Male factor infertility represents 35% of all infertility cases and the diagnosis is made by the presence of abnormal parameters on a semen analysis. Semen analysis has four main parameters which include the volume (≥ 1.5-2 mL), count (≥ 20 million/mL), motility (active/forward moving sperm ≥50%) and morphology (normal appearance ≥14% by Kruger’s criteria and >30% by the old WHO criteria). Male infertility can be divided into three major categories that include: abnormalities of sperm production, abnormalities of sperm function, and obstruction or absence of the ductal system. Unfortunately, majority of male factor infertility is idiopathic (cause unknown).
Abnormalities of the sperm production can be due to testicular failure (Y chromosome microdeletions or Klinefelter’s syndrome), damage to the testes (varicocele, cryptorchildism), toxins, radiation, infections (mumps), insufficient hormone production from the pituitary gland (FSH and LH) and use of androgenic compounds (testosterone). Abnormalities of sperm function can be due to an infection of the genital tract (prostatitis), varicocele (enlargement of the veins in the scrotum), anti-sperm antibodies, failure of sperm to attain the fertilization potential (acrosome reaction) and failure of sperm to bind and penetrate the egg (fertilization). Obstruction of the ductal system includes prior vasectomy (as a contraceptive approach), blockage of the ejaculatory or epididymal ducts and absence of the vas deference from birth (congenital absence of the vas deferens – CAVD).
Semen analysis should be done after 2-3 days of abstinence and not more than 7-10 days. If abnormal, it should be repeated for confirmation of the abnormal parameters and in the absence of sperm (azoospermia), urological evaluation is recommended. Semen analysis provides quantitative information about the sperm, and in some men with normal semen analysis quality of the sperm may still be compromised. A recently developed test called the sperm DNA integrity assay (SDIA) or sperm chromatin structure assay (SCSA) has been used to diagnose those cases of possibly unidentified male infertility with normal semen analysis. SDIA is a helpful tool for measuring clinically important properties of sperm nuclear chromatin integrity.
There are two components to this test, including the DNA Fragmentation Index (DFI) and high DNA stainability (HDS). Less than 15% of fragmentation and stainability are considered normal for either component and levels above 30-40% have been reported to rarely result in a live birth. SDIA has been shown to predict infertility and poor reproductive performance as it measures DNA damage. The DNA damage analysis may reveal a hidden abnormality of sperm DNA in infertile men classified as unexplained based on apparently normal standard sperm parameters.
Endocrine evaluation of men with low sperm count is also recommended. Hormones that are typically tested include FSH, LH, estradiol, testosterone, prolactin and TSH levels. Any abnormality in the levels of these hormones requires further assessment and patients are commonly referred to a urologist or an andrologist who specializes in male infertility for further work up and management. Couples with mild male factor infertility are typically treated with intrauterine inseminations or with IVF.
Genetic evaluation of men with low sperm count is recommended after initial evaluation to rule out any obstruction in the male genital system. Once an obstructive cause is ruled out in a patient with less than 5 million sperm per milliliter, a full chromosome analysis (karyotype) and testing for the Y chromosome microdeletions is recommended. If there are any abnormalities found in the chromosomal evaluation, genetic counseling is recommended to assess risk of passing on these genes to the offspring.
Although most men with abnormal semen parameters have a nor