Infertility (Male)

• Infertility Prevalence: 15% of couples
  • defined as the inability to conceive after at least one year of regular, unprotected sex.
  • affects 15–20% of couples.
• Male factors contribute to two thirds of Infertility
  • One third of Infertility cases due to male only
  • One third of Infertility cases due to both partners
• Causes
  • Idiopathic (40-50%)
  • Pre-testicular
    • Pharmacological
    • Secondary Hypogonadism (Hypothalamic-Pituitary Axis):2%
      • results from failure of the hypothalamic–pituitary axis to stimulate normal gonadal function. Causes include
        • congenital syndromes
          • Kallmann syndrome
        • brain tumours
          • Estrogen excess (e.g. tumor)
          • Pituitary Adenoma
          • Hyperprolactinaemia
        • trauma
        • drugs
          • Androgen Excess (e.g. Anabolic Steroids)
        • infection
        • systemic illness
  • Testicular
    • Varicocele (40%)
    • Testicular cancer
    • Radiation
    • Chemotherapy or pharmacological
    • Chromosomal abnormality
      • Y Deletions
        • Small Testes, low Sperm Count
      • Klinefelter Syndrome (XXY)
        • Learning Disorders, Tall Stature, Gynecomastia
        • Small Testes, Low Sperm Count
        • Low testosterone, increased FSH
      • Cystic Fibrosis is associated with vas deferens absence
        • Related genes: CFTR gene, 5T Allele
    • Genital radiation or Chemotherapy
    • Orchitis
      • Post-pubertal mumps
      • Sexually Transmitted Diseas
    • Environmental Exposures
      • Excessive Heat Exposure (hot tubs, saunas)
      • Toxic chemicals
      • Pesticides
    • Infection
    • Injury or trauma
    • Primary ciliary dyskinesia
    • Sertoli cell-only syndrome
    • Anti-sperm antibodies
    • Cryptorchidism (failed to descend)
  • Post testicular
    • Coital
    • Pharmacological
    • Nerve injury
    • Spinal cord injury
    • Systemic disease
    • Obstructive azoospermia or altered transport (10-20%)
      • Erectile Dysfunction
      • Retrograde ejaculation or other dysfunction
      • Hypospadias
      • Vas deferens absence (e.g. Cystic Fibrosis)
      • Vasectomy or Iatrogenic injury to the vas deferens
      • Epididymal absence

History

• History taken with both partners present
  • Prior Pregnancy and outcomes
  • General Factors
    • Age
    • Previous pregnancies
    • Number of contiguous months attempting conception
  • Symptoms of Sexually Transmitted Disease
    • Vaginal Discharge
    • Dysuria
    • Abdominal Pain
    • Fever
  • Menstrual History (wife)
  • Sexual History
    • Timing of intercourse in Menstrual Cycle
    • Frequency of intercourse
      • Optimally every day or every other day in Ovulation
    • Lubricant use (spermatotoxic)
    • History of Impotence
    • Dyspareunia
    • Technique
  • Comorbid condition
    • Diabetes Mellitus
    • Prior surgeries
      • Cryptorchidism
      • Testicular Torsion
      • Genitourinary ot retroperitoneal surgery
  • Social history
    • Gonadotoxin use (Medications that Impair Male Fertility)
    • Exposures: alcohol, smoking, occupational, environmental, lifestyle (heat exposure)
  • Review of Systems
    • Anosmia (Kallmann’s Syndrome)
    • Chronic Sinusitis and Bronchiectasis
      • Young’s Syndrome
      • Kartagener’s Syndrome (also with Situs inversus)
    • Visual field defect, Galactorrhea (Pituitary Lesion)

Exam

• General, height, weight
  • Secondary sexual characteristics:
    • Hair distribution: face, trunk, axilla, pubic
    • Muscle mass
    • Adiposity
  • Signs of Endocrinopathy (Hypogonadotropic Hypogonadism)
    • Thyromegaly
    • Dermatologic changes in hair or fat
  • Genital exam
    • position of meatus/Hypospadias
    • Assess testicular size
      • Normal >20 cm or >4 cm in diameter
    • Assess vas deferens and epididymis
    • Varicocele
  • Rectal exam
    • Assess Prostate Gland for Nodules or swelling

Evaluation

minimal assessment includes:

• FSH
  • if 2.5 times normal, indicates irreversible testicular failure
• morning testosterone levels
  • if low testosteroneà
    • repeat morning testosterone
    • free testosterone (measured or calculated from total testosterone, sex hormone-binding globulin and albumin, depending on local availability
    • LH
    • Prolactin

	FSH	LH	Testosterone	Prolactin
Hypogonadotropic hypogonadism	Low	Low	Low	Normal or high
Abnormal spermatogenesis	High or normal	Normal	Normal	Normal
Testicular failure or hypergonadotropic hypogonadism	High	High	Low	Normal
Prolactinoma	Normal or low	Normal or low	Low	High

Semen analysis is not definitive in determining a man’s fertility.

• Individuals with abnormal test results may still be able to conceive.
• Conversely, individuals with results within the reference range may be unable to conceive.

Collection Guidelines

• Abstinence period: 2-3 days is optimal.
  • Shorter periods can negatively impact sperm count.
  • Longer intervals can affect motility.

Step 1: Initial Semen Analysis

• Obtain 2 samples 2-3 months apart.
  • The interval reflects a >2 month sperm generation time.

Interpretation of Semen Analysis Results

Normal Semen Analysis

• Evaluate for female infertility.
• Discontinue gonadotoxins and lubricants used during intercourse.
• Reevaluate timing of intercourse during ovulation.

Abnormal Semen Analysis

• Varicocele present:
  • Consider referral to Urology for repair.
  • Note: Limited evidence suggests corrective surgery improves conception rates.
• No varicocele present:
  • Proceed to Step 2a.

Leukospermia (>1 million WBCs per ml)

• Perform PCR for chlamydia and gonorrhea, and semen culture.
  • Infections (e.g., urethritis, prostatitis, orchitis, epididymitis) are treatable causes of infertility.
• Treat infections as per sensitivities.
• Repeat semen analysis after treatment.

Azoospermia (No sperm present): 10-15% of cases

• Refer to a male infertility clinic for further evaluation.
  • Potential causes:
    • Vas deferens abnormality (e.g., absence, vasectomy)
    • Hypogonadotropic hypogonadism (secondary hypogonadism)
      • Causes: congenital syndromes, brain tumors, infiltrative diseases, trauma, drugs, infections, systemic illnesses.
• Management:
  • Avoid exogenous testosterone if the patient seeks infertility treatment.
  • Exogenous testosterone suppresses endogenous testicular testosterone production, impairing spermatogenesis.
  • Specialist input is required for managing hormonal abnormalities in infertile patients.

Step 2a: Evaluation of Semen Volume

• Is semen volume <1.5 ml?
  • No: Semen volume normal. Proceed to Step 3.
  • Yes: Semen volume <1.5 ml. Proceed to Step 2b.

Step 2b: Post-Ejaculatory Urine Analysis

• Positive for sperm: Retrograde ejaculation.
  • Consider pseudoephedrine 60 mg orally three times daily.
• Negative for sperm: Possible ejaculatory duct obstruction.
  • Measure Follicle Stimulating Hormone (FSH).
  • Refer to Urology and consider transrectal ultrasound.

Step 3: Evaluation of Sperm Concentration

• Sperm concentration >10-15 million/ml:
  • Refer to a male infertility clinic.
• Sperm concentration <10-15 million/ml (Oligospermia):
  • Suggests hypogonadism.
  • Primary hypogonadism: Increased FSH, decreased serum testosterone.
  • Secondary hypogonadism: Decreased FSH, decreased serum testosterone.
  • Refer to a male infertility clinic.
  • Measure FSH, serum testosterone, and serum prolactin.
  • Genetic counseling for sperm <5 million/ml.

Management Considerations in General Practice

• Alcohol: Moderate consumption (3-4 units/day) is unlikely to affect sperm quality, but excessive consumption is detrimental.
• Smoking: Associated with decreased semen quality.
• Obesity: BMI >30 kg/m² likely reduces fertility.
• Scrotal temperature: Elevated temperatures reduce semen quality.
• Drugs: Certain prescription, OTC, and recreational drugs interfere with fertility.
• Occupation: Exposure to heat, ionizing radiation, vibrations, pesticides, and solvents may reduce fertility.
• Frequency of intercourse: Timed around ovulation or every 2-3 days.

Indications for Referral to a Male Infertility Specialist

• Abnormalities identified in basic evaluation (hormonal, anatomical, pathological).
• Hormonal abnormalities, e.g., hypogonadotropic hypogonadism, may require a subspecialist endocrinologist.
• Couples with unexplained infertility (normal male and female investigations).
• Couples failing to conceive despite successful female factor treatment.
• Patients undergoing gonadotoxic treatment desiring future fertility.

Overview of Specialist Management of Male Infertility

• Hypogonadotropic hypogonadism:
  • Normalization of prolactin for hyperprolactinaemia (surgery, dopamine receptor agonist, ceasing causative drugs).
  • Gonadotropin treatment if normalization of testosterone does not occur after six months.
• Varicocele:
  • Correction improves pregnancy rates in patients with clinically detectable varicocele and abnormal semen analysis.
• Retrograde ejaculation:
  • Sympathomimetic agents (e.g., pseudoephedrine) to close the bladder neck.
  • Assisted reproductive techniques (ART) for sperm retrieval from post-ejaculatory urine.
• Anejaculation:
  • Penile vibratory devices or electroejaculation for sperm retrieval.
• Ejaculatory duct obstruction:
  • Transurethral resection of the ejaculatory ducts (TURED) with a 50% success rate.
• Obstructive azoospermia:
  • Reconstructive surgery (e.g., vasovasostomy, vasoepididymostomy) or ART techniques for sperm retrieval.
• Non-obstructive azoospermia:
  • Microsurgical testicular sperm extraction (microTESE) for sperm retrieval.
• Cryopreservation of sperm:
  • Recommended for patients undergoing treatments affecting fertility or with severe oligozoospermia.