Impact of Antioxidant Treatment on DNA Fragmentation Index
Condition: Male Infertility
MeSH terms: Infertility; Infertility, Male
Study type: Interventional

Summary: 
      Increased sperm DNA Fragmentation Index implies decreased male fertility in vivo and in
      vitro. There is need for developing new strategies for improvement of male fertility. The
      study aims to investigate whether high sperm DNA Integration Index can be treated by use of
      antioxidants.
    

Detailed description: 
      In the Western world, approximately 15-20% of couples experience infertility problems during
      their reproductive life. In this context ´'infertility' is defined as 12 months of
      unprotected intercourse without getting pregnant.

      Although there is limited access to reliable diagnostic methods, it is assumed that in at
      least 50% of all cases 'male subfertility' is a contributing or the main cause of the
      infertility of the couple. The gold standard in assessment of male reproductive function is
      standard semen analysis including evaluation of sperm number, motility and morphology.
      Although efforts have been made in to improve and standardise the methodology for semen
      analysis, there are no well established cut off levels for sperm concentration, motility or
      morphology which accurately predict the chance of pregnancy or indicate which assisted
      reproductive technique (ART) - the most frequent therapy for infertility- will ultimately be
      the most effective. This lack of diagnostic tools is not only hampering proper management of
      infertility but also represents a serious limitation in relation to the understanding of
      biological underpinnings of the disorder and as a consequence, the development of cause
      related treatment modalities.

      Although various novel alternative methods of assessing semen quality have been developed, so
      far, none have contributed to or altered our clinical approach to the treatment of infertile
      couples. During the passed two decades a lot of attention has been paid to impairment of
      sperm DNA integrity as a possible cause of male subfertility. There are different techniques
      currently available for the assessment of sperm DNA integrity e.g. Sperm Chromatin Structure
      Assay (SCSA®), Comet, TUNEL and sperm chromatin dispersion test. Generally, the use of these
      tests has shown an increased proportion of sperm with fragmented DNA structure among
      subfertile men as compared to proven fertile or men from general population. Although
      measuring different characteristics of the status of sperm DNA (e.g. presence of single and
      double strand breaks, propensity to damage and probable cause of the fragmentation),
      comparisons of the results obtained with two or more of these tests show a correlation
      coefficient of a magnitude 0.4 to 0.6, indicating that, although not completely overlapping,
      the tests to a certain extent assess some of the same characteristics of sperm DNA. Another
      interesting finding is that there is only a weak to moderate correlation between standard
      sperm parameters and measures of DNA integrity, the level of association (correlation
      coefficient ~ 0.6) the most pronounced being for motility. This means that assessment of
      sperm chromatin integrity adds to the information obtained by standard semen analysis.

      The most appraised, standardised and studied of the sperm nDNA tests is the SCSA® which is
      based on a very well defined protocol for handling of samples and subsequent data analysis.
      The robustness of the techniques was exemplified by a comparison of the SCSA® analysis of
      almost 200 samples results performed by two independent laboratories which found a
      correlation coefficient of 0.9 with mean difference between the DNA Fragmentation Index (DFI)
      results of about 1%. A further advantage of the SCSA® method over the remaining assessment
      techniques is the relatively large number of studies that have utilised the technique in
      clinical settings constituting a considerable record of the method's performance in
      predicting fertility outcome.

      Briefly, these data indicate that the chance of spontaneous pregnancy decreases at DFI levels
      above 20% and approaches zero if DFI exceeds 30%. This is also true for Intrauterine
      insemination (IUI). However, it seems that even spermatozoa from samples with high DFI can be
      used for in vitro fertilisation by standard IVF or ICSI, with some data suggesting that ICSI
      might actually be more efficient using samples with high (>30%) DFI. A finding, which may at
      first appear paradoxical but may be a reflection of the relative probability of fortuitously
      selecting a sperm with intact DNA. The data regarding fertilisation rate, embryo quality and
      risk of miscarriage in relation to DFI are also conflicting.

      The biological mechanisms responsible for DNA strand breaks and other types of impairment of
      sperm DNA integrity are not completely known. Amongst others incomplete DNA repair during
      spermiogenesis, abortive apoptosis and/or increased level of oxidative stress have been
      suggested as possible options .

      The overall aim of this project is to evaluate effect of restoring oxidant balance using
      Androferti, (Q Pharma Laboratories; Alicante, Spain) on sperm DNA integrity in subfertile men
      with high level of DFI.
    

Intervention name(s): Androferti; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double blind randomised placebo controlled study
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: sperm DNA strand breaks; antioxidants