Reproductive · Male Infertility
The facts most likely to be tested
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The semen analysis is the initial diagnostic test of choice, requiring at least one sample, with a repeat obtained 2-4 weeks later when the first is abnormal to confirm oligospermia or azoospermia.
A varicocele is the most common surgically correctable cause of male infertility, typically presenting as a bag of worms on physical exam that increases with Valsalva maneuver.
Patients with azoospermia and normal FSH levels warrant evaluation for obstructive causes, such as congenital bilateral absence of the vas deferens (CBAVD), which is highly associated with cystic fibrosis mutations.
Primary testicular failure is characterized by hypergonadotropic hypogonadism, evidenced by elevated FSH and LH levels alongside low testosterone.
Kallmann syndrome is a form of hypogonadotropic hypogonadism caused by a failure of GnRH-secreting neurons to migrate, classically presenting with anosmia or hyposmia.
Klinefelter syndrome (47,XXY) is the most common chromosomal cause of male infertility, presenting with small, firm testes, gynecomastia, and tall stature.
Exogenous testosterone therapy suppresses the hypothalamic-pituitary-gonadal axis, leading to decreased intratesticular testosterone and subsequent azoospermia.
Vignette unlocked
A 32-year-old male presents for evaluation of primary infertility after 18 months of unprotected intercourse. Physical examination reveals a soft, nontender mass in the left hemiscrotum that feels like a bag of worms and increases in size with Valsalva maneuver. Semen analysis demonstrates oligospermia with decreased motility. The patient's serum FSH, LH, and testosterone levels are within normal limits.
What is the most likely diagnosis and the underlying pathophysiology?
Varicocele caused by venous reflux due to incompetent valves in the pampiniform plexus.
The vignette describes the classic physical exam findings of a varicocele, which is the most common surgically correctable cause of male infertility as outlined in the second bet.
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High yield triage
Etiology / Epidemiology
Defined as failure to conceive after 12 months of unprotected intercourse. Varicocele is the most common reversible cause.
Clinical Manifestations
Often asymptomatic; look for bag of worms on exam. Testicular atrophy suggests primary hypogonadism.
Diagnosis
Semen analysis is the initial test of choice. Threshold: <16 million/mL sperm concentration (oligospermia).
Treatment
Treat underlying cause. Clomiphene citrate or FSH/hCG for hormonal issues. Avoid exogenous testosterone.
Prognosis
Success depends on etiology. Varicocelectomy improves parameters in ~60-80% of patients.
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Epidemiology & Etiology
Male factor contributes to ~40-50% of infertility cases. Primary causes include varicocele, cryptorchidism, and genetic disorders like Klinefelter syndrome. Environmental factors include smoking, alcohol, and heat exposure.
Pertinent Anatomy
The pampiniform plexus is the site of venous drainage for the testes. Dysfunction here leads to venous stasis and hyperthermia, which impairs spermatogenesis.
Pathophysiology
Infertility results from pre-testicular (endocrine), testicular (primary failure), or post-testicular (obstruction) pathology. Elevated scrotal temperature from varicocele causes oxidative stress and DNA damage. Hypothalamic-pituitary-gonadal axis disruption leads to low FSH/LH and secondary hypogonadism.
Clinical Manifestations
Physical exam should assess for testicular volume and presence of a varicocele, which feels like a bag of worms. Red flags include sudden onset of symptoms or a solid testicular mass, which warrants ruling out testicular cancer.
Diagnosis
Semen analysis requires at least one sample, with a repeat obtained 2-4 weeks later if the first is abnormal. Key parameters include volume ≥1.4 mL, concentration ≥16 million/mL, and total motility ≥42% (WHO 6th edition, 2021). If abnormal, order serum FSH and total testosterone to differentiate primary vs. secondary hypogonadism.
Treatment
Management is cause-specific. Varicocelectomy is indicated for men with infertility, a palpable varicocele, and abnormal semen parameters, as well as for symptomatic varicoceles. For hypogonadotropic hypogonadism, gonadotropin therapy (hCG with or without FSH) is used; Clomiphene citrate (a SERM) depends on an intact hypothalamic-pituitary axis and is used for idiopathic low testosterone rather than organic hypogonadotropic hypogonadism. Exogenous testosterone should be avoided in men seeking fertility (AUA/ASRM 2020) as it suppresses endogenous gonadotropin production and worsens infertility.
Prognosis
Prognosis is favorable for obstructive causes via surgical correction. Azoospermia carries a poorer prognosis, often requiring ICSI (intracytoplasmic sperm injection) for conception.
Differential Diagnosis
Varicocele: bag of worms sensation
Klinefelter syndrome: 47,XXY karyotype
Obstructive azoospermia: normal FSH; vas deferens palpable unless CBAVD
Testicular cancer: painless, firm, non-transilluminating mass
Hypogonadotropic hypogonadism: low FSH/LH and low testosterone