MFI - should we wait or should we start

[Smoothieyummy]

Im 37 and hubby is 40, so time is not on our side. We have been diagnosed with MFI (his semen analysis is normal but he has high dna fragmentation (33%) due to high ROS. My numbers are all good.

I’m at the cross road where I don’t know which one to choose:

Option 1: wait 3-6 months for him to improve the sperm issues by lifestyles changes and supplements. But in all honesty I’m not sure how much things will improve? My husband doesn’t drink doesn’t smoke, good BMI, he has already been on Impryl for almost a year but somehow that didn’t help and his oxidative stress (ROS) is still high which resulted in high dna frag. His other semen parameters are normal. My worry is the longer we wait, the older my eggs are going to get.

Option 2: start ICSI now, throw in zymot for sperm selection and pray for the best, it anything we can hopefully learn from the cycle. But then this means doing ICSI knowing the sperms are not at their best.

Any experience or thought you can share I would appreciate. Or anyone who has success with 33% DFI?

Hi OP,

We had a similar but different decision to make I was younger (~32) but had very low ovarian reserve and MFI due to poor morphology. Same as you that there wasn’t much DH could do lifestyle wise. We initially decided to target freezing embryos. Perhaps you could do this initially? It is cheaper in the short run but slightly more expensive in long run (if you use them), but we figured that if we didn’t need them for first baby if we got lucky naturally, it’d be great to have some in the bank for second child when it’d almost certainly be too late for me due to my reserve status. It also gave us a good idea of what our success rate might be and I found splitting freezing and transfers a bit less intense.

good luck whatever you decide.

Hi OP, suggest to see a urologist speciliasing in male fertility. We saw one privately but it was well worth it for us. Husband was found to have significant varicoceles and low testosterone which were both corrected. His DNA frag is same as your husband’s and SA’s have always been normal. If the urologist can not find anything to correct, I agree best next step is ICSI+zymot. Good luck!

Thanks for sharing. We are with Johnathan Ramsay, that’s why we know the cause of his DFI is due to ROS (oxidative stress).

Do you mind if I ask what did your husband do to correct the low testosterone? And is low T a cause of dna frag? My husband’s testosterone is not high, it’s within normal range but the lower end. Mr Ramsay didn’t raise any concern about that though.

@Smoothieyummy oh great to know you’re being looked after by Mr Ramsey, he was our first choice too but wait list for him was 10 weeks at the time so we saw Mr Tet Yap who was very impressive also. Husband was started on clomid for low testosterone but this was switched to anastrazole after a couple of weeks because clomid shot his estradiol up.
What was Mr Ramsey’s recommendation in terms of next step - did he suggest trying lifestyle changes first?
Edited to add: Mr Yap thought husband’s elevated dna frag was mainly caused by the varicoceles (so had embolisation via NHS) but he thought correcting the low testosterone may also help to cover all bases.

Mr Ramsey suggested some lifestyles changes such as losing weight and exercising more (DH’s BMI is 24.7 so he’s not big but he’s going to try to work out more, eat better and aim for 23 BMI) and frequent ejaculation (at least E times a week). We are due to have our next follow up with him to review the ROS result and next step. But given that he has been taking Impryl for almost a year (which is meant to help lower ROS) I don’t know how much more can be done, and don’t know why the Impryl hasn’t worked. He also doesn’t smoke and has stop drinking for 3 months now, but before that he was never a big drinker to begin with. DH also did an ultrasound scan and no issue with varicoceles.

I heard of dr Yap too, he’s also a well known andrologist and he and dr Ramsey have done several research papers together,

@Smoothieyummy if that’s the case maybe wait 3 months and see what happens? That gives you enough time anyway for lifestyle changes to take effect as that’s how long it takes a man to produce sperm apparently.
Mr Yap also advised the same thing re frequent ejaculations (every other day or three times a week if possible), and reduced abstinence time of 24hrs pre-sperm submission (in case you decide to go down the IVF route).
My husband was also on Impryl for three months before dna frag test but we don’t have results to compare with so not sure if it helped or not! Best of luck whatever you decide.

Thank you. Good luck to you too! Have you started or planning to start IVF? Did you your DH’s dnafrag improve after the embolisation?

I'm a little older than you OP and OH's DNA frag came back extremely high, in the 50s. We were devastated and hopped on a plane to see Dr Ramsey (we're Irish), luckily we managed to get a cancellation. He ran some tests and did a physical exam, said there was a small varicocele but didn't mention surgery as useful. Tests came back fine, no infections but slight oxidative stress and told us to get Impryl and head straight to ICSI with zymot. We're about to start our second egg retrieval, got 2 untested embryos out of 5 fertilised for first round.

I was a little annoyed the doctor didn't suggest anything else lifestyle wise as my OH is the opposite to me and needs doctors orders to take things seriously, but he's been taking the Impryl, high dose omega 3, vitamin D and selenium for months now and rarely drinks anymore, also reduced coffee down to once a day. I'd like to see him reduce his weight a little, BMI just below 25 but he's awful for the sugary snacks and it actually really upsets me. I'm thinking of setting him up with a nutritionist appointment as we're at a stage where it's difficult to talk to him, he finds it so upsetting.

Dr R recommended zymot for first few rounds and then Tese for the third if results aren't good. Also recommended ejaculate every 1-2 days including before egg retrieval. I'm going to get him to do a 12 hour hold this time as there's research to support lower frag with shorter holds.

Best of luck OP. I understand how upsetting this is. My vote would be IVF while implementing the changes and mitigation with zymot / shorter hold, as I feel like in late 30s the earlier you can start the process the better.

@wonderingwonderingwondering thank you for sharing and best of luck to you too! I know what you mean about it’s hard to talk to the DH and how he would only listen if it’s the doctor’s instruction. Mine is like that too.

Ive read about the 12 hours hold, it’s good you are doing that, I will do the same too when it comes to the sperm collection, but also nervous that DH may…struggle to produce.

For my DH, it’s pretty clear that his semen oxidative stress level is the culprit, despite he’s been on Impryl for almost a year. I’ve decided to now add moderate amount of antioxidants to his daily supplements. There’s a risk of having too much antioxidants as can cause reductive stress, so I’ll double check with dr R when we see him next.

We saw Mr Ramsay and had TESE on his recommendation, due to elevated DNA fragmentation. The sperm retrieved was actually worse than the sperm from our previous two cycles and no eggs fertilised using it. Just a word of warning as I felt like it was sold to us as a bit of a silver bullet and it was really costly too. We then went to see Prof Minhas who I actually much preferred (I found Mr Ramsay a little arrogant tbh!) He said he doesn't really recommend TESE and he certainly wouldn't have done so in our case. My partner had a borderline varicocele and Prof Minhas was really balanced and said it was worth trying as we were coming to the end of the road but it might not make a difference. We haven't tested the DNA fragmentation since the embolism but our most recent round three months later, we ended up with 7 blastocysts from 14 eggs which was a remarkable result for us. Our previous rounds we had 1) 2 from 9 eggs, 2) 2 from 9 eggs 3) total fertilisation failure on 20 eggs - I can only think that the embolism has had an effect but it could just be luck. Anyway, just wanted to offer another view in case helpful as the TESE is pricey and painful - it of course does work for some people though. Good luck with your future treatment.

And in terms of your original question OP, we've had no luck yet with elevated DNA fragmentation (42%) but as above, we have had much better results following an embolism although we haven't tested the sperm dna fragmentation since. Nothing else, including lifestyle changes and Impryl/Proxeed, seemed to make any difference. I'd be inclined to go straight to ICSI with zymot if I was you and if that's affordable. It's hard to see what will change in the next six months if your partner has already made lifestyle changes and seen no improvement and I do think a lot of the lifestyle improvements are pretty negligible anyway - there's far too many people I know who have poor lifestyles (drinking or smoking or recreational drug use or poor diet or lack of exercise - usually a combination of some or all of the above!) and have fathered children easily. Not to say that I don't think it's worth doing, it's all about the marginal gains and giving yourself the best chance but I think it's unlikely that you're going to see significant improvements unless you were starting from a position of a really terrible lifestyle - but it doesn't sound like you are!

thank you for sharing. In all the previous rounds/cycles, did you do ICSI and zymot too? Congrats on the 7 blastocysts!! That’s a fantastic number!

Did your DH also test his ROS/oxidative stress level? Was it normal or also high?

@Smoothieyummy thank you - I actually can't believe it and so nice to actually have some good news for once! We're PGTA testing them now so just waiting for results and praying for a good number. We've never actually used zymot but we have always had ICSI. Prof Minhas did recommend a sperm selection technique and mentioned zymot but the clinic said they'd prefer to go with the swim up method but I don't really know why (probably should have asked in retrospect but you have so much info thrown at you!). We did however use artificial oocyte activation this time round given our total fertilisation failure with the last round. However, we only used it on half the eggs as the clinic said its emerging science and wanted to hedge their bets and actually we ended up with better results from the stuff that didn't use the AOA (although it didn't cause any harm either). The only other thing we did on the recommendation of Prof Minhas was freeze some sperm. He basically suggested we should freeze as much as we could so on the day, if the sample is crap there is some back up to work with - and the more samples we freeze, the more chance we have of being able to find something good. However we ended up only freezing one as the quality had improved so the clinic was happy that they'd have enough choice from that and a fresh sample. And on the day the fresh sample ended up being better so they didn't use the frozen stuff. I don't know if we had the ROS tested - we had whatever Mr R recommended but I don't remember that being a part of it. If it was, it wasn't ever discussed as a factor or something to treat but we had issues with low morphology, low sperm count, retrograde ejaculations, a pseudomonas infection and high DNA fragmentation so maybe it wasn't worth looking into for us given all the other stuff we had going on 🤣

Thanks so much for sharing your experience, and those are incredible results, I'd be so so thrilled with that. Fingers crossed for you for the testing now, but you've got to be confident with those numbers.

I'd heard a few mixed things about Tese, but figured we'd play it by ear and see how the first few rounds go before making a call. I was a bit disappointed with the first round but attrition rates were normal for our age group, it was more a case of lower egg yield than ideal. I seem to have a much higher AFC starting this round and adjusted protocol so we'll see how it goes.

I found Dr R very compassionate and attentive, but was disappointed that the focus was solely on mitigation via IVF plan rather than an actual plan to reduce the %, which by all feedback was just so high. He did some testing and ruled out infections, hormone issues but nothing further. I'd love to explore the idea of embolization as he did mention a small varicocele, but I think we'll assess after this round before looking for a 2nd opinion. What was that process like with your partner, is it a relatively minor procedure, was there a significant wait or recovery time?

@wonderingwonderingwondering fingers crossed for this round, great news your starting from a higher AFC.

The embolisation my partner found okay. I think he was a bit sore for a few days but he was back to normal after about a week, maybe less. You do have to wait for the next cycle of sperm to have generated though - we were told 74 days. I was a bit upset about the wait but it did go quite fast! The TESE he found much more uncomfortable and it took him longer to heal from but nothing too terrible. We managed to get the embolisation on my partners health care too by saying it caused him pain. If you have any healthcare and want to pursue it then definitely look into that!