Normal WBC Count in Semen and IVF Implications
The normal upper limit for white blood cells in semen is 1 × 10⁶ WBC/mL (1 million WBC/mL), and leukocytospermia (WBC counts exceeding this threshold) is associated with reduced IVF success rates due to oxidative sperm damage. 1
Defining Normal WBC Counts
The World Health Organization threshold of 1 × 10⁶ WBC/mL defines leukocytospermia, which occurs in approximately 10-20% of male infertility patients and up to 29% in some series. 2, 3
Conventional sperm staining techniques cannot reliably identify WBCs—the peroxidase method is sufficient for quantifying granulocytes, but immunocytology is the gold standard for detecting all WBC populations. 2, 3
Round cells seen on routine semen analysis are NOT equivalent to WBCs—only 35% of patients with >1 million round cells/mL actually have true leukocytospermia when tested with immunohistochemical staining. 4
WBC Composition in Semen
Granulocytes comprise 50-60% of seminal WBCs, followed by macrophages (20-30%) and T-lymphocytes (2-5%). 2, 3
Special stains are required to differentiate germ cells from somatic cells when evaluating round cells in semen. 1
Critical Implications for IVF
Impact on Sperm Quality
Even WBC counts below the WHO threshold cause oxidative stress—samples with any detectable leukocytes (even between 0-1 × 10⁶/mL) show significantly higher ROS levels and lower antioxidant capacity compared to samples with no leukocytes. 5
Oxidative stress correlates directly with rising WBC count (r = 0.39; P < 0.001), meaning there is no truly "safe" minimum WBC level. 5
Leukocytospermia is associated with:
IVF-Specific Outcomes
WBCs are important prognostic factors for IVF-ET failure, as documented in multiple studies showing that leukocytospermia predicts poor IVF outcomes. 2, 3
Sperm damage by WBCs is mediated through reactive oxygen species, proteases, and cytokines, all of which can compromise fertilization potential. 2
Complete removal of WBCs from semen samples used for assisted reproduction may help reduce oxidative stress and improve outcomes. 5
Clinical Management Algorithm
When to Test for WBCs
Do NOT routinely perform semen cultures unless pyospermia is present, as routine cultures have not been prospectively demonstrated to benefit infertile couples. 1
Order specific WBC testing (peroxidase stain or immunocytology) when:
Source Identification
Approximately 80% of leukocytospermic samples are microbiologically negative, suggesting non-infectious inflammation. 2, 3
Low citric acid levels in leukocytospermic samples point to asymptomatic prostatitis as a common source. 2
Chlamydia trachomatis may trigger persistent inflammatory reactions leading to leukocytospermia even after the infection has cleared. 2, 3
Inflammations of the epididymis and testis likely have the largest impact on sperm because seminal plasma has strong anti-inflammatory properties that protect against brief WBC contact in prostatitis. 2
Important Caveats
The presence of >10 round cells/high-power field does NOT confirm pyospermia—immunohistochemical staining is required because most round cells are immature germ cells, not WBCs. 4
Counting round cells per milliliter correlates better with true WBC counts than counting per high-power field. 4
Genital tract inflammation facilitates antisperm antibody formation, which can compound fertility problems beyond direct oxidative damage. 2, 3
For IVF preparation, sperm washing procedures should aim for complete WBC removal rather than accepting any threshold, given that oxidative stress occurs even at very low WBC levels. 5