Some of the connections between genes and disease that we accept as fact may not be so strong after all. More >
This conference was created with the expert advice and counsel of Dr. Anthony J. Thomas, Jr., Head, Section on Male Infertility, Glickman Urological Institute, Cleveland Clinic Foundation. Dr. Thomas is an expert in andrology, the subspecialty of urology dealing with male reproductive function. I would especially recommend Dr. Thomas's book, written for the lay public, Overcoming Male Infertility, published in 2000.
Suppose you are one of the 10-15% of couples in Western countries who want children but are experiencing problems with fertility.(1) Where do you go for help? Just as there are many causes of infertility, there is a wide range of available remedies, from seeing your primary physician for a basic medical exam and information about the best timing of intercourse for conception to placing the entire reproductive process under the control of a specialist. When you do seek help, however, it can be helpful to have educated yourself about the current state of knowledge about infertility and infertility treatments. In this article, we will discuss male infertility, a problem that is far more common than many people realize.
Statistically, 30-40% of fertility problems are caused by problems with the male, and 30-40% by problems with the female. The remainder either are caused by a combination of problems on both sides or are unknown. The Centers for Disease Control collects data from fertility clinics doing in vitro fertilization. Their latest figures on infertility causes in couples in which the woman is under 35 are: 40% female, 23% male, 17% combined male and female, 10% more than one female factor and 10% unexplained.(2) By either measure, male infertility seems to be a significant factor in about 40% of couples who have infertility problems.
What Are Infertility, Subfertility, and Sterility?Doctors use these and other terms to define different types of fertility-related conditions. Even so, the definitions of the above terms have changed as technology has advanced.
Sterility is the absolute inability to procreate. For instance, a woman has no uterus or a man has no testes (the male sex organs). In years past, a woman with blocked fallopian tubes or a man with an obstructed vas deferens would be considered sterile and beyond help. With the advent of assisted reproductive technology (ART), however, this is no longer the case. Many couples who were once in this category can now get help.
Infertility is usually defined as the inability to achieve pregnancy after one year of frequent, unprotected intercourse. This is not an exact measurement. Over time many couples in this category may, in fact, achieve pregnancy. Statisically, after five years, nearly one half of so-called "infertile" couples do conceive.
Subfertility is used to describe the gray area between normal fertility and sterility; the term is often used interchangeably with infertility.
Fecundability, from "fecunditas," the Latin word for fertility, is the average pregnancy rate after one menstrual cycle. The normal rate in humans is 20%. Seventy-five percent of normally fertile couples are expected to have conceived in six months, and almost 100% by one year.
Normal fertility can be considered from the point of view of the couple, the female, or the male. We are going to look at male fertility — its biological steps and mechanisms, defects, the causes of those defects and what can be done to remedy them.
Normal Male FertilityAs male factors have been increasingly implicated as a major cause of infertility, investigators have focused on the underlying physical processes in men. If the sperm count is low, then why? Or, if the sperm count is normal, why do the sperm not fertilize?
That there are literally dozens of factors leading to a completely normal spermatozoon, the form of sperm that is present in semen. These involve the structure of the testis; the hormones that influence its function; the receptors for these hormones; the maturation process through which the germ cell develops into a spermatozoon; the composition of the seminal plasma; and all the enzymes, receptors, and reactions that make the sperm capable of fertilizing the egg. In these steps, there are dozens of occasions for mistakes and problems. First, let us look at how male fertility works when it works correctly.
Role of the PituitaryThe testis, or testicle, has two main parts. What is called the interstitial portion contains the Leydig cells, which produce the male hormone testosterone and are sensitive to another hormone called luteinizing hormone (LH). The other component is the seminiferous tubules, which contain the Sertoli cells and the germ cells; these are influenced by follicle stimulating hormone (FSH) and testosterone. LH and FSH are secreted by the pituitary gland in response to gonadotropin releasing hormone (GnRH), which is a substance secreted from nerve cells in a part of the brain called the hypothalamus. GnRH goes directly to the pituitary gland in pulses which range from once an hour or 1-2 times in 24 hours. There is a negative feedback loop by which GnRH is "turned off" by testosterone. FSH is also turned off by inhibin, a substance which is secreted by the Sertoli cell.
It is important to remember that GnRH is secreted in pulses, because if it is introduced to the body in a steady dose, for example by taking the drug leuprolide acetate (Lupron® or Zoladex®), the pituitary will stop secreting LH and FSH, testosterone levels will decrease; and spermatogenesis, or the production of sperm, will stop. A second important point is that excessive testosterone — whether given for replacement, bodybuilding, or other purposes — can inhibit GnRH and sperm production.
Finally, the pituitary hormone prolactin (PL) can sensitize the LH receptors on the Leydig cells that produce testosterone. Prolactin also affects the function of both the prostate gland and the seminal vesicles. Elevated PL, which is often caused by a growth called a pituitary adenoma, can therefore interfere with GnRH function.
(2) Comments have been made