Diagnosis and Treatment of Male Infertility -- More Confusion!

The commonest reason for male infertility is a low sperm count, and the commonest reason for this is what doctors call "idiopathic" which simply means, we do not know! This is one of the reasons why the diagnosis of male infertility is so frustrating for both patients and doctors - there are few tests available which allow us to pinpoint the cause of the problem. This also means that there is very little in the form of effective therapy which we can offer these men if we do not know what is wrong, how can we treat it?

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However, what about those conditions which we think we do understand? Let's discuss these in detail.

Varicocele

One of the commonest reasons for a low sperm count according to some doctors is a varicocele. A varicocele is a swollen varicose vein in the scrotum - usually on the left side. The condition occurs because blood pools in the varicose testicular veins (pampiniform plexus) since the valves in the veins are leaky and do not close properly. The reasons for infertility associated with a varicocele are unclear. Perhaps the accumulation of blood causes the testes to become hotter and so damage sperm production; or the pooled blood brims over with abnormal hormones which may change the way the testes make sperm. The effect of the varicocele on an individual's sperm count is variable and this may range from no effect whatsoever to causing a decreased sperm count. Varicoceles may also have a progressively damaging effect on sperm production, so that the sperm count may decline with time.

How is a varicocele diagnosed? The doctor examines the patient in the erect position and feels the spermatic cord the cord like structure from which the testis hangs. The patient is also asked to cough at this time. A varicocele feels like a "bunch of worms" and on coughing, this gets transiently engorged. Confirmation of this diagnosis is best done by a Doppler test at the same time. The Doppler is a small pen - like probe which is applied to the cord. It bounces sound waves off the blood vessels and measures blood flow by magnifying the sound of blood flowing through the veins. This can be recorded. Patients with a varicocele have a reflux of blood during coughing which shows up as a large spike on the tracing. Other tests which are done uncommonly to confirm the diagnosis of a varicocele include: Doppler ultrasound; special X-ray studies called venograms; and thermograms.

What are the areas of controversy about a varicocele? Most doctors are still not sure whether a varicocele causes a low sperm count or not! It is possible that the varicocele may be an unrelated finding in infertile men - a "red herring", so to speak. Strangely enough, only a quarter of men with varicoceles have a fertility problem. Thus, many men with large varicoceles have excellent sperm counts which is why correlating cause (varicocele) and effect (low sperm count) is difficult.

This means that surgical correction of the varicocele may be of no use in improving the sperm count - after all, if the varicocele is not the cause of the problem, then how will treating it help? In fact, controlled trials comparing varicocele surgery with no therapy in men who have varicoceles and a low sperm count have shown that the pregnancy rate is the same - so that it does not seem to make a difference whether or not the varicocele is treated!

Because surgery for varicocele repair is simple and straightforward , many doctors still repair any varicoceles they find in infertile men, following the dictum that it's better to do something rather than do nothing! However, keep in mind that varicocele surgery will result in an improvement in sperm count and motility in only about 30% of patients and it is still not possible for the doctor to predict which patient will be helped. Of course, just improving the sperm count is not enough - and pregnancy rates after varicocele repair alone are in the range of 15%. However, one danger of doing a varicocele repair is that when it doesn't help, patients get frustrated, and refuse to pursue more effective options, such as the assisted reproductive techniques. Today, most infertility specialists would advise infertile men with varicoceles to consider going in for IVF, rather than for varicocele surgery.

There are 4 methods available to repair varicoceles conventional surgery, microsurgery, laparoscopic surgery and radiologic balloon occlusion.

In conventional surgery, a small cut is made in the groin; the spermatic cord is lifted out of the scrotum; and the engorged veins are tied off. This is the commonest method used. The risks include: the risk of the varicocele recurring, which is about 20%, because some of the smaller veins are not identified and are missed during surgery; the risk of hydrocele formation - a collection of fluid around the testes, because lymph vessels are indirectly tied off too, so that more fluid is accumulated - the risk being about 5%; and inadvertent damage to the testicular artery (the blood supply to the testis) - which can actually decrease sperm production!

Microsurgery is a newer method, in which under an operating microscope, the surgeon individually ties off the enlarged veins in the spermatic cord. The testicular artery and lymphatic ducts can be preserved confidently, because the surgery is done under high magnification.

Radiologic balloon occlusion is not very commonly performed. In this minor procedure, a silicone balloon catheter is passed under X-ray guidance to the testicular vein; here the balloon is inflated and left in place permanently, thus blocking the engorged veins and repairing the varicocele.

The "subclinical varicocele": These are tiny varicoceles which cannot be felt by the doctor; but can be detected by Doppler examination. Whether correcting them is helpful or not is still a matter of individual opinion. Many surgeons will combine varicocele repair with medical therapy to try to increase the sperm count, but this is usually not effective.

Duct blockage

If the passage (reproductive tract) between the penis and testes is blocked there will be no sperm in the semen - azoospermia. Blockages can be caused by infection (gonorrhea, chlamydia, filarisias or TB) or by surgery done to repair hernias or hydroceles.

A long and complicated two or three hour microsurgery called a vasoepididymal anastomosis (VEA) can be attempted. This is highly specialised surgery which is best done by an experienced microsurgeon, since the tubes involved are so fine and delicate.

This is a technically difficult and intricate surgery because it needs to be done under high magnification. The surgeon tries to bypass the block, so that the sperm can reach the penis.

Surgical results can be poor for the following reasons:

Technical difficulty, because of the minute size of the tubes; Often be patency cannot be restored, and the sperm count remains zero. The anatomic patency rate is about 50% for most patients (which means that sperm can be found in the semen after surgery).

These sperm are often poor in quality and are successful in giving rise to a pregnancy in only about 25% of patients, as the sperm that make their way out may not be mature or motile since they have not spent enough time in the epididymis, which functions to mature the sperms in the body.

Secondary damage to the epididymis and duct system may have occurred because they have been subjected to high pressure for a long time, causing multiple leaks and blocks, making surgery less successful.

Damage to the functional lining of the epididymis, either as a result of the infection which caused the block or as a result of the high pressure, so that it no longer works effectively and sperms cannot mature here properly. The best chance of success is with the first surgical attempt - repeat surgery has a dismal success rate and is rarely worthwhile.

Congenital absence of the vas (the sperm-carrying tube)

For patients without a vas deferens (a problem they are born with, but which is diagnosed only much later on), the conventional treatment in the past consisted of creating a pouch surgically, into which the epididymis was made to open. This was called a spermatocele and sperm were aspirated from this and used for artificial insemination. However, pregnancy rates were very poor. The technique of PESA with ICSI (as described in the chapter on Microinjection) has revolutionised our approach to these men, and allows many of them to father a pregnancy.

Vasectomy

Men often have this operation to render them sterile once they have completed their family. This is safe, easy surgery which involves cutting the vas deferens (the sperm carrying tube) and sewing it shut, so that sperm passage is blocked. These sperm are absorbed into the body so that although ejaculation is normal, there are no sperm in the semen.

If the man changes his mind after a vasectomy, and wants to father another child, microsurgery can rejoin the cut ends so that the sperm can once more pass through into the semen. This reversal surgery is called vasovasostomy or VVA (vasovasal anastomosis). It is expensive and only a few doctors are adequately trained to perform the operation - and even then success is not guaranteed. The best results are when the reversal process is performed within 5 years after the vasectomy before the development of antisperm antibodies. Good surgeons have reported pregnancy rates of as high as 80% using meticulous microsurgical technique.

Immunity problems with sperm

If varicoceles are controversial, immune sperm problems are even more so. However, while the controversy surrounding varicoceles is now quite old, the immune problem is a relatively newer area, which means we have even more questions about this, and even fewer answers!

In one of Nature's quirks, men can develop antibodies to their own sperm; or the wife can develop these against the husband's sperm. What happens is that the body's defense mechanism destroys its own sperm; or the wife's hostile cervical mucus does so, as though the sperm were enemy bacteria or virus. This can happen after problems of inflammation, injury to the testes, surgery, infection or blockage.

Problems start with making a diagnosis. Antisperm antibodies are suspected when the sperm clump to one another (agglutinate) on a sperm test. A poor postcoital test, which shows all immotile sperm in the mucus is also a tip-off, because one of the reasons for this is cervical mucus hostility because of antibodies.

There are many tests available to detect sperm antibodies. Blood tests for antisperm antibodies can be done for both the wife and husband using ELISA methods. This is an easy test to do but interpreting it is hard what does a postive test mean? Could it be responsible for infertility? Most doctors don't think so, because they argue that the presence of these antibodies in the blood is of little clinical importance - but the debate goes on! These older tests are now considered to be obsolete. The newer antibody tests which are more reliable, are done on the sperm itself, using immunobead testing, and these can tell the doctor whether the antibodies are on the sperm head or tail. However, interpreting the significance of a positive result remains a vexed issue!

Treatment is equally confusing - and included testosterone injections in the past in order to suppress sperm production - the rationale being that if there are no sperm there will be no further formation of the battling antibodies! Corticosteroids have also been used successfully to stop a person from making antibodies, but these drugs can have significant side effects, as a result of which they are not considered standard therapy today. Today, washing the sperm in the lab to clean away the seminal fluid which contains the antibodies, along with timed intrauterine insemination (IUI), is the first-line treatment. For more difficult patients, where the antibodies are tightly bound to the sperm head, IVF and even ICSI may be needed.

Hormone imbalance

Unlike women, hormone imbalances in men are not a common cause of fertility problems. These problems can stem from organs as far apart as the brain or the testicles, and can show up in blood tests. They can arise because of:

Head injury
A tumour in the pituitary gland at the base of the brain
A tumor in the adrenal gland, above the kidneys.
Malfunctioning of the pituitary gland
Cirrhosis of the liver
Conditions present from birth, such as Klinefelter's syndrome (47, XXY syndrome)
A thyroid problem
One problem is that of hyperprolactinaemia (a high prolactin level). This is usually caused by a pituitary malfunction or tumour; and can be detected by a blood test. Patients with hyperprolactinemia often also have decreased libido and may be impotent. Treatment with bromocryptine to suppress the high prolactin levels is highly successful in achieving pregnancy.

Another problem is that of hypogonadotropic hypogonadism (poor functioning of the testes because of their inadequate stimulation by the gonadotropic hormones, FSH and LH produced by the pituitary). Most hypogonadotropic patients are hypogonadal - that is, they have low levels of the male hormone, testosterone. This means they have poorly developed secondary sexual characters; an effeminate appearance, scanty hair, decreased libido, and small flabby testes. This can be confirmed by blood tests which show low levels of FSH and LH. This can be treated by replacement therapy most commonly with the gonadotropin hormones ---- HCG and HMG. These are expensive injections and a fairly long course of treatment (6 months to 1 year) is needed for them to work but they are usually effective in enhancing sperm production in these men. An alternative for some of these men is therapy with GnRH analogs, which are administered via a pump.

Substance abuse

As Shakespeare said Alcohol, tobacco and drugs can all damage sperm production. "Alcohol increases the desire but takes away the performance." Not only are alcoholics unable to perform, but their liver function also deteriorates, resulting in excessive levels of the female hormone, estrogen, which has a severe sperm suppressing effect.

Drugs of abuse (such as marijuana) can also create malformed sperm with poor motility; they also alter hormonal balance and testicular function; and cause impotence and erection problems.

Tobacco is a potent toxin. It attacks the tail of the sperm so that it is unable to swim to its goal. The testicular artery can go into spasm because it is choked with nicotine. Prolactin levels in smokers tend to be higher, so sexual desire often disappears in smoke.

This is why men with low sperm counts are urged to stop smoking, drinking alcohol and abusing drugs. However, it is impossible to predict the extent to which sperm function will improve on stopping these toxins.

Undescended testes

Undescended testes are a tragic cause of male infertility, since often it is preventable. Some babies are born with one or both testicles up in their bellies instead of hanging down in the scrotum. Sometimes the condition might correct itself by the time the toddler is around 2 years old. (Don't worry unduly if you find the testes "disappearing occasionally" from the scrotum of a young boy. These are called "retractile" testes, and are very common.) However, if left unattended, the undescended testes tend to get damaged by the heat in the abdominal cavity; and they can even become cancerous in adult life. The child should be operated before two years of age or else fertility can be lost forever. Treatment with hormonal injections (HCG injections) to cause testicular descent is another alternative.
Torsion

If one of the testicles has undergone torsion (the technical term for twisting), it could be damaged since it is starved of blood.

Signs of torsion are an excruciating pain and swelling of the testicle. Sadly, it is often misdiagnosed as a testis infection, and left untreated. This causes the testis on that side to shrivel up and die (atrophy). The best way to make the diagnosis of torsion is with a Doppler ultrasound; and emergency surgery is needed rightaway, to untwist and fix the testis. The other testis must also always be fixed surgically to prevent it from undergoing torsion. Unfortunately, after testicular torsion, sperm antibodies are often produced and these may decrease sperm production in the other testis.

Infections

The commonest reason for azoospermia in India used to be smallpox --- the virus attacks and damages the epididymis, causing ductal obstruction. Tuberculosis also damages the epididymis, causing azoospermia. However, making a specific diagnosis of tuberculous epididymitis can be very difficult, because it is often a silent and indolent disease. Gonorrhea, chlamydia, syphilis and other STDs can also play havoc with the male genital tract, causing irreparable damage to its epithelium (internal lining). Mumps can also cause orchitis (inflammation of the testis) --- especially when it affects young men. This can cause severe damage to the testes, resulting in testicular failure.

What about other genital tract infections? Many doctors will do a semen culture, to look for a treatable cause of infertility, if the semen sample shows many pus cells. If the test is positive treatment with antibiotics is instituted. Male reproductive tract infections (such as prostatitis) are often chronic, and may require many weeks of antibiotic treatment. It is therefore important to recheck the semen culture after therapy, to ensure that treatment has been adequate. However, the relation between the presence of bacteria in the semen and male infertility is still unclear. Do the bacteria really cause the infertility? Does treating the infection help to improve fertility? More questions than answers, once again!

Medication and its effects

Some medications can play havoc with the sperm count or with the sex drive. These include:

Drugs for high blood pressure like reserpine, methyldopa, guanethidine, and propranolol; nitrofurantoin for urinary infection; corticosteroids; anabolic steroids for muscle building; and anti psychotic drugs.

A rare problem is that of anti cancer drugs and radiation therapy --- used to treat young men with Hodgkin's disease, lymphoma, leukemia and testicular tumours. In these men, the chemotherapy and radiation therapy used to treat the disease also wipes out sperm production, rendering them sterile. An option available today is to store the sperms (sperm banking) which can later be used for inseminating the wife to achieve a pregnancy.

Detrimental effects of heat

The testicles are in the scrotum because they can't make sperm at body temperature - they need a cooler environment so they hang outside the body where the temperature is 0.8 degrees centigrade cooler. Tightly encased groins because of jock straps, tight jeans, lungottis, and nylon briefs cause the testicles to be pressed back into the warmth of the body and literally cook the sperm to death --- especially when combined with hot tub baths and saunas. Working in hot sedentary jobs for long periods like foundries, boiler plants and engine rooms may also cause a lower sperm count as the testicles get too hot.

In the past, doctors used to advise men to wear loose fitting cotton trousers and cotton boxer shorts; and apply a cold ice water soaked towel around the scrotum at least two or three times a day. However, it is very unlikely that these measures help to improve the sperm count.

Occupational hazards

These affect fertility by upsetting the hormonal balance and suppressing sperm production. Dangerous chemicals include: heavy metals, like lead, nickel, mercury; insecticides, petrochemicals, pesticides, benzene, xylene, anaesthetic gases, and X- rays.

Ejaculation problems

Very often a perfectly fertile man may not be able to ejaculate. Since he can't make love he can't make babies. Some men can't have an erection (impotence) and some cannot achieve an erection sufficient for intravaginal penetration or ejaculation in the vagina.

An older theory held that 80% of impotency problems (which are very common) were rooted in psychological inhibition and fears which could respond to sex therapy and counselling. However, modern research has lowered this figure and estimates that 50% are due to physical causes ranging from inadequate blood flow to the penis, diabetes, neurologic defects, and hormonal problems.

How does the doctor suspect a physical problem? By asking a simple question --- Do you have wet dreams? If men have nocturnal ejaculations (wet dreams) this would suggest that the physical apparatus is sound, and that the problem is psychological.

Testing includes nocturnal penile tumescence (NPT) testing, which monitors for normal night-time erections; and measuring blood flow through the arteries of the penis (using Doppler methods).

Treatment that may be prescribed includes:

Viagra (sildenafil citrate) to induce an erection
Injections of papaverine and prostaglandins (chemicals which cause blood vessel to dilate)can be self- injected into the penis under medical supervision. These substance increase the blood flow to the penis, thus creating an erection.
A surgical implant or penile prosthesis to give an artificial erection.
Microsurgery to plug leaks in the veins of the penis. In some men who have leaky veins (venous incompetence), thus preventing the loss of turgidity of the erect penis.
The sperms can also be collected by masturbation and used for artificial insemination. This has a very high success rate, because there is really no fertility problem as such for these patients.

Retrograde ejaculation

This means that the semen goes backwards into the bladder instead of coming out of the penis, so that very little or no semen is ejaculated at the time of orgasm, and the urine looks cloudy after having sex. This occurs when the bladder sphincter muscle does not contract properly during orgasm, as a result of which the semen leaks back from the urethra into the bladder. This could be caused by prostate surgery, a spinal injury, diabetes, high blood pressure, medication and congenital problems. A simple way to diagnose retrograde ejaculation is to examine a man's urine after he ejaculates. If there are sperm in the urine, this confirms the diagnosis.

Self-help includes trying to have sex with a full bladder and while standing up, because this makes the muscle around the opening of the bladder more likely to stay closed. Some medications like decongestants can also help the sphincter muscle to close. Surgery can also be performed on the opening of the bladder to prevent it from misbehaving but this is not very successful.

An effective treatment option is to collect the sperm and use it for artificial insemination. After passing urine, the man alkalinizes his urine by drinking sodium bicarbonate; and then urinates immediately after ejaculation. The recovered sperm in the urine are processed and used for insemination. Pregnancy rates with insemination are usually low because the recovered sperm are often of poor quality, and sometimes IVF needs to be done with these sperm to give a reasonable chance of pregnancy.

Anejaculation

Some men find that they can get an erection, but they are unable to ejaculate. This is an uncommon problem, and is often not diagnosed correctly. Most of these men can be helped by teaching them to use a vibrator in order to ejaculate. A vibrator is a simple device, which is easily available at most chemists' shops, and is often called a body massager. The surface of this vibrates rapidly, and it is used to provide prolonged mechanical stimulation to the frenulum of the penis, until ejaculation occurs.

Electroejaculation for spinal cord problems

Men with spinal cord problems who cannot ejaculate can now be helped to father a pregnancy with the help of a new technique called electroejaculation. A probe is inserted into the man's rectum (under general anesthesia) and electrical stimulation delivered to the prostate in a gradually increasing fashion to induce an ejaculation. The man usually attains an erection and ejaculates in about five minutes. The recovered sperm can then be used for IUI, IVF or ICSI, depending upon their quality (which is usually poor).

Treating the couple

If the man has a low sperm count, since so little can be done with conventional therapy to improve the sperm count, today we usually offer them one of the assisted reproductive technologies. This might seem unfair, since the wife is being treated for what is essentially the husband's problem, but the fact of the matter is that there is very little effective therapy for a low sperm count. Since the fertility of the couple is the sum of the fertility potential of both the partners, a male factor problem can often be treated by treating the wife!

Conclusion

Conventional treatment of male infertility has poor success rates and leaves a lot to be desired. However, the availability of assisted reproductive technology in recent times has revolutionised our approach to male infertility, and using techniques such as IVF and ICSI, most men can be helped to have their own babies. This is a rapidly developing area, and the spectacular advances which have occurred in recent times are described in the chapters to follow.

Credits: Dr. Aniruddha Malpani, MD and DR. Anjali Malpani,