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Peer-reviewedCC BYHuman reproduction open

High sperm DNA fragmentation is associated with increased embryonic chromosomal abnormality: a retrospective study of 8 years involving 5637 couples undergoing ART.

4 affiliations
  1. 1NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Xiangya School of Basic Medical Sciences, Central South University, Changsha, China.
  2. 2School of Public Health, Hunan Normal University, Changsha, China.
  3. 3Health Science Center, Hunan Normal University, Changsha, China.
  4. 4Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha, China.

Abstract

Study question

Does sperm DNA fragmentation impair blastocyst chromosomal integrity?Summary answer

A high sperm DNA fragmentation index (DFI) is associated with an increased risk of blastocyst aneuploidy, particularly when the man has poor semen quality or when the female partner is aged ≥35 years.What is known already

Evidence linking sperm DFI to embryo development and blastocyst chromosomal integrity remains inconsistent, and controversy persists regarding its association with blastocyst aneuploidy detected by preimplantation genetic testing for aneuploidy (PGT-A). Existing studies have often been limited by small sample sizes, inconsistent DFI assays, and insufficient controls of key confounders.Study design size duration

This retrospective cohort study was conducted at a tertiary reproductive center. A total of 5637 infertile couples undergoing assisted reproduction between January 2016 and March 2023 were screened, and 3948 couples with complete data were included after applying standardized exclusion criteria.Participants/materials setting methods

All male partners who underwent sperm DNA fragmentation assessment using the Sperm Chromatin Structure Assay were included. Infertile couples were stratified by treatment modality, age of both partners, and male semen quality parameters. The primary outcome was blastocyst aneuploidy rate. Beta-binomial regression and zero-inflated beta-binomial regression were used to analyze embryonic outcomes, with model selection guided by the Akaike Information Criterion. Generalized linear mixed models were applied to account for clustering of multiple embryos within the same ovarian stimulation cycle.Main results and the role of chance

Higher DFI was associated with a higher rate of blastocyst aneuploidy. Compared to the low DFI group, the high DFI group had a significantly higher adjusted odds ratio (aOR) of aneuploidy (38.19% vs 24.42%, aOR = 1.35, 95% CI: 1.10-1.81, P = 0.042), while there was no substantial difference between the medium and low DFI group (25.78% vs 24.42%, aOR = 0.93, 95% CI: 0.76-1.13, P = 0.465). Particularly, when women were aged ≥35 years, the embryonic aneuploidy rate in the high DFI group was significantly higher than low DFI subgroup (52.02% vs 38.75%, aOR = 1.61, 95% CI: 1.12-2.32, P = 0.010). Also, among men with severe oligoasthenoteratozoospermia, high DFI significantly increased aneuploidy risk (36.81% vs 18.03%, aOR = 1.99, 95% CI: 1.11-3.57, P = 0.022). For all men aged <40 years, high DFI was associated with a reduced likelihood of high-quality blastocyst formation (aOR = 0.79, 95% CI: 0.64-0.99, P = 0.044).Limitations reasons for caution

Given the single-center retrospective design, residual confounding cannot be excluded despite rigorous statistical adjustment.Wider implications of the findings

Routine sperm DFI assessment may provide clinically meaningful information for infertile couples, particularly those with advanced maternal age or compromised male fertility. These findings support the integration of DFI into embryo risk stratification and individualized treatment planning, potentially improving reproductive outcomes and resource allocation.Funding

This work was supported by the National Natural Science Foundation for Young Scientists (72504291), Hunan Provincial Natural Science Foundation of China (2025JJ50703), and the Scientific Research Foundation of Reproductive and Genetic Hospital of CITIC-Xiangya (YNXM-202411).Disclosures

None of the authors have any conflicts of interest to disclose.Trial registration number

N/A.

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BibTeX
@article{lou2026high,
  title = {{High sperm DNA fragmentation is associated with increased embryonic chromosomal abnormality: a retrospective study of 8 years involving 5637 couples undergoing ART.}},
  author = {Li Lou and Pengcheng Xu and Pingyuan Xie and Huan Zhang and Yifan Gu and Fei Gong and Ge Lin and Guangxiu Lu and Jing Dai and Shujuan Ma},
  journal = {Human reproduction open},
  year = {2026},
  month = sep,
  doi = {10.1093/hropen/hoag082},
  url = {https://europepmc.org/article/MED/42870862},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - High sperm DNA fragmentation is associated with increased embryonic chromosomal abnormality: a retrospective study of 8 years involving 5637 couples undergoing ART.
AU  - Li Lou
AU  - Pengcheng Xu
AU  - Pingyuan Xie
AU  - Huan Zhang
AU  - Yifan Gu
AU  - Fei Gong
AU  - Ge Lin
AU  - Guangxiu Lu
AU  - Jing Dai
AU  - Shujuan Ma
PY  - 2026
DA  - 2026/09/16
JO  - Human reproduction open
DO  - 10.1093/hropen/hoag082
UR  - https://europepmc.org/article/MED/42870862
AB  - Study question  Does sperm DNA fragmentation impair blastocyst chromosomal integrity?Summary answer  A high sperm DNA fragmentation index (DFI) is associated with an increased risk of blastocyst aneuploidy, particularly when the man has poor semen quality or when the female partner is aged ≥35 years.What is known already  Evidence linking sperm DFI to embryo development and blastocyst chromosomal integrity remains inconsistent, and controversy persists regarding its association with blastocyst aneuploidy detected by preimplantation genetic testing for aneuploidy (PGT-A). Existing studies have often been limited by small sample sizes, inconsistent DFI assays, and insufficient controls of key confounders.Study design size duration  This retrospective cohort study was conducted at a tertiary reproductive center. A total of 5637 infertile couples undergoing assisted reproduction between January 2016 and March 2023 were screened, and 3948 couples with complete data were included after applying standardized exclusion criteria.Participants/materials setting methods  All male partners who underwent sperm DNA fragmentation assessment using the Sperm Chromatin Structure Assay were included. Infertile couples were stratified by treatment modality, age of both partners, and male semen quality parameters. The primary outcome was blastocyst aneuploidy rate. Beta-binomial regression and zero-inflated beta-binomial regression were used to analyze embryonic outcomes, with model selection guided by the Akaike Information Criterion. Generalized linear mixed models were applied to account for clustering of multiple embryos within the same ovarian stimulation cycle.Main results and the role of chance  Higher DFI was associated with a higher rate of blastocyst aneuploidy. Compared to the low DFI group, the high DFI group had a significantly higher adjusted odds ratio (aOR) of aneuploidy (38.19% vs 24.42%, aOR = 1.35, 95% CI: 1.10-1.81, P = 0.042), while there was no substantial difference between the medium and low DFI group (25.78% vs 24.42%, aOR = 0.93, 95% CI: 0.76-1.13, P = 0.465). Particularly, when women were aged ≥35 years, the embryonic aneuploidy rate in the high DFI group was significantly higher than low DFI subgroup (52.02% vs 38.75%, aOR = 1.61, 95% CI: 1.12-2.32, P = 0.010). Also, among men with severe oligoasthenoteratozoospermia, high DFI significantly increased aneuploidy risk (36.81% vs 18.03%, aOR = 1.99, 95% CI: 1.11-3.57, P = 0.022). For all men aged <40 years, high DFI was associated with a reduced likelihood of high-quality blastocyst formation (aOR = 0.79, 95% CI: 0.64-0.99, P = 0.044).Limitations reasons for caution  Given the single-center retrospective design, residual confounding cannot be excluded despite rigorous statistical adjustment.Wider implications of the findings  Routine sperm DFI assessment may provide clinically meaningful information for infertile couples, particularly those with advanced maternal age or compromised male fertility. These findings support the integration of DFI into embryo risk stratification and individualized treatment planning, potentially improving reproductive outcomes and resource allocation.Funding  This work was supported by the National Natural Science Foundation for Young Scientists (72504291), Hunan Provincial Natural Science Foundation of China (2025JJ50703), and the Scientific Research Foundation of Reproductive and Genetic Hospital of CITIC-Xiangya (YNXM-202411).Disclosures  None of the authors have any conflicts of interest to disclose.Trial registration number  N/A.
SN  - 2399-3529
ER  -