What is the appropriate treatment for a patient with oligospermia who has normal serum testosterone, luteinizing hormone (LH), follicle‑stimulating hormone (FSH), and normal testicular volume on ultrasound?

Treatment Approach for Oligospermia with Normal Hormones and Testicular Volume

In a patient with decreased sperm count but normal testosterone, LH, FSH, and normal testicular size on ultrasound, the priority is to identify any reversible causes (varicocele, lifestyle factors, medications) and consider empiric medical therapy or assisted reproductive technology rather than hormonal manipulation, as the normal hormonal profile indicates intact hypothalamic-pituitary-testicular axis function. 1

Initial Diagnostic Workup

Confirm the diagnosis with repeat semen analysis:

• Perform at least two semen analyses separated by 2-3 months, as single analyses can be misleading due to natural variability 1
• Assess sperm concentration, motility, and morphology according to WHO criteria 2

Physical examination must specifically evaluate:

• Presence of palpable varicocele on standing examination, as varicocele repair improves semen parameters and fertility in men with clinical (palpable) varicoceles and abnormal semen analysis 1, 3
• Testicular consistency and symmetry—size discrepancy >2ml or 20% warrants ultrasound to exclude pathology 4
• Vas deferens patency bilaterally to rule out congenital bilateral absence of vas deferens 3
• Epididymal abnormalities or masses 4

Essential laboratory tests beyond the basic hormonal panel:

• Calculate free testosterone using SHBG if total testosterone is borderline, as high SHBG can reduce bioavailable testosterone even when total testosterone appears normal 1
• Check serum prolactin to exclude hyperprolactinemia, which can disrupt gonadotropin secretion 1
• Assess thyroid function (TSH, free T4), as thyroid disorders commonly affect reproductive hormones and hyperthyroidism causes asthenozoospermia, oligozoospermia, and teratozoospermia that are reversible with treatment 1

Genetic Testing Indications

Genetic testing is mandatory in specific scenarios:

• Karyotype analysis is strongly recommended if sperm concentration is <5 million/mL, as chromosomal abnormalities occur in 10% of these patients 1, 2, 5
• Y-chromosome microdeletion testing (AZFa, AZFb, AZFc regions) is required if sperm concentration is <1 million/mL 1, 5
• Complete AZFa and AZFb deletions predict near-zero sperm retrieval success and contraindicate testicular sperm extraction 1

Treatment Algorithm Based on Etiology

If Clinical Varicocele is Present:

Varicocelectomy is strongly indicated when there is a palpable varicocele with documented oligospermia, as correction results in improvement in both semen quality and fertility rates 1, 3

• Varicocele repair can halt progression of testicular atrophy and potentially reverse some damage 1
• Expected outcomes include testosterone improvement, FSH reduction, and testicular volume stabilization 1
• Critical pitfall: Do not treat subclinical (non-palpable) varicoceles detected only on ultrasound, as this does not improve semen parameters or fertility rates 3

If No Varicocele or Reversible Cause is Identified:

Empiric medical therapy has limited but measurable benefits:

• Selective estrogen receptor modulators (SERMs) such as tamoxifen 20mg/day can increase sperm concentration and total sperm count, with a 40% pregnancy rate reported in one study 6
• Aromatase inhibitors may decrease estrogen production and improve spermatogenesis 1
• However, these benefits are modest and outweighed by the advantages of assisted reproductive technology 1

Assisted reproductive technology offers superior outcomes:

• IVF/ICSI provides the highest pregnancy rates and should be discussed early, particularly given female partner age considerations 1
• This approach is especially appropriate when total motile sperm count is <10 million on repeated semen analysis 1

Critical Actions to Protect Fertility

Never prescribe exogenous testosterone if fertility is desired:

• Testosterone replacement completely suppresses spermatogenesis through negative feedback on the hypothalamus and pituitary, causing azoospermia that can take months to years to recover 1, 2
• This is the single most important pitfall to avoid 1

Address modifiable risk factors:

• Smoking cessation, maintaining healthy body weight (BMI <25), and minimizing heat exposure to the testes 1
• Optimize metabolic factors, as obesity and metabolic syndrome impair male fertility 1
• Correct thyroid dysfunction if present, as achieving euthyroid status improves semen quality 1

Consider sperm cryopreservation:

• Bank 2-3 separate ejaculates if sperm concentration is declining or approaching 5 million/mL 1
• This provides insurance against future deterioration, as once azoospermia develops, even microsurgical testicular sperm extraction only achieves 40-50% sperm retrieval rates 1

Monitoring Strategy

Repeat semen analysis every 6-12 months to detect early decline in sperm parameters 1

Measure FSH, LH, and testosterone if sperm parameters decline, especially if concentration drops below 20 million/mL 1

Urgent urology referral is indicated if:

• Palpable testicular mass develops 1
• Rapid testicular atrophy occurs 1
• Severe oligospermia (<5 million/mL) develops, triggering need for genetic testing 1, 5

Understanding the Prognosis

The normal hormonal profile (testosterone, LH, FSH) with normal testicular size suggests the patient most likely has idiopathic oligospermia with preserved testicular reserve rather than primary testicular failure 1, 2. This pattern indicates:

• The hypothalamic-pituitary-testicular axis is functioning normally 2
• There is potential for improvement with treatment of reversible factors 1
• Natural conception remains possible, especially if total motile sperm count exceeds 10 million 1

However, FSH levels alone cannot definitively predict fertility status—up to 50% of men with non-obstructive azoospermia and elevated FSH still have retrievable sperm, and conversely, men with maturation arrest can have normal FSH despite severe spermatogenic dysfunction 1. Therefore, the semen analysis findings are more important than the hormonal profile for determining treatment strategy 2.