What are the evaluation and treatment options for an adult male with concerns about low sperm production?

Evaluation and Management of Low Sperm Production in Adult Males

Initial Diagnostic Approach

Begin with concurrent evaluation of both partners, as couple infertility involves male factors, female factors, or both in approximately equal proportions. 1

Essential First Steps

• Obtain one or more semen analyses as the cornerstone of initial evaluation 1

• Perform a comprehensive reproductive history including:

  • Duration of infertility and any previous fertility 2
  • Childhood illnesses (cryptorchidism, mumps orchitis) 3
  • Systemic illnesses, particularly diabetes 1
  • Sexual history and frequency of intercourse 3
  • Medication use, especially anabolic steroids, testosterone, opiates, or finasteride 1, 2
  • Occupational exposures to pesticides, lead, cadmium, or oil/gas extraction 1
  • Lifestyle factors: smoking, alcohol, diet quality, heat exposure 1, 2

• If semen analysis reveals abnormal parameters (concentration <16 million/mL, motility <50%, morphology <4%), refer to a male reproductive specialist for complete physical examination 1, 2

Critical Physical Examination Findings

• Testicular size and consistency (normal volume >12 mL; atrophy suggests primary testicular failure) 2, 4
• Presence of varicocele on standing examination (palpable varicoceles are treatable) 1, 2
• Vas deferens presence and consistency (absence suggests congenital bilateral absence) 2, 5
• Epididymal fullness or induration (suggests obstruction) 2, 3

Hormonal Evaluation

For men with abnormal semen parameters, measure morning serum testosterone, FSH, and LH to distinguish primary testicular failure from secondary hypogonadism. 1, 2, 4

Interpreting Hormone Patterns

• Primary testicular failure: Low testosterone with elevated FSH (>7.6 IU/L) and elevated LH 4, 5

• Secondary hypogonadism: Low testosterone with low or normal FSH and LH (potentially reversible while preserving fertility) 4, 5

• Isolated elevated FSH (>7.6 IU/L) with normal testosterone: Suggests impaired spermatogenesis; men with FSH >7.5 IU/L have 5-13 fold higher risk of abnormal sperm concentration 4

• Measure SHBG if total testosterone is borderline, as elevated SHBG (common in diabetes, hyperthyroidism, liver disease) reduces bioavailable testosterone despite normal total levels 2, 4, 5

• Check serum prolactin in men with reduced libido and erectile dysfunction, as hyperprolactinemia directly suppresses libido independent of testosterone 5

• Assess thyroid function (TSH, free T4), as both hypothyroidism and hyperthyroidism disrupt the hypothalamic-pituitary-gonadal axis and impair spermatogenesis 4

Genetic Testing Indications

Genetic testing is mandatory in specific scenarios to identify heritable conditions and guide treatment decisions. 1

• Karyotype analysis: Required for sperm concentration <5 million/mL to exclude Klinefelter syndrome (47,XXY) and other chromosomal abnormalities 1, 2, 4, 5
• Y-chromosome microdeletion testing (AZFa, AZFb, AZFc regions): Mandatory for sperm concentration <1 million/mL or azoospermia 1, 2, 4, 5
  • Complete AZFa and AZFb deletions result in almost zero likelihood of sperm retrieval and contraindicate testicular sperm extraction 1, 4
  • AZFc deletions may still allow sperm retrieval in 40-50% of cases 4

Treatment Algorithm Based on Etiology

For Correctable Conditions

• Varicocele repair: Correction of palpable varicoceles improves both semen quality and fertility rates; do not treat non-palpable varicoceles detected only on ultrasound 1

• Hypogonadotropic hypogonadism (low FSH, low LH, low testosterone):

  • Start hCG 1,000-2,000 IU subcutaneously 2-3 times weekly to stimulate intratesticular testosterone production 6
  • Add FSH analogues (75-150 IU subcutaneously 3 times weekly) after 3-6 months if sperm counts remain low 4
  • 75% of men achieve sperm in ejaculate with this regimen 4
  • Never use exogenous testosterone if fertility is desired—it completely suppresses spermatogenesis through negative feedback, causing azoospermia that can take months to years to recover 2, 4, 5

• Hyperprolactinemia: Treat with dopamine agonists (cabergoline or bromocriptine) or discontinue prolactin-elevating medications 5

• Thyroid dysfunction: Correct to euthyroid status before making definitive fertility conclusions, as both hypo- and hyperthyroidism reversibly impair spermatogenesis 4

For Idiopathic Oligospermia with Elevated FSH

• Selective estrogen receptor modulators (SERMs): Clomiphene citrate 25-50 mg daily can increase sperm concentration, though evidence for improved pregnancy rates is limited 4, 7, 8
• Aromatase inhibitors: Letrozole or anastrozole may improve spermatogenesis by decreasing estrogen and increasing testosterone, though benefits are modest 4
• FSH analogues: May improve sperm concentration in men with FSH 10-12 IU/L, representing a conditional recommendation with Grade B evidence 4

However, assisted reproductive technology (IVF/ICSI) offers superior pregnancy rates compared to empiric hormonal therapy and should be discussed early, particularly given female partner age considerations. 2, 4

For Non-Obstructive Azoospermia

Microsurgical testicular sperm extraction (micro-TESE) is the gold standard for sperm retrieval, achieving success in 40-60% of men despite elevated FSH. 1, 4

• Micro-TESE is 1.5 times more successful than conventional testicular sperm extraction and causes less testosterone suppression 1, 4
• Sperm retrieval rates remain approximately 50% even with FSH >10 IU/L and small testicular volumes 4
• Important caveat: Testosterone deficiency may worsen after micro-TESE, potentially requiring testosterone replacement once fertility goals are abandoned 4

For Obstructive Azoospermia

• Suspect ejaculatory duct obstruction when ejaculate volume <1.4 mL, pH <7.0, with normal testosterone and palpable vas deferens 1, 5
• Order transrectal ultrasound or pelvic MRI only when clinical criteria for ejaculatory duct obstruction are met 1, 5
• Surgical correction or sperm retrieval with IVF/ICSI are treatment options 1

Lifestyle Modifications and Risk Factor Management

Address modifiable factors that significantly impact spermatogenesis: 1, 2

• Smoking cessation: Smokers have slightly reduced fertility and poorer sperm morphology 1
• Weight optimization: Obesity (BMI >25) decreases testosterone and SHBG, worsens erectile function, and impairs spermatogenesis 1, 4, 5
• Avoid excessive heat exposure: Hot tubs, saunas, and tight underwear can temporarily impair sperm production 2
• Discontinue anabolic steroids immediately: Anabolic steroid use is strongly associated with reduced fertility and can cause prolonged azoospermia 1
• Minimize environmental exposures: Limit contact with pesticides (pyrethroids, organophosphates), lead, cadmium, and DEHP 1

Fertility Preservation Considerations

Men with elevated FSH (>10 IU/L) and small testicular volumes (<12 mL) should strongly consider sperm cryopreservation, as they are at high risk for progressive spermatogenic failure. 4

• Collect at least 2-3 ejaculates if possible to provide backup samples 4
• Once azoospermia develops, even micro-TESE only achieves 40-50% sperm retrieval rates 4
• Sperm concentration and motility decrease after cryopreservation, but DNA integrity is preserved 4

Health Implications Beyond Fertility

Male infertility is associated with increased morbidity and mortality that extends beyond reproductive concerns. 1

• Men with abnormal semen parameters have higher rates of testicular cancer than fertile men 1
• Men with azoospermia have higher rates of cancer in general 1
• Mortality rates are positively associated with abnormal semen analyses 1
• Infertile men have more comorbidities compared to fertile controls, making comprehensive health screening essential 4

Common Pitfalls to Avoid

• Never prescribe exogenous testosterone to men desiring fertility—it suppresses FSH and LH, causing azoospermia 2, 4, 5
• Do not rely on a single semen analysis; repeat testing after 2-3 months to account for biological variability 2, 4
• Do not treat non-palpable varicoceles detected only on ultrasound, as treatment does not improve outcomes 1
• FSH levels alone cannot definitively predict sperm retrieval success—up to 50% of men with non-obstructive azoospermia and elevated FSH have retrievable sperm 4
• Do not delay female partner evaluation, as female age is the most critical factor determining conception success 4