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It Takes Two to Tango

The Dance Begins

He is a 36-year old who has been trying to conceive with his 35-year old wife for 2 years. After 5 months of trying, the couple achieved a pregnancy she miscarried at 8 weeks. After trying for another 7 months, they conceived again and again lost the baby, this time at 9 weeks. The couple appears disheartened and broken as they tell the story in the office.

“I’m not sure what’s wrong with me…I can’t seem to carry a baby,” says the wife in tears. “My tests look great but for some reason, nothing lasts!” she continues. The husband then pipes in: “We checked on me after the first miscarriage and my sperm count was low. Could I be the problem?” Great question.

The Pregnancy Dance

Normally, the human sperm and egg meet in the fallopian tube soon after sex. Then, over the next several days, a highly orchestrated genetic dance begins. Within 2 days, the sperm molecularly “undresses” for the egg, revealing, in full nakedness, its genetic material. Inspecting the male genome, the egg surveys and corrects its imperfections, making it whole and usable. Based on how this dance goes, usually before day 3, the egg (now an 8-cell embryo) is compelled to make an executive decision: continue developing or stop the dance. This decision is probably the first of many quality control decisions the embryo makes as it develops and is highly dependent upon the acceptability of the sperm genome.

Sperm as Dance Partners

Can sperm contribute to early miscarriages? Yes, they can.

And this is despite the fact that you may never see this on any list of presumed causes of pregnancy loss. Here are the ways in which this is thought to happen:

Imbalanced Sperm Chromosomes. The classic example is when chunks of genetic material are misplaced within sperm chromosomes. Termed Robertsonian translocations, imbalanced sperm chromosomes can be found in perfectly healthy men and packaged into perfectly healthy-looking (e.g. morphologically normal) sperm. The only clue may be that the sperm concentration in the ejaculate is low (termed oligospermia).  When the egg and sperm genomes marry after fertilization, embryonic development is affected by the abnormal chromosomal balance in sperm, and the dance ends when the partners trip over each other’s feet. Fortunately, a blood test termed a karyotype can detect this in a man’s blood and preimplantation genetic diagnosis can be used with assisted reproduction to select for normally balanced embryos that lead to successful pregnancies.

Sperm DNA Breaks. More subtle issues with sperm can also lead to miscarriages. While the genetic payload is being prepared and packed for shipping in each sperm well before ejaculation, there may be subtle alternations in packaging quality that allow for breakages to occur in the sperm DNA ladder. Termed sperm DNA fragmentation, this problem is also found in perfectly normal-looking sperm at normal sperm concentrations and motilities. Ultimately, in the first few days of embryonic life, the egg in all of its wisdom may be unable to repair the breaks and fragments of sperm DNA and elects to stop developing. And the dance ends.

Unlike with chromosomal issues, poor DNA integrity can result from acquired rather than genetic causes. Such lifestyle factors include such as smoking, fevers, hot baths, illness, infections, medications (anti-depressants and Propecia), chemotherapy, radiation therapy, oxidant exposure (e.g. air pollution, solvents), older paternal age and the good ole’ varicocele, that bag of veins located above the testicle that overheats the factory through abnormal blood drainage pattern. Sperm DNA damage is also measurable through specialized sperm-based assays that detect DNA strand breaks. And unlike chromosomal issues, they may be correctable by lifestyle changes, improved health, or by repairing anatomical issues (varicocele).

So, think of chromosomal imbalances as men with two left feet and fragmented sperm DNA as men with shoes on the wrong feet. Either way, the dance just isn’t as smooth as it should be and it just stops in its tracks.

Antibodies and Epigenetics. Of course, there may be other ways that sperm contribute to miscarriage. Men are generally “allergic” to their sperm and some may develop antibodies to their sperm as a result. What is not clear is whether these antibodies induce a reaction from the female host to “attack” the embryo containing these same male allergic proteins. Additionally, the way sperm DNA is “fingerprinted,” termed epigenetics, may also influence pregnancy progression although this science is still in its infancy.

Men and Miscarriages: How Can They Help?

 

So, sperm matter when it comes to miscarriage. Because of this, my advice is:

  1. See a men’s reproductive specialist if you’re having trouble with miscarriages. A good history and a simple physical exam can assess possible risk factors and lead to lifestyle changes.
  2. Take great care of yourself. Stay healthy, avoid tobacco, exposure to smelly solvents, medications (when possible) and hot tubs and eat a diet rich in antioxidants.
  3. If you’re stuck with airport food, consider taking antioxidants vitamins such as that found in a good male pre-natal supplement.
  4. Similar to advice endlessly given to women, it may help to start when you’re young.

And when the tango begins, please be reminded of the power of the female egg: “Remember, Ginger Rogers did everything Fred Astaire did, but backwards and in high heels.” (Faith Whittlesey)

 

Dr. Paul Turek is founder of The Turek Clinic in San Francisco, a former professor and Endowed Chair at the University of California San Francisco, and a pioneer in innovative techniques for treating male infertilty . He was recently the recipient of a National Institutes of Health (NIH) grant for research designed to help infertile men become fathers. Check out Dr. Turek’s weekly blog on about common medical issues, solutions, and innovations at TurekOnMensHealth.com, where this blog post originally appeared.

Author:
Dr. Paul Turek
Fertility Clock Headlines, Fertility Headlines

One for the Guys: That Azoospermic Feeling

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 varying 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) or failure of the testicles to make sperm (nonobstructive). The most common reason for blockage is a vasectomy. Other causes include infections, prior surgery, injury or congenital absence of certain reproductive tract organs. 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, they have 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.

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.”

Treating Azoospermia

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. This gives them the chance to conceive naturally again. And most men with poor production as a cause of azoospermia will have pockets of sperm in the testicles that can be identified by techniques like sperm mapping and that can be used for high-technology pregnancies.

What I have learned after caring for hundreds of azoospermic men over two 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.

 

Dr. Paul Turek is founder of The Turek Clinic in San Francisco, a former professor and Endowed Chair at the University of California San Francisco, and a pioneer in innovative techniques for treating male infertilty. He was recently the recipient of a National Institutes of Health (NIH) grant for research designed to help infertile men become fathers. Check out Dr. Turek’s weekly blog on about common medical issues, solutions, and innovations at TurekOnMensHealth.com, where this blog post originally appeared.


Author:
Paul J. Turek, M.D.