Can We Accurately Assess DNA Damage in Sperm?
A host of tests designed to measure sperm DNA damage have been developed over the last few years. Results are generally reported as the percentage of sperm having fragmented DNA, the so called sperm DNA fragmentation index (DFI). Sperm that have been tested for their DNA integrity cannot then be used for treatment, they are destroyed by the test. So we may know the percentage of sperm with damaged DNA, but we can never know whether single live sperm has damaged DNA or not.
The various methods are broadly in agreement when assessing any particular sample, though the nature and severity of a specific DNA injury is not revealed. However, most of the methods require highly specialised equipment and are therefore more expensive than the traditional semen tests in common use.
What Things Can Damage the Sperm DNA?
The dense and compact packaging of DNA in the sperm helps to protect it against the outside world. However, DNA damage can still occur during the packaging process. These and other problems can occur during the manufacture of sperm, a process which takes around 3 months from start to finish and is wonderfully named Spermatogenesis. During this time of testicular spermatogenesis, sperm can be vulnerable to trauma of the testis or extremes of temperature. Injury to the testes or even an extremely hot bath may show up as a slight transient dip in semen count or motility up to 3 months after the event. Sperm quality usually recovers as sperm are continually being made in the testes, and sperm manufactured after the trauma are unaffected. This is one reason why there can be fairly large differences in the standard semen assessment parameters such as motility (ability to swim), morphology (shape) and sperm count in samples obtained from the same man over a period of months. Repeat semen analyses around 3 – 6 months apart are often recommended, especially where the sample only slightly sub-optimal.
Having been manufactured without defect, the sperm may still undergo DNA damage as they reside in the epididymis waiting for ejaculation. The main concern here is reactive oxygen species (ROS) which can react with DNA causing breaks and fragmentation. ROS themselves can be derived from immune cells which may invade the testis during infection or inflammation or from increased scrotal temperature and smoking. However, it is not always clear whether the DNA damage is entirely due to external factors, in some cases inherent defects in spermatogenesis may leave sperm more susceptible to DNA damage.
Can We Do Anything to Minimise Sperm DNA Damage?
The presence of ROS can be detected in semen samples, but it is not known exactly what threshold level of ROS we should regard as a threat to DNA integrity. It is possible that increasing antioxidants in the diet, such as vitamins A, C and E may help prevent high ROS levels. Smoking is a potent source of ROS and stopping has been shown to help semen quality in some smokers.
Overall, the advice to a man concerned about semen quality would be to eat a balanced diet containing sufficient antioxidants and to stop smoking. Medicinal antioxidant treatments have not been shown to be effective so far, but this is one area of research that is continuing.
Does Sperm DNA Damage Really Have an Impact on Fertility?
The question of how much impact DNA damage has on human fertility has generally been directed towards assisted reproductive techniques (ART), principally intracytoplasmic sperm injection (ICSI) in which a single sperm is manually selected and injected into the egg. Remember that only a single sperm out of maybe 300 million in a typical ejaculate actually completes the journey to and fertilises the egg. This is the reason nature favours the generation of huge sperm numbers and then allows them to race to the egg. We believe that this is a natural selection mechanism and that damaged or incomplete sperm fall by the wayside, only the fittest completing the journey.
The selection mechanism is absent when ICSI is performed and this is why research scientists have identified this as the most likely situation in which to look for any adverse effects of sperm DNA fragmentation. The main concern is whether there could be a risk of birth defects where a sperm with a high DFI is selected for ICSI. Research has also been directed to the question of whether patients with high levels of sperm DNA fragmentation are less successful in when having other forms.
If we cannot say that sperm DNA damage is responsible for an increased risk of birth defects can we say anything about whether it affects the chances of success in IVF? Well, there is some evidence that sperm DNA fragmentation is associated with reduced implantation rates in mice. The situation in the human is certainly different to the mouse, and the studies that have been conducted provide conflicting evidence. In some cases authors have suggested better outcomes when sperm DNA fragmentation is low whilst other studies have actually reported slightly better outcomes when the sperm DNA is more fragmented!
One of the major problems with this kind of investigation is that there are so many other confounding factors present, such as the types of patients included in any given study, the variation in semen quality in the individual, and other varied underlying causes of the couple’s fertility problems. Added to this is a lack of consensus about which of half a dozen different tests for sperm DNA fragmentation should be used and what level of sperm DNA fragmentation should be regarded as a threshold value to indicate poorer outcome.
Similar studies focussing on fertilisation rates have been conducted, and it is fair to say that the majority so far have shown little or no effect. None of this categorically rules out a role for sperm DNA damage, it is just that sometimes the only scientifically rational position to take is to say we do not have sufficient evidence at present.
Despite suggestions that sperm DNA fragmentation could be a marker of sperm quality and predictor of fertility treatment outcome, this has not generally been supported by the evidence so far. In some cases sperm DNA testing may be of value and recommended by your physician, but this will depend on individual circumstances. As analysis techniques improve and more refined studies are undertaken we may see a much larger role for sperm DNA fragmentation testing in the future, but it cannot be regarded as part of the routine semen assessment at the current time.
Sperm DNA fragmentation may vary considerably over time in a single individual.
The best way to reduce sperm DNA fragmentation is to eat fresh foods, particularly those containing antioxidants or vitamin C and E, and to stop smoking.