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Peer-reviewedCC BY 4.0Frontiers in Endocrinology

Parental determinants of blastocyst euploidy in a predominantly recurrent-pregnancy-loss PGT-A cohort: limited predictive value of female age, BMI, AMH and sperm DNA fragmentation

  1. 1Department of Reproductive Medicine, General Hospital of Northern Theater Command
  2. 2Department of General Surgery, Shengjing Hospital of China Medical University

Abstract

Background: Embryonic aneuploidy is a major factor affecting clinical outcomes in assisted reproduction. PGT-A improves embryo selection, but the clinical factors associated with euploidy remain debated.

Methods: This retrospective study included 588 PGT‑A cycles. We used embryo‑level GLMMs to evaluate the associations of female age, female BMI, AMH, male age, male BMI, and sperm DFI with embryo euploidy. We performed univariable and multivariable analyses, assessed model performance (AUC, R ² , calibration), and conducted internal validation via patient-clustered bootstrap (200 replicates). Subgroup analyses by female age were performed with FDR correction.

Results: Among 2,357 blastocysts, 1,299 (55.1%) were euploid. In univariable analysis, female age, male age, and male DFI were significantly associated with euploidy. After multivariable adjustment, only female age (OR = 0.87, p = 0.011) and male DFI (OR = 0.89, p = 0.006) remained independent predictors. Model performance was poor (apparent AUC = 0.571; bootstrap-corrected AUC = 0.574; apparent marginal R ² = 0.018 and conditional R ² = 0.036; apparent calibration slope = 0.985; bootstrap-corrected calibration slope = 0.913), indicating weak signal strength and limited generalizability. Subgroup analyses showed some nominal associations, but none survived FDR correction (all q > 0.05). Among 588 cycles with complete covariate data, 90.3% had at least one euploid blastocyst; among all 613 biopsied cycles and 637 started cycles, the rates were 89.89% and 86.50%, respectively.

Conclusion: Female age and male DFI were independently associated with euploidy, but the model’s discrimination remained poor after optimism correction (bootstrap-corrected AUC = 0.574; apparent calibration slope = 0.985, bootstrap-corrected calibration slope = 0.913), and these variables therefore lack sufficient value for clinical use. Subgroup analyses by female age were exploratory and hypothesis-generating, and no statistically significant age-modified association between male DFI and euploid embryos persisted after FDR correction. Future models incorporating embryo-specific data and larger samples are needed.

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BibTeX
@article{tan2026parental,
  title = {{Parental determinants of blastocyst euploidy in a predominantly recurrent-pregnancy-loss PGT-A cohort: limited predictive value of female age, BMI, AMH and sperm DNA fragmentation}},
  author = {Chang Tan and Xiliang Wang and Dan Tong and Pengshu Zou and Xun Liu and Yuexin Yu},
  journal = {Frontiers in Endocrinology},
  year = {2026},
  month = oct,
  doi = {10.3389/fendo.2026.1909930},
  url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1909930/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Parental determinants of blastocyst euploidy in a predominantly recurrent-pregnancy-loss PGT-A cohort: limited predictive value of female age, BMI, AMH and sperm DNA fragmentation
AU  - Chang Tan
AU  - Xiliang Wang
AU  - Dan Tong
AU  - Pengshu Zou
AU  - Xun Liu
AU  - Yuexin Yu
PY  - 2026
DA  - 2026/10/28
JO  - Frontiers in Endocrinology
DO  - 10.3389/fendo.2026.1909930
UR  - https://www.frontiersin.org/articles/10.3389/fendo.2026.1909930/full
AB  - Background: Embryonic aneuploidy is a major factor affecting clinical outcomes in assisted reproduction. PGT-A improves embryo selection, but the clinical factors associated with euploidy remain debated.  Methods: This retrospective study included 588 PGT‑A cycles. We used embryo‑level GLMMs to evaluate the associations of female age, female BMI, AMH, male age, male BMI, and sperm DFI with embryo euploidy. We performed univariable and multivariable analyses, assessed model performance (AUC, R ² , calibration), and conducted internal validation via patient-clustered bootstrap (200 replicates). Subgroup analyses by female age were performed with FDR correction.  Results: Among 2,357 blastocysts, 1,299 (55.1%) were euploid. In univariable analysis, female age, male age, and male DFI were significantly associated with euploidy. After multivariable adjustment, only female age (OR = 0.87, p = 0.011) and male DFI (OR = 0.89, p = 0.006) remained independent predictors. Model performance was poor (apparent AUC = 0.571; bootstrap-corrected AUC = 0.574; apparent marginal R ² = 0.018 and conditional R ² = 0.036; apparent calibration slope = 0.985; bootstrap-corrected calibration slope = 0.913), indicating weak signal strength and limited generalizability. Subgroup analyses showed some nominal associations, but none survived FDR correction (all q > 0.05). Among 588 cycles with complete covariate data, 90.3% had at least one euploid blastocyst; among all 613 biopsied cycles and 637 started cycles, the rates were 89.89% and 86.50%, respectively.  Conclusion: Female age and male DFI were independently associated with euploidy, but the model’s discrimination remained poor after optimism correction (bootstrap-corrected AUC = 0.574; apparent calibration slope = 0.985, bootstrap-corrected calibration slope = 0.913), and these variables therefore lack sufficient value for clinical use. Subgroup analyses by female age were exploratory and hypothesis-generating, and no statistically significant age-modified association between male DFI and euploid embryos persisted after FDR correction. Future models incorporating embryo-specific data and larger samples are needed.
SN  - 1664-2392
ER  -