In-depth analysis of the causes and classifications of male infertility, professionally safeguarding men's health.

Male Infertility

(I) Definition of Male Infertility

Male infertility is defined as the infertility of the female partner caused by the male partner after three years of unprotected cohabitation. Studies show that approximately two-thirds of couples who do not use contraception after marriage will conceive within three months, 75-80% within six months, and approximately 85% within one year. The American Fertility Association considers the inability to conceive after one year of unprotected cohabitation as infertility.

(II) Essential Conditions for a Normal Fertility in Men

1. Possessing normal reproductive organs and their functions.

2. Possessing normal sexual function, capable of delivering semen into the female reproductive tract. Normal male sexual function is a series of reflexive activities, a complex physiological process based on a healthy nervous, endocrine, and reproductive system, requiring close cooperation between both partners.

3. The male body should not contain antisperm antibodies that cause sperm agglutination and immobilization. Some men with infertility have normal reproductive organ structure and function, and normal sexual function, but sperm motility and fertilization capacity are affected by sperm antibodies in their blood or seminal plasma.

(III) Causes of Male Infertility

Male infertility is not an independent disease, but the result of multiple diseases or factors. Any disease or factor that interferes with the physiological processes of male reproduction can cause male infertility. Based on clinical manifestations, male infertility can be divided into absolute infertility and relative infertility. The former refers to complete lack of fertility, such as azoospermia; the latter refers to male fertility below the threshold required for normal female pregnancy, such as oligospermia. Based on the course of the disease, it can be divided into primary infertility and secondary infertility. Primary infertility refers to a couple who have never conceived after marriage, while secondary infertility refers to a couple who have had children before but have remained infertile for more than three consecutive years without using contraception.

1. Diseases and Factors Interfering with Hormonal Regulation of Male Reproductive Activity

The main endocrine glands related to male reproductive activity include the hypothalamus, pituitary gland, and testes, also known as the hypothalamic-pituitary-testicular axis. Diseases of these three endocrine glands themselves, or other diseases and factors interfering with these endocrine glands, can cause infertility.

2. Infertility Caused by Testicular Dysfunction

① Congenital absence of testes or testicular trauma.

② Testicular inflammation. Examples include: orchitis caused by mumps, testicular tuberculosis, syphilis, leprosy, and nonspecific orchitis.

③ Testicular dysfunction caused by vascular diseases. Examples include: varicocele and testicular torsion.

④ Testicular compressive atrophy. Examples include: thick-walled hydrocele and large inguinal hernia.

⑤ Iatrogenic or occupational X-ray exposure.

⑥ Interference with scrotal thermoregulation. Examples include: wearing tight clothing and frequent hot baths.

3. Systemic Factors Affecting Male Fertility

① Nutritional Disorders. Examples include rapid weight loss, deficiencies in vitamins A, E, C, and B, consumption of crude cottonseed oil, cirrhosis, and chronic renal failure.

② Industrial Waste and Environmental Pollution. Examples include lead, arsenic, and radioactive substances, which can cause sperm abnormalities or inhibit spermatogenesis.

③ Drug Effects. Examples include furans, alkylates, hormones, spironolactone, serotonin, monoamine oxidase inhibitors, cyclophosphamide, methotrexate, and large doses of aspirin.

④ Febrile Illnesses. Examples include severe bacterial and viral infections.

⑤ Allergic Reactions.

⑥ Unhealthy Habits and Addictions. Examples include excessive smoking and drinking, excessive stress and emotional fluctuations, and prolonged hot baths, all of which can damage spermatogenesis.

4. Infertility Caused by Epididymal Structural and Functional Disorders

Some patients, despite normal testicular development, experience azoospermia due to congenital epididymal defects causing obstruction of the vas deferens. Studies have shown that vasectomy can lead to epididymal duct dilation and seminal fluid stasis. The breakdown, decomposition, and absorption of sperm in the epididymis are the main reasons for the increased levels of antisperm antibodies in the blood after vasectomy. These structural and functional changes in the epididymis are also one of the reasons why some vas deferens anastomoses fail to restore fertility.

5. Infertility Caused by Ejaculatory Disorders

① Anejaculation. The causes of anejaculation can be divided into two main categories: psychogenic anejaculation and organic anejaculation. Psychogenic anejaculation accounts for over 90% and is mostly due to a lack of sexual knowledge or certain psychological factors and social trauma. Clinically, it manifests as the inability to ejaculate vaginally during intercourse, but ejaculation can occur through masturbation outside of intercourse, and nocturnal emissions may occur during sleep. Organic ejaculatory dysfunction is often accompanied by psychological factors. Organic causes include urogenital diseases, congenital spinal cord lesions or injuries, abnormal lumbar sympathetic ganglion function, use of drugs affecting the sympathetic nervous system such as guanethidine and phenothiazines, and physical weakness due to long-term chronic diseases. Patients with organic ejaculatory dysfunction do not ejaculate during masturbation or sleep.

② Retrograde ejaculation. Retrograde ejaculation is one of the causes of male infertility. It mainly occurs due to dysfunction of the bladder neck sphincter; during ejaculation, the bladder neck sphincter fails to close tightly, causing semen to flow back into the bladder instead of being expelled from the urethra. Certain surgical procedures can also cause retrograde ejaculation, such as prostatectomy and sympathectomy. Systemic diseases, such as diabetes, tabes dorsalis, sequelae of myelitis, spinal cord injury, multiple sclerosis, and drug effects, can all cause bladder neck contraction disorders, leading to retrograde ejaculation. Cysts, papillary protrusions, or congenital hypertrophy of the seminal colliculus can cause retrograde ejaculation because the ejaculatory ducts open near the middle of the seminal colliculus and excessive swelling of the seminal colliculus can prevent semen from being ejaculated from the urethra.

6. Infertility caused by obstruction of the vas deferens

Mechanical obstruction from the rete testis to the ejaculatory duct can cause obstructive azoospermia. In clinical practice, the possibility of obstruction of the vas deferens should be considered in patients with azoospermia. Obstruction is generally divided into two categories: congenital obstruction and acquired obstruction. Congenital obstruction is mainly due to congenital developmental problems, while acquired obstruction is mainly caused by infection and injury.

7. Infertility caused by immune dysfunction

8-10% of male infertility cases are related to immune dysfunction. Sperm-agglutinating antibodies in male serum and antisperm antibodies in semen can lead to male infertility. Under normal circumstances, the body's immune cells can only recognize foreign antigens. While their own tissues, such as sperm, can carry various antigens, they generally do not produce an immune response. Only under certain internal or external factors, when the body's tolerance is disrupted, self-antigens change, or immune-active cells mutate, will the immune system produce an immune response to self-antigens, thus causing an autoimmune reaction. If this further leads to tissue and cell damage or destruction, an autoimmune disease will develop. The main causes of antisperm antibodies are as follows:

① Disruption of the blood-testis barrier: Any damage to the blood-testis barrier can lead to the formation of antisperm antibodies. Vasectomy, vas deferens anastomosis, vas deferens obstruction, reproductive tract injury, testicular injury, cryptorchidism, reproductive tract infection, and varicocele can all disrupt the blood-testis barrier.

② Immunosuppressive dysfunction: Sperm and T lymphocytes share common antigens and can cross-react. This cross-reaction impairs the T cells' ability to suppress the immune response. Some male infertility patients lack immunosuppressive substances in their seminal plasma, causing their normal sperm cells to trigger an immune response in the reproductive tract, forming antisperm antibodies.

③ Genetic factors: The most important cause of immunologic infertility is the body's own immune response. However, not all men who experience an autoimmune response become infertile. Some believe that one possible reason is the influence of certain genetic factors. Studies have shown that immune response genes play a role in determining whether a person will have an immune response to sperm and the intensity of that response. It has been confirmed that the autoimmune response to sperm antigens is partly controlled by a single dominant chromosome gene. Changes in sperm surface antigens can enhance sperm immunogenicity. Sperm without sialic acid on their surface can be recognized and attacked by the body's immune cells, thus preventing them from reaching the fertilization site. Any pathogenic factor that can remove sialic acid from the sperm surface can trigger an autoimmune response. For example, bacterial or viral infections often cause sperm to lose sialic acid due to the action of sialidase in these pathogenic microorganisms, thus stimulating an antibody reaction. Some patients have a congenital deficiency of sialyl transferase, which can also cause autoimmune infertility. Clinically, some patients with unexplained idiopathic autoimmune infertility may be related to this congenital genetic defect.

8. The Influence of Mental and Psychological Factors on Male Fertility

Statistics show that male infertility caused by mental and psychological factors accounts for about 5%. It is generally believed that abnormal mental and psychological states lead to neuroendocrine disorders, interfering with testicular spermatogenesis. In addition, male sexual dysfunction caused by mental and psychological factors, such as impotence and ejaculatory dysfunction, is also a common cause of male infertility. Various types of stress responses, mechanical and traumatic sound and light, and emotional changes can all lead to spermatogenesis disorders. During a stress response, the brain directly or indirectly alters neurotransmission and hormone synthesis and release in the hypothalamus, thereby affecting the pituitary gland's release of gonadotropins. Furthermore, stress increases adrenaline secretion, serotonin secretion, and decreases monoamine oxidase activity; all of these factors can inhibit testosterone secretion and spermatogenesis.

9. Male Infertility Caused by Varicocele

According to literature reports, infertility caused by varicocele accounts for 9%–14% of male infertility, and the incidence of male infertility in patients with varicocele is significantly higher than in the general population.

10. Male Infertility Caused by Physical and Chemical Factors

Many physical and chemical factors, such as various environmental pollutants, temperature, chemicals, tobacco and alcohol, and nutrition, can affect fertility.