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Dr. K, what test can be done to tell us whether we have a production (non-obstructive azoospermia) or a delivery (obstructive azoospermia) problem?
A testicular biopsy will definitively tell you which type of azoospermia is present. This minor procedure can be safely performed as an outpatient and it takes around 30 minutes. A tiny incision is made in the scrotal skin that is taken down to the testicle where a small window is made to take a look inside the factory. A small rice kernal-sized sample is taken and sent to the pathologist to see what is going on in that tissue sample from the testicle.
Dr. K, the results came back from my testicular biopsy but what does it mean?
A testicular biopsy is your male fertility specialist’s way of trying to catch a glimpse of what is going on in the testicle factory. Are the assembly lines for sperm production present? Are they making complete sperm in sufficient numbers? Are they starting to make sperm but not able to complete the job and produce a finished product? A biopsy helps us categorize whether the azoospermia is due to a problem with production in the factory (non-obstructive azoospermia) or because there is a blockage in the pipes that carry the sperm out (obstructive azoospermia).
The following are a list of possible pathologies that they may find on the biopsy:
- Normal spermatogenesis: The assembly lines are present and are making the proper number of sperm from start to finish.
- Hypospermatogenesis: The assembly lines are present but there are not as many so that a reduced number of complete sperm are being made which is not enough to be seen in your ejaculate.
- Maturation Arrest: The assembly lines are present but they do not work properly. Sperm production is initiated but does not result in a finished product. Consequently, there are no mature sperm.
- Sertoli cell only: Also known as Germ Cell Aplasia, this condition means that there are no assembly lines present.
- Mixed pattern: Some combination of the above patterns.
Dr. K, my hormone profile shows that my FSH level is really high. Does it mean that I definitely have no sperm?
FSH or Follicle Stimulating Hormone is a hormone that is released by your brain to control sperm production in your testicular factory. FSH is like an email that says “Make More Sperm.” When the brain detects that sperm production is too low or absent, it starts sending lots of emails that say “Make More Sperm” and your FSH level is very high. While a high level of FSH suggests that something is not quite right with sperm production in the testicular factory, it does not specify what the exact problem is. More importantly, it does NOT predict whether sperm can be found if you carefully explored the testicles with a special procedure called a Microdissection of the Testicles (MicroTESE). Conceptually, while the vast majority of the testicle factory may be shut down, there can still be some isolated pockets of sperm or assembly lines that are still producing sperm. A recent study out of Cornell showed that FSH does not predict whether sperm can be found with a MicroTESE. Most importantly, a high FSH level was NOT a reason to not do a Microdissection (Ramasamy, et al. Abstract #1903, AUA 2008). Sperm were found in 60% of cases even when the FSH was >45.
Dr. K, do I need to do genetic studies for azoospermia and if so, which ones?
Two tests are recommended by the national American Urological Association: a Y-chromosome deletion test and a karyotype.
All the information and blueprint instructions for becoming a human being are recorded on our chromosomes which is like owning a copy of the Encyclopedia Brittanica. For men, the complete Encyclopedia series includes a total of 46 books of which one of them is the Y chromosome. A karyotype is our way of checking to make sure that your Encyclopedia series is complete. The librarian makes sure you are not missing any books, own too many copies and makes sure that no one has ripped out critical chapters or even switched chapters between books. For infertile men, including men with oligospermia, karyotype abnomalites can be found in 5.8% when it is only found in only 0.5% of fertile men. It is important to diagnose any genetic problems since it may identify potential health risks to the patient and to any offspring.
Up to 15% of men with azoospermia will be missing a part of their Y chromosome. The Y chromosome is where the blueprints are to instruct your body to become a man. On the Y-chromosome, there are specific pages of the blueprints that outline how sperm should be made. Some azoospermic men may be missing some or all of these pages, and some pages are more important than others. Specifically, if you are missing the AZFa and/or AZFb pages, then sperm will not be found in the testicle. Consequently, these men should not proceed with Microdissection of their testicles (MicroTESE). On the other hand, if the only page missing is the AZFc page, then finding sperm in the testicle is possible, and a MicroTESE is still a possible treatment option (Ferlin et al. J Clin Endocrinol Metab 2007; 92: 762-70, Hopps et al. Hum Reprod 2003; 18: 1660-5)
Science has barely scratched the surface in understanding the genetic risks associated with infertility. While we know that infertile men that have too few sperm (oligospermia) or none at all (azoospermia) may have abnormalities in their chromosomes (karotype or Y chromosome microdeletions), a natural concern is that infertile men may also be carriers for genetic diseases that we cannot detect on routine genetic tests. To help our couples make an informed decision about their reproductive options, SFCM has teamed up with the company Counsyl to offer a simple, non-invasive, saliva-based test to screen for more than 100 genetic diseases. It is called a Universal Carrier Screen. If you have questions, please feel free to call us or visit Counsyl’s website.
See a recent article on Counsyl in the New York Times Magazine
Dr. K, I was found to have an isolated microdeletion of the AZFc region of my Y chromosome. What are the chances that I may have sperm in my testicles if there aren’t any in my ejaculate?
Hopps et al. out of the group at Cornell published a very nice study looking at 42 men who were only missing the AZFc page from the Y chromosome. Of these men, 62% had no sperm in their ejaculate (azoospermia). Nine men who had always been azoospermic underwent a testicular microdissection, and sperm were retrieved for IVF/ICSI in 67% of these men. Obviously, it’s not 100% but hey, it’s definitely not zero which is the case for men who are missing the AZFa or AZFb regions of the Y chromosome. (Hopps et al. Hum Reprod 2003; 18: 1660-5).
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