Spectrum of Various Mosaicism Types According to Female Age: An Analysis of 36,506 Blastocysts Using Preimplantation Genetic Testing for Aneuploidy.

Background/

Objectives

Mosaicism in preimplantation embryos has important implications for embryo selection and reproductive outcomes. This study investigates the age-related frequency of mosaicism, analyzes its subtypes, and evaluates its clinical significance.

Methods

A total of 36,506 blastocysts were analyzed using next-generation sequencing-based preimplantation genetic testing for aneuploidy between January 2021 and December 2023. The overall frequencies of euploid, aneuploid, mosaic, and no-call embryos were 20%, 56%, 23%, and 1%, respectively. In this study, we propose a new classification. Embryos were classified into two categories: Mosaic-A, referring to embryos identified as mosaic in standard genetic testing reports, and Mosaic-B, which includes both Mosaic-A and aneuploid embryos containing mosaicism.

Results

The proportion of Mosaic-A embryos significantly decreased with maternal age (31% in women <35 years, 30% at 35-37 years, 23% at 38-40 years, 16% at 41-42 years, and 10% in women >42 years). By contrast, Mosaic-B embryos, which include Mosaic-A and aneuploid embryos with mosaicism, increased with age (46%, 49%, 53%, 56%, and 62% across the same age groups). Notably, as maternal age advanced, low-level complex mosaicism decreased, whereas high-level complex mosaicism significantly increased (p < 0.001, chi-square test for trend). Other mosaicism subtypes followed similar trends. These findings suggest that the increase in high-level complex mosaicism resulted from a higher incidence of post-zygotic mitotic errors occurring earlier in development and affecting a larger proportion of cells in older women.

Conclusions

This study underscores the significance of incorporating a broader classification of mosaicism, including Mosaic-A and B, to enhance understanding of the biological behavior of mosaic embryos according to age and highlights the clinical importance of cryopreserving high-level or complex mosaic embryos for transfer in women of advanced age.