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He is 40 years old and has been trying to conceive with his 35-year old wife for 2 years. After 5 months of trying, she miscarries at 8 weeks. After trying another 7 months, they lose another one, this time at 9 weeks. They are broken. What is going on here?
The Pregnancy Dance
Normally, the human sperm and egg meet in the fallopian tube soon after sex. 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 early embryo) makes an executive decision: continue developing or stop the dance. This decision is probably the first of many quality control events within the embryo as it develops. Funny thing is, the way the dance goes is highly dependent on 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 can 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 counts are 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 (karyotype) can detect this in a man’s blood and preimplantation genetic diagnosis can be used with IVF 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 sperm genetic payload is being prepared and packed for shipping 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 in normal numbers. 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 reasons. Lifestyle factors such as smoking, fevers, hot baths, illness, infections, medications (anti-depressants and Propecia), chemotherapy, radiation therapy, oxidant exposure (e.g. air pollution), older paternal age, poor diet and the good ole’ varicocele, that bag of veins located above the testicle are the usual suspects. Sperm DNA damage is also measurable through specialized assays that detect DNA strand breaks. And unlike chromosomal issues, they may be correctable by lifestyle changes such as weight loss, improved health, and diet and pre-pregnancy supplements.
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 to Help?
So, sperm do matter when it comes to miscarriage. Because of this, our advice is:
- See a men’s reproductive urologist 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.
- Take great care of yourself. Stay healthy, avoid tobacco and hot tubs and eat an antioxidant rich diet.
- Like your female partner, consider taking pre-pregnancy antioxidants vitamins
- Similar to advice endlessly given to women, it may help to start conceiving when you’re young.
Thank you, this was very informative.