Sperm DNA Fragmentation – summed up

Male infertility in many men is no longer a “hidden fact”. It is now acknowledged and accepted that, in nearly half the cases of infertile couples, it is the male who is the contributor. The identification of the source of the problem is important and, for that, the traditional semen analysis test has traditionally been the first step of evaluation and diagnosis of male infertility. It provides details on the external characteristics of the sperm such as the semen volume, vitality, motility, concentration and morphology of the sperm.

However, the semen analysis alone does not provide all inclusive details of the fertilizing potentiality of the sperm. More advanced methods are required to find the cause of infertility and its relationship with a successful conception.

SDF – Sperm DNA fragmentation or DFI – DNA Fragmentation Index has become more relevant, since many infertile men have shown increased levels of the sperm DNA Fragmentation.

SDF takes place during spermatogenesis when, as a result of factors such as abortive apoptosis, or defects in the sperm maturation process or DNA damage (mismatched bases, crosslinking, DNA strand breaks), the sperm DNA integrity is compromised and sperm are produced with highly fragmented DNA.
Apoptosis is a process of elimination of unfit cells in the body; however when some of these cells escape this apoptosis step, they proceed to become adult sperm albeit with defects and faulty genetic material. Sperm maturation involves replacement of histones by smaller proteins called Protamines. While these protamines assist in sperm DNA compaction, it hinders sperm DNA self repair in response to exogenous or endogenous environments. Twisting tensions from the double strand DNA helix can cause misfolding of the supercoiling DNA structures in the chromosome which can result in deviant DNA repair, leading to SDF or abnormalities in the chromatin structures. Oxidative stress is also one of the most prominent causes of SDF and can arise due to a number of factors. A Varicocele or inflammation in the external genital organs can induce ROS (reactive oxygen species) and increase chances of SDF. Other causes for SDF have been associated with infertility risks such as lifestyle and food habits, smoking, alcohol, environmental toxins, infectious diseases and pollutants.

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SDF can be categorised into SSBs and DSBs – single strand breaks in the DNA and double strand DNA breaks. Generally, single strand breaks are related to oxidative stress while double strand breaks possibly relate to an absence of DNA repair in meiosis (cell division in sexually reproducing organisms that reduce the number of chromosomes in gametes or sex cells). Exposure to external factors such as radiation and chemicals as well as internal processes such as DNA replication and repair can cause these breaks. SSBs are usually the cause of lack of clinical pregnancy or an increase in the time to conception. DSBs are generally confined to the sperm nuclear matrix and cause low embryo quality and higher risks of miscarriages or failure of implantation after ICSI treatment.

Research has shown that while there was no difference in general health (basic FSH levels and BMI) among patients with high, medium or low DFI, there was a significant contrast in semen factors such as sperm concentration and motility. While clinical pregnancy rates did not differ much, early abortion rates were increased among those with higher and medium DFI when compared with those who had low DFI.

The impact of SDF is seen on fertilization, development of embryo and transmission of paternal genetic traits during pregnancies. Recent studies have shown that high DFI does affect the quality of embryos but it does not impact oocyte fertilization or pregnancy rates following IVF. By pre-treating the semen before IVF fertilization, the rate and development of the embryo may be improved.

For this, the DFI testing is essential, as it shows the integrity of and damage to the sperm DNA. Detection of sperm damage can be carried out, the results of which will help a fertility expert to advise relevant treatment.

The 4 main tests available to evaluate the sperm DNA are the SCSA (sperm chromatin structure assay), TUNEL, SCD (sperm chromatin dispersion test) and Comet assay (single cell gel electrophoresis).

Andrology Center is the only authorized laboratory in India to carry out the authentic SCSA (sperm chromatin structure assay) test. With the use of a highly standardised laser equipment and specialised technology, accurate results are guaranteed, which assist both the Clinician and Patient in choosing the most beneficial medical treatment.