Sperm DNA Fragmentation

SPERM DNA FRAGMENTATION

The conventional semen analysis does not address the nuclear integrity of the spermatozoa. 37 % of men with normal semen profile have damaged DNA. The human spermatozoa has a peculiar structure as it is the smallest motile cell in the human body and has little or no cytoplasm. It has high content of polyunsaturated fatty acids in the cell membrane making it more prone to oxidative stress – free radical formation. Sperm DNA is highly compact and metabolically inactive; DNA histones are replaced by protamine in the sperm DNA for the DNA compaction.

What Is DNA Fragmentation?

DNA fragmentation is the separation or breaking of DNA strands into pieces. DNA fragmentation can be a testicular event or a post- testicular event.

Causes Of DNA Fragmentation:

  • Oxidative stress due to reactive oxygen species (ROS)
  • Imbalance between ROS and antioxidants.
  • Abortive apoptosis during spermatogenesis.
  • Unfavorable epididymal environment.
  • Environmental factors like radiation, pesticides, xenoestrogens etc.
  • Lifestyle factors like smoking, drinking and obesity.
  • The main source of ROS in semen includes leukocytes, abnormal/immature sperm, increased scrotal temperature, varicocele, advanced paternal age, estrogens.
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DFI (DNA fragmentation index) test is an effective method for measuring % sperm with fragmented DNA in the ejaculate.

Threshold Values:

  • ≤ 15% DFI = excellent to good sperm integrity
  • 15 to <25 % DFI = good to fair sperm DNA integrity
  • >25 to <50 % DFI = fair to poor sperm DNA integrity
  • ≥ 50 % DFI = very poor sperm DNA integrity

Why Should DFI Test Be Carried Out?

  • A high level of DNA fragmentation in sperm cells may represent a cause of male infertility that conventional examinations and tests – sperm concentration, motility, morphological assessment cannot detect.
  • The genetic integrity of sperm is important for normal embryo development.
  • Elevated levels of DNA fragmentation above the critical threshold will significantly compromise the possibility of successful implantation.
  • DNA fragmentation levels are closely correlated with miscarriage rates.

Indications Of Male Patients Who Can Benefit From The Test:

  • Poor blastocyst development
  • Failed IVF/ICSI cycle
  • Recurrent miscarriage
  • Advanced age
  • Varicocele
  • Poor semen parameters
  • Unexplained infertility
  • Exposure to heat, radiation, chemicals
  • Addiction- smoking, alcohol

Test Used To Detect Sperm DNA :

Sperm Chromatin Dispersion (SCD) Test – SCD is based on the principle that sperm with fragmented DNA fail to produce a characteristic halo of dispersed DNA loops that are seen in sperm with non-fragmented DNA, following acid denaturation and removal of nuclear proteins.

Treatment: Sperm DFI can be treated by lifestyle management and by giving an empirical oral antioxidant therapy for 3 months. Male partners can be asked to repeat Sperm DFI after 3-4 months of therapy and accordingly further treatment can be decided.

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