Sperm DNA Fragmentation

What is Sperm DNA Fragmentation?

Sperm DNA Fragmentation refers to the level of damaged DNA found inside the sperm head.

  • It is estimated that 25% of infertile men have higher levels of Sperm DNA Fragmentation.
  • Approximately 10% of patients undergoing fertility treatment can test normal in a basic Semen Analysis, but have elevated levels of DNA Fragmentation.

A Semen Analysis gives information about the physical characteristics of the sperm i.e. how it swims, how it looks, but this examination cannot tell us what's going on inside the sperm.

If the level of DNA fragmentation exceeds 30% then a couple’s chance of delivering a baby, through Intra Uterine Insemination (IUI) treatment, fall from 19.0% to just 1.5%. Failed treatment cycles can be avoided by checking the level of Sperm DNA Fragmentation before treatment begins. Increased levels of sperm DNA fragmentation can cause recurrent pregnancy loss and increase the risk of cancer in offspring.
This is why fertility experts are now recommending Sperm DNA Fragmentation testing.

When should a patient consider sperm DNA fragmentation testing?

Main indications include:

  1. Unexplained infertility
  2. Oligozoospermia (low sperm count)
  3. Repeated pregnancy failure in IUI/IVF/ICSI treatments
  4. Recurrent miscarriage
  5. Recent episode of high fever
  6. Previous chemotherapy or radiotherapy treatment
  7. Clinical varicocele (distended veins)
  8. Males aged over 45 years


What can cause high levels of Sperm DNA Fragmentation?

Medication (e.g. Anti-depressants), smoking, drinking, infectious diseases, fever, industrial waste products, varicocele, age and long periods of sexual abstinence.

What steps can be taken to reduce Sperm DNA Fragmentation?

Sperm DNA Fragmentation levels have been shown to improve by taking 1g of vitamin C and 1g of vitamin E daily for 2 months (Ref. 1 & 2) or by taking a supplement rich in antioxidants (Ref. 3)

Read more on our Nutritional Info page.

Why are Sperm cells more susceptible to DNA Fragmentation?

From the time the sperm is generated in the testes until the time it reaches the egg, sperm DNA is left without protection. Sperm cell DNA is more exposed than the DNA of other cells in the body as the sperm head is packed with only the minimal amount of essential bio-molecules required to sustain its journey to the egg. It lacks the protection factors present in other cells of the body.
This is why sperm cell DNA is more exposed and likely to incur damage.

What happens when Sperm DNA is damaged?

When a sperm penetrates an egg, the DNA of both cells combine together. The female’s egg contains many DNA repair mechanisms, which attempt to repair sperm DNA damage incurred during the sperms journey to the egg. These repair mechanisms can mask the effects of damaged sperm DNA during the early stages of embryonic development, such that embryos created through IVF/ICSI will appear normal to the embryologist in the laboratory.
The more serious consequences of sperm DNA damage can manifest later in fetal development and lead to early miscarriage.

What does testing involve?

Sperm DNA fragmentation Testing allows us to examine the structure of the DNA within the sperm head.
SCSA (Sperm Chromatin Structure Assay) is the name of the testing method used by Fertility Check.

The SCSA method

SCSA uses flow cytometry to access the level of fragmented DNA within a sperm head. It is a highly automated and statistically robust technique. The flow cytometer measures the fluorescence ratio between green and red in a semen sample. A special dye fluoresces green when bound to native DNA but red when bound to fragmented DNA (Ref. 4).
This is currently the method of choice for most fertility clinics but the equipment and licensing are expensive. Samples need to be shipped abroad and the turnaround time for results is 1-2 weeks.

What does the result mean?

SCSA testing tells you the DFI (DNA Fragmentation Index) level in a semen sample. A DFI value above the threshold level of 30% suggests a problem with semen quality. Higher values correlate with reduced success rates in IUI (Intra-Uterine Insemination). The Bungum study conducted in 2004 involved 998 IUI treatment cycles at Viborg Hospital, Denmark. It showed that high levels of DNA fragmentation reduced IUI success rates from 16%→4% (Ref. 5).

High levels of DNA fragmentation have also been reported to influence fertilization rates and embryo quality (Ref. 6 & 7). This leads to poor ART outcomes and repeated miscarriage (Ref. 8 & 9).



Producing a semen sample for Sperm DNA Fragmentation Testing

Procedure

Once the patient has registered their details with a fertility clinic, then a package is sent to them in the post containing

  1. Instructions
  2. Sample production details and a brief patient history questionnaire - form
  3. Sterile sample pot (Not to be opened until sample production)
  4. Biohazard bag

Note: To ensure privacy and discretion all post materials are in nondescript brown envelopes. Outer packaging does not contain any company logos. C5 envelopes containing sample pots are approximately 5cm in diameter weighing approximately 40g. It is your responsibility to ensure this envelope can be received through your letterbox without damage.

  • A sexual abstinence period of not more than 5 days or less than 2 days is recommended before producing a semen sample for testing. If more than 5 days have passed since the patient has ejaculated, then sperm are likely to have a higher level of DNA fragmentation. If a patient has ejaculated in less than 2 days then semen volume and sperm numbers can be lower.
  • Wash hands and the genital area thoroughly before the production of a semen sample for testing. This reduces the likelihood of skin cells or clothing fabric in the semen sample.
  • Do not use lubricants, latex condoms, powders or perfumes that are likely to be toxic to sperm, during sample production
  • Special non-toxic condoms are available commercially. These can be used to collect a sample for analysis during intercourse. Care must be taken in following manufacturers instructions, especially when closing the condom and transporting the sample to the laboratory.
  • Ensure the sample is produced into a correctly labeled sample pot i.e. the name and address are correct. Do not open the sterile sample pot until ready to produce a semen sample.
  • Following sample production, the sample pot must be closed TIGHTLY and the sample pot must be kept WARM during transport to the laboratory.
  • Place the sample pot in a biohazard bag and keep either next to the skin or in a warm pocket during transport to the laboratory.
  • Too much cold or heat will kill the sperm.
  • The form explaining sample production details should be filled out. It will quickly outline the patient’s sexual abstinence (in Days), the time the sample was produced and whether the sample collected was complete i.e. all the semen fluid fractions were collected in the pot.
  • A brief patient history questionnaire is also contained on this form and should be completed and returned, for a more accurate assessment of the patient’s results.
  • These forms and the tightly sealed sample pot in the biohazard bag, should be delivered to the clinic within 1 hour of production. This is the optimal time frame within which to test the sample.

In Summary

  • Register with a fertility clinic
  • Abstain from sex 2→5 days before sample production
  • Wash hands & genitals thoroughly before sample production
  • Do not use latex condoms or other sperm-toxic substances
  • Check the sample pot is labeled correctly with your personal details
  • Once the sample is produced, close the pot lid tightly
  • Keep the pot warm between 20→37degrees (Close to your skin)
  • Fill out the sample production details and patient history questionnaire form
  • Deliver this form and the sample in the biohazard bag, to the laboratory within 1 hour of production
Results and Repeat Testing

When a Semen Analysis is booked with Sperm DNA Fragmentation testing, then results for the Semen Analysis are available that day over the phone or in person, when a consultation is booked. The final report is issued when the DFI value for the Sperm DNA Fragmentation testing is returned 1-2 weeks later.

A ‘Remarks’ section will be included in the test report, which will summarize the significance of the test results.
Note: The quality of semen samples will vary between ejaculates. Results will be affected by factors such as:

  • Period of sexual abstinence
  • Level of stimulation
  • Stress
  • Illness
  • Or whether the semen sample is complete i.e the whole semen sample was captured in the sample pot

Note: Should a patient provide a fertility clinic with either an incomplete sample for testing or compromised sample for testing (e.g. prolonged time interval since sample production, over exposure of sperm to hot/cold, or use of spermatotoxic substances in sample production), then the fertility clinic cannot be held responsible if an accurate test cannot be carried out.

Back to Male Fertility Testing →



References
  1. Akmal, M., Qadri, J. Q., Al-Aili, N. S., Thangal, S., Haq, A. & Saloom, K. Y. (2006) Improvement in human semen quality after oral supplementation of vitamin C. J Med Food, 9, 440-2.
  2. Greco, E., Iacobelli, M., Rienzi, L., Ubaldi, F., Ferrero, S. & Tesarik, J. (2005) Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J Androl, 26, 349-53.
  3. Tremellen, K., Miari, G., Froiland, D. & Thompson, J. (2007) A randomised control trial examining the effect of an antioxidant (Menevit) on pregnancy outcome during IVF–CSI treatment. Aust N Z J Obstet Gynaecol, 47, 216-21.
  4. Evenson, D. P. and Jost, L. K. (1994) Sperm chromatin structure assay: DNA denaturability. In: Darzynkiewicz Z, Robinson JP, Crissman HA, eds. Methods in Cell Biology. Vol 42, 2nd ed. Orlando, Fla: Academic Press: 159 –176.
  5. Bungum, M., Humaidan, P., Axmon, A., Spano, M., Bungum, L., Erenpreiss, J. & Giwercman, A. (2007) Sperm DNA integrity assessment in predicion of assisted reproduction technology outcome. Hum Reprod, 22, 174-9.
  6. Muriel, L., Garrido, N., Fernandez, J. L., Remohi J., Pellicer, A., De Los Santos, M. J. & Meseguer, M. (2006a) Value of the sperm deoxyribonucleic acid fragmentation level, as measured by the sperm chromatin dispersion test, in the outcome of in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril, 85, 371-83.
  7. Muriel, L., Meseguer, M., Fernandez, J. L., Álvarez, J., Remohi, J., Pellicer, A. & Garrido, N. (2006b) Value of the sperm chromatin dispersion test in predicting pregnancy outcome in intrauterine insemination: a blind prospective study. Hum Reprod, 21, 738-44.
  8. Velez De La Calle, J. F., Muller, A., Walschaerts, M., Clavere, J. L., Jimenez, C., Wittemer, C. & Thonneau, P. (2008) Sperm deoxyribonucleic acid fragmentation as assessed by the sperm chromatin dispersion test in assisted reproductive technology programs: results of a large prospective multicenter study. Fertil Steril, 90, 1792-9.
  9. Henkel, R., Hajimohammand, M., Stalf, T., Hoogendijk, C., Mehnert, C., Menkveld, R., Gips, H., Schill, W. B. & Kruger T. F. (2004) Influence of deoxyribonucleic acid damage on fertilization and pregnancy. Fertil Steril, 81, 965-72.
  10. Carrell, D. T., Liu, L., Peterson, C. M., Jones, K. P., Hatasaka, H. H., Erikson, L. & Campbell, B. (2003) Sperm DNA fragmentation is increased in couples with unexplained recurrent pregnancy loss. Arch Androl, 49, 49-55.

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