A User’s Guide To Azoospermia
At the beginning of the office visit, I like to ask men with no sperm in the ejaculate who are unable to conceive a simple question: “What crossed your mind when you first heard that you were azoospermic?” The answers vary greatly but are very telling:
- “It must be a mistake.”
- “I shouldn’t have joined that fraternity in college…”
- “It wasn’t the best sample I’ve ever done.”
- “I was simply and utterly devastated.”
- “I was in shock and then got really depressed.”
- “It changed my life … I always thought that I would be a father.”
The Meaning of Azoospermia
Azoospermia is the lack of sperm in the ejaculate. It can be due to a blockage in the system (obstruction). The most common reason for blockage is a vasectomy. Other causes include infections, prior surgery, injury or congenital absence of certain reproductive tract organs.
Azoospermia can also be due to a failure of the testicles to make sperm (nonobstructive). Failure to make sperm can be due to exposures (hot tubs), medications, varicocele, a history of undescended testicles, cancer and cancer treatment. However, the largest chunk of men with poor sperm production have none of these issues. Instead, there is a subtle genetic cause: either they are missing genes on the Y chromosome or have other chromosomes harboring subtle alterations that do not otherwise affect their health or lives.
One way to think about sperm production in men with poorly functioning testicles is to compare it to a mug with coffee in it. Say the mug is filled with ¼ cup of coffee. If you hold or shake the mug, you may not see any coffee spill over the side. In this case, you might assume that the mug has no coffee inside. But, if you peer into the mug directly, you will see that there is actually coffee in the mug. Similarly, the testicle makes more sperm (coffee) than is found in the ejaculate (spilling over the cup). There exists a threshold of sperm production, over which sperm shows up in the ejaculate and below which it will not. So, now you know the secret of making fathers out of “sterile” men with poorly functioning testicles.
So, like Captain Renault in the movie “Casablanca,” most men with azoospermia are “shocked, shocked!” because they feel so normal in every other way. And the vast majority are normal (as normal as men can get) in every other way. Most of the things they worry about, like college indiscretions, are exposures that are entirely reversible with time. My response is usually to allay fear and guilt by saying: “This is not something that you have done to yourself; let’s see if we can do something about it at this point.”
Do you think it is possible to have your own children with absolutely no sperm in the ejaculate? Why yes. It happens on a daily basis in my practice.
Honestly, the word “sterility” has really lost much of its meaning nowadays with advances in reproductive technology.
In fact there is a whole lot that we can do with azoospermia. Men with blockages can often be unblocked with microsurgery, one of my favorite things to do. We routinely grab sperm from behind vasectomy sites to use with assisted reproduction to conceive. This gives men the chance to conceive naturally again.
Poorly functioning testicles may not make sperm evenly throughout their substance. But most men (up to 60 percent) with nonobstructive azoospermia can have sperm. In many cases, there are “pockets” or “islands” of sperm within a sea of otherwise empty tissue.
You just need to look hard enough.
Sperm From a Rock
Clinically, these pockets or islands make sperm retrieval more difficult and have pushed this technology to a high art. To find sperm, fertility specialists use several sophisticated approaches in men with nonobstructive azoospermia. The traditional testis biopsy works about 30 percent of the time to find sperm and, as a consequence, is no longer the de rigueur technique for this problem. Fine needle aspiration “mapping”, which I invented about 25 years ago , is easily twice as good as a biopsy in finding sperm and much less invasive. Lastly, “microdissection” of the testis is another alternative and involves an all-out surgical assault on the testicle to find sperm, making it the most invasive approach. The elegance and complication rates for these approaches vary widely, but their intent is the same: to find enough sperm to allow biological fatherhood.
Importantly, when expertly performed, these techniques will find sperm in the majority of cases. We recently reported on a series of couples who used these scarce sperm and the fertility results were excellent.
For the remainder, there is hope as even newer “no touch” scanning technologies are on the horizon …
Some Azoospermia Is True
Yes, there are situations in which azoospermia can mean complete sterility and no usable sperm either in the ejaculate or the testicle. Chemotherapy and genetics are two classic causes of genuine azoospermia. Donor sperm and adoption are current family building options in these cases. Hopefully, our artificial testicle will be making sperm for these patients in the not-too-distant future.
Azoospermia Reflects Health
We and others have shown that some forms of azoospermia can have implications for future health, including higher risks of developing testicular cancer, prostate cancer and low testosterone levels. So, think of azoospermia as a soft indicator of potential health issues and follow through with that visit with the specialist!
Digging Deeper Into Unexplained Male Infertility
He stared back at me, his face blank. He didn’t like my answer. We had examined the known genetic causes of azoospermia and had come up dry. “I really don’t know why you’re azoospermic, but I’d say it’s still very likely to be genetic, but currently undefined.” Not much to work with, but it’s where we are at the moment.
“Unexplained male infertility” is when the evaluation reveals nothing to explain the problem. Everything, including the semen analysis, is stone cold normal. But, when the semen analysis shows no sperm and similarly, all medical, hormonal and genetic testing comes up clean, then this is called “unexplained azoospermia.” In this case, the Y chromosome testing looks fine and the rest of the chromosomes look pristine.
Down deep, I know that some men have trouble accepting this rather vague answer and that some men don’t. Either way, it’s my belief that you deserve a better answer.
Here’s what’s on the slate for explaining cases of azoospermia in the future:
- Look in other places. Our genetic testing focuses heavily on the Y chromosome, which makes sense since it’s the male chromosome and it harbors a bunch of male fertility genes. Believe it or not though, the girlish X chromosome could harbor just as many male fertility genes!
- Look at the beginning. The testicle develops within the early fetus when sperm precursor stem cells migrate to what will become the testicle proper and populate it. Failure of this migration caused by faulty developmental genes could leave the house “empty” of sperm as an adult.
- Look at the path. The quality control process in the sperm making business is intense. Maybe that’s why every sperm is sacred. Our studies show that important quality checkpoints are present when chromosomes mix and match (recombination) during If these molecular “dances” do not go well, infertility could result.
- Look at other paths. Changing the DNA sequence of a gene is called a “genetic mutation.” But what is it called when you alter a gene without causing a mutation? Yes, I am getting technical here, but these stealth genomic changes are fascinating and have recently been associated with male infertility. Not only that, they may be inherited from one generation to the next.
So, men are a lot more complicated than they appear. I’ll admit that saying that azoospermia is “genetic but undefined” is an excuse for now, but stay tuned as this science is sizzling.
Fertility From Sterility
What I have learned after caring for hundreds of azoospermic men over three decades is that they really don’t care what their sperm counts are as long as they can be fathers. And once they are fathers, it is clear that that “azoospermic feeling” goes away, as it should.