Friday, June 13, 2008

Sperm DNA Fragmentation

I've recently gotten lots of comments on my blog in regards to the SCSA test. Lots of doctors (and thus their patients) seem to think this test is a waste of time. I have done a little research on the topic and found a good web site that explains the procedure and how it can effect fertility.

There may not be ways to fix sperm DNA problems but it certainly will tell you why you are not pregnant. It's like egg quality...there is no real way to fix egg quality but it would be nice to narrow down what the problem is. Unlike eggs sperm regenerates every 90ish days. Thus sperm quality CAN be helped to some extent. Woman are born with their eggs. Some say you can fix egg quality and some don't.

Here is what I found on that web site. I personally don't think this test is a waste of time. CCRM does this test on all couples and their statistics are through the roof. (then again they do all kinds of tests that other RE's don't want to "waste" their time doing. Personally I think the more tests you get done the better. I'd rather find out exactly what my problems are before I do IVF. Here I am doing a 6th IVF and we still don't know for sure what is causing my embryo's to be abnormal. Here is the link to that web site if you find the below quote hard to read:

Also oddly enough the way they describe what happens to the embryo's due to Sperm DNA problems is exactly what happen to mine. They all arrest around the day 3 stage. It could be sperm issues, egg issues or a combination of both but I for one would like to know what is causing the issues so we can try to fix it or at least accept it and move on.

The Sperm Chromatin Structure Assay (SCSA) and DNA Fragmentation: What Is It and What Does It Mean?
This article from a Resolve 2006 newsletter
Until several years ago the belief among most reproductive specialists (including myself) was that if a man had live sperm then they were suitable for use with IVF / ICSI and if the female partner didn’t get pregnant or a miscarriage ensued then it was probably an egg quality issue. Several studies had implied that the conventional sperm parameters (count, motility and morphology) as measured on a routine semen analysis had no bearing on success when ICSI was used. Many couples pursued egg donation after failed IVF attempts because the husband’s semen parameters were relatively normal and yet conception hadn’t occurred.
Some of these same couples were still unable to conceive even with the “better quality” donor eggs leaving both the doctors and the couples frustrated and perplexed. Some couples then went on to use both egg donors and surrogates thinking it was both an egg quality and implantation issue, again without success. The only commonality was the husband’s sperm.

About a year and a half ago a relatively new concept was introduced to clinical practice; sperm quality was dependent on the amount of damage to the sperm DNA or DNA fragmentation. Simply put, DNA is arranged in a double helix or ladder configuration with side rails and rungs. If the rungs are broken, then the ladder is unsteady and won’t function properly. What has recently been shown in several studies is very interesting and in some ways unexpected. Sperm DNA fragmentation has little or nothing to do with the parameters that we measure on the routine semen analysis. It has little to do with the shape of the sperm or whether the sperm are moving. It is a completely independent variable. Men with otherwise normal semen analyses can have a high degree of DNA damage and men with what was called very poor sperm quality can have very little DNA damage. More importantly what has also been demonstrated is that the degree of DNA fragmentation correlates very highly with the inability of the sperm to initiate a birth regardless of the technology used to fertilize the egg such as insemination, IVF or ICSI. Sperm with high DNA fragmentation may fertilize an egg and embryo development stops before implantation or may even initiate a pregnancy but there is a significantly higher likelihood that it will result in miscarriage. By testing for sperm DNA fragmentation, many cases of formally “unexplained” infertility can now be explained. Many of those couples who have been previously unable to conceive with what would be considered extreme measures have been diagnosed with high sperm DNA fragmentation and treated. It is now very clear to see that having this information about the quality of the sperm can be tremendously helpful to couples and their physicians.

There are several ways to test for sperm DNA fragmentation; the most widely used and statistically robust test is called the Sperm Chromatin Structure Assay or SCSA. The patient semen samples are frozen and shipped in a liquid nitrogen container to the SCSA reference laboratory in South Dakota. The sperm are thawed out and a stress is applied (low pH). The sperm are then labeled with a special orange colored dye that only attaches to the ends of broken DNA within the sperm cell. If the DNA is intact then no dye will attach to the sperm. A machine called a flow cytometer is used to analyze ten thousand sperm from the sample. The sperm are passed single file by a beam of light that hits the dye inside the sperm cell and reflects light at a specific wavelength causing the sperm to appear either orange (damaged) or green (normal). A computer counts the percentage of green versus orange-labeled sperm and software allows for creation of a graphic plot of the percent of damaged sperm giving an index known as the DNA fragmentation Index (DFI).

The data from thousands of patients has been analyzed and correlated with the patient’s clinical outcomes and references ranges were compiled. A normal sample has less then 15% of the sperm with DNA damage. Men with poor fertility potential have greater then 30% of their sperm damaged. A DFI Between 16% and 29% is considered good to fair fertility potential but becomes poorer as it approaches 27%. These numbers are thresholds meaning that above 30% the outcome for most couples was failure to have a birth even though only 30+ percent of the sperm were damaged. Under 15% most couples achieved success. The logical questions that arose were: what about the rest of the undamaged sperm in the sample? Why don’t those sperm work? What causes sperm DNA fragmentation? Can the DNA fragmentation be reduced and the sperm improved? If so, How?
DNA fragmentation can be thought of as a marker for other types of damage to the sperm. It is a kin to seeing the tip of the iceberg. Apparently, in semen samples with greater then 30% DNA fragmentation, other abnormalities are occurring with the non-fragmented sperm that the SCSA doesn’t measure and that is why samples used with DFIs above this level do not usually result in births.

The causes of high DNA fragmentation are those same causes of male factor infertility that we have known about for years such as chemical/toxin exposure, heat exposure, varicocele, infection, age, smoking, testicular cancer, radiation, and anything that increases the free radical levels in the semen among a list of many other things. It is very important to understand that sperm DNA fragmentation can change with time and it can be improved in many cases. The goal of a male factor evaluation is to seek out the causes of poor sperm quality and try to correct them so conception can occur naturally or to improve the sperm quality for IVF and maximize the chances of success. In situations where DFI can’t be improved there is evidence to suggest that removing the sperm directly from the testicle via biopsy and using it with ICSI may lead to better outcomes then using poor quality ejaculated sperm. Other options include counseling patients regarding the use of donor sperm either by insemination or fertilizing a portion of the eggs harvested for ICSI with donor sperm and a portion with the patient’s sperm, once again to maximize odds.

The clinical utility of the SCSA is readily apparent. All men with an abnormal semen analysis are candidates for this test as well as men with normal semen analyses who have failed IVF for unexplained reasons. Those couples using egg donors or surrogates may also benefit from screening prior to going thru the procedures because the effort and costs are so great. Men with poor DFI should have a male factor evaluation including a physical examination by a male reproductive specialist. These new concepts have a significant implication on how we practice and what we recommend to couples but we must bear in mind that this test does not have a predictive values of 100% as healthy babies have been born from men with high DFI but this is fairly uncommon.


Anonymous said...

I think CCRM sends sample to a lab in North Dakota (or South maybe?) to run this test. Maybe you should find out which lab and contact them.

Staci said...

I had a consult with Dr. Schoolcraft at CCRM at one point to go over my case. When I mentioned that my DH had a SCSA result of 29.8% and asked if I should have the test repeated since it had been a few years, he told me it was not an issue; that they have seen successful pregnancies with results as high as 60 something percent. He really did not seem to put much value on this test. Maybe there is another Dr. there that does though?

Regarding this article from Resolve, I would check to make sure it wasn't actually written by the man who designed the test. I noticed that the majority of articles I found like this were, in fact, written by him.

Don't get me wrong. I honestly am just as confused as you about this whole issue and do feel that it's asking a lot to have someone believe that sperm quality plays no role at all in things.

Anonymous said...

But in the instances of blood disorders and cystic fibrosis in children, the two biological parents must be on hand. I know how children can matter to some but the donated children have problems all of their own.

Amy said...

I'm brain dead today. I'm not following what you are saying.

Anonymous said...

Has your Doctor recommended TESE for your DH as a means to get at less fragmented sperm? We are doing our 2nd round of IVF/ICSI this month and DH will do TEST due to his high level of fragmentation and our low fertilization rate with our first cycle.

Anonymous said...

This post seems to indicate that it may be possible to lower the fragmentation level. What are some ideas for accomplishing this? I'll try anything at this point.

Amy said...


"This post seems to indicate that it may be possible to lower the fragmentation level. What are some ideas for accomplishing this? I'll try anything at this point."

hmmm...good question. I'd actually have to research that one. Not all doctors even believe in this test. Actually lots of them don't do this test at all. Some thing's I've read says to take vitamins (like fertility blend for men) and that over time it may be able to improve the quality of sperm. I guess I'd have to find out what causes DFI to happen in the first place. I mean men aren't born with all their sperm like woman are eggs. Men replenish about every 3 months. So essentially you'd think this is fixable (unless it's genetic and then it may be a tad harder but I don't think it's impossible)

I'll have to do more research on the topic. if I find anything I'll make another blog entry on it.

Anonymous said...

Does anyone know how the Anonymous girl's IVF/ICSI/TESE go? I am in the middle of mine and would like to hear some good news from someone :-)

Anonymous said...

My husband has a fragmentation rate of 48%. We have been trying for 1 and 1/2 years now. Currently we are trying antioxidant and acupunture therapy to see if we can get a reduction. My fertility doctor did not recommend IVF right now. He wants us to try FSH therapy first to increases our odds. IVF is our last resort. But now I'm thinking of asking him about ICSI with testicular sperm I have red some papers that say that testicular sperm show less degree of fragmentation compared to ejaculated sperm.

I am curious to know if there are couples out there who concieved even with a high rate of fragmentation.

Amy said...

Anonymous-I had this test done recently through the Sher institute and my hubby's came back excellent at only 6% fragmentation. I highly recommend going IVF/ICSI with testicular sperm. Where did you get the test done? I'm shocked your RE didn't tell you that you need IVF/ICSI to get pregnant.

Anonymous said...

Amy 2... I am on my second IVF/ICSI cycle (shooting for March 6th) and I also discovered after my first IVF/ICSI cycle that my husbands DFI was high. I was shocked that his sperm specialist did not think it was important to tell my doctor. It seems clear to me that this is a very important factor. It only makes sense. Anyway, you are doing the right thing with the antioxidants and acupunture. Luckily I started my husband on antioxidants and "Fertile ONE for Men" over 6 months ago and his sperm has shown signs of improvement. If your husband will stick to acupunture - great. My husband quit going after 5 months. IT could take up to 9-12 months to see improvements. Some men do not have the patience for it. And although he has not been tested in 6 months for DFI, during this IVF/ICSI cycle, he will be having his sperm removed directly from his testes. I will let you know the outcome. The first IVF/ICSI, we had 7 embryos - 4 perfect, 3 in and nothing. I am hopeful this time now that we are doing testicular sperm removal!

Amy said...

My husbands SDNA test showed he's in the high fertility category so he's fine. He's never done acupuncture or supplements(that was me)

Amy said...

To clarify they like the fragmentation to be under 30% and anything under 15% is great and my husbands was only 6% :)

Egg Donors said...

Great Post.....

I found your site on stumbleupon and read a few of your other posts. Keep up the good work. I just added your RSS feed to my Google News Reader. Looking forward to reading more from you down the road!

Thanks for sharing....

Anonymous said...

Here is an interesting study. Although the study size was small it shows definite improvement in DNA fragmentation rates by using antioxidants (500 mg Vitamin C twice a day and 500 mg Vitamin E twice a day).

To summarize the study (I am a pharmacist, so I have some experience reviewing drug studies) in the group that was given the antioxidant therapy for 2 months, all 32 patients saw improvement in their DNA fragmentation rates. This group saw an improvement in their DNA fragmentation rate from an average of 22% prior to taking the antioxidant therapy to an average of 9.1% after they received antioxidant therapy. The group that was given placebo instead of antioxidant therapy saw not improvement in their DNA fragmentation.

Here is another study that shows that the rate of pregnancy using ICSI was significantly increased in patients that were given 2 months treatement of Vitamin C and Vitamin E.

In this case male patients with high DNA fragmenetation rates who had previously failed ICSI were given 2 months of Vitamin C and Vitamin E (recommend 500 mg of each twice a day). Of the patients treated 76% saw an improvement in their DNA fragementation and a second ICSI procedure was preformed. During the second ICSI procedure there was a clinical pregnancy rate of 48.2% versus 6.9% rate pre-treatment.

This information suggests that mean should try treatment with Vitamin C and Vitamin E before looking at more invasive treatments such as having sperm removed from the testes.

I just found this information and have started this treatment with my hubby, however he has been taking Coast Fertility vitamins for men and has seen his DFI go from 29% to 21% in a couple of months, so I do thing that vitamins work at least in some cases.

I hope that this is helpful. Take Care and Good

Anonymous said...

Hi, we have been through 6 cycles of IVF, mostly ICSI and usually got about 2 thirds fertilize but then not make it to transfer. Out of all those cycles we only had 2 transfers, none frozen and 2 cycles where none fertilized at all which was heartbreaking.

Before the last cycle my husband discovered he has about 25% fragmentation. The last cycle they used a high resolution microscope because of this but struggled to find enough good sperm to inject. We had none fertilize again.
What I'm wondering is does that mean it was 100% fragmented? Surely if it was 25%, some would have fertilized? Even the doctor said that he doesn't know what else to do except keep trying...

Any ideas or has anyone even seen this before? Thanks

Anonymous said...

Thank you for your very informative website. Interesting facts on DNA fragmentation. My husband has over 40% DNA frag, I've done 8 IVFs and lost count how many IUIs over the past 4.5 years. Good luck to you trying to get pregnant. I'm going to give up now as I've been thru the wringer while I find the Doctors always check out the female & only once 2 months ago, after 5 years does someone look @ my husband for possible issues! Good luck, I hope you get there!

Amy said...

Have you looked into embryo adoption? It's really inexpensive. Just a thought. This is the only way my husband and I will ever be able to get pregnant so we have move onto embryo adoption.

Anonymous said...


I had a DNA fragmentation of 50%,
along with asthenozoospermia. (I'm
not sure if they are correlated).
On diagnosis, my Doctor put me on Zinc and vitamin suppliments. We were able to conceive naturally within 2 months of start of medicatins, and my wife is into her fourth month now.

Anonymous said...

Question for the person who had a DFI of 50% and got pregnant naturally? Do you mind me asking what your sperm motility, count were like? MY hubby has high DFI as well, we failed our first IVF/ICSI, and now his DFI went from 68% (without vitamins) to 37% after a few months of Fertil Pro, and then it started going back up to 50% and the latest result is 87%. He's stopped all alchol and red wine, and it seems the DFI is going up!!

Anonymous said...

I stumbled upon this blog while trying to read more about DNI & its significance in IVF/ICSI. We have been married close to 6 years now and decided to undergo ICSI 2 years ago as we found it most suitable for us after extensive investigation for our infertility issue. Ours is a case of male factor infertility;my husband is oligoasthenospermic.

I was able to produce 24 oocytes right in the first attempt and we got 19 well fertilized embryos of that. But the celebration did not last long when one fresh cycle & one frozen cycle failed in quick succession. I did not go back to my clinic for the next 2 years! Last month I decided to give one last shot at the remaining embryos and now that cycle has failed too. We are not left with any more embryos now (we lost many embryos in the thawing process too) & my doctor suggested a fresh cycle when I am ready for it...although I am not sure how many more years I am going to take to gear up to it again now!

Meanwhile my doctor also suggested a sperm DNA fragmentation index for my husband along with a SLE & APLA screening for me and that is how I landed upon this website today. Your blog has been a little encouraging at a time when I am almost ready to give up! Thank you for the useful information that you decided to share in your blog. I am already feeling a little positive about going back to my doctor in a few months maybe.

Mohammed iraqi said...

Dear Sir
I have SD level of 22% my wife had 12 abortions with any successful pregnancy we did a lot of investigations and all normal
is the defragmentation levl is the cause
please answer me

Anonymous said...

@Mohammed Iraqi: Hi - I just wanted to point out to most posters here (and Mohammed) that many languages only have the word "abortion" (which is usually preceded by "involuntary" or "voluntary.") In English the loss of an embryo is called "miscarriage."

Anonymous said...

My husband has a high DNA fragmentation > 50% and also low sperm morphology 2% normal.

We are so confused and scared to try any of the invasive treatment and very disappointed with no proper guidance. I have also suffered 2 miscarriages in the last one year.

WE are on antioxidant supplements , but only time will tell us if its effective.

Does anyone know of alternate treatment like Homeopathy?

Anonymous said...

Gooogle diclofenac (its an nsaid for arthritis)and sperm fragmentation there is an artical that says the drug helps with the fragmentation. We have been on this journey a long time. We have no problem getting pregnant it just dissolves right around week 3-4from lmp

Anonymous said...

We have been trying for 5 years. The final diagnosis after IVF failure was "unexplained infertility." We then went to an endocrinologist who specializes in infertility. He discovered that my husband has very high fregmantation. He prescribed gonadotropins to him for 3 months. (I am sorry I don't have the brand-name of the drug). The MD told us that after treatment he will be fertile for 2-4 months. He expects us to conceive naturally. However, IVF might be needed again.
This is all very promising! I still don't know if it will actually work, but I wanted to share it with you because I know that for those who try knowledge is treasure!
Good luck!