The Puzzle of Mosaicism: Mechanisms and Clinical Implications in Preimplantation Genetic Testing

Chromosomal mosaicism in preimplantation embryos, characterized by cells with varying genotypes, arises due to mitotic errors after fertilization. These errors, including anaphase lag, mitotic nondisjunction, or cytokinesis failure, typically occur during early embryonic divisions when maternal factors predominantly regulate development. The impact of mosaicism on embryonic viability varies based on the stage and nature of the chromosomal errors, potentially reducing implantation rates and increasing miscarriage risks. However, mosaic embryos can occasionally self-correct through apoptosis of abnormal cells or selective growth of euploid cells, enabling the development of healthy blastocysts.

Advancements in genetic screening, particularly next-generation sequencing (NGS), have improved mosaicism detection, although challenges remain in accurately interpreting its clinical significance. NGS identifies mosaicism with higher sensitivity than previous methods like fluorescence in situ hybridization (FISH) or array comparative genomic hybridization (aCGH). Nonetheless, discrepancies in detection rates and sampling errors complicate clinical decision-making.

Patients undergoing preimplantation genetic testing must be counseled on the potential outcomes of transferring mosaic embryos, especially when euploid options are unavailable. While mosaic embryos offer a chance for pregnancy, they carry an increased risk of miscarriage and uncertain long-term outcomes. Personalized genetic counseling and improved screening methodologies are essential for refining patient care and optimizing in vitro fertilization (IVF) outcomes. Further research is needed to understand the mechanisms and implications of mosaicism, ensuring evidence-based practices in embryo selection and transfer.