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Are Mosaic Embryos the Past and Future of IVF?

Not every embryo starts off containing 46 perfect chromosomes; some have “aneuploidy,” that is, too few or too many chromosome copies. Aneuploidy is common and affects as many as 80 percent of human embryos and because aneuploidy has been linked to decreased IVF success, miscarriage and certain genetic disorders, “mosaic” embryos, those with both normal and abnormal (aneuploid) cells, have not been considered the best embryos for IVF transfer.

Research published on March 4, 2019 in Genome Research from the Oregon Health and Science Center, one of the world’s best primate research centers, confirms that in a nonhuman primate model, embryos with mosaicism are able to adapt to their genetic abnormalities and continue into fetal development with healthy IVF outcomes. Using advanced time-lapse imaging and single-cell genetic sequencing techniques to accurately track the development of mosaic embryos of a rhesus monkey, Dr. Shawn Chavez and the Oregon team identified a unique relationship between mosaicism and two other well-known biological processes: cell fragmentation and blastomere exclusion.

Following natural conception, as well as after IVF, the large embryonic cells formed by the division of a fertilized egg, are known as blastomeres, and these early blastomeres may break down into smaller pieces called cellular fragments. As blastomeres either divide normally or fragment, the embryo appears to able to have a “red light” signal, identifying which blastomeres have genetic abnormalities and stopping these cells from further development. By five to six days of development (the stage that an embryo implants into the uterus), these abnormal cells have been visibly excluded from the embryo, suggesting that mosaic IVF embryos could be considered for use in transfer with resulting developmental success and livebirth.

This investigation has implications for human IVF and could positively impact IVF processes for humans in the near future. For example, in patients with only mosaic embryos available for transfer, these findings as well as previous human reports (e.g., Grifo and colleagues) suggest that in some cases, these embryos can result in apparently normal pregnancies.

No doubt, prior to preimplantation genetic diagnostic testing, mosaic embryos were unwittingly transferred and, no doubt, some of the eight million IVF babies born since 1978 began as mosaic embryos! The team at the Oregon National Primate Research Center has ongoing research employing live-cell time-lapse imaging to better understand the relationship between aneuploidy, cell fragmentation and blastomere exclusion within the early embryo.

Reference:

Brittany L. Daughtry, Jimi L. Rosenkrantz, Nathan H. Lazar, Suzanne S. Fei, Nash Redmayne, Kristof A. Torkenczy, Andrew Adey, Melissa Yan, Lina Gao, Byung Park, Kimberly A. Nevonen, Lucia Carbone, Shawn L. Chavez. Single-cell sequencing of primate preimplantation embryos reveals chromosome elimination via cellular fragmentation and blastomere exclusion. Genome Research, 2019; 29 (3): 367 DOI: 10.1101/gr.239830.118

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