DNA Fragmentation

DNA fragmentation is a form of DNA damage, whereby DNA strands break off into small pieces, compromising molecular integrity. DNA fragmentation in the sperm has been strongly associated with male infertility and poorer ART outcomes, with impaired embryo development, recurrent pregnancy loss and birth defects. Therefore, investigating its presence is an important part of male factor infertility assessment and is performed by measuring the DNA Fragmentation Index (DFI). DFI is the ratio of sperm cells with fragmented DNA over the overall number of sperm cells in the sample, expressed as a percentage.

While definition may vary amongst laboratories, in general DFI is considered normal when under 15%, 15-30% is associated with effects on fertility, particularly in the presence of additional abnormal sperm parameters (See semen analysis) and over 30% is considered high and has a considerable impact on fertility.

Although routine semen analysis remains a reliable assessment tool, it does not always reliably predict fertility and pregnancy success rate on its own. Combined with the fact that a significant proportion of men with infertility have been found to also have increased DFI while their semen analysis is normal, DFI measurement might be particularly indicated in the following cases:

  • Presence of risk factors for increased DFI:
    • Advanced reproductive age (>40 years)
    • Urogenital tract infections
    • Smoking
    • Drug abuse
    • Exposure to pollutants and contaminants
    • Varicocele
    • Elevated testicular temperature
    • Chronic illnesses (diabetes)
    • Malignancy and related treatments
    • Poor diet and obesity
  • Unexplained infertility
  • Recurrent pregnancy loss, recurrent implantation failure, intrauterine insemination failure
  • Previous failed IVF or IVF/ICSI
  • When testicular rather than ejaculated sperm is considered as an option

If increased DFI is detected, the main treatment strategy is to eliminate the etiological factors and wait for the new sperm to form in a couple of months. Therefore, the available treatment options include:

  • Evaluation and repair of varicoceles
  • Reducing long hot baths and tight-fitting underwear
  • Adopting a healthier lifestyle
  • Reducing or ceasing smoking/drugs
  • Vitamin and antioxidant supplementation

In the cases where these methods prove ineffective, advanced sperm selection methods may be employed. While they do not improve sperm quality directly, they ensure that only higher quality sperm is used in IVF/ICSI and increase the chances of normal DNA integrity sperms reach and fertilize the oocytes.