Reproductive immunology - is there anything to it?

[ginandtonicformeplease]

We were lucky enough to get a BFP on our first cycle, but then had a MMC at 9 weeks. I just had a second cycle, but that resulted in a BFN.

We just went to see our consultant and I'm not sure of the way forward now (we still have some frosties to transfer). Due to my 'young'(!) age - 36 - and that the two embryos transferred and failed were top quality, he wants to run some tests to see if there is anything else preventing it working.

These tests are for Natural Killer cells. He was very upfront and said that there have been no large scale studies on it but his clinic and one other clinic in London believe the science behind it and so if there are no other factors then they will investigate this. These tests cost £1200 as they send the blood to Chicago.

They also want to run a test for thrombophilia. As there is a family history of strokes, it wouldn't surprise me if I have a predisposition to thrombosis.

Most of the time I'm very good and don't google, just trust what the doctor says. However, I'm on the fence about this one - as there have been no large scale studies into NK cells, and the experts themselves all disagree about the theory behind it. Part of me just thinks that we should go for another FET and hope third time lucky, the other part of me knows that I wouldn't forgive myself if we went for another FET and it was either BFN or another miscarriage.

I'm at a loss as to what to do. We've had to self-fund the entire thing, and I'm aware that there are some clinics out there who just trade on hope. In the past our doctor has told us not to bother with add-ons that he doesn't think are worth it, so I've never felt like he's been just trying to make money off us.

Hi Gin - I'm curious about this as well. I had an early miscarriage about ten years ago, and I recently had a chemical pregnancy after my second IVF cycle. I really think I had some chemicals when I was a lot younger and still had eggs (I'm 38, need donor eggs due to premature ovarian failure). My instinct tells me there is something stopping a pregnancy progressing, but the tests are expensive on top of already expensive IVF.

I'm starting my third cycle now, but if I have a chemical, I think I'll probably do the tests.

OP sorry just curious so to basically dumb it down for me, do u mean they think your body is essentially rejecting the pregnancy like someone could reject a donor organ? Ive heard ppl mention this before your body can essentially react to it as a foreign body?

2fingers Yes, that's probably a pretty good analogy. The theory is that these NK cells stop an embryo developing if one managed to implant, and more generally stops embryos implanting at all.

Red We have MFI, the doctors said my eggs are fine, so in theory ICSI should sort the problem out. As it hasn't, they're now looking for another reason but the tests are so expensive. As I'm not generally a googler when it comes to health, I'd never heard of them before so wondered if anyone had any experience - negative as well as positive.

@ginandtonic i would honestly just fo the tests hun i know its a LOT of money im looking into private ivf myself but i feel like its worse to live with regrets..the what ifs games its not a gd headspace to b in. I want to feel if none of this works at least i know ive tried everything. I hope someone can help you out x

I knw they havent done a lot of research into it yet but it does seem so logical doesnt it? Why have docs not thought of this before? you can get diseases that your body attacks its own cells so why not an embryos?

Have the thrombophilia tests first and then consider the NK tests.
I have three friends with similar issues and none of them were recommended this kind of testing until after at least 3 miscarriages — obviously that’s not ideal either but a single miscarriage could just be bad luck.

Dame Do you know if that was NHS or private? I know that NHS waits for at least 3 miscarriages before it will do any investigation - in some areas I think it's gone up to 5 - which seems a lot Togo through before any testing.

2fingers We don't have an infinite amount of money. If we spend it on testing then that's one less FET that we can spend it on. It's very easy to go for every test available as IVF clinics live on hope but I need to consider everything before making the decision. The theory behind NK cells first came about in the 1960s so they thought of it a while ago!

Watching with interest.

My clinic raised this, but also said it was as yet unproven. His view was that you could spend the money on the test, and then the treatment, or just take the treatment and save the money on the test.

He said if it was something we felt strongly about, there was little downside to throwing everything at our next (and probably last) cycle.

Still not decided...

I wouldn't. Purely because the success rates of IVF are naturally low, if it was 80-90% and you were still not pregnant, or you were on your 5th/6yh cycle I'd think maybe there is an extra reason, but surely the most likely reason is that it just hasn't stuck yet.

Only one of the three was in the UK but the test wasn’t covered.
Waiting until three MCs, while awful, seems to be pretty standard in all the four countries I have infertile friends in and even at private clinics so it may not only be NHS resource problems.
One of them did immunosuppressive treatment without having any tests and just had a baby after 5 MCs.

Yh i know i get it no one wants to live in debt trying to get pregnant but also no one wants to live with regret its a catch 22. Im going through it to trying to balance the pros and cons of waiting a yr for nhs ivf

2fingers Unless your age is really against you, if you have the opportunity to have an NHS cycle I would grab it with both hands. We were going through the tests when our CCG withdrew any funding, so although they could tell us the problem there was then no help for us.

Botanica It's interesting that your consultant said that - ours was very much of the opinion that it only affects 10-20% of women, so there's no point in having the treatment if the test is negative. I'd be happy having intralipids without a test, not so much taking steroids.

@ginandtonic trust me im grateful im allowed a free run of ivf on the nhs but i think ur underestimating how long a yr feels thats another yr of my life on hold another yr of anxiety depression and stress it takes its toll on ur mental health. As u said theres no guarentee itl even work after the yr long wait

A failed transfer and pregnancy loss are much more likely to be due to genetically abnormal embryos rather that an issue with your body, at 36 you have a 1 in 2 chance of each embryo being abnormal so it could well be the other embryos transferred had aneuploidy. There's no real evidence behind a lot of immunology so personally if it was me I wouldn't bother and would use the money towards more treatment or PGS. I had some extra meds empirically - prednisilone, clexane and prontogest as I asked for them and I did get a BFP on cycle 4 but MMC, I then paid £1,200 for Chicago bloods that would of allowed me intralipids but by the time I had cycle 5 I decided not to bother so did the previous meds again and had a baby

Lauren What made you have the tests but then decide not to continue on that path? As we've got the embryos frozen already if we went down the genetic testing route they'd have to be thawed, tested, re-frozen and then any good ones thawed again before transfer. We have asked about that but the consultant doesn't think it's worth the risk and wouldn't recommend it. Plus it's about 5k so we wouldn't have the money to pay for a transfer after! I do understand what you're saying about it could just have been bad luck that the two embryos picked were bad ones - the doctor said that if I were 40+ he wouldn't be recommending these tests, as two failures wouldn't be surprising.

At the moment I'm leaning towards just having the thrombosis tests due to family history of strokes. DH is leaning towards getting every test done. This is the first time in the whole journey (4+ years) that we've disagreed on the best plan of action.

If i'm honest paying for the NK was just a knee jerk reaction to my MMC, the clinic didn't push it I asked for it, the reason I didn't pursue that route was I then had a 2 year gap and started working in a fertility clinic so had a lot more insight into things. With the PGS a lot of clinics are negative about it and say the damage rate is high etc but in the early days of PGS people biopsied on day 3 so it was higher than it is with blasts, personally for me if I had a few embryos I would be of the mindset of just transferring them without PGS testing but if I had a lot I would consider it as the emotional and financial implications of transferring multiple aneuploids are pretty high.

Thanks Lauren, that's very helpful. I don't usually google health related issues so have never pushed for anything, just always gone with the clinic's recommendations.

I have another long term health condition that I'm on multiple medications for - I'm wary of adding another cocktail of drugs into the mix as nobody knows how they'll all interact.

Just in case anyone reads this in future - my acupuncturist suggested going to the GP to get at least some of the tests done on the NHS. Surprisingly he's ordered a whole host, obviously not the NK cells but thrombophilia, auto immune and quite a few others.

I never thought I'd be taking advice from an acupuncturist, but she specialises in treating fertility and so has a good idea of what loads of clinics do. I'm still not sure what we'll do about the NK cells test but I feel better for getting some started.

That's great news hope you get some answers

Thanks Lauren so do I! The GP was asking me about the cost of private treatment and seemed staggered by it, and the fact that the payment doesn't include blood tests and medication.

The acupuncturist did mention that most clinics she works with don't actually test for NK cells but just give patients intralipids anyway as they don't do any harm - this made me wonder why ours pushes for the test.

If I'm honest I have found the opposite, it's really really hard to get intralipids without NK testing first. I'm wondering if she treats a lot of patients having treatment abroad as they do it empirically elsewhere in Europe

The clinics she named were all in the UK, not in London though.

I really do feel that it's one step forward two steps back - I've just had a call from the GP to say that he shouldn't have given me the test order without a letter from the consultant. So I've emailed the consultant to see which ones he'd like done. Tbh I'm a bit worried the consultant will be put out that I'm trying to get some done on the NHS rather than through them.

I just wish I knew what was for the best. Sometimes I wonder whether we should just accept we aren't meant to be parents.

The consultants at my clinic will do blood forms for GPs happily, they don't mind where people get them done and are happy for them to save money where possible. Let me know if you find somewhere that does intralipids without NK as all I could find was a place in Wales when I rang loads of places, it was 2-3 years though. I know CARE and Zita West won't do them without tests

We're with Zita West (I found them on a MN thread and liked them when we went for a consultation!). We have found them really helpful, especially when things go wrong - OHSS, MMC, BFN. I guess I'm just in two minds about the NK cells as it's so expensive just for the testing. DH is leaning on the get tested side only because he thinks it would stop another miscarriage (I ended up in A&E, it was pretty awful and he doesn't want to see me go through that again. I've explained that there's always a chance of losing a baby but I think for him anything to lessen that chance.

If it's in your head I think you need to consider doing it or you will always wonder 'what if' and that's a horrible position to be in. I was happy to skip them as I knew if it didn't work out I wouldn't think it was skipping the intralipids so I felt comfortable with the decision. I did however want to stay on my fragmin, prontogest and steroids