Infertility

Male infertility refers to a male’s inability to cause pregnancy in a fertile female. In humans it accounts for 40-50% of infertility. Male infertility is commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.^[4]

Pre-testicular causes

Pre-testicular factors refer to conditions that impede adequate support of the testes and include situations of poor hormonal support and poor general health including:

• Hypogonadotropic hypogonadism due to various causes
  • Obesity increases the risk of hypogonadotropic hypogonadism.^[6] Animal models indicate that obesity causes leptin insensitivity in the hypothalamus, leading to decreased Kiss1expression, which, in turn, alters the release of gonadotropin-releasing hormone (GnRH).^[6]
• Drugs, alcohol
• Strenuous riding (bicycle riding,^[7] horseback riding)
• Medications, including those that affect spermatogenesis such as chemotherapy, anabolic steroids, cimetidine, spironolactone; those that decrease FSH levels such as phenytoin; those that decrease sperm motility such as sulfasalazine and nitrofurantoin
• Genetic abnormalities such as a Robertsonian translocation

Tobacco smoking

Male smokers also have approximately 30% higher odds of infertility.^[8] There is increasing evidence that the harmful products of tobacco smoking kill sperm cells.^[9][10] Therefore, some governments require manufacturers to put warnings on packets. Smoking tobacco increases intake of cadmium, because the tobacco plant absorbs the metal. Cadmium, being chemically similar to zinc, may replace zinc in the DNA polymerase, which plays a critical role in sperm production. Zinc replaced by cadmium in DNA polymerase can be particularly damaging to the testes.^[11]

DNA damage

Common inherited variants in genes that encode enzymes employed in DNA mismatch repair are associated with increased risk of sperm DNA damage and male infertility.^[12] As men age there is a consistent decline in semen quality, and this decline appears to be due to DNA damage.^[13] (Silva et al., 2012). These findings suggest that DNA damage is an important factor in male infertility.

Testicular factors

Testicular factors refer to conditions where the testes produce semen of low quantity and/or poor quality despite adequate hormonal support and include:

• Age
  See also: Paternal age effect
• Genetic defects on the Y chromosome
  • Y chromosome microdeletions
• Abnormal set of chromosomes
  • Klinefelter syndrome
• Neoplasm, e.g. seminoma
• Idiopathic failure
• Cryptorchidism
• Varicocele (14% in one study)^[14][15]
• Trauma
• Hydrocele
• Mumps^[16]
• Malaria
• Testicular cancer
• Defects in USP26 in some cases^[17]
• Acrosomal defects affecting egg penetration
• Idiopathic oligospermia – unexplained sperm deficiencies account for 30% of male infertility.^[18]

Radiation therapy to a testis decreases its function, but infertility can efficiently be avoided by avoiding radiation to both testes.^[19]

Post-testicular causes

Post-testicular factors decrease male fertility due to conditions that affect the male genital system after testicular sperm production and include defects of the genital tract as well as problems in ejaculation:

• Vas deferens obstruction
• Lack of Vas deferens, often related to genetic markers for Cystic Fibrosis
• Infection, e.g. prostatitis
• Retrograde ejaculation
• Ejaculatory duct obstruction
• Hypospadias
• Impotence