Professor Co-Leads BCR Study on Infertility and Recurrent Early Pregnancy Loss

Balanced chromosomal rearrangements (BCR-translocations or inversions) are a relatively common reason for infertility (2.2%), recurrent pregnancy losses (6-9%) and an underlying cause of unbalanced structural rearrangements seen in numerous clinical syndromes.

The Reproductive Genetics team at the CReATe Fertility Centre, led by Dr. Svetlana Madjunkova and Professor with UofT ObGyn Dr. Clifford Librach, in collaboration with Dr. Jared Simpson (OICR) just published a groundbreaking study on detection of chromosomal rearrangements in embryos in the New England Journal of Medicine (NEJM). For the first time, they describe a new method, based on a cutting-edge technology called nanopore sequencing, to distinguish embryos having the balanced chromosome rearrangement vs those which don’t. Using this technology, they developed comprehensive pre-implantation genetic testing for structural rearrangements (PGT-SR) to achieve breakpoint assessment resolution down to a single base. This now allows parents to avoid passing BCRs on to their offspring and future generations.

“Carriers of balanced translocation (BCR) have a high reproductive risk, and have a risk to have children with chromosomal abnormalities, and in some cases risk for neurodevelopmental or neuropsychiatric conditions," said Dr. Librach. "BCR carriers ideally would prefer to avoid passing on the chromosomal structural rearrangement to their children and future generations. The current approach to avoid these complications involves PGT-SR to select balanced euploid (46 chromosome) embryos for transfer. However, distinguishing embryos carrying the BSR vs. non-carriers, as well as detection of possible cryptic microdeletions/duplications at breakpoint sites, is not possible using standard next generation sequencing (NGS). The main limitation is related to the short DNA reads from standard NGS, making detection of breakpoints virtually impossible, even with extensive high depth sequencing and complicated bioinformatics analysis. Here, we performed long-read sequencing using Oxford Nanopore Technologies handheld MinION™ sequencer to accurately allow the detection and mapping of structural rearrangements. This is the first report using this new technology for this purpose in a clinical setting."

Dr Librach’s Reproductive Genetics team at CReATe is continuing research activities to develop and improve approaches to advance assisted reproduction technologies and help patients create healthy families.

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