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 gollowing:
• 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.