February 26, 2020

Thanks to recent research conducted by scientists at the Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU), a new avenue to in vitro fertilization (IVF) could soon be opened for prospective parents who were previously told it was unadvisable or impossible.

A perfect embryo contains 46 perfect chromosomes, but some have more, and others have fewer. The result is a common abnormality known as aneuploidy, which occurs in as many as 80 percent of human embryos. Because aneuploidy has been linked to a risk of in vitro fertilization failure, miscarriage and certain genetic orders or birth defects, mosaic embryos— those with both normal and abnormal cells—have not been considered ideal candidates for IVF transfer.

For prospective mothers who only produce mosaic embryos, this can mean the IVF journey may end before it begins. But that could change very soon.

The ONPRC study, led by Shawn L. Chavez, PhD, an assistant professor of reproductive and developmental sciences at ONPRC at OHSU, and an assistant professor of obstetrics and gynecology, and physiology and pharmacology in the OHSU School of Medicine, is the first to confirm mosaic embryos can adapt and persist in development in a nonhuman primate model, resulting in positive IVF outcomes.

Using advanced time-lapse imaging and single-cell sequencing techniques to precisely track the development of mosaic embryos of a rhesus macaque, Chavez and team identified a relationship between mosaicism and two other biological processes: cell fragmentation and blastomere exclusion.

In utero and after IVF, large cells formed by the division of a fertilized egg, known as blastomeres, may break down into small pieces called cellular fragments. These fragments, it seems, can serve as a sort of cellular cleanup crew.

“We found that both the blastomeres and their fragments can act as trash bins within the embryo. As DNA-carrying cells divide and/or fragment, the embryo appears to naturally identify which blastomeres have genetic abnormalities and stop them from further development,” said Chavez.

He further explained that by the stage in which an embryo would implant into the uterus, these abnormal cells or DNA have been visibly excluded from the rest of the embryo, suggesting that imperfect IVF embryos could be considered for use in transfer and could possibly endure in utero.

According to Paula Amato, MD, an associate professor of obstetrics and gynecology in the OHSU School of Medicine, this discovery could positively impact IVF processes for humans in the future.

 “While selecting embryos with a normal chromosome complement is preferred and carries a high chance of pregnancy success, it is not a guarantee,” she explained. “For patients with only mosaic embryos available for transfer, these findings suggest that in some cases, these embryos will result in apparently normal pregnancies.”

Ongoing research will use live-cell time-lapse imaging to better understand the relationship between aneuploidy, cell fragmentation and blastomere exclusion within the embryo. The scientists believe these results could open up new avenues for testing mosaic human embryos.

“We expect that the overall results will be similar to the story of the ‘dark horse,’” said Chavez. “While not perceived as a contender at the start of the IVF race, a mosaic embryo may still be capable of winning and resulting in something wonderful.”

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