DNA fragmentation test

What is a sperm DNA fragmentation test?

Over the years, a number of tests assessing sperm DNA damage have been developed.

The results produced by a DNA fragmentation test reveal the percentage of DNA damage within a representative number of individual sperms, and they are presented as the DNA Fragmentation Index (DFI) for an examined semen sample. A high DFI means that a high percentage of sperms within the sample has undergone DNA fragmentation, and a low DFI means that the majority of sperms within the sample maintains their genetic integrity.

A high DFI is considered to be a cause for infertility and poor-outcome Assisted Reproductive Technique (ART), but conclusive evidence remains to be established.

The purpose of sperms is to deliver the male DNA contribution to an egg after fertilization. If their genetic contribution is damaged, and fertilization happens, further developmental stages of the early hybrid cell, composed of egg-and-sperm DNA, may be either halted or allowed to proceed. This will depend on the actual DNA damage and the capacity of the hybrid cell or early embryo to repair it.

When we find a patient with high DFI, our approach depends on the clinical situation. Sometimes, it is easy to identify the factor responsible for DNA fragmentation on sperm (for instance, smoking or high alcohol consumption), and correct it. We also recommend a parallel course with antioxidants, which is the most popular and recognized treatment for this condition.

Who may need a sperm DNA fragmentation test?

This test is recommended to men that have faced an infertility issue, and a classical semen analysis has not been able to pinpoint the problem.

A DNA fragmentation test is essential, especially in cases that there has been a previous ART failure, unexplained infertility, or repeated miscarriages. A low or high DFI might be able to shed more light in understanding these cases.

DNA sperm integrity is sensitive to extremes of temperature, to chemical, toxic or radiation exposure (including treatment for cancer), cigarette smoking, high alcohol or drug consumption, medical conditions (for instance, varicocele, sexual transmitted diseases), or testicular injury.

Sperm production in the testes is a continuous process, with a sperm maturation cycle taking about 11-12 weeks. Management of the risk factor(s), treatment for the responsible medical condition, or testicular healing after an injury may be able to reverse the negative effects on sperm DNA within a period of 3-6 months. In those cases, a repeat semen analysis in conjunction with a DNA fragmentation test will be able to show the improvement.

How is a sperm DNA fragmentation test done?

DNA fragmentation testing is done by one of our andrology technologists in the laboratory following sperm collection for analysis.

After semen processing, sperms are treated with an acidic solution that allows the release of their DNA (Halosperm®). Following, small suspensions of these treated sperms are mixed with a drop of a gelatinous medium on a glass slide and observed under fluorescence microscopy. While sperms are dispersing within the gelatinous material, their released DNA, if non-fragmented, produces a characteristic halo around it that is visible under the microscope. However, if it is fragmented, the halos observed are either very small or not produced at all*. A DFI is calculated by assessing a representative number of sperms from the collected semen sample.

What can a sperm DNA fragmentation test tell us about the success of ARTs?

Currently, there is not a set threshold for levels of DNA fragmentation with a negative effect on fertility and ART outcome. This is because there are so many confounding factors for DNA fragmentation, in addition to extensive variation of individual circumstances and other underlying causes of infertility.

High DFIs have been associated with poor-outcome ARTs, but this has not been always the case and different studies** have drawn conflicted conclusions on the matter.

Efforts in standardizing the test assessing DNA fragmentation across clinics in the US, UK and Europe may improve our understanding in the future.

Here in AAFC, we use the sperm DNA fragmentation test in conjunction with other diagnostic tests in order to understand persistent infertility, previous ART failure and repeated miscarriages. We can help you take an informed reproductive decision and offer you support, when necessary. Our specialist doctors will provide you with a comprehensive consultation for all other available / applicable options and explanations.

References

* Fernandez JL, Muriel L, Rivero MT, Goyanes V, Vazquez R, Alvarez JG (2003). The Sperm Chromatin Dispersion Test: A Simple Method for the Determination of Sperm DNA Fragmentation. J Androl. 24(1): 59-66. (Pubmed; PMID: 12514084)

** Zhao J, Zhang Q, Wang Y, Li Y (2014). Whether sperm deoxyribonucleic acid fragmentation has an effect on pregnancy and miscarriage after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis.  Fertil Steril. 102(4): 998-1005. (Pubmed; PMID: 25190048).