Male Infertility

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Assisted Reproductive Technology Is Not The Only Treatment

By Robert W. Hudson MD, PhD, FRCPC,

The inability to achieve a spontaneous pregnancy continues to affect approximately 1:7 couples. Studies have shown that a male factor is involved in nearly 50% of such situations, with the male being the primary contributor in 1/3 of cases.

There has been a tremendous advancement in our understanding of sperm-egg interaction over the last decade and a half and the success of assisted reproductive technology (ART) over the last 10 to 15 years has resulted in pregnancies, for many couples, that would not have been possible before. The development of reliable ART techniques has allowed even men with extremely low sperm counts the opportunity to have children of their own.

 Because of the success of ART, some clinicians, and even some patients, have stated that there is little value investigating men who present as part of a subfertile couple. They say that one should just offer the couple ART. This may not always be the best therapeutic regime.

There are several reasons why the male partner of a couple seeking fertility should be investigated and why therapy, other than ART, should be considered.

 • There may be geographical, societal or financial issues that makes ART difficult, or even impossible, for some couples.

 • Some causes of male subfertility may be correctable.

 • Some situations of reduced sperm density or motility may be associated with other diseases that may impact adversely on the individual if not corrected.

 • Reduced sperm density or motility may be associated with subtle, or apparent defects in testosterone production.

 • There is well established evidence that men have a fall in testosterone with age (andropause). This fall may occur earlier and be more profound in those men with conditions associated with defects in testicular function. Therefore, the manifestations of the andropause, including the development of osteoporosis, muscle wasting and weakness, sleep disturbances, mood disorders, etc., may occur earlier and be more profound in these men.

As a result, it is difficult to make a convincing argument against investigating the male when a seminal abnormality is found.

 Regulation of Testicular Function

 The two functions of the testes, sperm production and hormone production, are intimately related.

 Testicular function begins in the brain, in an area called the hypothalamus. The hypothalamus secretes a hormone (GnRH) which stimulates the pituitary gland. The pituitary, in turn, stimulates the testes to produce testosterone and sperm. The testes help regulate their own function by sending hormone signals to the brain and pituitary gland.

Disruption of any part of the hypothalamic-pituitary-testes connection can result in a reduction in both sperm and testosterone production.

The presence of chronic diseases such as diabetes mellitus, kidney disease, or GI disease also may adversely affect testicular function in some patients.

 Causes of Male Infertility

 A number of conditions may disrupt the normal control of testicular function.

 Hypothalamic Pituitary Disease

 Tumours near the hypothalamus or in the pituitary gland may result in a reduction in their stimulation of the testes, with a reduction in both sperm production and testosterone secretion. Tumours in these areas may produce adverse effects in addition to their effect on fertility. The function of other glands, controlled by the pituitary, such as the thyroid and adrenal glands, may be compromised, leading to other health problems.

 Some conditions affect testicular function directly. These can be congenital or may occur after birth. Patients may be born with abnormalities of chromosome (congenital), or undergo damage to the testes after birth – e.g. Develop inflammation after mumps, have severe injuries, or be exposed to chemotherapy or irradiation. Some men have a condition called a varicocele – dilated veins in the scrotum. These varicocele may impact on sperm production and, in some men, hormone production.

 Genital Tract Disease

 Obstruction to the channels by which the sperm leave the testes may not permit the sperm to be released. The causes can be congenital or acquired.

Some men may have antibodies against their sperm. The cause is usually not known but these antibodies may reduce sperm motility.

 Thyroid disease, either hyperthyroidism or hypothyroidism sometimes impacts adversely on testicular function and fertility potential. Usually, with correction of the thyroid disorder, fertility is restored. The presence of chronic illnesses may impact adversely on male fertility. Optimal control of these diseases may result in improved fertility potential.

 Investigation of Male Infertility

 In order to try to define the cause of reduced fertility, a complete history and physical exam and laboratory investigation should be undertaken to assess the overall health of the individual and to identify the presence of any chronic or recently acute illnesses. Specific attention should be paid to determine the presence, or absence, of any signs of any diseases which can impact adversely on testicular function.

 The hallmark of the assessment is the semen analysis wherein the sperm density, the motility and the characteristics of the spermatozoa are determined. At least two semen analyses should be performed one month apart. The specific lab requirements for obtaining the sperm should be followed accurately. If abnormalities are found further testing will depend on the nature of these abnormalities and the information obtained through the history and physical examination.

 A measure of testosterone and the pituitary hormones LH, FSH and prolactin should be undertaken. Elevated levels of FSH and LH with low or low normal testosterone levels indicate that the problem lies in the testes. It is likely that no therapy will improve the situation. Under these circumstances, one can consider doing genetic studies. ART may be successful in achieving a pregnancy, but if there are genetic abnormalities, counseling should be undertaken regarding potential transference of the abnormalities to the baby.

 If LH, FSH and T are low and prolactin is high, further assessment of the pituitary gland with special radiological tests is in order.

 There are therapies which are available that are specific for some causes of male infertility. Some of these treatment regimens may improve fertility and impact positively on other aspects of the individual's health.

 1. Hypothalamic-Pituitary Disease

 Tumours of the hypothalamus, or the pituitary, often can be removed surgically. These tumours most often are benign. With respect to fertility, treatment with GnRH, or the pituitary hormones LH and FSH may help restore fertility. Testicular function often returns to normal.

 As stated previously, no therapy, apart from ART, likely will affect fertility status.

The exception is the varicocele. The success rate for an increase in semen parameters and pregnancy rates is good.

 3. Genital Tract Disease

 Obstructions of the genital tract often can be improved with surgery. The advances in microsurgical techniques over the last decade have improved the success rate, greatly, for many patients. Infections can be treated successfully by specific antibiotics, improving sperm motility and pregnancy rates.

 There is no question that the advances in our understanding and use of ART have resulted in many successful pregnancies for couples over the last decade and a half. Many more men have been able to have their own children through ART. However, an evaluation of the male presenting for assessment of his fertility needs must be undertaken carefully to identify, and treat, those conditions that may impact not only on his fertility, but also on his overall health.

ABOUT THE AUTHOR: Dr. Robert W. Hudson is Professor and Chair, Division of Endocrinology and Metabolism, Queen's University, and The Kingston General Hospital, Kingston, Ontario.