Medical Conditions That Can Impact Sperm Quality
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) and Male infertility
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, and live births are possible with treatment. [Massin N. ClinEndocrinol 2012]
Benign Prostatic Hypertrophy (BPH) and male infertility
BPH is when the prostate enlarges over time and causes blockage of the urinary channel (resulting in symptoms such a slow urinary stream and incomplete bladder emptying). Untreated BPH has been associated with an increased risk of ejaculatory problems. [Avellino G. FertSteril 2017]. However, many of the treatments for BPH can further worsen male fertility potential. Some of the surgical treatments for BPH (such as transurethral resection of the prostate/TURP) can result in retrograde ejaculation, while many of the medications used to treat BPH can reduce sperm production and quality as well as cause ejaculatory problems. One medication option which is effective for BPH symptoms and does not have any significant negative impact on male fertility are PDE-5 inhibitors such as daily tadalafil. [Gacci M. EurUrol 2016] For more information on surgical and medical treatments of BPH and their impact on male fertility, please see the “Ejaculatory Dysfunction” and “Medications and Supplements” sections of this website.
Beta-thalassemia and male infertility
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, with rates of hypogonadotropic hypogonadism reported in up to 90% of men with this problem. [Wiwanitkit V. IranJReprodMed 2012]. Elevated levels of oxidative stress and sperm DNA fragmentation have also been reported in men with beta-thalassemia, and iron deposits within the testicles can also lead to testicular failure as well.
Cancer Treatment and male infertility
See the "Cancer and Male Fertility" section for more information.
Celiac Disease and male infertility
Celiac disease is an autoimmune disease of the small intestine which is triggered by exposure to dietary gluten. 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, leading to decreases in sperm density, motility, and morphology. [Freeman HJ. WorldJGastroent 2010] There is some evidence that these negative hormonal and fertility effects can be improved with avoidance of gluten containing foods.
Chemotherapy and male infertility
See “Cancer and Male Fertility" link above.
Ciliary Diseases and male infertility
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. [Sha Y. AsianJAndrol 2014]
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 general health implications.
Cirrhosis/Liver Disease and male infertility
Men with liver disease have higher rates of male infertility due to increased rates of:
1) Hypogonadism and pituitary dysfunction
2) Elevated estradiol levels
3) Testicular atrophy
4) Erectile dysfunction
5) Gynecomastia (breast enlargement)
Partial improvements in hormonal function have been seen after successful liver transplantation surgery. [Foresta C. J.EndocrinolInvest 2014]
Congenital Adrenal Hyperplasia (CAH) and male infertility
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. CAH can cause infertility problems in 2 ways: increased androgen production and benign testicular tumors. [Tanaka M. ReprodMedBiol 2018] From a hormonal standpoint, in men with CAH the substances that usually serve as precursors to making 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 these 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 predictably negative impact on sperm production, and 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. Milder variants of CAH can also be present, in which cortisol production is only partially blocked and these men typically develop milder symptoms later in life.
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.
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.
Treatment of CAH involves the replacement of corticosteroids (typically in the form of medications like dexamethasone) which can reduce the production of adrenal androgens. If hormonal abnormalities persistent, then treatment of hypogonadism can be undertaken (such as HCG injections). Approximately 75% of testicular adrenal rest tumors regress with treatment which may relieve obstruction in some men as well. [Tanaka M. ReprodMedBiol 2018]
Covid 19 (SARS-CoV-2)
Infection with the SARS-CoV2 coronovirus has been associated with testicular involvement and dysregulation of the HPG axis. Severe reductions in semen parameters are seen in some patients, but recovery usually occurs within 3 months. Reversible changes in testosterone levels have also been found. The Covid-19 vaccines have not been found to have any appreciable sustained negative impact on semen parameters and male fertility potential. [Gonzalez DC. JAMA 2021][Danders GC. FertSteril 2021][Lifshitz D. ReproBiomedOnline 2022]
Crohn’s Disease and male infertility
See “Inflammatory Bowel Disease” section below
Cryptorchidism and male infertility
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, about 10% of men with infertility problems have a history of an undescended testicle. [Cheng E. CanUrolAssocJ 2011]. The normal position of the testicles within the scrotum allows them to remain two to three degrees cooler than the rest of the body, but 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.
If left untreated, approximately 13% of men unilateral and up to 98% of men with bilateral undescended testicles become azoospermic. [Cheng E. CanUrolAssocJ 2011]. 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. It is recommended that orchidopexy be performed around 6 months of age to try and prevent permanent damage to the testicular germ cells. [Trussel J. CurrUrolRep 2004]. Even with prompt treatment, approximately 35% of men still have abnormalities in their semen parameters. With delayed treatment, semen abnormalities are found in 20–75 percent of men with one undescended testicle and 50–90 percent of men with two undescended testicles.
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
Depression
Depression has been associated with decreased semen parameters in some men. A study of 1000 healthy sperm donors found had a baseline sperm count of 62 million sperm/cc. Mild and moderate depression were only associated with small decreases in density (60-61 million/cc). However, donors with severe depression had significantly lower average sperm counts of 50 million/cc. Motilities were unchanged for mild and moderate depression, and only relatively small changes were seen in men with severe depression (64% vs. 60%). [YiXiang Y. JUrol 2022]
Diabetes and male infertility
Diabetes can negatively impact male fertility potential in several ways. Men with Type 1 diabetes can have autoimmune-related damage to the testicles and epididymis, while Type 2 diabetics tend to have problems related more to insulin resistance including inflammatory changes and oxidative stress. [Condorelli RA. FrontEndocrinol 2018] Both types of diabetes can damage nerves and blood vessels in the body, the result of which can be endocrine abnormalities, decreased semen parameters, and increased levels of DNA fragmentation. v
Sperm transport is also often impaired in men with diabetes. [La Vignera S. Andrology 2012] This can manifest itself in several ways:
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 and/or atonic seminal vesicles (makes them unable to contract and propel sperm into the urethra; electroejaculation does not work well in these patients)
Tight control of blood sugars levels can help to limit further damage to a man’s fertility, though it may not be able to reverse the changes already present. For more information on the management of sperm transport problems, see the “Erectile Dysfunction” and “Ejaculatory Problems” sections of this website.
Epididymitis and male infertility
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
Hemochromatosis and male infertility
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 primary testicular failure. [Osta RE. BasicClinAdnrol 2017]
Histiocytosis
Histiocytosis is a rare clonal neoplastic disorder characterized by the accumulation of Langerhans cells in different locations throughout the body. Though more common in children, in adults it presents as multisystem granulomatous infiltrates. Common locations for involvement include the liver, spleen, bone, and lymph nodes. Cell accumulation can also affect the pituitary gland causing local destruction of tissue. Usually the posterior pituitary is most commonly impacted results in diabetes insipidus (DI) due to ADH deficieny. TSH, growth hormone, and ACTH levels can also be diminished. About 50% of patients with DI also have involvement of the anterior pituitary with subsequent reductions in FSH and LH production. Case studies have reported men with histiocytosis X who present with infertility as their presenting complaint. Treatment usually involves corticosteroids and chemotherapy. [Kumar C. GulfJOnc 2021]
Hypospadias and male infertility
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. Residual scar tissue or anatomic abnormalities can sometimes cause blockage issues with sperm transport. Persistent problems with an abnormal location of the urethral meatus in adulthood can be corrected surgically, or the problem can be bypassed by using sperm collection combined with intrauterine insemination.
Inflammatory Bowel Disease and male infertility
Inflammatory bowel disease (IBD) usually has an onset in the young adult time frame and includes Crohn’s Disease (CD) and ulcerative colitis (UC). IBD can negative impact male fertility through poor nutrition, sexual dysfunction, active inflammation/oxidative stress, and bowel surgery. [Park YE. WorldJMensHealth 2019] Medications used to treat IBD can also impact semen parameters as well. Alcohol use has been shown to exacerbate inflammation in men with IBD, as can tobacco use in men with CD. [Shin T. WorldJGastrointPharTher 2016].
Approximated 25-35% of men with UC and 70-90% of with CD will eventually require surgical intervention. [Shin T. WorldJGastrointPharTher 2016]. Minor procedures such as fistula repairs generally do not impact fertility. However, larger surgeries such as proctocolectomies can disrupt pelvic nerves and result in erectile and ejaculatory dysfunction in up to 8-25% of men.
The following is a review of medications used to treat IBD:
1) Sulfasalazine- commonly used in the treatment of IBD, but also has uses in the management of rheumatoid and psoriatic arthritis. Numerous studies have shown that this medication is known to have a reversible negative impact on semen parameters in the majority of men who take it. [Mouyis M. SemArthRheum 2019] Studies have shown improved parameters and pregnancy in men wth IBD changing to mesalamine (5-ASA). The mechanism of action for the anti-fertility effect of sulfasalazine is currently not known. [Alhamam A. FertSteril 2023]. Most studies have not shown adverse pregnancy outcomes in men who conceive while taking sulfasalazine. [Mouyis M. SemArthRheum 2019]
2) Mesalamine (5-ASA)- this medication is generally felt to be much safer for male fertility than sulfasalazine. There have been case reports of decreased semen parameters in men started on mesalamine, but the general recommendations are to only stop this medication in men with very stable IBD. [Kjaergaard N Scand J Gastroent 1989]
3) Corticosteroids- used to treat relapses of IBD but not generally used for maintenance therapy. Short term use of corticosteroids generally not negative impact semen parameters or health, though prolonged use in high doses can lead to significant general health problems.
4) Thiopurines- include azathioprine and its active metabolite (6-MP)- used and an adjunct treatment for IBD. Although no significant changes are generally seen in sperm counts, one study did find lower sperm motility. [Grosen A. J Crohns Colitis 2019]. The literature also suggests a small potential increased risk of miscarriage and congenital abnormalities of offspring. It is therefore recommended to use contraception for men taking azathioprine and 6-MP. [Semet M. Andrology 2017].
5) Methotrexate- dihydrofolate reductase inhibitor that can be used both as a cytotoxic chemotherapeutic agent as well as to treat inflammatory arthritis. Reversible decreases in semen counts have been reported in some men taking methotrexate for psorias [Sussman Arch Derm 1980] and small studies have shown increases in sperm DNA fragmentation as well. [Ley D. Gastroenterol 2018]. Earlier recommendations were to stop the medication 3 to 4 months prior to starting to try to conceive. However, subsequent studies have not confirmed decreases in semen parameters or DNA fragmentation in men on methotrexate for rheumatology problems. [Grosen A. Inflamm Bowel Dis 2022][Perez-Garcia LF. AnnRheumDis 2023]. In summary, the majority of studies have shown no negative impact of methotrexate on semen parameters and that low-dose methotrexate used in the treatment of inflammatory disorders does not increase the risk of fetal malformations. [Mouyis M. SemArthRheum 2019]. A study of 223 children born to men taking methotrexate confirmed no increased risk of congenital anomalies, pre-term births, or being small for gestational age. [Zaren P. FertSteril 2023]
6) Calcineurin inhibitors- these include cyclosporin A (CSA) and tacrolimus. Used for immunosuppression as calcineurin activated immune T cells. There is only limited data on the fertility impact of these medications in humans. [Alhaman A. FertSteril 2023]. In rats, the use of CSA has been associated with decreased testicular weight along with lower testosterone levels and semen parameters. To date, only small studies in humans have been performed, but these do not appear to show any significant decrease in male fertility potential. [Haberman JUrol 1991].
7) Antitumor necrosis factor (anti-TNF) medications: infliximib, natalizumab, vedolizumab, ustekinumab- these are biologic agents which are monoclonal antibodies against TNF-alpha, an immune system cytokine. Multiple studies have not found a negative impact on male fertility, semen parameters, or sperm DNA integrity. [Alhaman A. FertSteril 2023].
General recommendations for IBD medications: In men taking sulfasalazine, it is recommended to change to mesalamine at least 4 months prior to trying to conceive. In men taking mesalamine who have abnormal semen parameters, a trial of short periods off mesalamine could be tried if the man’s IBD symptoms are stable. There is insufficient evidence to support the stopping of methotrexate in men who need this medication to control their symptoms. [Shin T. WorldJGastrointPharTher 2016].
Inguinal Hernia Repair and male infertility
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 young 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.
Myotonic Dystrophy and male infertility
Myotonic dystrophy is a progressive disease characterized by muscle wasting, heart problems, cataracts, and hormone abnormalities. Endocrine defects as well as testicular atrophy lead to low sperm counts or even azoospermia in the majority of men with myotonic dystrophy. [Kim WB. KorJUrol 2012]. In any sperm which are present, increased rates of abnormalities with capacitation and acrosome reactions have also been reported. [Hortas ML. HumReprod 2000]
Orchitis/Mumps and male infertility
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) and male infertility
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 and male infertility
Polycystic kidney disease is a genetic abnormality that involves extensive cystic changes within the kidneys. Progression to end stage renal disease can have a negative impact on semen parameters. Cystic changes can also be seen in the seminal vesicles, which can cause blockages as well as impact their ability to contract during ejaculation. [Vecchi ML. NephrolDialTranspl 2003] 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 and male infertility
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.
In men who have had a previous treatment for posterior urethral valves, there are several potential issues related to fertility. One is that about 10–15 percent of these patients also have a history of undescended testicles at birth which can impact semen parameters. Up to 50% of men with a history of treated posterior urethral valves report slow or dry ejaculates likely related to anatomic changes from their persistently dilated posterior urethral areas with retrograde flow of the ejaculate into this area. A 2013 study found that the majority of patients had semen parameters that still fell within the normal range, but that there was an increased risk of elevated numbers of white blood cells in the ejaculate (pyospermia). [Pereira PL. JPedUrol 2013]. Rates of erectile dysfunction were also higher than the general population for that age range.
Prader-Willi Syndrome and male infertility
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. In addition to hypogonadism, undescended testicles are also common in this population. Despite a 2019 study showing that about 20% of males with Prader-Willi Syndrome have “favorable” histology on testicular biopsy in terms of the presence of germ cells, no recorded pregnancies have been reported to date in men with this syndrome. [Matsuyama S. EndocrinolDiabMetab 2019] (see "Hormone Testing and Interpretation" for more information).
Prostatitis and male infertility
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 and male infertility
Prune belly syndrome (also called Eagle Barrett 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, as is retrograde ejaculation. Small numbers of sperm are sometime present in the ejaculate, but there are no documented cases of men with this syndrome achieving successful pregnancies by natural intercourse. The use of ejaculated or extracted sperm have been used successfully in combination with IVF/ICSI. [Fleming SD. FertSteril 2013] 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 and male infertility
See the "Cancer and Male Fertility" section for more information.
Renal Failure and male infertility
Renal failure can lead to problems with male fertility through several mechanisms. End stage renal disease (ESRD) has been associated with hormonal abnormalities and erectile dysfunction. Disturbances in pituitary function leading to decreased testosterone levels have been documented in up to 50% of men on hemodialysis (HD). [Lundy SD. TranslAndrolUrol 2019]. Changes in semen parameters are common in men with ESRD, with large numbers of men showing decreases in sperm counts, motility, and morphology.
Renal transplantation can offer improve semen parameters and fertility potential in men with ESRD. The transplantation surgery itself can potentially lead to blockage of the vas deferens, damage to the blood supply of the testicles, and disruption of the nerves which control ejaculation, but rates of these complications are relatively low. [Lundy SD. TranslAndrolUrol 2019]. Studies have shown a doubling of testosterone levels in men following transplantation. [Lim VS. AmJMed 1975]. Semen parameters also improve in the majority of men, though a subset still have decreased sperm counts and even azoospermia. [Lundy SD. TranslAndrolUrol 2019] Sexual function also often improves in men following renal transplant surgery.
Immunosuppressive medications are generally needed in men undergoing renal transplantation, and there are some concerns as to the impact of these on male fertility.
1) Calcineurin inhibitors (CNIs)- these commonly used immunosuppressive medications include cyclosporin A (CSA) and tacrolimus. In rodent models, CSA has been found to have a negative impact on testicular function and semen parameters [Gawish AM. JBasApplZoo 2016], although human studies have not shown dramatic decreases in fertility potential of men taking these medications. [Semet M. Andrology 2017]. Animal studies on tacrolimus point to less of a negative impact on semen parameters, but data from human studies are limited. [Lundy SD. TranslAndrolUrol 2019]. The impact on hormone levels appears to be similar between men taking CSA and tacrolimus. [Kantarci G. TranplantProc 2004]. Recommendations are that CSA does not need to be discontinued in men who are trying to conceive, but no recommendations are currently available for tacrolimus due to a lack of data. [Semet M. Andrology 2017].
2) mTOR (rapamycin) inhibitors- these medications include sirolimus, everlimus, and temsirolimus and inhibit lymphocyte proliferation. These medications have been associated with reversible negative changes in semen sperm counts and motility along with decreased pregnancy rates. [Zuber J. AmJTransplant 2008]. Testicular atrophy and azoospermia have also been reported with the use of mTOR inhibitors. [Alhaman A. FertSteril 2023]. Potential teratogenic changes seen in sperm with animal models. It has been recommended to cryopreserve sperm in men to be started on medications like sirolimus and use contraception while men are taking this medication. [Semet M. Andrology 2017].
3) Mycophenalate [Cellcept]- antimetabolite immunosuppressant agent used in transplantation patients and inflammatory conditions like SLE. This medication has been shown to decrease semen parameters in animals, though this has not been studied in human studies. [Lundy SD. TranslAndrolUrol 2019] Human studies have not shown significant negative impacts on male fertility or adverse birth outcomes in children fathered by men taking mycophenalate. [Mouyis M. SemArthRheum 2019]
4) Corticosteroids- Studies have not shown significant long-term negative effects on sperm production in men taking shorter course of oral corticosteroids. [McDonald JH. JUrol 1956]. Long-term high dose corticosteroid use has the potential to impact the hypothalamic-pituitary-gonadal axis, and can lead to a number of other general health problems such as osteoporosis, thinning of the skin, weight gain, fluid retention, and an increased risk of infection and tumors. [Alhamam A. FertSteril 2023] In the treatment of immunologically-related fertility problems such as anti-sperm antibodies, low dose corticosteroids have been associated with improved semen parameters. [Omu AE. EurJObsGenReprodBiol 1996]
Retractile Testicles and male infertility
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. More common in children, this issue is present in some adult men as well. This has been shown to increase the temperature of the testicles in some men, possibly impacting semen parameters but clinical data on this is very limited. Some findings have suggested that early surgical treatment could help to avoid problems, although these recommendations have not been confirmed in large studies.
Sarcoidosis and male infertility
Sarcoidosis is a multi-system disease characterized by the formation of granulomas (areas of inflammation) in the lungs and throughout the body. The disease usually has an onset in 20 to 40 year old age range, and in a minority of men the granulomas can form within the testicles, epididymis, and vas deferens. [Canguven O. KorJUrol 2011] Decreased fertility can result from local destruction of testicular tissue as well as the blockage of sperm flow leading to decreased sperm counts and even azoospermia. There have been some case reports of improved fertility with corticosteroid treatment.
Sickle Cell Anemia and male infertility
Sickle cell anemia is a genetic abnormality in the body’s synthesis of hemoglobin (which carries oxygen in the blood) which 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. [Habibi A. Blood 2017] 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 along with testicular atrophy, and an estimated 70-100% of men with sickle cell anemia have abnormalities on semen analysis testing. [Berthaut I. Haematolgica 2008]
Hydroxyurea is an antimetabolite medication used in the treatment of sickle cell anemia (as well as leukomia and other malignancies). Early animal studies showed that this medication could cause decreases in sperm density, motility and morphology. [Fiscor G. MutatRes 1980]. Later human studies unfortunately found that hydroxyurea often also has a significant negative impact on most men taking the medication. The HYDREP study found that 86% of men taking hydroxyurea had decreasing total sperm counts at 6 months and these decreases could be severe, leading to complete azoospermia in some cases. [Bachir D. Blood 2012] Case studies have shown that impairments in sperm production can sometimes recovery upon cessation of treatment but often persist. [Grigg A. IntMed J 2007]. It has been strongly recommended for men to cryopreserve sperm prior to starting hydroxyurea therapy. Newer alternative treatments for sickle cell anemia with no expected negative impact on semen parameters include crizanlizumab (Adakveo) which is a monoclonal antibody therapy. Another treatment option not felt to have significantly impact male fertility is voxelotor (Oxbryta) which works by restoring RBCs to their normal shape.
SPINA BIFIDA and male infertility
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. From a fertility standpoint, men can have abnormalities of both sperm production as well as erectile and ejaculatory issues. [Deng N. TranslatAndrolUrol 2018]. Rates of undescended testicles are also higher in this population. In general, the higher the level of the spinal cord lesion, the greater the impact on male fertility potential. In terms of treatment, some adult males with spina bifida have small amounts of sperm in their ejaculate which can be used with IVF/ICSI. For men with azoospermia, electroejaculation is sometimes effective in retrieving sperm. Surgical sperm extraction can also be used in combination with IVF/ICSI as well.
Spinal Cord Injury and male infertility
See “Spinal Cord Injury" section for more details.
Testicular Cancer and male infertility
Testicular cancer is a risk factor for male infertility in that the disease itself can decrease semen parameters and the treatments for it can further decrease fertility potential as well. [Parekh NV TranslAndrolUrol 2020]. At the time of diagnosis and before any treatment, about 50 percent of men with testicular cancer have a low sperm count (oligospermia) and 10 percent have a total absence of sperm (azoospermia). Elevations in sperm DNA fragmentation are also common in men with testicular cancer pre-treatment. [Paoli D. FrontEndocrinol 2018] 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 in addition to local destruction of spermatogenic cells by the tumor. 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.
Standard first line treatment for testicular cancer is radical orchiectomy, in which the testicle with the tumor is completely removed. 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 to begin with as a result of the cancer. Sometimes other surgeries are needed, such as a retroperitoneal lymph node dissection (RPLND) in which the lymph nodes deep within the abdomen (where cancer cells from the testicles often spread first) are removed. Unfortunately, the nerves which control ejaculation are in this area, so early surgical techniques left the majority of these men unable to ejaculate. Newer nerve sparing RPLND techniques have now been developed with ejaculatory dysfunction rates of <10%. [Parekh NY TranslAndrolUrol 2020]
Depending on the tumor type and degree of spread, 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 and Male Fertility” sections for more information).
In general, testicular cancer is curable in most men with modern treatment modalities, and the majority of men have a return of sperm following treatment for their testicular cancer. Men with a history of testicular cancer have about a 33% decreased chance of fathering a child within 5 years of their cancer treatment, and 20% decreased after 5 years. [Paoli D. FrontEndocrinol 2018]. However, up to 22% of men who are able to father a child need the assistance of advanced treatments from the female side such as IVF. [Parekh NY TranslAndrolUrol 2020]. Some men unfortunately also have permanent azoospermia following treatment of their testicular cancer, especially if they needed chemotherapy/radiation treatments. In some of these men, sperm can be found for IVF/ICSI with the use of microscopic testicular sperm extraction (microTESE). [Shiraishi K. Urology 2014] However, to try and prevent these situations, it is very important for men who are diagnosed with testicular cancer and would like to have children in the future to 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 (aneuploidy) in the sperm.
Testicular Torsion and male infertility
Torsion is a urologic emergency in which the testicle twists within the scrotum, thereby cutting off its blood supply and requires immediate surgical repair. Injury to the testicle occurs from ischemia and oxidative stress, and the degree of damage depends on the severity of the loss of blood flow as well as length of time before blood flow is re-established. Irreversible ischemic damage generally occurs if the torsion is not reversed within 4 to 8 hours, and sometimes the testicle needs to be removed due to extensive damage. [Sharp AV. AmFamPhys 2013]. Decreases in sperm counts and quality have been shown to occur in men with prior testicular torsion that was repaired presumably due to ischemic damage of the testicular tubules. [Jacobsen FM. WorldJMensHealth 2019]
Urethral Stricture Disease and male infertility
Scar tissue in the urethra can occur due to trauma, instrumentation (such as prior traumatic catheterization placement), previous surgeries (such as hypospadias repair), and infections from sexually transmitted diseases. If severe enough, urethral strictures can partially block the flow of sperm causes and interfere with the process of emission (flow of sperm from the genital ducts into the urethra) thereby decreasing semen parameters. [Yeboah ED. IntJFertMenopausStud 1994]. Surgical treatments (such as dilation of scar tissue or urethroplasty) can be undertaken, but even when these surgeries are successful at opening up the urethral channel, they do not always result in improvements in semen parameters. [Kalozny A. JSexMed 2018]. There is also the risk that surgeries to treat urethral stricture disease can result in scar tissue in the area of the verumontanum, resulting in ejaculatory duct obstruction and complete azoospermia in some men (see “Ejaculatory Dysfunction" section for more details on ejaculatory duct obstruction).
Young’s Syndrome and male infertility
Young’s syndrome (Sinusitis-Infertility Syndrome) is a rare genetic condition in which the mucus in the respiratory and genital ductal systems is abnormally thick. [Mohammed SK. Young Syndrome 2019]. 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.