IntroductionInfertility is defined as the failure of a couple to become pregnant after one year of regular, unprotected intercourse. In both men and women the fertility process is complex, and, in many cases, infertility is caused by a combination of problems in both partners that conspire to prevent conception. About 10% to 15% of couples experience some form of infertility, and, in approximately 40% of these cases, male infertility is the major factor. Another 40% of infertility problems are caused by abnormalities of the woman’s reproductive system, and the remaining 20% involve couples who both suffer reproductive difficulties.
Experts suggest that sperm counts tend to fluctuate widely from year to year and also from season to season. Sperm counts appear to differ by region. Temperature and climate may play some role in the differences seen from country to country and from year to year.
Auto AntibodiesAutoimmunity is a condition in which the antibodies of the immune system attack specific cells in the body, mistaking them for micro foreign invaders. In the case of male infertility, such so–called auto antibodies target the sperm. Most commonly, such auto antibodies develop after vasectomy when sperm continue to be produced but, instead of being confined to the reproductive passages, they leak out into the body where the immune system perceives them as foreign invaders and develops antibodies to attack them.
Even if a procedure to reverse the vasectomy is performed, such antibodies often persist. Antibodies to sperm can also appear in men without previous vasectomies and have been reported to be present in 10% of all sub–fertile men. The causes of antibodies in these cases are usually not known. Other Vasectomy–Induced Factors. The important immune factors that trigger the autoimmune process are called leukocytes. Among their other harmful effects is the production of particles called oxygen–free radicals (also called reactive oxygen metabolites), which are particularly injurious to sperm. Vasectomy may also change other factors that affect fertility. Studies report, for instance, that the malfunctioning epididymis after vasectomy reduces normal amounts of a protein called P34H, which is on the surface of the sperm and serves to enhance fertility.
Artificial InseminationArtificial insemination (AI) places sperm directly in the cervix (called intra cervical insemination) or uterus (called intrauterine insemination or IUI). It is useful for women who have structural problems, when the cervical mucus is unreceptive, when donor sperm are required, when the male partner’s semen contains very low numbers of sperm, or when unexplained infertility exists in both partners. In order to prepare for AI, a woman usually takes fertility drugs in advance. The man must produce sperm at the time the woman is ovulating. The sperm are subjected to certain so–called “Washing” procedures and are then inserted into the uterine cavity through a long, thin catheter.
Assisted Reproductive Technologies (ART)
General GuidelinesAssisted reproductive technologies (ART) are procedures that either use donated eggs or employ techniques that retrieve eggs from the ovary and re implant them. Fertilization may occur either in the laboratory or in the uterus. The most common procedure is in vitro fertilization (IVF). More recent ART procedures include gamete intra fallopian transfer (GIFT), zygote intra fallopian transfer (ZIFT), and intra cytoplasmic sperm injection (ICSI).
Success RatesThe success rates of ART procedures are now approaching that of normal couples in appropriate candidates. Many women, however, are not good candidates for GIFT and ZIFT. These procedures are also more invasive than IVF. It should be noted that even women who become pregnant may require more than one fertility cycle.
In general, the success rates with ART are lower for older women and those with uterine abnormalities as the primary cause of infertility. The chances of success are also greater with the clinic’s own success rate, if eggs are the women’s own, or if a previous pregnancy was successful. Age, however, is the most important determinant when a woman uses her own eggs. Rates for ART are relatively high for both pregnancies and live births among women in their 20s but they decline after 30 and go sharply downward toward the end of the decade and afterward. The use of donor eggs has made it possible for many older women, even some who are postmenopausal, to bear a child. (Success rates using donor eggs depend on the age of the donor, not the age of the recipient.) Freezing eggs allows them to remain viable for long periods, after thawing, about half are able to be fertilized.
Assisted Reproductive Technologies
Specific ProceduresIn Vitro Fertilization (IVF). About 71% of ART procedures use in vitro fertilization (IVF) with the woman’s own eggs. An in vitro procedure is one that is performed in the laboratory. With in vitro fertilization (IVF), the partners’ sperm and egg are placed together in a laboratory dish, where, it is hoped, fertilization will occur. It is the most common assisted reproductive treatment. The best candidates for IVF are women with damaged fallopian tubes, and some experts believe it is a better option than attempting surgical repair. It is also used when infertility is unexplained and when the male partner has the infertility problem. Most IVF programmers do not take women over 42. The physician induces super ovulation using fertility drugs so that several eggs can be harvested from the ovary before they have been released from the follicles. (Some women prefer to try a natural cycle, which produces only one egg.) It does not appear that using higher doses of fertility drugs for subsequent cycles is beneficial in women who have a poor response the first time. To harvest eggs, the physician uses either laparoscopy, inserting the instruments through an incision at the navel, or a probe inserted into the vagina and guided by ultrasound. The physician uses a needle to drain the liquid from the follicles and retrieves several eggs. The process requires light anesthesia and is performed on an outpatient basis. The eggs and sperm are combined in a petri dish, and 48 hours later, when the eggs are fertilized, they are re implanted into the woman’s uterus as embryos. Most centers now implant three to four embryos at a time, and the remainder can be frozen for future use. Experts are devising a formula to reduce the risk for multiple births based on the woman’s age and the number and quality of embryos that should be transferred back into the uterus.
Gamete/Zygote Intra fallopian Transfer. Gamete intra fallopian transfer (GIFT) and zygote intra fallopian transfer (ZIFT) are adaptations of IVF. A woman must have at least one functioning fallopian tube, GIFT and ZIFT are used in unexplained infertility, severe endometriosis, and in male infertility. In GIFT, the eggs are harvested as in IVF but not fertilized. They are mixed with the sperm and immediately injected back into the fallopian tube through a long, thin catheter. The sperm and egg are placed exactly where they would be in natural fertilization. The success rate is slightly higher for GIFT than for IVF. The ZIFT procedure fertilizes the eggs in the laboratory, as in IVF, but then implants them in the fallopian tubes, as in GIFT. The advantage to this procedure over GIFT is that the physician and couple are assured that fertilization has taken place and the eggs can be examined for defects.
Intracytoplasmic Sperm InjectionIntracytoplasmic sperm injection (ICSI) is a highly sophisticated technique for injecting one single sperm into an egg using microscopic and micromanipulation instruments. It is used for couples who have failed IVF or when the man has severe infertility problems and now constitutes about 30% of ART cycles that use the woman’s own eggs. It is the most effective procedure when male infertility is the problem.
Other Experimental ART ProceduresNew techniques involving micromanipulation of sperm are being developed for the one–third of infertile men who have severely low sperm counts, a high percentage of abnormal sperm, tubular obstruction, or no vas deferens. One investigative approach involves culturing poor sperm with the egg in very small micro chambers, thereby increasing the odds that the sperm will find the egg. A technique called sub zonal sperm microinjection injects one to 15 sperm under the zona (the tough outer shell of the egg). Zona dissection involves puncturing the zona and then incubating the egg in a droplet of 10,000 to 50,000 highly motile sperm. There is concern that puncturing the egg may damage it. Also, since a small number of sperm are randomly selected and not competing in a hostile environment, a weak sperm will have as good a chance as the strongest. This increases the risk for genetic defects in the infant. An experimental technique called FASIAR (follicle aspiration, sperm injection, and assisted follicular rupture) may prove to be a significantly less expensive treatment and also reduce the risk of multiple births. After ovulation induction, the physician punctures the follicle and retrieves the eggs and fluid in a syringe that also contains sperm. The mixture is then re injected near the ruptured follicle. The procedure can be done in the physician’s office. Procedures called round spermatic nuclear injection (ROSNI) and elongated spermatic (ELSI) use immature sperm aspirated from the testes and injected into the egg using ICSI. The sperm can either be fresh or frozen. The procedures are controversial. However some countries are prohibiting this approach. Some centers are developing IVF techniques that allow a longer time for the embryo to develop in the laboratory (five days instead of two to three). This enables the embryo to reach the blast cyst stage, which is the natural embryonic stage for implantation in the uterus.
Preparing Sperm for IUI and ARTBefore fertilization using IUI or ART can take place, the sperm must be collected and prepared for optimal chances for success. Sperm can be fresh or frozen in advance. Studies are reporting that frozen sperm provides excellent results and can be used confidently for fertilization procedures. A number of methods have been devised for this. It should be noted that in some cases of severely low sperm count, a biopsy is used to remove sperm from the testicles. If multiple incisions are required, the size of the testes may be reduced afterward and may even reduce androgen levels to the extent that replacement therapy may be needed. Men should be aware that success rates are lower than average in such cases. New techniques using needle aspiration may prove to be effective for sperm retrieval in some men and reduce such risks.
A sperm’s energy output is twenty times greater once it is removed from the seminal fluid, so researchers have devised methods for washing sperm that have a dramatic effect on the ability of sperm to move towards the egg. The simplest method involves mixing the sperm with nutrient fluid or culture media in a test tube and then centrifuging (spinning) it for about five minutes. The heavy sperm settle on the bottom, forming a dense button of millions of pure sperm. The fluid left on top is siphoned off. This procedure may be repeated again. This simple method of sperm washing, however, does not eliminate heavy debris, such as dead sperm, white blood cells, or bacteria.
Swim–Up TechniqueThe swim–up technique is not only a useful diagnostic procedure but also achieves the goal of removing sperm from semen. It is superior to sperm washing, because the live sperm will swim up to the culture media leaving behind most of the debris, although some may float up into the medium. The strongest sperm, which are those at the top of the medium, can be collected for in vitro fertilization or artificial insemination. A good swim test yields about 1/2 million very active sperm.
Percutaneous Epididymal Sperm Aspiration (PESA)A technique called percutaneous epididymal sperm aspiration (PESA) uses a needle to obtain mature sperm from areas in the upper parts of the epididymis. PESA is useful in men with tubular obstruction and even in those with no vas deferens.
Other Methods of SeparationOne technique uses a special device called a Jondet tube, which contains a doughnut–like plug at the bottom with the opening in the center forming a tiny well. The sperm are placed on the plug and a culture media is added to the tube. Active sperm attempt to swim off the plug and up into the culture media, but gravity pulls them into the well at the bottom of the tube from which they cannot escape. Another method uses layers of a very dense fluid called Percoll, which is centrifuged with the sperm and forces the best sperm to the bottom of the test tube.
Sperm EnhancementA number of techniques can improve the ability of sperm to fertilize an egg. Injections of stimulants, such as caffeine, may enhance motility for a period of time. (No one has yet been able to show increased fertilization rates from this process, but the timing of the enhancement has not been perfected.) Calcium improves sperm cap citation and is sometimes added to the sperm washing solution, although like the stimulants, the precise degree of improvement is not clear. Sperm stored for 24 hours in a solution containing slightly heated egg yolk have a higher fertilization rate in IVF procedures Treatment with platelet activating factor (PAF) has also been shown to increase the penetration ability of sperm.
ComplicationsMultiple Births. About 38% of all ART births are multiple ones, with 5.8% being triplets or more. The increased incidence of such births poses a risk for complications, including caesarean sections, prematurely, and low birth weight. If the treatment produces multiple embryos the mother must decide if she will carry all of them to term, which increases health risks for both her and the developing fetuses. Aside from complete abortion, her only other option is embryo reduction, in which the physician removes one or more embryos, which can endanger the remaining embryos. The best approach is to limit the number of implanted embryos in the first place.
Risks for the WomanIn one study of women who conceived only one child, the only risks that IVF posed for a mother were a higher rate of urinary tract infections before delivery and a much higher rate of caesarean sections (41.9% for IVF vs. 15.5% for natural conceptions). Other complications associated with ART procedures include spontaneous abortions (12.9%) and ectopic pregnancies (0.5%). It should be noted that infertile women in general have a poorer than average chance for full–term pregnancies regardless of whether they conceive spontaneously or with fertility treatments.
Risk for Birth Defects and Developmental Issues in Children. Although, in general, analyses of studies indicate that there is no higher risk for birth defects with ART procedure, long–term studies are needed on the newer procedures. To date, frozen eggs do not appear to pose a risk for developmental problems in children conceived using them, but follow–up studies are needed. Of concern are recent studies indicating that men with low or non–existent sperm counts due to genetic factors and who conceive using ICSI are at risk of transmitting these same genetic defects to their offspring.
Environmental FactorsExposure to Chemicals. Some experts believe a decline in fertility may be due to the exposure of male fetuses during pregnancy to environmental chemicals with o estrogen–like effects. Such chemicals include pesticides, such as DDT, aldrin, dieldrin, PCPs, dioxins, and furans. Although tests of single chemicals containing oestrogen have reported little dangers, other studies indicate that combinations of estrogen–containing chemicals may be very harmful. Overexposure to oestrogen reduces the number of Sertoli cells (the cells necessary for the initial development of sperm). In addition to the effect on fertility, some researchers believe such overexposure may also contribute to testicular cancers. Aside from the o estrogen–like chemicals, other environmental pollutants or stresses can affect sperm quality and count, although the effects of most have not been proven.
Oxygen–Free RadicalsHigh levels of oxygen–free radicals (damaging particles that are naturally released and are produced by certain environmental toxins) have been found in the semen of 40% of infertile men. Such particles are known to injure cells, including causing genetic changes that increase the risk for heart disease and cancer. Evidence now strongly indicates that they can also damage sperm.
Exposure to Heavy MetalsTrace amounts of metals in semen seem to inhibit the function of enzymes contained in the acrosome, the membrane that covers the head of the sperm. Chronic exposure to heavy metals such as lead, cadmium, or arsenic can affect sperm quality. The effect on fertility of small particles of metals released into the air from incinerators or manufacturing plants or present in urban air pollution is not yet known.
Radiation TreatmentRadiation treatments and x–rays affect any rapidly dividing cell, so cells that produce sperm are quite sensitive to radiation damage. Cells exposed to significant levels of radiation may take up to two years to resume normal sperm production, and, in severe circumstances, may never recover. Genetic Factors
Genetic FactorsAside from inherited diseases that cause infertility, certain genetic factors may play a large role in many cases of male fertility. Much research has focused on a group of deletions in certain regions of the Y chromosome known as AZF. This defect appears to be a major genetic cause of severe male infertility and may be responsible for between 2% and 21% of cases of inadequate sperm. Another area of genetic research targets the gene for apolipoprotein B, which is known to play a key role in cholesterol metabolism, may also be a factor in infertility. It should be noted that genetic mutations may occur not only through inheritance but also from environmental assaults.
Guidelines for Treating Male Infertility?Many men diagnosed as sterile in past years would be considered treatable now, even some men with spinal cord injuries. Unless a man produces no sperm at all, recent developments in treatment have made fertility possible for many men willing to undergo treatment and bear the expense. Before undergoing more advanced procedures, some simple lifestyle changes should be attempted.
Timing Sexual Activity for Best ResultsBoth male and female hormone levels fluctuate according to the time of day and they also vary from day to day and month to month. Male hormone levels along with sexual interest are highest in the morning. In men, sexual activity (as well as conception) is highest in October. A woman’s sexual peak is usually around the second week of her menstrual cycle, when there is a surge in female hormones. (A menstrual cycle is counted starting from the first day of a woman’s period.) This surge also triggers ovulation, studies indicate conception is most likely when intercourse occurs during the two days before or on the day of ovulation.
Lifestyle ChangesA man who wants to increase his sperm count should avoid cigarettes and any drugs that may affect sperm count or reduce sexual function. Getting sufficient rest, moderate exercise, and a healthy diet low in fat and rich in whole grains, fruits, and vegetables is always a good idea. Overweight men should try to reduce. Those who exercise excessively might cut back (but not stop altogether). Stress may contribute to reduced sperm quality. It is not known if stress reduction techniques can improve fertility but they may help couples endure the difficult processes involved in fertility.
Some research has focused on antioxidant vitamins C and E. Vitamin C may help the body absorb trace elements of zinc, copper, magnesium, potassium, and calcium, which improve the vitality and longevity of the sperm. In one study, vitamin E improved fertility in men who had normal sperm count but evidence of excess free–oxygen radicals. Men with low levels of zinc might consider supplements. Benefits of herbal remedies, such as ginseng, have not been proven.
To prevent overheating of the testes men should avoid hot baths, showers, and steam rooms. Although studies now indicate that tight underwear and pants pose no threat to fertility, there is no harm in wearing looser clothing. To avoid low sperm count per ejaculation, sexual episodes should be limited to once every two to three days, except during periods when the women estimates she is ovulating. Recent studies have indicated 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.
Planning for Treatment OutcomesThere is often no way to predict which couples will eventually conceive, some with multiple problems will overcome great odds, while seemingly fertile couples fail to conceive. Many of the new treatments are remarkable, but a live birth is never guaranteed. The emotional stress of failure can be devastating even on the most loving and affectionate relationships. Even in the absence of failure, the road to pregnancy can be very difficult. Couples must be prepared to make many sacrifices, both financial and emotional, before undergoing this process. A successful pregnancy often depends on repeated attempts. Some couples become addicted to treatment, and continue with fertility procedures until they are emotionally and financially drained. Partners should decide in advance how many and what kind of procedures they believe will be financially and emotionally acceptable and attempt to determine a final limit. They should also explore in advance alternatives such as adoption, childlessness, and donor sperm. Determining all options as early as possible in the process can reduce anxiety during treatments and feelings of hopelessness if they don’t work out. It should be noted that even a successful pregnancy may not end emotional difficulties, particularly if it results in a multiple birth.
Hormonal AbnormalitiesLow levels of testosterone from any cause may result in defective sperm production. Hypogonadism is a severe deficiency in gonadotropin–releasing hormone (GnRH). It is usually present at the time of birth, although it can develop later in life from tumors of the pituitary gland, other brain tumors, or radiation treatments. In rare cases, it can develop without any apparent cause after puberty. In such cases, it may be brought on by excessive exercise, malnutrition, or illness. Genetic causes of pituitary gland malfunctions can prevent production of reproductive hormones, but such conditions are very rare contributors to male infertility. They include a disorder known as selective deficiency of FSH and LH, hypogonadism, Kallman’s syndrome, and panhypopituitarism (in which the pituitary gland fails to make almost all hormones). In some cases, Leydig cells are defective and unable to respond to testosterone.
Other Causes of InfertilityThe same conditions that cause retrograde ejaculation (e.g.., diabetes, multiple sclerosis, bladder neck or prostate surgery, and spinal cord injury) may also be responsible for failure to ejaculate. Chronic prostatitis (inflammation of the prostrate gland) can also cause sperm motility problems. Abnormalities of the thyroid or adrenal glands may have an indirect effect on fertility. Other medical conditions that can affect male fertility include any severe injury or major surgery, heart attack, liver failure, chronic anemia, kidney failure, obesity, or starvation.
Drugs and MedicationsThe effects of medications on sperm quality and count have not been rigorously studied, and many medicines are commonly prescribed without knowing whether they impair fertility. Anabolic steroids are known to severely impair sperm production. Cocaine or heavy marijuana use appears to temporarily reduce the number and quality of sperm by as much as 50%. Sperm actually have receptors for certain compounds in marijuana that resemble natural substances and which may impair the sperm’s ability to swim and may also inhibit their ability to penetrate the egg.
Sexual ProblemsIn less than 1% of males with infertility problems, a problem with sexual intercourse or technique will affect fertility. Impotence, premature ejaculation, dyspareunia (painful intercourse), or psychological or relationship problems can contribute to infertility, although these conditions are usually very treatable.
Lifestyle FactorsStress may interfere with the hormone GnRH and reduce sperm counts. Smoking impairs sperm motility, reduces sperm lifespan, and may cause genetic changes that affect the offspring. (Alcohol does not appear to affect fertility unless it is so abused that it has caused liver changes.) Obesity and excessive endurance exercise may also reduce sperm production, but losing weight and reducing exercise levels can reverse the problem. Low levels of dietary selenium and zinc, which are necessary for the formation and maturation of sperm, are associated with an increased risk of infertility. Some experts believe that vitamin C deficiency causes the sperm to clump together (agglutinate), which impairs movement. Frequent intercourse was suspected for awhile of reducing fertility because of the time required to replenish sperm, but this is unproved. A number of studies have found no negative effects on fertility from wearing tight trousers, briefs, or athletic supports, even every day. Men are at risk for infertility, however, only when the testes are exposed for prolonged periods to internal body temperatures, which occurs only rarely, such as in men with undescended testicles.
Other Male Fertility Treatments
Hormones and Other DrugsHormone therapy has been effective for women with infertility problems but has been disappointing in men except in a few specific cases. Gonadotropin–releasing hormone (GnRH) is very useful for men with gonadotropin deficiency and hypogonadism. Sperm production occasionally responds to low doses of estrogen and testosterone or testosterone alone, menotropins (Pergonal, Repronal), clomiphene citrate (Clomid), human chronic gonadotropin (HCG), or human follicle stimulating hormone (r–hFSH). A few other drugs may be helpful for specific cases. Bromocriptine (Parlodel) counteracts excess prolactin manufactured by the pituitary. Infections and leukocytospermia (an excess of white blood cells) are treated with antibiotics.
Treatment for Retrograde Ejaculation and Failure of EmissionMen with retrograde ejaculation and failure of emission caused by surgery, severe disease, or spinal cord injury are treated with various methods. Retrograde ejaculation can be managed by first having the man take sodium bicarbonate four times a day to reduce the acidity of the urine. After ejaculation, the man urinates or has a catheter (a tube) inserted to withdraw urine, which is then submitted for washing techniques to separate out the sperm. Using any of these methods, the sperm are collected for intrauterine insemination or assisted reproductive techniques.
Techniques for Men with Spinal Cord InjuryProcedures that assist ejaculation are helping men with spinal cord injury conceive children. Ejaculation was achieved in all men in one study group with the use of vibratory or electronic stimulation. The sperm was then inserted into the women using self–insemination, IUI, IVI, or ICSI. Nearly a third of the couples achieved pregnancy, a success rate that approaches natural conception.
Vasectomy ReversalFor men who wish to conceive after vasectomy, they may try ART procedures or reversal surgery (vasovasostomy). For men who have failed vasovasostomy, however, a repeat procedure appears to be less expensive than embarking on fertility treatments at that time.
VasovasostomyIn vasovasostomy (reversal surgery) the severed ends of the vas deferens are reconnected to re–establish the flow of sperm. The reversal procedure is difficult, it involves sewing together the two ends of both tubes, each with pinhead sized openings. Laser surgery is being investigated and may prove to require lesser skills, reduce operating time, and result in fewer complications. The chances for pregnancy increases with shorter the duration between vasectomy and the reversal operation..
VasoepididymostomyA vasoepididymostomy is used to clear obstruction in the epididymis, which is a common reason, by reversal surgery (Obstruction can also occur as birth defect). Vasoepididymostomy is a very difficult operation involving the tiny tubules of the epididymis, which are 1/300 of an inch wide with a wall thickness of 1/1000 of an inch, and requires great surgical skill. Pregnancy rates are around 20% after this procedure.
Treating Antisperm AutoantibodiesART is the best approach at this time for men with evidence of antisperm auto antibodies due to vasectomy or other causes. High doses of corticosteroids may be useful in conjunction with intrauterine insemination. Their effectiveness however, is not proven and they have potentially serious side effects with prolonged use. Interesting research is testing a factor called fertilization antigen (FA–1), which may be able to remove auto antibodies from the sperm surface. Some experts believe however, immune factors are not significant in causing infertility, and that many men can still conceive despite antibodies to their sperm.
Varicocele RepairRepair of a varicocele (varicocelectomy) in men with infertility problems is a common surgical practice. The procedure involves tying off the swollen and twisted veins. Recovery takes six days and most men cannot resume full activity for about three weeks.
A non surgical technique called varicocele embolisation may eventually prove to an effective and less painful treatment for varicoceles. It involves inserting a narrow tube through a small incision in the neck or leg. Tiny steel plugs are passed through the catheter that block off the affected veins. It takes 15 to 45 minutes under local anaesthetic.
Studies are conflicted over whether repair of varicoceles actually improves fertility in many men. For example, although one 1998 study comparing four different surgical approaches reported that in all groups sperm concentration significantly improved, another study reported that counseling was as effective as varicocele repair in achieving pregnancies. Some experts believe that surgery may be useful in some younger men, but because the condition may be progressive IVF, procedures are probably more effective for older men. Others also argue that the procedure is not at all beneficial for improving fertility in men whose varicoceles are too small to be detected without imaging techniques.
Miscellaneous Surgical ProceduresObstructions in the area of the ejaculatory ducts have been successfully treated by excising or scraping the area where the prostate gland surrounds the urethra. Undescended testicles of young boys may be repositioned surgically to prevent later infertility. It is important to diagnose this condition and perform the operation before age two to prevent the destruction of most of the sperm–producing cells, which occurs if the testicles remain in the abdomen.
Physical or Structural AbnormalitiesCryptorchidism is a failure of the testes to descend from the abdomen into the scrotum during foetal life. It is associated with mild to severe impaired sperm production. In one study, even one undescended testicle may impair fertility. In cryptorchidism, the testes are exposed to the higher degree of internal body heat, but this may not totally explain the damage in germ–cell production when it occurs. Some men are born with structural problems, such as blockage in the epididymis or ejaculatory ducts, or other problems that later affect fertility. One center reported that 2% of men seeking treatment had no vas deferens. The genetic disease cystic fibrosis, for example, is associated with this abnormality. Victims of Klinefelters syndrome carry two X and one Y chromosomes (the norm is one X and one Y), which causes destruction of the lining of the semi niferous tubules in the testicles during puberty, although most other male physical attributes are unimpaired.
Kartagener’s syndrome, a rare disorder that is associated with a reversed position of the major organs, also includes immotile cilia (hair–like cells in lungs and sinuses, which also form the tails of the sperm). Germ cells may also be affected by this condition. In the very rare condition, anorchia, a man is born without any testes. Syringomyelia, a disease of the spinal cord, results in no ejaculate at all (aspermia). Hypospadias, a birth defect in which the urinary opening is on the underside of the penis, increases the risk for low sperm count later on and if not surgically corrected can prevent sperm from reaching the cervix.
CancerBirth rates among cancer survivors are only 40% to 85% of the expected rates. Certain cancers, particularly testicular cancer, impair sperm production, often severely. The major cancer treatments impair both egg and sperm cells. The closer radiation treatments are to reproductive organs the higher the risk for infertility. Fortunately, while men may fail to produce sperm for as long as five years after radiation therapy, sperm production may eventually recover. Chemotherapy with alkylating agents or other drugs that can harm reproductive function tends to affect fertility more severely in men than in women. New regimens are helping to improve fertility rates.
InfectionsThere is some controversy over the effect of infections on infertility. Simply detecting the presence of an infection in infertile men does not necessarily mean that it has any relationship to the infertility itself. Sexually transmitted diseases, particularly repeated Chlamydia trachomatis infections, can trigger events leading to male infertility, although it is mainly implicated in female infertility. Mycoplasma is an infectious organism that appears to fasten itself to sperm cells and render them less motile. Mumps after puberty causes damage to the testicles in 25% of men afflicted with the disease. An infection in the testes, even after successful antibiotic treatment, may leave scar tissue that blocks the epididymis.
Retrograde EjaculationRetrograde ejaculation occurs when the muscles of the urethra do not pump properly during orgasm and sperm are forced backward into the bladder instead of forwarding out of the urethra. This condition is a common consequence of bladder neck or prostate surgery and may also be caused by diabetes, multiple sclerosis, and spinal cord injury. It can also be a temporary side effect of certain drugs such as tranquilizers or hypertension medication.
Tests used to Diagnose Male Infertility
Physical ExamA urologist will usually perform a physical examination to detect any abnormalities, such as a varicocele in the testes and prostate problems. Checking the size of the testicles is also helpful. Smaller–sized and softer testicles along with tests that show low sperm count are strongly associated with essential problems in sperm production, a low–sperm count in men whose testicles have normal size and consistency indicate possible obstruction. The temperature of the scrotum can be determined with a test called scrotal thermography. The physician may also take a urine sample to detect sperm in the urine (indicating retrograde ejaculation).
Semen AnalysisThe basic test to evaluate a man’s fertility is a semen analysis. To perform this test, a man collects a sample of his semen in a collection jar during masturbation either at home or at the physician’s office. For those for whom religion or culture prohibits masturbation, a silicon semen collection device (stockiest–Rocket) may be available that will enable collection of a sample during sexual intercourse. A man should abstain from ejaculation for several days before the test, because each ejaculation can reduce the number of sperm by as much as a third. (The maximum number of sperm is usually obtained by abstaining for about four days.)
Proper collection procedure is important, since the highest concentration of sperm is contained in the initial portion of the ejaculate. The sample should be kept at body temperature and delivered promptly, because if the sperm are not analyzed within two hours or kept reasonably warm, a large proportion may die or lose motility. A semen analysis should be repeated at least three times over several months. Both the man and the woman should be present when the physician discusses the result of this analysis so that both partners will understand the implications. The analysis should report any abnormalities in sperm count, motility, and morphology as well as any problem in the semen.
Sperm CountA low sperm count should not be viewed as a definitive diagnosis of infertility but rather as one indicator of a fertility problem. Counts of less than 20 million per milliliter are currently considered strong indicators of infertility, although pregnancy is sometimes possible even with such low counts.
Sperm MotilityMotility (the speed and quality of movement) is graded on a 1 to 4 ranking system. Grade 1 sperm wriggle sluggishly and make little forward progress. Grade 2 sperm move forward, but they are either very slow or do not move in a straight line. Grade 3 sperm move in a straight line at a reasonable speed and can home on an egg accurately. Grade 4 sperm are as accurate as Grade 3 sperm, but move at terrific speed. Sperm that clump together may indicate that antibodies to the sperm are present. This test may be particularly valuable for predicting the success of artificial insemination although less useful for those are candidates of the ICSI fertilization technique, in which the sperm is inserted directly into the egg and motility plays almost no role.
Sperm MorphologyMorphology is the structure of the sperm. About 60% of the sperm should be normal in size and shape for adequate fertility. Determining the morphology of the sperm is particularly important for the success of the fertility treatments in vitro fertilization (ART) and intracytoplasmic sperm injection (ICSI).
Seminal FluidThe seminal fluid (semen) itself is analysed for abnormalities. Most men ejaculate 2.5 to 5 cc (1/2 to 1 teaspoon) of semen. Amounts greater than 1 cc but lower than 2.5 cc may indicate prostate problems or frequent intercourse. A semen sample that is less than 1 cc could indicate a blockage of the ejaculatory ducts or other tubular abnormalities. No ejaculate at all may signal retrograde ejaculation. High amounts of ejaculate may, in some cases, also contribute to infertility. Normal semen is liquefied within 20 minutes by certain enzymes, if it remains sticky, however, fertility may be impaired. An absence of fructose (sugar) and sperm indicates that an obstruction has occurred either in the vas deferens or the epididymis, since fructose is added to the semen in the epididymis. Conversely, if there is fructose in the semen but no sperm, then the channel from the epididymis is open but there is a defect in sperm production. Infections may be detected. Low levels of a substance called inhibin B, which appears to be produced only in the testes, may indicate blockage or abnormalities in the seminiferous tubules. Similarly, low levels of another compound, alpha–glucosidase, indicate blockage in the epididymis.
Fertilization TestsThe hamster test, or micro–penetration assay test, uses the sperm sample to fertilise hamster eggs that have had their covering removed to allow penetration. If less than 5% to 20% of the eggs are fertilized, infertility is diagnosed. This test is not used often, it is very expensive, does not test the ability of the sperm to penetrate the egg’s covering, may lead to an incorrect diagnosis of infertility, and so may be no more useful than less expensive semen analyses. A newer procedure, the human zona penetration test, uses sperm to fertilize dead human eggs, which are usually obtained from an ovary that was removed for medical purposes. (Like the hamster test, the procedure cannot result in a living embryo.) Researchers hope it will provide the same information as the hamster test and also indicate whether the sperm can penetrate the outer coating of an egg.
Postcoital TestThe postcoital, also known as Simms–Huhner, test is designed to evaluate the effect of a woman’s cervical mucus on a man’s sperm. To perform this test, a woman is asked to come into the physician’s office within two to 24 hours after intercourse at mid–cycle (when ovulation should occur). A small sample of cervical mucus is obtained and examined under a microscope. A problem is detected if the physician observes no surviving sperm or no sperm at all. If results are poor, the woman’s cervical mucus should also be cultured for the presence of infection. The test can indicate that a problem exists but cannot determine its cause in most cases. The test also cannot evaluate sperm movement from the cervix into the fallopian tubes or the sperm’s ability to fertilize an egg.
Swim–Up TestThe swim–up test may prove to be a good method for testing the ability of sperm to escape from the semen into the cervical mucus. A specially prepared semen sample is placed in a tube. A culture media (a substance in which organisms can multiply) is placed on top of the sample. The medium is a hospitable environment for sperm, and those that are healthy will swim up to it. After an hour or more, the culture is examined, and the number of sperm that have reached the medium is compared to the number still remaining in the semen. The result gives a fair estimation of the number of sperm potentially capable of fertilization. The swim–up test has the added advantage of providing healthy sperm for intra–uterine insemination and assisted reproductive techniques.
Hormone TestsIf sperm counts are low, blood tests may be taken to determine levels of the hormones FSH, LH, and testosterone. Normal results, however, do not ensure fertility. For example, germ cells may produce adequate amounts of sperm in response to normal hormone levels, but there may be a defect in sperm maturation or a blockage in the sperm transport system that does not depend on hormones but does reduce the final sperm count. Usually, only if the testicles are very defective will FSH hormone levels rise abnormally.
Sperm AntibodiesIf a man has had a vasectomy reversed and still cannot conceive or if semen analysis shows sperm clumping together, blood tests for anti–sperm antibodies will be conducted. The primary negative effect of these antibodies is to bind the sperm to the woman’s cervical mucus, preventing the sperm from swimming further up.
Testicle BiopsyOccasionally, a testicle biopsy may be performed in which tissue samples are removed under anesthesia. A biopsy is most useful for detecting obstruction in the transport system when sperm production looks normal but the count is low. The standard biopsy procedure requires incisions (called an open approach) and can be painful afterward. The procedure is valuable not only for diagnosis of infertility and predicting fertility treatment success, but it may also be used in some cases to retrieve sperm for fertility procedures. The use of needle aspiration, which is less invasive, is proving to be as effective in evaluating infertility as the open approach and may also be used to retrieve sperm for assisted reproduction techniques in some cases.
UrinalysisA urine analysis is important when sexually–transmitted infections are suspected as a cause of infertility.
Imaging TechniquesUltrasound 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 effect on fertility). A vasogram is an x–ray used in conjunction with an opaque liquid injected into the vas deferens to reveal an obstruction. A testicular biopsy and the sperm count together, however, are better initial diagnostic tools for this purpose. A vasogram is best used by surgeons before an operation to locate the blockage they are attempting to clear.
VaricoceleA varicocele is a varicose vein of the testicle found in 15% to 20% of all men and in 25% to 40% of infertile men. (A varicose vein is one that is abnormally enlarged and twisted.) Varicocele may partially obstruct the passages through which sperm pass. Studies also suggest that varicoceles may impair sperm quality through unknown mechanism.
Some experts believe that varicoceles may prevent the enzymes contained in the acrosome on the head of the sperm from initiating fertilization. It should be noted, however, that some evidence supports that idea that varicoceles play only an insignificant role in infertility. One eight–year study of men with and without varicoceles found no differences in sperm quality or in the ability to conceive.
What Causes Abnormalities?Infertility can result from many different factors. The specific cause of sperm abnormalities cannot be established in most cases. It may be the end result of one or a combination of factors that include chronic illness, malnutrition, genetic defects, structural abnormalities, and environmental factors. Partial obstruction anywhere in the long passages through which sperm pass can reduce their sperm counts.
General Problems with Sperm Production and Quality
Infertile spermMore than 90% of male infertility is due to low sperm counts, poor sperm quality, or both. In 30% to 40% of cases of sperm abnormalities, the cause is unknown. Abnormal sperm production is categorized by the following terms. oligospermia (less than 10 million sperm per cubic centimeter of semen), azoospermia (no sperm), dysspermia (low–quality sperm), or aspermia (no ejaculate). One study reported that fertilization rates were 71% for men with a single defect in sperm count, motility, or morphology (structure), 50% for a double defect, and 39% for triple defects. Although it has been thought that fertility and sperm quality decline after age 40, a recent study has reported that sperm number, structure, and motility (the ability to move) do not decline until beyond age 64.
Low Sperm CountA normal sperm count is considered to be 20 million/mL. A lower than normal sperm count can be caused by a variety of defects, which usually occur later in sperm development, since most men have an adequate number of sperm–creating germ cells. When the cause is not known, which occurs in half the cases, the condition is known as idiopathic oligospermia.
Sperm count may vary widely over time as well, so a single test that reports a low count may not be a representative result. Temporary low counts can be caused by many conditions, including high fever, stress, various drugs, chemotherapy, environmental toxins, overheating, and lack of sleep.Complete failure of the testes to produce any sperm is relatively rare, affecting less than 5% of infertile men. Low counts do not preclude fertilization if the woman is fertile. In the past, less than 40 million sperm per cubic centimeter (cc) in the ejaculate was believed to cause infertility. Now, however, if the woman is fertile and young, it is believed that a sperm count as low as 10 million cc can accomplish conception over time, even without treatment.