Almost 50% of all cases of infertility are in fact likely to be associated with a malefactor. A semen analysis that is meant to measure up sperm concentration, motility and morphology have classically been made use of as the gold standard test in order to determine a man’s fertility.
Yet, this test does not indeed provide any such information about the genetic constitution of the sperm, which is rather essential for normal embryo development. Thus, a high level of DNA damage in sperm cells may indeed represent a cause of male infertility that conventional examinations cannot in fact detect.
Sperm DNA and Semen Parameters
Sperm DNA fragmentation is no doubt significantly higher in infertile men and while men with poor semen parameters are indeed more likely to have high sperm DNA fragmentation, high sperm DNA fragmentation is also found in men with normal semen parameters who may be diagnosed with unexplained infertility.
Sperm DNA and Embryo Development
Embryos that have been derived from sperm whose DNA is highly fragmented have a poor prognosis. High sperm DNA fragmentation is indeed more likely to affect embryos from day two of development once the paternal genome is switched on and it impairs subsequent blastocyst culture.
There is some evidence to suggest that DNA damage in the embryo could indeed result in cell degeneration and gene mutations, thus leading to arrested embryo development, miscarriage, abnormalities in the offspring and increased susceptibility to childhood cancers.
Sperm DNA, Pregnancy and Miscarriage
In couples where the male partner has a high percentage of sperm with fragmented DNA, many of the studies do indicate that the chances of a successful pregnancy are significantly reduced. One systematic review article does suggest that current sperm DNA fragmentation tests do have limited capacity to predict the chance of pregnancy following assisted conception treatment, however, several large studies, systematic reviews and meta-analyses that have revealed that high sperm DNA fragmentation is associated with reduced natural pregnancy rates and assisted conception pregnancy rates as well as live birth rates.
In addition, sperm with rather high DNA fragmentation does lead to higher miscarriage rates from spontaneous conceptions, as well as following assisted conception treatment. Overall the results of these studies that lend support for the value of testing for sperm DNA fragmentation in order to identify possible causes for unexplained infertility, failed IVF treatment cycles or recurrent miscarriage.
Causes of Sperm DNA Fragmentation
A major causative factor for sperm DNA damage is no doubt oxidative stress on account of excessive production of reactive oxygen species. Other factors do include defects in sperm chromatin packaging and DNA repair mechanisms as well as abnormalities in the regulation of programmed cell death (abortive apoptosis) which is indeed vital for regulating sperm production. Increased sperm DNA fragmentation is a fact associated with a variety of exogenous factors listed in the table below.
Factors Influencing Sperm DNA Fragmentation
- High fever
- Elevated testicular temperature
- Advanced age
- Poor diet
- Drug use
- Cigarette smoking
- Exposure to environmental and occupational pollutants
Indications for Male Patients
Who May Benefit from a Sperm DNA Fragmentation Test?
- Unexplained infertility
- Arrested embryo development
- Recurrent miscarriage in partner
- Poor blastocyst development
- Multiple failed IVF/ICSI treatment
- Recurrent miscarriage in partner
- Advanced age
- Poor semen parameters exposure to harmful substances
What is the DNA fragmentation test?
The test we offer is the sperm chromatin structure assay. This test is no doubt an effective method for measuring DNA damage in thousands of sperm in an ejaculate. It does measure the susceptibility of sperm DNA to denaturation when it is exposed to heat or acids. Sperm is stained with a fluorescent probe that does interact with the DNA molecule.
The fluorescence signal does change when the DNA is fragmented, and this is monitored using a flow cytometer. The SCSA test has indeed been developed making use of human and animal models over the last 35 years and is one of the most statistically robust tests available for sperm DNA fragmentation. It is a standardized, validated CLIA approved test with high reproducibility.
Treatment for Sperm DNA Fragmentation
Some causes of DNA fragmentation that cannot indeed be treated, but if the damage is caused by oxidative stress, then a change in lifestyle and a diet that is designed to protect against oxidative stress may also help reduce the levels of DNA fragmentation in some of these cases.
Although initial studies thus making use of antioxidant supplementation to reduce DNA damage are promising, care must be taken in overprescribing and more evidence is required. Treatment of infection with antibiotics may indeed also be beneficial in reducing sperm DNA damage, but again it is essential that there is a clear identification of bacteria before antibiotics are indeed prescribed.
Varicocele is, of course, the leading known cause of male infertility and it is in fact associated with sperm DNA damage. There is now much-growing evidence to show that varicocele repair may, in fact, improve sperm DNA integrity. Initiatives to reduce the levels of fragmentation can also be assessed by undertaking a second test three months after the first.
Initial reports do suggest that DNA damage, in fact, occurs at the post-testicular level, so that testicular sperm may indeed have a healthier DNA integrity than ejaculated sperm. Furthermore, several studies do show that ICSI may be a more effective treatment than IVF for sperm with high DNA fragmentation since its impact on fertilization and pregnancy rates are not as detrimental compared to IVF.
This view is indeed borne out by a large Swedish study based on 1633 IVF or ICSI cycles which reported a significant decrease in fertilization rate, embryo quality and live birth rate following IVF using sperm with high DNA damage, whereas the outcomes with ICSI treatment were not of course much affected by the quality of the sperm DNA.
Advantages of a Sperm DNA Fragmentation test
The test does provide a reliable analysis of sperm DNA integrity that may rather help to identify men who are at risk of failing to initiate a healthy ongoing pregnancy. Information about sperm DNA integrity may also help in the clinical diagnosis, management, and treatment of male infertility and may be of prognostic value in assessing the outcome of assisted conception treatment. Identification of high levels of DNA fragmentation in the sperm may also guide the clinician as to whether sperm donation may be appropriate. Sperm DNA fragmentation testing may, in fact, help couples make an informed choice regarding their subsequent course of treatment.