“When I wasn’t able to get my wife pregnant... that was a gut punch. I questioned my ability to function as a man. There is no 'water cooler talk’ about fertility among men.” —a husband on infertility during an interview
The sperm's passage to the egg is a difficult journey. Out of the 100-300 million sperm that are ejaculated, only 400 sperm survive the orgasm and then only about 40 sperm survive the challenges posed by the environment to reach the egg. Even under normal conditions, only about 5-15% of these millions of sperm are considered normally shaped (1). Contrary to popular belief that fertility issues are found more often in women, according to the American Society of Reproductive Medicine, infertility issues are split evenly between men and women. About a third of infertility problems are due to female infertility, and another 40-50% are due to male infertility (2). In the remaining cases, infertility affects both partners or the cause is unclear. Earlier, we explored causes and treatments for female-factor infertility (3), and today we will review causes and treatment possibilities for male-factor infertility. First a little vocabulary lesson (4):
Semen: thick, white fluid that contains sperm and is released during ejaculation (5)
Sperm concentration: number of sperm per milliliter of semen
Sperm count: total number of sperm in the sample
Sperm motility: the sperm’s ability to move in a more or less straight line
Sperm morphology: shape of sperm
In any fertility work-up, both partners should be tested if pregnancy fails to occur after one year of regular unprotected sexual intercourse. Testing should be performed after six months if the female partner is over age 35 or if either partner has known risk factors for infertility (6).In addition to a medical history and physical exam, specific tests for male infertility include:
Semen analysis is the most useful diagnostic test for male factor infertility and is able to detect a genuine infertility issue in 9 out of 10 men with a genuine infertility issue. It is a simple test that assesses the sperm health by analyzing the formation and maturity of sperm, how the sperm acts in the seminal fluid, and provides insight on sperm count, motility, and morphology (7). Semen analysis may be performed more than once and may also include testing the urine for the presence of semen (8). Please note that a semen analysis alone is not necessarily a definitive indicator of either infertility or fertility. A semen analysis may provide information on sperm concentration, count, motility, and morphology.
The analysis may also provide information about semen, including thickness, acidity, and sugar content (5).The amount of semen is important. Most men ejaculate about 2.5 to 5 milliliters (mL) or 1/2 to 1 teaspoon of semen. Significantly lower amounts may be a sign of low hormones, prostate problems, diabetes, or retrograde ejaculation (9).
Male-factor infertility can be caused by a variety of factors, such as sperm health, which can stem from factors that are pre-testicular (affecting hormone regulation), testicular (affecting sperm production), or post-testicular (affecting the sperm’s ability to leave the body during ejaculation) (10). In some cases, the sperm may be immature, abnormally shaped or unable to swim. The remaining cases of male infertility may be caused by a range of conditions including anatomical problems, hormonal imbalances, and genetic defects (11).
Sperm abnormalities can be caused by a range of factors, including congenital birth defects, disease, chemical exposure, and lifestyle habits (11). In many cases, the causes of sperm abnormalities are unknown. Below are the 3 different classifications of sperm abnormalities.
Sperm count varies widely over time, and temporary low counts are common, therefore, a single test that reports a low count may not be a representative result. A sperm count of less than 15 million/mL is considered low sperm (12). Azoospermia refers to the complete absence of sperm cells in the ejaculate. Many health, lifestyle, or environmental factors can contribute to low sperm count, including partial obstruction anywhere in the long passages through which sperm travel (12).
Sperm motility is the sperm's ability to move. To swim through the cervical mucus and penetrate the hard outer shell of the egg, the sperm need to swim at a certain speed and in a more or less straight line. If 60% or more of sperm cells have normal motility, the sperm is considered to have normal motility (13). If less than 40% of sperm move in a straight line, sperm motility is considered low.
When considering treatment, keep in mind that sluggish sperm may have genetic or other defects that render them incapable of fertilizing an egg. You may want to ask your doctor about testing the sperm for genetic diseases. Poor sperm motility may be associated with damaged DNA and may increase risks of passing on genetic diseases (14).
Normal sperm structure has an oval head and a long tail. If the shape, or morphology, is abnormal, the sperm cannot fertilize an egg. A semen analysis will look for about 60% of the sperm in a sample to be a normal shape and structure for adequate fertility (15).
The treatment of male infertility depends upon the underlying cause. Several months to years of treatment may be necessary to achieve fertility, depending on the treatment. Medication: If a semen analysis reveals low sperm count as well as an increased white blood cell and bacteria count, sexually transmitted infections (STIs) or other infections may be contributing to the problem. In the case of an STI, medication can be prescribed to treat the condition (see more on STIs below). Assisted Reproductive Technologies (ART): If the underlying cause of the abnormal sperm can't be treated, ART can often help. Couples should discuss the pros, cons, and success rates of these techniques with an infertility specialist. Intracytoplasmic sperm injection (ICSI) is an ART procedure that is performed in conjunction with IVF. With ICSI, a single sperm from the male partner is injected directly into a woman's egg (oocyte) in the laboratory. This technique can be useful in many cases of low sperm count. The pregnancy rate with ICSI is approximately 20 to 40% per transfer, depending on the specific reason for subfertility (16). If a man's semen completely lacks sperm or has very poor sperm quality in the ejaculate, sperm can sometimes be directly removed from the testes via microsurgical epididymal sperm aspiration (MESA and TESA). MESA and TESA are surgical techniques recommended when there are few or no sperm in the ejaculate. If sperm can be found and extracted from the testis, the sperm will be used for ICSI and the fertilization rate of the oocyte is not very different from IVF. Thus, men with no sperm in the ejaculate can have a potential of fathering a child using these techniques (17).If sperm cannot be found or extracted, you and your partner can talk to a fertility specialist about other options, such as donor sperm or adoption. It is most certainly not easy to learn that having a biological child together may not be a possibility. Couples having gone through this recommend seeking the help of a support group or therapist.
Blockage of the Reproductive Tract
Some men have scarring, growths, or other problems in the epididymis or ejaculatory ducts that block sperm from getting out. Some men lack the vas deferens, the tube that carries sperm from the testicles through the penis. Low semen levels in ejaculate may be associated with structural abnormalities in the tubes transporting the sperm.Men who have a blockage can talk to their doctor about surgery to fix the blockage. If it is not successful or surgery is not preferable, another option is ART using sperm retrieved from the testes.The surgical procedures, MESA and TESA, may be recommended when there are few or no sperm in the ejaculate as a result of vasectomy, congenital absence of the vas deferens or epididymis, prior failed surgery or epididymal scarring from infection. Almost all vasectomies (male sterilization) can be reversed, however, pregnancy rates following a vasectomy reversal may vary from 30% to over 90% depending on the results of the procedure. However, the more time that has passed since the vasectomy, the less likely vasectomy reversal is successful to restore fertility (18).
Male infertility could also be due to problems in the hypothalamus and pituitary gland (parts of the brain that regulate hormone production), which can affect sperm production and sexual function (19). Men also produce follicle stimulating hormone (FSH) and luteinizing hormone (LH) that are required for sperm production (20). 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 hormone disorders.Thyroid problems also can lead to low levels of testosterone, FSH, and LH (21).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 (22). Testosterone is required for sperm production, but low testosterone does not cause infertility so if your partner takes a home test and the results are low, that’s not necessarily cause for concern (23). Hypogonadism is uncommon and can be present at the time of birth or developed later in life (22). 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 (22).
Medication may be prescribed for certain hormonal imbalances. Blood tests to measure testosterone and FSH levels are usually taken first. If testosterone levels are low, then LH is measured.If a thyroid issue is diagnosed, medication typically helps restore erectile function and may also improve issues with sperm quality and quantity over time (24). Human chorionic gonadotropin (HCG) supports the production of testosterone in the male reproductive organs. Clomiphene citrate helps the hypothalamus and pituitary glands produce the chemical that stimulates LH and FSH production. These, in turn, regulate testosterone production and improve sperm production. In this case, treatment with human chorionic gonadotropin (hCG), recombinant human follicle stimulating hormone (rhFSH), also called gonadotropin treatment, is often given.Gonadotropin treatment is started with injections of hCG three times per week (or sometimes every other day) for up to six months. Blood tests are used to monitor blood testosterone levels and to adjust the dose if necessary. If sperm cells do not appear in the semen after six months of treatment, recombinant human follicle stimulating hormone (rhFSH) is added; this is also given by injection. The success rate for this therapy is high as most men will eventually develop sperm in the ejaculate; however, it may take several years of treatment to achieve normal fertility.
A varicocele is a dilation of a vein (like a varicose vein) in the scrotum (25). 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 (26). They can raise testicular temperature, which may have effects on sperm production, movement, and shape. The reason a varicocele affects the sperm may be related to a higher than normal temperature in the testicles, poor oxygen supply, and poor blood flow in the testes (25).
Many men with varicoceles are able to father children without treatment, but if the varicoceles cause infertility, pain, testicular atrophy, or you are considering assisted reproductive techniques (ARTs), surgical varicocele repair may be needed. The purpose of the surgery is to seal off the varicocele and redirect blood flow to normal veins, which may improve or cure infertility (25).
Infertility related to ejaculatory dysfunction is one of the most serious problems in younger men. Premature ejaculation is defined as nearly always occurring either before vaginal penetration or less than one minute after penetration, and an inability to delay ejaculation during all or most penetrations. Delayed ejaculation is when orgasm is delayed or cannot be achieved even after adequate stimulation (27).Another problem is retrograde ejaculation, which is when semen is released backward, into the bladder. This can be caused due to trauma, nerve damage, birth defects and diseases including diabetes and multiple sclerosis (27). Retrograde ejaculation also is linked to certain prescription drugs, including those for mood disorders and high blood pressure (28). Hypospadias is a birth defect in which the urinary opening is on the underside of the penis instead of at the tip and may cause impaired ejaculation if not surgically corrected (29). Hypospadias is usually corrected with surgery, if necessary, between the ages of six and 12 years old (30).
Premature ejaculation is only a problem of fertility if ejaculation occurs before entering the vagina and/or has had a negative impact on a couple's intimate life. Premature ejaculation can be due to anxiety, over-excitement, prostate health issues, prescription medications, cold medications and some depressive conditions. Some men are simply super sensitive and tend to arouse easily. Treatment may involve sex therapy (ie: start-stop method) or medications to treat the underlying cause (31). In cases involving retrograde ejaculation, medications may be prescribed to help if the cause is from nerve damage. If your doctor believes the retrograde ejaculation is due to medications you are currently taking, they may instruct you to discontinue medications (don’t do this without discussing it first!) to see if that helps (28). The same is true for treating delayed ejaculation (32).
Male sexual dysfunction is a common issue and may be worsened significantly by the stress of infertility (33). Sexual dysfunction may be from physical reasons such as low testosterone levels, medication, and smoking or substance abuse, or psychological reasons such as marital or relationship problems, depression, work-related stress and anxiety (34).
Medications and hormone therapy may be available to address sexual dysfunction depending on the nature of the problem and the cause. Psychological therapy may also help address this issue if it is caused by anxiety, stress, or other mental and emotional distress (35), especially if performance anxiety is an issue (36).
Age-related sperm changes in men are a gradual process, similar to age-related fertility changes in women (37). Aging can adversely affect sperm concentration, motility, and morphology. With increasing age, the genetic quality of sperm declines and the likelihood of birth defects and chromosomal abnormalities increases (38).
Sexually Transmitted Infections
Sexually transmitted infections (STIs) may cause fertility issues in both the male and female partners. Repeated gonorrhea infections may cause urethral strictures or scarring, and inflammation of the epididymis and/or testicle (epididymo‐orchitis). Chlamydia may be transferred to your partner and cause a host of issues in the female reproductive system. A bacterial infection called ureaplasma urealyticum may impair sperm motility and gene regulation (39). Additionally, when found in sperm, herpes virus has been associated with reduced fertility, and the herpes simplex virus decreases production of new sperm (40).
In many cases, infertility due to STIs can be treated. In one study, after treating 95 infertile men with antibiotics for four months, the researchers found that their sperm DNA fragmentation improved 36; during this time 13% of them managed to get their partners pregnant. By the end of the treatment period, 86% of the couples became pregnant (41).
Certain small changes may naturally improve sperm quality and quantity. Semen is continuously produced in the male body, and takes approximately 74 days to mature, meaning that positive lifestyle changes today can result in improvements in sperm quantity and/or quality in less than 3 months! Here are a few lifestyle factors that can affect sperm quality. Nutrition: Sperm respond positively and rapidly to diet changes, such as decreasing sugar consumption and increasing consumption of fruits, vegetables, and nuts (42). Testicular Overheating: One study showed that repeated overheating, which can result from exposure to hot tubs, jacuzzis, or hot baths, may lower sperm count and impair sperm motility and production. The good news is that these negative effects were reversible in about half of the participants of a particular study (43).Substance Abuse: Long-term, excessive use of alcohol not only affects semen quality but also has a negative effect on male reproductive hormones. Recreational drugs such as cocaine, marijuana, and MDMA (ecstasy) have also been shown to have negative effects on male fertility and sperm function (44). Anabolic steroid abuse has also been associated with negative effects on male fertility that may or may not be reversible (45).Smoking: Tobacco use reduces sperm motility, concentration, and viability (44). Obesity: Emerging evidence suggests that obesity may impair hormones, sperm function, and sperm composition. The good news is that diet and exercise may reverse the damage to sperm function (46).Bicycling: Prolonged bicycling may affect sperm and erectile function. One study showed that low to intensive training on a bicycle for 16 weeks had a negative impact on semen volume, sperm motility, morphology, concentration, and quantity (47). In addition, pressure from the bike seat can sometimes damage blood vessels and nerves that are responsible for erections. If you ride a bike often and are trying to conceive, consider alternate exercises and training. If you experience pain, numbness, or tingling during a ride, take a break (48). Emotional Stress: Studies suggest that stress may interfere with certain hormones which affects sperm production. Stress is clearly associated with male infertility, but the degree of impact needs more study (49).Environmental Factors and Toxins: Toxins in everyday household products and conventional foods may impact hormonal health. Fruits and vegetables with a high volume of residual pesticides were found to be associated with lower sperm counts and increased abnormally shaped sperm (50). Try switching to non-toxic cleaners and hygiene products, and organic food.
Sometimes treatment is not currently available for some types of male infertility or infertility can not be explained. For example, there is no known treatment when the sperm-producing structures of the testes have been severely damaged during active military duty, cancer treatments, or a car accident. Other issues arise in men with certain chromosomal abnormalities such as Klinefelter syndrome and small deletions in the Y (male-specific) chromosome where no known treatment is available yet (51). Medical conditions also may affect male fertility and 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. According to a 2017 review of available, FDA-approved medications, 65 were noted to be damaging to sperm production, including the anti-bacterial agents like nitrofurantoin, antidepressants like clomipramine hydrochloride, and antihypertensive agent such as nifedipine. Unfortunately, evidence supporting these claims in animals or humans is lacking and further research is needed (52).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.
The good news is that many treatments are available for male-factor infertility. Treatment, of course, depends on the issue and may require medication and surgery. If you seek fertility help, always ask if your condition can be treated in other ways, why a test or procedure is recommended, what the results could mean, and the statistical success rate in general and for the specific clinic you’re considering.
De Croo, I., Van der Elst, J., Everaert, K., De Sutter, P., & Dhont, M. (2000). Fertilization, pregnancy and embryo implantation rates after ICSI in cases of obstructive and non-obstructive azoospermia. Human reproduction, 15(6), 1383-1388.
Nikoobakht, M. R., Aloosh, M., Nikoobakht, N., Mehrsay, A., Biniaz, F., & Karjalian, M. A. (2012). The role of hypothyroidism in male infertility and erectile dysfunction. Urology journal, 9(1), 405-409.
Sansone, A., Di Dato, C., de Angelis, C., Menafra, D., Pozza, C., Pivonello, R., ... & Gianfrilli, D. (2018). Smoke, alcohol and drug addiction and male fertility. Reproductive biology and endocrinology, 16(1), 3.
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