Male Fertility: Evaluating Male Infertility

"Dr. Perloe," Steven S. said as he sat down on the examining table, "this may sound like a dumb question, but how can I be infertile? I thought people like that wouldn't be able to 'get it up.' "

I smiled. "That's not a dumb question at all. But 'getting it up' and getting them out are two different things." I sat on the stool beside the table.

Steven still looked anxious. "You mean you can have one problem without the other?"

"Yes, you can have a completely normal sex drive and still not make enough sperm to get your wife pregnant."

"What a relief." He relaxed and the tension left his face. "I almost didn't have the courage to ask you."

"Please don't ever feel that way, Steven." I picked up his completed medical history form. "Let's see what we can do to raise your sperm count."

Steven's concern about virility is common among men. Although we see a connection between virility and fertility with a few hormonal disorders, sexual impairment is fairly rare.

In this chapter you will discover how your life-style, general health, and sexual experiences may be affecting your fertility. And you'll learn more about how your doctor can identify the source of your fertility problem.

To get your wife pregnant, you must be able to make and ejaculate viable sperm. To accomplish this, a number of mechanisms must be in good working order. I divide my fertility formula into the following categories: pretesticular, testicular, posttesticular, and ejaculatory processes. The interruption of any one of these four processes accounts for about 80 percent of male fertility

problems. The other 15 to 20 percent are very rare conditions or disorders that cannot be diagnosed at this time.

Before covering each of the fertility formula factors in depth, I'd like to give you an overview of the four processes. In the next two chapters I'll discuss these areas in greater detail.

Pretestlcular Function (Hormones)
Disturbances in the hormonal system cause about 10 percent of male fertility problems.

Your brain plays a key role in regulating the hormones that affect the development of sperm (spermatogenesis). The process begins when your hypothalamus (a part of your brain) emits a substance (gonadotropin-releasing hormone, or GnRH) that stimulates your pituitary gland, located at the base of your brain. Your pituitary gland then emits LH (luteinizing hormone) and FSH (follicle-stimulating hormone). These stimulate testicular development and sperm production. LH also initiates the testicular production of testosteroneùa hormone responsible for virility, male secondary sex characteristics, and the support of sperm production. (If you got through that, the rest will be a cinch!)

A number of conditions can interfere with the development and timely delivery of these hormones. When the system breaks down, low sperm production (oligospermia) or no sperm production (azospermia) may result. If you have a pretesticular problem, you have a good chance of responding to hormone replacement therapy.

Testicular Function
Testicular failure represents about 55 percent of male fertility problems.

To respond to hormone stimulation properly, your testicles, or testes, must be capable of producing sperm (spermatogenesis). To assess your testicular potential, I need to know if your testes descended into your scrotum on time; if they have been damaged by a varicocoele (a varicose vein in the scrotum) or by excessive heat, toxins, disease, or trauma; or if for some genetic reason they failed to develop normally. If the damage or failure is severe, nothing much can be done to improve testicular performance. However, testes damaged by varicocoeles (which are found in 40 percent of men with fertility problems) frequently respond to surgical repair. And testes impaired by toxic substances often recover when the toxins are removed.

Posttesticular Function
Tubal obstruction, including vasectomy, accounts for about 6 percent of male infertility.

Your posttesticular system of ducts must be capable of storing and delivering your sperm. Sperm delivery system problems include obstruction or interruption of the tubes as a result of congenital malformation, disease, surgery, or trauma. Laser surgery and microsurgical techniques offer excellent chances for duct repair and restored fertility. Newer techiques allow the urologist to remove sperm directly from the testicle. These sperm can then be injected directly into your wife's eggs.

Ejaculatory Disturbance, Impotence, and Sexual Problems
Ejaculatory disturbances, impotence, and sexual problems may prevent you from delivering sperm to your wife's vagina. These disorders represent about 10 percent of male fertility problems.

Premature ejaculation, delayed ejaculation, and impotence may stem from surgery, medication, or physiological disturbances which respond well to hormone replacement therapy. Altering sex techniques and counseling often overcome psychologically based sexual performance difficulties.

Making the Diagnosis Is Not Always Easy
Fitting you neatly into one of these categories is not always easy. Sometimes a man will have mild or moderate symptoms or he will have several different problems, so complaints and test results will appear confusing or in conflict. For these reasons, I caution my patients not to jump to conclusions from preliminary test results and not to attempt self-diagnosis. If you have a fertility problem, the only way you can get an accurate diagnosis is to have a complete fertility workup, combined with careful analysis by a professional.

Many people suspect that doctors never read those long complicated history forms you fill out. This isn't true, especially with fertility evaluations. Your general medical history, life-style, and current symptoms provide vital clues that help your doctor pinpoint potential difficulties.

Travel, Work, Hobbies, and Activities
We know that certain chemicals can adversely affect sperm development (spermatogenesis) and lower sperm counts. Since Steven S. had a low count (oligospermia), I wanted to find out if he had ever come in contact with toxic chemicals like lead, pesticides, polystyrene, xylene, benzene, mercury, Agent Orange, anesthetic gases, and solvents. Long-term exposure to these chemicals can cause irreversible damage; however, removing the toxin can often restore fertility.

One unusual case surfaced a couple of years ago when a thirty-two-year-old chemical technician with oligospermia was referred to me by his company doctor. When I questioned Paul W., I discovered that several times each day he used various chemical solutions to clean metal parts. He told me that he often didn't use his safety mask because he couldn't see well with it on. After I talked to the company safety director about the composition of the cleaner, I advised Paul that some of the chemicals he used had been linked to depressed sperm production. "Either use the mask or find another job," I told him. I guess he took me seriously, because without any further treatment I found a marked regeneration of sperm three months later. Before the year was out, his wife was pregnant.

Accidental and medically prescribed exposure to large amounts of radiation to the gonads (to combat a malignant tumor, for example) can also impair sperm production. If your tissue damage is not extensive, however, some degree of fertility may regenerate. (Note: Normal, diagnostic X-ray studies do not impair fertility.)

We also know that excessive exposure to heat can interfere with sperm production. One reason that your sperm-producing testicles are located in your scrotum is to lower their temperature one or two degrees below your body's. I remember one man I treated who worked out at the gym four times a week and afterward soaked in the 106 degree whirlpool. His biceps were bigger than my thighs. When I found his low sperm count, I asked him to give up the whirlpool. Several months later I received a phone call from him saying his wife was pregnant.

Some jobs may overheat your scrotum (from the temperature, not from your boss breathing down your neck) for example, the foundry worker or the sedentary long-distance truck driver. Oligospermia in the wheelchair-bound paraplegic also may be due to excessive scrotal heat. In some situations changing from jockey shorts to boxer shorts may offer a solution. Removal of the heat exposure will usually resolve this type of fertility problem.

It's thought that a varicocoele may also damage testicular tissue because of the excessive heat caused by the pooled blood. Some doctors even diagnose varicocoele by measuring the temperature difference between the right and left sides of the scrotum (measuring scrotal temperature, however, is not standardized and is frequently unreliable).

If you travel frequently, you may not be able to have sex during your wife's fertile time of the month. For example, due to business commitments, Richard and Margaret B. often found themselves in different cities on her fertile days. With only twelve or thirteen opportunities per year for pregnancy, and with only a 20 percent chance of achieving pregnancy each time, infrequent sex can seriously hamper your odds for success. If you have some control over your travel schedule, you can improve your odds for pregnancy by staying at home and having sex during your wife's most fertile days. The rest of the month you can travel all you like. Or, you may choose to have your sperm frozen so that an insemination can be performed in your absence. Infrequent sex can also lead to decreased sperm motility and abnormal sperm morphology (shape). I'll tell you later how to calculate which days are best.

Drugs, Alcohol, and Cigarettes
Since the 1950s more and more people have experimented with "street" drugs and many have continued using them, especially marijuana. If you've smoked marijuana over a long period of time, your semen analysis may show lower sperm motility and higher incidences of abnormal sperm morphology. Both of these factors are critical for fertility.

I'd noticed that Richard B. checked marijuana use on his history form, so I wanted to talk with him about it.

I explained, "We don't understand exactly how it works but we do know that there seems to be a correlation between sperm motility and marijuana use. If you want to maximize your chances, I recommend that you stop smoking."

His expression became serious. "Margaret and I have waited a long time for this baby. I'll do anything that will improve our chances."

I don't think Richard was totally convinced, but he did stop smoking. When his semen analysis improved in just two months, I think he was pleasantly surprised.

We also know that central nervous system depressants such as barbiturates, heroin, and other narcotics cause impotence and ejaculatory disorders. If you stop using these drugs, usually these symptoms resolve themselves.

Chronic alcohol use can lead to impotence, poor sperm quality, and further complications from liver damage. If alcohol damages your liver, you may have elevated estrogen (female hormone) levels. When a man's female hormones become excessive, they suppress his sex drive and interfere with his sexual performance. If you stop drinking alcohol, these conditions may reverse provided your liver can recover.

Though not conclusive, there is indication that some of the hundreds of chemicals in cigarettes may interfere with fertility by elevating the number of abnormal sperm forms. It's difficult to know, however, how smoking may affect any one individual. If you have concerns about the effects of smoking on you, the best strategy might be to cut down or quit smoking entirely.

Stress and Excessive Exercise
We know that stress and excessive exercise can interrupt the normal flow of hormones from the woman's hypothalamus and pituitary. These abnormal hormone levels can interfere with her menstrual cycles and with her fertility.

Some believe that endorphins (natural narcotics) released by the brain to minimize pain and stress may block the normal release of GnRH, which is essential for maintaining male and female reproductive hormone balance. An example of this would be the abnormal (infrequent or absent) menstrual cycles often seen in women who run fifteen to twenty miles a week. Because of the many similarities in the hypothalamus-pituitary hormone system of men and women, there also may be similarities in their responses to stress and excessive exercise.

If you believe that your life-style is too emotionally or physically stressful, try cutting back. Run fewer miles, try to avoid emotional situations, and incorporate more relaxing activities into your schedule.

Medical Disorders
A number of childhood and adult diseases can adversely affect fertility. Some of the changes are only temporary; for example, a high fever (over 102 degrees) may cause your scrotum to overheat and your sperm to die. Usually this type of problem resolves itself in a few months.

Some diseases, however, exert a more lasting effect. For example, cystic fibrosis, tuberculosis, and adult mumps can destroy vital testicular tissues and leave you permanently sterile. Consult with your doctor before you write yourself off, however, because these diseases do not affect everyone the same way.

If you have ever contracted sexually transmitted infections such as gonorrhea, chlamydia, syphilis, and ureaplasma, scar tissue left by the inflammation can partially or totally block your sperm ducts. Bacteria, viruses, and your own white blood cells (Iymphocytes) can attack your sperm and reduce your fertility. Finding white blood cells and dead tissue cells in your semen alerts me to the presence of an active infection. These infections are usually limited to the lower parts of the male genital tractùurethra, prostate, and seminal vesicles. Seldom does the infection travel further in toward your testicles. If infection does reach your testicles, it can cause serious damage.

With the exception of prostatitis, which can be difficult to clear up, sexually transmitted infections will usually respond to antibiotics. If your genitourinary tract becomes scarred from repeated infections, the damaged ducts can often be repaired with microsurgery.

It's vital that your sexual partner also be treated for infection because you can pass the disease back and forth between you. As you'll learn later, sexually transmitted diseases produce far more devastating damage in their female victims.

Systemic diseases such as high blood pressure, colitis, diabetes, and hepatitis can deteriorate sperm quality and cause impotence and ejaculatory disorders. When I found that Michael T. had diabetes, for example, I wanted to investigate its effects on his fertility. Sickle-cell anemia, most frequently found in people with black heritage, may also reduce sperm concentration. Insufficient thyroid hormone has also been linked with low sperm motility and other hormone imbalances. I will discuss the specific treatment options available for these disorders in Chapter 8 .

Kidney problems may also affect your fertility. I remember an executive with a major oil company who developed chronic kidney disease in his mid-forties. He'd had two daughters by his first wife; but his disease-induced fertility problem prevented his new wife from having a child of their own. "My wife really cares desperately about carrying our child," he pleaded. I worked very closely with his nephrologist and together we managed to get him a kidney transplant. With his disease under better control, his sperm count improved, and miraculously the couple produced a baby.

Reports of breast disorders such as tenderness, soreness, and milky discharge or neurological problems characterized by visual disturbances, dizziness, chronic headaches, and/or seizures may lead me to suspect multiple sclerosis, nerve damage, or a problem with the pituitary. Since your brain and your master pituitary gland are vital for maintaining your sex hormone balance, any interruption in their function can impair your fertility. I'll discuss the roles your brain and pituitary gland serve in much greater detail in Chapter 8.

Surgeries
If you have no sperm in your semen (azospermia), but have normally sized testicles and normal hormone levels, you probably have blockage in the ducts between your testicles and your penis. If a hernia repair or lower abdominal surgery is part of your medical history, I'd be suspicious that you had an accidental vasectomy (severing of the vas deferens or duct coming from the testis during surgery). I remember one man who was quite surprised when I told him that a hernia repair he had when he was six years old caused his fertility problem. After microsurgery to reverse the accidental vasectomy, his sperm count came up to 40 million. Skilled surgeons can reverse both accidental and elective vasectomies 90 percent of the time if the reversal is performed within ten years of the vasectomy. Chapter 8 will tell you how this surgery can be done with such precision.

I also need to know if you've incurred nerve damage from a colon resection. This injury can cause both erection and ejaculation problems. If you've had bladder or prostate surgery, you may suffer from retrograde ejaculation. This condition causes you to ejaculate into your bladder instead of out your penis. You can read more about how we manage this problem in Chapter 8.

If you've had surgery for the removal of an adrenal, scrotal, or pituitary tumor, I may suspect an endocrine (hormone) imbalance. Once they're correctly diagnosed, hormonal deficiencies often respond well to hormone replacement therapy. The diagnostic procedures and treatment regimens I use for hormonal problems are detailed in the next chapter.

Medications
We know that certain medications lower fertility by depressing sperm production or impairing sexual performance. For example, if you take high blood pressure medication (antihypertensives) such as reserpine, methyldopa, and guanethidine; or if you consume alcohol or narcotics, you may have difficulty maintaining an erection and suffer from ejaculation failure. In addition, these drugs can lower your sex drive. Hypertension is often treated with medications called calcium-channel blockers (Captopril, Vasotec, nifedipine). These medications appear to effect the ability of the sperm to bind to and fertilize the egg.

Cytotoxic drugs, anabolic steroids, cimetidine (Tagamet for ulcers), sulfasalazine, spironolactone, opiates, and colchicine all may cause depressed sperm production. We also know that antimalarials, tetracycline, amebicides, nitrofurantoin (for bladder infections), propranolol (Inderal), and barbiturates may cause fertility problems. If you take methotrexate for psoriasis or cancer, you may even suffer irreversible germ cell damage in your testes. Many of the drugs I've mentioned are generic; that is, they are the names for the basic chemical compounds. You can check to see if the medication you're taking contains any of these compounds by looking in the Physician's Desk Reference at your library or by asking your doctor. Often by simply altering your medication your doctor can restore your fertility.

Chemotherapy and radiation therapy for cancer may have irreversible effects on fertility. However, if some of your testicular germ cells remain intact, your sperm production may resume when treatment stops. Since every case is individual, you should check with your doctor about your particular situation.

Sexual Development
I also need to know about your sexual development. For example, if you had undescended testes, I need to know if and when you underwent surgery to correct the problem. If you had the surgery before you were six, your testes may be fine. Otherwise, cellular damage that impairs sperm production may have occurred. It's also helpful for me to know if you went through puberty exceptionally early or late (the normal range is nine to sixteen). Sometimes this clues me in to hormone problems.

Sexual Performance
If you have difficulty getting and maintaining an erection, I want to check your general health, your nervous system, your hormone levels, and your exposure to toxic chemicals or medications. Any one of these factors can cause physical impotence. if necessary, your doctor may want a second opinion from a psychologist, neurologist, or psychiatrist. I'll discuss more about treating impotence and erection problems in Chapter 8.

If you become too excited and almost always ejaculate before inserting your penis into your wife's vagina, you'll never get your sperm into her cervix. And you both will be pretty frustrated with your sexual life. Premature ejaculation can often be solved by using the sexual techniques and positions I describe in Chapter 8.

I also need to know how often you have sex and what techniques you use. One of my patients told me, for example, that his father had advised him to have sex three times a day. While this "prescription" for pregnancy may sound reasonable, it actually lowered my patient's fertility potential. He could not possibly make enough sperm that frequently.

It's also helpful for me to know if you've previously fathered a child, or if your wife has had an abortion or miscarriage during her partnership with you. With this information I can establish that you were fertile at one time and begin looking for problems that developed since then. Repeated miscarriages also alert me to the possibility of a genetic problem with either the man or woman.

Since fertility problems often run in families, I need to know if your mother, father, brothers, or sisters have encountered any difficulties. For example, if your mother had a history of repeated miscarriages when she was pregnant with you, she may have taken a drug called DES. Knowing whether or not you were exposed to DES could help me determine if you're suffering from DES-caused testicular abnormalities. I also need to know if your family has a history of hormonal problems such as diabetes, hypothyroidism, or adrenal gland malfunctions. Adding your family history to other clues may help me decide on which areas to investigate more closely.

Your doctor will recommend doing a semen analysis and postcoital test. If these are normal, the doctor's focus will shift toward detecting problems with your wife. If your semen analysis reveals abnormalities, however, your doctor will perform a physical examination and various laboratory tests on you. Your doctor will use the results of your abnormal semen analysis and postcoital test (both discussed in chapter 6), to guide the rest of the investigation into your fertility problem. The following discussion will help you understand what procedures and tests are available and when they should be used.

Oligospermia (fewer than 20 million sperm per milliliter)
If your sperm count shows a concentration lower than 20 million sperm per milliliter, I'll first try to eliminate toxic substances or recent illnesses as possible causes. If your history or life-style does not provide any clues, I will examine your scrotum to determine if your testicular size is normal. Under-developed testicles may be caused by a number of problems which I discuss in detail later. I will also look for the presence of a varicocoele (varicose vein in the scrotum), which may be impairing your sperm production. See chapter 8 for a complete discussion of varicocoeles.

If I find a stress pattern in your semen analysis (low count, poor morphology, and low motility), I'll order blood tests to determine your hormone levels. And if I suspect a genetic problem such as Klinefelter's syndrome, I may recommend checking your chromosomes (karyotyping). chapter 8 describes in detail what these tests will reveal and the treatment regimens available for improving sperm production.

If you do not respond to treatment for oligospermia, you are a prime candidate for artificial insemination with your own sperm (AIH) or in vitro fertilization, in which a surgeon retrieves your wife's eggs (ova) and uses your sperm to fertilize them in a petri dish. The fertilized egg (embryo) is then transferred to your wife's uterus in the hope that it will implant and develop into a baby. The first in vitro "miracle baby" was born less than ten years ago. Now in the United States alone over one hundred clinics offer these services. I'll discuss in vitro fertilization and many other technologically advanced options in later chapters.

Severe Oligospermia (fewer than 10 million sperm per Milliliter)
If your semen analysis shows fewer than 10 million sperm per milliliter, I will check your hormone levels and the size of your testicles. I'll measure your FSH hormone level to determine if your pituitary gland is stimulating your testes to make sperm. If FSH is elevated (indicating testicular failure) and you are not making sperm, the odds of improving your underlying condition are bleak, although in vitro fertilization may work. If I find that your hormones are deficient and your testicles are small, hormone replacement therapy may help you develop normal testicular function.

When your sperm concentration is this low, I may also recommend that a urologist perform a testicular biopsy, which will tell me the condition of your testes at the cellular level. I need to know if your germ cells are dividing and producing immature sperm cells. I also want to know if you have Sertoli, or nurse, cells to shepherd and nurture the immature sperm cells through their five or so stages of maturation. The biopsy will also tell me if your Leydig cells are capable of producing testosterone (male hormone), which is vital for sexual performance and sperm development. I can also see if your testicular (seminiferous) tubules are intact.

If the biopsy reveals that your testicular structures are irreversibly damaged, I probably cannot do anything to improve your sperm production. If the biopsy shows me that your testes are understimulated by hormones, I can prescribe replacement hormones, which may initiate testicular development and establish spermatogenesis. If the biopsy shows me that your testes are normal, then I know that your vas deferens (tube leading from your testicles toward your penis) is partially blocked. Microsurgery may be able to restore the path. Chapter 8 will tell you what can cause these problems and the treatments available to improve oligospermia.

Azospermia
I evaluate azospermia, the condition in which the semen contains no sperm, the same way I evaluate severe oligospermia. However, in addition to performing the tests I do for a severely oligospermic man, I will also test your semen to see if it coagulates and if it contains fructose (sugar). (Azospermic men usually do have semen, because sperm and semen are made in different organs.) Your seminal vesicles make fructose and the chemicals that cause your semen to coagulate. If you were born without seminal vesicles or if your ejaculatory duct is blocked, your semen will not coagulate. I may also examine your urine after ejaculation to see if you have retrograde ejaculation. An ultrasound examination may show a blockage of the ejaculatory ducts where they enter the prostate. Chapter 8 tells you more about the procedures used to manage these problems.

When Do You Need a Vasogram or Testicular Biopsy?
Vasograms (X rays of your ducts) and biopsies of your testicles may damage delicate genital structures. Therefore, your doctor should exhaust all other measures before using these more invasive diagnostic procedures. With less invasive tests, such as an ultrasound of the prostate, I can predict pretty well whether or not you have an obstruction. However, I may need to order an X ray to determine where an obstruction or absent tubal structure exists. This procedure is usually performed under anesthesia at the same time that you are prepared for corrective surgery.

1. If you have severe oligospermia or azospermia; low or normal FSH levels; and do not respond to hormone replacement therapy.

    

2. If you are azospermic; have normal hormone levels and normal testicular size.

1. If you are azospermic and have a normal testes biopsy, you definitely have a tubal blockage. (See Chapter 8 for a complete discussion of tubal blockage and corrective techniques.)

    

2. If you are oligospermic because your testes are performing at an abnormally slow rate, you have hypospermatogenesis.

    

3. If you are azospermic because your testes cannot complete the sperm maturation process, you have maturation arrest.

Hypospermatogenesis
If the biopsy finds hypospermatogenesis (perhaps a phase of maturation arrest), you will show diminished germ (germination) cell activity and marked germ cell loss. Since the germ cells are the precursors of sperm, you will produce low numbers of sperm or no sperm at all. Chemical toxins, drugs, and varicocoeles may cause hypospermatogenesis.

Maturation Arrest
With maturation arrest, one of the most frequent biopsy findings in male fertility, your germ cells divide and produce early sperm forms, and other testicular structures will appear normal. At one stage in their maturation, however, sperm development halts throughout all your testicular tubules. The condition may be complete (azospermic) or partial (oligospermic). Chemical toxins, drugs, and varicocoeles may cause maturation arrest. If your FSH level is high, indicating severe testicular damage, it may be too late for treatment. However, things are brighter if your FSH level is low or normal. Removing the toxins and/or repairing your varicocoele will often restore spermatogenesis.

Testicular Function
Testicular failure represents about 55 percent of male fertility problems.

To respond to hormone stimulation properly, your testicles, or testes, must be capable of producing sperm (spermatogenesis). To assess your testicular potential, I need to know if your testes descended into your scrotum on time; if they have been damaged by a varicocoele (a varicose vein in the scrotum) or by excessive heat, toxins, disease, or trauma; or if for some genetic reason they failed to develop normally. If the damage or failure is severe, nothing much can be done to improve testicular performance. However, testes damaged by varicocoeles (which are found in 40 percent of men with fertility problems) frequently respond to surgical repair. And testes impaired by toxic substances often recover when the toxins are removed.

Posttesticular Function
Tubal obstruction, including vasectomy, accounts for about 6 percent of male infertility.

Your posttesticular system of ducts must be capable of storing and delivering your sperm. Sperm delivery system problems include obstruction or interruption of the tubes as a result of congenital malformation, disease, surgery, or trauma. Laser surgery and microsurgical techniques offer excellent chances for duct repair and restored fertility. Newer techiques allow the urologist to remove sperm directly from the testicle. These sperm can then be injected directly in