A recent study led by scientists at the Loke Centre for Trophoblast Research, University of Cambridge, suggests that a common test used in fertility clinics to assess embryo viability during IVF may overestimate the number of embryos with abnormalities.
The research team developed a new imaging technique that allows real-time observation of embryos as they develop. This method revealed that some abnormalities in embryos arise later in development than previously believed. As a result, current tests may detect errors in cells destined to become the placenta rather than those forming the fetus. Abnormalities in placental cells are less likely to impact fetal health.
Pre-implantation genetic testing for aneuploidy is often offered to older women or those with recurrent miscarriages or multiple IVF failures. When such testing finds chromosomal abnormalities, embryos may be discarded, potentially requiring patients to undergo additional cycles of treatment.
Professor Kathy Niakan, Director of the Loke Centre for Trophoblast Research and Co-Chair of Cambridge Reproduction, stated: “Having a baby through assisted conception can be very challenging. Most embryos fail to develop or to implant, and even those that are good quality may not be transferred. Much more basic research is needed to inform future clinical practice and improve rates of assisted conception.”
To better understand early embryo development, Professor Niakan and colleagues collaborated with researchers at the Francis Crick Institute to create a high-resolution live imaging method. The details were published in Nature Biotechnology.
The technique involves tagging DNA inside cell nuclei with a fluorescent protein so it can be seen under a microscope. Using light-sheet microscopy, researchers observed 3D embryo development without causing damage.
Dr Ahmed Abdelbaki, first author and postdoctoral researcher at the Loke Centre for Trophoblast Research, said: “This is the first time that this very gentle method, with much higher resolution, has been used. It meant that we could watch the embryos as they developed over a two-day period, the longest continuous time that this process has been observed.”
Co-author Professor Ben Steventon from the Department of Genetics at the University of Cambridge added: “The unique design of the microscope allows for multiple precious embryos to be watched simultaneously, and from both sides. This has allowed the team to catch events that have previously been missed. It’s a proof of the power of direct observation to uncover unexpected findings in human biology.”
The study found abnormal cell divisions could occur late in embryo development. Professor Niakan explained: “We were extremely surprised to discover that abnormal cell divisions can happen from scratch at a very late stage of human development. It was only by using a new imaging technique that it was possible to see this happening.”
Of 13 embryos analyzed by the team, about 10% of cells showed chromosomal abnormalities arising from issues during DNA copying or division processes.
These abnormalities typically appeared in outer blastocyst cells—the layer sampled during pre-genetic testing—which forms the placenta.
Professor Niakan’s group is now investigating whether similar spontaneous abnormalities occur within inner cell layers.
Embryos used in this research were donated by families treated at Bourn Hall Clinic and Create Fertility following successful pregnancies.
The work received support from Wellcome, Francis Crick Institute (funded by Cancer Research UK, Medical Research Council and Wellcome), and Engineering and Physical Sciences Research Council.