Special Edition: SCSA

Welcome to a Special Edition of Conceive This! As we have all learned, our doctors all have an opinion. Didn't you ever wonder how my doctor's opinion completely contradicts your doctor's opinion? Do you wonder how they actually reach their conclusions about things? Maybe you did wonder, or maybe you could care less. I always wonder.

For every test, for every medication, for every diagnosis, I didn't just want to hear, "You must do X, Y, Z." I wanted to know what X, Y, and Z were. I wanted to know what research had been done on X, Y, and Z. I wanted to know what the textbooks said about X, Y, and Z. I wanted to know how X, Y, and Z impacted the reproductive system, the circulatory system, the 'you-so-crazy' system.

In this special edition, we will take some time to educate ourselves about the SCSA test, evaluate the evidence surrounding it, and make comparisons regarding just how shitty our comparative semen specimens really are. This special edition is not meant to influence your decision to have an SCSA, to give an opinion about your choice of having done an SCSA, or to cause you to scream at your doctor for have/not having made this test available to you. As with most things in life, you can do whatever the hell you want...you just better know what the hell you're doing.

If you have male-factor infertility, or even if you have had recurrent pregnancy loss or implantation failure, your doctor may suggest performing an SCSA test. The SCSA is a test that examines the DNA within the sperm for fragmentation. Fragment-who-tion? This test checks the DNA within the sperm for damage, breakage, and general nastiness. Why do we care about DNA nastiness? Well, as many of you know, those perfect little babies we desire are made up of 46 chromosomes. 23 of those chromosomes come from the egg, and 23 come from the sperm. When those 23 chromosomes combine, an embryo is formed, well, technically a zygote is formed, but whatever.

If fertilization occurs, the egg will chug along on it's own devices for about 3 days or so. Why? Sperm DNA damage does not appear to affect fertilization or the 2nd or 3rd cell division. On the 3rd day of division, when the embryo is around 4-8 cells, the 46 chromosomes activate.

Ding! The lights of potential life turn on, and the embryo's own DNA will control cell division and differentiation from 8 cells to two-thousand-hundred-gazillion-trillion cells. However, if the DNA from either the egg or the sperm is damaged, things won't proceed up to twothousandgazilliontrillion cells. Instead, things may proceed up to 12 cells, or 100 cells, or 259 cells...and then self-destruct in a process called apoptosis. Bam!.......the process goes haywire, the instructions are lost, and the embryo 'arrests'...which is a friendly way of saying 'stops dividing and disintegrates.'

This may happen once. This may happen twice. This may happen over and over and over until you run out of money or choose to move on. Is there a way to know if this may happen to you over and over and over again? The simple answer is no, however scientists, embryologists, and reproductive embryologists would love to be able to predict the future in this sense.....so invention happened.

You may think that the acronym 'SCSA' stands for 'Super Crappy Sperm Analysis', and in all reality, that is exactly what it is. SCSA actually stands for 'sperm chromatin structure assay.' What does that mean? The SCSA is a test that is able to measure the approximate percentage of sperm cells containing damaged DNA. Knowledge regarding the percentage of DNA fragmentation provides knowledge and information, but can it help guide treatment?

How does this test work? Easy. You send about 0.5mL of frozen sperm to a lab along with a few hundred dollars, and you wait a few weeks. When your sperm arrive at the lab, they will be defrosted and given a color job. They are treated with a special orange dye that attaches to broken DNA...so the damaged sperm will light up like a game hunter in a protective 'don't shoot me' jacket. After the touch-up, ten-thousand sperm will be analyzed by a machine called a flow cytometer, where they are lined up single file and passed under a beam of light that detects the orange dye. So, the super-crappy sperm are orange, and the normal sperm look green (because that grass is always greener). Your results are sent to you as a DNA Fragmentation Index, or DFI, which is the percentage of crappy sperm within the sample.

Why might this be important? The DFI has been associated with fertility potential as per the following:

Less than 15% DFI: Excellent potential
15%-30% DFI: Fair to Good potential
More than 30% DFI: Buh-bye. Poor potential.

So? And? What does this mean? Well, like all good opinions, it depends on who you ask. After reviewing a multitude of studies, there are some common themes that emerge...and some common controversies.

Number one common theme: If your DFI is >30%, shell out some cash and pay for IVF/ICSI. Most studies indicate very poor fertility potential if the percentage of damaged sperm is in the poor category, hence the name 'poor', as in, 'if you are in this category you will be poor by the time you get pregnant because you will have spent all your money on fertility treatments'. Fear not, because there are reported healthy pregnancies in patients with a DFI >60%....though I only found reports of this after IVF/ICSI.

Number two common theme: High DNA fragmentation is without a doubt correlated to severe male factor infertility. The crappier the sperm, the higher the liklihood that the DNA is damaged. However, high levels of DNA fragmentation have been found in sperm that a conventional semen analysis would not have tagged as severely abnormal. Signs that the DNA integrity may be compromised? Unexplained infertility, arrested embryo development, poor blastocyst development, multiple failed IVF/ICSI treatment, recurrent miscarriage in partner. Of course, remember. These same signs exist when egg quality is an issue...because even if it's the egg it is always a question of the DNA.

Do I need this test? The SCSA, like many diagnostic tests, provides information. It may or may not help you to make a decision. When the SCSA was first introduced, many studies were done. The initial studies pretty much said everyone should have an SCSA because it was impossible to get pregnant if your DFI was >30%. Indeed, it is more difficult, but after the initial flood of studies reporting the necessity of this test, several others came out that contradicted the first. These studies cited pregnancies even with elevated DFI in patients who utilized IVF/ICSI. Information may be a good thing. It may help you choose between an IUI and IVF. It may help you with nothing. It may provide you with relief, it may also provide you with anxiety. Do you need the test? It's up to you and your doctor.

What does the American Society of Reproductive Medicine say?
The guidelines set forth by the ASRM are what reproductive endocrinologists abide by...generally speaking. You can read what the ASRM has to say about the utility of sperm DNA testing here.

The summary is this:

• "Existing data on the relationship between abnormal DNA integrity and reproductive outcomes is limited.
• Sperm DNA damage is more common in infertile men and may affect reproductive outcomes in selected couples, including those with spontaneous miscarriage or idiopathic infertility.
• At present, the results of sperm DNA integrity testing alone do not predict pregnancy rates achieved with intercourse, IUI, IVF and ICSI.
• Currently, there is no proven role for routine DNA integrity testing in the evaluation of infertility.
• Treatments for abnormal DNA integrity have not been shown to have clinical value"

(The Practice Committee of the American Society of Reproductive Medicine, 2008).

That being said, the multitude of studies may speak for themselves. Every physician will have an opinion. Information is not necessarily a bad thing. However, if that information will not change your ultimate treatment goals, well, do you really care to know? Some do. Some don't.

What did I do? I read all about the SCSA and went to our initial consultation all but demanding it. My physician explained to me that he does utilize the SCSA in cases where couples want to try using timed intercourse or IUI, he does not recommend the test in cases where IVF/ICSI will be utilized. Why? It is simply not needed. Even if the sperm DNA were severely fragmented, the recommendation would be to attempt A.R.T. with IVF/ICSI, since the research has shown it is possible (though less likely) to achieve that fabled state of pregnancy even with a high level of sperm DNA fragmentation.

Given our embryo progression with our first IVF, the assumption can be made that my husband does have a high percentage of DNA fragmentation. The signs? Excellent fertilization and embryo development up to day three...followed by slowed development and embryo arrest after day 3. Although it is encouraging that four blastocysts were attained, we had implantation failure on our first attempt with two very good looking embryos. Classic.

Does that mean it can't happen? Does that mean it won't happen? No. I could get pregnant on the next round. Who knows. I do know that an SCSA won't tell me if my FET will work. It won't tell me my next fresh cycle won't work. It may provide me with relief if it came back at an 'acceptable' percentage...or it may cause me undue anxiety if it came back at 55%.

My paranoid opinion: Although there are cases where pregnancy was achieved in cases where DNA fragmentation was high...there seems to be more evidence that, even with ICSI, it is far less likely to conceive when there are high levels of sperm damage. Suspicious Murgdan says, "ASRM won't advocate for using DFI as a predictive value, because they would then have to stop recommending repeated expensive IVF/ICSI attempts in cases where pregnancy was unlikely due to severe MFI. REs want to make money. They don't make money by proving IVF won't work for you before you've even tried it."

The coolest thing I learned while researching this? The oocyte can repair DNA Fragmentation. Check it out.

"Metaphase II oocytes can repair, to some extent, DNA damage in sperm after fertilization by pre- and post-replication repair mechanisms. This will depend mainly on the extent of sperm DNA fragmentation and the cytoplasmic and genomic quality of the oocyte. The latter would be expected to be higher in oocytes from younger women. Therefore, the efficiency of the oocyte to repair DNA damage in the spermatozoon would be expected to decrease with female age."(Alvarez, J. G. (2005) The predictive value of SCSA. Human Reproduction)

"Protection against high DNA fragmentation may be afforded by younger oocytes which are much more efficient at DNA repair of defective sperm than older oocytes, so a couple coming for assisted conception treatment where the sperm DNA fragmentation level is high has a better prognosis if his partner is young." (The Doctor's Laboratory).

I think my thirty-something oocytes have a lot of work to do....

If you want more information about the SCSA or DNA fragmentation, you could read here, here, and here. So? Did you do the SCSA? If so, what were your results?

If you've read this far, you know one thing for certain...I'm a nerd. Also, maybe you learned something. Maybe you learned nothing and already knew all of that, but at least I learned something, notably that I'm buying my eggs a gift certificate to Home Depot. The next Special Edition will discuss Hyaluronic Acid Binding and the PICSI study. Aren't you on the edge of your seat?