Infertility, Male

Essentials of Diagnosis

• Male infertility is common, contributing to approximately 50% of infertility cases

• Causes include decreased or absent sperm production or function, or obstruction of the male genital tract

• Abnormal semen quality may indicate poor health or increased risk for certain health conditions

General Considerations

• Infertility is defined as the inability of a couple to conceive a child after 1 year of regular, unprotected sexual intercourse

• Infertility affects 15–20% of couples who wish to conceive

• Approximately 50% of cases result from male factors

• Simultaneous evaluation of the female partner is warranted (see Infertility, Female)

• Evaluation is indicated at 1 year

• Male infertility is associated with a higher risk of testicular germ cell cancer; thus, these men should be counseled appropriately and taught testicular self-examination

Symptoms and Signs

• History

  • Prior testicular insults (torsion, cryptorchism, trauma)

  • Infections (mumps orchitis, epididymitis, sexually transmitted infection)

  • Environmental factors (excessive heat, radiation, chemotherapy, prolonged pesticide exposure)

  • Medications

    • Testosterone, finasteride, cimetidine, selective serotonin reuptake inhibitors (SSRIs), and spironolactone may affect spermatogenesis

    • Phenytoin may lower follicle-stimulating hormone (FSH)

    • Sulfasalazine and nitrofurantoin may affect sperm motility

    • Tamsulosin may cause retrograde ejaculation

  • Drugs (eg, alcohol, marijuana)

  • Sexual function, frequency and timing of intercourse, use of lubricants, and each partner's previous fertility are important

  • Loss of libido, headaches, visual disturbances, or galactorrhea may indicate a pituitary tumor

• Past medical or surgical history

  • Chronic disease, including obesity; cardiovascular, thyroid or liver disease (abnormalities of spermatogenesis)

  • Diabetes mellitus (decreased spermatogenesis, retrograde or anejaculation)

  • Radical pelvic or retroperitoneal surgery (absent seminal emission secondary to sympathetic nerve injury)

• Physical examination: signs of hypogonadism, such as underdeveloped sexual characteristics, diminished male pattern hair distribution (axillary, body, facial, pubic), body habitus, gynecomastia, and obesity

• Evaluate testicular size (normal size ~4.5 × 2.5 cm, volume 18 mL)

• Examine for varicocele in the standing position, with Valsalva maneuver

• Palpate the vasa deferentia and epididymides

Laboratory Tests

• Semen analysis after 3 to 5 days of ejaculatory abstinence (see Infertility, Female)

• Evaluation of the hypothalamic-pituitary-gonadal axis

  • Initial testing should include serum testosterone and FSH

  • Specific abnormalities in these hormones should prompt additional testing, including serum LH, and prolactin

  • Elevated FSH and LH and low testosterone (hypergonadotropic hypogonadism) in primary testicular failure

  • Low FSH and LH and low testosterone in secondary testicular failure (hypogonadotropic hypogonadism) of hypothalamic or pituitary origin

  • Elevation of serum prolactin may indicate the presence of prolactinoma

  • Elevation of estradiol may impair normal gonadotropin production and impact normal spermatogenesis

Imaging Studies

• Scrotal ultrasound

  • Can aid in characterizing the testes

  • May detect a testicular mass or a subclinical varicocele

• Transrectal ultrasound to evaluate the prostate and seminal vesicles

• MRI

  • Head: Imaging of the sella turcica should be performed in men with markedly elevated prolactin or hypogonadotrophic hypogonadism to evaluate the anterior pituitary gland

  • Pelvis and scrotum: Consider imaging in men for whom the testes cannot be identified in the scrotum by physical examination or ultrasound

• Imaging of abdomen: Consider in men with unilateral absence of the vas deferens to exclude absence of the ipsilateral kidney

Diagnostic Procedures

• Patients with low volume ejaculation should have post-ejaculation urine samples centrifuged and analyzed to exclude retrograde ejaculation

• Men with sperm concentrations less than 10 million/mL should consider testing for Y chromosome microdeletions and a karyotypic abnormalities

  • Gene deletions from the long arm of the Y chromosome may cause azoospermia or oligozoospermia with age-related decline in spermatogenesis that is transmissible to male offspring

  • Karyotyping may reveal Klinefelter syndrome (XXY male)

Medications

• Genitourinary tract infections should be treated with antibiotics

ENDOCRINE THERAPY

• Hypogonadotropic hypogonadism

  • Chorionic gonadotropin, 2000 international units intramuscularly three times weekly, once primary pituitary disease has been excluded or treated

  • If sperm counts fail to rise after 12 months, recombinant FSH therapy may be initiated (150 international units subcutaneously three times weekly)

EJACULATORY DYSFUNCTION THERAPY

• Alpha-adrenergic agonists (eg, pseudoephedrine, 60 mg three times daily orally) or imipramine, 25 mg three times daily orally

• Collect post-ejaculation urine for intrauterine insemination

• Electroejaculation or vibratory stimulation in cases of absent emission

Surgery

• Varicocelectomy

  • Surgical ligation is accomplished via a subinguinal incision with the aid of a surgical microscope

  • Doppler ultrasound is the gold standard approach given its high success and low complication rates

• Percutaneous venographic embolization of varicoceles is feasible but incurs both radiation and intravenous contrast exposure

• Ductal obstruction may be corrected by transurethral resection of the ducts in the prostatic urethra

• Obstruction of the vas deferens after vasectomy may be managed by microsurgical vasectomy reversal or by surgical sperm retrieval in combination with in vitro fertilization

Therapeutic Procedures

• Education

• Healthy lifestyle habits should be reinforced, including diet, exercise, and avoidance of gonadotoxins (such as tobacco smoke, marijuana, excessive alcohol)

• Proper timing for intercourse

• Avoidance of spermicidal lubricants

• Removal of toxins or medications

• Assisted reproductive techniques: intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection (ICSI)

When to Refer

• Couples with infertility or who are concerned about fertility potential

• Men with known genital insults (cryptorchidism, varicocele) or genetic diagnoses (cystic fibrosis, Klinefelter syndrome) that preclude natural fertility

• Reproductive-aged men with newly diagnosed cancer or other disease that may require cytotoxic therapies with interest in fertility preservation