What is pyospermia​?

Pyospermia is an abnormal laboratory finding of a high volume of leucocytes (white blood cells) in male semen, usually detected during a fertility screen sample analysis.¹ It can be enumerated as the presence of more than one million leukocytes in 1 mL of semen. It plays a significant role in male infertility, as large numbers of white cells can be correlated with inferior sperm functionality, negatively impacting fertilisation capabilities.² Underlying infectious or inflammatory disorders have been linked as the main cause of leucocytospermia.¹

Male fertility correlates with the quantity and quality of sperm in ejaculated semen. Infertility can be described as a disease of the male or female reproductive system, defined by the failure to achieve a clinical pregnancy after 12 months of regular unprotected sexual intercourse.⁴ The male factor is the leading cause of infertility in 20% of cases and contributes to the issues in about 50%.³ There are numerous origins for male factor infertility, with infectious processes contributing to about 15% of such cases.⁴

What are the causes of pyospermia?

Pyospermia has a number of causes, including Bacterial (Urinary Tract Infections/ Sexually Transmitted Infections), Fungal, Viral and Parasitic. It can be difficult to distinguish between the etiological causes of pyospermia early on in the course of the disease, as all causes demonstrate similar symptoms and a similar clinical presentation. Microscopy and culture laboratory findings help us differentiate, and the follow-up treatment options differ depending on the causative agent. However, risk factors can differ; for bacterial infections, these include having unprotected sex, poor genital hygiene and regular urinary tract infections. For fungal infections, risk factors include antibiotic overuse and immunosuppression, i.e. being an HIV or diabetes sufferer.  

How can bacteria cause pyospermia?

What are the most common bacteria identified as causes of pyospermia?

Male genital tract infections are difficult to detect as they are asymptomatic in many cases. Therefore, in cases of male infertility, the clinician should request a urogenital microbiological workup. The most common causative uropathogens identified in pyospermia are:

• Staphylococcus aureus
• Staphylococcus saprophyticus
• Escherichia coli

In a study by Mostafa et al. (2022 on 140 patients with pyospermia, 92 of them (65.7%) yielded a bacterial growth incidence rate of above 28.3%, 19.6% and 13.0% respectively.³ Other UTI agents included Proteus mirabilis, Klebsiella pneumonia, Proteus vulgaris and Pseudomonas aeroginosa, with STI agents including cases of Chlamydia trachomatis and Neisseria gonorrhea.³

How exactly can bacterial infections lead to pyospermia​?

Bacterial infections can invade the male reproductive organs via ascending infection or hematogenous spread.¹ They can trigger an inflammatory response, which attracts leukocytes to the infection site (the testes, epididymis), leading to their buildup in seminal fluid. These WCC release reactive oxygen species (ROS), which are oxygen-free radicals responsible for damaging the lipid components of the sperm membrane, along with enzymes and cytokines.¹ Lipid peroxidation (LPO) is initiated. Once the ROS has penetrated the cell membrane and infiltrated the cell, it then attacks and destroys the mitochondrial DNA. Adenosine triphosphate (ATP) production is decreased, leading to loss of energy for sperm, impaired motility and activity, ultimately contributing to male infertility.^1,7 Bacteria can also directly adhere to the sperm surface by fibres called ‘pili’, decreasing sperm motility and causing sperm cell death.⁷

What risk factors are associated with bacterial infections​ and pyospermia?

Bacterial infections are potentially treatable causes of male infertility. However, due to the rising resistance against common antibiotics and patients' poor compliance with their treatment regimen, the usefulness of antibiotics in resolving complicated GTI or restoring fertility may be impeded.³

How can fungi cause pyospermia?

How significant are fungal infections in pyospermia​?

Although a less common cause of pyospermia, fungal infections have become an emerging cause of concern, particularly in immunocompromised individuals, with studies contributing 2-10% of pyospermia cases to a fungal cause.  The most frequently isolated fungal pathogens include Candida albicans, Aspergillus species and Cryptococcus species in extremely rare cases. Fungal infections are most frequently asymptomatic.

How exactly can fungal infections lead to pyospermia​?

The male urogenital tract becomes colonised with the fungal organism and causes urethritis, balanoposthitis, ulcers, pseudotumors and prostatitis.⁵ The colonisation triggers an immune response, leading to white blood cell infiltration into the site. These WCC release ROS, causing oxidative stress in addition to pro-inflammatory cytokines (IL-6, TNF-α). This creates a hostile environment for sperm, causing sperm DNA to break down, reducing motility and disrupting normal sperm morphology, decreasing survival rate and fertilisation potential. Some fungal infections can also cause blockages in the vas deferens, preventing sperm from reaching the urethra, pre-ejaculation. Persistent infections can lead to pain, discomfort, or erectile dysfunction.⁶

What risk factors are associated with fungal infections​ and pyospermia?

• Diabetes
• Poor hygiene habits
• Immunosuppression
• Unprotected sexual contact with an infected person
• Antibiotic use reduces the numbers of normal urogenital flora, allowing fungi to flourish.
• Smoking and excessive alcohol consumption ³

How is pyospermia diagnosed?

What is the typical clinical presentation and symptoms​ associated with pyospermia?

In a bacterial or fungal case of pyospermia, the following symptoms may or may not present, as most cases are asymptomatic:

• Low-grade urogenital pain (testicular, pelvic discomfort)
• Pain or burning sensation when urinating.
• Blood in semen
• Ejaculatory dysfunction
• Urethral discharge (suggestive of fungal infection)
• Low sperm count

What laboratory investigations​ are performed in order to diagnose pyospermia?

• Semen analysis – a sample is provided after masturbation following 3-5 days of sexual abstinence
• Microscopic evaluation is performed to enumerate the WBCs to determine true pyospermia of ≥1 million WBCs/mL of semen
• The peroxidase test allows the scientist to differentiate between immature sperm cells   (peroxidase negative) and WBCs (peroxidase positive)  
•  Conventional ‘gold standard’ diagnostic techniques, including Gram staining and semen culture with organism growth taking from 48 hours to several weeks for slow-growing organisms⁷
• Fungal staining can be performed when clinical suspicion suggests.
• Molecular techniques, notably Polymerase chain reaction (PCR), which helps to identify the organism to species level with a faster turnaround time than traditional methods
• A combination of PCR and semen culture is suggested. This enables a quick organism identification along with antibiotic testing
• Biopsy – if conditions persist following treatment, a biopsy can assess underlying testicular conditions, such as malignancy, or determine if spermatogenesis is occurring in the testes⁸
• Ultrasound or imaging can be prescribed if genitourinary structural abnormalities are suspected⁸

What are the suggested treatment strategies for pyospermia?

Treatment strategies for pyospermia depend on the underlying cause.

1. Antibiotic therapy- For a bacterial infection, treatment is typically guided through identification of the organism growing on semen culture and follow-up sensitivity testing. Most commonly identified organisms
   • Staphylococcus species can be treated with Intravenous Vancomycin or Daptomycin or oral Nitrofurantoin or Trimethoprim/sulfamethoxazole (TMP/SMX) in complicated cases⁹
   • Escherichia coli are usually prescribed with Ciprofloxacin (complicated cases), Cephalexin,  Trimethoprim/sulfamethoxazole (TMP/SMX) or Fosfomycin in cases of resistant E. coli¹⁰
   • STIs, commonly chlamydia and gonorrhea, are prescribed Azithromycin
2. Antifungal therapy- For a fungal infection, treatment is typically guided through identification of the organism growing on semen culture and follow-up sensitivity testing. The most commonly identified organisms of Candida species would be treated with Fluconazole IV or orally as the antifungal agent of choice.^1. If the species shows resistance to fluconazole, Amphotericin B would be prescribed. **Some Candida species can form biofilms, leading to persistent, recurrent infections resistant to antifungal therapies.⁵ This can cause seminal tract obstruction, testicular dysfunction, urogenital abscesses and anti-sperm antibody formation, leading to infertility⁵**
3. Anti-inflammatory agents- Nonsteroidal anti-inflammatory drugs (NSAIDs) can be prescribed to help reduce inflammation⁷
4. Increased ejaculation frequency can help flush out excess white blood cells

What are the prevention and management strategies for pyospermia?

To reduce the risk of infections that contribute to pyospermia, consider the following preventive measures:

• Improving and maintaining genital hygiene, practising safe sex to reduce the risk of sexually transmitted infections and getting regular STI screens
• Communicating information with sexual partners to ensure they receive treatment for STIs if necessary to prevent further spread
• Treating UTI/STI infections promptly and appropriately, managing underlying conditions, especially those of immunocompromised persons, for example, keeping diabetes under control with its recommended treatment protocol
• Introducing some lifestyle modifications:
  • Hydration: Increasing water intake may assist in removing toxins from our body and aid in improving semen quality
  • Reducing smoking and excessive alcohol can help reduce inflammation and oxidative stress, which leads to infertility
  • Dietary Changes: Improvements in diet through increasing the amount of antioxidant-rich foods, fruits, nuts and vegetables  (e.g., to increase vitamin C, vitamin E, zinc, selenium). This may help reduce oxidative damage, including supplementation with probiotics or antioxidants if needed⁷
• Avoiding exposure to environmental toxins and irritants

There are no universal guidelines for the routine screening of pyospermia in asymptomatic men. However, regular screening may be considered useful, particularly in men with recurrent genitourinary infections who are at the early stages of trying to conceive with their partner.¹²

Summary

• Fungal pyospermia should be suspected in antibiotic-resistant, recurrent, or unexplained infertility cases. Nonetheless, to further improve diagnostics, identification of antibiotic resistance and treatment of patients, novel culture-independent diagnostic methods need to be developed.⁷ NGS technology is expected to play an increasingly important role in diagnostic microbiology
• Emphasis on timely diagnosis and appropriate treatment to preserve male fertility