In an adult male with reduced sperm count and motility suspected of asymptomatic chronic prostatitis (Category III chronic prostatitis/chronic pelvic pain syndrome), what is the recommended first‑line treatment regimen, including appropriate antibiotics, an alpha‑adrenergic blocker, a non‑steroidal anti‑inflammatory drug, antioxidant supplementation, lifestyle modifications, and dosing?

Treatment of Asymptomatic Chronic Prostatitis with Reduced Sperm Parameters

Antibiotic therapy for asymptomatic chronic prostatitis (Category IV) is NOT recommended, as there is no evidence that treating this condition improves natural conception rates, even when sperm parameters are abnormal. 1

Key Evidence Against Antibiotic Treatment

The most recent and highest-quality guideline—the 2025 European Association of Urology guidelines on male infertility—provides definitive guidance on this exact clinical scenario:

• Only chronic bacterial prostatitis (NIH Category II) warrants antibiotic therapy for fertility purposes, and even then, antibiotics may improve sperm quality but have not been proven to increase natural conception rates. 1

• For chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS, Category III), there is no evidence that antibiotic treatment increases the probability of natural conception, despite potential improvements in sperm parameters. 1

• Asymptomatic inflammatory prostatitis (Category IV) is often left untreated because its clinical significance for fertility remains unknown. 2

Recommended Treatment Algorithm for Male Infertility with Suspected Asymptomatic Prostatitis

First-Line: Lifestyle Modifications (Strong Evidence)

All infertile men should implement lifestyle changes as primary therapy, as these interventions improve both sperm parameters and overall cardiovascular health:

• Weight loss if overweight or obese 1
• Regular physical exercise 1
• Smoking cessation 1
• Cardiovascular risk factor screening, as infertile men have higher cardiovascular and overall mortality compared to fertile controls 1

Second-Line: Antioxidant Therapy (Conflicting Evidence)

Antioxidant supplementation may be considered, though evidence remains conflicting:

• A Cochrane meta-analysis of 61 studies (6,264 men) showed antioxidants may improve live birth rates, but the quality of evidence was low. 1
• When high-risk-of-bias studies were removed, the benefit on live birth rates disappeared. 1
• No specific antioxidant formulation or dose can be definitively recommended based on current evidence. 1

Third-Line: Prebiotic/Probiotic Supplementation (Emerging Evidence)

Prebiotic/probiotic compounds may improve sperm parameters:

• One RCT (56 men with idiopathic infertility) showed significant improvements in sperm concentration, motility, normal morphology, and DNA integrity with prebiotic/probiotic treatment versus placebo. 1
• Further high-powered RCTs are needed before this can be strongly recommended. 1

When to Consider Antibiotics (Only in Specific Scenarios)

Scenario 1: Documented Chronic Bacterial Prostatitis (Category II)

If the patient has documented recurrent urinary tract infections with the same uropathogen localized to the prostate via Meares-Stamey testing:

• Fluoroquinolones are first-line if local resistance is <10%: 3

  • Ciprofloxacin 500-750 mg orally twice daily for 4-12 weeks 3

• Alternative agents if fluoroquinolones are contraindicated or resistance is high:

  • Trimethoprim-sulfamethoxazole (only if susceptibility confirmed) 3
  • Doxycycline 100 mg orally every 12 hours (particularly for men <35 years to cover Chlamydia trachomatis and Mycoplasma species) 3

Scenario 2: Suspected Sexually Transmitted Infection

If the patient is <35 years old or has risk factors for STIs, consider empiric coverage:

• Doxycycline 100 mg orally every 12 hours for 7 days to cover Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma species 3
• OR Azithromycin 1 g orally as a single dose for Mycoplasma coverage 3
• Sexual partners within the preceding 60 days must be referred for evaluation and treatment 1, 3
• Abstain from sexual intercourse until 7 days after therapy initiation and after partners are treated 1, 3

Scenario 3: Asymptomatic Chlamydia Infection

A recent case-control study suggests that treating asymptomatic Chlamydia infection may improve sperm parameters, though it remains unclear whether this improves conception rates. 1

• If Chlamydia testing is positive: Treat with doxycycline or azithromycin as above 3

Critical Pitfalls to Avoid

Do NOT Use Prolonged Empiric Antibiotics

• Fluoroquinolones for 4-6 weeks are commonly prescribed for CP/CPPS, with 50% of men reporting symptomatic relief, but this approach is more efficacious only if prescribed soon after symptom onset. 2
• In longstanding, previously treated CP/CPPS, antimicrobials cannot be recommended. 4
• For truly asymptomatic patients (Category IV), antibiotics have no proven benefit for fertility. 1, 2

Do NOT Assume All Prostatitis Is Infectious

• 90% of prostatitis syndrome cases are CP/CPPS (Category III), not bacterial prostatitis. 5
• Pathogenic organisms can be cultured only in acute and chronic bacterial prostatitis (Categories I and II). 5
• The utility of antimicrobial treatment for CP/CPPS remains debatable, as it is unclear whether this condition is of infectious origin. 5

Do NOT Overlook Partner Evaluation

• If STIs are suspected or confirmed, all sexual partners within 60 days must be evaluated and treated to prevent reinfection. 1, 3
• Re-exposure to an untreated partner is a common cause of recurrent urethritis and prostatitis. 3

Adjunctive Therapies (If Symptomatic CP/CPPS Develops)

If the patient later develops pelvic pain or urinary symptoms consistent with CP/CPPS:

Alpha-Blockers (First-Line for Symptomatic CP/CPPS)

• Recommended as first-line medical therapy, particularly in alpha-blocker-naïve men with moderately severe symptoms and relatively recent onset. 4
• Cannot be recommended in men with longstanding CP/CPPS who have previously failed alpha-blockers. 4
• Common agents include tamsulosin, alfuzosin, or doxazosin (specific doses not provided in guidelines). 2, 4

Anti-Inflammatory Agents

• NSAIDs for pain symptoms may provide symptomatic relief. 2
• Long-term NSAID use is limited by side effect profile. 6
• Anti-inflammatory therapy is not recommended as primary treatment but may have an adjunctive role in multimodal regimens. 4

Multimodal Therapy

• Combination of alpha-blockers, antibiotics (if indicated), and anti-inflammatories showed better symptom control than single-drug treatment in CP/CPPS. 6

Phytotherapy

• Quercetin, pollen extract (cernilton), and Serenoa repens extract showed positive effects on symptoms and quality of life without side effects. 6
• Early data on quercetin and cernilton are intriguing, but larger multicenter RCTs are required before high-level recommendations can be made. 4

Pelvic Floor Physical Therapy

• Pelvic floor training/biofeedback may be more effective than pharmacotherapy, but randomized controlled trials are needed to confirm this. 2
• Recommended if relief from first-line therapies is not significant. 2

Summary Algorithm

1. Confirm the diagnosis: Asymptomatic prostatitis (Category IV) versus symptomatic CP/CPPS (Category III) versus chronic bacterial prostatitis (Category II). 2, 5

2. For truly asymptomatic Category IV prostatitis with abnormal sperm parameters:

   • Do NOT use antibiotics 1
   • Implement lifestyle modifications (weight loss, exercise, smoking cessation) 1
   • Consider antioxidant supplementation (low-quality evidence) 1
   • Consider prebiotic/probiotic supplementation (emerging evidence) 1

3. If documented chronic bacterial prostatitis (Category II):

   • Ciprofloxacin 500-750 mg orally twice daily for 4-12 weeks (if local resistance <10%) 3
   • Treat sexual partners if STI suspected 1, 3

4. If symptomatic CP/CPPS develops:

   • Alpha-blockers as first-line 4
   • NSAIDs for pain 2
   • Consider multimodal therapy (alpha-blocker + antibiotic + anti-inflammatory) 6
   • Refer for pelvic floor physical therapy if inadequate response 2

5. Screen for cardiovascular risk factors in all infertile men 1