From Errors during Cell Division to Clinical Outcomes: A Review about Mosaic Embryos

Abstract

Mosaicism, a condition characterized by the coexistence of chromosomally normal (euploid) and abnormal (aneuploid) cells within an embryo, poses significant challenges in assisted reproductive technologies (ART), including in vitro fertilization (IVF). Euploid cells have the appropriate number of chromosomes, essential for healthy development, whereas aneuploid cells, with either too many or too few chromosomes, can impair embryo viability, increase miscarriage risk, and reduce IVF success rates. This review provides an overview of mosaicism types, errors causing the aneuploidy, and implications for embryonic viability and pregnancy outcomes. The severity of mosaicism mostly depends on the proportion of aneuploid cells. Low-level mosaicism, involving a smaller fraction of abnormal cells, has a lesser impact on development and pregnancy outcomes, while high-level mosaicism can compromise embryo survival. Additionally, the nature of the chromosomal abnormalities, such as whole chromosome gains or losses, further influences developmental potential. Chromosomal instabilities may originate either during meiosis, the process of gamete formation, or during post-fertilization mitotic divisions. Meiotic errors, often associated with advanced maternal age, result in uniform aneuploidy across all embryonic cells and do not contribute to mosaicism. Conversely, mitotic errors, including anaphase lagging, spindle checkpoint failures or slow/stalled replication fork, occur during early embryonic divisions and are the primary source of mosaicism. These errors cause the initial identical cells to acquire different chromosomal compositions as the embryo divides, leading to a mosaic state. Pre-implantation Genetic Testing for Aneuploidy (PGT-A) is a valuable tool for identifying chromosomal abnormalities in embryos prior to transfer. PGT-A is not universally implemented, and variability in testing methodologies across clinics may lead to inconsistent outcomes, including the unnecessary discarding of potentially viable embryos. To address these concerns, this review states the importance for standardization in testing protocols and embryo assessment criteria. It proposes a hierarchical approach to embryo selection, prioritizing euploid embryos, followed by low level mosaic embryos, and reserving high level mosaic embryos as a last option. Finally, this review discusses the future of embryo selection, emphasizing advancements such as non-invasive genetic testing and artificial intelligence-driven assessment tools. These technologies could improve success rates, minimize ethical dilemmas surrounding embryo disposition, and enhance the safety and effectiveness of reproductive treatments