Is it likely that men with significantly reduced testicular volume, specifically 4ml, will produce some sperm?

Sperm Production Likelihood with 4ml Testicular Volume

Men with 4ml testicular volume are extremely unlikely to produce sperm, as this represents severe testicular atrophy far below the 12ml threshold associated with impaired spermatogenesis, and volumes below 10ml are typically associated with azoospermia. 1, 2

Understanding the Clinical Significance of 4ml Testicular Volume

Testicular volumes below 12ml are definitively considered atrophic and associated with significant pathology, including impaired spermatogenesis. 1 The evidence is particularly stark for volumes as low as 4ml:

• Patients with testicular volumes less than 10ml are typically azoospermic (complete absence of sperm), according to Japanese cohort data examining the relationship between testicular volume and semen parameters 2
• Testicular volumes between 10-20ml are associated with severe oligozoospermia (very low sperm counts), while volumes below 10ml cross into the azoospermic range 2
• Mean testicular size strongly correlates with total sperm count and sperm concentration, with this correlation being the strongest among all semen parameters 1, 2

The Biological Basis for This Relationship

The relationship between testicular volume and sperm production is direct and physiological:

• Testicular volume reflects the mass of seminiferous tubules where spermatogenesis occurs - smaller testes simply have less functional tissue capable of producing sperm 1, 3
• At 4ml, the testicular volume is approximately one-third of the 12ml threshold for atrophy, representing profound loss of spermatogenic tissue 1
• Biofunctional sperm parameters worsen with near-linear correlation as testicular volume decreases, including mitochondrial function, DNA integrity, and chromatin compactness 3

Hormonal Patterns Expected with 4ml Testes

Men with such severe testicular atrophy typically demonstrate:

• Markedly elevated FSH levels (often >7.6 IU/L and frequently much higher), as the pituitary attempts to compensate for testicular failure 4, 5
• The FSH elevation reflects the negative correlation between FSH and spermatogonial numbers - higher FSH indicates fewer sperm-producing cells 4
• This pattern is characteristic of non-obstructive azoospermia due to primary testicular dysfunction 4, 5

Rare Exceptions and Important Caveats

While the overwhelming likelihood is azoospermia, there are critical nuances:

• Up to 50% of men with non-obstructive azoospermia may have retrievable sperm with microsurgical testicular sperm extraction (micro-TESE), even with elevated FSH and small testicular volumes 4
• This does NOT mean sperm are present in the ejaculate - it means that with surgical extraction, isolated pockets of spermatogenesis might be found 4
• Micro-TESE retrieval rates are approximately 29.5% in Japanese cohorts with non-obstructive azoospermia, though success rates vary by etiology 6
• Importantly, testicular volume itself did not significantly predict micro-TESE success in multivariate analysis, suggesting that even severely atrophic testes may harbor focal areas of sperm production 6

Essential Diagnostic Workup

For any man with 4ml testicular volume, the following evaluation is mandatory:

• Perform at least two semen analyses with centrifugation to confirm azoospermia or determine the degree of oligospermia 4, 5
• Measure FSH, LH, and testosterone levels to distinguish primary testicular failure from secondary hypogonadism 4, 5
• Obtain karyotype analysis and Y-chromosome microdeletion testing (AZFa, AZFb, AZFc regions) if azoospermia or severe oligospermia is confirmed, as genetic abnormalities occur in 10% of these patients 4, 5
• Complete AZFa and AZFb deletions result in almost zero likelihood of sperm retrieval and would contraindicate surgical extraction attempts 4

Clinical Bottom Line

The realistic expectation for a man with 4ml testicular volume is azoospermia in the ejaculate. 2 However, this does not mean absolute sterility - microsurgical sperm extraction may retrieve sperm in approximately 30-50% of cases for use with assisted reproductive technology. 4, 6 The key distinction is between sperm in the ejaculate (extremely unlikely) versus retrievable sperm through surgical extraction (possible but not guaranteed).