Environmental factors include high-temperature working environments (e.g., steel industry, bakeries, etc.), occupations requiring sitting for long periods (e.g., long-haul driving), occupational exposure to chemicals (e.g., ethylene glycol monomethyl ether), medications (e.g., anabolic steroids, opioid narcotics, cocaine, marijuana, and methamphetamines), exogenous hormones, radiation, and chemotherapy. Acquired causes include trauma, infection, testicular cancer, and systemic disease, including hypothyroidism, immunologic, and malignancies. Anatomic factors include varicocele and obstructions of the vas deferens, epididymal, and ejaculatory duct, resulting in azoospermia. Developmental and structural factors include genetic causes such as Klinefelter’s syndrome and cystic fibrosis, cryptorchidism, gonadal failure or hypergonadotropic hypogonadism, and impaired sperm transport. Sperm defects include spermatogenetic arrest and anomalies of sperm structure. Hormonal causes and androgen resistance include hyperprolactinemia, hypogonadotropic hypogonadism, congenital adrenal hyperplasia, and androgen resistance syndrome. Ejaculation problems include anejaculation, retrograde ejaculation, and sexual dysfunction.

Varicocele is the most common contributing factor of male infertility. Males with varicocele have large veins in the testes that produce heat, which may affect the amount and shape of sperm. Most often varicoceles are found on the left side but can be unilateral or bilateral. Varicocele is found in 15% of healthy men and up to 35% of men with primary infertility. The exact pathophysiology of varicoceles and its impact on male infertility is not well understood.

The major reproductive-related causes of male infertility include testicular deficiency and post-testicular impairment. Testicular deficiency causes disruptions in spermatogenesis and considers congenital, acquired, or idiopathic testicular failure. Post-testicular impairment is related to ejaculatory dysfunction or obstruction in sperm delivery.

The major disease-related causes of male infertility include medical conditions such as diabetes, cystic fibrosis, infections, and some autoimmune disorders can cause testicular failure.

Trauma to the testes can affect spermatogenesis, and unhealthy habits such as heavy alcohol consumption, smoking, drug use, and anabolic steroid use may disrupt the testicular or ejaculatory function. The risk of male infertility increases with a BMI below 18.5 and a BMI equal to or greater than 25. Regular alcohol consumption may negatively affect semen morphology and volume, while occasional alcohol intake does not appear to impact semen quality. Moderate caffeine consumption (400 mg/day) appears to be safe and may even positively affect human Sertoli cells. In contrast, heavy consumption may impair Sertoli cell function and lead to abnormal spermatogenesis. Additionally, exposure to pesticides and insecticides in fruits and vegetables may impact semen quality, making it worth considering getting fruits and vegetables from reliable sources to minimize exposure.

Age is an essential factor for male fertility. While age is a more considerable factor in female factor infertility, difficulty conceiving has been reported in couples in which the male partner is 40 years or older. As men age, hypogonadism can result from declining testosterone.

Declining semen quality, including sperm concentration and sperm count parameters, has decreased globally by approximately 50-60% over the last 40 years. The etiology of suboptimal semen quality mostly likely involves oxidative stress, environmental, and genetic factors, although it remains poorly understood Several characteristic features of male infertility can determine sperm quality, including oligozoospermia, asthenozoospermia, and teratozoospermia or an insufficient number of spermatozoa of typical structure. Low sperm count and issues in quality have been observed as 90% of the causes of male factor infertility. See spermatogenesis for more information.

Oxidative stress causes damage to the sperm plasma membrane impairing sperm function. About 30-80% of cases of reduced male fertility can be attributed to the effects of oxidative damage on sperm. Additionally, since regulated levels of ROS are needed for normal spermatogenesis and fertilization, uncontrolled levels of ROS are harmful to fertilization rates and in pregnancy and live birth rates. Furthermore, ROS may impair sperm motility and interfere with their ability to connect with the oocyte. See spermatogenesis for more information.

Male infertility can be evaluated by a physician or other qualified health professional through proper history and physical examination. Male infertility is typically analyzed through semen analysis which looks at the sperm concentration, motility, and morphology. Males with azoospermia and severe oligospermia should consider genetic testing. Additionally, testis biopsy and transrectal ultrasound may be useful in diagnosing male infertility. Other assessment methods include reproductive hormone analysis and, recently, the molecular composition of sperm cells to analyze the degree of oxidative stress or DNA fragmentation. Some researchers use the DNA fragmentation index (DFI) to determine pregnancy success, with a DFI greater than or equal 30% associated with reduced fertility. In contrast, a 3-5% DFI is observed in healthy men.