ERA testing after multiple implantation failures. Anyone had it done?

[seven201]

I've had four transfers so far (first 3 from 1 batch, fourth from a second egg collection) and 4 BFNs. I have a naturally conceived 4 1/2 year old and had a natural pregnancy with early miscarriage a bit over 3 years ago. My lining struggles to get to thickness, I have polycystic ovaries (on sukkarto), a fibroid, slightly high thyroid thingy (on levothyroxine), high bp (on meds) and a midline septum (ridge/divide in the uterus). I had surgery to unblock a tube 2 years ago. I'm in the healthy weight range.

My clinic have suggested PGS testing (we have 5 embryos in the freezer) but I'm really not keen on it as I've read about actually fine embryos being shown as poor and therefore being disposed of.

They also suggested ERA (endometrial receptor assessment). Has anyone had that done and found it useful? I just hate anything that delays the next FET but I think maybe it will be worth it?

Any other suggestions? Last FET I was on lots of estrogen, extra progesterone injections, clexane, neupogen infusion, aspirin and probably a whole load of other stuff I've forgotten.

I am so fed up with it all!

Hi all, @Gardenlady543 I spoke to you before under username foreveraintenough - we were on a monthly thread together.

So I got my results today and I was told I also have 0% lacto whatever. So you are not the only one gardenlady. My consultant said he has never seen that before. I told him you also had 0 and he said we must be the only two in the world (not reassuring).

I also had lots of bad bacteria - staphylococcus and streptococcus- he said if you think about it the good stuff should be fighting the bad stuff but when there’s no good stuff it can flourish. He’s recommended a repeat before doing a transfer and to take Canesflor daily for 2 weeks (usually only for one week) and then weekly. After I take antibiotics.

Gutted. We have so many problems. Took us 6 rounds of IVF to get 4 embryos. Sent some off for PGS and came back inconclusive so don’t know if we can make normals. I have a never seen before vaginal abnormality they can’t figure out that may mean I’ve a weak cervix, I’ve high natural killer cells so need steroids and now zero good bacteria.

I read back over the thread gardenlady where you said you wonder if the 0% has to do with your lining being thin - my lining was actually fine so from our sample size of 2 it’s not necessarily related.

Should add after 6 days of progesterone (Crinone) my progesterone was 4.3 and should be at least 50 so also need to try figure that out too. Never easy. We initially started IVF for male factor as my DH has a low sperm count but now it’s looking more like I am the issue.

@Cream123 yeah I'm interested to know as well because bacteria and the immune system go hand in hand, it will be interesting to see whether they think low nk cells could have caused the bad bacteria. Or whether the level of bacteria led to high nk cells. I mean I doubt anyone knows to be honest but would be interesting to see his take on it.

@Alwayswithhope2 I thought it was you! So many people keep changing their names, it's hard to keep up. Oh wow I'm
glad I have a 0% lactobacillus buddy! Do you have some of the chronic endometritis bacteria then? I luckily didn't have any of those bacteria types but obviously I was still full of the dysbiotic ones. So my friend is under Mr Gudi and she mentioned my case to him. He has had two people come back with 0% and both only needed the one course of treatment, he always repeats. And when my specialist called the lab they said 0% is not unheard of. But a lot of specialists have never seen it before.

Your specialists plan has made me feel a bit better about things not working in my recent cycle, as there is a chance my flora is still not resolved so it seems like a good idea for me to pursue the mock cycle and repeat the test.

I am so glad you found out about this, I know it feels like you're collecting diagnoses; I feel like that too. So far I have: a fibroid, thin lining and light periods, arcuate uterus, c4m2 mutation, pa1 mutation, very bad microflora result, transfer window out of sync, progesterone hypersensitivity, ridiculously raised estradiol in FET for no reason, paraovarian fluid collection. 3 of these things have never been seen before by my clinic in anyone else! However if you test everyone for all this stuff, everyone will be found to have something. The microflora is treatable, so try not to worry :)

@Gardenlady543 re your discussion with @Cream123 I have had immune testing done and it came back with raised natural killer cells needing steroids for transfer. I asked today about the steroids and how the bad bacteria are causing inflammation so would steroids work on that and he said that it’s a different type of inflammation so the steroids wouldn’t suppress it. So I’m not sure of the link between NKC and bacteria in Endometrium.

Yes he mentioned chronic endometris to me. I need to research it. That’s reassuring to hear about the 0% going up. The plan for me is to take antibiotics then the macrobiotics and to repeat the Emma/Alice and hopefully both will have improved.

Then if I can go for a FET if they do improve. They found my receptive window in the ERA but don’t know if it’s reliable with my progesterone being so low so my consultant has emailed the people who process the test in Spain to find out.

Collecting diagnosis is exactly it! It amazes me how many people just get pregnant naturally. So with the perfect lining thickness , balance of Bacteria and perfect micro biome, receptive lining, correct levels of progesterone, good sperm quality, good egg quality, chromosonally normal, progresses easily until Day 5 when it implants. It’s mind boggling it just all comes together for so many people 🤷‍♀️

One thing I’ve learnt is the supplements and healthy eating do very little. I have naturally fermented yoghurt every morning straight from a farm, same with this sheep’s cheese I have for lunch it’s all natural good bacteria and my pre natal supplement have probiotics in them. Didn’t do a thing! The consultant said I probably have lovely gut bacteria!

What is your next steps garden lady? Will you take a break for a bit or do your repeat then break?

That's interesting about your result @Alwayswithhope2 I wonder if the high amounts of bad bacteria caused the high NK cells.

You will be on a similar timeframe to me with this repeat, so we can chat about how we're getting on. I'm waiting for my period after the unsuccessful FET at the moment, then I'll do the natural cycle and repeat the EMMA.

That's really good that they found the transfer window, I'm wanting to repeat the ERA at my 145 hour recommendation to see if it was correct. Your progesterone is low. I had mine checked the day before transfer in my first FET it was 46 when I was on 1 x lubion and 1 x cyclogest. So I got told to take another cyclogest. Can they increase up the progesterone and then repeat the ERA at the same time as your EMMA repeat, so they know if you're receptive when the progesterone level is good enough?

You are right in how little control we have over things. Me and my husband have done everything right all our lives. It made no difference, we're still here having IVF. I had the most probiotic rich diet possible, but as your specialist has pointed out once the bad bacteria flourishes like this, the good can't compete. We need the antibiotics to shift it to recolonise with the good stuff.

@seven201 hope ur friend managed to do your bum!!!
@alwayswithhope my progesterone was 24 one cycle with 1 lubion and 2 cyclogest. I’ve managed to get it closer to 100 with 2 lubion and 3 cyclogest. Very expensive that’s for sure. Good you found out before your transfer.

Should have read bum injections obv!!!!

@Gardenlady543 yes we are on a very similar time line. I am thinking about getting my natural cycle tracked at the clinic so see wha my progesterone is after ovulation. Just out of interest as initially when I did fertility tests (years ago now) it said I ovulated and my progesterone was fine.

I would wonder about the bad bacteria and lack of good being linked to all the invasive procedures I’ve had - you seem to have a lot too. I wish I could’ve done this test before my 1st ivf to see what state my uterus was in then compared to after 3 mock embryo transfer, 5 egg collection, 2 embryo transfers, tube check, x2 ERA etc.

This was my 2nd ERA. First found I was pre receptive and then this one was on day 6 and found I was receptive so it does seem to be accurate enough. Given you’re having the biopsy anyway could be no harm to repeat ERA for that time and get the confirmation. Now we’ve found window consultant not keen to repeat it with higher progesterone dose. He thinks by going straight onto heavy progesterone dosage the minute the embryo is in it will hopefully go up so then I’ve got implantation window and higher progesterone. I don’t know. I’m too tired mentally to think about it logically.

Thanks @Cream123 for that info on the progesterone. I’m in Ireland and we get all our meds for €100 regardless of amount (but then we get 0 funding for IVF) but it’s good not to have to worry about meds cost. I’ll be asking for all the progesterone 😂

I hope you guys managed to have a nice weekend. I had a nice day with family but again up and down as my two siblings younger and older than me have kids so it’s so obvious to me my arms are empty and I feel like it’s so obvious to everyone else too.

@Cream123 thank you. My friend was great at doing my bum injection. Her husband kept offering to do it instead .

My transfer is on Thursday but cases in the secondary school I work in have been going up. I don't work Mondays so I've only got tues, weds and half of Thursday to get through though. I'm just going to stay as far away as possible and keep my mask on. There's no way I'd be allowed time off. My appt last week was initially refused.

@seven201 have u had your vaccine?
That’s so funny about the husband - I just burst out laughing!

I’m still having brown spotting nearly every day. It’s so worrying :( my scan is on Thursday and I’m so worried. I wasn’t worried last week as thought it was over but now it is or isn’t I don’t know!

@Cream123 gosh what a nightmare for you with these constant scans! Really hope this weeks result is as good as last weeks.

@seven201 not long to go now, yes avoid contact with people at work like the plague over the next few days!

@ForeverAintEnough3 you've changed your name again? So I think that potential causes for the dysbiotic microflora are: the coil, surgery and IVF. I had a mirena coil for six years prior to starting to conceive and I imagine that the bad bacteria went up into my uterus with that and then colonized it. I expect it's been this bad the whole time I've been trying to conceive which seems to provide some form of explanation for why I seem to have very good egg quality and create very good embryos with my husband but yet they never implant. What is more difficult to explain though is why this recent FET didn't work when everything was thrown at me and the issue should've been treated with the course of antibiotics and probiotics.

That's really good that they confirmed the receptive window with a second ERA. That's what I'm hoping to do with mine.That's interesting their thoughts about progesterone, I think the difficulty is once they find the receptive window with a particular dosing of progesterone, changing that dose could then alter the window. So they really need to get the dosing right before doing the ERA in the first place. I'm now wondering whether I should have mine increased further as some people can get the progesterone in the hundreds and get told it looks fantastic, surely there's always room for some improvement.

@seven201 good luck for Thursday. It’s so close now x

@Cream123 sorry about the constant worry and the brown spotting. It's just such a tense time. Is it Thursday your scan?

I've had one dose of Pfizer. Got the next booked in for 2 1/2 weeks after my transfer but will only go ahead if I'm not pregnant. It's not the right attitude I know but I just never have much hope that it will work. I've been standing as far away from the students as possible. Another class was sent home this morning after a positive pcr test. What's annoying is the whole class minus the positive child was in yesterday despite them having a positive lateral flow on Sunday evening. But you have to wait for the positive pcr before sending the rest home.

God it’s all so stressful as it is let alone with covid in the mix. Glad u have had at least one jab and just be careful what else can u do.
Thanks @seven201 am so unbelievably stressed just want knocking out till Thursday night and being told the outcome!

Sounds like it's a big day on Thursday for both of you.

I had my estradiol checked today, this was the whole reason I couldn't go straight into a mock cycle.

And it was 140, I am CD4 of my natural cycle and the normal range for the follicular phase is 45-854. So this seems to be evidence that it's come down, so it seemed to be the meds being prescribed at too high of a dose causing the level of 8000.

@Gardenlady543 what a relief! That’s insane it goes so high!!!! When is ur repeat era are u doing it before or after the nk biopsy?

@Cream123 yeah, one less thing for me to worry about! So I'm so confused about what to do next, I watched this YouTube video which is a journal club about a research article

The study authors had looked at people with a morphologically normal uterus having euploid embryo transfers (doi.org/10.1016/j.fertnstert.2020.07.002), the chance of implantation with the first is 69.9%, for those that were unsuccessful the chance with the second is 59.8%, and for those who needed a third it's 60.3%. The authors say they even looked at those who were unsuccessful three times and on the fourth the chance of a live birth was still 56%. Their conclusions are that only 3-4% would not have success after 4 euploid transfers, so investigations aren't needed until this kind of time. They feel that recurrent implantation failure exists but don't know at what point it should be diagnosed or further explored. I think my case is tricky and warranted the early investigations because my embryos look great but never implant. In the YouTube discussion they say that endometritis can be a cause of implantation failure. I didn't have the bacteria that cause endometritis but I don't think this means I didn't have it, clearly the microflora were affecting my lining which seems to have improved after the course of treatment. So I guess the question is: do I assume that's now corrected and start counting the first transfer I has after the investigations and treatment as #1 and say I was unlucky but if I keep having euploid embryos transferred the chances are that I will be successful and at least have the same chance of success with the next three. Or do I re-examine their endometrium to see if the bacteria is definitely resolved and check the receptivity, given there isn't any evidence that it's fully resolved and it was pretty horrendous. I'm inclined to recheck which will mean I'll do the mock cycle after this natural cycle, I'll then have a natural cycle while awaiting results and then do another transfer probably around October. With nk stuff hopefully fitting in around this.

Yeah I’ve read that study. I don’t know - personally I would go down the route of all investigations. I had ashermans and no one told me I had it despite having 200 scans and no number of euploid would have worked - something was wrong. And I pushed it and eventually I was right. I had normal periods and my doctors said my lining was just “one of those things” on my scan. Once it was fixed I got my bfp. I know my history is totally diff to yours but I could have not pushed looking into things and just transferred 10 more embryos to get bfn each time. Eventually giving up.

However going down all the tests def brings stress….it depends on ur personaility I suppose. I mean some people told me that having 6mc by age 32 was just one of those things god knows how many more I would have had if I had listened to those docs. My uterus is literally scarred from my fertility hx and I don’t think it could take any more losses….

What I mean is if I were u I would recheck and do the nk biopsy! I think bronsens just knows a lot about implantation failure he will have seen a lot of people like u and give u some advice and hope and ideas of where to go next. But that’s just me!

I haven’t really worked out why I mc though so not sure it’s been that helpful for me

@Cream123 yeah I think I'm in agreement that it's best to do the era and Emma and nk cells and then move back into the treatment. If I had read that study after my 2nd FET I would have thought I should postpone investigations and just transfer euploid embryos. I suspect I would have been in the 3-4% where it wouldn't have worked though. Because natural conception should have worked with my embryos, the whole thing made no sense.

I would have thought that the average patient doesn't have horrendous microflora (like me) or Ashermans (like you) and they're the ones who end up in the 96% of people where it works. I really hope that both of us have fixed the underlying issues now and that you have success with this pregnancy and I get success soon!

@Cream123 ha i'd like knocking out for next two and a half weeks!

@Gardenlady543 it sounds like a good idea to me to repeat the era and Emma and do the nk thing (I admit I don't really know what that is!). I think just getting the Emma results would be worth the delay as you've been so worried if the 0% is fixable.

@seven201 yeah I think so too, I hope my specialist doesn't persuade me otherwise when we have our review appointment next week.

I hope you're doing ok, not long to go now!

I agree with your approach @Gardenlady543 I’m another who only had 2 failed transfers (only 1 was a blastocyst other was a morula) and then pursued for more tests. I just felt some working wasn’t right with my early bleeds in TWW and now have discovered the progesterone issue and that my implantation window was wrong never mind the Emma/Alice results.

I feel consultants sometimes approach it as not needing to waste money on extra stuff as it might well work on next embryo. Ignoring that the cost of a round of ivf is far in excess of some extra tests (or for you in U.K. using up an NHS round).

I’m glad your estradol went down. Hopefully that means this breast scan will be all good too. And yes I did name change again sorry 🙈

@seven201 good luck with your transfer tomorrow.

@Cream123 how are you doing?

@ForeverAintEnough3 yeah my breast appointment is Monday afternoon. They seem to be back to normal now, so I think the changes were down to the huge estradiol. It's also reassuring that the estradiol has come down as the "oestrogen releasing tissue" that the specialist said could have been a cause, could have been in the breast. I'm still going to go to the appointment, because I think, any opportunity to have a look into this stuff should always be taken, just in case. There's always stories about people who didn't feel a check up was necessary and then they end up regretting it in the future.

It's interesting that you pursued the further tests at the same time as me. I had the same "something isn't right" feeling.