Causes of Male Infertility
More than 90% of male infertility cases are due to low sperm counts, poor sperm quality, or both. The remaining cases of male infertility can be caused by a range of conditions including anatomical problems, hormonal imbalances, and genetic defects.
Sperm abnormalities are a critical factor in male infertility. These abnormalities include:
Risk factors for male infertility include:
In addition to a medical history and physical exam, specific tests for male infertility include:
Treatment for male infertility should first address any underlying medical conditions that may be contributing to fertility problems. Drug therapy may be used to treat hormonal disorders. Surgery may be used to repair varicoceles and correct any obstructions in the reproductive tract.
If fertility issues remain unresolved, intracytoplasmic sperm injection (ICSI) is commonly used in combination with in vitro fertilization (IVF) to achieve pregnancy when male infertility is a factor. ICSI involves injecting a single sperm into an egg obtained through IVF. The fertilized egg is then implanted back into the woman. Pregnancy success rates depend on many different factors.
Infertility is the failure of a couple to become pregnant after one year of regular, unprotected intercourse. About a third of infertility problems are due to female infertility, and another third are due to male infertility. In the remaining cases, infertility affects both partners or the cause is unclear. [For information about female infertility, see In-Depth Report #22: Infertility in women.]
Male fertility depends on the proper function of a complex system of organs and hormones:
Sperm are made in hundreds of microscopic tubes, known as seminiferous tubules, which make up most of the testicles.
Surrounding these tubules are clumps of tissue containing Leydig cells, which produce testosterone when stimulated by luteinizing hormone (LH).
Sperm Development. The life cycle of sperm takes about 74 days:
Ejaculation. When a man experiences sexual excitement, nerves stimulate the muscles in the epididymis to contract, which forces the sperm out through the penis:
Semen. In addition to providing the fluid that transports the sperm, semen also has other benefits:
The Path to the Egg. The sperm's passage to the egg is a difficult journey.
More than 90% of male infertility cases are due to low sperm counts, poor sperm quality, or both. The remaining cases of male infertility can be caused by a number of factors including anatomical problems, hormonal imbalances, and genetic defects.
Sperm abnormalities can be caused by a range of factors, including congenital birth defects, disease, chemical exposure, and lifestyle habits. (See Risk Factors section.) In many cases, the causes of sperm abnormalities are unknown.
Sperm abnormalities are categorized by whether they affect sperm count, sperm movement, or sperm shape. They include:
Retrograde ejaculation occurs when the muscles of the bladder wall do not function 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 result from several conditions:
Any structural abnormalities that damage or block the testes, tubes, or other reproductive structures can affect fertility:
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. It is usually the result of rare genetic diseases that affect the pituitary gland. These conditions 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. Hypogonadism can also develop later in life from brain or pituitary gland tumors or as a result of radiation treatments.
Certain inherited disorders can impair fertility. Examples include:
A varicocele is an abnormally enlarged and twisted (varicose) vein in the spermatic cord that connects to the testicle. Varicoceles are found in about 15% of all men and in about 40% of infertile men, although it is not clear how much they affect fertility or by what mechanisms. They can raise testicular temperature, which may have effects on sperm production, movement, and shape.
Age-related sperm changes in men are not abrupt, but are a gradual process. Aging can adversely affect sperm counts and sperm motility (the sperm's ability to swim quickly and move in a straight line). The genetic quality of sperm declines as a man ages.
Repeated Chlamydia trachomatis or gonorrhea infections are the sexually transmitted diseases 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.
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:
Occupational or other long-term exposure to certain types of toxins and chemicals (such as herbicides and pesticides) may reduce sperm count by either affecting testicular function or altering hormone systems. Estrogen-like and hormone-disrupting chemicals such as bisphenol A, phthalates, and organochlorines are particular potential concerns. Chronic exposure to heavy metals such as lead, cadmium, or arsenic may affect sperm quality. These chemicals generally affect men who have long-term and intense occupational exposure to them. At this time, there is no strong evidence supporting a serious harmful effect on fertility in men who have normal limited exposure to these chemicals.
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. Certain types of medications can impair sperm production.
Infections in the Urinary Tract or Genitals. Infections that may affect fertility include prostatitis (inflammation 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.
Cancer and Its Treatments. Cancer treatments such as chemotherapy and radiation can damage sperm quality and quantity, causing infertility. The closer radiation treatments are to reproductive organs, the higher the risk for infertility. There is also some evidence that male infertility is itself a risk factor for testicular cancer.
In any fertility work-up, both male and female partners are tested if pregnancy fails to occur after a year of regular unprotected sexual intercourse. It should be done earlier if a woman is over age 35 or if either partner has known risk factors for infertility. A work-up can not only uncover the causes of infertility but also detect other potentially serious medical problems, including genetic mutations, cancer, or diabetes.
The doctor will ask about any medical or sexual factors that might affect fertility:
A fertility specialist, usually a urologist, will perform a physical examination. A physical examination of the scrotum, including the testes, is essential for any male fertility work-up. It is useful for detecting large varicoceles, undescended testes, absence of vas deferens, cysts, or other physical abnormalities.
A urine sample to detect sperm after ejaculation may rule out or indicate retrograde ejaculation. It also may be used to test for infections.
The basic test to evaluate a man's fertility is a semen analysis. The sperm collection test for men who can produce semen involves the following steps:
The man and woman should both be present when the doctor discusses the results of this analysis so that both partners understand the implications. The analysis report should contain results of any abnormalities in sperm count, motility, and morphology as well as any problem in the semen. However, semen analysis alone is not necessarily a definitive indicator of either infertility or fertility.
A semen analysis will provide information on:
Semen Volume and Concentration. The seminal fluid (semen) itself is analyzed for abnormalities. The color is checked and should be whitish-gray.
The amount of semen is important. Most men ejaculate 2.5 - 5 milliliters (mL) (1/2 - 1 teaspoon) of semen. Either significantly higher or lower amounts can be a sign of prostate problems, blockage, or retrograde ejaculation.
The semen will be tested for how liquid it is. Abnormal results may suggest prostate gland problems or lack of sperm.
Other factors may also be measured:
Sperm Count. A low sperm count should not be viewed as a definitive diagnosis of infertility but rather as one indicator of a fertility problem. In general, a normal sperm count is considered to be 20 million per milliliter of semen.
Sperm Motility. Motility (the speed and quality of movement) is graded on a 1 - 4 ranking system. For fertility, motility should be greater than 2.
More than 63% of sperm should be motile for normal fertility, but even men whose motile sperm constitutes only about a third of the total sperm count should not rule out conception. Testing for sperm motility is important for predicting the success of assisted reproductive technologies and which men might be candidates for the intracytoplasmic sperm injection (ICSI) fertilization technique, in which the sperm is inserted directly into the egg and motility plays almost no role.
Sperm Morphology. Morphology is the shape and structure of the sperm. Determining the morphology of the sperm is particularly important for the success of the fertility treatments in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).
Blood tests are used for measuring several factors that might affect fertility:
Hormonal Levels. Men produce both male hormones (testosterone) as well as pituitary hormones (FSH and LH). Tests for these hormone levels are indicated if semen analysis is abnormal (especially if sperm concentration is less than 10 million per milliliter) or there are other indications of hormonal disorders.
Low levels of FSH, LH, and testosterone may indicate a diagnosis of hypogonadotropic hypogonadism. Very high FSH levels with normal levels of other hormones indicate abnormalities in initial sperm production. Usually this occurs only if the testicles are severely defective, causing Sertoli cell-only syndrome, in which sperm-manufacturing cells are absent. Other hormones, such as prolactin, estrogen, or stress hormones may be measured if there are symptoms of other problems, such as low sexual drive or the presence of breasts.
Infections. Blood tests can determine the presence of any infections that might affect fertility, including HIV, hepatitis, and Chlamydia.
Ultrasound imaging may be used to accurately determine the size of the testes or to detect cysts, tumors, abnormal blood flow, or varicoceles that are too small for physical detection (although such small veins may have little or no effect on fertility). It can also help detect testicular cancer.
Cervical Mucus Penetration Test. This post-coital test is designed to evaluate the effect of a woman's cervical mucus on a man's sperm. Typically, a woman is asked to come into the doctor's office within 2 - 24 hours after intercourse at mid-cycle (when ovulation should occur). A small sample of her cervical mucus is examined under a microscope. If the doctor observes no surviving sperm or no sperm at all, the cervical mucus will then be cultured for the presence of infection. The test cannot evaluate sperm movement from the cervix into the fallopian tubes or the sperm's ability to fertilize an egg.
Micro-Penetration Assay Test. This test checks to see if sperm can penetrate hamster eggs that have had their covering removed. If fewer than 5 - 20% of the eggs are penetrated, infertility is diagnosed. It may be useful for determining the best assisted reproductive treatment options for men with infertility.
Genetic testing may be warranted in men who are severely deficient in sperm and who show no evidence of obstruction, particularly in men undergoing the intracytoplasmic sperm injection (ICSI) procedure. Genetic testing can help identify sperm DNA fragmentation, chromosomal defects, or the possibility of genetic diseases that can be passed on to children. If genetic abnormalities are suspected in either partner, counseling is recommended.
Treatment for infertility should first address any underlying medical conditions that may be contributing to fertility problems. Drug therapy may be used to treat hypogonadism and other hormonally related conditions. Surgery is used to repair varicoceles and correct any obstructions in the reproductive tract. However, there is some controversy over whether varicocele embolisation or surgery actually improves fertility. Some studies indicate that varicocele treatment may not help improve a couple’s chances of conception.
If fertility issues remain unresolved, intrauterine insemination (also called artificial insemination) and assisted reproductive technologies such as in vitro fertilization should be considered. Intracytoplasmic sperm injection is commonly used in combination with in vitro fertilization in cases of male factor infertility. [See Assisted Reproductive Technologies section in this report.] The couple can also discuss with a fertility specialist other options such as donor sperm or eggs.
Choosing a good fertility clinic is important. Those offering assisted reproductive techniques are not always regulated by the government, and abuses have been reported, including lack of informed consent, unauthorized use of embryos, and failure to routinely screen donors for disease.
The clinic should always provide the following information:
Adolescents and adult men undergoing cancer treatments who may want to father children in the future should consider banking and freezing their sperm for later use in assisted reproductive therapies. This technique is called sperm cryopreservation. Sperm cryopreservation is recommended by the American Society of Clinical Oncology as the method with the highest likelihood of success for male cancer survivors. However, these banking methods are not appropriate for pre-adolescent boys being treated for childhood cancers such as leukemia. Researchers are investigating ways that stem cell transplantation may someday help these children regain their fertility while avoiding leukemia relapse.
Assisted reproductive technologies (ART) are medical techniques that help couples conceive. These procedures involve either:
Fertilization may occur either in the laboratory or in the uterus. In the U.S., the number of live birth deliveries from ART has dramatically increased in the last decade. About 40,000 live births (deliveries of one or more infants) occur in the U.S. each year using assisted reproductive technologies.
Technically, the term ART refers only to fertility treatments, such as in vitro fertilization (IVF) and its variants, which handle both egg and sperm. Therefore intrauterine insemination (artificial insemination) is not officially considered a form of ART.
Before fertilization using intrauterine insemination (IUI) or intracytoplasmic sperm injection (ICSI) can take place, the sperm must be collected and prepared.
When a man has no available sperm in the ejaculate (usually from blockage, vasectomy, or lack of vas deferens), the sperm must be retrieved from the testes or the epididymis. Various microsurgical techniques are used for retrieval. The procedure may be done under local or general anesthesia, using a spring-loaded biopsy device, a thin needle, incisions, or microsurgical techniques. Most procedures can be done on an outpatient basis, and the patient returns home the same day. There is no conclusive evidence that one procedure works better than another.
Testicular Fine Needle Aspiration. With testicular fine needle aspiration (TFNA), the surgeon uses a fine needle to remove sperm. This can be performed with local anesthetic and by surgeons who do not have experience in microsurgeries.
Microsurgical Epididymal Sperm Aspiration. Microsurgical epididymal sperm aspiration (MESA) uses microsurgical techniques to collect sperm that are close to blocked portions of the epididymis. It involves an open incision and may be done under general or spinal anesthesia in a hospital setting, although the patient can often go home the same day. The doctor accesses the epididymis and retrieves sperm with an extremely fine needle-like device. It has the advantage that it can retrieve the largest number of sperm compared to other procedures. However, as with any invasive procedure, it carries some risks of complications, such as bleeding or infection.
Percutaneous Epididymal Sperm Aspiration. Percutaneous epididymal sperm aspiration (PESA) uses a needle to obtain mature sperm from areas in the upper parts of the epididymis (the coiled tube where sperm are stored before ejaculation). It is performed under local anesthesia, sometimes in the doctor's office, is less expensive than other techniques, and recovery is fairly painless. However, it has less of a chance of achieving sufficient sperm than MESA, and there is also a chance of hitting a blood vessel, causing bleeding.
Testicular Sperm Extraction. Testicular sperm extraction (TESE) is a microsurgery that removes a small amount of tissue from one or more areas of the testes using incisions and microsurgery techniques. The tissue is placed in a culture and chopped into tiny pieces, and the sperm are extracted. It is a complex process, however, and may cause more pain than other sperm retrieval procedures.
Testicular Sperm Aspiration. Testicular sperm aspiration (TESA) uses a needle-like biopsy device to draw a small sample of testicular tissue. Multiple attempts are sometimes required to retrieve sperm.
Sperm washing is done to prepare the sperm for use in ART procedures. Methods for washing sperm can help remove chemicals (prostaglandins) that can cause the woman’s uterus to contract and cramp. Sperm washing can also help remove sexually transmitted viruses, such as HIV and hepatitis, which could potentially be transmitted to the woman during fertility treatment. There are three basic methods for sperm washing:
Sperm can be fresh or frozen in advance. Frozen sperm provide excellent results for fertilization procedures. Fresh sperm, however, are preferred by some centers for cases when low sperm count is not caused by obstruction.
Artificial insemination (AI) is the least complex of fertility procedures and is often tried first in uncomplicated cases of infertility. AI involves placing the sperm directly in the cervix (called intracervical insemination) or into the uterus (called intrauterine insemination, or IUI). IUI is the standard AI procedure.
Intrauterine insemination may be used under the following circumstances.
The intrauterine insemination procedure is as follows:
The administration of fertility drugs and sperm retrieval is timed so that the process can coincide with time of ovulation.
If a woman fails to conceive after IUI, she may be a candidate for in vitro fertilization (IVF). [For more information on intrauterine insemination, see In-Depth Report #22: Infertility in women.]
Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology (ART) used for couples when male infertility is the main factor. It is used in combination with in vitro fertilization (IVF). It involves injecting a single sperm into an egg obtained from IVF. [For more information, see In-Depth Report #22: Infertility in women.]
The procedure is very simple:
The greatest concern with this procedure has been whether it increases the risk for birth defects. Many, but not all, studies have reported no higher risks of birth defects in children born using ICSI procedures. However, if the father’s infertility was due to genetic issues, this genetic defect may be passed on to male children conceived through ICSI.
Because several embryos are implanted to increase the chances for pregnancy success, multiple births are frequently an outcome of IVF/ICSI. Multiple pregnancies increase the risks for a mother and her babies. In particular, there is increased risk for premature delivery and low birth weight. These factors can cause heart and lung problems and developmental disabilities in children.
IVF/ICSI can also pose specific risks for the woman. These risks include ovarian hyperstimulation, a condition induced by the fertility drugs used in the procedure. Ovarian hyperstimulation can result in dangerous fluid and electrolyte imbalances as well as increased blood pressure and higher risk for blood clots.
Another concern has been whether the ICSI procedure is overused. ICSI use has increased 5-fold over the past decade and is now used in most ART procedures, even though the proportion of men receiving treatment for male infertility has remained the same. Some doctors recommend ICSI for women who have failed prior IVF attempts or who have few or poor-quality eggs, even if their male partners have normal semen measurements. According to the Society for Assisted Reproductive Technology, there is little evidence that ICSI helps improve pregnancy success for couples who do not have a problem with male factor infertility.
Success Rates. Not all IVF/ICSI cycles result in pregnancy, and not all IVF-achieved pregnancies result in live births. When the woman’s own eggs are used, results are better with fresh embryos than frozen embryos. Success rates provided by fertility clinics are not always a reliable indicator as they depend on many variables, including the age of the patients. The chances for success are best for women younger than age 37.
Both male and female hormone levels fluctuate according to the time of day, and they also vary from day to day and month to month. Some timing tips might be helpful.
Fertility and Seasonal Changes. Some studies have reported higher sperm counts in the winter than in the summer. For women, fertility rates as measured by treatment success are highest in months when days are longest.
Monitoring Basal Body Temperature. To determine the most likely time of ovulation and therefore the time of fertility, a woman should take her body temperature, called her basal body temperature. This is the body's temperature as it rises and falls in accord with hormonal fluctuations.
By studying the temperature patterns after a few months, couples can begin to anticipate ovulation and plan their sexual activity accordingly.
Frequency of Intercourse. It is not clear how often a couple should have intercourse in order to conceive. Some doctors think that having sex more than 2 days a week adds no benefits. In addition, frequent sexual activity lowers sperm count per ejaculation. Some studies have indicated, however, that having intercourse every day, or even several times a day, before and during ovulation, improves pregnancy rates. Although sperm count per ejaculation is low, a constantly replenished semen supply is more likely to result in a fertilized egg.
Everyone should eat a healthy diet rich in fresh fruits, vegetables, and whole grains. Replace animal fats with monounsaturated oils, such as olive oil. Certain specific nutrients and vitamins have been studied for their effects on male infertility and sperm health. They include antioxidant vitamins (vitamin C, vitamin E) and the dietary supplements L-carnitine and L-acetylcarnitine. To date, there is no conclusive evidence that they are effective.
Other tips for helping fertility include:
The fertility treatment process presents a roller coaster of emotions. There are almost no sure ways to predict which couples will eventually conceive. Some couples with multiple problems will overcome great odds, while other, seemingly fertile, couples fail to conceive. Many of the new treatments are remarkable, but a live birth is never guaranteed. The emotional burden on the couple is considerable, and some planning is helpful:
American Urological Association. The Optimal Evaluation of the Infertile Male. AUA Best Practice Statement. Revised 2010.
Bensdorp AJ, Cohlen BJ, Heineman MJ, Vandekerckhove P. Intra-uterine insemination for male subfertility. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD000360.
Davies MJ, Moore VM, Willson KJ, Van Essen P, Priest K, Scott H, et al. Reproductive technologies and the risk of birth defects. N Engl J Med. 2012 May 10;366(19):1803-13. Epub 2012 May 5.
Evers JH, Collins J, Clarke J. Surgery or embolisation for varicoceles in subfertile men. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD000479.
Hammoud AO, Gibson M, Peterson CM, Meikle AW, Carrell DT. Impact of male obesity on infertility: a critical review of the current literature. Fertil Steril. 2008 Oct;90(4):897-904
Jain T, Gupta RS. Trends in the use of intracytoplasmic sperm injection in the United States. N Engl J Med. 2007 Jul 19;357(3):251-7.
Khera M, Lipshultz LI. Evolving approach to the varicocele. Urol Clin North Am. 2008 May;35(2):183-9, viii.
Levine BA, Grifo JA. Intrauterine insemination and male subfertility. Urol Clin North Am. 2008 May;35(2):271-6.
Practice Committee of American Society for Reproductive Medicine. Guidelines for reducing the risk of viral transmission during fertility treatment. Fertil Steril. 2008 Nov;90(5 Suppl):S156-62.
Showell MG, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD007411.
Van Peperstraten A, Proctor ML, Johnson NP, Philipson G. Techniques for surgical retrieval of sperm prior to intra-cytoplasmic sperm injection (ICSI) for azoospermia. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD002807.
Walsh TJ, Croughan MS, Schembri M, Chan JM, Turek PJ. Increased risk of testicular germ cell cancer among infertile men. Arch Intern Med. 2009 Feb 23;169(4):351-6.
Weedin JW, Khera M, Lipshultz LI. Varicocele repair in patients with nonobstructive azoospermia: a meta-analysis. J Urol. 2010 Jun;183(6):2309-15. Epub 2010 Apr 18.
Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril. 2009 Nov;92(5):1520-4. Epub 2009 Oct 14.
Zhu JL, Basso O, Obel C, Bille C, Olsen J. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ. 2006 Sep 30;333(7570):679. Epub 2006 Aug 7.