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Approximately
one in six couples are affected by infertility and there
are a number of factors, both male and female, that
can cause the condition. In fact, in nearly 30% of cases
the cause is attributed to the female, in 30% the cause
is attributed to the male, in 30% the cause is attributed
to both and in 10% of cases the cause is unknown. In
at least 30% of male factor cases, the actual cause
of infertility is unknown. The methods for evaluation
of male infertility have typically been limited to a
semen analysis measuring count, motility and morphology
of the sperm. New studies suggest that sperm with certain
levels of DNA fragmentation serve as a strong predictor
of reduced male fertility. The Sperm Chromatin Structure
Assay (SCSA) is a test that is offered to measure the
level of DNA fragmentation in the sperm, to enhance
the diagnosis of and treatment for male infertility.
Research
indicates that sperm with high-levels of DNA fragmentation
have a lower probability of producing a successful pregnancy.
A review of data on hundreds of semen samples show that
patients with a DNA fragmentation level of greater than
30% are likely to have significantly-reduced fertility
potential, including a significant reduction in term
pregnancies and a doubling of miscarriages. Sperm that
appears to be normal by traditional semen analysis parameters
(motile, morphologically normal sperm) may even have
extensive DNA fragmentation. In an effort to achieve
the most effective measurement of male fertility potential,
the SCSA reports the percentage of the following four
major populations of sperm present in a semen sample:
- Sperm
with a low level DNA fragmentation
- Sperm
with increased susceptibility to DNA denaturation
classified into a moderate and a high level of defragmentation
- Sperm
with immature chromatin due to less chromatin condensation,
allowing for a higher degree of DNA stainability
The
SCSA is performed using an instrument called a flow
cytometer in which cells that have been stained with
a fluorescent dye are sent through a glass channel in
liquid suspension. The cells pass through a laser beam
and the light from the beam causes the dye to emit fluorescent
light of a certain color. When performing an SCSA, the
colors measured are red and green; green fluorescing
sperm have very low levels of fragmented DNA and red
fluorescing sperm have moderate to high levels of fragmented
DNA.
While
the semen analysis has been the standard for male fertility
analysis in the past, the introduction of the SCSA offers
many advantages over existing clinical assays for a
number of reasons. First of all, the SCSA can measure
5000 individual sperm in just seconds and the data provides
both a diagnostic and prognostic evaluation of the male's
potential for subfertility or infertility. Another advantage
of note is the fact that the data are from objective,
machine-defined criteria rather than from biased human
eye measurements as with a standard semen analysis.
In addition to having a higher level of repeatability
than that of any other semen parameter, the SCSA randomly
measures all cell types in the semen sample as opposed
to evaluation of only washed samples.
In
a study of 700 in vitro fertilization (IVF) cases in
which intracytoplasmic sperm injection (ICSI) was performed,
pregnancy occurred in less than 1% of the cases when
the percentage of sperm with damaged DNA was greater
than thirty. Another study confirmed greater than 30%
DFI (% sperm with damaged DNA) as a significant lack
of fertility potential, 15-30% DFI as reasonable potential
and less than 15% DFI as high fertility potential. In
this study, 84% of men who fell into the "high
fertility potential" category with a DFI of 15%
or lower conceived within the first three months.
There
are a number of factors that may help explain why a
certain individual has high DNA fragmentation in the
sperm, resulting in low fertility potential. When examining
SCSA studies, length of sexual abstinence, age (significant
increase in DFI after age 46), smoking history and exposure
to high levels of air pollution all factor into significant
variations in results. Sperm chromatin structure is
also compromised in patients with leukocytospermia,
febrile illness and testicular cancer. Significant exposure
to prolonged heat in the testicles can also contribute
to high levels of fragmentation; for example, excessive
hot tubbing, truck driving and avid cycling are all
key factors in poor SCSA results. Drug use, exposure
to chemicals or radiation and testicular trauma are
other potential causes of abnormal results. The SCSA
is also helpful in identifying men who may have a varicocele,
a tangle of veins surrounding the testicle. Surgical
correction of varicoceles significantly restores fertility
potential in about two-thirds of the cases.
The
SCSA is not a replacement for the semen analysis as
the tests analyze different levels in the sample and
should both be performed. When the results of both tests
are analyzed, the patient can feel confident that he
has all the information available about his chances
of initiating a pregnancy through assisted reproductive
technologies.
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