Sperm DNA Fragmentation

Sperm DNA Fragmentation

March 02, 2005
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Intracytoplasmic sperm injection (ICSI), a procedure where a single sperm is injected into an egg, went into widespread use in the US in the early 1990's. With it came the view that as long as a man had any sperm, he could father a child. In many ways ICSI was a remarkable procedure, allowing thousands of infertile males to have children. And ICSI worked even when the sperm didn't swim well, had poor morphology or were surgically recovered from the epididymis or testicle. It appeared as though there was no physical obstacle to fertilization as long as a live sperm was available for injection.

Now, with over 10 years experience with this procedure, and regardless of sperm or egg quality, we understand that on average 70-80% of all eggs will fertilize following ICSI. If we physically place the sperm inside the egg, fertilization happens most of the time. However, fertilization is not a very reliable measure of sperm quality, or even egg quality, and the rate at which your eggs fertilize has little bearing on whether or not your embryos will implant after transfer. Eggs recovered from women aged 40 and older, where we know that egg quality is poor, will fertilize at the same rate as younger eggs. Similarly, sperm with poor morphology will fertilize eggs at the same rate as sperm with normal morphology.

After fertilization, if embryo quality is poor, or if embryos fail to implant after transfer, we tend to implicate the eggs as the likely source of the problem. It is very hard to pin the blame on the sperm and we usually have very little evidence that would implicate the male partner in the failure. After all, much time and effort was needed to get the eggs, the egg is mostly responsible for preimplantation development, and the developing embryo was placed safely in the uterus. The tiny sperm brought only the male's genetic material or DNA, and we saw that that was safely inside the egg at fertilization.

Even when we start to worry about the DNA, eggs are much better known for genetic problems than sperm. Down syndrome is the classic example, as it is well known that the incidence increases with increasing maternal age. Genetic problems in children due to paternal age are less well known and in fact less than 10% of Down Syndrome cases arise as a result of a genetic error in the sperm.

In trying to visualize what DNA looks like, you have to think of a ladder. DNA is a double strand that is held together by the rungs, and the ladder is twisted and coiled. In sperm or eggs the DNA is organized on 23 distinct structures called chromosomes. Each chromosome is simply a very long twisted and coiled ladder.

When we count chromosomes in sperm and eggs, sperm have the right number about 90% of the time and for eggs this varies according to maternal age. For women over age 40, we would expect at least 50% of their eggs to have an incorrect number of chromosomes. These abnormalities don't appear to stop eggs from fertilizing, but the majority of the resulting embryos either won't implant or will miscarry early in pregnancy.

Because we know that sperm don't carry a lot of chromosomal abnormalities, we have to dig deeper to find problems that may cause infertility. The sperm chromatin structure assay (SCSA) is a test developed to look at the integrity of the DNA. Basically it looks at the structure of the ladder and determines if the strands are coming apart due to broken rungs. The more severe the DNA fragmentation is, the less likely that the sperm can establish a viable pregnancy.

To have the test performed, we ship a frozen semen sample to Donald Evenson, PhD, in Brookings, South Dakota www.scsadiagnostics.com. There the sperm are assessed and any sample with less than 15% DNA fragmentation is considered normal. Levels of fragmentation up to 30% may cause reduced fertility, and men with greater than 30% fragmentation are considered to have significantly reduced potential to father a child.

Environmental stresses such as smoking, exposure to other chemicals or toxins, or any other chemical or physical stresses that the sperm may be subjected to may cause or contribute to high levels of sperm DNA fragmentation. In the testes it takes over 70 days to make each sperm, so the potential for exposure to stress is high. Consequently, it's important for men to look after their health in the months leading up to their attempts to conceive. As always it's good to eat well, exercise, avoid illnesses, hot tubs and exposure to toxins and take your vitamins. We particularly recommend vitamins C and E, beta-carotene and anti-oxidants for sperm health. We don't routinely recommend the SCSA for our male patients since sperm fragmentation is likely to affect a very small number of men. The significance of a high fragmentation index is still under debate as there are reports in scientific literature of pregnancy successes despite a bad test result. Further, it is unclear what the prognosis is for men that succeed in reducing their fragmentation score by taking their vitamins and living healthier lives. An alternative solution for men with high fragmentation is to use donor sperm, however most couples choose to use their own sperm despite high fragmentation.

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