ERA/EMMA/ALICE Testing thread 4

[Janefx40]

New thread ladies! @Gardenlady543 @MyEasterEggs @seven201 @VenusStarr @Violette22 @Yuliaaa

Hi @thislittlebird I've seen your posts on other threads. I'm sorry you're going through this. I wrote my history a couple of pages ago. The ladies on here have been very welcoming. I have an appointment with Dr Shehata at the CRP Clinic in September as I've suffered a miscarriage with my first fresh cycle (third overall loss). I can see there are a lot of positive stories here for the CRP but I can't see any official stats.
I'm not sure if ERA/ALICE/EMMA can help with recurrent early miscarriage. Does anyone know? I'd like to do all the tests the CRP Clinic recommend (assuming I have something to transfer as am also planning to PGT test this time, something I didn't do with my poor little 5BB Embryo).

@birdbybird hi! I’ll look up your history on the other page. Oh god, I’m on all the threads lol. Been hanging out on ttc and infertility boards for a couple of years now, unfortunately.

I’ve encounter some of the folks on here on other threads too. I nearly posted a couple of weeks ago anticipating my second failure but I thought, no, I’m jumping the gun, calm down. But here I am now! I think we’ll likely do a double transfer for our last two because we have to pay the clinic after the third, and I think I’d rather spend that money on meds for my next private round. Or on more tests!

I’ll Google CRP, not sure what that is.

@thislittlebird

Hi, I’m sure we’ve chatted before I recognise your username.

So there’s a few things going on, you might want to consider sending your history for a second opinion at CHR, I think it was about $350 and could help to highlight tests to try. https://www.centerforhumanreprod.com/contents/services/second-opinion-program

So here are the things that are jumping out at me:

• Age, you will already know the chance of a euploid embryos goes down with age and with untested embryos you may have just transferred two aneuploids without knowing it. Sounds like you’ve got 2 embryos left so at your age you could do a double transfer next time or test them or go through with 2 single transfers and then think about testing the next set if they don’t work.
• MFI, ICSI should help to overcome this, you may want to look into the sperm chip sorting method for next time if they didn’t use it this time.
• Your collection cycle sounds perfect from the numbers, 12 mature eggs is great, 9 fertilizing with ICSI is what’s expected and 4 to blast again as expected. So I wouldn’t be pushing to change anything there.
• ?PCOS, I’ve been in this boat too I have a high AFC but normal hormones and regular cycles, so I don’t fit the criteria either. I was told it could be more likely in my case as I have a fairly high FSH with a very good AMH. Usually when FSH is high, AMH is low. I did the male hormone panel through medichecks which you may want to consider, it tested for: FSH, LH, oestradiol, testosterone, free testosterone, free androgen index, prolactin and DHEA. I also did a fasting insulin resistance test and was told if it was abnormal I’d be started on metformin (I would prioritize this if I were you since you’re prone to thrush).
• Low progesterone, look at the regime you’re using and get it optimized, I’m wondering if I should go onto PIO, it’s not used that much in the UK. You can add in lubion with the cyclogest which should get your values and may be as good as PIO. Next cycle have a blood test the day before the transfer and increase up the dose if it’s low (nobody has decided what low is, some people like over 20, others 30, my specialist likes over 50).
• Microbiome issues, you’ve read my post on this so you’ll know what I’ll say. You could either do a EMMA ALICE or a menstrual fluid test through fetilysis. I know this is the ERA EMMA ALICE thread but I’m currently not that convinced about the ERA so the menstrual fluid test might be something to consider if you’re not considering doing a ERA. Checking your vagina pH is something you can do pretty easily yourself and will tell give you a basic check for if you might have bacterial vaginosis. Using a vaginal probiotic and balance active around once a week could also be useful.
• Immune issues, to explore this you’ll need to see a RI, I’m under Dr Gorgy, I think between us here we’re under most of the UK specialists in RI.
• Other useful things, repeat your blood tests, just standard routine bloods, I developed hypothyroidism likely as a result of IVF hormones so don’t think you’re invincible to a new unexpected issue. Here’s a list of things you can check, your GP should be able to do this for you:

⁃ Full blood count ⁃ Urea and electrolytes ⁃ Bone profile ⁃ Liver function tests ⁃ Coagulation screen ⁃ CRP ⁃ Thyroid function tests ⁃ Vitamin D ⁃ Haematinics (Iron, B12 and folate) ⁃ Fasting glucose ⁃ Fasting cholesterol ⁃ HbA1c

• If you want to go further and look into a autoimmune screen and thrombophilia screen you’ll need to pay for this most likely with a RI if you’re under a NHS clinic.
• Imaging, this is incredibly important and I think it’s ridiculous people on the UK don’t have this as standard. If you haven’t had a saline scan, HSG or hysteroscopy then get one of the first two, as ultrasounds miss a lot.

I think for me as I had never ever had a positive with good embryos, it was enough for me to worry after 2 unsuccessful transfers. My euploid rates where then extremely good again pointing to an issue.

@birdbybird I'm going to get so confused with 2 birds on this forum! Sorry to hear about the panic attack that must have been scary!

I have never had a positive test in 3 years.

Yep, I'm vegan.

My history is long and complicated, but here goes...

Started TTC 3 years ago, regular cycles, tracked from the beginning, always caught the fertile time, but every single month BFN.

Initial tests were fine, TSH 1.2, hormones all normal, husbands sperm looked great. I had a small fibroid but it was outside the cavity and I was told it wouldn't be an issue. And my AFC was very good.

Fresh cycle November 2020, 12 mature eggs, 9 blasts, my specialist described them as the highest rates of high quality embryos she'd ever seen. The embryologist said it was so rare to work with such high quality embryos.

Day before the fresh transfer I got a rash and was later diagnosed with progesterone hypersensitivity but we went ahead with the transfer, BFN.

Medicated FET in February 2021, again BFN.

I then thawed my embryos and PGT A tested them, of the 7, 1 didn't survive the thaw, of the other 6, 5 were euploid.

I had a full thrombophilia screen, it picked up the MTHFR mutation, an abnormal PAI-1 and the C4M2 mutation, but nothing to write home about. I just started taking methylfolate and was put on heparin in cycles.

I did ERA EMMA ALICE, was found to be pre receptive by 24 hours and had 0% lactobacillus and a mix of dysbiotic bacteria. Took co amoxiclav and probiotics. There were issues getting the sample so Ashermans syndrome was mentioned and I ended up seeing a specialist and having a HSG which was normal. Meanwhile I saw Prof Brosens and had Nk biopsies which were normal.

Transfer number 3 was May 2021, my estradiol for some reason was 10 times higher than it should have been and I ended up getting breast changes that needed to be biopsied. BFN as per usual (euploid embryo).

My specialist thought my lining is weird, thin towards the bottom, so I have a hysteroscopy, there are cervical adhesions but nothing that would explain anything.

I then repeat the ERA EMMA ALICE, I'm still only early receptive so they told me to take another 12 hours of progesterone and my microbiome is still 0% lactobacillus, so I treat again (aggressively this time with metronidazole and clarithromycin and a shedload of probiotics). I was worried about my microbiome worsening if I repeat the test so I go straight into a transfer, euploid embryo, again BFN. I sent off the menstrual fluid to be tested and it had a normal microbiome.

I then peruse immune tests through fetilysis, I have raised NK cells and a complete DQA1 match with my husband.

I have a blood test to check my thyroid and I have developed hypothyroidism, TSH 12.1 and low T4. I go on treatment and it comes down and see an endocrinologist and get diagnosed with hashimotos.

I have had issues with thin lining in natural cycles that seemed to get better last year but my periods became light again so went for an ultrasound and I now have a submucosal fibroid that needs removing and my lining is 5-6mm.

I see Dr Gorgy about the immune stuff and he recommends a Nk activity biopsy which has come back as normal, he recommended donor pooled LIT for the DQ match, I had the first one last week. He had me tested for insulin resistance which I don't have. I think he's going to start me on hydroxychloroquine, I'm speaking to him on Monday.

I'm due to have the fibroids removed in about a month and the surgeon will look for endometriosis (just in case) at the same time.

It's likely I will be aiming for my next transfer around November with the fibroids removed, my thyroid under control and on the immune stuff that's recommended.

Thanks for the detailed reply @Gardenlady543, let me try to respond to the different parts - long reply incoming!

Age - yeah, I'm aware it could be aneuploids, but I didn't feel with only 4 we had enough to test, and obviously only have 3 transfers on the NHS anyway. I think we're going to do the double next time, we have a 3AB and a 5AC remaining, transfer will likely be in late September if the schedule remains the same. I don't see the point in paying Guys for one final transfer. I'd rather move on to a new egg collection in October/November tbh. So I suppose I'm thinking what can I test in the time between now and then?

MFI - yeah we had ICSI at Guys, they said they managed to get his motile sperm percentage up to 50% in the centrifuge, is this the same thing you mean? Sorry, not familiar with chip sorting.

Eggs/Embryos - yeah, we were happy with 4 embryos, and would be again. Obviously more is great but I think that's not bad for our age + mfi + my mystery many follicles that isn't PCOs.

PCOS - what's your FSH/AFC/AMH, out of curiosity? My FSH and LH are very low, 1.something and I've worried this could be an issue, it seems very low. I don't know who I could see about that though? My AMH is 31 or around that, and I responded well to 150 gonal f, and 5mg letrozole before that, albeit no BFP. What is the male hormonal panel? Is it male hormones tested in women? I've had most of those tests and they've all been normal. I have not had free testosterone, free androgen index and DHEA. I might have had some other androgen tests, I asked my GP to test for PCOS and he ran some but I'd have to look up what, prolactin was in there. I'm pretty sure I had the insulin one when I went to the GP for the PCOS tests, I'll ask my doctors surgery to send me the results (they may have done already).

Progesterone - I'm definitely going to ask the consultant what they're going to do about this, assuming Lubion will be their answer. My progesterone has been as low as 10 naturally, and as high as 108 on cyclogest + letrozole. Not sure what it was today, but low probably.

Microbiome - I'm interested in Fertilysis, do you remember how long it takes for the test to arrive and the results? If I'm understanding it correctly. Is it something you buy on their website? Am I understanding right, it's a sub for EMMA ALICE but not ERA, which you don't rate? Do you or anyone else here recommend a vaginal PH kit? I've seen them online and not sure which are good.

Immune issues - does Dr Gorgy specialise in immunes? Is there anyone else people have been to who does the same thing?

⁃ Full blood count - had this
⁃ Urea and electrolytes - not sure
⁃ Bone profile - had this
⁃ Liver function tests - had this
⁃ Coagulation screen - not sure
⁃ CRP - not sure what this is
⁃ Thyroid function tests - had these
⁃ Vitamin D - have not had this and want to
⁃ Haematinics (Iron, B12 and folate) - not had these - any suggestions for where to get these? My GP surgery is hard to get an appointment with, I might not have the time to wait weeks for a non-urgent appointment.
⁃ Fasting glucose - I think I have had this, will check
⁃ Fasting cholesterol - I have high cholesterol but I'm normal weight, I've suspected this could be a PCOS/PCO symptom since all of this has been happening, not sure though
⁃ HbA1c - I think I've had this, will check

Honestly not sure what thrombophilia and autoimmune screens are exactly, I'll look them up

I've had a Hycosy, which was all ok - I'm assuming that's not saline if you didn't mention it?

I've never had a positive but obviously not tested my embryos, but I'm definitely going to see what i can get done between now and September.

Oh, we also had DNA Frag for my husband, which came back mostly normal despite his poor motility. I guess that kinda makes sense since we were able to make embryos.

Sorry, I keep adding things. The other thing is we have done natural modified cycles so far, because of my hormonal migraines. I'm considering whether to do a medicated but I'll be honest, I don't want to. I'm scared what the oestrogen will do to my migraines/how damaging it might be. I'm pretty sure it causes migraines and thrush in me.

And, because I can't shut up, my lining has been good on natural cycles. 7.7mm this month 8 something the previous time.

@thislittlebird

Age - I think the plan to do a double and then cycle again and consider Pgt a for the next batch if you have enough is a good plan.

MFI - it's good that your partners DNA fragmentation was ok, centrifuge can cause more damage to sperm. Microfluidic chips mean the sperm have to swim through membranes and it helps sort the sperm without damaging them.

PCOS
My results were:
July 2020 FSH 8 AMH 17 AFC 34
December 2021 FSH 11 AMH 20 AFC 28
January 2022 FSH 8 AMH 14
March 2022 FSH 8.5

When I got the second opinion they said I could have PCOS phenotype D and expected low androgens if that was the case. But my hormones were all fine and e insulin resistance test was also fine so I don't think I have PCOS.

What is the male hormonal panel?
It’s just the test that you can order on medichecks to check all those hormone,
medichecks.com/products/male-hormone-check-blood-test
It’s fine to order it as a woman, medichecks told me lots of women do.

Fertilysis
You order online, the kit comes out within a few days. When you get your period you collect a few drops of the blood and put it in the freezer then mid cycle you take a vaginal swab and arrange the courier to collect the samples and they will email the results to you around 10 working days later.

It uses the same method as EMMA ALICE, detection of bacteria RNA. The difference is it's testing the menstrual blood rather than a biopsy which is not particularly comfortable to have. It's also cheaper.

ERA is a test for receptivity, if you’re doing natural FETs ERA probably isn’t needed, it’s harder to manipulate the window of implantation in natural cycles and there will be between-cycle variability. A lot of specialists aren’t keen on ERA, I was quite positive about it, but I never implant even with their timing so I don’t know. I’ve been speaking to some people that ended up ignoring their ERA result and doing the usual progesterone timing and got success.

Do you or anyone else here recommend a vaginal PH kit?
This is the cheapest one I found, you really don’t need anything fancy, it’s just pH paper, you will need to put a cotton bud up then rub it on the strip, you want the pH to be under 5.5, if it’s above that you probably have bacterial vaginosis and need treatment
amzn.eu/d/gjboHe5

Immune issues - does Dr Gorgy specialise in immunes?
Yes

Blood tests:
You could repeat them all, as a lot are pretty standard.
⁃ CRP - is an inflammatory marker, an alternative is ESR, I mean it’s not essential but if you’re doing bloods you may as well do one.
⁃ Thyroid function tests - had these- do them again lol I developed hypothyrodism during IVF! You need TSH less than 2.5.
⁃ Vitamin D - have not had this and want- good do it
⁃ Haematinics (Iron, B12 and folate) - not had these - these are important so do them.
any suggestions for where to get these?
If your gp won’t do them, use medichecks.

Honestly not sure what thrombophilia and autoimmune screens are exactly,
These are what are tested for as a implantation failure panel. Thrombophilia tests look for whether the blood is more likely to clot due to a genetic issue, if it is they will likely add heparin into your treatment. Autoimmune screen is to look for autoantibodies.

Mine tested for

Autoantibody screen

• Thyroid peroxidase
• ANA
• Mitochondrial antibodies
• Smooth muscle antibodies
• Gastric parietal
• LKM
• Anticardiolipin IgG and IgM
• Beta 2 glycoprof igG and IgM

(I’m really annoyed it didn’t test for thyroglobulin antibodies)

Thrombophilia screen

• PT
• INR
• APTT
• Fibrinogen
• Antithrombin II
• Protein C
• Free protein S antigen
• PAI-1 4G/5G
• MTHFR

I've had a Hycosy
That’s good, that will be more detailed than a ultrasound.

I personally would stick with natural modified FETS, I want to do this but can’t as I have issues with my lining.

@Gardenlady543 I've not seen that outcome where the FSH is high but the AMH/AFC isn't. And it sounds like you don't have an explanation for it yet?

Fertilysis - so I assume it'll miss this period if I order today, which will be due as soon as I stop the cyclogest on Thursday, and I will be able to test my next period in a month, doesn't sound like it'll be here in time for this one. I'd definitely prefer this to anything invasive, I feel sick thinking about more invasive tests.

ERA - glad you don't rate it/don't recommend it. It's one I can ignore, since I'm hoping to stick with natural. I was considering whether to try a medicated cycle, but my hormonal migraines and thrush seem to be triggered by oestrogen and when you mentioned breast lumps it reminded me I need to be cautious if I can be, I've had a large fibroadenoma before and I don't want to trigger any of that if I can. I wish I could trust the consultant would recommend what's best for my history but I have to be honest, they don't seem to cater anything to me. I have to remind them of all my concerns about excess oestrogen each time.

Vaginal PH Kit - ordered! Is there a specific time of the month you're supposed to do these? I can feel the irritation starting yesterday, which is normal the day before my period starts. But then it usually goes away once my period kind of clears everything out.

Blood tests - CRP says it's about risk of heart disease and I'm pretty sure it would come back saying yes. I have a history of stroke and heart disease on both sides, as well as my own high cholesterol which my mother also has. I've been tested for this and they said it's not familial hypercholesterolemia , which is why I wondered if we both have it as a symptom of busy ovaries, for want of a better word, because it can be a symptom of PCOS. No idea really, just wondering because she took years to conceive her first kid. I found this Superdrug test which seems to cover a ton of things, including vitamins and CRP. Might be better value than individual ones with medichecks for me. superdrug.meliohealth.co.uk/health-check and the fertility one also seems to include some useful things: healthclinics.superdrug.com/services/female-fertility-hormone-screen/

Thrombophilia - this feels like something I should get with my family history, did you use medichecks for this? Same question for the autoantibody screen?

Do you have any explanation for the lining issues you've had?

I think @birdbybird's idea of a folder of all my test results, or a spreadsheet, might be a good idea.

I've not seen that outcome where the FSH is high but the AMH/AFC isn't. And it sounds like you don't have an explanation for it yet?
Nope and only the second opinion doctor picked up on it, they thought it pointed to PCOS but I guess that’s been ruled out. As I had a good egg collection, I guess it doesn’t matter.

Fertilysis - so I assume it'll miss this period if I order today,
You could carry on with the progesterone to try and hold off a period while you wait for the kit to arrive. You need to collect the blood in the first few hours of a period.

I was considering whether to try a medicated cycle, but my hormonal migraines and thrush seem to be triggered by oestrogen and when you mentioned breast lumps it reminded me I need to be cautious if I can be.
Yeah this is my concern, the fibroids and hypothyroidism likely came on as a result of hormones. But there’s not much choice for me due to my thin lining.

Vaginal PH Kit - ordered! Is there a specific time of the month you're supposed to do these?
The pH will change slightly, during your cycle, during your period it will go up, it goes up slightly around the time of ovulation as well. But in general it should give you an idea of the pH of the vagina, you're best leaving it a few days after your bleed though as menstrual blood is alkali so it takes a few days to reset.

Blood tests - CRP says it's about risk of heart disease
I think you’re talking about ANP, CRP is an inflammatory marker, c reactive protein. It goes up in infections and when there is inflammation.

I found this Superdrug test which seems to cover a ton of things, superdrug.meliohealth.co.uk/health-check
Looks good

and the fertility one also seems to include some useful things: healthclinics.superdrug.com/services/female-fertility-hormone-screen/
This one is quite expensive and repeats things that the first one looks for, it also doesn’t have things like DHEA which is a good one to check (I looked into this for the PCOS). It does include thyroid hormones though so do make sure they are checked in a test somewhere for this. Medichecks does packages as well, so you may want to sit down and go through what’s available on both sites and decide where would be cheapest.
The hormone tests need to be CD3 by the way.

Thrombophilia - this feels like something I should get with my family history, did you use medichecks for this?
I think this one’s need to be done by a fertility clinic/RI. My friend didn’t bother as her specialist routinely uses heparin in her cycles. If your specialist is willing to add in heparin you don't need them. Mine picked up the MTHFR mutation which is pretty common, it's probably better if everyone just switches from folic acid to methylfolate just in case they have this. Some prenatal vitamins have methylfolate in.

Same question for the autoantibody screen?
My friend managed to find all the autoantibodies I mentioned on medichecks.

Do you have any explanation for the lining issues you've had?
Not really. Before I started IVF it was 5mm in a natural cycle, it thickens up fine with stims and in medicated FETS.
But then they had issues getting my ERA biopsy in a medicated mock cycle as the lining was described as patchy.
I had a HSG to see if I had Ashermans syndrome, which was fine.
I then had a hysteroscopy which didn’t reveal any issue with the lining.
I thought the lining issues were resolved with the microbiome treatment as I got up to 8mm in natural cycles last year.
But then I found out I had hypothyroidism and treated it and my lining shrunk down again, so my theory is that the lining has always been thin (maybe due to low oestrogen) but hypothyrodism caused it to thicken up (endometrial hyperplasia).
I’m now being told the submucosal fibroid could be causing the thin lining as the lining is stretched over it and in addition the fibroids could be affecting the blood supply (but they weren't there in the past). I’ll have to see what happens to the lining once they’re out.
I’ve just send off a biopsy for CD138 which is a test for endometritis, so it will be good to see what that shows.

@thislittlebird that post was for you

@Gardenlady543 Quick fertilysis question before I order, is it the basic or full microbiome package? Guessing it's full, thought I should check before I hand over 700 euros.

@thislittlebird I did full as it tests for more types of bacteria. Check out if you might want to do any of there other tests before ordering. As the courier cost is quite expensive.

I have done

• DNA fragmentation
• Immune panel
• Semen microbiome
• Menstrual microbiome

@Gardenlady543 for the immune panel, what did that tell you in your case? I'm trying to get a sense of if it's worth it, it's not cheap.

@thislittlebird
I did this one
fertilysis.com/tests/reproductive-immunology/fertilysis-full-reproductive-immunology

Mine was a bit cheaper as they weren't able to do KIR when I ordered. But that meant I had to pay Gorgy for it.

If you do the immune tests with fetilysis you need to arrange to have your blood taken as well and centrifuged which will add onto the cost.

With Gorgy the tests cost:
NK assay, Th1/Th2, LAD, DQA1 £1300
KIR £240

Hi ladies, I’ve lost track of the thread over the last week or so but wanted to hop on and see how you’re all getting along. I know it’s been a trying time for most of you 😞

We’re moving home over the next week so I’m tied up with that, but have my TEG test rebooked with Raj Rai in two weeks so I’m glad that’s back on the cards again.

Officially told the clinic I’m postponing until next again cycle so FET will be second half of September sometime, depending on how my cycle goes.

Still taking supplements but my nutrition has gone out the window which makes me anxious. Can be a vicious cycle 💛

@MyEasterEggs hello! Exciting to be moving home. New house or new area? Hope the move goes well.

@Gardenlady543 help! I think I may have BV. Never had it before but I feel sore generally down there and (sorry TMI) there's a slight fishy smell. Do I have time to get this sorted before starting our FET? I have about 2 weeks.

@Janefx40
BV doesn't usually cause soreness that's thrush, but is you pH high? If so either get to the gp for antibiotics today or order this one

www.theindependentpharmacy.co.uk/bacterial-vaginosis-bv/metronidazole-400mg-tablets

They have a few different postal options to get it to you quickly. Metronidazole spares lactobacillus so you should be fine. Follow up with the acid tablets and vaginal probiotics.

@Gardenlady543 thanks. Just tested and PH seems normal. Mine tends to be a very light greeny blue as normal so never quite like the colour chart but closest to normal or possibly the very lowest rung of abnormal.

@Janefx40 just pop to the pharmacy and get a thrush pessary. It won't do any harm. Keep an eye on the smell, if it gets more fishy then go for antibiotics.

Thank you!!! If I do need antibiotics do I need 14 tablets or 28? I may order now just in case so I have them ready to go.

@Janefx40 dose for bacterial vaginosis is 400mg twice a day for 5-7 days. So you'd probably be fine with the 14.

@Gardenlady543 How early do you mean? My period hasn't properly started yet and the kit is coming tomorrow. I'm having brown discharge still (I think), is it that stage or when you get fresh blood? I decided to stop the progesterone, can't face keep taking it, not sure whether to take it or not.

I've done my first PH kit test and it came up as the colour of 5.0, not sure what that means yet, some online sources are saying it's a bit high, some saying fine, obviously my period is due tomorrow properly so that might change it.

Will need to look into other tests I want to do right now, can't spend all the money in one go :/