What are the recommended treatments to increase sperm count in a reproductive‑age male with documented low sperm concentration?

Treatment to Increase Sperm Count

For men with documented low sperm count, assisted reproductive technology (ART) with IVF/ICSI offers the most reliable path to achieving pregnancy and should be prioritized over medical treatments, which have limited and inconsistent benefits. 1

First-Line Approach: Assisted Reproductive Technology

• IVF with ICSI is the primary treatment option for severe oligospermia (low sperm count), providing the best chance for a healthy pregnancy as long as viable sperm are present. 1
• Medical treatments for idiopathic low sperm count have limited efficacy and may delay more effective ART options, emphasizing the importance of timely intervention. 1
• For couples with low total motile sperm count on repeated semen analysis, IUI success rates are reduced, and treatment with ART (IVF/ICSI) should be considered. 2

Lifestyle Modifications: Strongest Evidence Base

Before considering any medical therapy, implement these evidence-based lifestyle changes for at least 3 months:

• Weight loss to achieve BMI 18.5-25 kg/m² through diet and exercise improves sperm parameters in obese men with infertility. 1, 3
• Complete tobacco cessation provides the strongest evidence for improving male fertility, as smoking increases sperm DNA fragmentation by approximately 10% and alters hormonal profiles. 1, 3, 4
• Regular physical exercise enhances overall sperm quality and should be implemented before any supplementation. 1, 3
• Avoid heat exposure (hot tubs, saunas, tight underwear) based on moderate evidence to enhance semen quality. 3
• Limit alcohol consumption, as chronic use raises sperm DNA fragmentation by approximately 10% and disrupts the hypothalamic-pituitary-gonadal axis. 4

Medical Interventions: Limited but Conditional Use

Hormonal Treatments (Only for Specific Indications)

• For men with low testosterone and low sperm count, aromatase inhibitors, human chorionic gonadotropin (hCG), or selective estrogen receptor modulators (SERMs) may be used, though evidence is Grade C (conditional recommendation). 2
• Clomiphene citrate (25-75 mg daily) increases sperm concentration by a mean of 8.38 × 10⁶/ml and total motility by 8.14%, with pregnancy rates averaging 17% during treatment. 5, 6
• FSH analogues may improve sperm concentration, pregnancy rates, and live birth rates in idiopathic infertility, though evidence is limited (Grade B). 2, 1

Critical Contraindication

• Never prescribe testosterone monotherapy to men interested in current or future fertility, as it completely suppresses spermatogenesis through negative feedback and can cause azoospermia requiring months to years to recover. 2, 1, 7

Supplements and Antioxidants: Questionable Clinical Utility

• The benefits of supplements (antioxidants, vitamins) are of questionable clinical utility in treating male infertility, with inadequate data to recommend specific agents (Grade B evidence). 2
• The European Association of Urology (2025) states that evidence for antioxidant therapy remains conflicting and of low quality, recommending against routine use. 3
• A Cochrane review of 61 studies (6,264 infertile men) showed that after removing high-risk-of-bias trials, antioxidant therapy did not increase live-birth rates. 3
• If antioxidants are requested by patients, vitamin C 1000 mg twice daily for 2 months may be offered only after counseling about limited evidence, with reassessment at 2-3 months. 3
• Zinc, vitamin D (in cases of deficiency), L-arginine, and ashwagandha show modest promise based on limited randomized trials, but should not replace proven treatments. 8

Treatment Algorithm for Low Sperm Count

Step 1: Baseline Evaluation (0-1 month)

• Perform at least two semen analyses following WHO criteria (≥16 million/ml is normal). 3
• Measure FSH, LH, total testosterone, and SHBG to calculate free testosterone. 1, 7
• Conduct physical examination for varicocele, testicular size/consistency, and vas deferens abnormalities. 1
• Obtain karyotype analysis and Y-chromosome microdeletion testing if sperm concentration is <5 million/ml. 1, 7

Step 2: Lifestyle Optimization (3-6 months)

• Implement weight loss (if BMI >25), smoking cessation, regular exercise, and heat avoidance. 1, 3, 4
• Repeat semen analysis after 3 months to assess response. 1

Step 3: Medical Intervention (if applicable)

• For hypogonadotropic hypogonadism: Treat with hCG followed by FSH analogues, which successfully initiates spermatogenesis in 75% of men. 1
• For idiopathic oligospermia with low testosterone: Consider clomiphene citrate 25-75 mg daily or aromatase inhibitors for 3-6 months. 2, 5, 6
• For clinical varicocele with abnormal semen parameters: Varicocelectomy improves sperm DNA integrity and fertility outcomes. 1

Step 4: Escalation to ART (if no improvement after 6-12 months)

• Proceed directly to IVF/ICSI if semen parameters remain abnormal or no pregnancy occurs after 12 months of conservative management. 1, 3
• Female partner age is the most critical factor determining conception success; delays in definitive treatment reduce overall success rates. 1, 3

Common Pitfalls to Avoid

• Do not delay proven fertility treatments while trialing antioxidants or supplements, as female partner age-related fertility decline continues during the trial period. 3
• Do not use antioxidants as monotherapy; lifestyle modifications have stronger supporting evidence. 3
• Do not prescribe testosterone to men desiring fertility, as it will cause azoospermia. 2, 1, 7
• Do not rely on single semen analysis; natural variability requires at least two analyses separated by 2-3 months. 1, 3
• Do not ignore underlying conditions such as varicocele, hormonal imbalances, or genetic abnormalities that require specific treatment. 1

Special Considerations

• For non-obstructive azoospermia (no sperm in ejaculate): Microsurgical testicular sperm extraction (micro-TESE) offers 40-50% sperm retrieval rates even with elevated FSH, and is 1.5 times more successful than conventional TESE. 2, 1, 7
• Sperm cryopreservation should be considered if any treatments that might further impair fertility are planned, banking 2-3 separate ejaculates to preserve fertility options. 1
• Genetic counseling is essential for men with severe oligozoospermia (<5 million/ml), as some cases have genetic causes that affect treatment success and offspring risk. 1, 7