues, however, seems to overcome the major drawbacks of current methods.”
By using NGS scientists will be able to produce complete chromosome information to reveal serious gene defects as well as abnormalities often resulting in miscarriages. NGS-based analysis can be completed in only 16 hours, eliminating the need for embryo freezing while scientists await results. NGS testing also could reduce the costs of embryo screening, an expensive add-on to the costs of IVF.
This particular study was designed to test the accuracy and predictability of NGS in embryo selection. The validation was performed on multiple cells from cell-lines with known chromosome abnormalities, gene defects (cystic fibrosis) or mitochondrial DNA mutations. Once the research team demonstrated a high accuracy levels, the method was applied clinically and ultimately resulted in two IVF single embryo transfers, both leading to healthy pregnancies. The first pregnancy yielded delivery of a healthy boy in June.
Wells reports, “Many of the embryos produced during infertility treatments have no chance of becoming a baby because they carry lethal genetic abnormalities. Next generation sequencing improves our ability to detect these abnormalities and helps us identify the embryos with the best chances of producing a viable pregnancy. Potentially, this should lead to improved IVF success rates and a lower risk of miscarriage. … Next generation sequencing is a way which could make chromosome testing more widely available to a greater number of patients, improving access by cutting the costs. Our next step is a randomized clinical trial to reveal the true efficacy of this approach – and this will begin later this year.”
Wells received his doctoral degree in Genetics University College London. He has been actively involved in pre-implantation genetic diagnosis and the study of human gametes and embryos for almost two decades. Following supervisory responsibilities in the molecular diagnostics field at the UCL Centre for PGD in London, Wells moved to the United States where he joined Reprogenetics, one of the largest providers of PGD services in the United States. In 2003 he initiated Reprogenetics’ highly successful single gene PGD program. Reprogenetics now provides PGD services to more than 150 IVF centers in the United States. Wells later joined the faculty of YaleUniversityMedicalSchool, where he spent four years as an Assistant Professor, before returning to the United Kingdom in 2007.
Wells’ research group currently is located in the Nuffield Department of Obstetrics and Gynaecology at the University of Oxford. His current research program is focused on increasing understanding of the molecular genetic processes underlying gametogenesis and pre-implantation development. The group has attracted funding from multiple public and private organizations, including the National Institutes of Health and the Medical Research Council (UK). Wells currently serves on the Editorial Boards of several international medical journals, including Molecular Human Reproduction, Reproductive Biomedicine Online and Prenatal Diagnosis. Dr Wells is a Fellow of the Royal College of Pathologists, UK.
In the field of public information related to applications of his research, Wells is associated with myfuturebaby.com, a web portal that promotes information on the ABC’s of fertility as well as diagnosis and management of infertility factors.