Azoospermia - Treatment and Evaluation for Male Infertility

Azoospermia is the complete lack of sperm in the ejaculate. It occurs in 5% of infertile men. If this is the case, then one or both of two conditions may be present:

A) There is a problem with sperm production.

B) There is a blockage such that sperm production, although normal, cannot reach the ejaculate.

One important point concerning this diagnosis is that although no sperm are found in the ejaculate, there are often usable sperm found in the testis, as not all sperm that are made in the testis actually make it into the ejaculate. There is a "threshold" effect with sperm production, such that if production of sperm is high enough in the testis, then sperm"spill over" into the ejaculate. However, if that critical level of sperm production is not met, there may still be mature sperm in the testis that do not make it into the ejaculate. This concept is the basis for the statement that "sterility may beget fertility." As an internationally recognized pioneer in managing this condition, Dr. Turek sees hundreds of men every year with this diagnosis and he offers a brief, thorough, state of the art evaluation for this problem.

First, a thorough review of medical problems, exposures, past surgery, medications, and family history is undertaken in the office to help define causes of azoospermia. Then, a brief, well-performed physical examination is performed. Third, blood tests are taken that include testosterone and follicle stimulating hormone (FSH). Fourth, two semen samples are needed. With each sample, a standard semen analysis is performed. If no sperm are found, then the semen sample undergoes an additional evaluation in which the sample is "spun" down in a centrifuge to concentrate small numbers of sperm at the bottom of the tube. This "pellet" of the ejaculate is then examined thoroughly for sperm by an experienced lab technician. If 10 sperm or even 1 sperm is present in the pellet analysis, then conditions such as reproductive tract obstruction are painlessly disproved. In Dr. Turek's experience, there is a 20% chance that men with no sperm on semen analyses performed without a centrifuged pellet will have sperm if such a procedure is performed in his laboratory. Again, the value of finding even a small number of sperm in the pellet analysis is very significant because: 1) it means that complete obstruction is unlikely, and 2) it means that men may have the option of using ejaculated sperm for conception with assisted reproduction and may be able to avoid sperm retrieval procedures for this purpose. Based on this evaluation, if it is not entirely clear as to whether there is a problem with sperm production or a blockage, then further testing may be needed.

If, based on the above evaluation, it is not entirely clear as to whether there is a problem with sperm production or one of a blockage in the ducts of the reproductive tract, then the next step is to examine the testis itself and assess sperm production. This can be done in several ways, but the classic approach is to perform a testis biopsy under local anesthesia. This allows for the direct inspection of a small piece of testis tissue to determine whether sperm production is normal or not. Testicular tissue contains (a) sperm-producing cells that are found in tubules called seminiferous tubules, and (b) cells between the tubules that are called interstitial or Leydig cells. The Leydig cells are the major hormone-producing cells. The biopsied tissue is specially stained and examined microscopically for both cell types by a pathologist. If it shows that sperm production is normal, then a blockage exists in the system, usually beyond the testis. Remember that a biopsy does not tell us where the obstruction is located within the system. The most common testis biopsy patterns observed in a testis biopsy specimen are listed below. Dr Turek has created a systemic way to interpret the testis biopsy that he has taught others for years to decide what pattern is present (see figure below).

In Dr. Turek's experience, the testis biopsy has several limitations. For one, it is invasive. Second, it only provides information on the area that is biopsied and tells us nothing about sperm production in the rest of the testis. Third, how clinicians read the biopsies varies widely, making the interpretation unclear, a fact that does not help the patient. In fact, Dr Turek has published on this issue of how testis biopsy interpretations vary in a series of testis biopsies from patients who had had the biopsy procedure done before they consulted with him. In this study, he compared his interpretation of the biopsies from patients to the readings made by the pathologists from the community in which the biopsies were performed. He found that in 40% of cases, the interpretation that he made was different from the pathologist's interpretation and that in 25% of cases, patient care was altered dramatically as a result of his re-review. An example of a significant alteration in care is a biopsy in which the community pathologist read as having no sperm but Dr. Turek's reading suggested that there were sperm. For these reasons, the testis biopsy currently plays a limited role in the cutting edge care of azoospermic men. In addition, this is why Dr. Turek offers to re-review the testis biopsy slides that are sent to him as part of his Second Opinion Clinic.

Is There Something Less Invasive than a Testis Biopsy
for Evaluating Azoospermia?

Because of the recognized limitations of the testis biopsy, about 10 years ago Dr. Turek pioneered a nonsurgical, less invasive alternative to the testis biopsy that is termed fine needle aspiration (FNA) "mapping" for men with azoospermia. He has performed over 800 cases over the last decade and "FNA mapping" is now popular throughout the world.

FNA "mapping" involves using a very fine needle to "map" out sperm production in the testis without making a surgical incision. Applying fine needle technology to the testis is not a new idea, but in fact is almost 100 years old. What's new is Dr. Turek's concept of "mapping" the testis to specifically locate sperm and determine whether men are candidates for assisted reproduction to help them become fathers. Mapping is important because it can help couples decide whether it is reasonable to spend thousands of dollars on an IVF cycle and testis sperm extraction (TESE). This procedure takes less than an hour and is performed in the office under local anesthesia. Recovery is rapid and complications are rare ( less than 1%). The figure shows how FNA mapping is used in the clinical pathway of male infertility due to azoospermia.

FIGURE 2. THE CLINICAL PATHWAY USED BY DR. TUREK TO DECIDE IF MAPPED PATIENTS ARE CANDIDATES FOR ASSISTED REPRODUCTION.

More information on FNA mapping can be found elsewhere on this website. There is also information about preparing and recovering from the FNA mapping procedure that might be of some help to you.

Conditions that cause azoospermia are listed in Table 1. If at all possible, treating the specific condition that is causing the azoospermia may reverse the process and lead to sperm production. This is especially true for azoospermia due to hot tubs or hot baths or testosterone supplements. In other cases, such as genetic infertility, this is not possible and assisted reproduction offers the best solution to family building.

Clinically, it is important to determine whether men with azoospermia have an obstruction as a cause of the problem as this can be treated and reversed with microsurgery. If sperm production is normal, as determined by a biopsy or FNA mapping, then the azoospermia is caused by an obstruction. Typically, in an obstructed man without an obvious reason for the problem, a blockage can be found in the epididymis 65% of the time, in the vas deferens 30% of the time and in the ejaculatory duct 5% of the time. The actual location of the blockage can be pinpointed with microsurgery, and the procedure involves opening the vas deferens and inspecting the entire length of the tube with colored dye or with the help of X-rays. Surgery can be performed at most of these sites to repair the blockage. Indeed, Dr. Turek specializes in this kind of microsurgery and has superb success rates for achieving moving sperm in the ejaculate and pregnancy in cases of blockages in the epididymis (the most difficult area to repair in the system) not due to vasectomy (Table 2).

In cases of nonobstructive azoospermia in which sperm production is not normal, then it is assumed that obstruction does not exist. In a few cases, this condition is medically treatable (Kallman syndrome, hyperprolactinemia); in most instances however, the only hope for building a biological family is to use sperm retrieved from the testis with assisted reproduction in the form of IVF and ICSI. One of the most difficult aspects of nonobstructive azoospermia, is that while testis sperm retrieval in men with obstruction is not difficult, there is a failure to obtain sperm for ICSI in up to 50% of men with nonobstructive azoospermia. In addition, recognized clinical features like testicular size, history of ejaculated sperm, serum FSH level, or biopsy reading, do not accurately predict whether or not sperm will be recovered from the testis. Importantly, it has become clear to Dr. Turek that as the number of samples from the testis is increased, the chances of finding sperm also increase.

FIGURE 3. CHANCE OF FINDING TESTIS SPERM IN NONOBSTRUCTIVE MEN BY SAMPLE NUMBER (MAP=8 SAMPLES).

Currently, several strategies are used to find sperm in these men and to minimize trauma to the testis during sperm harvest. This kind of thinking is important to minimize the emotional and financial costs associated with cancelled IVF cycles. This kind of thinking has also led Dr Turek to pioneer the FNA mapping technique, which is well suited for these patients. Indeed, Dr Turek is a thought leader and is internationally renowned for his comprehensive approach to the management of men with nonobstructive azoospermia.