Medical Conditions and Male Fertility

Medical conditions and male infertility problems

The following is a list (in alphabetical order) of some of the more common medical problems that can be associated with decreased male fertility. This is not a complete list, but it does address some of the more common fertility-related general medical problems.

 

Androgen Insensitivity Syndrome (AIS)

Men with AIS have problems with their androgen receptors and therefore the cells of their body do not recognize testosterone. Since their cells cannot bind to and utilize testosterone, these men suffer from severe hypogonadism despite very high levels of testosterone in their bloodstreams. The physical characteristics of these men depend on the severity of the abnormalities of their androgen receptors. In complete AIS, there is no testosterone action at all in the cells. Though genetically male, these patients are born with female genitalia at birth and look like females, though they have no internal female sex organs. In men with partial AIS, there remains some level of testosterone action in the cells. Therefore these men can have some development of male genitalia, ranging from partial development to normal development. On blood testing, these men have elevated levels of LH and testosterone. Depending on the severity of the receptor defect, men with partial AIS can have fertility issues ranging from mild sperm abnormalities to complete azoospermia.

 

Beta-thalassemia

Beta-thalassemia involves a problem with normal hemoglobin synthesis (hemoglobin carries oxygen in the blood). Men with this problem require repeat blood transfusions over their lifetimes. These blood transfusions can result in a buildup of iron deposits within different parts of the body. If enough iron builds up within the pituitary gland, this can decrease FSH and LH release. Iron deposits within the testicles can also lead to testicular failure.

 

Cancer Treatment

See the "Cancer and Male Fertility" section for more information.

 

Celiac Disease

Celiac disease is an autoimmune disease of the small intestine. Symptoms including abdominal pain, diarrhea, constipation, and fatigue can occur if someone with celiac disease consumes gluten, a protein found in wheat and a number of other grains. Some men with celiac disease have been reported to have increased levels of androgen resistance, in which the body’s cells are not as responsive to testosterone as they should be; this can potentially lead to abnormalities of semen parameters. There is some evidence that these negative hormonal and fertility effects can be improved with avoidance of gluten containing foods.

 

Chemotherapy

See “Cancer and Male Fertility" link above.

 

Ciliary Diseases

Cilia are small hair-like structures commonly found in the respiratory tract, where they help sweep out foreign objects and bacteria that are inhaled. Cilia also form the tails of sperm, providing them with the ability to swim. There are several genetic abnormalities that can impair the ability of the cilia to move properly, resulting in sperm that are alive, but cannot swim. These include immotile cilia syndrome and Kartagener’s syndrome.

In immotile cilia syndrome (ICS), the cilia do not work properly, and therefore people with this disease have chronic respiratory infections due to an inability to effectively clear mucus, bacteria, and foreign objects from the lungs. Cilia are also found in the sinuses and middle ear, so these patients often suffer from chronic sinusitis. Men with ICS are typically infertile, as the tails of the sperm do not function. The sperm are alive but cannot swim up the fallopian tubes to fertilize any eggs. The diagnosis can be made with special testing called electron microscopy (which is not widely available outside of large research universities). Pregnancy can be achieved using the sperm in conjunction with IVF/ICSI.

Kartagener’s syndrome is a form of ICS in which the man also has situs inversus, a condition in which the locations of the major organs are reversed within the body (i.e., the heart is located on the right side of the body instead of the left). This reversal of organs typically does not have any significant health implications.

 

Cirrhosis/Liver Disease

Men with liver disease have higher rates of:

      1) Hypogonadism

      2 )Elevated estradiol levels

      3) Testicular atrophy

      4) Erectile dysfunction

      5 )Gynecomastia (breast enlargement)

 

Congenital Adrenal Hyperplasia (CAH)

CAH involves a genetic abnormality that disrupts the ability of the adrenal glands to make cortisol. In normal circumstances, the adrenal glands also produce about 10–20 percent of the androgens in the body. In men with CAH, the substances that usually serve to make cortisol are instead converted into elevated levels of androgens. Men with CAH typically have early onset of puberty due to the higher than normal circulating levels of androgens. In adulthood, these elevated levels of adrenal androgens have a negative feedback effect on the pituitary gland, resulting in suppression of FSH and LH production. This has a predictable negative impact on sperm production. Milder variants of CAH can also be present, in which cortisol production is only partially blocked; these men typically develop milder symptoms later in life.

 

The diagnosis of CAH usually involves blood testing for adrenal-related abnormalities, including:

      1) Elevated 17-OHP (normal: 31—220 ng/dL)

      2) Elevated ACTH (normal 9–52 pg/mL)

      3) Elevated androstenedione (normal: 60–270 ng/dL)

 

Adrenal imaging should also be performed to rule out the presence of an adrenal tumor as the source of elevated blood androgens.

From a fertility standpoint, men with CAH typically present with low sperm count (oligospermia) or a zero sperm count (azoospermia), low FSH levels, testicular atrophy, and high testosterone levels. Benign testicular rest tumors are present in 25–50 percent of men with CAH, and these can cause local testicular damage or obstruction in some cases. Treatment of CAH involves cortisol replacement, typically in the form of dexamethasone. Effective treatment of CAH can reverse the adverse fertility hormone profile and restore fertility in some men. The benign testicular rest tumors can also shrink or disappear when the CAH is successfully treated.

 

Crohn’s Disease

Crohn’s disease is a type of inflammatory bowel disease that can lead to nutrient deficiencies. A deficiency of zinc can lead to fertility issues in some men with Crohn’s disease.

 

Cryptorchidism

Cryptorchidism is a term used to describe the condition of having undescended testicles, in which one or both testicles have not dropped down into the scrotum by the time of birth. This occurs in approximately 3–5 percent of full-term babies, with higher rates in premature infants. By one year of age, the testicles will have spontaneously descended into their normal position in the scrotum in 75 percent of full-term and 95 percent of premature infants born with cryptorchidism.

From a fertility perspective, the normal position of the testicles within the scrotum allows them to remain two to three degrees cooler than the rest of the body. When the testicles remain stuck in the inguinal region or abdomen, their environment is much warmer than it should be. This typically results in permanent damage to the testicles if they are not brought down into the scrotum in a timely manner. The higher the testicle position within the body, the higher the temperature and thus the greater the potential damage to the testicle.

Studies have shown that testicular spermatogenic cells usually do not suffer any irreversible damage if the testicles come down into the scrotum between six and fifteen months of age. By two years of age, however, 30 percent of undescended testicles have suffered permanent damage, and this percentage increases further with advancing age. The American Academy of Pediatrics recommends treatment for cryptorchidism if the testicle has not descended on its own by the time a child has reached one year of age. Surgical treatment involves orchidopexy (also called orchiopexy), in which the testicle is brought down into the scrotum and fixed in this position with permanent sutures.

Semen abnormalities are found in 20–75 percent of men with one undescended testicle (and 50–90 percent of men with two undescended testicles) who received delayed treatment or no treatment.

 

Other problems associated with cryptorchidism include:

      1) Increased risk of congenital epididymal abnormalities (such as obstruction)

      2) Increased risk of testicular cancer (thus I recommend that men who had an undescended testicle do regular self-exams for testicular

                    lumps, with ultrasound evaluation of any lump found)

      3) Increased risk of testicular torsion

      4) Increased risk of developing an inguinal hernia

 

Diabetes

Diabetes is a common cause of neurologic and vascular damage, because of to the negative impact of persistently elevated blood sugars on the body’s nerves and blood vessels. The influence of diabetes on ejaculation and erectile function depends upon the degree of neurologic and vascular injury, and can take one or more of several forms, including:

 

1) Retrograde ejaculation (from incomplete closing of the bladder neck)

2) Anejaculation (from paralysis of reproductive tract smooth muscle, which has been replaced by fibrotic tissue)

3) Failure of emission (sperm are not deposited into the urethra)

4) Erectile dysfunction (affects approximately 35–75 percent of men with type 1 diabetes)

5) Calcification of the seminal vesicles (makes them unable to contract and propel sperm into the urethra; electroejaculation does not work well in these patients)

 

See the “Erectile Dysfunction” and “Ejaculatory Problems” sections of this website for more detailed information.

 


Epididymitis

Inflammation or infection of the epididymis (epididymitis) is a relatively common finding in young men. Symptoms can range from none at all to severe scrotal pain (which can mimic testicular torsion). Epididymitis can be caused by an infection as well as by non-infectious inflammation; the latter is more common in men trying to conceive. In older men, the most common cause of infectious epididymitis is E. coli bacteria, while in men under thirty-five, the most common causes are sexually transmitted diseases such as chlamydia and gonorrhea. Epididymitis can lead to pyospermia, which can have a negative impact on sperm numbers and quality (see “Reversible Semen Analysis Factors" section for more information on pyospermia).

Some risk factors for non-infectious epididymitis include:

      1) Lifting heavy objects

      2) Travel that includes prolonged periods of sitting

      3) Bike/motorcycle riding

 

Glucocorticoid Excess

Glucocorticoids are steroid hormones made naturally by the body in the adrenal glands. Too high a level of glucocorticoids in the body can potentially lead to a decrease in LH in some men, which can lead to hypogonadism and an abnormal semen analyses. Excess glucocorticoids can occur because corticosteroid medications (such as prednisone) have been taken for extended periods of time, or because of Cushing’s disease, in which the body is producing too many of its own corticosteroids

 

Hemochromatosis

Hemochromatosis is a genetic abnormality involving dysregulation of the absorption of iron. The resulting iron overload can cause abnormal deposits of iron to build up in the pituitary gland and testicles. If enough iron accumulates in the pituitary gland, FSH and LH release can be impaired. Excessive iron deposits within the testicles can also lead to testicular failure.

 

Hypospadias

Hypospadias is a congenital problem characterized by an abnormal location of the meatus (the opening on the penis). Mild cases of hypospadias, in which the opening is still near the tip of the penis, do not typically impact male fertility significantly. However, if the meatus is not near the tip of the penis, then the sperm are not deposited close to the cervix during intercourse and ejaculation. Most cases of severe hypospadias in the United States are identified and corrected during early childhood. Persistent problems in adulthood can be corrected surgically, or the problem can be bypassed by using sperm collection combined with intrauterine insemination (see "Female Fertility Treatments").

 

Inguinal Hernia Repair

The vas deferens and blood supply of the testicles pass through the inguinal canal on their way to the scrotum. During repair of an inguinal hernia, these structures can be inadvertently damaged, with the risk being higher in hernia repairs during childhood, when these structures are significantly smaller. The risk of damaging the vas deferens during an inguinal hernia repair in adults is about 1–2 percent, with somewhat higher rates for repeat hernia repairs and repairs in children. The risk of significantly damaging the blood supply to the testicle during a hernia repair is generally felt to be around 1 percent.

About 3–4 percent of men who have had an inguinal hernia repair also have ejaculatory dysfunction (see “Ejaculatory Problems” section for more information).

The cause is not completely clear, but one idea is that the mesh that has been placed in the body during the repair process causes nerve entrapment. The resulting nerve inflammation and irritation can cause pain during sexual intercourse and ejaculation, leading to ejaculatory disorders. Potential treatments include careful mesh incision and transection of the ilioinguinal and iliohypogastric nerves by a pain specialist, if conservative treatments (such as corticosteroid or local anesthetic injections into the area) have not been effective.

 

Myelodysplasia/Spina Bifida

Congenital abnormalities of the developing neural tube during fetal development can result in the abnormal formation of some of the vertebral bodies that normally protect the spinal cord. Depending on the severity of the defect, varying amounts of the spinal cord contents may protrude out of the vertebral body, resulting in permanent neurologic damage. This nerve damage can lead to varying degrees of erectile and ejaculatory problems in some men.

 

Myotonic Dystrophy

Myotonic dystrophy is a progressive disease characterized by muscle wasting, heart problems, cataracts, and hormone abnormalities. Eighty percent of men with muscular dystrophy have significant testicular atrophy and sperm production problems.

 

Orchitis/Mumps

Orchitis is inflammation and/or infection of the testicles. Inflammation in this area can be caused by bacteria, viruses, or non-infectious causes. Orchitis can be a source of pyospermia (although epididymitis and prostatitis are more common causes of pyospermia). Orchitis is typically painful, but in some men it can be a chronic, asymptomatic problem.

See "Reversible Semen Analysis Factors" for more information on pyospermia.

Mumps is the most common cause of viral orchitis. Orchitis develops in about 20–30 percent of men who contract mumps after puberty, and one in ten of these cases involves both testicles. Intense swelling and inflammatory changes can accompany the orchitis, and typically cause significant scrotal pain. If not managed with early high-dose corticosteroids or interferon, mumps orchitis often results in permanent damage to the testicle, which can atrophy and become nonfunctional. The atrophic changes typically occur within the first six months, but sometimes they can take years to develop. In men with untreated mumps orchitis, approximately 10–15 percent will have fertility problems if only one testicle was affected, and 30–90 percent if both testicles were involved.

Other viruses that are known to sometimes cause orchitis include echovirus, group B arbovirus, and Epstein-Barr virus (mononucleosis).

 

Pituitary Insufficiency (Hypopituitarism)

The pituitary gland is the major hormone control center of the brain. Pituitary function can be diminished for a number of reasons, including tumors, infections or inflammation, vascular injury, radiation, trauma, and surgery. Various congenital problems (such as Kallman’s syndrome—see "Genetics" section) can also severely impact the pituitary’s function. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), growth hormone (GH), and prolactin can all be affected by pituitary gland problems. Symptoms depend on the clinical situation and on which hormone levels are impacted. Tumors in the region of the pituitary gland can be completely asymptomatic, or they can cause symptoms such as headaches and vision changes.

 

Polycystic Kidney Disease

Polycystic kidney disease is a genetic abnormality that involves extensive cystic changes within the kidneys. These cystic changes can also be seen in the seminal vesicles, which can impact their ability to contract during ejaculation. Mild cases can sometimes be managed with intercourse once or twice a day during the woman’s fertile phase. In more severe cases, no fluid is transported through the ejaculatory ducts, and sperm extraction must be employed in order to retrieve sperm for IVF/ICSI.  For more information on sperm extraction, see Management of Obstructive Azoospermia in the "Azoospermia" section of this website.

 

Posterior Urethral Valves

Infants may sometimes have abnormal flaps of tissue in the urethra, which result in obstruction of the flow of urine. If left untreated, these posterior urethral valves can lead to urinary retention, recurrent urinary tract infections, abnormal reflux of urine from the bladder back up the ureters, and kidney damage and/or failure. Treatment of posterior urethra valves typically involve resection of the valves through a small scope placed up through the penis.

Approximately 50 percent of men with a history of posterior urethral valves have abnormalities of their semen parameters. About 40 percent of these men report a lack of forceful ejaculation. Some also experience retrograde ejaculation into a dilated posterior urethra area. About 10–15 percent of these patients also have a history of undescended testicles at birth.

 

Prader-Willi Syndrome

This abnormality is caused by a genetic abnormality on chromosome 15 and is characterized by obesity and mental retardation, among other findings. Pituitary gland hypofunction is common in these patients, resulting in significant hypogonadism (see "Hormone Testing and Interpretation" for more information).

 

Prostatitis

Inflammation of the prostate is something urologists see relatively often. Symptoms can range from none (the most common situation) to severe irritation when urinating (similar to a urinary tract infection). Most cases of prostatitis in young men are due to non-infectious inflammation; however, bacteria are the cause of the problem in up to 10–20 percent of cases. Prostatitis can cause male fertility problems due to the presence of pyospermia (see “Reversible Semen Analysis Factors" for more information on pyospermia).

 

Prune Belly Syndrome

Prune belly syndrome is a genetic abnormality resulting in lax abdominal muscles, along with bilateral undescended testicles and a small, underdeveloped prostate gland. Abnormal development of the vas deferens, seminal vesicles, and epididymis is also common. There are no documented cases of men with this syndrome achieving successful pregnancies by natural intercourse, but extracted sperm have been used successfully in combination with IVF/ICSI. As with most genetic diseases, genetic counseling is strongly recommended prior to fertility treatments to discuss the potential risk of transmitting this condition to offspring.

 

Radiation Therapy

See the "Cancer and Male Fertility" section for more information.

 

Renal Failure

Decreases in kidney function can cause the following problems, all of which may have a negative impact on fertility:

      1) Nutritional deficiencies

      2) Elevated estradiol

      3) Elevated prolactin

      4) Low testosterone

      5) Decreased libido

      6) Erectile dysfunction

Hemodialysis, used to treat kidney failure, itself has been associated with decreased levels of testosterone and increased levels of estradiol. Semen parameters have been shown to inversely correlate with the length of time a man has been on dialysis. Kidney transplantation can reverse many of the sexual and fertility abnormalities associated with renal failure and dialysis. Even though immunosuppressive drugs, such as cyclosporine, are known to potentially have a negative impact on semen parameters, they tend to have less of a negative fertility impact on most people than does dialysis.

 

Retractile Testicles

Retractile testicles are a mild form of undescended testicles in which the cremasteric muscles in the scrotum are hyperactive, thereby drawing the testicles high up within the scrotum for prolonged periods. This has been shown to increase the temperature of the testicles in some men, possibly impacting semen parameters. Some findings have suggested that early surgical treatment could help to avoid problems, although these recommendations have not been confirmed in large studies.

 

Sarcoidosis

This is a multi-system disease characterized by granulomas (areas of inflammation) in the lungs and throughout the body. The cause is unknown. These granulomas can involve the epididymis in some men, leading to obstructive azoospermia.

 

Sickle Cell Anemia

This is a genetic abnormality in the body’s synthesis of hemoglobin (which carries oxygen in the blood). It causes red blood cells to form an abnormal sickle shape, leading to various complications throughout the body. Sickle cell patients are at an increased risk of experiencing micro-infarcts of the pituitary gland and testicles, thereby damaging their function over time. Repeat blood transfusions can also result in a buildup of iron within the pituitary gland and testicles, causing further damage. Many men with sickle cell anemia therefore often have hypogonadism, testicular atrophy, and abnormal semen analyses.

 

Spinal Cord Injury

See “Ejaculatory Dysfunction" section for more details.

 

Testicular Cancer

Testicular cancer can cause fertility problems in multiple ways:

1) At the time of diagnosis, before any treatment, 50 percent of men with testicular cancer have a low sperm count (oligospermia) and 10 percent have a total absence of sperm (azoospermia). This decrease in sperm production is likely a result of stress on the body as well as a by-product of the immune system’s efforts to fight the cancer. Of men who had azoospermia when their cancer was diagnosed, approximately 40 percent will see return of some sperm to the ejaculate after the affected testicle has been removed.

2) Orchiectomy (surgical removal of the testicle) is the standard first-line therapy for testicular cancer. Removing one of the testicles can obviously have an impact on future sperm production, although sometimes, as described above, removing the affected testicle can improve sperm count if it was low or zero as a result of the cancer.

3) Following orchiectomy, radiation and/or chemotherapy are sometimes necessary to treat or prevent metastatic disease. Both radiation and chemotherapy can have a significant negative impact on sperm production (see “Cancer Treatments,” above).

 

Men who are diagnosed with testicular cancer but would like to have children in the future should always attempt to freeze sperm prior to treatment. If no sperm are present prior to orchiectomy and the patient will need subsequent radiation or chemotherapy, they can try to freeze sperm again after the orchiectomy and before starting radiation or chemo. Ideally, sperm should not be frozen after radiation or chemotherapy has started, due to the potential for those treatments to cause DNA changes in the sperm.

 

Testicular Torsion

Torsion is a very painful medical problem in which the testicle twists within the scrotum, thereby cutting off its blood supply. This is a medical emergency that requires immediate surgical repair. If the blood supply is not restored to the testicle within six to ten hours, irreversible damage to the testicle often results.

 

Urethral Stricture Disease

Scar tissue in the urethra typically does not significantly affect the flow of sperm, unless it has progressed to the point where the patient is in complete urinary retention and is emptying his bladder by other means (such as via a suprapubic urinary catheter inserted through the lower abdominal wall). Surgeries to treat urethral stricture disease, however, can result in scar tissue in the area of the verumontanum, resulting in ejaculatory duct obstruction in some men (see “Ejaculatory Dysfunction" section for more details on ejaculatory duct obstruction).

 

Young’s Syndrome

Young’s syndrome is a rare condition in which the mucus in the respiratory and genital ductal systems is abnormally thick. This results in a triad of symptoms: bronchiectasis (irreversible dilation of lung passages), recurrent sinusitis, and obstructive azoospermia. The thick mucus results in a blockage of sperm transport, typically within the epididymis. Sperm can be extracted surgically and used in conjunction with IVF/ICSI.  See the "Azoospermia" section for more details.