As a Ph.D. student, I was interested in naturally acquired (pre-existing) sperm DNA damage. How could this be not important, if half of the DNA which will become a template for the entire human being comes from the sperm. Even a sea urchin can understand it cannot be good.
I was reading manuscript after manuscript about the links between this damage and fertilization, pregnancies etc and the data looked very convincing and clear cut.
One day, I decided to apply one of the pre-existing DNA damage measuring techniques, Ocridine Orange (OA), to evaluate the sperm DNA integrity for one of my own project. To my astonishment, I discovered that every single technique to measure DNA damage required one or another treatment of the cells that was itself inducing DNA damage.
This means that when such technique is applied to the sperm cell, it measures not a pre-existing (intrinsic or natural) damage, but that of artificially induced by the technique itself! In essence, I (and everyone else) was measuring how resistant is the sperm DNA to an array of physical and chemical agents that sperm has absolutely no chance to encounter in the male of female reproductive tract. And yes, SCSA, TUNEL, OA and every other test used today to measure "sperm DNA integrity" is only measuring how hard it is to damage sperm DNA in the artificial hazardous environment, which sperm never encounters in real life.
Imagine you are buying a parachute and its certificate says: "Tested for resistance to acids, solvents and electric current". How is test relevant for your comfort that parachute will open? Well, it is not and the same goes for the above sperm DNA integrity tests. They are simply irrelevant.
To be fair, these tests will also indirectly measure the percentage of dead sperm cells in the sample (but this is something that can be easily and reliably detected by a standard semen analysis) and, probably to significant extend the ratio of protamines to histones in sperm nucleus.
Believe me or not, but 99% of my colleagues, including those who are deeply involved into the study of this subject, are in denial that the DNA damage they find was induced by them during the testing. Instead, they will probably explain that damage by "free radicals" and will send you to a doctor to recommend some kind of anti-oxidants.
Free radicals induced damage of sperm DNA is another semenology legend-on-duty. There are probably hundreds of articles describing increased free radicals level in seminal plasma of infertile men. There are, however, absolutely no direct evidences that free radicals found in seminal plasma (their source is white blood cells, not sperm cells) can be responsible for sperm DNA damage.
But wait a second! Has it even been proven that such a thing as pre-existing sperm DNA damage exists? Actually it was not. On contrary, there are two studies where sperm DNA damage was tested under conditions that did not induce any artificial damage, by injecting them into the mouse eggs. As you probably guessed, there was no damage found in any kind of sperm cells as long as they were moving before injection. In other words, there is no sperm damage as long as the sperm cell is alive. The same type of test demonstrated that when normal sperm is subjected to non-physiological conditions and killed, their DNA is indeed damaged. But once again, those sperm cells are dead and have no relevance for anything.
There are evidences of sperm damage during in vitro culture regardless of culture conditions. http://www.ncbi.nlm.nih.gov/pubmed/8501190
Embryo quality or pregnancies is not affected by DNA damage in sperm. Review of embryo quality is not affected by sperm DAN damage.
Furthermore, even slight deviation from physiological conditions during in vitro culture of the sperm cells has been shown to induce DNA breaks in sperm cells. We should also question if there is such a thing as physiological in vitro conditions, because apparently, even a mere in vitro culture under normal conditions induces DNA breaks or makes sperm cells susceptible to DNA damage.
Why there were no more studies like that and instead there are hundreds of studies on testing DNA damage with SCSA and similar techniques?
Well, because it is by far easier than sperm injection, you can get get whatever result you like and it will look scary and significant, so that the patient feels that the money were well spent. "Wow, I had no idea that my DNA is so fragmented!".
One of the reasonable questions to ask, what are
Several studies, including large recent meta-study practically rules out any significance of the sperm DNA integrity tests, regardless of how this "damage" came about.
I have to mentioned at this point, that all sperm DNA measurement techniques were borrowed from the cell biology other than reproductive biology. As imperfect as those techniques are, they can be used in the somatic cells, because the DNA in all of them is packed similarly and they can actually go through so-called apoptosis (programmed cell death) that includes "self-inflicted" DNA breaks. It has never been shown that a mature, motile (live) sperm cells is able to undergo apoptosis, nor the significance of apoptosis at this stage could be justified.
Whereas all somatic cells DNA is wrapped around histones, in the sperm, majority of histones are replaced with protamines and to pack the sperm DNA even further those protamines are linked together with disulfide bonds.
As the sperm cell slowly moves from the testicle toward ejaculation, it continues to "mature", acquiring more disulfide bonds, DNA is getting packed more tightly and as a result and it is becoming "harder" to break. Because this process is very imprecise and no normal values have been established, no DNA damage measuring technique can be used to measure sperm DNA integrity... unless it comes from stallions, but not your fellow playboys, who live under variety conditions, have diverse genetic background and were not bread at the factory. In humans, unlike stallions, any sperm test will vary widely from playboy to playboy, from day to day and month to month.
The bottom line, if you have tried it yourself and perhaps a couple of IUIs, just put those couple hundreds dollars that toward your IVF cycle.