I have small testicles (volume less than 12–14 mL); does this indicate infertility and what assessments and management should I pursue?

Small Testicular Volume and Fertility Assessment

Small testicular volume (<12–14 mL) does not automatically mean infertility, but it strongly correlates with reduced sperm production and warrants comprehensive evaluation including semen analysis, hormonal testing, and genetic screening when indicated. 1

Understanding the Clinical Significance

Testicular volume below 12 mL is definitively considered atrophic and associated with impaired spermatogenesis, but many men in this range still produce sperm—just at lower concentrations than men with normal-sized testes. 1 The key distinction is that testicular volume strongly correlates with total sperm count and sperm concentration, meaning smaller testes typically produce fewer sperm, but not necessarily zero sperm. 1

Research confirms this relationship: testicular volume positively correlates with sperm concentration and progressive motility in infertile men, with volumes below 15 mL being significantly more common in infertile versus fertile men (median 15.0 mL vs 22.5 mL). 2 Biofunctional sperm parameters—including mitochondrial membrane potential, DNA fragmentation, and chromatin compactness—worsen in near-linear correlation as testicular volume decreases. 3

Essential Diagnostic Workup

Semen Analysis

Perform at least two semen analyses separated by 2–3 months to establish baseline fertility status, as single analyses are misleading due to natural variability. 1 Compare results to WHO reference values: sperm concentration ≥16 million/mL, total sperm number ≥39 million per ejaculate, progressive motility ≥30%, and morphologically normal forms ≥4%. 4

Hormonal Evaluation

Obtain morning serum FSH, LH, and total testosterone between 08:00–10:00 hours on at least two separate occasions to characterize the hypothalamic-pituitary-testicular axis. 1

• FSH >7.6 IU/L indicates impaired spermatogenesis and reduced testicular reserve, though up to 50% of men with elevated FSH and non-obstructive azoospermia still have retrievable sperm. 1, 5
• Elevated LH with low testosterone suggests primary testicular failure. 1
• Low or normal LH with low testosterone points toward secondary (hypothalamic-pituitary) dysfunction. 1

When total testosterone is low, measure free testosterone by equilibrium dialysis and SHBG to differentiate true hypogonadism from alterations in binding proteins. 1

Genetic Testing

Karyotype analysis is mandatory when semen analysis shows severe oligospermia (<5 million/mL) or azoospermia, as chromosomal abnormalities occur in 10% of these patients. 4, 6 Klinefelter syndrome (47,XXY) is the most common genetic cause of primary testicular failure with small testicular volume. 1

Y-chromosome microdeletion testing (AZFa, AZFb, AZFc regions) is required when sperm concentration is <1 million/mL. 4, 1 Complete AZFa and AZFb deletions predict near-zero sperm retrieval success and contraindicate testicular sperm extraction. 1, 5

Physical Examination Priorities

Assess for palpable varicocele, as correction of clinical varicoceles improves both semen quality and fertility rates. 4, 1 Evaluate testicular consistency, epididymal abnormalities, and vas deferens patency. 1

Do not treat non-palpable (subclinical) varicoceles found only on ultrasound, as treatment does not improve fertility outcomes. 4

Imaging Considerations

Scrotal ultrasound is indicated when:

• Size discrepancy between testes >2 mL or 20% exists 1
• Physical examination is difficult (large hydrocele, inguinal testis, epididymal enlargement) 1
• History of cryptorchidism is present, given increased cancer risk 1

Use the Lambert formula (Length × Width × Height × 0.71) for accurate volume calculation, as the traditional ellipsoid formula (0.52 coefficient) systematically underestimates volume by 20–30%. 1 The Prader orchidometer provides a good clinical surrogate but overestimates volume, especially in small testes. 1, 7

Cancer Risk Stratification

Men younger than 30–40 years with testicular volume <12 mL have a ≥34% risk of intratubular germ cell neoplasia (TIN) in the contralateral testis if testicular cancer develops. 1 If TIN is left untreated, approximately 70% progress to invasive testicular cancer within 7 years. 1

History of cryptorchidism combined with volume <12 mL markedly increases malignancy risk and mandates intensified surveillance. 1 Teach testicular self-examination and monitor for rapid testicular atrophy or development of masses. 1

Consider contralateral testicular biopsy in high-risk scenarios: age <30 years with volume <12 mL, history of cryptorchidism, or presence of testicular cancer. 1

Management Algorithm

If Semen Analysis Shows Normal Parameters

• Repeat semen analysis every 6–12 months to detect early decline 1
• Avoid exogenous testosterone or anabolic steroids completely, as these suppress spermatogenesis through negative feedback and can cause azoospermia requiring months to years for recovery 4, 1
• Optimize modifiable factors: smoking cessation, maintain healthy body weight (BMI <25), minimize scrotal heat exposure 1
• Consider sperm cryopreservation (2–3 separate ejaculates) if parameters show declining trend, especially if approaching 20 million/mL or dropping below 5 million/mL 1

If Semen Analysis Shows Oligospermia or Azoospermia

• Complete genetic testing (karyotype and Y-chromosome microdeletion) if concentration <5 million/mL 4, 1
• Evaluate and treat palpable varicocele if present, as repair can improve testosterone levels, reduce FSH, and stabilize testicular volume 1
• Never initiate testosterone replacement if fertility is desired, as it will cause complete azoospermia 4, 1
• For non-obstructive azoospermia, microsurgical testicular sperm extraction (micro-TESE) achieves sperm retrieval in 40–60% of cases despite elevated FSH, and is 1.5 times more successful than conventional TESE 1, 5
• Discuss assisted reproductive technology (IVF/ICSI) early, as it offers superior pregnancy rates compared to empiric hormonal therapy 1

If Secondary Hypogonadism is Identified

Human chorionic gonadotropin (hCG) injections can stimulate testosterone production and improve spermatogenesis, with 75% of men achieving sperm in ejaculate. 5 FSH analogues may be added after testosterone normalizes if sperm counts remain low. 5

Critical Pitfalls to Avoid

Do not start testosterone therapy without clarifying fertility intentions, as exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis and eliminates intratesticular testosterone production, causing azoospermia. 1

Do not rely on testicular volume alone to predict fertility—semen analysis is mandatory, as even "normal-sized" testes can have impaired spermatogenesis. 1

Do not perform transrectal ultrasonography or pelvic MRI as part of initial evaluation unless semen analysis suggests ejaculatory duct obstruction (acidic, azoospermic semen with volume <1.4 mL, normal testosterone, palpable vas deferens). 4

Address reversible causes before making definitive conclusions: correct thyroid dysfunction, optimize metabolic parameters (diabetes control, weight loss), and discontinue gonadotoxic medications (opioids, corticosteroids). 1, 5