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Research Spotlight

Cancer Risk in Men with No Sperm in Semen (Azoospermia)

September 30, 2013

Michael L. Eisenberg, MD
All species want to reproduce and humans are no different.  In fact, up to 25% of all the genetic material or “DNA” in a man’s body contributes to successful reproduction.  However, many men are unable to easily achieve a pregnancy.  Estimates suggest that about 1 in 7 couples in the United States have fertility problems.  Among these couples, many men will have poor sperm production which causes  fertility issues.  In the most severe form of male infertility, men produce no sperm in their ejaculate, so called “azoospermia.”  Azoospermia is not uncommon and occurs in about 10% of all infertile men and up to 1% of all men in the United States.  Given current population estimates, this suggests approximately 600,000 men between the ages of 15 and 45 have azoospermia.
The cause of azoospermia can either be due to a blockage in the sperm transport system  (thus preventing sperm from moving from the testicle to the penis) or a production problem.  It turns out that if sperm are not produced in sufficient quantity in the testicles, then no sperm will appear in the ejaculate.  It appears that a large portion of these cases are caused by genetic abnormalities.  As we learn more, we find the same genetic abnormalities seen in azoospermia are sometimes seen in several cancers.   In some ways this makes sense.  In order to produce sperm, the body needs to efficiently and perfectly replicate several cells to produce billions of sperm.  In cancer, the normal cell replication pathways get disrupted leading to uncontrolled cell growth.  As such, the same defects that lead to azoospermia may also be responsible for the development of cancers.
We examined a group of 2,238 men who presented for an infertility evaluation in Texas between 1989 and 2009.  Among these men, 451 had azoospermia while the rest had sperm in their semen.  We then determined how many of these men developed cancer in the years after their infertility evaluation.  When looking at the infertile men, there was a 70% higher risk of cancer.  Importantly, this represented all types of cancer including testicular, prostate, brain, lung, pancreas, stomach, intestine, thyroid, kidney, skin, and lymphoma.  Next, we looked specifically at the azoospermic men, and there was a 300% higher risk of cancer.  Thus, the highest risk of developing cancer among infertile men was the azoospermic men. 
It is important to note that the overall risk of cancer in this group remains low.  However, the study provides evidence that infertile men are at risk for developing later health problems, especially men with azoospermia.  It is too early to suggest that all azoospermic men should be regularly screened for cancer, but men should continue to receive regular medical care, such as annual check ups and counseling on a healthy lifestyle in the years after an infertility evaluation.  If you are infertile and do not have a primary care doctor, it would be a good idea to get one.
As a reminder to infertile couples----- Having  azoospermia or absence of sperm in the ejaculate does not mean that there is no hope to have a biologic child.  Up to half of these men will have pockets of sperm production in the testicles which can be identified by a urologist and used with in vitro fertilization to help create a healthy baby.

Eisenberg MLBetts PHerder DLamb DJLipshultz LIIncreased risk of cancer among azoospermic men. Fertil Steril. 2013 Sep;100(3):681-685.