Common IVF test misses some genetic abnormalities in embryos

During in vitro fertilization (ECO), embryos undergo genetic testing before transfer to the uterus, but researchers have found that a widely used test cannot detect genetic abnormalities that develop in embryos just before implantation. However, it is unclear what this means for selecting embryos most likely to developing into a healthy pregnancy.

A procedure called preimplantation genetic testing for aneuploidy (PGT-A) is performed approximately 5 to 6 days after fertilization. It involves removing a few cells from the outer layer of the embryo to check for extra or missing chromosomes, which can increase the risk of miscarriage. But this test is only a snapshot in time: The embryo's cells continue to divide and multiply before implantation, potentially introducing genetic changes that go undetected.

So, Ahmed Abdelbaki from the University of Cambridge and his colleagues recorded the development of human embryos for 46 hours after they were thawed, simulating the timeline between testing and implantation. Typically, implantation of the embryo after it is transferred to the uterus takes from 1 to 5 days. Previous attempts to do this were only able to image embryos for about 24 hours because they are very sensitive to the light emitted by conventional microscopes. Instead, the team used a light microscope, which illuminates only a thin section of the embryo at a time, reducing exposure to light and allowing for longer observations.

Researchers injected a fluorescent dye that binds to DNA into 13 human embryos, allowing them to monitor the formation of genetic abnormalities in real time. They observed 223 cells dividing in the samples and found that 8 percent of the cells showed chromosome misalignment. This occurs when chromosomes line up in the center of a cell before dividing into two cells. A mismatch greatly increases the risk that the resulting cells will have extra or missing chromosomes, which can prevent implantation, increase the chance of miscarriage, or cause conditions such as Down syndrome.

This suggests that “later there may be [genetic] changes in the embryo after the point at which we screen for PGT-A,” says Lily Zimmerman at Northwell Health in New York State.

These errors were limited to the outer layer of cells that make up the placenta, not those in the center of the embryos that develop into fetuses. Previous studies have shown that embryos with certain genetic abnormalities in their outer cells may still leads to successful pregnancy. So it's possible that these genetic errors won't affect the viability of the embryos, Abdelbaki says.

“In my opinion, this study really shows that there is still a lot more research to be done in terms of screening embryos to see if they are [they] genetically normal or abnormal,” says Zimmerman. And it's unclear how genetic errors that occur between screening and implantation might affect the viability of embryos, she says. The study also looked at only a small number of embryos, so it's difficult to know whether these results apply to embryos more broadly, she says.