Male Infertility Causes

What is non-obstructive azoospermia?

Azoospermia means that no sperm are found in the ejaculate. In non-obstructive azoospermia, or NOA, the problem is not a blockage preventing sperm from getting out. Instead, sperm production within the testicle is significantly impaired.

One of the most important things I tell patients, however, is that azoospermia does not necessarily mean that the testicle makes absolutely no sperm. Sperm production is often not uniform throughout the testicle. A man may have little or no sperm production throughout most of the testicle but still have small, isolated areas where sperm are being produced.

Finding those areas is the fundamental principle behind microsurgical testicular sperm extraction, or microTESE.

What causes non-obstructive azoospermia?
There are many possible causes. These include genetic abnormalities such as Klinefelter syndrome or Y-chromosome microdeletions, previous chemotherapy or radiation, undescended testicles, severe testicular injury or infection, certain medications, hormonal abnormalities, and previous testosterone or anabolic steroid use.

In many patients, however, we never identify a single definitive cause. That is why I believe the evaluation needs to be comprehensive. I don't simply look at a semen analysis. I take a careful history, examine the patient, evaluate his hormones and, when appropriate, perform genetic testing.

Our goal is to understand why he is azoospermic and whether there is a reasonable opportunity to recover sperm.

Does azoospermia mean that I make absolutely no sperm?

No. This is probably the single most important concept for patients with non-obstructive azoospermia to understand.

A semen analysis tells us whether sperm are getting into the ejaculate. It does not tell us with certainty that there isn't a small area somewhere within the testicle that is still producing sperm.

I often explain this to patients using a model of the testicle. The seminiferous tubules - the tiny structures where sperm are produced - are not necessarily homogeneous. One area may produce no sperm while another area only millimeters away may contain active sperm production.

That is why simply taking a random testicular biopsy can miss sperm that are present elsewhere. A meticulous microsurgical search gives us the opportunity to identify those isolated areas of sperm production.

How is non-obstructive azoospermia properly diagnosed?
I generally want to see at least two properly performed semen analyses, and the specimens should be centrifuged so that the laboratory can carefully examine the pellet for even very small numbers of sperm.

Occasionally a man who has been told that he is azoospermic actually has extremely rare sperm in the ejaculate. Finding even a few sperm can potentially alter our treatment strategy and, in some cases, allow those sperm to be frozen.

The evaluation also includes a detailed reproductive and medical history, physical examination and appropriate hormonal and genetic testing. We also need to distinguish true non-obstructive azoospermia from obstructive azoospermia, because they are fundamentally different conditions and are treated differently.

Why do I recommend at least two semen analyses and centrifugation?
Sperm production can fluctuate, and one semen analysis represents only one moment in time.

When a laboratory reports that there are no sperm, I want the specimen centrifuged and the concentrated pellet carefully examined. We are looking for what is sometimes called cryptozoospermia - extremely rare sperm that might otherwise be missed.

Before telling a man that he makes no sperm in his ejaculate, I want to be as certain as possible that this is actually true.

I have been treating male infertility for approximately 35 years, and one of the principles I have learned is that details matter. When someone is trying to have a biological child, finding even a very small number of sperm can be enormously important.

6. What hormone and genetic testing should be performed?
he evaluation is individualized, but I typically assess the hormones important to male reproductive function, including FSH, LH and testosterone, with additional hormonal testing when clinically appropriate.

For men with non-obstructive azoospermia, genetic testing is also extremely important. This commonly includes a karyotype to look for chromosomal abnormalities and Y-chromosome microdeletion testing.

These tests do more than potentially explain why the patient is azoospermic. They may also help us counsel him regarding the likelihood of finding sperm and whether a genetic abnormality could potentially be transmitted to a child.

For example, certain complete Y-chromosome deletions are associated with essentially no likelihood of retrieving sperm, while men with other deletions can still have sperm production. That is information I want before taking someone to the operating room.

7. Can sperm still be found in the testicle when there are no sperm in the semen?
Yes - and this is exactly why microTESE was developed.

With non-obstructive azoospermia, sperm production may occur in extremely small, isolated areas of the testicle. The challenge is finding those areas while disturbing as little normal testicular tissue as possible.

During microsurgical sperm retrieval, I examine the seminiferous tubules under significant magnification. We look for tubules that appear more promising and systematically examine different regions of the testicle rather than simply removing a large amount of tissue at random.

The question I ultimately want to answer for every patient is very simple: Does this man make sperm?

I want to answer that question as thoroughly as possible while preserving as much testicular tissue and function as possible.

What are the chances of finding sperm in a man with non-obstructive azoospermia?
One of the important things to understand is that most men with non-obstructive azoospermia are not necessarily making absolutely zero sperm within the testicle. In many cases, there is a very small amount of sperm production occurring in isolated areas - it simply is not enough for sperm to appear in the ejaculate.

That is why I tell patients that non-obstructive azoospermia is often a problem of finding very limited, focal sperm production, rather than assuming that sperm production is completely absent.

The seminiferous tubules are not uniform. One region of the testicle may show essentially no sperm production, while a very small area somewhere else may contain the sperm we are looking for. The purpose of microTESE is to carefully identify and examine those more promising areas.

In my experience with the mini-incision microsurgical testicular sperm extraction technique that I developed, we are able to find sperm in approximately 60-70% of appropriately selected men with non-obstructive azoospermia.

No surgeon can guarantee that sperm will be found. There are certainly men who have no retrievable sperm production. But the fact that there are no sperm in the ejaculate does not mean that there are necessarily no sperm anywhere within the testicle.

My objective is to find that small amount of sperm production when it exists, while removing as little testicular tissue as possible and preserving testicular function.

Can medications or hormonal treatment improve sperm production before sperm retrieval?
Sometimes - but it depends entirely upon the cause.

If sperm production has been suppressed by testosterone therapy or anabolic steroids, for example, stopping those medications and using appropriate hormonal treatment may allow the testicle to begin producing sperm again. Certain men with identifiable endocrine abnormalities can also benefit substantially from medical treatment.

The situation is different when the testicle itself has primary impairment of sperm production. There are medications that may be used in selected patients to optimize the hormonal environment, but there is no medication that reliably causes every man with non-obstructive azoospermia to begin producing sperm.

I therefore individualize treatment rather than putting every patient on the same medication regimen.

If sperm are found, how can they be used to achieve a pregnancy?
Sperm retrieved from the testicle in a man with non-obstructive azoospermia generally need to be used with in vitro fertilization and intracytoplasmic sperm injection, or IVF/ICSI.

With ICSI, an embryologist takes an individual sperm and injects it directly into an egg. If fertilization occurs, the resulting embryo can develop and ultimately be transferred to the woman's uterus with the goal of achieving a pregnancy and, ultimately, the birth of a child.

This is why finding even a relatively small number of viable sperm can be so meaningful. We don't necessarily need millions of sperm when we are using ICSI - we need enough usable sperm for the eggs that are available.

Over the last 35 years, I have had the privilege of helping thousands of couples pursue the possibility of becoming parents. For a man who has been told that he has no sperm and may never be able to have a biological child, finding sperm can be a life-changing moment.

The first step is determining why the azoospermia exists, whether treatment can improve the situation and, when appropriate, whether a carefully performed microsurgical sperm retrieval offers a reasonable opportunity to find sperm.