Medical Health Encyclopedia

A varicocele is an abnormally enlarged and twisted (varicose) vein in the spermatic cord that connects to the testicle. Varicoceles are found in 15 -  20% of all men and in 25 - 40% of infertile men, although it is not clear how or even if they affect fertility. They tend to occur more commonly (85 percent) on the left side. Some theories supporting their possible effect on infertility include the following:

Click the icon to see an image of a varicocele.

• Varicoceles may partially obstruct the passages through which sperm pass.
• Varicoceles may elevate temperature in the testes.
• Varicoceles may produce higher levels of nitric oxide, a substance that has beneficial effects on blood flow and other functions but which might, in excess, injure sperm.
• Varicoceles may block oxygen supply to the sperm.
• Varicoceles have been associated with abnormalities in cellular material in the sperm. One study suggested that some men may have genetic defects that cause both varicoceles and impaired sperm, rather than the varicocele itself causing infertility.

Some reports indicate that only varicoceles that are large enough to be felt (termed palpable) may impact fertility. On the other hand, an eight-year study of men with and without varicoceles, however, found no differences in sperm quality or in the ability to conceive. Furthermore, the few well-conducted studies on repair of varicoceles suggest that the procedure does not improve pregnancy rates. Their effect on fertility remains unclear.

Testosterone Deficiencies and Hypogonadism.

Hypogonadism is the general name for a severe deficiency in gonadotropin-releasing hormone (GnRH), the primary hormone that signals the process leading to the release of testosterone and other important reproductive hormones. Low levels of testosterone from any cause may result in defective sperm production.

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Hypogonadism is uncommon and is most often present at the time of birth, usually the result of rare genetic diseases affecting the pituitary gland that may include selective deficiencies of the hormones FSH and LH, Kallman syndrome, or panhypopituitarism, in which the pituitary gland fails to make almost all hormones. It can also develop later in life from brain or pituitary gland tumors or as a result of radiation treatments. Defects in the gene on the X chromosome that regulates receptors that bind to androgens--male hormones--may also prove to be very important causes of male infertility.

Click the icon to see an image of the pituitary gland.

Autoantibodies

Autoimmunity is a condition in which microbe-fighting agents of the immune system called antibodies attack specific cells in the body, mistaking them for foreign microinvaders. In the case of male infertility, these so-called autoantibodies ("self" antibodies) target the sperm. Antibodies bind to specific parts of the sperm, such as the head or tail and, depending on the site of attachment, cause various problems:

• Sperm may stick together (agglutinate).
• They may fail to interact with cervical mucous.
• They may be unable to penetrate the egg.

Some experts believe that in most cases the presence of these antibodies will not prevent conception unless a large percentage of sperm are affected.

Vasectomy and Anti-Sperm Antibodies. Vasectomy, the primary sterility procedure in men, is the most common cause of sperm autoantibodies (also called anti-sperm antibodies). Experts believe their typical development is as follows:

• Vasectomy works by severing the vas deferens, the tube that carries sperm from the testicles to the urethra (which leads out of the penis).
• After vasectomy, sperm continue to be produced but, instead of being confined to the reproductive passages, they leak out into the body.
• Here, the immune system may perceive them as foreign invaders and develop antibodies to attack them.

Such antibodies often persist, even if a man restores sperm flow by a successful reversal procedure (vasovasostomy). The persistence of anti-sperm antibodies may result in infertility.

Click the icon to see an illustrated series detailing vasectomy.

Other Causes of Autoantibodies. Antibodies to sperm can also appear in men without previous vasectomies and have been reported to be present in 10% of all men with fertility problems. They may be linked to genital infections or injury, although the cause is usually not known.

Retrograde Ejaculation

Retrograde ejaculation occurs when the muscles of the urethra do not pump properly during orgasm and sperm are forced backward into the bladder instead of forward out of the urethra. Sperm quality is often impaired.

Retrograde ejaculation can be the consequence of a number of conditions:

• Surgery to the lower part of the bladder or prostate  (this is the most common cause of retrograde ejaculation)
• Diabetes
• Multiple sclerosis
• Back surgery
• Spinal cord injury

Medications such as tranquilizers, certain antipsychotics, or hypertension medications also may cuase temporary retrograde ejaculation.

Testicular Dysgenesis Syndrome and Other Physical or Structural Abnormalities

Any structural abnormalities that affect the testes, tubes, or other reproductive structures can have a profound effect on fertility.

Testicular Dysgenesis Syndrome. Testicular dysgenesis syndrome is a recently observed occurrence of three conditions--impaired sperm production and quality, testicular cancer, and genital tract abnormalities. All three of these conditions are increasing--not necessarily all three in one individual--but in the male population generally. Environmental factors that increase damage from oxidants are believed to be responsible.

The genital abnormalities identified with this syndrome are undescended testes and hypospadias, each of which is associated with infertility:

• Undescended Testes (Cryptorchidism). In some cases, there is a failure of the testes to descend from the abdomen into the scrotum during fetal life. Cryptorchidism is associated with mild to severe impairment of sperm production. In one survey, 38% of men who as youngsters had two undescended testicles and 10% of men with one undescended testicle were infertile, compared with 5% of men who had normal testes. Even one undescended testicle may impair fertility. In cryptorchidism, the testes are exposed to the higher internal body heat, but this may not totally explain the damage in sperm production that can occur. (Note: Men who suffer from this condition should be aware that even if the testicle is surgically moved to the scrotum, their risk of testicular cancer is significantly increased, warranting careful self-exams and regular follow-up with a doctor.)
• Hypospadias. This is a birth defect in which the urinary opening is on the underside of the penis, can prevent sperm from reaching the cervix if not surgically corrected.

Click the icon to see an image of an undescended testicle.

Click the icon to see an image of hypospadius.

Blockage in the Tubes that Transport Sperm. Some men are born with a blockage in the epididymis or ejaculatory ducts or other problems that later affect fertility. One center reported that 2% of men seeking treatment had no vas deferens.

Anorchia. In the very rare condition known as anorchia, a man is born without any testes.

Syringomyelia. This is a disease of the spinal cord, results in no ejaculate at all (aspermia).

Cancer and Its Treatments

Birth rates among cancer survivors are only 40 - 85% of the expected rates. Certain cancers, particularly testicular cancer, impair sperm production, often severely. The major cancer treatments such as chemotherapy and radiation may impair sperm quality and quantity. The closer radiation treatments are to reproductive organs, the higher the risk for infertility. Fortunately, while men may fail to produce sperm for as long as five years after radiation therapy, sperm production may eventually recover in many. Chemotherapy with alkylating agents or other drugs that can harm reproductive function tends to affect fertility more severely in men than in women. New regimens are helping to improve fertility rates.

On an encouraging note, in spite of concerns that cancer treatments may affect sperm DNA, a 2002 study found no higher rate of genetic abnormalities in the sperm of cancer survivors compared to men without a cancer history. Adolescents and older men undergoing cancer treatments who may want to father children should consider banking and freezing their sperm for later use in assisted reproductive therapies. However, these banking methods are not appropriate for pre-adolescent boys being treated for childhood cancers such as leukemia. (The chemotherapy used to treat leukemia often causes male infertility.) Researchers are investigating ways that stem cell transplantation may someday help these children regain their fertility while avoiding leukemia relapse.

Infections

There is some controversy over the effect of infections on infertility. Simply detecting the presence of an infection in infertile men does not necessarily mean that it has any relationship to the infertility itself. Some experts believe that the immune response to some infections may release inflammatory factors and oxidants, chemically unstable particles that can damage sperm. The exact impact of this process on sperm is unclear, however. Infections may alter the liquidity of semen and sperm motility, although these are likely to be temporary effects. Among the infections most implicated in infertility are the following:

Sexually Transmitted Diseases. Repeated Chlamydia trachomatis or gonorrhea infections are most often associated with male infertility. Such infections can cause scarring and block sperm passage. Human papillomaviruses, the cause of genital warts, may also impair sperm function.

Mycoplasma. Mycoplasma is an infectious organism that appears to fasten itself to sperm cells and render them less motile.

Mumps. When mumps develops after puberty, it damages the testicles in 25% of men afflicted with the disease. (Interferon, an anti-viral drug, may help prevent infertility in adult males with active mumps, but the drug is highly toxic and caution is essential.)

Glandular Infections in the Urinary Tract or Genitals. Glandular infections that may affect fertility include prostatitis (in the prostate gland), orchitis (in the testicle), semino-vesculitis (in the glands that produce semen), or urethritis (in the urethra), perhaps by altering sperm motility. Even after successful antibiotic treatment, infections in the testes may leave scar tissue that blocks the epididymis.

Other Conditions Associated with Infertility

Medical Conditions. Other medical conditions that can affect male fertility include any severe injury or major surgery, diabetes, HIV, thyroid disease, Cushing syndrome, heart attack, liver or kidney failure, and chronic anemia.

Personality Traits. One interesting 2003 study reported an association between low sperm counts in men and certain negative personality traits, notably alexthymia (the inability to express emotions using words) and psychoticism (disconnection with reality). Research is needed to determine if these findings have any validity.

Medications

The effects of medications on sperm quality and count have not been rigorously studied and many medicines are commonly prescribed without knowing whether they impair fertility. Anabolic steroids (which are those abused by weight lifters and other athletes) deserve special notice because they are known to severely impair sperm production. Among the other drugs that can affect male fertility are cimetidine (Tagamet), sulfasalazine (Azulfidine), salazopyrine, colchicine, methadone, methotrexate (Folex), phenytoin (Dilantin), corticosteroids, spironolactone (Aldactone), thioridazine (Mellaril), and calcium channel blockers.