Board Review

A 33-year-old man is evaluated for infertility. As part of this evaluation, azoospermia is identified on two sequential semen analyses. His medical history is otherwise notable for chronic sinusitis. He takes no medications.

On physical examination, vital signs are normal. BMI is 24. There is no evidence of inguinal hernia. A small left-sided varicocele is present that empties when the patient is recumbent. Testicles are of normal size. Absence of the vas deferens is noted bilaterally.

Which of the following is most likely responsible for this patient's infertility?

A) Anabolic steroid abuse

B) Cystic fibrosis

C) Klinefelter syndrome

D) Varicocele

E) Y chromosome microdeletions

Answer: B - Cystic fibrosis

Objective: Diagnose cystic fibrosis as a cause of congenital bilateral absence of the vas deferens and azoospermia.

Key Point

Congenital bilateral absence of the vas deferens is a common cause of obstructive azoospermia and is frequently associated with cystic fibrosis.

Congenital bilateral absence of the vas deferens is a common cause of obstructive azoospermia and is frequently associated with cystic fibrosis (CF). It may also present with unilateral absence of the vas deferens. Many patients are unaware that they have CF because they may have a mild form that causes only nonspecific symptoms such as chronic sinusitis. Partner testing for CF-carrier status should be encouraged to assess the likelihood of transmission to a subsequent generation. Sperm production is often normal in these patients; however, the absence of the vas deferens limits any observable sperm in the ejaculate. Therefore, testicular biopsy is necessary to retrieve sperm for use in advanced reproductive techniques (ART) such as in vitro fertilization and intracytoplasmic sperm injection. Utilization of donor sperm is an alternative for couples not interested in ART.

Androgen abuse is common among elite and professional athletes and in young men. Physical examination findings may include excessive muscular bulk, acne, gynecomastia, and decreased testicular volume. Low sperm counts also may be present with exogenous androgen use. Androgen abuse can result in hypogonadism and infertility, which occasionally are irreversible. This patient's normal physical examination, normal testicular volume, and absence of the vas deferens argue against this diagnosis.

Primary hypogonadism is due to testicular failure and is defined as a low testosterone level with elevated luteinizing hormone and follicle-stimulating hormone levels. Primary hypogonadism can have congenital or acquired causes. The most common congenital cause is Klinefelter syndrome (47,XXY karyotype). The extra sex chromosome results in malformation of the seminiferous tubules and typically of the Leydig cells. Physical examination is likely to reveal small, firm testes and decreased virilization. Additional manifestations include oligospermia and infertility. Klinefelter syndrome does not result in obstructive azoospermia due to absence of the vas deferens.

A clinically palpable varicocele typically affects fertility by lowering sperm motility through a local heat effect. A scrotal bulge may be noted by the clinician, and the patient may note pain that is worse with the Valsalva maneuver. Azoospermia would not be caused by varicocele alone.

Y chromosome microdeletions can be associated with oligospermia or azoospermia and small testicular volume. This chromosomal abnormality is not associated with absence of the vas deferens and is therefore not a likely cause of this patient's findings.

Stahl PJ, Schlegel PN. Genetic evaluation of the azoospermic or severely oligozoospermic male. Curr Opin Obstet Gynecol. 2012 Aug;24(4):221-8. Link Out