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Infertility in Men

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of male infertility.

Causes

In a 2001 study, the causes of infertility in men seeking to conceive were the following:

  • Vasectomy. In the study 56% of men were seeking a reversal of this procedure. Thirty years ago, this was a factor in only 5% of men seeking help for fertility.
  • Varicocele (14%). A network of veins carries blood away from the testicles and back up into the body. If these veins become enlarged, twisted, and swollen (similar to varicose veins in the leg), this condition is termed a varicocele. Varicoceles can impair testicular function and fertility.
  • Unknown infertility (8%).
  • Absence of sperm (6%). There are many biologic and environmental factors that can lead to low sperm count. For instance, abnormalities in production or obstruction of the tubes that carry sperm can reduce sperm levels. A condition called Sertoli cell-only syndrome is one in which the cells that produce sperm (the Sertoli cells) are absent. This can be a congenital problem that a man is born with or caused by infection, injury, medication, radiation, or genetics. In addition, other conditions may cause infertility in men.

Age

The effect of aging on male fertility is not clear. Some growing evidence suggests that it may be a factor (although not to the extent that it is in women). One earlier study suggested that sperm number and quality do not decline until beyond age 64, but a subsequent 2000 trial reported reductions in sperm count and quality between the second and fifth decade of life. Another study reported that fertilization rates during fertility treatments were over 60% for men under 39 but fell to slightly over half after age 40. Genetic defects in sperm have also been observed to increase with advancing age, although the implications for fertility are unclear. A 2002 study indicated that when men with genital infections were not considered, there was no difference in fertility rates between older and younger men.

Temporary and Lifestyle Causes of Low Sperm Count

Nearly any major physical or mental stress can temporarily reduce sperm count. Some common conditions that lower sperm count, temporarily in nearly all cases, include the following:

Emotional Stress. Stress may interfere with the hormone GnRH and reduce sperm counts.

Sexual Issues. In less than 1% of cases, impotence, premature ejaculation, or psychological or relationship problems contribute to male infertility, although these conditions are usually very treatable. Lubricants used with condoms, including spermicides, oils, and Vaseline, can affect fertility. Astroglide, Replens, or mineral oil may not be as harmful to sperm. However, oil-based lubricants can damage latex condoms and should be avoided.

Testicular Overheating. Overheating, such as from high fevers, saunas, and hot tubs, may temporarily lower sperm count. Persistent exposure to high temperatures during work may even impair fertility. One French study suggested that driving for only two hours a day can increase temperature in the scrotum and reduce sperm count. This study was small, however, and more research is needed. A number of trials have found no negative effects on fertility from wearing tight trousers, briefs, or athletic supports, even every day.

Substance Abuse. Cocaine or heavy marijuana use appears to temporarily reduce the number and quality of sperm by as much as 50%. Sperm actually have receptors for certain compounds in marijuana that may impair the sperms ability to swim and also inhibit their ability to penetrate the egg. Alcohol does not appear to affect fertility, unless it is so abused that it causes liver damage.

Smoking. Smoking impairs sperm motility, reduces sperm lifespan, and may cause genetic changes that affect the offspring. One 2002 trial found that men or women who smoke have lower success rates with assisted reproductive technologies. An earlier study reported that men who smoke also have lower sex drives and less frequent sex.

Malnutrition and Nutrient Deficiencies. Deficiencies in certain nutrients, such as vitamin E, vitamin C, selenium, zinc, and folate, may be particular risk factors for infertility

Obesity. Some studies, but not all, have found an association between obesity in men and infertility.

Bicycling. Bicycling has been linked to impotence in men and also may affect fertility. Pressure from the bike seat may damage blood vessels and nerves that are responsible for erections. Mountain biking, which involves riding on off-road terrain, exposes the perineum (the region between the scrotum and the anus) to more extreme shocks and vibrations and increases the risk for injuries to the scrotum. A study in Austria found that men who mountain bike are far more likely to have scrotal abnormalities, including calcium deposits, cysts, and twisted veins. Men who cycle can reduce such risks by the following:

  • Taking frequent rests while biking.
  • Wearing padded bike shorts.
  • Using a padded or specially contoured bike seat that is raised high enough and sits at the proper angle.

Genetic Factors

Problems in the genes that regulate male fertility and in the genetic material of sperm itself are important contributors to infertility problems in men. In fact, even in men with no known fertility problems, 19% of the sperm are genetically defective. Certain inherited medical conditions also contribute to male infertility. Defective genes themselves can be inherited, produced by environmental assaults (such radiation exposure), or both. Of some concern is the possibility that these mutations will be pass to offspring in men who undergo fertilization techniques that retrieve sperm and directly fertilize to the egg. (Under natural conditions, genetically abnormal sperm would be very unlikely to reach and fertilize the egg.)

Defective Genetic Material. Sperm carry half the genetic material necessary to make a human being. Infertile men have been reported to have a relatively high percentage of sperm with broken or damaged DNA (the molecular chain that makes up a gene).

Genetic Factors Specifically Affecting Sperm Production or Quality. Abnormalities in genes that specifically regulate sperm production and quality are major factors in male infertility. Some research suggests that about 10% of cases of male infertility may be due to problems, most likely genetic, in the acrosome. The acrosome is the enzyme-filled membrane cap on the sperm--its warhead--that is critical for piercing the egg. In one study, pregnancy was impaired if 7% or more of sperm had abnormalities in the acrosome.

Inherited Disorders that Affect Fertility. Certain inherited disorders can impair fertility. Examples include the following:

  • Cystic fibrosis patients often have missing or obstructed vas deferens (the tubes that carry sperm). In fact, in men whose infertility is caused by an inborn missing vas deferens have a 60% chance that they carry the gene for cystic fibrosis (even if they don't have the disease itself).
  • Klinefelter syndrome patients carry two X and one Y chromosomes (the norm is one X and one Y), which leads to the destruction of the lining of the seminiferous tubules in the testicles during puberty, although most other male physical attributes are unimpaired.
  • Kartagener syndrome, a rare disorder that is associated with a reversed position of the major organs, also includes immotile cilia (hair-like cells in lungs and sinuses that have a structure similar to the tails of sperm). Sperm motility may then also be impaired by this condition.
  • Polycystic kidney disease, a relatively common genetic disorder that causes large cysts to form on the kidneys and other organs during adulthood, may cause infertility as the first symptom if cysts develop in the reproductive tract.

Environmental Assaults

Exposure to toxins, chemicals, or infections may reduce sperm count either by direct effects on testicular function or by altering hormone systems, although the extent of the impact and specific environmental assaults involved are often controversial. Some experts believe it is contributing to a general worldwide decline in male fertility.

Free Radicals (Oxidants). The primary suspects in the link between environmental assaults and infertility are free radicals, also called oxidants. These are unstable molecules, usually containing oxygen, that are released as a by-product of many natural chemical processes in the body. Infections, chemicals, and other environmental assaults can produce high levels of these particles. And, high levels can do harm, even affect the genetic material in cells. Sperm are particularly vulnerable to the damaging effects of this oxidation process. There have been reports that significant levels of oxidants occur in the semen of about 25% of infertile men. Additional investigation is under way.

Exposure to Estrogen-Like and Hormone-Disrupting Chemicals. European studies have increasingly reported a worsening in male reproductive health and an increase in testicular and prostate cancers. Many investigators strongly suspect environmental causes, particularly excessive chemicals that disrupt hormones, as a major cause for both these events. Estrogen-like chemicals found in pesticides and other chemicals are of particular concern. Overexposure to estrogen in male animals reduces the number of Sertoli cells (the cells necessary for the initial development of sperm). Some hormone-disrupting chemicals under investigation include the following:

Prostate cancer
Treatment of prostate cancer varies depending on the stage of the cancer (i.e., spread) and may include surgical removal, radiation, chemotherapy, hormonal manipulation or a combination of these treatments.
  • Bisphenol A is a widely used chemical found in plastic food containers and bottles that has provoked concern. It has potent estrogen-like effects in low dose. Use of the chemical in female rats has produced prostate abnormalities in their male offspring.
  • Phthalates, chemicals used to soften plastics, are under particular scrutiny for their ability to disrupt hormones. Specific phylates of special concern include dibutyl phthalate (DBP), which is found in many products, including cosmetics and clay products sold to children (Fimo, Sculpey). Animals exposed to phylates have significantly impaired sperm count and abnormalities in their reproductive structures, such as the testes. In addition, there is some concern that exposure in pregnant women may affect the offspring,
  • Organochlorines are compounds that combine chlorine and organic substances--usually petrochemicals. Many have estrogen-like effects, including those previously used to make plastics (PCBs) and pesticides (e.g., DDT and p,p-DDE). Some, such as dioxins and furans, are byproducts of many chemical processes. Fortunately, most of these chemicals have been banned, but they were heavily used in manufacturing before 1970 and are still widespread within the population. Studies have reported that when men had a history of moderate or high on-the-job exposure to pesticides containing organochlorines their fertility rates were lower than men without such exposures. Studies in 2002 found a strong correlation between high levels of polychlorinated biphenyls (PCBs) or p,p-DDE with reduced sperm quality and quantity. In one of the studies, even men with healthy sperm with high organochlorine levels had a lower sperm count than those with lower levels of these compounds.
  • Because of the connection between estrogen and infertility, there has been some concern that plant-based estrogens (phytoestrogens), such as the isoflavones found in soy and other foods, may impair sperm. One study of men who took isoflavone supplements for two months found no negative effects on their reproductive health.

Most evidence on the hormone of chemical estrogens has occurred in animals and birds. Tests of single chemicals containing estrogen have reported little danger for people. Some studies suggest, however, that exposure to more than one of these chemicals may be very harmful. At this time, there is no strong evidence supporting a serious harmful effect in people who have normal exposure to these chemicals. Major efforts are underway to determine the extent of any possible harm from these chemicals.

Hydrocarbons and Other Industrial Chemicals. In one 2000 study, workers in a rubber factory who were chronically exposed to hydrocarbons (ethylbenzene, benzene, toluene, and xylene) had lower than average sperm counts and sperm qualities. (In one 2001 study, men who smoked and worked in petrochemical plants had particularly poor sperm quality.) Still, not all major studies have confirmed the effects of these chemicals and evidence showing any significant effect on fertility is weak.

Exposure to Heavy Metals. Chronic exposure to heavy metals such as lead, cadmium, or arsenic may affect sperm quality. Trace amounts of these metals in semen seem to inhibit the function of enzymes contained in the acrosome, the membrane that covers the head of the sperm.

Radiation Treatments. X-rays and other forms of radiation affect any rapidly dividing cell, so cells that produce sperm are quite sensitive to radiation damage. Cells exposed to significant levels of radiation may take up to two years to resume normal sperm production and, in severe circumstances, may never recover.

Low Semen Levels

Men with fertility problems because of low semen levels when they ejaculate may have a structural abnormality in the tubes transporting the sperm. (A normal amount of semen is 2.5 to 5 mL, or about 1/2 to 1 teaspoon.)

Varicocele

A varicocele is an abnormally enlarged and twisted (varicose) vein in the spermatic cord that connects to the testicle. Varicoceles are found in 15% to 20% of all men and in 25% to 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:

Varicocele 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.

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.

The pituitary gland 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.

Vasectomy - series 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 bladder neck (the lower part of the bladder) or prostate is the most common cause of retrograde ejaculation.
  • Diabetes.
  • Multiple sclerosis.
  • Back surgery
  • Spinal cord injury.
  • A temporary side effect of certain drugs, such as tranquilizers, certain antipsychotics, or hypertension medications.

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 physician.)
  • 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.
Before and after testicular repair Click the icon to see an image of an undescended testicle.
Hypospadius 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% to 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.

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.

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