Effect of varicocele surgical repair on antisperm antibody positivity rate in patients with clinical varicocele: a systematic review and meta-analysis.
Li S, Chen T, Gao B, Zhong C • Frontiers in endocrinology • 2026
Varicocele repair was associated with a significantly lower ASA positivity rate compared with preoperative levels (RR = 0.42; 95% CI: 0.35–0.52; P < 0.00001), with the lowest pooled RR observed in the microsurgical subgroup (RR = 0.32).
Key Findings
Results
Varicocele repair was associated with a significantly lower antisperm antibody (ASA) positivity rate compared with preoperative levels.
Pooled risk ratio (RR) = 0.42; 95% CI: 0.35–0.52; P < 0.00001
Analysis included 10 studies with 13 comparisons and 722 patients
A random-effects model was used to calculate pooled RRs
Data were sourced from studies identified through systematic search of PubMed, Web of Science, Embase, Cochrane Library, CNKI, VIP, Wanfang, and SinoMed up to April 30, 2026
Results
Subgroup analysis by surgical technique showed that all three surgical approaches were associated with lower postoperative ASA positivity rates, with microsurgical repair showing the lowest pooled RR.
Microsurgical subgroup had the lowest pooled RR of 0.32
Laparoscopic and high ligation subgroups also showed lower postoperative ASA positivity rates
A significant subgroup difference was observed across surgical techniques (P = 0.01)
Subgroup analyses were pre-specified by surgical technique
Results
Sensitivity analyses confirmed the robustness of the primary finding across different analytical approaches.
Excluding studies with back-calculated data yielded a pooled RR of 0.43, consistent with the primary analysis (RR = 0.42)
Excluding studies with a 6-month follow-up yielded a pooled RR of 0.40, also consistent with the primary analysis
Both sensitivity analyses confirmed the direction and magnitude of the primary result
Results
Three studies reporting continuous ASA levels could not be pooled due to extreme heterogeneity and were described narratively.
These three studies were excluded from the quantitative meta-analysis and reported narratively instead
Extreme heterogeneity precluded meaningful pooling of continuous ASA level data
Discussion
The clinical utility of ASA testing for surgical decision-making in varicocele patients remains uncertain despite the observed reduction in ASA positivity after repair.
The authors note that varicocele repair 'may influence immune-related alterations reflected by ASA positivity'
The paper states that 'the clinical utility of ASA testing for surgical decision-making remains uncertain'
The study design consisted of before-after studies, limiting causal inference due to the absence of a control group
Publication bias assessment was conducted as part of the analysis
Methods
The systematic review included studies from both English-language and Chinese-language databases to minimize publication bias.
Eight databases were searched: PubMed, Web of Science, Embase, Cochrane Library, CNKI, VIP, Wanfang, and SinoMed
Search was conducted up to April 30, 2026
Only before-after studies reporting ASA positivity rates or ASA levels in men with clinical varicocele were eligible for inclusion
What This Means
This research suggests that surgical repair of varicocele — an enlargement of veins in the scrotum that is a common and treatable cause of male infertility — is associated with a meaningful reduction in the rate of antisperm antibodies (ASA) in affected men. Antisperm antibodies are immune proteins that the body can produce against its own sperm, potentially impairing fertility. Analyzing data from 10 studies covering 722 patients, the researchers found that after varicocele surgery, men were on average 58% less likely to test positive for antisperm antibodies compared to before surgery. Among different surgical approaches, microsurgery showed the strongest reduction in ASA positivity.
The finding held up across multiple sensitivity analyses, suggesting the result is not driven by any single study or methodological choice. However, three studies that measured ASA as a continuous level (rather than simply positive or negative) showed such extreme variation between studies that their results could not be meaningfully combined, highlighting that measurement of ASA is not yet standardized across research settings.
This research suggests that varicocele repair may reduce immune-related interference with sperm by lowering antisperm antibody levels, which could be one mechanism by which the surgery may improve fertility outcomes. However, the authors caution that it remains unclear whether ASA testing should influence decisions about whether to pursue surgery, and all included studies compared patients to themselves before and after surgery rather than to an untreated control group, which limits the strength of conclusions that can be drawn. Further controlled research would be needed to clarify the role of ASA in surgical decision-making for varicocele.
Li S, Chen T, Gao B, Zhong C. (2026). Effect of varicocele surgical repair on antisperm antibody positivity rate in patients with clinical varicocele: a systematic review and meta-analysis.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1925219