Does Sperm DNA Fragmentation cause chromosomal abnormalities in the embryos?

[PaulaDag]

Hi everyone,

Am so upset. We've just received my partners DNA fragmentation test results back and was somewhat surprised its says "48% DFI very poor pregnancy outcomes".

We have ISCI anyway due to some borderline suboptimal semen analysis results but clinic didn't ever recommend DNA Frag but I insisted as if this cycle doesn't work we want to be informed if trying naturally going forward.

The clinic has always said its my eggs due to age causing the failed transfers (we've had some top and some fairly graded embryos transferred so far - 5AA, 5BA, 5BB & 5BC ) and our 4 natural miscarriages but now I am wondering if this can cause failed transfers and miscarriages too? We did have 2 blastos that collapsed and arrested on day 4 in the second cycle, could this be a cause?

Can it cause abnormal chromosomes in the embryos or is it just that it stops fertilisation (so therefore not an issue for us as we already have ICSI)?

We've always thought we just need one normal egg and if all else fails we'll go to egg donor but know I'm wonder if it affects the embryo, will it also affect a donor egg and so I won't get pregnant?

We've had 3 cycles of ICSI so far and just finished cycle 1 (egg collection last week) of a 3 cycle embryo banking package and wondering if the 4 embies we just froze are now duds? We froze 2 x 5AA, 1x5AC and 1 x 5BC which the embryologist says it great for my age but i can't help feeling we transferred a 5AA before in the 2nd cycle and it didn't take so i don't feel excited or hopeful anymore

I've just bought some Impryl and Proxeed Plus for my partner but I'm wondering if the clinic will suggest delaying the 2nd and 3rd egg collections due to this? I don't want to due to my eggs and age. Consultation is next week.

I've been doing some research and my clinic doesn't do IMSI or PICSI anyway and HFEA say its not proven etc. Is ISCI sufficient for DNA Frag?

If it circumvents the issue as the embryologist picks the best sperm then fine, but how can they see whats inside the sperm, i guess they can't just like my eggs.

I don't really understand what DNA Frag causes - do you? Is it low fertilisation (not been a problem for us so far), low graded blastos/embryos (again not a major problem for us so far). We've had 3 failed transfers of 4 embryos we was attributed to my old eggs. Now we have another hurdle and i am exhausted.

High DNA frag must cause too few or too many chromosomes? Not sure. So much for just need to find that one good egg 😔

Any experience, guidance would be much appreciated.

xx

[Purpledoggy]

So sorry to hear this lovely. How frustrating to find out now! But, it may yet be something you can fix. Sperm DNA comes into play after 3 days so it is possible it may have contributed to embryos conking out after this point 😕

I found this recent review on DNA frag and interventions if it is of help. May be worth a read since written by someone in the know. ncbi.nlm.nih.gov/pmc/articl...

There is a well known doc called Mr Ramsay who is famous for sorting out DNA fragmentation-not seen him myself but seen his name pop up here loads. Sending hugs.

Xx

[soccerkt6]

Hi lovely

I'm so sorry that you've just had this added to your plate. Good on you for insisting on having the test done though. It kills me that more clinics/ doctors aren't proactive about suggesting the test after multiple failed cycles, especially when there's already evidence of other sperm issues.

To answer a few of your questions:

-High sperm DNA fragmentation can definitely be a factor in recurrent miscarriage. It would also make sense that it could play a role in failed transfers.

-High fragmentation can sometimes impact fertilisation but not always. For example, we had a conventional IVF cycle and 12 of my 14 mature eggs fertilised normally. It wasn't until 90% of them stopped developing/slowed down after day 3 that docs started to suspect that my husband might have high fragmentation.

-Only consider donor eggs once your husband's numbers improve. Or, at least also consider donor sperm if you can’t get his numbers to improve. Sperm is 50% of the equation when creating embryos, so pairing damaged sperm with a donor egg still isn't a great recipe for success.

-Unfortunately, ICSI really doesn't do anything for DNA damage. As you say, embryologists are picking the best-looking sperm but there's simply no way to tell visually whether or not a sperm has damaged DNA.

-The best selection methods for helping with DNA fragmentation are either PICSI or MACS. There's been a study that they're both about equally effective, with PICSI being slightly preferable for 'older' eggs (over 30 years old) and MACS being preferable for younger eggs (under 30). If neither of those is an option, IMSI is a better choice than standard ICSI. It's kind of a bummer that your clinic doesn't do PICSI or IMSI. Do they offer MACS?

-Is it possible to go ahead with your upcoming egg collections as planned but just have them freeze the eggs for now? I probably wouldn't want to fertilise them with your partner's sperm until he's had a chance to improve his numbers.

It's good that you've already purchased some Impryl and Proxeed. I would also suggest contacting the urologist Dr Ramsay and getting in to see him. He'll be able to run some tests to see if they can determine the cause of your partner's fragmentation. Supplements are key but if your partner has varicocele or infections that are causing the high fragmentation those will need to be dealt with as well.

I'm so sorry again that you're dealing with this. IVF is exhausting to begin with and the frustration when you run into yet another problem feels like to too much to bear sometimes. Get some sleep tonight and you can tackle this in the morning. The good news is that there are solutions to this problem. It might not feel it now, but you're better off knowing this now so you can make the most of your next two egg collections. Sending you all the best xxxxx

[soccerkt6 in reply to soccerkt6]

Sorry, I also meant to ask if you're certain that your clinic doesn't do PICSI or IMSI. My clinic's website doesn't mention anything about PICSI/ MACS/ IMSI so it appears that they don't offer it, but when we learned about my husband's high DNA fragmentation they mentioned that PICSI was an option. So it's worth ringing the clinic and asking what your options actually are. xx

[Llizzie]

Hello. My husband has 52% DNA frag or did the last time we checked. We have seen Mr Ramsay twice who was great. He found husband has “prize-winning” varicoele and two hernias in his groin so he suspects this is heating up his sperm. We can’t operate on them because my husband as a significant heart condition and damaged veins.

He also found two infections which were treated with antibiotics and my husband took proceive plus alternated with Proxeed. He gave up drinking and we overhauled our diet.

When we approached the clinic Mr Ramsay recommended (I asked), I expected them to say we’d need to go to donor. What the clinical director said was - we would never recommend a couple go straight to donor on the basis of DNA fragmentation alone. There may be couples getting pregnant naturally with this level and we just don’t know. There’s not enough research yet.

I had very low hopes. I have good AMH but am 38. First cycle we had IMSI which I asked for (+ICSI) 14 eggs retrieved, 12 mature, 8 fertilised, only one made to a 4AB blast. That blast is still going as I’m 7 weeks pregnant. We did do 24 hours abstinence as were told quality may be higher.

I’m still petrified that the high DNA frag means it won’t stick but I’m amazed we got this far. Everything I’d read told me we wouldn’t get here - though we did see a huge drop off between day 3 and 5 in terms of embryos. My mum likes to remind me it takes one good sperm and one good egg and we weeded out the weak ones. I do wonder if we did his DNA frag again whether it has improved because of the treatment of his infections and he’s been so good at giving up alcohol. What I do know is that we moved his count and motility up significantly through just cutting out processed foods, hot baths, cycling and tight boxers.

DNA fragmentation testing is relatively new and it’s impact is still being worked through. I would recommend seeing if you can get to a cause with a urologist - it might be fixable. In our case it isn’t without putting my husband at risk - but it has helped him come to terms with his diagnosis.

I remember the hours I spent googling for answers when we got those DNA frag results in January. Some men go through a TESE procedure where they get sperm from the testicles - before it gets damaged on the way out. There are options.

It’s really tough. Keep talking to each other and hoping. Your journey isn’t over yet xxx

[Squeak1955 in reply to Llizzie]

What does Mr Ramsey test for exactly and is it possible to have the tests carried out on NHS. If tests have to be carried privately do you have any idea of prices?

[Llizzie in reply to Squeak1955]

My husband had an ultrasound, a physical examination, an Examen COMET test and detailed semen analysis including an infection screening. It was not cheap probably around £1,500 including consultation fees. Urologists do exist in the NHS so you could try to push for a referral but you’ll need some basis for that. If found, the NHS doesn’t routinely offer varicoele repair for fertility reasons so I’m not sure that can be done unless it’s causing other issues. xx

[soccerkt6 in reply to Squeak1955]

Hi squeak, my husband has had an ultrasound to check for varicocele and a urinalysis to check for infections, both through our GP.

To check for varicocele, you'll have to have a proper reason to request the ultrasound. In my husband's case, he had a small lump (it wasn't even a lump really, it felt more like a bundle of nerves) that he could feel on one of his testicles. He told that to the GP and requested an ultrasound to check for varicocele, which they were happy to do.

For the urinalysis, he basically just asked the GP if they could order a urinalysis to check for infections, because genitourinary infections are linked to male infertility and it was the only thing that hadn't been checked yet. I think our GP took pity on him and ordered the tests. 😆

So it's definitely possible to have some of the investigations done through the NHS, though you're kind of dependent on having a nice GP who's willing to support you. xx

[Squeak1955 in reply to soccerkt6]

Thank you soccerkt6, that is so helpful x

[Lozza8]

Would having pga(is that right?) testing help maybe? It would tell you which ones were normal/abnormal? I’ve never got far enough to have it so perhaps I’m wrong.

[Running79 in reply to Lozza8]

PGTA testing can help, but it’s on the amber list on the HFEA website. I’ve had it done due to my age, but apparently it can class embryos as abnormal which may not have been

[Lozza8 in reply to Running79]

I’ve heard it is a bit controversial