What is “azoospermia”?

Azoospermia is the medical term used when there are no sperm in the ejaculate. It can be “obstructive,” where there is a blockage preventing sperm from entering the ejaculate, or it can be “nonobstructive” when it is due to decreased sperm production by the testis.

Is azoospermia common?

Yes. Around 10 percent of infertile men and 1 percent of all men have azoospermia. Imagine a stadium with 50,000 men attending a game — around 5,000 to 7,500 of those men will have infertility, and 500 of those men will be azoospermic!

What causes azoospermia?

We know of many potential causes, including some genetic conditions such as Klinefelter’s syndrome, medical treatments such as chemotherapy or radiation, recreational drugs such as some narcotics, and anatomical abnormalities such as varicoceles or absence of the vas deferens on each side. Perhaps the most obvious cause would be a vasectomy, which prevents sperm from joining other fluids in the ejaculate. In most cases, though, azoospermia is likely due to factors we don’t fully understand, such as genetic conditions, poor testicular development as a fetus/child or environmental toxins.

I had a semen analysis showing azoospermia — what should I do?

Aside from seeing a specialist in male infertility, the first step would be to get a repeat semen analysis at a lab that has a lot of experience doing semen and sperm tests, because results can vary a lot from test to test and lab to lab. Also, having small numbers of sperm can change the management/treatment options drastically, so the first step should be getting proper confirmation of the finding.

Can we tell whether it is due to a blockage problem versus a “factory” problem?

Not with 100 percent accuracy, but we have some good indicators. First, a very careful physical exam is crucial to assess the reproductive structures. In addition, lab tests such as FSH and inhibin B can give an indication of testicular function.

Does having azoospermia mean that the testis makes no sperm?

Not necessarily. The testis can be making sperm, but it might not be enough to have any noticeable amount come out in the ejaculate.

Should azoospermic men undergo a diagnostic testis biopsy?

In the past, almost all men with azoospermia underwent a biopsy to distinguish obstructive from nonobstructive causes and to try to get an even more specific diagnosis. However, in modern practice, biopsy is rarely performed alone. In most cases, we can predict with high accuracy whether or not a man has an obstructive cause of azoospermia. Since we have started performing testicular dissections to search for sperm, we have learned that different areas of the testis might show different patterns of nonobstructive azoospermia. For example, one area might show decreased production of mature sperm (hypo spermatogenesis or maturation arrest), while another area might show the complete absence of sperm precursor cells (Sertoli-cell-only syndrome). Thus, in the modern era, doing a diagnostic biopsy does not often change the ultimate management for men with nonobstructive azoospermia. For those men, we offer microdissection testicular sperm extraction (microTESE), which gives the best chance of finding sperm that can be used for assisted reproductive techniques (ART). Sometimes, at the time of the microTESE, we will send a tiny specimen for pathological evaluation to rule out a precursor to malignancy called intratubular germ cell neoplasia (ITGCN).

What treatments are available? What is the best treatment?

Of course, it depends on the cause, but for any given patient, the best treatment is a customized approach based on many factors, such as partner’s age and reproductive function, physical exam findings, blood test results, long- and short-term family goals and even finances. Depending on the suspected causes, many treatments may be available. If there is a blockage (or history of vasectomy), reconstruction might be the best treatment for some men. In others, removing offending agents such as medications or recreational drugs might be the first step. Sometimes there may be hormonal abnormalities that need to be addressed, and in a fraction of men, treatment could increase sperm production. In some men, surgery to fix anatomical abnormalities or varicoceles can be pursued, and in others the best option is to go directly into the testicle to attempt retrieval of sperm that could be used for ART. It is very important that these procedures are performed by the few physicians with proper training, expertise and experience to optimize outcomes and chances of retrieving sperm. Finally, men with azoospermia should always remember that countless couples across the world have formed families with unsurpassed happiness and love by becoming parents by using donor sperm or by adopting an infant or child. After being evaluated (see below why it is so important to be evaluated), these are completely acceptable paths for couples to choose.

Isn’t testosterone made by the testis? Can a man have normal testosterone and be azoospermic?

Yes and yes. Sperm come from “germ cells” in small tubules within the testis. Testosterone comes from “Leydig” or “interstitial” cells in between the tubules. Since Leydig cells are more resilient than germ cells, they will often function partially or fully, even in a damaged or poorly formed testicle.

Why should men with azoospermia be evaluated and counseled by a specialist?

After getting a diagnosis of azoospermia, men are undoubtedly concerned about their chances of starting a family, but often they do not think about the potential relationship of infertility to their general health. However, studies have found significant medical conditions (including cancer) in up to 6 percent of infertile men who were thought to be healthy, and the risk seems to correlate with semen and hormonal abnormalities. More importantly, evaluation by a specialist is imperative to rule out any dangerous underlying medical conditions, to help couples optimize their chances of building the family they desire and to give guidance regarding risk and screening for medical conditions later in life.

What procedures are used to retrieve sperm?

For men with obstructive azoospermia, there is often an abundance of sperm within the reproductive structures, and various procedures can be used to obtain sperm. These include testicular sperm extraction, testicular sperm aspiration, microsurgical epididymal sperm aspiration and others. The choice is based on both patient factors, patient priorities and the preferences of the reproductive endocrinologists. For men with nonobstructive azoospermia, various approaches are available, but the procedure most likely to find usable sperm for use with in vitro fertilization and intracytoplasmic sperm injection is microTESE. When performed by an experienced expert in the field, this procedure involves careful dissection through the tubules of the testis to search for the tissue most likely to be actively making sperm. This allows for maximum yield of sperm with maximum preservation of other tissues in the testis, including the Leydig cells that produce testosterone.

I have more questions — what should I do?

Contact a specialist regarding your individual evaluation or management.

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