Comprehensive Evaluation and Management of Male Infertility with Low Testosterone and Abnormal Semen Parameters
Immediate Next Steps
The next best step is to obtain a complete hormonal panel including repeat morning testosterone, calculate free testosterone using SHBG, measure prolactin to exclude hyperprolactinemia, and perform at least one additional semen analysis after 2–3 months to confirm the pattern of asthenozoospermia and failed liquefaction. 1
This patient presents with a constellation of findings suggesting primary testicular dysfunction with reduced testicular reserve: low testosterone (2.11 ng/mL ≈ 7.3 nmol/L), borderline-low semen volume (1.1 mL), failed liquefaction, increased viscosity, asthenozoospermia, and metabolic derangements (hypertriglyceridemia). The FSH of 3.39 mIU/mL is not elevated, which is atypical for primary testicular failure but does not exclude it—FSH levels alone cannot definitively predict fertility status, and men with maturation arrest can have normal FSH despite severe spermatogenic dysfunction. 1
Critical Diagnostic Priorities
1. Confirm the Hormonal Pattern
Repeat morning testosterone measurement (08:00–10:00 h) on at least two separate occasions to establish a reliable baseline, as FSH and testosterone show pulsatile secretion and single measurements can be misleading. 1
Measure SHBG and calculate free testosterone using equilibrium dialysis, because total testosterone of 2.11 ng/mL may underestimate bioavailable testosterone if SHBG is low (common in metabolic syndrome), or overestimate it if SHBG is elevated. 1
Check serum prolactin to exclude hyperprolactinemia, which can disrupt gonadotropin secretion and suppress both LH and FSH, leading to secondary hypogonadism that mimics primary testicular dysfunction. 1
The LH of 6.1 mIU/mL is in the normal range, which argues against classic primary testicular failure (which would show elevated LH). However, the pattern of low testosterone with normal-to-low FSH and normal LH raises the possibility of secondary (hypogonadotropic) hypogonadism or a mixed picture. 1, 2
2. Repeat Semen Analysis
Perform at least one additional semen analysis after 2–3 months to confirm the pattern of asthenozoospermia, failed liquefaction, and low volume, as single analyses can be misleading due to natural variability. 1, 3
The failed liquefaction after 2 hours and increased viscosity suggest either accessory gland dysfunction (prostate/seminal vesicles) or incomplete sample collection. 4 Low semen volume (1.1 mL, normal ≥1.5 mL) can be artifactual (incomplete collection), structural (ejaculatory duct obstruction, congenital absence of vas deferens), or functional (retrograde ejaculation, hypogonadism). 4, 2
Post-ejaculate urinalysis should be performed if retrograde ejaculation is suspected (especially if the patient has diabetes, prior pelvic surgery, or takes alpha-blockers). 4
Address Reversible Metabolic and Endocrine Factors
Hypertriglyceridemia and Metabolic Syndrome
Triglycerides of 251.7 mg/dL and VLDL of 50.3 mg/dL are significantly elevated and indicate metabolic dysfunction. Men with low sperm counts have higher rates of metabolic syndrome, insulin resistance, elevated triglycerides, and lower HDL cholesterol compared to fertile controls. 5
Optimize metabolic parameters through weight loss (if BMI >25), dietary modification, and exercise, as obesity and metabolic syndrome impair male fertility and can disrupt the hypothalamic-pituitary-gonadal axis. 1, 5 Weight normalization and metabolic optimization may improve hormonal parameters in some cases. 1
Consider statin therapy if lifestyle modifications fail to reduce triglycerides below 200 mg/dL, as persistent hypertriglyceridemia is associated with cardiovascular risk and may worsen testosterone levels. 5
Low Testosterone with Normal LH/FSH: Consider Secondary Hypogonadism
The combination of low testosterone (2.11 ng/mL) with normal LH (6.1 mIU/mL) and low-normal FSH (3.39 mIU/mL) is not consistent with primary testicular failure, which would show elevated LH and FSH. 1, 2
This pattern suggests secondary (hypogonadotropic) hypogonadism or functional hypogonadism due to metabolic stress, obesity, or chronic illness. 1, 2 Low or low-normal LH with low testosterone indicates pituitary dysfunction and requires prolactin measurement. 1
If prolactin is elevated, obtain MRI of the pituitary to exclude prolactinoma or other sellar masses. 2 One case report describes a 32-year-old man with decreased ejaculatory volume (0.35 mL) and severe oligospermia who was found to have acquired hypogonadotropic hypogonadism with castrate testosterone levels, low FSH/LH, and a partially empty sella turcica on MRI. 2
Genetic Testing and Structural Evaluation
When to Perform Genetic Testing
Karyotype analysis and Y-chromosome microdeletion testing (AZFa, AZFb, AZFc regions) are mandatory if repeat semen analysis confirms severe oligospermia (<5 million/mL) or azoospermia. 1, 5 Chromosomal abnormalities occur in 10% of men with severe oligospermia or azoospermia. 1
Complete AZFa and AZFb deletions predict near-zero sperm retrieval success and would contraindicate testicular sperm extraction (TESE), regardless of testicular volume. 1, 6
AZFc deletions are associated with variable clinical presentation including oligospermia or azoospermia, with sperm successfully retrieved via micro-TESE in 53–75% of cases. 6
Testicular Volume Assessment
Physical examination with Prader orchidometer should assess testicular volume, consistency, presence of varicocele, and vas deferens/epididymal abnormalities. 1, 6 Testicular volumes <12 mL are definitively considered atrophic and associated with impaired spermatogenesis, elevated FSH, and increased risk of intratubular germ cell neoplasia (TIN). 6, 7
If testicular volume is <12 mL or there is a size discrepancy >2 mL between testes, obtain scrotal ultrasound to exclude structural pathology, testicular masses, or varicocele. 6, 7
Men with testicular volume <12 mL and age <30–40 years have a ≥34% risk of TIN in the contralateral testis if testicular cancer develops, and if untreated, 70% progress to invasive cancer within 7 years. 6
Treatment Considerations
Critical Pitfall: Avoid Exogenous Testosterone
Never prescribe exogenous testosterone therapy if fertility is desired, as it will completely suppress spermatogenesis through negative feedback on the hypothalamus and pituitary, causing azoospermia that can take months to years to recover. 1, 2
If Secondary Hypogonadism is Confirmed
Human chorionic gonadotropin (hCG) injections can stimulate testosterone production and improve spermatogenesis in men with hypogonadotropic hypogonadism. 1, 2 In the case report cited above, treatment with hCG alone normalized testosterone levels, sperm concentration, and semen volume, resulting in successful conception. 2
FSH analogues may be added after testosterone normalizes on hCG if sperm counts remain low, though benefits are measurable but limited. 1
If Primary Testicular Dysfunction is Confirmed
Assisted reproductive technology (IVF/ICSI) offers superior pregnancy rates compared to empiric hormonal therapy and should be discussed early, especially given female partner age considerations. 1
Microsurgical testicular sperm extraction (micro-TESE) offers sperm retrieval rates of 40–50% even with elevated FSH in non-obstructive azoospermia, and is 1.5 times more successful than conventional TESE. 1, 7
Address Failed Liquefaction and Increased Viscosity
- Failed liquefaction and increased viscosity may respond to enzymatic treatment (e.g., chymotrypsin) or mechanical disruption during assisted reproduction, but the underlying cause (accessory gland dysfunction vs. incomplete collection) must be clarified first. 4
Fertility Preservation
Sperm cryopreservation should be performed immediately if any sperm are present in the ejaculate, banking 2–3 separate collections with 2–3 days abstinence between collections, to provide insurance against technical failures, poor post-thaw recovery, or need for multiple treatment attempts. 1 This is especially critical given the patient's reduced testicular reserve and metabolic risk factors. 5
Monitoring and Long-Term Health Implications
Men with abnormal semen parameters have higher rates of testicular cancer and increased mortality rates compared to fertile men. 5, 3 Infertile men have more comorbidities, including metabolic syndrome, insulin resistance, osteoporosis, and cardiovascular disease. 5
Repeat semen analysis every 6–12 months to detect early decline in sperm parameters, as single analyses can be misleading. 1, 3
Teach testicular self-examination given the increased cancer risk associated with metabolic syndrome and potential testicular atrophy. 6, 7
Avoid gonadotoxic exposures including exogenous testosterone, anabolic steroids, chemotherapy, and radiation, which can cause additional impairment to fertility. 1, 7