What causes testicular damage and lack of sperm?

Causes of Testicular Damage and Lack of Sperm Production

Testicular damage and lack of sperm production (azoospermia) are commonly caused by congenital conditions like cryptorchidism (undescended testes), genetic abnormalities, hormonal imbalances, and acquired conditions such as testicular trauma, infections, and environmental exposures.

Congenital Causes

Cryptorchidism (Undescended Testes)

• Affects approximately 1% of all infants and is a significant risk factor for infertility 1
• Part of testicular dysgenesis syndrome (TDS), a developmental disorder caused by genetic and environmental influences during pregnancy 1
• Degeneration of germ cells in undescended testes begins after the first year of life and progressively worsens 1
• Men with history of bilateral cryptorchidism have significantly reduced paternity rates (35-53%) compared to those with normal testicular descent 1
• Delayed treatment significantly increases risk of infertility - correction should be performed before puberty 2

Genetic Abnormalities

• Karyotype abnormalities are the most common known genetic causes of male infertility 1
• Chromosomal numerical anomalies like Klinefelter syndrome (47,XXY) can cause severe impairment of spermatogenesis 1
• Y-chromosome microdeletions are found in approximately 5% of males with severe oligospermia (sperm concentrations 0-1 million/mL) 1
• Complete AZFa and AZFb Y-chromosome microdeletions result in almost zero likelihood of sperm retrieval 3

Acquired Causes

Testicular Trauma and Injury

• Physical trauma to testes can cause temporary or permanent damage to sperm production 4
• Recovery from trauma-induced azoospermia is possible in some cases, even without surgical intervention 4

Testicular Inflammation and Infection

• Inflammatory cells are present in 15% of testicular biopsies from infertile patients 5
• Pro-inflammatory cytokines directly affect germ cell survival through receptors like IL-6R, TNFR1, Fas and IL-1R expressed on germ cells 5
• Epididymitis and epididymo-orchitis caused by bacterial infections (N. gonorrhoeae, C. trachomatis, enteric bacteria) can impair fertility 6

Testicular Atrophy

• Presents clinically with low testicular volume, normal sperm volume, and high FSH values (typically >7.6 IU/L) 3
• Despite severe atrophy, spermatogenesis may persist in small, isolated foci within the testes 3
• Associated with non-obstructive azoospermia (NOA), defined as absence of sperm in ejaculate after centrifugation 3

Environmental and Lifestyle Factors

• Environmental exposures to endocrine-disrupting chemicals may contribute to testicular dysgenesis syndrome 1
• Anabolic steroid use suppresses spermatogenesis and interferes with fertility 1
• Diet high in fats and meats (versus fruits and vegetables) may negatively impact male fertility, though evidence quality is low 1
• Smoking has been linked to small impacts on sperm concentration, motility, and morphology 1

Clinical Presentation and Diagnosis

Semen Analysis Findings

• Azoospermia: Complete absence of sperm in ejaculate 1
• Oligozoospermia: Low sperm concentration 1
• Asthenozoospermia: Reduced sperm motility 1
• Teratozoospermia: Abnormal sperm morphology 1

Laboratory Evaluation

• Elevated FSH (>7.6 IU/L) suggests testicular failure/non-obstructive azoospermia 1
• Low testosterone levels with elevated LH indicates hypogonadism, common in men with history of undescended testes 2
• Hormonal levels (FSH, LH, inhibin B, AMH) correlate variably with sperm retrieval outcomes 3

Health Implications Beyond Fertility

• Men with abnormal semen parameters have higher rates of testicular cancer 1
• Men with azoospermia have higher rates of cancer in general than fertile men 1
• History of cryptorchidism increases testicular cancer risk 3.6-7.4 times compared to general population 1
• Mortality rates have been positively associated with abnormal semen analyses 1
• Latent, rarely decompensated hypogonadism is a potential long-term consequence of undescended testes 2

Prevention and Management

• Early orchidopexy (surgical correction of undescended testes) before puberty reduces risk of testicular cancer and improves fertility potential 1
• Men with history of cryptorchidism should perform regular testicular self-examinations due to increased cancer risk 1
• Therapies with antioxidant and anti-inflammatory agents have shown success in experimental models of testicular damage 5
• Microsurgical testicular sperm extraction (micro-TESE) may be an option for men with non-obstructive azoospermia 7