Factors associated with de novo aneuploidy across different preimplantation genetic testing cycles: a retrospective cohort study.

OBJECTIVE

Previous studies on factors influencing embryonic aneuploidy have produced inconsistent results. This study aimed to identify predictors of de novo aneuploidy in distinct patients undergoing preimplantation genetic testing for structural chromosome rearrangements (PGT-SR), aneuploidy (PGT-A) and monogenic disorders (PGT-M).

METHODS

We analyzed associations between maternal age, paternal age, anti-Müllerian hormone (AMH), maternal body mass index (BMI), controlled ovarian stimulation (COS) protocol, sperm parameters, blastocyst expansion degree, inner cell mass (ICM) grade, trophectoderm (TE) grade, and de novo aneuploidy using generalized linear mixed models (GLMM).

RESULTS

The incidence of de novo aneuploidy was 19.5% (PGT-SR), 32.1% (PGT-A), and 31.2% (PGT-M). Multivariate analysis showed that advanced maternal age and blastocyst expansion degree were significant predictors in the PGT-SR cohort. In the PGT-A cohort, significant associations were observed for maternal age, AMH, PGT indication, expansion degree, ICM grade, and TE grade. In the PGT-M cohort, TE grade was significantly associated with aneuploidy in women aged ≥ 30 years. No independent effects were found for semen parameters or stimulation protocols in any cohort. Whole-chromosome aneuploidies most frequently involved chromosomes 22, 16, and 21. There were no dominant chromosomes for segmental-chromosome aneuploidy. Notably, the aneuploidy rate remained consistently low (~20%) in women aged ≤ 30 years.

CONCLUSION

In this study, advanced maternal age (≥35 years) emerged as a robust predictor of de novo aneuploidy. The expansion degree ex hibited an association with de novo aneuploidy across both the PGT-SR and PGT-A cohorts. The TE grade seemed to be correlated with de novo aneuploidy, especially in the PGT-A cohort, and the TE grade exhibited stronger predictive performance compared to the ICM grade. No independent predictive effect was detected for semen parameters or stimulation protocols. These findings support the implementation of individualized risk assessment and embryo selection in distinct PGT patient cohorts.