What is male infertility?

Causes and Symptoms

To create a baby requires three things: healthy sperm from a man, a healthy egg from a woman, and a healthy, mature uterus. Anything that blocks the availability of the sperm, egg, or uterus can cause infertility. Infertility can be thought of as an abnormal, unwanted form of contraception.

Many different factors may be responsible for infertility. In general, these factors may be infectious, chemical (from inside or outside the body, such as pharmaceuticals, toxins, or illegal drugs), or anatomical. Genetic factors may be responsible as well, since genes control the formation of body chemicals (such as hormones and antibodies) and body structures (one’s anatomy). The way that these factors work is illustrated by male infertility.

Sperm are made in a man’s testes (or testicles). Because the creation of sperm is controlled by genes and hormones, abnormalities in these can cause infertility. Sperm are initially formed in the seminiferous tubules, extremely narrow, tightly coiled tubes in the main body of the testes; from there, the sperm are released into another set of tubes to the rear of the testes called the epididymis, where they become mature. Sperm are stored in the epididymis until being released into the vas deferens and then the urethra before leaving the body during intercourse. A blockage of any part of this reproductive tract, or premature release of sperm from the epididymis, can cause infertility.

A blockage of reproductive ducts can occur as a result of a bodily enlargement, such as swollen tissue, a tumor, or cancer. An infection usually causes tissue swelling and can leave ducts permanently scarred, narrowed, or blocked. Infection can have a direct detrimental effect on the production of normal sperm. Cancer and the drugs or chemicals used to treat cancer can also damage a man’s reproductive tract.

Another factor that may be important to male fertility is scrotal temperature. The temperature in the scrotum, the sac that holds the testes, is somewhat lower than body temperature. The normal production of sperm seems to be dependent upon a cool testicular environment.

One cause of male infertility is varicoceles—basically varicose veins of the testes—which occur when one-way valves fail in the veins that take blood away from the testicles. When these venous valves become leaky, blood flow becomes sluggish and causes the veins to swell. Many men with varicoceles are infertile, but the exact reason for this association is unknown. The reasons sometimes given are increased scrotal temperature and improper removal of materials (hormones) from the testis.

Mature sperm capable of fertilizing an egg are normally placed in the female reproductive tract by the ejaculation phase of sexual intercourse. The sperm are accompanied by fluid called seminal plasma; together, they form
semen. A blockage of the ducts that transport the semen into the woman or toxic chemicals, including antibodies, in the semen can cause infertility.

For
conception to take place—that is, for an egg to be fertilized after sperm enters the female tract—a healthy egg must be present in the portion of the female reproductive tract called the Fallopian tube, and sperm must move through the female tract to that egg. If the egg is absent or is abnormal, or if healthy sperm cannot reach the egg, failure to conceive will result. The female factors that determine whether sperm fertilize an egg are the same as the male factors: anatomy, chemicals, infection, and genes.

For those who seek help with fertility issues, there are many methods available. Female infertility may be treated, depending upon the cause, by surgery, hormone therapy, or in vitro fertilization. Treatment of male infertility may be by surgery, hormone therapy, or
artificial insemination. Artificial insemination is often performed when the couple is composed of a fertile woman and an infertile man.

The first step for artificial insemination is for a physician to determine when the woman ovulates or releases an egg into the Fallopian tube. At the time of ovulation, semen is placed with medical instruments in the woman’s reproductive tract, either on her cervix or in her uterus.

The semen used by the physician is obtained through masturbation by either the infertile man (the patient) or a fertile man (a donor), depending on the cause of the man’s infertility. The freshly produced semen from either source usually undergoes laboratory testing and processing. Tests are used to evaluate the sperm quality. An effort may be made to enhance the sperm from an infertile patient and then to use these sperm for artificial insemination or in vitro fertilization. Other tests evaluate semen for transmissible diseases. During testing, which may require many days, the sperm can be kept alive by cryopreservation, or freezing. Freshly ejaculated sperm remains fertile for only a few hours in the laboratory if it is not cryopreserved.

There are several processes that might enhance sperm from an infertile man. If the semen is infertile because it possesses too few normal sperm, an effort can be made to eliminate the abnormal sperm and to increase the concentration of normal sperm. Sperm may be abnormal in four basic ways: They may have abnormal structure, they may have abnormal movement, they may be incapable of fusing with an egg, or they may contain abnormal genes or chromosomes. Laboratory processes can often eliminate from semen those sperm with abnormal structure or abnormal movement. These processes usually involve replacing the seminal plasma with a culture medium. Removing the seminal plasma gets rid of substances that may be harmful to the sperm. After the plasma is removed, the normal sperm can be collected and concentrated. Pharmacologic agents can be added to the culture medium to increase sperm movement.

Testing for transmissible diseases is especially important if donor semen is used; these diseases may be genetic or infectious. There are many thousand genetic disorders. Most of these disorders are very rare and can be transmitted to offspring only if the sperm and the egg both have the same gene for the disorder. It is impossible, therefore, to test a donor for every possible genetic disorder; he is routinely tested only for a small group of troublesome disorders that are especially likely to occur in offspring. Tests for other disorders that the donor might transmit can be performed at the woman’s request, usually based upon knowledge of genetic problems in her own family.

Much of the genetic information about a person is based on family history. Special laboratory procedures allow the genetic code inside individual cells to be interpreted. For this reason, it is important to store a sample of donor cells, not necessarily sperm, for many years after the procedure. These cells provide additional genetic information that might be important to the donor’s offspring but not known at the time of insemination.

Semen can also be the source of some infectious diseases. Syphilis, gonorrhea, chlamydia, and acquired immunodeficiency syndrome (AIDS) are examples of sexually transmitted infections (STIs) that can be transmitted by donor semen. Screening history and testing are done on donors, but they cannot ensure that there will be no chance of infection. For example, the human immunodeficiency virus (HIV) may be newly present from recently acquired infection, but screening tests depend on the presence of antibodies, which do not show up immediately after someone is infected.

Cryopreservation of sperm is important to artificial insemination for two major reasons. First, it gives time to complete all necessary testing. Second, it allows an inventory of sperm from many different donors to be kept constantly available for selection and use by patients. Sperm have been cryopreserved for over twenty years and then thawed and used successfully.

Cryopreservation involves treating freshly ejaculated sperm with a cryoprotectant pharmaceutical that enables the sperm to survive when frozen; the cryoprotectant for sperm is usually glycerol. Survival of frozen sperm is also dependent upon the rate of cooling, the storage temperature, and the rate of warming at the time of thawing. Sperm treated with a cryoprotectant have the best chance of survival if they are cooled at a rate of about 1 degree Celsius per minute and stored at a temperature of –150 degrees Celsius (about –240 degrees Fahrenheit) or colder. An environment of liquid nitrogen is often used to attain these storage temperatures. The storage temperature must be kept constant to avoid the damaging effects of recrystallization.

Human sperm can be shipped to almost any location for artificial insemination. Sperm is usually cryopreserved before shipment and thawed at the time of insemination.

Treatment and Therapy

The use of artificial insemination to treat two kinds of male infertility will be considered here. The first example is male infertility that cannot be treated by other means. The second example is a fertile man at high risk for becoming infertile because of his lifestyle or because he is receiving treatment for a life-threatening disease.

The first example might occur when a heterosexual couple, having used no contraception for a year or longer, has been unsuccessful in conceiving a baby. In 40 percent of infertility cases, the woman has the major, but not necessarily the only, problem preventing the pregnancy. In 40 percent of the cases, the man is the major factor. In 20 percent, each person makes a contribution to the problem, or the problem is unidentified. Therefore, both partners must deal with the infertility and be involved in the treatment.

The solution to a couple’s infertility involves evaluation and therapy. The couple will be evaluated in regard to their present sexual activity and history, such as whether either one has ever contributed to a pregnancy. The medical evaluation of both partners will include a physical examination, laboratory tests, and even imaging techniques such as x-rays, ultrasonography, or magnetic resonance imaging (MRI). For the man, the physical examination will include a search for the presence of varicoceles, and the laboratory tests will include a semen analysis.

Varicoceles are probably the most readily detected problem that may cause male infertility. They are three times more common in infertile men than in men with proven fertility. This association does not prove that varicoceles cause infertility, however, because surgery that corrects a varicocele does not always correct infertility.

If the medical evaluation determines that the female partner has a normal reproductive tract and is ovulating on a regular basis, and if it determines that the male partner has too few normal sperm to make a pregnancy likely, the couple may be asked to consider adopting a baby or undergoing artificial insemination. With artificial insemination using a sperm donor, if the woman becomes pregnant, half of the baby’s genes come from the mother, and the other half of the genes come from the donor, usually a person unknown to the couple. The physician performing artificial insemination may provide the couple with extensive information on several possible donors. Such information might include race, ethnic origin, blood type, physical characteristics, results of medical and genetic tests, and personal information, but the donor usually remains anonymous. The semen from each donor has undergone laboratory testing and cryopreservation. The frozen semen is then thawed at the time of insemination.

Although the idea of artificial insemination is simple, it usually involves some very complicated emotions. Although a couple may be very happy about all other aspects of their lives together, they may be disturbed to learn of the man’s infertility. If the couple chooses artificial insemination using a sperm donor, later, they must decide whether to tell the child about the circumstances of his or her birth. Sometimes, a child who originated through artificial insemination may try to learn the identity of the donor.

Although male-factor infertility is the situation that benefits most from insemination and semen cryopreservation procedures, these procedures might be requested by a fertile couple that is at risk for male-factor infertility. Such couples may fear that the man’s lifestyle, such as working with hazardous materials (solvents, toxins, radioisotopes, or explosives), may endanger his ability to produce sperm or may harm his genetic information. The man could be facing medical therapy that will cure a malignancy, such as Hodgkin’s disease or a testicular tumor, but may render him sterile. A man facing such a situation may benefit from having some of his semen cryopreserved for his own future use, in the event that he does become infertile.

There are ways to compensate for decreased semen quality. The semen may be processed in ways to increase the concentration of normal sperm. The processed semen may be placed directly into the woman’s uterus (intrauterine insemination) rather than on her cervix, or in vitro fertilization (IVF) may be used. In this procedure, the sperm and eggs are mixed in a laboratory and the resulting embryo is implanted in the woman. For men with difficulties in sperm production, IVF may be achieved using intracytoplasmic sperm injection (ICSI), which involves the implantation of one sperm directly into an ovum, thus avoiding the need for large numbers of sperm. All these techniques have proved helpful to infertile couples wanting children.

Perspective and Prospects

Studies have shown that about 15 percent of American couples are unable to conceive after one year of unprotected sex, and 10 percent do not conceive after two years. By the early 1990s, artificial insemination produced more than thirty thousand American babies yearly. This procedure advanced in the United States during the latter half of the twentieth century in large measure because of changes in attitudes, more than new medical knowledge.

The medical knowledge to treat male infertility has been available for several centuries, even when the biological basis for pregnancy was not understood. The Bible records stories of patriarchal families that knew the problem of infertility (Abraham and Sarah, Jacob and Rachel) and even indicates, in the story of Onan and Tamar (Genesis 38:9), that semen was understood to be important to reproduction. The possibility of therapeutic insemination was mentioned in the fifth century Talmud. Arabs used insemination in horse breeding as early as the fourteenth century, and Spaniards used it in human medicine during the fifteenth century.

The presence of sperm in semen was first observed by the Dutch scientist Antoni van Leeuwenhoek in the seventeenth century, but their importance and function in the fertilization process was not recognized until the nineteenth century. In 1824, Jean Louis Prévost and J. A. Dumas correctly guessed the role of sperm in fertilization, and in 1876, Oskar Hertwig and Hermann Fol proved that the union of sperm and egg was necessary to create an embryo.

Artificial insemination became an established but clandestine procedure in the late nineteenth century in the United States and England. Compassionate physicians pioneering artificial insemination encouraged secrecy to protect the self-esteem of the infertile man, his spouse, the offspring, and the donor. In an uncertain legal climate, the offspring might have been viewed as the illegitimate product of an adulterous act. Even by the beginning of the twenty-first century, many Americans continued to stigmatize masturbation and artificial insemination. Social attitudes, especially traditional notions of masculinity, have limited the acceptability of artificial insemination to many infertile couples worldwide.

Cryopreservation of sperm became practical with the discovery of chemical cryoprotectants, reported in 1949 by Christopher Polge, Audrey Smith, and Alan Parkes of England. In 1953, American doctors R. G. Bunge and Jerome Sherman were the first to use this procedure to produce a human baby. Cryopreservation made possible the establishment of sperm banks; prior to this development, sperm donors had to provide the physician with semen immediately before insemination was to take place.

Researchers continue to theorize about new fertility-enhancing techniques using sperm. In 2003, scientists discovered that sperm have a type of chemical sensor that causes the sperm to swim vigorously toward concentrations of a chemical attractant. While researchers long have known that chemical signals are an important component of conception, the 2003 findings were the first to demonstrate that sperm will respond in a predictable and controllable way. The findings provided strong evidence that the egg signals its location to the sperm and the sperm respond by swimming toward the egg, a process which could prove promising for future contraception and infertility research. Scientists note that these findings might allow specific tests to be developed to determine if the egg is making the attractant or if the sperm have the receptor, thus helping in identifying those couples who are infertile because of poor signaling between the sperm and egg.

Artificial insemination and other alternative means of reproduction give rise to thorny issues of personal rights of various “parents” (social, birth, and genetic) and their offspring. In the United States, a few states have addressed these issues by enacting laws, usually to grant legitimacy to offspring of donor insemination. In the United Kingdom, Parliament established a central registry of sperm and egg donors. Offspring in the United Kingdom have access to nonidentifying donor information; these children are even able to learn whether they are genetically related to a prospective marriage partner.

Bibliography

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