What are the recommendations for using Clomid (clomiphene citrate) to increase sperm production?

Clomiphene Citrate for Male Infertility: Evidence-Based Recommendations

Direct Answer

Clomiphene citrate (Clomid) is NOT recommended as a primary treatment for male infertility because it provides minimal benefit compared to assisted reproductive technology (ART), and current guidelines emphasize that the small improvements in sperm parameters do not translate to meaningful improvements in pregnancy rates or live births. 1, 2

Guideline Position on Clomiphene and SERMs

The 2021 AUA/ASRM guidelines explicitly state that while clomiphene and other selective estrogen receptor modulators (SERMs) are often prescribed off-label in infertile men with normal testosterone levels, the benefits are small and outweighed by the distinct advantages of ART (such as IVF), which offer higher pregnancy rates and earlier conception timeframes. 1

The 2025 European Association of Urology guidelines acknowledge that SERMs may increase pregnancy rates and sperm parameters, but emphasize that the quality of evidence is low, with few placebo-controlled studies, and no conclusive recommendations can be drawn regarding SERM use in idiopathic infertility. 1

When Clomiphene May Be Considered (Limited Scenarios)

Hypogonadotropic Hypogonadism

• Clomiphene may have a role in men with low testosterone AND low/low-normal LH levels (secondary hypogonadism with intact pituitary function), though hCG and FSH are preferred for this indication. 1
• This is distinct from idiopathic infertility with normal hormones, where clomiphene has minimal benefit. 1

Specific Clinical Context

• If clomiphene is used despite limited evidence, the historical approach involves 25 mg daily for 25 days with 5 days rest, continued for 6-9 months (not the traditional 3 months). 3, 4
• Recent data suggest testosterone levels plateau at 6 months, while sperm concentration improvements may not appear until 9 months, making the traditional 3-month evaluation insufficient. 5
• A higher dose of 50 mg daily may be tried in non-responders to 25 mg. 4

Critical Limitations and Pitfalls

Pregnancy Outcomes vs. Sperm Parameters

• Most studies show improvements in sperm concentration but NOT in pregnancy rates, which is the outcome that matters for patients. 6
• Only 1 of 9 clinical studies identified in a comprehensive review detected statistically significant benefit on pregnancy rates, despite many showing sperm concentration increases. 6

Time Delay Risk

• Using clomiphene delays more effective ART options, which is problematic given that female partner age and ovarian reserve are critical time-sensitive factors. 1, 2
• The cost-to-benefit ratio is questionable, as men require 6-9 months of treatment for minimal incremental pregnancy rate improvements. 1

Not FDA-Approved

• Clomiphene is not FDA-approved for use in men, and the incidence of side effects with long-term treatment remains unknown. 4

Recommended Clinical Algorithm

Step 1: Hormonal Evaluation

• Obtain FSH and testosterone levels in all men with oligozoospermia or abnormal semen parameters. 1
• If testosterone is low with low/low-normal LH, consider secondary hypogonadism and refer to endocrinology or male reproductive specialist. 1

Step 2: Identify Treatable Causes

• Evaluate for varicocele (treat if clinical varicocele present with abnormal semen and unexplained infertility). 1
• Screen for accessory gland infections and treat appropriately. 1
• Assess for anabolic steroid use (discontinue immediately as it suppresses spermatogenesis). 1

Step 3: Primary Treatment Recommendation

• For severe oligozoospermia or oligoasthenoteratozoospermia (OAT): Recommend IVF with ICSI as first-line treatment, as it provides the most reliable path to healthy pregnancy. 2
• For moderate oligozoospermia with good female ovarian reserve: Consider varicocelectomy if clinical varicocele present, or proceed directly to ART. 1

Step 4: If Empiric Medical Therapy Pursued Despite Limited Evidence

• Counsel patients that evidence is insufficient to recommend clomiphene, and that ART offers superior outcomes. 1, 6
• If patient insists on trial: 25 mg daily for 25 days with 5-day rest, plan for minimum 6-9 months before assessing efficacy. 5, 4
• Monitor testosterone and semen analysis at 3,6, and 9 months. 5, 4
• Consider 50 mg daily if no response to 25 mg. 4

Additional Considerations

Lifestyle Modifications (Always Recommend)

• Weight loss for obese patients, smoking cessation, and regular exercise may improve sperm parameters and should be advised regardless of other treatments. 2

Genetic Counseling

• Men with severe oligozoospermia (<5 million/mL) should undergo genetic testing (karyotype, Y-chromosome microdeletions) before treatment, as genetic abnormalities may limit response and have implications for offspring. 1, 2

Antioxidants

• Evidence for antioxidant therapy is conflicting; a Cochrane review showed potential live birth rate improvement, but when high-risk-of-bias studies were removed, the benefit disappeared. 1

Monitoring During Treatment

• Periodic gonadotropin levels and semen analyses should be performed during clomiphene therapy. 4
• At least two semen analyses one month apart are needed due to natural variability. 1, 2