Male Infertility

Aka: Male Infertility, Male Subfertility, Infertility in Men

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II. Epidemiology

  1. Infertility Prevalence: 15% of couples
  2. Male factors contribute to two thirds of Infertility
    1. One third of Infertility cases due to male only
    2. One third of Infertility cases due to both partners

III. Causes

  1. Idiopathic (40-50%)
  2. Primary Hypogonadism (Testicular Failure): 30-40%
    1. Varicocele (40%)
    2. Medication of drug use (See Gonadotoxin)
    3. Exposures
      1. Excessive Heat Exposure (hot tubs, saunas)
      2. Toxic chemicals
      3. Pesticides
    4. Testicular surgeries or injury
    5. Cryptorchidism
    6. Chromosomal abnormality
      1. Y Deletions
        1. Small Testes, low Sperm Count
      2. Klinefelter Syndrome (XXY)
        1. Learning Disorders, Tall Stature, Gynecomastia
        2. Small Testes, Low Sperm Count
        3. Low Testosterone, increased FSH
      3. Cystic Fibrosis is associated with vas deferens absence
        1. Related genes: CFTR gene, 5T Allele
    7. Genital radiation or Chemotherapy
    8. Orchitis
      1. Post-pubertal mumps
      2. Sexually Transmitted Disease
  3. Obstructive azoospermia or altered transport (10-20%)
    1. Erectile Dysfunction
    2. Retrograde ejaculation or other dysfunction
    3. Hypospadias
    4. Vas deferens absence (e.g. Cystic Fibrosis)
    5. Epididymal absence
  4. Secondary Hypogonadism (Hypothalamic-Pituitary Axis):2%
    1. Hypogonadotropic Hypogonadism
    2. Androgen Excess (e.g. Anabolic Steroids)
    3. Estrogen excess (e.g. tumor)
    4. Pituitary Adenoma
    5. Hemochromatosis
    6. Kallman Syndrome
    7. Infiltrative Disorder
      1. Sarcoidosis
      2. Tuberculosis

IV. History

  1. See Infertility for coital factor history
  2. Childhood illnesses (e.g. mumps)
  3. Comorbid condition
    1. Diabetes Mellitus
  4. Prior surgeries
    1. Cryptorchidism
    2. Testicular Torsion
    3. Genitourinary ot retroperitoneal surgery
  5. Social history
    1. Gonadotoxin use (Medications that Impair Male Fertility)
    2. Toxin exposures (e.g. Heavy Metals, Pesticides)
    3. Substances (Tobacco, Alcohol, ilicit drug use)
  6. Sexual History
    1. Sexually Transmitted Infection history
    2. Erectile Dysfunction
    3. Libido
  7. Review of Systems
    1. Anosmia (Kallmann's Syndrome)
    2. Chronic Sinusitis and Bronchiectasis
      1. Young's Syndrome
      2. Kartagener's Syndrome (also with Situs inversus)
    3. Visual Field Defect, Galactorrhea (Pituitary Lesion)

V. Exam

  1. Body Mass Index
    1. Obesity impacts semen quality and Erectile Dysfunction
  2. Signs of Endocrinopathy (Hypogonadotropic Hypogonadism)
    1. Thyromegaly
    2. Dermatologic changes in hair or fat
  3. Genital exam
    1. Hypospadias
    2. Assess testicular size
      1. Normal >20 cm or >4 cm in diameter
    3. Assess vas deferens and epididymis
      1. Vas deferens may be absent on exam in Cystic Fibrosis
    4. Varicocele
  4. Rectal Exam
    1. Assess Prostate Gland for Nodules or swelling

VI. Evaluation

  1. Step 1: Semen Analysis
    1. Obtain 2 samples at 2-3 months apart
      1. Best samples are after 2 to 5 days of abstinence
      2. Three month interval between tests reflects a >2 month sperm generation time
    2. Normal Semen Analysis
      1. Evaluate for Female Infertility
      2. Discontinue Gonadotoxins
      3. Discontinue lubricant use with intercourse
      4. Reevaluate timing of intercourse during Ovulation
    3. Abnormal Semen Analysis
      1. Varicocele present
        1. Consider referral to Urology for repair
        2. Inadequate data to suggest corrective surgery improves conception rates
          1. Baazeem (2011) Eur Urol 60(4): 796-808 [PubMed]
      2. No Varicocele present
        1. Go to Step 2a Below
    4. Leukospermia (>1 million WBCs per ml)
      1. Diagnosis requires additional staining of WBCs
      2. May be consistent with Prostatitis
      3. Treat with Doxycycline 100 mg PO bid for 2 weeks
      4. Repeat Semen Analysis after treatment
    5. Azoospermia (No sperm present): 10-15% of cases
      1. Refer to Male Infertility clinic
      2. Further evaluation will distinguish causes
        1. Vas deferens abnormality (absence, Vasectomy)
        2. Hypogonadotropic Hypogonadism
        3. Testicular abnormality
  2. Step 2a: Is semen volume <1.5 ml?
    1. No: Semen volume normal: Go to Step 3
    2. Yes: Semen volume <1.5 ml: Go to Step 2b
  3. Step 2b: Obtain post-ejaculatory urine analysis
    1. Positive: Retrograde Ejaculation
      1. Consider Pseudophedrine 60 mg orally three times daily
    2. Negative: Possible ejaculatory duct obstruction
      1. Follicle Stimulating Hormone (FSH)
      2. Refer to Urology (and Transrectal Ultrasound)
  4. Step 3: Evaluate sperm concentration
    1. Sperm >10-15 million/ml
      1. Refer to Male Infertility clinic
    2. Sperm <10-15 million/ml (Oligospermia)
      1. Suggests Hypogonadism
        1. Primary Hypogonadism presents with increased FSH and decreased Serum Testosterone
        2. Secondary Hypogonadism presents with decreased FSH and decreased Serum Testosterone
      2. Refer to Male Infertility clinic
      3. Follicle Stimulating Hormone (FSH)
      4. Serum Testosterone
      5. Serum Prolactin
      6. Genetic Counseling for sperm <5 million/ml

VII. Management: Non-specific options

  1. In Vitro Fertilization (with or without intracytoplasmic sperm injection)
    1. Standard approach to Male Infertility without reversible cause
  2. Hormonal agents
    1. Antiestrogens
    2. Gonadotropins
    3. Attia (2013) Cochrane Database Syst Rev (8): CD005071 [PubMed]
  3. Antioxidants
    1. Zinc supplementation
    2. Vitamin E Supplementation
    3. L-Carnitine supplementation
    4. Showell (2011) Cochrane Database Syst Rev (1): CD007411 [PubMed]

VIII. References

  1. (2004) Fertil Steril 82(Suppl 1):S102-6 [PubMed]
  2. De Krester (1997) Lancet 349:787-90 [PubMed]
  3. Kolettis (2003) Am Fam Physician 67(10):2165-72 [PubMed]
  4. Kolettis (2001) J Urol 166:178-80 [PubMed]
  5. Lindsay (2014) Am Fam Physician 91(5): 308-14 [PubMed]
  6. Sharlip (2002) Fertil Steril 77:873-82 [PubMed]
  7. Sigman (1997) Urology 50:659-64 [PubMed]

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