Sperm DNA fragmentation

Fertilization, whether occurring naturally as a result of intercourse or in the laboratory by IVF needs a healthy egg and a healthy sperm. The sperm has received much attention recently. The sperm is necessary to carry DNA from the male to the female egg, allow fusion of the sperm with the egg and even provide the raw materials needed for the egg to start (the centrosome)

Sperm DNA contributes half of the offspring’s genetic material. If the DNA is abnormal in some way such as fragmented DNA, it may cause a breakdown in the reproductive process and therefore lower the chance of a healthy baby.

The DNA in sperm is protected from damage by wrapping itself tightly around proteins inside the sperm head. However, during the maturation of sperm in the male reproductive tract, sperm gradually loses its ability to fix damaged DNA. There is some suggestion that when the DNA is “packaged” correctly, the sperm may be more susceptible to the effect of harmful molecules called “free radicals”.

In addition, there are other factors that may result in an increase in the percentage of spermatozoa with DNA damage. Among them, the most important are cigarette smoking, genital tract infection, testicular cancer, especially Hodgkin’s disease, heat, exposure to pesticides, and air pollution.

Sperm DNA fragmentation Tests

The tests used for the assessment of sperm DNA fragmentation can be divided into direct and indirect tests. The direct tests try to detect the actual DNA breaks, while the indirect tests try to determine the susceptibility of sperm DNA to break after an external insult, such as acid treatment.

Commonly used direct tests:

• Terminal Deoxynucleotidyl Transferase-mediated Nick End Labeling (TUNEL),
• Single Cell Gel Electrophoresis (COMET)
•  In-Situ Nick Translation (NT) assay

Commonly used indirect test:

• Flow cytometric acridine orange assay (sperm chromatin structure assay, SCSA )
• Acridine Orange test (AO),
• DNA Break Detection-Fluorescence In Situ Hybridization (DBD-FISH)
• Sperm Chromatin Dispertion test (SCD).

There are very important limitations of all these tests

1.  There is no test that can differentiate between “important” DNA fragmentation and “unimportant”. Only a portion of human DNA has important functions. If DNA fragmentation occurs in areas that have no function, it may not matter at all. The current tests only measure the total amount of fragmentation.
2. No clear distinction on what is a normal amount of fragmentation. Many studies using a variety of tests have shown that the average amount of fragmentation in fertile men is lower than the average amount in infertile men. However, there is an extensive overlap between the values found in fertile and infertile men.
3. The amount of fragmentation in sperm can vary by a lot depending on which test is used and even using the same test from lab to lab.

Sperm DNA fragmentation in IVF

Over the last several years, sperm DNA fragmentation has been promoted as a promising method to predict the outcome of IVF cycles. Numerous studies (some good and some bad) have examined the relationship between sperm DNA fragmentation and pregnancy rates with IVF. Unfortunately, the results have been conflicting In a recent study, doctors combined the results of thirteen studies looking at the impact of sperm DNA fragmentation on IVF pregnancy rates . Although a link was found, it was so weak that it can not be considered clinically important. In other words, there is not enough adequate evidence to discriminate between couples who will or will not conceive in IVF cycles.

Time tells the tale

Looking at the published medical data over time, one can see how the purported impact of sperm DNA fragmentation has changed. Initially, it was reported that there would simply be no pregnancies in med who had high levels of fragmentation. Later, however, the same centers that published data stating there would be no pregnancies, changed their minds and then started to say that pregnancies would occur but that fertilization or embryo development would be lower. The most recent assertion is that it doesn’t affect these other things but that couples will miscarry more often.

It is also important to note that much of the data supporting the use of DNA fragmentation tests have been published by the same centers that are promoting their labs to do these tests. There is an obvious bias here that is rarely mentioned in the medical literature.

Since this type of testing is still considered experimental, most insurance companies will not cover the cost. Sperm DNA fragmentation testing is very expensive, often running 5-10 times more than a semen analysis .

Conclusion

1. There is not enough evidence to support the routine use of DNA fragmentation testing in fertility centers
2. There is not enough evidence to conclude that sperm DNA fragmentation testing will help predict the success of IVF or ICSI procedures