You have heard me talk about a variety of different sperm tests such as the semen analysis
and Cap Score.
There is however, another type of sperm test that I have not discussed.
These are tests that look at whether there is fragmentation in sperm DNA.
Is this a worthwhile test?
Stay tuned.
What are sperm?
Sperm are very small delivery vehicles to get the genetic material from a male into
the egg of the female.
The genetic material inside of sperm is called DNA.
You have probably seen drawings of the structure of DNA like this one.
This is called a double helix.
In order to fit inside of the very small sperm, these double helix strands of DNA are twisted
and wrapped around tiny blocks of proteins.
It is thought that this tight packaging helps the DNA from being damaged until the sperm
reaches the egg and delivers the DNA.
Sometimes, however, this protection isn't enough.
The DNA strands might develop breaks.
Doctors refer to this as DNA fragmentation.
While many cells contain enzymes to repair broken DNA, sperm cells lack this ability.
Broken or fragmented DNA strands stay broken until the sperm reaches and fertilizes the
egg.
There are many factors that have been associated with an increase in the percentage of sperm
with DNA damage.
These include cigarette smoking, infections, testicular cancer, chronic heat exposure,
exposure to pesticides, and even air pollution.
There are several tests that are used to determine whether sperm has DNA breaks.
The actual names of these tests are long and complicated so I will refer to their shorter
names.
DNA fragmentation tests can be divided into two groups: direct tests and indirect.
The direct tests try to detect actual DNA breaks and include the TUNEL test, the COMET
test and the Nick Translation or NT test.
Indirect tests look at how easily the sperm DNA is damaged after adding some harmful chemical
such as acid treatment.
The most commonly used indirect tests are the SCSA test, Acridine Orange test, the DBD-FISH
test and the Halo test.
The first big problem with these sperm DNA fragmentation tests is that they use all these
different methods to get a result.
But they don’t always agree with each other.
For example, a sperm sample which looks abnormal with the TUNEL test may be normal with the
SCSA test.
This makes it impossible for fertility experts to compare the results of studies that use
different methods.
When evaluating how good a test is, doctors can use a tool called ROC curves.
This gets kind of complicated but all you need to understand is this.
A really good test has a curve that looks like this.
If the ROC curve looks like this, then it is completely useless and is really no better
than flipping a coin.
A recent study looked at the ROC curves for the four most common sperm DNA fragmentation
tests, this is what they found.
Each one was little better than a coin flip
Another problem with this testing is that nobody can agree how and when to do the testing.
Should a man abstain from ejaculation for 1 day, three days or not all?
When the sperm is collected, should the lab analyze it right away?
Or should the sperm be prepared in some way first?
These changes can all result in significant changes in the amount of sperm that show evidence
for fragmentation
A final problem is that there isn’t agreement on the cutoff for deciding what percentage
of sperm with DNA fragmentation is abnormal.
Studies have used cutoffs ranging from 7% to 15% to 40%
OK, lets say that despite all of these limitations, your doctor insists on ordering a sperm fragmentation
test and has some protocol for how to collect and prepare the sperm for the test.
Do abnormal tests identify couples with a lower chance for having a live born baby with
IVF?
Well, some studies have shown lower pregnancy rates but some have not.
When there are many small studies that have different conclusions, combining them into
a larger study, which is called a meta-analysis can help to clarify confusing results.
This meta-analysis looked at the results of 30 studies to determine the impact of sperm
DNA fragmentation test on IVF.
The researchers found that there was no difference in the pregnancy rates whether sperm had higher
or lower amounts of fragmentation with any of the commonly used tests.
Our infertility TV bottom line is this.
Sperm DNA fragmentation test are interesting and deserving of further study.
They are not however adequate to determine which couples might achieve pregnancy during
an IVF cycle.