What is my first step if I’m diagnosed with azoospermia?
A semen analysis showing azoospermia does not necessarily mean you won’t be able to have a biological child.
Azoospermia is the term that’s used when a standard semen analysis finds no sperm in the ejaculate. Fortunately, a standard semen analysis that shows the absence of sperm in the ejaculate does not rule out the possibility that:
- Sperm are being produced but not delivered to the semen
- Interventions may help the man produce sperm
- A more extensive semen analysis may find a small number of sperm not seen on a conventional analysis which then can be specially frozen and available
- Small numbers of sperm may be found in the testicle itself.
The good news is that even with one found sperm, a man may be able to have a biological child through advanced reproductive techniques, by taking an individual sperm and injecting it directly into an egg (IVF/ICSI.)
Azoospermia: Diagnosis, Treatment, Finding Sperm
Evaluation: Determining the Cause
The first step after receiving the diagnosis of azoospermia is an evaluation with a urology specialist to determine whether the cause is due to a problem with sperm production or sperm delivery.
If sperm delivery is the problem, retrieving sperm is the next step.
If sperm production is the problem, maximizing sperm production is the next step.
Maximizing Sperm Production
Sperm production problems may be caused by a hormone imbalance, testicular failure or varicocele. If, for example, the doctor believes that the quality and/or quantity of sperm are being affected by a varicocele (an enlarged groups of veins in the scrotom), a varicocelectomy can be performed to repair the damaged veins. This may improve sperm production and sometimes lead to sperm in the ejaculate.
Conducting Sperm Search
If the specialist believes that sperm might indeed exist, even after sperm production has been maximized but still can’t be found in the ejaculate, he may suggest one of the following advanced techniques:
Extended Sperm Search & Microfreeze (ESSM)
This technique may be able to find small numbers of sperm through advanced processing techniques. These sperm may then be used in in-vitro fertilization (IVF) or intracytoplasmic sperm insertion (ICSI). This procedure involves a specially trained andrologist spending multiple hours looking through the entire semen specimen in minute amounts and, if isolated sperm are found, freezing them in a miniscule quantity of fluid so that they can be easily relocated when needed for insemination.
In those cases where appropriate interventions have been tried and where the ESSM did not locate sperm in the ejaculate, there may be the possibility of harvesting sperm directly from the testes. In 30% of azoospermic men there may be small number of sperm, which have been produced in the testis, but exist in such small quantities that they do not reach the semen. An in-office procedure called Sperm Mapping can determine if there are sperm producing areas in the testes, and where they are. If sperm are found on the sperm mapping, then the couple can proceed with in-vitro fertilization and an open sperm retrieval procedure, called micro-TESE (Testicular Sperm Extraction).
If you’ve been diagnosed with Azoospermia and are interested in exploring your options, Dr. Werner and his team of specialists are here to help. Contact us for more information.
The goal of the diagnostic evaluation and testing is to determine whether the causes for Azoospermia are due to a problem with sperm production or sperm delivery.
The simplest test is the physical exam. Since most of the bulk of the testes is comprised of sperm producing elements (the seminiferous epithelium), if the size of the testicle is severely diminished, this is usually because of issues with the sperm producing part of the testicle. (Many men with small testes and problems with sperm production still have normal testosterone levels, though many will not. This is because the testosterone is made by a different type of cells in the testes, called Leydig cells.)
During a physical exam, the ductal systems can be felt. If they are absent, the patient has what is called congenital bilateral absence of the vas deferens (CBAVD). In most cases, this is due to the patient’s genetic make-up and requires chromosomal analysis as part of the evaluation and treatment. The good news here is that the vast majority of these men have normal sperm production, but of course can’t get the sperm into the ejaculate because the ducts that carry them there are absent.
Also, during examination of the ductal structures, the epididymis may feel as though it is enlarged and/or firm. Generally, it is flat and the middle cannot be felt. If the epididymis is enlarged and hard there may be a blockage.
The scrotum is examined for the presence of dilated veins (varicoceles). (Their presence can be confirmed by a scrotal ultrasound, which is done non-invasively by applying a probe to the scrotal skin.)
Follicle stimulating hormone (FSH) is the hormone, made by the pituitary, which is responsible for stimulating the testes to make sperm. When the sperm-producing capacity of the testes is diminished, the pituitary makes more FSH in an attempt to make the testes do their job. Therefore, if a man’s FSH is significantly elevated, there is a strong indication that his testicles are not optimally producing sperm, and he has non-obstructive azoospermia. If a man has a very low FSH, then he is lacking the ability to make FSH, which is needed by the testis to promote sperm production. This may actually be good news in terms of treating the azoospermia, as many men have sperm in the ejaculate after treatment with FSH.
Testosterone, prolactin, luteinizing hormone (LH), and thyroid stimulating hormone (TSH) are also measured to assess a man’s hormonal status. These may reveal problems that can significantly impact sperm production.
This is an area of active research.
At this point, it is recommended that all men receive basic genetic testing, called a karyotype. This measures the number of chromosomes and look sat the large blocks of genetic material to make sure they are in the right place. Extra whole chromosomes or chromosomal material, or chromosomal material in the wrong places, can have a significant effect on sperm production.
There are tests for specific genetic abnormalities on the male (Y) chromosome in the areas that code for sperm production that can cause low levels of sperm or complete and irreversible azoospermia. They are called Y microdeletions. If a son were to inherit one of the mutations that caused a significant decrease in sperm production, he would be expected to have the same problem.
Screening for the mutations that can cause cystic fibrosis is sometimes suggested, as if present can cause problems with the sperm ducts.
Post Ejaculatory Urinalysis (PEU)
It is possible that ejaculation is occurring “backwards”; instead of being pushed forward and ejaculated out of the tip of the penis, the sperm is being pushed into the bladder. This is not medically dangerous, as it is then washed out when the man urinates the next time after ejaculation.
To test for this, we have the patient empty his bladder and then ejaculate into a cup. He is then asked to urinate again into a different specimen container, which is the post ejaculatory urinalysis. If there are significantly more sperm in his urine than his ejaculated specimen (if there is one) he has ejaculated backwards. Sometimes, this can be corrected by oral medication. If not, the urine can be prepared so that it does not damage the sperm as much, and the sperm is then harvested from the post-ejaculatory urine.
In order to rule out a blockage of the ejaculatory duct, an ultrasound of the ejaculatory duct and seminal vesicles is often performed. In this test, the ultrasound probe is placed in the rectum since the ducts lie near the rectal wall. Also, the ejaculatory duct traverses the prostate (a gland that can be felt through a man’s rectal wall.) If the seminal vesicles are dilated, this indicates that they may be full of semen because they cannot empty properly. Cysts blocking the ejaculatory ducts by exerting pressure on their walls, or calcifications in the ejaculatory ducts themselves, may also be noted. A cyst, in some cases, may be unroofed by operating through the urethra to open it, thus decompressing the ejaculatory duct. If the blockage occurs within the ejaculatory duct, the blocked part may be removed in a similar operation.
WHAT CAUSES AZOOSPERMIA?
The first question to answer is whether the problem lies in the sperm production or in its delivery. Is it that the testes are not producing adequate numbers of sperm to see them in the ejaculate, or are adequate numbers of sperm being produced, but they can’t get into the ejaculate?
The initial evaluation is to distinguish between these two conditions. If the testes are making adequate number of sperm but none are in the ejaculate (called “obstructive azoospermia” or OA), the sperm must be obtained by either restoring the normal flow of sperm through the full reproductive tract or retrieving it.
If the testes are not producing adequate sperm to see them on a regular semen analysis (called “non-obstructive azoospermia” or NOA), we need to explore whether treatment can make the sperm production better, even to the point of finding just a few sperm on the Extended Sperm Search & Microfreeze (ESSM) procedure. If no sperm are found with ESSM, a relatively non-invasive technique called Sperm Mapping can help predict whether sperm would be found on a more invasive technique where the sperm are actually harvested called micro-TESE.
The following briefly describes causes for both production and delivery problems:
Sperm Production Problems (Non-Obstructive Azoospermia, or NOA)
The three major causes for lack of sperm production are hormonal problems, testicular failure, and varicocele.
Hormonal Causes of No Sperm
The testicles need pituitary hormones to be stimulated to make sperm, specifically FSH and LH. If these are absent or severely decreased, the testes will not maximally produce sperm and possibly not produce any sperm at all.
Importantly, men who take androgens (steroids) for body building, either by mouth or injection, shut down the production of hormones needed for sperm production, and thus often shut down sperm production completely or decrease it significantly. Fortunately, this can almost always be reversed.
A prolactin producing tumor, a prolactinoma (which fortunately is almost never metastatic and usually treated with medication) can significantly decrease sperm production.
Thyroid problems can also have a negative effect on sperm production.
Testicular Failure Causing Azoospermia
In general, this means that the sperm-producing part of the testicle (the seminiferous epithelium) isn’t making adequate numbers of mature sperm. This failure may occur at any stage in sperm production for several reasons. Either the testicle may completely lack the cells that divide to become sperm (this is termed “sertoli cell-only syndrome”) or there may be an inability of the sperm to complete their development (this is termed a “maturation arrest.”) This situation may be caused by diagnosable genetic abnormalities, which must be screened for prior to any other diagnostic or therapeutic procedures.
Varicoceles Can Reduce Sperm Production
As we’ve discussed in other sections, a varicocele is a dilated vein in the scrotum (much like varicose veins in the legs). These veins are dilated because the blood does not drain properly from them. These dilated veins allow extra blood to pool in the scrotum, which has a negative effect on sperm production. This condition may be corrected by minor out-patient surgery.
Sperm Delivery Problems (Obstructive Azoospermia, or OA)
Ductal Absence or Blockage Can Result in No Sperm Production
Generally, a sperm delivery complication is caused by a problem in the ducts that carry the sperm, or problems with ejaculation.
The sperm-carrying ducts may be missing or blocked. Both sides of the patient’s vas deferens may be absent from birth. Or he may have obstructions either at the level of the delicate tubular structure draining the testes (the epididymis) or higher up in the more muscular vas deferens. He may have become mechanically blocked during hernia or hydrocele repairs. Of course, a previous vasectomy would be a known cause of ductal obstruction.
Sperm are stored in sacs called the seminal vesicles, and then are deposited in the urethra, which is the tube through which men urinate and ejaculate. The sperm must pass through the ejaculatory ducts to get from the seminal vesicles to the urethra. If these are blocked on both sides, no sperm will come through, even if some fluid does.
Finally, there may be problems with ejaculation. Before a man ejaculates, the sperm must first be deposited in the urethra. This process is called emission. There may be neurological damage from surgery, diabetes, or spinal cord injury that prevents this from happening. Also, for the sperm to be pushed out the tip of the penis, the entry to the bladder must be closed, which happens naturally and unconsciously during normal ejaculation. If it does not close, the sperm will be pushed into the bladder (rather than out the tip of the penis) and then subsequently washed out when the patient urinates.
Potential Next Steps
Once we determine whether the cause of the Azoospermia is related to sperm production issues or sperm delivery issues, an appropriate procedure can be discussed and implemented.
Extended Sperm Search & Microfreeze (ESSM)
Extended Sperm Search & Microfreeze may be able to find sperm that even a careful conventional semen analysis with a post ejaculatory urinalysis misses. This may be because the numbers are so low, that they are not seen in a random drop of sperm used for a conventional semen analysis. Even if the specimen is spun down with a centrifuge, and the pellet at the bottom evaluated, unless every drop is looked at thoroughly low levels of sperm may be missed.
An ESSM is performed by dividing the entire semen sample into 200 microliter droplets and carefully scanning the drops under a high-powered microscope. Any live sperm located can be moved with a micromanipulator into a micro-drop on a specialized freezing receptacle so that it can be successfully frozen, and both be alive and be able to be found when thawed and needed for injection into his partner’s eggs.
Sperm mapping refers to a procedure where multiple fine needle biopsies (fine needle aspirations or FNA) are done on the testes in order to see if there are any areas where sperm are produced. The reason why this is useful is that the testes are “heterogeneous;” different areas of the testes have different patterns of sperm production. Thus, even if most of the areas of the testes produce no sperm, there may be some just one or several areas that do. Testes mapping, therefore, tells us if there are some areas of sperm production in the testes, and where they are so they are easier to find subsequently when sperm need to be harvested for use.
If no sperm are found on the testes mapping, it can be presumed that there are no sperm produced anywhere in the testes and no further evaluation or treatment is possible. This saves the couple from having the man go through an open testicular biopsy (micro-TESE) and prevents a couple from undergoing a fruitless in vitro fertilization cycle.
Testicular Sperm Extraction (micro-TESE)
In most centers, the next step after a diagnosis is made of complete azoospermia is micro-TESE. (We hope that in the future, all men will have ESS done prior to this step.) This procedure is done as an outpatient in a surgical setting, with anesthesia, and involves opening the scrotum and testis, and then taking numerous samples (biopsies) of the testis. These are immediately evaluated to see if sperm are found, and if so, the sperm are then injected directly into his partner’s eggs (ICSI), whether already frozen or being retrieved that day.
If extra sperm are found, these can be frozen and used in subsequent IVF cycles, and we recommend the tissue be evaluated and frozen in the same way as done in an Extended Sperm Search, as this makes it more likely that a few sperm can be isolated and subsequently thawed successfully and found!
Varicoceles is a dilated or enlarged group of veins in the scrotum which can harm the testicles and decrease sperm count. Fortunately, it can be successfully treated. Dr. Werner is one of the only urologists in this area to perform the gold standard technique — microscopic sub-inguinal varicocelectomy with ultrasound guidance. Once the procedure is performed, sperm is no longer blocked from the ejaculate.
Azoospermia Diagnosis & Treatment Conclusions
Most men facing a semen analysis fear the diagnosis of azoospermia. However, that diagnosis does not necessarily mean that the man will never have a biological child.
Accurate diagnosis, evaluation, treatment, and management of azoospermia is complicated and should be performed by a specialist in male infertility.
A complete diagnostic evaluation must be performed to determine whether the issue is a production (non-obstructive azoospermia) or delivery (obstructive azoospermia) problem.
If the issue is in the delivery of the sperm, the focus is on retrieving, and often freezing the sperm.
If the issue is a production problem, the first step is to attempt to maximize sperm production (usually through hormonal treatment or varicocelectomy, if appropriate.)
If after treatment is completed there are still no sperm seen in a conventional semen analysis, an Extended Sperm Search & Microfreeze (ESSM) should then be performed to try to find and freeze even a few sperm.
If the ESSM is unsuccessful in finding and freezing sperm, we typically recommend a Sperm Mapping.
If the Sperm Mapping shows sperm in one or more locations, a testicular sperm extraction (micro-TESE) can be performed, combined with in-vitro fertilization. The sperm found during the micro-TESE can be frozen using the microfreeze techniques, which makes it more likely they will survive the thawing process and can be easily found when needed.
Last updated: November 2019