Male Infertility

Background

• Infertility is defined as the inability to conceive after 1 year of unprotected sexual intercourse.
• The worldwide incidence of infertility for reproductive-aged couples is 8%-12% (and up to about 15%) worldwide. In the United States, male factor infertility may affect about 9% of male persons aged 15-44 years.
• The cause of infertility involves male factors alone in 30% of infertile couples.
• Common risk factors for male infertility include:
  • genital tract obstruction due to congenital abnormalities, infection, trauma, or postsurgical complications
  • genetic conditions such as karyotypic chromosomal abnormalities associated with impaired testicular function, Y-chromosome microdeletions, X-linked genetic disorders, and sperm chromosomal aneuploidy
  • endocrine pathology, such as hyperprolactinemia
  • gonadotoxic factors, including exposure to chemotherapy or radiation therapy
  • Idiopathic factors such as obesity, smoking, alcohol, stress, diet, and age

Evaluation

• Assess medical and reproductive history, and perform physical exam and semen analysis (Strong recommendation).
• Consider endocrine evaluation, genetic testing, or imaging studies in infertile male persons with inconclusive results on history, physical, and semen analysis.
  • Consider hormonal testing including follicle-stimulating hormone (FSH)/luteinizing hormone (LH) and serum total testosterone in male persons with impaired libido, erectile dysfunction, oligozoospermia or azoospermia, atrophic testes, or hormonal abnormality (Weak recommendation), to identify specific clinical states contributing to infertility.
  • Genetic testing:
    • Offer cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation testing to male persons (and to their female partners) with structural abnormalities of the vas deferens or idiopathic obstructive azoospermia.
    • Offer karyotype testing to male persons with azoospermia or oligospermia (sperm cell count 5-10 million/mL).
    • Offer Y chromosome microdeletion analysis to male persons with sperm cell count < 5 million/mL and especially in those with sperm cell count < 1 million/mL, but do not offer it to those with pure obstructive azoospermia.
  • Consider scrotal ultrasound in male persons with infertility, due to increased risk of testicular cancer in this population (Weak recommendation).

Management

• For male persons with hypogonadotropic hypogonadism:
  • Offer either combined human chorionic gonadotropin (hCG) plus FSH or pulsed gonadotropin releasing hormone (GnRH) via pump therapy (Strong recommendation).
  • Induce spermatogenesis with hCG, human menopausal gonadotropins, recombinant FSH, or highly purified FSH (Strong recommendation).
  • Offer testosterone only to symptomatic patients with primary and secondary hypogonadism who are not considering parenthood (Strong recommendation); otherwise, do not use testosterone as treatment for infertility in male persons interested in parenthood (Strong recommendation).
• For male persons with idiopathic infertility:
  • Consider an FSH analogue to increase sperm concentration, pregnancy rate, and live birth rate (Weak recommendation).
  • Avoid antioxidants, selective estrogen receptor modulators (SERMs), and steroidal (testolactone) or nonsteroidal (anastrozole and letrozole) aromatase inhibitors (AIs) (Weak recommendation).
• For male persons with hyperprolactinemia, consider dopamine antagonists.
• For male persons with obstructive azoospermia, consider microsurgical vasovasostomy or epididymovasostomy for azoospermia due to epididymal or vasal obstruction.
• For male persons with nonobstructive azoospermia, offer surgery for sperm retrieval in male persons eligible for assisted reproductive technology (such as intracytoplasmic sperm injection [ICSI]) (Strong recommendation), but do not perform surgery in those male persons with complete AZFa and AZFb microdeletions (Strong recommendation).
• For male persons with varicocele:
  • Consider varicocelectomy in male persons with palpable varicocele, infertility, and abnormal semen parameters, in those with increased DNA fragmentation and otherwise unexplained infertility, or in those who received unsuccessful assisted reproductive techniques (including recurrent pregnancy loss, failure of embryogenesis and implantation) (Weak recommendation).
  • Avoid varicocelectomy in male persons with nonpalpable varicocele only detected on imaging studies (Strong recommendation), and do not consider it in male persons with azoospermia (Weak recommendation).
• Consider sperm retrieval for in vitro fertilization (IVF) via ICSI in male persons with surgically uncorrected azoospermia, failed microsurgical vasectomy reversal, congenital bilateral absence of vas deferens, and those with a female partner of advanced age or requiring in vitro fertilization.