ArticleFrontiers in endocrinology2026
Clinical and morphological correlates of embryonic mosaicism: a retrospective cohort study of 10,469 blastocysts in PGT-A cycles.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Chromosomal mosaicism presents a significant clinical and diagnostic challenge in preimplantation genetic testing for aneuploidy (PGT-A) cycles. While the meiotic origins of uniform aneuploidy are well-established, the predictors and mechanisms driving mosaicism remain less understood. This study aimed to investigate the clinical and embryological factors associated with the occurrence of mosaic embryos. Method: This retrospective cohort study analyzed 10,469 biopsied blastocysts derived from 2,484 PGT-A cycles between January 2019 and June 2024. The cohort included couples treated for advanced maternal age (AMA), recurrent miscarriage, or recurrent implantation failure. We evaluated the associations between parental baseline characteristics (e.g., age, semen quality), blastocyst morphological parameters (developmental day, expansion stage, inner cell mass [ICM] grade, and trophectoderm [TE] grade), and the incidence of mosaic embryos detected via next-generation sequencing (NGS). Multivariate GEE regression was performed to identify independent correlates. Results: The results revealed that mosaicism most frequently involved chromosomes X, 16, and 18. Upon evaluation of the biopsied cohort, multivariate analysis identified advanced maternal age as an independent factor associated with mosaic embryo formation (OR = 1.63, P < 0.01). Furthermore, suboptimal blastocyst morphological characteristics showed a strong correlation with mosaicism, including delayed development to Day 6 (OR = 1.25), lower expansion stage (stages 3 + 4 vs. 5 + 6; OR = 1.86), lower ICM grade (grade B vs. A; OR = 1.37), and lower TE grade (grade C vs. A+B; OR = 1.45) (all P < 0.05). Subgroup analyses confirmed consistent association between delayed blastulation, poor morphological scores, and a higher likelihood of mosaicism across diverse indications. Notably, unlike aneuploidy-which is predominantly associated with parental age and teratozoospermia-mosaicism primarily arises from postzygotic mitotic instability, a phenomenon uniquely correlated with lower morphological grading. Conclusion: Advanced maternal age and suboptimal blastocyst morphological development are independently and strongly associated with the occurrence of chromosomal mosaicism. These findings highlight the distinct pathophysiological mechanisms and associated clinical profiles between aneuploidy and mosaicism, providing valuable reference data for prioritizing embryo selection strategies, genetic counseling and future research in PGT-A practice.
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