Introduction

Have you heard of pyospermia? Also known as leukocytospermia, this condition occurs when there is an excessive number of white blood cells (WBCs) in a man’s semen. If left untreated, pyospermia can negatively impact long-term reproductive health, contributing to oxidative stress, DNA damage in sperm, and reduced fertility, yet many men are unaware they even have it. Depending on the severity, treatment options can range from antibiotics and anti-inflammatory medications to surgical intervention. In this article, we’ll discuss how it affects fertility, and when surgery might be necessary to help you understand what pyospermia is.

What is pyospermia and why does it matter?

A hidden cause of infertility

In our native immune system, white blood cells (WBCs) play a crucial role in our health protection. WBCs are increasingly produced in response to wounds, inflammation, or infections. Although they play a protective role in our body, an abnormally high number of white blood cells in semen can cause damage. 

A concentration greater than one million round cells per milliliter of ejaculate confirmed by peroxidase staining is considered an abnormal condition, and this may lead to a condition known as pyospermia or leukocytospermia. An unusually high number of WBCs in pyospermia may impair fertility. It is observed in up to 23% of men undergoing evaluation for infertility.^1,2 However, it is also vital to recognise the complexity of pyospermia’s causes. Some studies have shown that the presence of white blood cells in semen does not always correlate with bacterial infection. Examples of noninfectious factors are environmental toxins, autoimmune conditions, and congenital abnormalities. Some reports indicated that about 15 percent of men have male genital l tract infections (MGTIs). MGTIs could contribute to an increase in the amount of WBCs in semen. 

MGTIs are the third most common cause of male infertility—after idiopathic infertility (28.4%) and varicocele (18.1%)—with some studies reporting prevalence rates as high as 36.7%.³

What is the mechanism?

During the immune response, white blood cells (WBCs) release reactive oxygen species (ROS), which are essential regulators of key fertilisation processes, and they play a critical role in fighting infections. ROS are related to the following responsibilities under physiological conditions.

Firstly, ROS are related to the active degree of sperm, which can trigger vigorous tail moments, helping to penetrate the zona pellucida. In addition, ROS takes part in sperm capacitation through tyrosine kinase phosphorylation (a redox-dependent step), and they activate phospholipase A2, which facilitates the release of enzymes to breach the oocyte’s outer layer (acrosomal reaction).

However, excessive levels of ROS can disrupt the redox balance, which is required for healthy sperm function. The elevated amount of ROS causes the overreaction of the semen’s antioxidant defense mechanisms, leading to oxidative stress.

This imbalance damages sperm through three primary mechanisms: lipid peroxidation, DNA fragmentation, and mitochondrial dysfunction.⁴

What are the diagnostic approaches to Leukocytospermia?

The direct counting of round cells is cost-effective and recommended by the American Urological Association (AUA). But the results could be unreliable, as it could be challenging to distinguish leukocytes from other similar cells under microscopy. A round cell’s count outnumbers or equals 1.0 × 10⁶ per milliliter is considered confirmatory testing. 

Immunochemistry provides specific identification of granulocytes, lymphocytes, and macrophages by detecting monoclonal antibodies (e.g., CD45/CD53); however, its clinical utility is limited by high costs, lack of standardised protocols and time-intensive procedures, despite endorsement by ASRM and AUA for confirmation.

The seminal granulocyte elastase test is another way to reflect granulocyte activity and inflammation by measuring elastase-inhibitor complexes (Ela/α1-PI) in seminal plasma.

Elevated levels (≥230 µg/L) correlate with genital tract infections and are more common in infertile men. The test’s expense and limited standalone diagnostic value hinder routine use. In addition, peroxidase staining measures peroxidase-rich granulocytes and macrophages based on a benzidine-based reaction result. 

In practice, combining methods improves accuracy, such as initial screening with peroxidase staining or elastase testing, followed by immunochemistry for confirmation. Clinicians must weigh expenses, accessibility, and diagnostic precision when selecting approaches, particularly in infertility evaluations where accurate leukocyte quantification guides treatment decisions.⁷

When is surgery needed for pyospermia?

There is currently no formal guideline for leukocytospermia in terms of suitable treatment from either the American Urological Association (AUA) or the American Society for Reproductive Medicine (ASRM). The Canadian Urological Association (CUA) suggests that treatment is not indicated in general, although antimicrobial therapy may be considered in cases of male infertility. According to the European Association of Urology (EAU), antibiotics may improve certain sperm parameters; still, there is no solid evidence regarding their improvement in increasing pregnancy rates. While some studies found that the application of antibiotics or antioxidants might improve sperm quality and reduce leukocyte levels, overall findings remain conflicting and inconclusive.

Non-surgical Interventions

Currently, pyospermia is primarily managed through non-surgical treatments, including antibiotics, anti-inflammatory agents, antioxidants, and lifestyle changes. Genital tract infections are common and can also be found in men without symptoms. Genital tract infections are often due to bacteria such as E. coli, Staphylococcus, and Klebsiella. In addition, lifestyle adjustments are an option. Some smokers suffer from pyospermia, as inflammation is triggered by tobacco toxins and particles. Similarly, chronic alcohol use and cannabinoids may damage testicular tissue, increasing leukocyte presence in semen.

Surgical interventions

Currently, there is no direct surgical treatment specifically for leukocytospermia. However, surgery may be applied in some cases where an underlying anatomical or obstructive issue is caused by persistent inflammation and white blood cell elevation in semen.

Firstly, leukocytospermia could be exacerbated by non-infectious factors, such as substance abuse and varicocele, defined as excessive dilatation of the pampiniform venous plexus of the spermatic cord, even though genital tract infections are a common cause.

Varicocele, affecting 10–20% of the general male population, is far more prevalent in infertile men: 35–40% of those with primary infertility and 45–80% of those with secondary infertility.^5,7 Due to anatomical differences, Varicocele often arises on the left side of the vein. The left gonadal vein drains into the left renal vein at a near-perpendicular angle, creating higher hydrostatic pressure compared to the right side, where the gonadal vein connects directly to the inferior vena cava.⁸ Varicocelectomy is a surgical correction of the dilated scrotal veins. It may improve semen quality by restoring normal blood flow, reducing scrotal temperature, and alleviating oxidative damage.

In addition, pyospermia can also be caused by an obstruction in the ejaculatory ducts, which prevents normal semen flow. Structural anomalies of the ejaculatory ducts are easily detected and monitored by high-resolution transrectal ultrasonography (TRUS). Compared to vasography, TRUS is less invasive. Even if there are no pathognomonic signs of ejaculatory duct obstruction, the situation in patients ought to remain assessed and diagnosed carefully. Once the diagnosis is confirmed, Transurethral Resection of the Ejaculatory Ducts (TURED) may be recommended to restore normal semen flow, reduce inflammation, and improve fertility outcomes.⁶

In cases where sperm cannot be ejaculated naturally, either due to blockages or non-obstructive causes, surgical sperm retrieval methods such as Testicular Sperm Extraction (TESE) or Microsurgical Epididymal Sperm Aspiration (MESA) may be used.

Psychological and emotional support

Last but not least, it’s important not to overlook the emotional and mental sides of infertility and chronic reproductive issues that can take on men and their partners. Pyospermia is similar to other fertility challenges, it can lead to stress, anxiety, and even relationship strain. Mental health support and fertility counseling should be offered and considered as an essential part of a comprehensive treatment plan to help patients overcome difficulties when they face invasive treatments or long-term uncertainty.

Summary

Pyospermia, also known as leukocytospermia, is a disorder in which semen contains an excessive amount of white blood cells, which possibly impacts fertility in males. The reasons for pyospermia could be infections ( i.e., bacteria) or non-infectious factors ( i.e., chemicals, habits). Pyospermia is treated mainly by non-surgical treatment, for example, antibiotics, antioxidants, or lifestyle adjustments, in most circumstances. Surgical treatment, such as varicocelectomy, TURED, or sperm retrieval procedures, is taken into consideration when there are structural obstructions or abnormalities. In short, to maintain fertility and enhance reproductive health, early diagnosis and specialised treatment are essential.