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Fertility Clinic Testing for Sperm DNA Fragmentation
By Leigh Ann Woodruff, February 15, 2012
If you and your partner are having trouble conceiving, and his conventional sperm parameters — sperm count, motility (speed) and morphology (shape) — are normal, the problem could still be because of sperm. Talk to your fertility doctor about screening the sperm for sperm DNA fragmentation, and this may give you more insight into why you are not getting pregnant. A high level of DNA fragmentation may compromise the possibility of a successful pregnancy no matter what fertility treatment is used.
"It is likely that sperm DNA fragmentation levels are on the rise due to increased reproductive toxicants in our environment," says Donald P. Evenson, Ph.D., HCLD, president and director of SCSA Diagnostics. "Dramatic cases are those working with pesticides and heavy metals like lead; however, in cities with high levels of air pollution and a documentation of infertility and miscarriages, the levels of sperm DNA fragmentation have been very high."
According to a 2008 report practice committee for the American Society for Reproductive Medicine (ASRM), while there currently is no proven role for routine DNA integrity testing in the evaluation of infertility, sperm DNA damage is more common in infertile men and may affect reproductive outcomes in selected couples, including those with recurrent spontaneous miscarriage or idiopathic (unexplained) infertility.
"The ASRM consensus committee report published in 2006, and then reprinted in 2008 had a major error in it showing that the Odds Ratio (OR) for natural and IUI pregnancy was about 1.7 when it, in fact, was an error as pointed out in our rebuttal publication in Fertility and Sterility," says Dr. Evenson. "The real odds are 8-10, and if that number had been used, and if they had added the data on the IUI patients in Sweden showing the same odds ratio, the conclusions would have been different of more strongly recommending a DNA fragmentation test, especially for the idiopathic couples."
What Is Sperm DNA Fragmentation?
DNA is the hereditary material in humans and other organisms and consists of two long polymers of simple units with backbones — DNA strands — made of sugars and phosphate. The information in DNA is stored as a code made up of four types of molecules called bases, which are attached to the DNA strands. The order, or sequence, of these bases determines the information available for building and maintaining an organism.
DNA fragmentation occurs when there is an alteration to the bases or a physical break in one or both of the DNA strands.
"Sperm DNA fragmentation is the physical breaking of one or both DNA strands in sperm chromosomes," Dr. Evenson explains. "If this occurs within a gene needed for embryo growth and is not repaired, the consequence may be the death of the embryo."
Testing for Sperm DNA Fragmentation
Testing for sperm DNA fragmentation is similar to the regular method of semen analysis at a fertility clinic. A semen sample is obtained and is sent to a sperm DNA fragmentation center for testing. Tests used include the Halosperm kit based on the Sperm Chromatin Decondensation (SCD) technique in which approximately 100 sperm are characterized as to whether they have expanded nuclei, with five grades of expansion, or no expansion (good sperm); the Tunel assay; the Comet assay; and the Sperm Chromatin Structure Assay (SCSA), developed by Dr. Evenson.
"New sperm DNA fragmentation tests are being developed, including the light microscope based SCD and Comet tests as well as the Tunel test," says Dr. Evenson. "Since the SCSA and Tunel test can be done with the precision flow cytometer instrumentation measuring thousands of sperm per sample rather than a hundred, these have much greater statistical robustness than light microscope tests."
Obtaining sperm for sperm DNA fragmentation testing can be done together with the semen analysis at a fertility clinic, explains Dr. Evenson. "A small portion of the fresh semen is placed into a small vial, frozen in an ultra-cold freezer or liquid nitrogen container and sent by Federal Express to a diagnostic laboratory."
At present, the SCSA is the only test of sperm DNA/chromatin for which validated clinical interpretation criteria exist. With the SCSA test, 5,000 individual sperm are measured in a high-precision flow cytometer. The test measures the presence of DNA strand breaks and the percentage of sperm with abnormal proteins that inhibit pregnancy success. The test determines the percentage of sperm with fragmented DNA and the degree of DNA damage and provides a DNA Fragmentation Index (DFI) score to indicate the likelihood of sperm contributing to infertility problems. The following scores indicate fertility potential for natural conception and intrauterine insemination:
- Less than or equal to 15 percent DFI: Excellent to Good fertility potential
- 15 percent to 25 percent DFI: Good to Fair fertility potential
- Greater than 25 percent DFI: Fair to Poor fertility potential
Causes of Sperm DNA Fragmentation
In about 25 to 30 percent of couples seeking clinical investigation of infertility, the men have sperm DNA fragmentation at a level that places the man into the category of a longer time to natural or IUI pregnancy (greater than 25 percent DFI), according to Dr. Evenson.
Oxidative stress — stress on the body that is caused by the cumulative damage of free radicals that is not adequately neutralized by antioxidants — is a main contributor to sperm DNA fragmentation. Sperm DNA fragmentation is associated with infections, drug use, cigarette smoking, exposure to environmental and occupational pollutants, advanced age, varicocele, illnesses with high fevers, elevated testicular temperature (laptop computers, hot tubs), chronic diseases such as diabetes, cancer and cancer treatment, and poor diet.
The epidemic of obesity is also a contributing factor to damaged sperm, which is more common among overweight or obese men. "In part, this is likely due to overhanging belly fat that insulates the testis for the required cooling of the testis," Dr. Evenson explains. "The reason men have a scrotum is that normal sperm production requires a temperature of about 2 degrees below body temperature."
Can You Treat Sperm DNA Fragmentation?
With the development of intracytoplasmic sperm injection (ICSI), some fertility doctors are not as focused on the quality of the sperm because the single sperm can be injected into the egg for fertilization. Other fertility doctors will attempt to avoid ICSI and try to decrease sperm DNA fragmentation to a level that is compatible with natural fertility.
According to Dr. Evenson, reducing the amount of sperm DNA fragmentation includes such things as "having a urologist evaluate the man to determine if a varicocele is present and, if large, surgically repair it. Several studies have shown this not only brings down the DFI but increases pregnancy success," he says.
Other recommendations to reduce sperm fragmentation and boost male fertility include:
- Keep the testes cool — no hot tubs or long hot baths, and wear boxer shorts
- Stop smoking.
- Eat a diet rich in antioxidants because oxidative stress is the primary culprit for breaking DNA.
- Avoid some medications such as cortisone and SSRIs.
- Get examined for urogenital infections.
- Eat a healthy diet full of colorful fruits and vegetables.
- Ask your doctor about supplementary vitamins and antioxidants such as vitamins C and E, co-enzyme Q-10 and supplements containing carnitine.