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.
© Mark Perloe, MD
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