Objective: To analyze the data available on the biologic significance of white blood cells (WBC) in semen of infertility patients.

Data resources: The relevant literature was reviewed.

Results: It is not possible to identify reliably WBC by conventional sperm staining techniques. The peroxidase method is sufficient for quantification of granulocytes, but immunocytology is the gold standard for the detection of all WBC populations in semen. Granulocytes are the most prevalent WBC type in semen (50% to 60%), followed by macrophages (20% to 30%) and T-lymphocytes (2% to 5%). The prevalence of leukocytospermia (> 10(6) WBC/mL semen) among male infertility patients is approximately 10% to 20%. There is controversy on the significance of WBC in semen. Whereas some authors did not observe sperm damage in the presence of leukocytospermia, others have found evidence that WBC are significant cofactors of male infertility: [1] seminal WBC numbers were higher in infertility patients than among fertile men; [2] leukocytospermia was associated with decreased sperm numbers and impaired sperm motility; [3] WBC damaged sperm function and hamster ovum penetration in vitro and were important prognostic factors for IVF-ET failure. Because of absence of clinical symptoms, the origin of WBC is difficult to determine. Normally, most WBC appear to originate from the epididymis because vasectomized men show very few WBC in semen. On the other hand, leukocytospermic samples show low citric acid levels, pointing to asymptomatic prostatitis as a source of WBC in semen. Surprisingly, approximately 80% of leukocytospermic samples are microbiologically negative. In some cases Chlamydia trachomatis might have triggered a persistent inflammatory reaction leading to leukocytospermia. Sperm damage by WBC can be mediated by reactive oxygen species, proteases and cytokines. Furthermore, genital tract inflammation facilitates the formation of sperm antibodies. As seminal plasma has strong anti-inflammatory properties and because there is only short contact between sperm and WBC in prostatitis and seminal vesiculitis, inflammations of the epididymis and testis are likely to have the largest impact on sperm.

Conclusions: There is ample evidence that WBC can affect sperm function. Further studies are needed to define cofactors that increase or decrease the risk of sperm damage by WBC.