Unlocking the Genetic Code: Understanding Segmental Aneuploidy and Low Mosaic Embryo Transfers
The ASRM Joint Meeting in Denver, CO covered a range of topics related to reproductive medicine, including segmental aneuploidy and low mosaic embryo transfers. In her presentation, Nisha Mathew, MS LCGC Genetic Counselor at Seattle Reproductive Medicine, highlighted the importance of understanding the genetic makeup of embryos for successful IVF outcomes.
The DNA master codebook of the human body is made up of ACTGs, which are read in a specific code to create the instructions for our body's development. Chromosomes, condensed DNA packages, play an important role in this process. In healthy individuals, there are 46 chromosomes, inherited from the egg and sperm sources, respectively.
Aneuploidy, an extra chromosome such as in the case of Down syndrome, can be detected by preimplantation genetic testing for aneuploidy (PGTA), reducing the risk of miscarriage. As the age of the egg increases, there is an increased risk of aneuploidy. Aneuploidy originates from the egg and arises from how the genetic material divides.
Two types of cell division exist in human cells: meiosis and mitosis. Meiosis creates reproductive cells, while mitosis occurs in all other cells in the body. During meiosis, an egg cell with 23 chromosomes should be fertilized with a sperm cell with 23 chromosomes. The embryo undergoes several mitotic cell divisions to reach the blastocyst stage, where we can see the inner and outer layer of cells that form the trophectoderm, which makes up the cell mass, and the other layer that makes the baby. Genetic testing from trophectoderm gives us a good representation of what is going on with the baby. However, errors can occur during the process of mitosis and cell division.
PGT-A is used to detect aneuploidy, where embryos are classified as euploid normal, aneuploid segmental, or aneuploid whole chromosome (monosomy or trisomy). Mosaic embryos can also be labeled as low or high level embryos, set by the laboratory based on the percentage of abnormal cells. Different PGT-A labs can set different ranges for high or low level mosaic embryos.
A mosaic embryo is a combination of normal and abnormal cells in the mixture. It is possible that the biopsy of trophectoderm may have had chromosomally normal or abnormal cells in the mixture, or there may have been an artifact in the mixture. When compared to other types of mosaic embryos, a 2021 study of 1,000 embryo transfers showed that euploid embryos had more favorable outcomes than all mosaic outcomes. The segmental group performed similarly to the low segmental group, while the low whole chromosomal embryos performed less favorably. The high-level mosaic group fared the worst. A non-selection study showed that low-level mosaicism is similar to euploid and that there is no evidence that low-level mosaicism affected miscarriage rates or increased chromosomal abnormalities when transferring mosaics.
In conclusion, understanding the genetic makeup of embryos is crucial for successful IVF outcomes. PGT-A can help detect aneuploidy, and mosaic embryos can be labeled as low or high level based on the percentage of abnormal cells. While the outcomes of mosaic embryo transfers can vary, studies have shown that low-level mosaicism is similar to euploid and does not increase the risk of miscarriage or chromosomal abnormalities. These findings suggest that low-level mosaic embryos may still be a viable option for couples undergoing IVF.
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