The Sperm DNA Integrity assay (SDIA) like the Sperm Chromatin Structure Assay

(SCSA) is a tool for measuring clinically important properties of sperm nuclear chromatin integrity. Chromatin is that portion of the cell nucleus which contains the entire DNA of the nucleus in animal or plant cells.

The results correlate well with the potential of sperm from a given male to produce embryos that would be sufficiently “competent to produce a live birth. The SDIA utilizes the metachromatic features of acridine orange (AO), a DNA probe, and the principles of flow cytometry (FCM).

SDIA data are not well correlated with classical sperm quality parameters and have been solidly shown to predict sub/infertility and poor reproductive performance. The SDIA measures DNA damage. The degree of abnormalities in the genetic material of the sperm is expressed numerically as the DNA Fragmentation Index (DFI). DNA damage may be present in sperm from both fertile and infertile men. Therefore, this sperm DNA damage analysis may reveal a hidden abnormality of sperm DNA in infertile men classified as unexplained based on apparently normal standard sperm parameters.

Infertile men with abnormal sperm characteristics exhibit increased levels of DNA damage in their sperm. Sperm from infertile men with normal-appearing sperm may have DNA damage to a degree comparable to that of infertile men with abnormal-appearing sperm. The data suggests that an abnormal SDI assay is more likely to occur in cases of abnormal semen parameters.

Cancer treatments are well known to adversely affect male fertility. Reduction of sperm output arises from the cytotoxic effects of chemo-or radiotherapy upon the spermatogenic epithelium.

Optimal sperm chromatin packaging seems necessary for full expression of the male fertility potential. SDI assays emerge as predictors of the probability to conceive and carry the pregnancy to viability.

The improvement seen in sperm motility after treatment is not associated with a similar improvement in sperm DNA integrity (SDIA assay results). These data suggest that sperm processing techniques will not minimize sperm DNA damage and the potential transmission of genetic mutations in assisted reproductive cycles.

It is important to add that most current data available on the significance of abnormal SDIA results in infertile couples seeking treatment has emanated from non-IVF pregnancies.

Preliminary data suggests the following:

• The viable (>12 weeks) IVF pregnancy rate (and thus presumably also the birth rate) could be as much as 2 times lower in women under 33yrs of age, whose husbands have abnormal SDI assays ( with a DFI of <30%). Results become progressively worse with advancing maternal age such that at 35 yrs+, the viable pregnancy rate could be as much as 3-4 times lower.
  

• Although it is possible for abnormal SDIA results to sometimes spontaneously revert back to normal, this probably occurs quite infrequently.
  

• Although abnormal SDIA results are detected in men with apparently normal semen analyses, abnormal results are more commonly seen in cases of men who have abnormal sperm parameters (abnormal sperm count, motility and/or morphology)
  

• There is some suggestion that the use of antioxidant therapy ( Pycnogenol 200mg daily, L-Carnitine 3 grams per day, acetyl carnitine
  
  
  500mg per day, Vitamin C 1,000mg per day, Vitamin E 800IU per day and acupuncture and certain herbal medicines) taken for several months, can causes the SDI assay to revert to normal in many cases.
  

There is some suggestion that men who have varicoceles ( a collection of distended veins in the scrotum) associated with an abnormal SDI assay may experience a reversion of the SDI assay back to normal, 3-6 months following surgical or radiological ablation of the varicocele. Of course acupuncture and herbal medicine will enhance and stimulate blood flow to the testicles facilitating a more rapid recovery with greater possibility of healthy sperm production after a varicocelectomy.

In summary, an abnormal SDI assay augers poorly for the outcome of fertility treatment in general and IVF/ICSI in specific. In such cases, the fertilization rate and pregnancy rates are reduced and the chance of early pregnancy loss appears to be increased significantly. An abnormal SDIA result does not totally preclude a successful pregnancy.

The prognosis worsens progressively as the age of the egg provider advances beyond 33 yrs. Although abnormal SDIA results rarely revert to normal spontaneously this can and does happen on occasion.

Selective surgical ligation of a varicocele and medical anti-oxidant treatment may be effective in restoring the SDIA to normal. Antioxidant properties are to be found in Vitamins C and E and herbal medicine specific to this situation.

It is quite likely that the SDIA or the SCSA will in time become regarded as required baseline tests (to be performed, regardless of their basic traditional semen analysis parameters (count, motility and sperm morphology) in all cases of recurrent pregnancy loss and IVF where the sperm provider has not previously participated in a pregnancy that has proceeded beyond the 12th week (the traditional point of likely viability).

It should be noted that when the typical sperm analysis reveals normal count, morphology and motility this does not mean that sperm DNA fragmentation is not manifest. In other words, unless the SDIA test is specifically run, fragmentation issues will not be revealed. This type of case then may be labeled ‘idiopathic' infertility.

It is our opinion based on clinical experience that ideally, both the man and the women should be treated even if there is no apparent male factor evident. The reason for this is that stress has been shown to reduce sperm count. Going through the tortuous trial of trying to conceive leaves many couples extremely stressed out. So, which at the time of sperm analysis everything appears normal, over time, due to the stress inherent with the situation, the sperm quantity may in fact be effected.

Therefore, including acupuncture, herbal medicine and the proper supplements can be seen as either reactive (if pathology is evident) or proactive (if pathology is not evident). It is our opinion that proactive behavior often obviates the need to be reactive. Prevention is key.

Dr. Mike Berkley has been treating male factor fertility disorders since 1996 with amazing results. He works exclusively in the area of reproductive medicine and enjoys working in conjunction with some of New York’s most prestigious reproductive endocrinologists. Sign up for his free newsletter at www.BerkleyCenter.com.