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

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.