Male Fertility: Maximizing Your Fertility Potential

"Dr. Perloe, we keep getting conflicting information about male fertility treatment. Could you clarify the current thinking for us?" the RESOLVE leader asked.

"The first part of the male formula is what I call pretesticular function. This means that your hormone system must be functioning properly in order to stimulate your testicles to make sperm.

"The second ingredient I call the testicular component. This means that when stimulated by your sex hormones, your testicles must be capable of producing sperm. Testicles can be congenitally deformed or they can be damaged by chemical toxins, illness, systemic disease, or trauma." I saw Steven S.'s hand go up. "Yes, Steven?"

"But I thought your testicles made your sex hormones. If your testicles aren't working, how can your hormones be stimulating them?"

"Your testicles do produce the male hormone testosterone. However, your brain and your pituitary gland, located at the base of your brain, produce chemicals that tell your testicles when to make testosterone and when to make sperm. Without these signals from your brain and pituitary, your testicles may fail to mature and fail to make sperm.

"The third ingredient of the male fertility formula is posttesticular function. The ducts leading from your sperm-producing testicles must provide a clear and continuous path for your sperm to travel out of your penis. Congenital tubal defects, surgeries, and blockage from infections may clog up these pathways."

"What can be done for blocked tubes?" Michael T. asked.

"Today with the aid of microsurgery, most tubal problems can be corrected, including vasectomy reversals." I turned to the chalkboard and wrote down the fourth factor, ejaculatory disturbances, impotence, and sexual problems . "These are the final ingredients of the male fertility formula," I said. "You must be able to deliver your sperm to your wife's cervix in order to make a baby." I set the chalk in the tray and turned back toward the group.

"There are some exceptions to this. Some delivery problems can be overcome with artificial insemination. For example, some men ejaculate backward into the bladder. When this happens, we can retrieve the ejaculated sperm and use artificial insemination techniques to get the sperm to their destination."

"What if the man can't perform?" a woman across the room asked.

"There are two types of sexual performance problems—physiological impotence and psychological impotence. Often it's difficult to separate the two, since men with impaired sexual performance frequently have psychological problems regardless of the source of their difficulty. Physiological impotence may be caused by toxic chemicals, hormone deficiencies, "street" drugs, medications, and nerve damage, for example. A complete fertility evaluation should reveal the source of the problem. And even with physiological impotence, counseling may be needed to ease the difficulties associated with inadequate sexual performance.

"These are the four ingredients necessary for male fertility." I started toward my chair. "If any one of them is out of order, you may have a fertility problem. Working together, you and your physician must identify the deficient factor and direct treatment toward improving that function."

The Male Hormone System

The Hypothalamus and Pituitary Start the Action
Approximately every ninety minutes a specialized area in your brain (hypothalamus) secretes GnRH (gonadotropic-releasing hormone). GnRH signals your pituitary gland, located at the base of your brain, to produce LH (luteinizing hormone) and FSH (follicle-stimulating hormone). LH tells your testes to secrete the male hormone testosterone. Testosterone stimulates your sexual desires and develops and maintains your male secondary sex characteristics such as hair growth and deep voice. Together, testosterone and FSH stimulate your testes to produce sperm (spermatogenesis). Your body's ability to make and regulate these hormones is vital for maintaining your virility and sperm production.

Feedback Hormones from Your Testicles
You have feedback hormones—testosterone and inhibin—that keep a check and balance on your GnRH, LH, and FSH levels. Once the Leydig cells in your testicles produce enough testosterone, your hormone control 00 systems cut back on GnRH and LH production. When the Sertoli cells, which respond to FSH stimulation, produce enough inhibin, the pituitary cuts back FSH production. Examining figure 8-1 will help you visualize your fertility hormone control system. These relationships will become more clear in the discussions that follow.

Cell Division
Each day your testicles make millions of sperm. Your testicles are composed of a number of different types of cells which support and surround masses of microscopic seminiferous tubules. Your sperm grow and mature within these tubules. The germ cells (germinal cells or basic sperm cell factories) line these tubule walls. When they are stimulated by the Sertoli cells, the germ cells divide (mitosis) to produce one primary spermatocyte that contains a full complement of your forty-six chromosomes (genetic material). The germ cells remain intact to divide repeatedly throughout your reproductive life. The primary spermatocytes, containing forty-six chromosomes, however, proceed to divide by a special process called meiosis. Meiosis produces four spermatids (immature sperm) containing twenty-three chromosomes each. These spermatids are destined to fertilize your wife's egg, containing twenty-three of her chromosomes. At this point cell division ends and the sperm maturation process begins.

Sperm Maturation
The spermatids remain attached to your tubule wall, where they are nurtured by the Sertoli, or nurse, cells. It takes about ninety days for the sperm to grow, mature, and travel through the tubules to a central storage area called the epididymis. Here the sperm become powerful swimmers. After each ejaculation, it takes about forty hours for your epididymis to refill with mature sperm (this is why too-frequent intercourse can impair fertility).

Each microscopic sperm carries all the genetic information necessary to fertilize the egg. Half of your sperm carry an X chromosome (inherited from your mother) and half carry a Y chromosome (inherited from your father). If an X-carrying sperm fertilizes your wife's egg (ovum), you'll have a baby girl. If a Y-carrying sperm fertilizes the ovum, you'll have a baby boy. In this way the husband's genetic contribution determines the baby's sex.

The Sperm Delivery System
When you ejaculate, your sperm rush through a number of channels between your epididymis and the opening of your penis. (You can view the course that your sperm travel during ejaculation in figure 8-2 below.)

At the moment of ejaculation, your epididymis expels the sperm into the pulsating muscular walls of your vas deferens. While coursing through your vas deferens, the sperm pass the seminal vesicles. These secrete fructose (a sugar to feed your sperm), seminal fluids (to protect your sperm), and a chemical that coagulates your semen soon after it enters your wife's vagina. Then your sperm speed through your ejaculatory ducts past your prostate gland, which secretes additional seminal fluids, including a chemical that liquefies your coagulated semen within an hour after ejaculation. As your semen (sperm plus your seminal fluids) rushes past the bladder, a muscle (sphincter) squeezes the bladder opening shut. This guides the semen on course through your urethra and out of your penis.

Erection, Orgasm, and Ejaculation
Erection, orgasm, and ejaculation are three distinct processes controlled both by your conscious mind and by involuntary neural responses. To get sperm to your wife's cervix, all three of these processes must be working properly.

Erection
Erection may occur when you have an erotic thought or when your penis is touched. During an erection, nerves signal the blood vessels in your erectile tissue to dilate and become engorged, and your penis swells and becomes rigid. Friction from manual and vaginal stimulation sends more signals to the brain and stimulates orgasm and ejaculation. Psychological factors can stimulate or interfere with your erection; however, once you reach orgasm your automatic reflex actions run their course.

Orgasm and Ejaculation
Orgasm is the name given to the physiological and sensory thrill that accompanies ejaculation. The first stage of orgasm, called ejaculatory inevitability, occurs two to four seconds before ejaculation. During this interval you sense your imminent ejaculation and cannot continue to control the process. Your prostate gland and your seminal vesicles start to pulse. The second stage of orgasm begins when you involuntarily expel semen in several convulsive waves. Typically you ejaculate about one teaspoon of semen, which contains 40 to 150 million sperm. The first squirt (semen fraction) generally contains the largest number of sperm.

After orgasm, most men and many women experience a recovery (refractory) period during which they cannot have another orgasm. This period may last many minutes and sometimes several hours. You may also experience an erection refractory period.

As I discuss the various causes of male fertility problems, the statistics in table 8-1 will help you place each condition into proper perspective.

Table 8-1

Where Can Things Go Wrong?

In the rest of this chapter I will describe how each of the four fertility factors may malfunction, how specific disorders can be diagnosed, and how they can be corrected.

Several things can go wrong with your hypethalamus-pituitary endocrine system:

• Your brain can fail to pulse GnRH properly.

   

• Your pituitary can fail to produce enough LH and FSH to stimulate your testes.

   

• Your testes' Leydig cells may not produce testosterone in response to LH (pituitary) stimulation.

   

• Your body may produce other hormones and chemical compounds which interfere with your sex-hormone balance.

Any one of these conditions can impair your sperm production. To help you understand the treatment for these hormonal disorders, I'd like to explain what medications are available and how they are prescribed to improve male fertility.

An Overview of Hormonal Treatment
If your pituitary hormones (LH and FSH) are low, but you do have a working hypothalamus and pituitary gland, clomiphene citrate (Serophene, Clomid) should stimulate your hypothalamus to pulse GnRH at regular intervals. When your hypothalamus properly releases GnRH, your pituitary gland will respond by producing LH and FSH. If Serophene does not improve LH and FSH levels, then I will suspect that your pituitary gland may be malfunctioning. (Since Serophene is an oral medication, it is more convenient and less expensive than your other options.)

If your pituitary cannot manufacture the missing sex hormones, you can take hormone supplements. Injections of hCG (human chorionic gonadotropin) will increase your LH supply and often stimulate your testes to produce testosterone and sperm. If your response to hCG is inadequate, I might add Pergonal (FSH and LH) to stimulate sperm production. Pergonal and hCG treatments can be quite expensive, since they require regularly repeated injections.

If these treatment regimens are successful, sperm production and quality will begin to improve within three to four months.

Hyperprolactinemia
Hyperprolactinemia (elevated prolactin) can be difficult to diagnose because your FSH, LH, and testosterone levels will be normal. We find elevated prolactin, a hormone associated with nursing mothers, in 10 to 40 percent of infertile males. Mild prolactin elevation produces no symptoms; however, greater elevations can reduce sperm production, impair your sex drive, and cause impotence. Hyperprolactinemia responds well to a drug called Parlodel (bromocriptine). A prolactin-secreting tumor will also respond to Parlodel; however, surgery and/or radiation therapy may be necessary.

Hypothyroidism
Found in 1 percent of infertile men, hypothyroidism (low thyroid hormone) can cause poor semen quality, poor testicular function, and/or disturbances in sex drive. You will be lethargic, intolerant of cold, and overweight. Because the pituitary gland is trying its best to stimulate your unresponsive thyroid gland, your pituitary-produced TSH (thyroid-stimulating hormone) level will be elevated. Elevated prolactin levels, frequently found with this disorder, may cause impotence.

You can sometimes bring on hypothyroidism by eating a diet high in iodine—for example, kelp or seaweed—or taking multimineral tablets. Chronic ingestion of iodides in cough syrups (formerly used in treating asthmatic bronchitis) may also produce these symptoms. In addition, hypothyroidism may be caused by radioactive thyroid medications and autoimmune diseases.

Correcting your diet or beginning thyroid hormone replacement therapy should elevate your sperm count to previous levels. I must emphasize that unless you have low thyroid, thyroid hormone replacement therapy will not improve your sperm quality.

Stress and Excessive Exercise
When a woman is under a great deal of stress, we can use Serophene to regulate the GnRH pulses from her hypothalamus and restore ovulation. It seems logical to assume that Serophene may help a man in the same situation. Although we don't know the therapeutic effects for certain, I have observed some semen improvement when Serophene has been used with these men.

I especially remember Ted M., who was the typical "Type A" personality. Ted had a borderline sperm count, smoked five packs of cigarettes and drank ten cups of coffee a day, and was a workaholic. I prescribed Serophene and also counseled with him about restructuring his habits. With some help from his friends in RESOLVE, Ted began a moderate exercise program and got his nicotine and caffeine habits under control. Within five months his count began improving and a year later he fathered a child.

Congenital Adrenal Hyperplasia
Pound in 1 percent of infertile males, congenital adrenal hyperplasia may be suspected when a semen analysis shows a low sperm count, an increased number of immature sperm cells, sperm with long tapered heads, and low motility. These abnormalities occur when the pituitary is suppressed by increased levels of adrenal androgens. Men with this disease may also have hypertension (high blood pressure) and edema (water retention). Early onset of the disease may result in ambiguous genitalia at birth or reaching puberty at an early age. Adult onset may be characterized by infertility, high blood pressure, and/or water retention.

Cortisone replacement therapy will lower your androgens and allow your pituitary to function normally. Therefore, indirectly, cortisone replacement therapy will elevate your sperm count.

Some of these situations are not so easily managed. One time I had the unfortunate job of counseling one of my bearded male patients who was genetically a she. Because the adrenal androgens (male hormones) had dominated this person's hormonal system since before birth, male secondary sex characteristics developed. Fortunately this finding is quite rare.

Hypogonadotropic Hypopituitarism
Hypogonadotropic hypopituitarism is a spectrum of diseases with a complicated name that means low (hypo-) pituitary gland output of LH and FSH. Other stages of this disease are called isolated gonadotropin defect and panhypopituitarism, in which the entire (pan-) pituitary gland is affected.

These diseases arrest sperm development and cause the progressive loss of germ cells from the testes. In addition, the seminiferous tubules and Leydig cells (which produce testosterone) also deteriorate. If the condition persists for a long time, you will have no sperm production at all. (See chapter 7 for a discussion of maturation arrest.) When the disease is associated with a pituitary tumor, elevated prolactin levels may also cause impotence.

Clifford J. showed signs typical of this progressive degeneration. Over a period of three to four years he gradually lost his heavy beard, became less interested in sex, and eventually could not sustain an erection. His blood tests revealed low LH, FSH, and testosterone levels, and his sperm count was 10 million per milliliter. I prescribed Serophene in hopes of improving his sperm count and sexual performance. Fortunately he responded to the drug, and six months later his sperm count increased to 18 million. After performing AIH four times, his wife became pregnant. Following fertility treatment, I discontinued the Serophene (it's too expensive to take all of the time) and continued giving him a testosterone supplement to maintain his virility and sexual performance.

Panhypopituitafism
Complete pituitary gland failure (panhypopituitarism) lowers your growth hormone, ACTH level, thyroid-stimulating hormone (TSH), and LH and FSH levels. If you have this rare disease, you will have multiple symptoms that include impotence, decreased sex drive, loss of secondary sex characteristics, and normal or undersized testicles. Your hypothyroidism (low thyroid hormone) will cause you to gain weight, be intolerant of cold, and feel lethargic. If the disorder began early enough in your life, you may even be a dwarf. The hormonal deficiency is often caused by a tumor, surgery, or trauma to the pituitary gland.

No amount of stimulation can improve the performance of the damaged pituitary gland, so I will work with an endocrinologist to supplement the missing pituitary hormones. The thyroid hormone supplement as well as other hormone replacements will restore general health and vigor. At that point I administer hCG to stimulate the testicles to produce testosterone and to begin making sperm.

Kallman's Syndrome
Kallman's syndrome is a congenital hypothalamic dysfunction. If you are born with this unusual condition, you will have underdeveloped testicles and possibly a harelip, cleft palate, color blindness, and/or the inability to smell. Affected men have varying degrees of sexual infantilism (prepuberty) and no sperm production. Since the hypothalamus fails to stimulate the pituitary adequately, FSH, LH, and testosterone levels are low. I treat Kallman's syndrome similarly to hypogonadotropic hypopituitarism. Although at first it seems hopeless, men afflicted with Kallman's syndrome can achieve normal puberty and eventually become fertile.

Delayed Puberty
Individuals with isolated pituitary growth hormone deficiency do not sexually mature until their mid to late twenties. Hormone supplements can make them look virile, but until they go through puberty, they won't be fertile. Pergonal and/or hCG injections can bring on puberty, although if left alone, sexual maturity and fertility will be achieved in time.

Fertile Eunuch
If you have this rare disorder, your virilization (acquisition of adult sex characteristics) will be moderately advanced, but you will not have completed sexual maturation and testicular growth. If I biopsied your rather small testicles (a procedure not usually needed to diagnose this condition), I'd find evidence of sperm production and thus the potential for fertility. Since the arrest of sperm production and low testosterone levels are caused by an LH deficiency, administering hCG will raise both hormone levels and stimulate sperm production.

What Causes Testicular Failure?
Let's suppose that your hypothalamus and pituitary are working well. The fact is that some conditions prevent your testicles from responding to pituitary hormone stimulation. Testicular failure, as it's called, can be caused by genetic abnormalities or by damage from drugs, injury, radiation, excess heat, adult mumps, a varicocoele, or toxins from your environment. Sensing abnormal testicular function, your brain responds by telling your pituitary to pump out more FSH to stimulate sperm production. In fact, elevated FSH is the primary diagnostic indicator for testicular failure.

Unfortunately there isn't much that can be done for primary testicular failure, which is caused by a genetic mistake. The malformed testes are unable to produce sperm and no amount of stimulation will improve their function. However, if you have this problem, you and your wife need not go childless. You are a prime candidate for artificial insemination with donor sperm (AID). With AID your baby will inherit your wife's genes and traits and will be your own through your marital bonds and love. I'll talk more about AID techniques in a later chapter.

We have a better chance of treating secondary testicular failure (acquired damage). If, before too much testicular damage occurs, you discontinue potentially harmful medications and illicit drugs; avoid contact with toxic substances such as pesticides; reduce excess heat exposure; or have a varicocoele surgically repaired, you may once again produce sperm. Below is a discussion of what causes testicular failure and the methods available for improving fertility.

Continued