Nanopore sequencing in reproductive care

Abstract Aneuploid pregnancies, characterized by abnormal chromosome numbers, can result in miscarriages, fetal malformations, and developmental delays. Detecting chromosomal aberrations is crucial in prenatal and fertility care. In assisted reproductive techniques (ART), transferring euploid embryos improves treatment outcomes and reduces complications for both mother and fetus. However, individuals with balanced chromosomal rearrangements (BCRs) have a higher risk of infertility, recurrent miscarriages, and producing abnormal offspring due to unbalanced rearrangements. They may also be more susceptible to neurodevelopmental conditions. Preimplantation genetic testing for structural rearrangements (PGT-SR) allows for selection of embryos without chromosomal abnormalities, but current standard preimplantation aneuploidy screening (PGT-A) cannot differentiate between embryos with and without BCRs. In line with this, parental karyotypes are crucial for assessing infertility, but backlogs and time constraints often limit their use. Rapid diagnostic approaches are needed for prenatal and preimplantation aneuploidy detection. Our study aimed to accurately discriminate embryos with and without BCRs and detect hidden imbalances and complex rearrangements using PGT-SR with MinION/GridION Oxford Nanopore sequencing. We analyzed 51 IVF-PGT-SR cycles and 380 blastocysts from 34 at-risk couples. STORK was also used for rapid aneuploidy detection in 480 embryo and fetal samples. Our findings demonstrate the utility of long-read nanopore sequencing for high-resolution clinical PGT-SR, aneuploidy screening in embryos and fetal samples, and rapid molecular karyotyping in infertile patients. This represents a novel solution for comprehensive genetic analysis in reproductive medicine. Biography Dr. Svetlana Madjunkova, MD, MSc, PhD, is Senior Director and Head of Reproductive Genetics Department at CReATe Fertility Centre, Toronto, Canada and adjunct faculty with the Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, at the University of Toronto. Svetlana is a Board Director of the Canadian Fertility and Andrology Society, a Board Director of the Preimplantation Genetic Diagnosis International Society, and Chief Operating Officer of Reprobiogen. She has established a high-complexity lab to provide advanced clinical preimplantation testing, fertility-related genetic testing, and translational research in reproductive biology aimed at improving embryo selection, preimplantation testing, and further research in reproductive failure and improving outcomes in ART.