It Takes Two to Tango

The Case of the Month is an actual patient from The Turek Clinic. It is presented to highlight Infertility Awareness Week.

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)