What is the best course of treatment for a 25-year-old male with a history of mild left varicocele, low testosterone (hypogonadism), and abnormal semen analysis results, including low percent motile sperm, low rapid progression, and deviation in morphology, who is concerned about male infertility?

Management of Male Infertility with Mild Varicocele, Low Testosterone, and Abnormal Semen Analysis

For this 25-year-old male with mild left varicocele, low testosterone (191 ng/dL), and abnormal semen parameters, the priority is repeating semen analysis after proper abstinence, followed by varicocele repair if confirmed abnormal, combined with lifestyle optimization—while absolutely avoiding testosterone replacement therapy to preserve fertility. 1

Immediate Diagnostic Steps

Repeat Semen Analysis with Proper Collection

• At least two semen analyses separated by 2-3 months are mandatory to establish a true pattern, as single analyses can be misleading due to natural variability and the 64-74 day spermatogenic cycle. 1, 2
• The patient's 2-day abstinence period was inadequate—repeat with 2-3 days abstinence to obtain accurate baseline parameters. 1
• Each analysis should assess volume, concentration, motility, morphology, and pH to differentiate obstructive from non-obstructive causes. 1

Complete Hormonal Evaluation

• Measure LH, total testosterone, and calculate free testosterone to distinguish primary testicular dysfunction from secondary hypogonadism. 1
• The testosterone level of 191 ng/dL is significantly low and requires further characterization—normal FSH and LH with low testosterone suggests the varicocele is impairing Leydig cell function rather than primary testicular failure. 3, 4, 5
• Check prolactin to exclude hyperprolactinemia as a reversible cause of hypogonadism. 1

Physical Examination Specifics

• Re-examine for varicocele grade while standing, as grade influences treatment decisions—though testosterone improvement occurs independent of clinical grade. 1, 6
• Measure testicular volumes bilaterally using Prader orchidometer—volumes <12 mL suggest testicular atrophy and increased risk of progressive spermatogenic decline. 1, 7
• Palpate vas deferens and epididymides to exclude congenital bilateral absence of vas deferens (CBAVD). 1

Treatment Algorithm Based on Confirmed Findings

If Semen Analysis Confirms Oligospermia with Palpable Varicocele

Microsurgical varicocelectomy is the recommended intervention for this patient with clinically palpable varicocele, documented low testosterone, and abnormal semen parameters. 1

Evidence Supporting Varicocele Repair

• Varicocelectomy improves serum testosterone in 83% of men with preoperative levels <400 ng/dL, with mean increases of 109 ng/dL. 6
• Varicocele repair can improve semen parameters including sperm concentration, motility, and morphology while potentially increasing natural conception rates. 1
• Microsurgical repair is superior to observation for men with clinical varicoceles and impaired semen parameters, as it addresses both fertility and testosterone deficiency. 3, 8, 5
• The improvement in testosterone occurs independent of varicocele grade, making even mild varicoceles appropriate for repair when associated with hypogonadism. 6

Advantages Over Testosterone Replacement

• Varicocele repair preserves and potentially improves fertility, whereas testosterone replacement therapy completely suppresses spermatogenesis through negative feedback. 1, 8, 5
• A one-time microsurgical procedure eliminates the need for lifelong testosterone therapy with ongoing monitoring. 8
• Varicocelectomy addresses the underlying pathophysiology rather than simply replacing the deficient hormone. 4, 5

Lifestyle Optimization (Concurrent with Surgical Planning)

Weight reduction and regular physical exercise are essential adjunctive measures that can improve both testosterone levels and semen parameters. 1

• Maintain BMI <25, as obesity and metabolic syndrome impair male fertility and testosterone production. 1, 9
• Avoid gonadotoxic exposures including heat (hot tubs, saunas, tight underwear), smoking, and excessive alcohol. 1
• Optimize sleep, stress management, and nutrition to support the hypothalamic-pituitary-gonadal axis. 1

Critical Pitfalls to Avoid

Never Prescribe Testosterone Replacement Therapy

Exogenous testosterone is absolutely contraindicated in men desiring current or future fertility, as it suppresses FSH and LH through negative feedback, causing azoospermia that can take months to years to recover. 1, 9, 7

Do Not Delay Genetic Testing If Severe Oligospermia Confirmed

• If repeat semen analysis shows sperm concentration <5 million/mL, obtain karyotype analysis and Y-chromosome microdeletion testing (AZFa, AZFb, AZFc regions). 1, 7
• Complete AZFa or AZFb deletions predict near-zero sperm retrieval success and would alter counseling. 1, 7

Avoid Empiric Medical Therapy

• Selective estrogen receptor modulators (SERMs), aromatase inhibitors, and antioxidants have limited benefits that are outweighed by assisted reproductive technology advantages. 1, 9
• These agents should not delay definitive treatment with varicocele repair or ART. 1

Fertility Preservation Considerations

Sperm Cryopreservation

Consider banking 2-3 ejaculates before varicocelectomy if semen parameters are severely compromised, as this provides insurance against technical failures or poor post-thaw recovery. 1, 7

• Cryopreservation is particularly important if testicular volumes are <12 mL or FSH becomes elevated on repeat testing. 7
• Each collection should be split into multiple vials to allow staged use for future ART cycles. 1, 7

Expected Timeline and Monitoring

Post-Varicocelectomy Follow-Up

• Repeat semen analysis at 3 and 6 months post-operatively to assess improvement, as the complete spermatogenic cycle takes 64-74 days. 1, 2
• Recheck testosterone levels at 3 months—expect mean increases of approximately 100 ng/dL based on published series. 6
• Monitor for testicular volume stabilization or improvement, which indicates halted progression of varicocele-related damage. 7, 3

If Semen Parameters Remain Abnormal After Repair

• Proceed to assisted reproductive technology (IVF/ICSI) if natural conception does not occur within 6-12 months of documented improved parameters. 1, 9
• IVF/ICSI offers superior pregnancy rates compared to continued expectant management or empiric medical therapy. 1, 9

Partner Evaluation

The female partner requires concurrent fertility evaluation, as male factor contributes to 40-50% of infertility cases but female age is the most critical determinant of conception success. 9

• Female partner evaluation should include ovarian reserve testing (AMH, FSH, antral follicle count) and assessment for ovulatory dysfunction. 9
• If female partner is >35 years or has known fertility factors, consider earlier referral to reproductive endocrinology rather than prolonged expectant management. 9