For couples who have had recurrent miscarriages, the woman has probably gone through multiple tests. The man may not have had any testing at all, or maybe only a sperm analysis. But there are other tests for the man that are not routinely offered. One of those is a sperm DNA fragmentation test. DNA fragmentation is damage to the genetic code carried by the sperm, and it is not assessed by a sperm analysis. Could this test be helpful for those with infertility or recurrent unexplained miscarriage?
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What is sperm DNA fragmentation?
Sperm DNA fragmentation is damage to the sperm’s genetic material that can be caused by a number of different factors. The main job of the sperm is to fertilize the egg and carry the father’s genetic code for the new embryo. Unfortunately, even if the genetic code carried by the sperm is damaged, it is still capable of fertilizing an egg.
How does sperm DNA fragmentation impact fertility?
So if a sperm with damage to the genetic code fertilizes the egg, does that damage cause the new embryo to be unable to develop properly? So far, the research on sperm DNA fragmentation seems to indicate that higher levels of fragmentation decrease the chance of a successful pregnancy. Some studies show no change in fertilization rates at different levels of sperm DNA fragmentation, but other studies show lower fertilization rates for those with high sperm DNA fragmentation.
Research does show that lower DNA fragmentation is associated with faster growth of the embryo in the first 10-14 days after fertilization. These early embryos were also more likely to be viable when DNA fragmentation levels were lower. And while the available studies vary regarding successful pregnancy and DNA fragmentation, the majority of them show that men with a lower sperm DNA fragmentation rate will have higher pregnancy rates and live birth rates and a lower chance of miscarriage. High sperm DNA fragmentation rates have a negative impact on rates of pregnancy even when couples use IVF!
What causes sperm DNA fragmentation?
Some factors leading to increased sperm DNA fragmentation cannot be changed. Having a history of chemotherapy could cause sperm DNA fragmentation. Advancing age can also result in higher levels of defragmentation.
But other causes of sperm DNA fragmentation can be improved or fixed. If you’ve been trying to conceive (TTC), you may have already heard about some causes of sperm DNA fragmentation related to lifestyle. These include smoking, consuming alcohol, or a higher temperature of the scrotum. Oxidative stress (an imbalance between antioxidants and free radicals) can also cause fragmentation. Oxidative stress has several causes, but it can be improved with diet.
Certain medical conditions can also lead to increased sperm DNA fragmentation, including varicoceles or infections.
A varicocele is an enlargement of vessels in the spermatic cord, and it is associated with increased oxidative stress and higher levels of sperm DNA fragmentation. Some men with varicocele are fertile, but interestingly, fertile men with varicocele show lower levels of oxidative stress. Meanwhile, the oxidative stress levels are elevated in the men who are infertile or with recurrent pregnancy loss. A varicocele can also have negative impacts on other semen parameters that are tested on a sperm analysis.
Subclinical genital infections also are associated with high sperm DNA fragmentation. Subclinical means that the person is showing few or no symptoms of infection, even though the infection is present. That means the infection is less likely to be caught and treated, and the man may have no idea that the infection is potentially contributing to the couple’s fertility problems. One study assessed 172 men who were struggling with infertility, and 35% of them were found to have a bacterial infection. Sperm DNA fragmentation levels were found to be higher in those men who had a bacterial infection.
Testing for sperm DNA fragmentation
Sperm analysis does not assess DNA fragmentation. However, sperm DNA fragmentation could impact some factors that are tested in the sperm analysis. Men with higher levels of DNA fragmentation are more likely to have lower sperm volume or concentration. It was also associated with lower sperm motility. Both sperm volume/concentration and motility are assessed in a sperm analysis. Sperm analysis is a common starting place for testing for men, and it is more likely to be covered by insurance.
In some cases, a man with a normal semen analysis can still have high sperm DNA fragmentation. So while a semen analysis is a good starting point, some men may need to get a test that specifically assesses sperm DNA fragmentation. Unfortunately, a sperm DNA fragmentation test is less likely to be covered by insurance. But for those who are searching for answers, the cost of the testing may be worth it. Companies like SCSA diagnostics and Legacy can provide DNA fragmentation testing. If this is something that you are interested in, you will likely need to see a fertility specialist or a reproductive urologist, as many other medical professionals simply do not know enough about sperm DNA fragmentation.
Treatment for sperm DNA fragmentation
Some causes of sperm DNA fragmentation like smoking, consuming alcohol, or a higher temperature of the scrotum offer an opportunity for improving sperm quality, because they can be changed with a healthier lifestyle. Reducing stress or exercising may be helpful.
Adding antioxidants to the diet has also been shown in some studies to reduce sperm DNA fragmentation and improve pregnancy rates, while other studies do not show improvement. Taking an antioxidant is a fairly cheap and low risk intervention, so it seems like it is worth a try as long as you take a supplement and dose that’s approved by your doctor. Some of the antioxidants that have been studied include vitamin A, C, and E, micronutrients like L-carnitine, N-acetyl cysteine, zinc, selenium, and CoenzymeQ.
If a medical condition is causing sperm DNA fragmentation, the medical condition may need to be treated before TTC. Men with infertility or recurrent pregnancy loss due to a varicocele may need to undergo varicocele repair. Those with infection may need a course of antibiotics prior to resuming TTC.
Citations
- Stavros S, Potiris A, Molopodi E, Mavrogianni D, Zikopoulos A, Louis K, Karampitsakos T, Nazou E, Sioutis D, Christodoulaki C, Skentou C, Gerede A, Zachariou A, Christopoulos P, Panagopoulos P, Domali E, Drakakis P. Sperm DNA Fragmentation: Unraveling Its Imperative Impact on Male Infertility Based on Recent Evidence. Int J Mol Sci. 2024 Sep 22;25(18):10167. doi: 10.3390/ijms251810167. PMID: 39337652; PMCID: PMC11432134.
- Lira FT Neto, Campos LR, Roque M, Esteves SC. From pathophysiology to practice: addressing oxidative stress and sperm DNA fragmentation in Varicocele-affected subfertile men. Int Braz J Urol. 2024 Sep-Oct;50(5):530-560. doi: 10.1590/S1677-5538.IBJU.2024.9917. PMID: 39106113; PMCID: PMC11446552.
- Eini, F., Kutenaei, M.A., Zareei, F. et al. Effect of bacterial infection on sperm quality and DNA fragmentation in subfertile men with Leukocytospermia. BMC Mol and Cell Biol 22, 42 (2021). https://doi.org/10.1186/s12860-021-00380-8