Help! What test to do after 3 failed IVF?! before the next one?

[avocado2019]

Hi, there,
I need some help of advice/experiences. Feeling really difficult now.
age 39, AMH 13.5
1st ISCI, 1 4BB frozen, 3 crap emboss frozen as well
2nd ISCI, 1 blastocyst + 1 morula both transferred, failed
did sperm investigation, raised sperm DNA fragmentation, also poor sperm quality due to motility and abnormal form 96%
partner took supplement for 3months, then,

3rd IMSI Nov 2019, disaster as clinic used the wrong sperm ( old sperm sample instead of the one produced for Nov), no blastocyst, failed

FET Dec 2019, not working

feeling very very low. clinic offered discount on a new cycle. I asked about whether I should do any test before “just do another cycle”, doc listed out Thrombophilia Screen (THROMB), NK cells, TH1:TH2, Thyroid antibodies, Chromosome karyotype (both male and female),

Doc said normally after 3 failed transfers they’d advice these test, so i can do it if i have another failed transfer, but if I want to treat the next cycle as the ‘last’ cycle, I can go ahead do the testing. Doc basically think it’s the number game just need to keep going.

My own research including test of ERA, Hysteroscopy. Doc said the routine scan didn’t suggest necessity for hysteroscopy so no need, ERA is only for frozen transfer.

I am trying to get my head around to work out a plan, but also don’t know what is better. Hope to hear your advice or experience. Many thanks!

Hi OP
I'm in a similar position- go for 3rd egg collection tomorrow

My first 2 cycles were short protocol and egg quality was rubbish - even with ICSI and both times collecting 12 eggs only 4 fertilised

My clinic doesn't believe in ERA so doesn't offer it and the HFEA website says there isn't much evidence that it improves success rates

Instead of karyotyping we did PGS on our second round - one blast came back complex abnormal (not allowed to transfer) and the other a mosaic (did transfer but BFN) so suspect our recurrent miscarriages are down to egg/chromosome issues

We decided rather than to just keep going on the same protocol to change things - this cycle is a natural modified one - clinic said no point forcing my body to create lots of eggs - let it choose the one or two best ones as at the end of the day that's what it's designed to do. So this cycle is very low stim injections every other day with tamoxifen tablets daily (similar effect to clomid). I have 2 follicles which they are going to collect tomorrow

This one part of a 3 cycle package so on the next one they said they would maybe do daily 150 Bemfola stim instead of every other day to try and get a couple more than 2 follicles but at the moment we are focussing on quality rather than quantity as it's clear from the previous cycle that forcing quantity isn't working for us

I forgot to say I also had all the blood tests you mentioned except NK cells as my clinic has me on prednisolone anyway for transfers which is the treatment for it anyway - perhaps ask your clinic about proscribing that?

Dear @itwasalovelydreamwhileitlasted. Oh my god I ll keep my fingers crossed for you today and hope you get very successful EC!!!

Thanks a lot for taking time giving your comments. It's interesting that your doctor switch to low stim and let body select. My doctor on the contrary don't believe in "letting body naturally select" and believe in the only factor of age that determine quality. So his phylosophy is basically we need to get as many eggs as possible so we have the chance to get more embryo to select. My first two rounds of fresh cycle I have high fertilisation rate.

Through research on the internet, NK cells testing seems recommending if one has multiple miscarriages. I had a miscarriage back in early 2017, but 2 BFN in my last two embryo transfer, so should I wait to see if miscarry happens again to check this or better do it earlier so as not to waste embryo?

I figure if you are on your 3rd fresh cycle and had already all those test done maybe I should have them tested indeed, as my next one would be my 4th!

Good luck for today and fingers crossed for you!!!!

Hi both
Hope EC went well @itwasalovelydreamwhileitlasted
I am in a similar situation and wondering what to do next. Just found out our fifth transfer (two blastocysts) hasn’t worked.
We’ve had two early miscarriages and three failed transfers (across two fresh cycles). We have three frozen blasts remaining. My AMH is relatively high and egg quantity doesn’t seem to be the issue but clearly there’s an issue with either egg quality or receptivity. I’m already on steroids and my clinic haven’t suggested further tests as steroids are their treatment anyway. My clinic have suggested another cycle with OE but I’m not sure I’ve got it in me to do this along with two more FETs and then need to move to DE as am now 40 and feel worn down by it all. If I do another cycle with OE perhaps I should PG test these and the 3 embryos together to avoid unnecessary transfers and gain clarity on egg quality? Has anyone taken this approach? TIA.

@GreyGoose1980 I PGS tested on my second cycle as a last test to figure out why were were having so many miscarriages (5) and I guess we got our answer in that both blastocysts came back abnormal/mosaic - in the U.K. you're not allowed to transfer abnormals so you could end up with nothing to transfer so it's a massive risk which is why I'm not PGS testing future blasts.

To test your frozen ones they have to be thawed biopsied and then refrozen so there are risk they may not survive the procedure

I'd rather try different drug regimes to try and improve quality rather than PGS which has just been downgraded by the HFEA anyway x

Thanks for sharing your experience @itwasalovelydreamwhileitlasted and best wishes for the next few weeks xx

Hi, @GreyGoose1980 thanks for sharing. Congratulations that you got so many high quality blastocyst embryo in freeze within 2 fresh cycles! Wow well done! If you egg quality isn't the issue why not stick with OE for a bit longer? of course if you prefer OE.
Thanks @itwasalovelydreamwhileitlasted thanks for sharing the information on PGS in UK. Wow i have no idea of that those abnormal/mosaic result embryos are not allowed to transfer. It make sense that if I end up with 2 i'd def transfer them both directly. Maybe worthwhile to do PGS for 3+ embryos when you don't know which to transfer?
@GreyGoose1980 I would think embryos are quite precious would you want to investigate receptivity more? I have read quite a number of posts who did ERA and found that the endometria is more receptive if transfer one day earlier or later, some others did scratch.
Good luck!

Thanks @Avocado2019
Also really sorry to hear that the clinic made a mistake with the sperm sample and hope they compensated you as much as possible. Can I check if you have used the sperm since your DH took the vitamins? My DP also did this for 3 months following defrag test initially ordered as many of our embryos in our first cycle failed between day 3 and 5. We then retested and defrag was then measured as normal and we increased the number of blastocysts between cycle one and two (although ultimately have not been successful yet). With me egg quantity isn’t an issue but I think egg quality may be as I have not done PGS and from what I’ve read it statistically seems more likely than receptivity to be the cause. My clinic have not mentioned ERA. I don’t know much about ERA. I have medical FETs and have always been led to believe in that instance transfer day doesn’t impact much between day 20 and 22 and have transferred on day 19 for fresh and between 20 and 22 for frozen. I will discuss this further with them though and look into receptivity more. My cycles are between 28 and 32 days long so not sure if ERA is only for those with very regular cycles too? If anyone has any further info on this that would be really helpful. I have also always been fine with the idea of donor eggs - I just really want the experience of having a baby whether there’s a genetic link or not which makes me want to ensure I focus on the option with the highest odds which seem so much better for ‘younger’ eggs.
Also are any of you tempted to change clinic? My clinic is convenient, responsive etc I just can’t help thinking a change may just help me out as DP and I haven’t achieved results yet? Or is it better to stick with a clinic who know my history as I have no complaints? TIA.

Hi my clinic advised era after 3 failed cycles / think we did between 4 and 5

And it did show I needed more progynova And lining wasn’t receptive at day 19/20 which they do fets

And when we did cycle 5 that was the one that worked

I did take for ages as away on holiday but it kept my lining at 1.1 and triple later at scan and that was the only bfp I had in 10yrs of ttc

Dd is almost now 3 and my miracle and world

We had 3 failed short protocol cycles in 2018 and early 2019 (I have stage 4 endo and hubby low motility) in September we did long protocol which involved 4 months of injection that put me into temporary menopause and then stims ahead of egg collection 13 eggs collected only 3 fertilised and only 1 made it to day 5 for fresh transfer. We were devastated but transferred that singleton and am currently 22 weeks pregnant with our first baby.

Yes all those tests are useful plus whatever extras including thyroid etc that need to be included plus treated with an appropriate protocol before you start the cycle. I had 3 unsuccessful transfers until I got the BFP that produced my baby, because of these tests (I was 38 and all of the tests flagged something wrong!).

Hi ladies, sorry I was feeling really low over the weekend and didn't put up strength to check the forum. Congratulations @brotherforbear , @blondeshavemorefun and @grumpyhoonmain, it's so nice to hear story of success!

@Blondeshavemorefun that's indeed a miracle baby! must be a super strong bean! Could I ask looking back would you ever consider if you did the era in earlier rounds it'll make any difference?

Grumpyhoonmain, that's reassuring that you think all the tests are helpful. Could I ask are those tests (plus others you named) were recommended by your Dr. ? My Dr. just suggested us try another cycle with slightly higher stimulation meds, it was me who asked if we should do more tests before rushing into the next cycle then he listed out the tests saying if we want the next cycle to be the "last cycle" we can go on to test them all (so we won't regret). So I am a bit split, reason 1 being our next cycle is a much discounted one which we have no problem to top up the remaining cost, however I don't' have £2K this month to go through all the test, however my finance will be much better in 2 months time by which time I can afford the test. I guess psychologically it is very difficult to "do nothing", so doing another cycle during the in-between time and if it doesn't work , by that time, I'll have the money to do the test. However I don't know if this thought means we are "wasting" a cycle. reason 2 being i felt it might be right to follow Dr. advice rather that insisting on testing. Totally split.

Thanks again ladies I am very thankful for this space!

Hi, @GreyGoose1980, regarding the ERA, I have read this thread www.mumsnet.com/Talk/infertility/2796994-IVF-after-the-age-of-39, look for the 3rd post from @alifemoreordinary , I think @Blondeshavemorefun posted there as well. I think I will definately do this before my next FET (as I was told ERA doesn't apply for fresh transfer as there is no choice of choosing transfer date). But I can relate that in my 2nd cycle, we have 13 eggs collected, 12 fertilised, 6 top quality embryos till day 3, then only 1 survived as top quality on day5 and another one as morula. both transfered BFN. that's why we were sent to investigate sperm. dna fragmentation is out of normal, low testosterone, (like everything's low). But it is encouraging to hear your story that sperm quality does improve after supplement. I am thinking maybe we should do another dna fragmentation test just to see the difference?

To answer your question, unfortunately we haven't got any chance to test my partners sperm after the supplement (due to the mistake). Since yesterday I started to toss the idea of surgically retrieve sperm, as this is one possible consideration in the dr's(urology) letter. my partner's quite negative about "surgical", but some post on this forum suggested this worth consideration as this way avoids the fragmented sperm. but I am doing more research now.

@avocardo. Yes for me it was worth it coz it did show I needed longer on the progesterone

But for many on here the era showed all was fine

I think it’s worth having done as then rules the transfer day being wrong out if all comes back fine

It may have been fluke that out 5th finally worked

Or may have been the fact I took for longer

Who knows why ivf works for some first cycle and others 4/5/6+ cycles

@blondeshavemorefun thanks! yes! When I started 1st cycle I felt really excited (on the positive sense). I'm always very curious on new things and very pro-tech. so the 1st cycle was really fun for me ( both my parents are doctors so grew up in hospital environment, and i quite enjoy the experiment on injecting myself ..no kidding..). After failed 1st cycle I wasn't very sad thought it's just a test run, if i prepare for 3 cycles then we'll succeed in the 2nd.

it was a real numb after 3 cycles unsuccessful. very shock, disbelieve, don't know what to do. And also very fearful now about the egg collection. Feeling full of bruise physically, emotionally and, of course financially. And thinking should I just prepare myself for "it's not gonna to happen".

only since a few days ago I have started to come around, decided to try for more. Very glad you stuck to the end, but have to tell myself that not everyone's lucky.

Get your clinic to split off all the ‘Level 1’ tests that the NHS considers as definite risks for pregnancy / conception / infertility / miscarriages - these are the tests your GP, if supportive, could do for you for free as part of the NHS. Or at the very least you could shop around to obtain via private Gp services.

Then ‘all’ you need to pay for are the Level 2 tests.

Sorry I missed the cock up with old sperm

Clinic should do whole cycle for free. Not a discount - their cock up

I would be tempted to say to them you will be seeking legal advise

Tbh we were going to give up after 2nd failed

But stopped for a year. Saved. Borrowed and went again

Helped that time as abroad we had more embryos as higher drugs and icsi that uk didnt do and 4&5 fets

I don’t know how much money you have spent and if you can afford to go one more time or decide to give up

We just couldn’t :( and yes got into debt but dd is worth it

But

As you know it’s not guaranteed - you could spend another 10k and not have a baby

It’s a very personal decision when to give up x

Thanks @blondshavemorefun yes it was a cock up - quite unbelievable. clinic offer free treatment but we pay medications, saying that the bad outcome could be sperm quality or egg quality. We mentioned that we understand perfectly that even with the newer sperm the outcome may not be better, but it's like a contractual thing that the plan is to test the sperm with supplement, so to discuss the cause of bad outcome is not relevant. We asked the doc to check with management if we don't have to pay for meds. Waiting for response now.

I guess my character is that kind of i probably have to try till i completely bankrupt (almost now). But family has helped and I will have more income later in the year (but that'll be when i turned 40 so very nervous with the thought having to wait), so I guess I could probably afford a few more rounds if abroad, but not that many if in UK.

One thing keep touching my nerve is I always have the doubt if the procedure of EC might cause damage of ovary or vagina tissues, e.g. leaving a tiny cyst if not healing smoothly, so I am always worried too many EC cycles, that my health will have to in later years. I have asked this to my Doc but he told me this is not sth to worry about.

Thanks for sharing your experiences @Blondeshavemorefun @GrumpyHoonMain
@avocado2019.
@Avocado2019 - we found a second DNA fragmentation test useful as it measured the impact of the vitamins (and lifestyle changes - DP gave up alcohol and coffee). Presumably you could still arrange this test now if your DH has been on the vitamins for over three months. I also agree that the clinic should fund the cost of the ivf meds to eliminate all financial detriment) X

I just wanted to give an update following my egg collection on Saturday

Natural modified cycle this time - low dose stims every OTHER day with tamoxifen tablets (similar effect to clomid) - collected 2 eggs

Well both fertilised and both top quality grade 1 on day 3. This is significantly better than my first 2 cycles where I was on a standard stims short protocol - 12 eggs collected each time - less than 50% fertilisation rate no top quality ok day 3 and ended up with 2 average blastocysts each time

This time 100% success rate so looks like changing protocol and allowing body to do more natural selection has worked better for me so far.

The only difference other than paring the protocol right back is I swapped from coq10 to ubquinol and added in royal jelly tablets

Have you had a lap? I had one after my third failed cycle (third transfer) and my next transfer worked. They cleared out the endo and put me on the down reg protocol ( was previously on short protocol). I'm currently 7 weeks. Will never know if it was the tests/extra treatment that worked but I couldn't carry on putting good embryos back without success. Turns out my case was mismanaged and I should have been offered a lap before I started IVF xx

That sounds really promising @itwasalovelydreamwhileitlasted. Thinking of you.
@FingersXssd83 - Thanks for posting. Can I ask if you had been already diagnosed with endo, or was this only discovered as a result of the lap? x

@itwasalovelydreamwhileitlasted thank you for sharing! such encouraging news with the top quality embies! really glad for you!
you seem to be much more pro on supplement, I have just discovered the book "It starts with the egg" and bought CoQ10 yesterday. I remembered back in Sep the consultant mentioned this while she mainly refer us to do sperm investigation. I am so upset with myself didn't take this seriously and I could have started 3 months earlier!

@greygoose1980 thanks for the tip. I have spoken to Dr. today and we decided we will do another dna fragmentation test for the sperm. But I will also ask partner to make an effort on coffee and alcohol. He hasn't worked on that . Anyway Dr. said he has meeting with finance and can get back to us tomorrow whether clinic want to cover the med. Thanks for the consideration.

@FingersXssd83 hey congratulations you are now on the other side of the river . I asked the dr. about lap, he said there hasn't been anything indicating from the scans that I need a lap so he doesn't think this is necessary. Did you required a lap or it is suggested by Dr.? Many thanks!

@avocado2019
Thankyou!
I wasn't that read up on supplements until I had my first egg collection and was shocked/devastated at my apparent lack of egg quality. I had been taking pregnacare for years but after that ivf cycle I changed to Proceive Max which has the most "stuff" in it that I could find and I fell pregnant naturally the month after the failed IVF transfer with my crap quality embryo. I miscarried unfortunately but I have a history of miscarriage anyway and it was the first BFP I had had in 18 months which was progress in itself!

This time seems to have made the most difference which I do think is a combination of reducing my stims to the bare minimum and the supplement changes. I also cut out my 2 cans of Diet Coke/Coke Zero 4 weeks ago - I read an article that drinking diet drinks (because of the aspartame) can reduce IVF success by as much as 25%

Obviously the proof will ultimately be in having a successful pregnancy but for the first time in 3 ivf cycles I feel a bit more hopeful x