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Causes of infertility in men can be explained by deficiencies in sperm formation, concentration, or transportation. This general division allows an appropriate workup of potential underlying causes of infertility and helps define a course of action for treatment.

Male infertility. Normal male ductal anatomy.

Signs and symptoms

The initial step in the evaluation of an infertile male is to obtain a thorough medical and urologic history. Such a history should include consideration of the following:

  • Duration of infertility
  • Previous fertility in the patient and the partner
  • Timing of puberty (early, normal, or delayed)
  • Childhood urologic disorders or surgical procedures
  • Current or recent acute or chronic medical illnesses
  • Sexual history
  • Testicular cancer and its treatment
  • Social history (eg, smoking and alcohol use)
  • Medications
  • Family history
  • Respiratory disease
  • Environmental or occupational exposure
  • Spinal cord injury

The physical examination should include a thorough inspection of the following:

  • Testicles (for presence, size, consistency, and bilateral symmetry)
  • Epididymis (for presence bilaterally, as well as any induration, cystic changes, enlargement, or tenderness)
  • Vas deferens (for presence bilaterally, as well as any defects, segmental dysplasia, induration, nodularity, or swelling)
  • Spermatic cord (for varicocele)
  • Penis (for anatomic abnormalities, strictures, or plaques)
  • Rectum (for abnormalities of the prostate or seminal vesicles)
  • Body habitus

Depending on the findings from the history, detailed examination of other body functions may also be warranted.

Diagnosis

The semen analysis is the cornerstone of the male infertility workup and includes assessment of the following:

  • Semen volume (normal, 1.5-5 mL)
  • Semen quality
  • Sperm density (normal, >20 million sperm/mL)
  • Sperm motility (normal, >60% of sperm having normal movement)
  • Sperm morphology (>60% of sperm should be normal, and fewer than 2-3% should be immature)
  • Signs of infection – An increased number of white blood cells (WBCs) in the semen may be observed in patients with infectious or inflammatory processes
  • Other variables (eg, levels of zinc, citric acid, acid phosphatase, or alpha-glucosidase)

Other laboratory tests that may be helpful include the following:

  • Antisperm antibody test
  • Hormonal analysis

Imaging studies employed in this setting may include the following:

  • Transrectal ultrasonography
  • Scrotal ultrasonography
  • Vasography

An abnormal postcoital test result is observed in 10% of infertile couples. Indications for performing a postcoital test include semen hyperviscosity, increased or decreased semen volume with good sperm density, or unexplained infertility.

If the test result is normal, consider sperm function tests, such as the following:

  • Capacitation assay
  • Acrosome reaction assay
  • Sperm penetration assay
  • Hypoosmotic swelling test
  • Inhibin B level
  • Vitality stains

Testicular biopsy is indicated in azoospermic men with a normal-sized testis and normal findings on hormonal studies to evaluate for ductal obstruction, to further evaluate idiopathic infertility, and to retrieve sperm.

Management

The following causes of infertility, if identified, can often be treated by medical means:

  • Endocrinopathies
  • Antisperm antibodies
  • Retrograde ejaculation
  • Poor semen quality or number
  • Lifestyle issues
  • Infections

Surgical interventions to be considered include the following:

  • Varicocelectomy
  • Vasovasostomy or vasoepididymostomy
  • Transurethral resection of the ejaculatory ducts
  • Sperm retrieval techniques
  • Electroejaculation
  • Artificial insemination
  • Assisted reproduction techniques
  • In vitro fertilization
  • Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT)
  • Intracytoplasmic sperm injection

Medical Care

Limited numbers of medical treatments are aimed at improving chances of conception for patients with known causes of infertility.

Endocrinopathies

A number of patients with hypogonadotropic hypogonadism respond to GnRH therapy or gonadotropin replacement.

HCG is an LH analogue that may be used alone or in combination with HMG for Leydig cell stimulation.

Clomiphene citrate and tamoxifen are antiestrogens that block the negative feedback loop at the pituitary level, allowing a potentially increased release of gonadotropins.

Patients with CAH may respond to therapy with glucocorticoids, while those with isolated testosterone deficiency may respond to testosterone replacement.

Exogenous testosterone decreases intratesticular testosterone production, thus inhibiting Sertoli cell function and spermatogenesis.

Treat patients with hyperprolactinemia with bromocriptine, a dopamine antagonist, or cabergoline.

Antisperm antibodies

Patients with antisperm antibody levels greater than 1:32 may respond to immunosuppression using cyclic steroids for 3-6 months. However, patients need to be aware of the potential side effects of steroids, including avascular necrosis of the hip, weight gain, and iatrogenic Cushing syndrome.

Retrograde ejaculation

Imipramine or alpha-sympathomimetics, such as pseudoephedrine, may help close the bladder neck to assist in antegrade ejaculation. However, these medicines are of limited efficacy, especially in patients with a fixed abnormality such as a bladder neck abnormality occurring after a surgical procedure.

Alternatively, sperm may be recovered from voided or catheterized postejaculatory urine to be used in assisted reproductive techniques. The urine should be alkalinized with a solution of sodium bicarbonate for optimal recovery.

More recently, the injection of collagen to the bladder neck has allowed antegrade ejaculation in a patient who had previously undergone a V-Y plasty of the bladder neck and for whom pseudoephedrine and intrauterine insemination had failed.[18]

Semen processing

Patients with poor semen quality or numbers may benefit from having their semen washed and concentrated in preparation for intrauterine insemination.

Couples with an abnormal postcoital test result due to semen hyperviscosity may benefit from a precoital saline douche or semen processing with chymotrypsin.

Lifestyle

Patients should be encouraged to stop smoking cigarettes and marijuana and to limit environmental exposures to harmful substances and/or conditions.

Stress-relief therapy and consultation of other appropriate psychological and social professionals may be advised.

Infections should be treated with appropriate antimicrobial therapy.

 

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