Semen DNA frag test vs karyotype Q

BzeetyD · November 2012

Hi - I have lots of Qs today. And I couldn't find anything addressing this in the IFV blog.

Is a karyotyping test (which we've had) going to tell us the same thing as a semen DNA frag test?

Our karyotyping test was normal for both of us and we're doing ICSI already.

I asked our RE at our last WTF and she said that since we were doing karyotyping, it was kind of the same thing - or would tell us the same thing... but I'm seeing a therapist who deals with IF (and I've been seeing her for 1.5 years) and last night when I was talking about our options, she was concerned that we hadn't had it (and she knows we've done KT).

I want to ask about it today at our WTF.

Moving forward, if our 4th IVF cycle doesn't work we're looking at DE or adoption and if sperm integrity is an issue then we'd likely go with DIA.

BzeetyD · November 2012

Look at me - answering my own question! Embarrassed

Posting this for others and for prosperity sake.

Sperm testing: how to interpret the results

Category: Diagnoses

There are many sperm tests available; some results will be more relevant to you than others.

Which results should matter to you? Well, it all depends on context of course, and to help you understand sperm tests better, I thought I would post about it below, by highlighting the 4 things we really want to know about sperm.

1. Can the sperm reach the egg?

First things first: the sperm have to reach the egg.

When a couple is having intercourse (or when donor sperm is placed on the cervix), sperm will exposed to the somewhat acidic vaginal milieu. It isn?t a particularly hospitable place for sperm, and many won?t get past this stage. In fact, 99% of sperm will die within 20 minutes.

We want some sperm to be well protected for there to be a chance of pregnancy. Fortunately, they are safer when surrounded by cervical mucous, and by the seminal fluid itself. Therefore we like to see a good volume of seminal fluid, usually between 1.5 and 5.0cc, to be confident that the sperm will be safe enough to have that chance to swim up into the uterus and beyond.

Still, many sperm won?t make it. Probably about 90,000 sperm will get up into the uterus, from an average 90 million or so in the ejaculate. This is why the number of sperm is so helpful, measured as the concentration, usually 20 million/ml or more. When you start with more sperm, it becomes more likely that enough will arrive at the final destination.

Of course, they won?t be able to swim anywhere if they don?t have good motility (usually >40% have normal motility) and they won?t be able to swim quickly and in a straight line if they have an abnormal shape, measured as morphology (usually >30% have normal morphology).

If all four parametes above are normal, it becomes highly likely that the sperm have the ability to reach eggs. Lower-than-average numbers leads us to wonder if the sperm are even being given the chance fertilize eggs at all.

2. Can the sperm penetrate the egg?

Once they get arrive at the end of the fallopian tube, sperm have to stick on, and burrow their way into, the egg. This ability stick-on-and-burrow is not measured by the usual sperm tests (though motility and morphology correlate somewhat with this ability). To find this out with greater accuracy, you will need to do sperm penetration and binding assays. Not every clinic is able to offer this extra level of testing. And to be fair, the most precise way of all to measure this ability is to do IVF, where the lab can watch your sperm try to enter your partner?s eggs.

3. Is the sperm carrying good DNA?

At the end of the day, sperm is just a vector for DNA. When a sperm swims well and penetrates an egg, it will all be for naught if the DNA it carries isn?t able to do the job and help to create a healthy embryo.

The most common way to approximate the quality of the DNA carried by sperm is to do a karyotype, in which we test the man?s DNA in his blood cells or cheek cells. No, a karyotype isn?t the same thing as the DNA in the sperm -errors can be introduced during sperm development that are not found in any other cell in the body- but it is a reasonable place to start. We will also test the man for specific genetic errors (such as cystic fibrosis or Y microdeletions) when clinically indicated.

Yes we would rather test the DNA in individual sperm, but current technology limits our ability to do so. ?Five probe FISH analysis?, for example, looks at individual sperm, but it is a highly specialized investigation that only a few centres in North America offer. Though I offer it to some patients, its value seems to be limited and in most situations, the karyotype will be sufficient.

4. Are the epigenetics of the sperm?s DNA intact?

Until recently, we though that our genetic health was determined solely by DNA, but now we realize that how the DNA is held together (imprinting) is critically important too. If the DNA is not ?packed together? properly, it may be not interpreted properly?.and a variety of different problems (including lack of pregnancy) may result.

We test the epigenetics of sperm through DNA integrity assays, also known as a DNA fragmentation index (DFI) or sperm chromosome structure assay (SCSA). These have proven to be very useful tests in a modern clinical practice when male factor subfertility is suspected.

From: https://www.fertility.ca/2008/06/sperm-test-results-do-they-matter/

Mrs.McIrish · November 2012

Breezy-

Just chiming in on the sperm DNA frag issue because that is what I happen to be researching at the moment. Fragmented DNA in sperm can cause miscarriages. What did your embryos look like on day 5 (ie what stage were they?)

It is possible to have normal SAs but still have fragmented DNA. I would definitely get the test done before you move forward on another IVF and especially before you spend $$ on DE. I'm afraid that my DH may have highly fragmented DNA since our embryos were good on day 3 and really slow on day 5. We never had any reason to suspect this as DH's SAs are all in normal ranges. We knew my eggs were crap and never got back day 3 with my OE so this was our first time to see what happened between day 3 and 5. ICSI won't fix fragmnented DNA. Vitamins/antioxidants may help lower it though.

BzeetyD · November 2012

Mrs.McIrish:
Breezy-

Just chiming in on the sperm DNA frag issue because that is what I happen to be researching at the moment. Fragmented DNA in sperm can cause miscarriages. What did your embryos look like on day 5 (ie what stage were they?)

It is possible to have normal SAs but still have fragmented DNA. I would definitely get the test done before you move forward on another IVF and especially before you spend $$ on DE. I'm afraid that my DH may have highly fragmented DNA since our embryos were good on day 3 and really slow on day 5. We never had any reason to suspect this as DH's SAs are all in normal ranges. We knew my eggs were crap and never got back day 3 with my OE so this was our first time to see what happened between day 3 and 5. ICSI won't fix fragmnented DNA. Vitamins/antioxidants may help lower it though.

This is why we're looking into it. I want to be sure we're nailing down our issue as closely as possible before we lose any more $ on this endeavor of love.

Our embryos generally look pretty good on day 3 and sometimes good on day 5. I've had 2 5dt - 1st one was kinda crappy embies (doc was non-plussed), 2nd one was very good (Doc was quite excited), our 3dt had 2 pretty decent looking embies (Doc was enthused). Never have had any make it to freeze and I don't know if that's an EQ issue or a sperm issue - or both.

Sophistikitty · November 2012

We both had karyotyping done and DH had DNA fragmentation testing done as well. Our karyotyping was normal and DH?s DNA fragmentation came back at 22.2% (basically normal, not fantastic but not terrible). Like McIrish said, I have read that is possible to have a great SA and terrible DNA fragmentation. I realize you have already answered your own question but I would definitely try to get DH?s fragmentation tested. It may give you some answers and if nothing else make you feel more confident in your choices moving forward.

hootie123 · November 2012

We've never done the DNA test - both of my previous REs did not see a point to do it since it wouldn't change what they do anyway (ICSI). And even now we've tried donor sperm and that didn't work either. But my new RE wants to rule out everything before we do our next cycle - so we are going to do it. And if it is high we will go back to using donor sperm. The test is really not that expensive in the scheme of things. We're also doing the karyotyping bloodwork since I've never had that either. And we're doing the immune bloodwook - natural killer cells and the DQ Alpha match - and the same lab is going to run the sperm DNA frag for us - my husband is going to love shipping his sperm in the mail (LOL!).

Mrs.McIrish · November 2012

hootie123:
We've never done the DNA test - both of my previous REs did not see a point to do it since it wouldn't change what they do anyway (ICSI). And even now we've tried donor sperm and that didn't work either. But my new RE wants to rule out everything before we do our next cycle - so we are going to do it. And if it is high we will go back to using donor sperm. The test is really not that expensive in the scheme of things. We're also doing the karyotyping bloodwork since I've never had that either. And we're doing the immune bloodwook - natural killer cells and the DQ Alpha match - and the same lab is going to run the sperm DNA frag for us - my husband is going to love shipping his sperm in the mail (LOL!).

While I agree that it wouldn't change treatment as ICSI is already done, for me, it will be difference between giving up if it comes back high. I can't keep spending $$ on DE if we have highly frag'd sperm too. Too risky for "maybe" vitamins to work or to just keep trying to see if a "good" sperm is picked by embryology. DH has already balked big time to using DS so for us, this is it. One more chance with DE but I won't bother if the frag comes back really bad.

You are right in the scheme of things that $375 for the test is a drop in the bucket in the scheme of all this BS. The mushroom shipper should be interesting!

I'm sorry DS didn't work for you guys. I hate when you can't figure out what the issue is.

hootie123 · November 2012

Mrs.McIrish:
While I agree that it wouldn't change treatment as ICSI is already done, for me, it will be difference between giving up if it comes back high. I can't keep spending $$ on DE if we have highly frag'd sperm too. Too risky for "maybe" vitamins to work or to just keep trying to see if a "good" sperm is picked by embryology. DH has already balked big time to using DS so for us, this is it. One more chance with DE but I won't bother if the frag comes back really bad.
You are right in the scheme of things that $375 for the test is a drop in the bucket in the scheme of all this BS. The mushroom shipper should be interesting!

I'm sorry DS didn't work for you guys. I hate when you can't figure out what the issue is.

It's so frustrating! I had one RE tell me that we just needed persistence - like 4 IVFs in a row was not presistent enough.

I really hope things work out for you too.

Anasara · November 2012

We haven't done frag testing but if this next IVF is a bust I am going to make DH get it done before we do another cycle. His motility is low but his overall #s are better than average. Still, even with ICSI our fert rate has only been 50%. I admit that sometimes my mind wanders to the fact his parents are second cousins (Indian arranged marriage) & maybe there's an issue there.

Mrs.McIrish · November 2012

Anasara:
We haven't done frag testing but if this next IVF is a bust I am going to make DH get it done before we do another cycle. His motility is low but his overall #s are better than average. Still, even with ICSI our fert rate has only been 50%. I admit that sometimes my mind wanders to the fact his parents are second cousins (Indian arranged marriage) & maybe there's an issue there.

Is your DH taking any antioxidants in the meantime?? I think you need to get him on them ASAP> Don't even take a chance! My DH's SA numbers across the board are great and our fert rate is good. It means nothing for whether the dna is fragmented though. ICSI doesn't fix it. I'd personally get the test but at the least, put him on a vitamin protocol!!!

may2806 · November 2012

DNA frag test is different than karyotyping. Some REs don't "believe" in the frag test or think it gives any info that would change anything; I'm not exactly sure why, I just know it's a somewhat controversial test. My RE didn't offer it to me but my RI (immunologist) did. Ours was normal, but we felt better just having covered that base just to make sure. I think it's worth having done just to know.

annalisel · November 2012

This is all very interesting. My DH aggressively asked about the fragmentation test to 2 REs at 2 large clinics. Both said that it was unnecessary. They also said that their DE success rates were not lower when the man has a poor quality semen analysis (count, motility, morph). I wonder if they have never correlated fragmentation with success rates? This seems odd given one of the clinics publishes research papers.

Sophistikitty · November 2012

I would push for it. Speaking for myself, I felt that before moving to DE I needed to know no stone was unturned. Yes, I am am 41 but that wasn?t enough to convince me. I know that I am coming from a slightly different place than some of the other ladies that have commented though... Most have not had any inkling of a male factor issue.

When we started our IF journey DH?s morphology was horrid and motility not much better, so there was always a nagging voice to have more testing. After seeing a reproductive urologist (before our first IVF) and faithfully maintaining a daily supplement schedule his SA numbers returned to normal range. However, it was only after our first failed IVF and seeking second opinions that we were actually able to get his DNA fragmentation tested.

I know this view is not for everyone but I really feel that the more testing you can have (on either side) the better. In my case, it truly was what made me be at peace with my decision to move on to DE.

**Edit**: Apologies for the comment, ?most have not had any inkling of a male factor issue?... When I wrote my post McIrish & Bzeety were at the forefront of my mind... Should have looked at all the siggies before posting. Sorry for that.

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