Advanced Sperm Functional Testing

 

Figure 1: Sperm DNA Fragmentation testing (SDF). TUNEL assay, Promega.

Figure 2: Sperm Chromatin condensation analysis using the Aniline Blue stain.

Figure 3: Seminal Oxidative Reductive Potential testing system. Mioxsys system.

Sperm DNA Fragmentation and Oxidative Reductive Potential Testing

Male infertility is a relatively common medical condition affecting up to 12% of men globally. The Centres for Disease Control and Prevention (CDC) report a 9.4% infertility rate among men in the USA. Male partners are found to be solely responsible for 20–30% of infertility cases and contribute to approximately 50% of cases overall. Many clinicians rely on conventional semen analyses as a surrogate measure of a man’s ability to father a child. However, this approach seems to be an oversimplification of the assessment of male fertility potential due to large intra- and inter-individual variations in conventional semen parameters and is unable to precisely predict the likelihood of pregnancy. Advanced tests of sperm function have been proposed as alternative methods that can enhance the diagnostic accuracy of male infertility particularly in cases of unexplained infertility, one or more abnormal semen parameters, recurrent pregnancy loss or failure of intrauterine insemination.

At Cape Fertility we offer advanced sperm functional testing which includes the assessment of Sperm DNA Fragmentation, Sperm Chromatin Condensation and seminal Oxidative- Reductive Stress testing.

The integrity of genetic material in the sperm is crucial for successful fertilisation and normal embryo development. Sperm DNA fragmentation (SDF) is a term used to describe the genetic material within the sperm, which could impact the fertility potential of the male, IVF/ICSI outcomes and has been shown to be associated with miscarriage. A conventional semen analysis cannot assess the sperm at the molecular level and, as result aid the detection of DNA fragmentation. The ORP test is novel in the area of infertility. The MiOXSYS system provides an estimation of the static oxidation-reduction potential (sORP). It represents the integrated measure of the existing balance between total oxidants and reductants in a biological system.

Studies in the literature have shown that:

  • Abnormal Sperm DNA fragmentation and oxidative stress levels affects blastocyst development
  • The higher the DNA fragmentation levels, The higher chances of failed assisted conception treatment and miscarriage
  • Sperm DNA fragmentation is higher in sub-fertile men with abnormal sperm parameters
  • Men with normal sperm parameters are also found to have high sperm DNA fragmentation and abnormal levels of oxidative stress

Advantages of the Sperm functional testing

  • Provides a comprehensive analysis of sperm DNA integrity, Sperm chromatin packaging and seminal oxidative reductive potential that may help to identify men who are at risk of subfertility
  • Provides information that helps in the clinical diagnosis, management and treatment of male fertility
  • Provides prognostic value in assessing the outcome of assisted conception treatment

High rates of sperm DNA fragmentation and pregnancy potential

  • Normal, healthy pregnancies do occur in couples where the male partner has high percentage of sperm with fragmented DNA, although the chances are significantly reduced, as the percentage of sperm bearing low levels of DNA fragmentation is much lower
  • Embryos derived from sperm with highly fragmented DNA have poor prognosis
  • DNA fragmentation could result in initiation of apoptosis (natural cellular death) and mutations resulting in blastocyst arrest, miscarriage and abnormalities in the offspring
  • Spermatozoa with high DNA fragmentation fertilising younger oocytes than older oocytes carry a better prognosis of successful pregnancy, as the are much more efficient at DNA repair of defective sperm

Causes of Sperm DNA Fragmentation

In men, the major contributing factor for sperm DNA fragmentation is oxidative stress, which can be associated with one or more of the following:

  • Infection
  • Pyrexia
  • Elevated testicular temperature
  • Recreational drugs
  • Smoking
  • Alcohol
  • Stress
  • Diet
  • Environmental and occupational pollutants
  • Advanced chronological age
  • Varicocoele

Indications for men who may benefit from sperm functional testing

  • Unexplained infertility
  • Arrested embryo development
  • Poor blastocyst development
  • Multiple failed IVF/ICSI treatments
  • Recurrent miscarriage
  • Advanced chronological age
  • Varicocoele
  • Poor semen parameters
  • Exposure to harmful substances

Treatment of abnormal sperm functional testing

It depends essentially on the cause. If the damage is caused by free radicals, a change in lifestyle and diet designed to protect against oxidative stress may help reduce the levels of DNA fragmentation. Other treatment options include:

  • Antibiotics in the co-existence of an infection
  • Life style changes – drugs, smoking and occupation
  • Diet – fresh foods, particularly those containing antioxidants and vitamin C&E
  • Varicocoele surgery
  • Testicular aspiration of sperm (DNA damage occurs at the post-testicular level, hence testicular sperm may have a better DNA integrity than ejaculated sperm)
  • ICSI rather than IVF

Initiatives to reduce the levels of fragmentation or oxidative stress can be assessed by undertaking a second test three months later.

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