Preimplantation Genetic Testing for Aneuploidies
Mosaicism is a biological phenomenon that results in populations of cells with distinct genetic compositions in the same individual. Mosaicism in embryos is primarily caused by errors in mitosis during the early stages of development. Mitosis is the process of cell division that allows an embryo to grow. Each cell divides into two “daughter” cells that are meant to be genetically identical to the original “parent” cell. Mitotic nondisjunction is a random event where chromosomes fail to distribute equally into daughter cells, resulting in cells with missing or extra chromosomes. When this occurs in a small group of embryonic cells, the embryos will contain a mix of chromosomally normal and abnormal cells. While nondisjunction during mitosis leads to mosaicism, nondisjunction during meiosis – a different cell division process – leads to an embryo with a cell population containing 100% of the same aneuploidy type.
Mosaicism can occur on several levels: gene, sub-chromosome, and chromosome. Sub-chromosome refers to mosaicism of chromosome segments rather then the entire chromosome. Only the sub-chromosome and chromosome levels are considered in preimplantation genetic screening.
Clinical outcome is variable, although only a minority of mosaic embryos result in healthy pregnancies. Compared to a euploid embryo, a mosaic embryo is much more likely to result in implantation failure, miscarriage, or a newborn affected with a genetic disorder.
The impact of mosaicism in IVF is still in preliminary research stages and should be considered carefully when making a clinical decision. Genetic counseling is highly recommended when considering the transfer mosaic embryos. Studies recommend that patients undergo an additional IVF cycle to obtain a euploid embryo instead of transferring a mosaic embryo.
Previda® testing uses next-generation sequencing combined with complex bioinformatic algorithms to count chromosome copy number accurately and precisely. When chromosome copy number deviates from the normal status (2n), but does not reach a full monosomy (n) or trisomy (3n) status, it is classified as mosaic. An embryo is called low level mosaic if 20-40% of the cells are deemed abnormal.