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Greater seminal vesicle volume is associated with higher sperm DNA fragmentation and lower motility, but not with sperm output: a cross-sectional study of 1,482 men

This cross-sectional study of 1,482 men reveals that greater seminal vesicle volume and abnormal echotexture are significantly associated with higher sperm DNA fragmentation and lower motility, though not with sperm output, suggesting that enlarged seminal vesicles can help identify men who may benefit from DNA fragmentation testing.

Original authors: Jingping Li, Chong Chen, Huimei Zheng, Weikang Chen, Shai Li, Lin Chai, Yikan Feng, Maolin Su

Published 2026-09-02

📖 5 min read🧠 Deep dive

CC BY 4.0

Original authors: Jingping Li, Chong Chen, Huimei Zheng, Weikang Chen, Shai Li, Lin Chai, Yikan Feng, Maolin Su

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

When a man seeks help for infertility, doctors usually begin by looking at the sperm itself. They count how many there are, check how well they swim, and examine their shape. These are the standard measures of male fertility, much like checking the engine oil and tire pressure of a car. However, there is a hidden layer of quality that these standard tests often miss: the integrity of the genetic code inside the sperm. This code, known as DNA, carries the instructions for building a new life. If this DNA is broken or fragmented, it can lead to failed pregnancies or miscarriages, even when the sperm count and swimming ability appear perfectly normal. For years, the cause of this hidden damage has been a mystery in many cases, leaving doctors without a clear way to predict who might be at risk or how to fix it.

Researchers in Hangzhou, China, decided to look for clues in a different place. Instead of focusing solely on the sperm, they turned their attention to the seminal vesicles, two small glands that sit just behind the bladder. These glands do not produce sperm; instead, they pump out the fluid that makes up most of the semen, acting as a protective bath for the sperm as they travel. The team wondered if the size or appearance of these glands, visible through a specialized ultrasound scan, could reveal something about the health of the sperm's DNA. They studied nearly 1,500 men who had undergone both a standard fertility evaluation and a detailed ultrasound of their reproductive organs. By comparing the measurements of these glands with the level of DNA damage in the men's sperm, the researchers uncovered a clear and surprising link.

The study found that men with larger seminal vesicles were significantly more likely to have high levels of DNA fragmentation in their sperm. The relationship was not a simple straight line; as the volume of the glands increased, the risk of DNA damage rose sharply, particularly in the men with the largest glands. In fact, for every noticeable increase in gland size, the likelihood of having a high level of DNA damage jumped by nearly double. This connection held true even after the researchers accounted for other factors that could influence fertility, such as the man's age, whether he had varicose veins in the scrotum, or how long he had waited since his last ejaculation. The data showed that men with the largest glands were far more likely to have sperm with broken DNA than men with average-sized glands.

Interestingly, this increase in gland size did not seem to affect the number of sperm a man produced. The study showed that while larger glands were linked to damaged DNA and slower swimming sperm, they did not change the total count of sperm or the concentration of sperm in the fluid. This distinction is crucial because it suggests the problem happens after the sperm are made. The sperm are created in the testicles, but they mature and pick up their fluid coating in the glands and tubes that follow. The fact that the sperm count remained steady while the DNA quality and swimming speed dropped points to a specific issue occurring in this post-testicular environment, likely involving inflammation or a blockage that prevents the glands from emptying properly.

The researchers also looked at the texture of the glands on the ultrasound images. Some glands appeared smooth and uniform, while others looked patchy or clumpy, a sign often associated with infection or inflammation. Men with these abnormal textures were also more likely to have damaged DNA. However, when the researchers looked at both the size and the texture together, the size of the gland was the stronger predictor. It appears that an enlarged gland is a more reliable sign of trouble than the texture alone, though the two often occur together. This finding suggests that a simple measurement of the gland's volume could serve as a red flag, helping doctors identify which men might need a specific test for DNA damage, a test that is not routinely performed on everyone.

To see if this issue could be treated, the team followed a small group of men who had been diagnosed with enlarged or inflamed glands and were treated with antibiotics. In the few men who were retested after the treatment, the level of DNA damage dropped significantly, and their sperm's swimming ability improved. While this was a small group and not a controlled experiment, the results hint that the problem might be reversible if the underlying inflammation is treated. The study does not prove that antibiotics will fix the issue for everyone, but it provides a strong biological reason to believe that treating the glands could improve sperm quality.

The authors conclude that an enlarged seminal vesicle is a tangible sign that a man's sperm may be suffering from hidden genetic damage. For men struggling to conceive, especially those whose standard tests look normal, this finding offers a new path forward. A simple ultrasound measurement could help doctors decide who needs further testing for DNA fragmentation, potentially saving couples from unnecessary treatments or failed pregnancies. While the study cannot yet say exactly why the glands enlarge or confirm that antibiotics are the cure for all, it establishes a clear connection between the size of these glands and the health of the sperm's genetic code, turning a routine scan into a powerful tool for understanding male fertility.

Technical Summary: Seminal Vesicle Volume, Sperm DNA Fragmentation, and Motility

Problem Statement
Sperm DNA fragmentation (SDF) is a critical determinant of reproductive success, associated with lower conception rates, poorer embryo development, and higher pregnancy loss. However, the etiology of high SDF is often unclear, particularly in men with unremarkable routine semen analysis (concentration, motility, morphology). While post-testicular factors such as oxidative stress and genital tract inflammation are known contributors, the specific role of seminal vesicle structure remains under-investigated. Previous studies have linked accessory gland infections to altered DNA fragmentation, but quantitative relationships between seminal vesicle volume/echotexture and SDF have not been systematically examined. This study addresses the gap in identifying clinical correlates of high SDF to guide selective testing.

Methodology
This was a retrospective cross-sectional study conducted at a single reproductive medicine center in Hangzhou, China, involving 1,482 men undergoing fertility evaluation.

Cohort Selection: Men were included if they underwent transrectal ultrasonography (TRUS) covering the seminal vesicles and a sperm DNA fragmentation index (DFI) test. The ultrasound was performed on the same day or within 90 days prior to the DFI test. The final analysis required complete data for bilateral total seminal vesicle volume, age, varicocele status, and abstinence intervals.
Exposure Definitions: The primary exposure was bilateral total seminal vesicle volume, calculated using the prolate-spheroid formula ( $0.52 \times \text{length} \times \text{diameter}^2$ ). Secondary exposures included largest-side volume, anteroposterior diameter, and echotexture (categorized as normal, heterogeneous, or flocculent).
Outcomes: The primary outcome was DFI $\ge$ 30% (high fragmentation) and continuous DFI. Key secondary outcomes included progressive motility, total motility, and semen volume. Comparison outcomes were sperm concentration and total sperm number.
Statistical Analysis: Logistic and linear regression models were adjusted for age, varicocele, and abstinence intervals (modeled as natural cubic splines). Associations were assessed per 1 standard deviation (SD = 2.73 mL) increase in volume. Non-linearity was tested using natural cubic splines. A separate exploratory cohort of 24 men with seminal vesicle abnormalities who received antibiotic monotherapy was analyzed for pre- and post-treatment changes.
Validation: Internal validation using bootstrap resampling was performed to assess model discrimination (Area Under the Curve, AUC). Sensitivity analyses covered abstinence specifications, examination intervals, and alternative DFI thresholds.

Key Results

Volume and DFI: Greater bilateral seminal vesicle volume was significantly associated with higher DFI. Each 1 SD increase in volume (2.73 mL) corresponded to an adjusted odds ratio (OR) of 1.83 (95% CI 1.60–2.10) for DFI $\ge$ 30%. The relationship was monotone but departed from linearity ( $P=0.006$ ), with the risk of high DFI rising sharply in the upper volume quintiles (adjusted OR 4.68 for the highest vs. lowest quintile).
Volume and Motility: Increased volume was associated with lower sperm motility. A 1 SD increase in volume correlated with a 17.0% reduction in progressive motility and a 13.7% reduction in total motility.
Volume and Sperm Output: Crucially, seminal vesicle volume showed no significant association with sperm concentration (−3.2%, $P=0.19$ ) or total sperm number (+1.9%, $P=0.48$ ). This pattern suggests the mechanism acts post-testicularly, affecting chromatin integrity and motility acquisition rather than spermatogenesis.
Echotexture: Heterogeneous or flocculent echotexture was associated with higher DFI (adjusted OR 4.23 per category increase). However, when adjusted for volume, the independent contribution of echotexture weakened, suggesting volume and abnormal texture are correlated features of the same underlying pathology.
Predictive Value: Adding seminal vesicle volume to a clinical model (age, varicocele, abstinence) improved the AUC for predicting DFI $\ge$ 30% from 0.657 to 0.729.
Antibiotic Response: In the small exploratory cohort of 24 men treated with antibiotics, the median DFI decreased by 13.5 percentage points, and progressive motility increased by 4.0 percentage points, while sperm concentration remained unchanged.

Significance and Claims
The paper claims that enlarged seminal vesicles serve as a specific clinical marker for identifying men at risk of high sperm DNA fragmentation and reduced motility, independent of sperm count. The findings suggest that the pathology lies in the post-testicular environment, likely involving inflammation, altered emptying, or partial obstruction, rather than defects in spermatogenesis.

The authors posit that because seminal vesicle dimensions are routinely recorded during TRUS for other indications, these measurements can help direct DFI testing toward men most likely to benefit, particularly those with unexplained infertility. The study supports the hypothesis that an enlarged seminal vesicle identifies a potentially modifiable subgroup, where anti-infective or anti-inflammatory interventions might improve sperm quality, though the authors explicitly state that the efficacy of antibiotics requires confirmation in controlled trials. The study concludes that while the association is robust, causality cannot be established due to the cross-sectional design, and prospective studies are needed to validate these ultrasound findings as a clinical tool.

Technical Summary: Seminal Vesicle Volume, Sperm DNA Fragmentation, and Motility

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