# 4th IVF failure – what else can we do?



## Deferred Dreams (Jun 23, 2015)

My husband and I are feeling utterly broken. We have done 4 fresh IVF cycles and 1 FET, and have just had a BFN on the latest. I haven't posted before, but have been lurking for some time, and these forums have been a great source of information and helped in feeling less isolated through such a difficult period of life. I think in general we have a good sense of perspective – life isn't always fair, people have to deal with much worse, etc. – but we feel so helpless and upset and angry at times.

I am 34, DH is 36. We began treatment in 2014 with 'unexplained infertility' after spending 18 months ttc. I have never seen a positive pregnancy test.

After superficial tests (normal, my AMH was 29 in November 2014), semen analysis (normal) and HSG (normal), we had two rounds of conventional IVF (11 and 15 eggs retrieved, respectively) – the first, we transferred a 3AB blastocyst and froze others which had low odds because they had been slow developing and were of very average quality. This ended in a BFN. Our subsequent FET ended in a BFN. Our second fresh cycle ended with the transfer of 2 early blastocysts, and none to freeze. Again, BFN.

My husband then had a DNA fragmentation test and his result was above average at 27%. I had immunology and blood tests. All my results were normal apart from a slight elevation of CD56 – I believe the normal level is 12%, mine was 14%. My doctor doesn't seem to think this is clinically relevant, and I know there is a lot of mystery and controversy surround this area of diagnosis and treatment. I should add that I am an identical twin and my sister conceived within two weeks of trying – we don't know how significant this is, but it is hard to dismiss altogether.

We did our third cycle at the Lister (who we have been very happy with thus far) using IMSI. This revealed that my DH's sperm is far from optimum quality, and we came to the conclusion that this may be the primary cause of our infertility and behind our average quality embryos and failure in previous cycles (without ICSI/IMSI). 18 eggs retrieved this cycle, 12 mature, 9 fertilised and 6 reached blastocyst stage. We had day-5 CGH testing on them, and all came back with chromosome abnormalities, so there was no embryo to transfer. This was devastating, but because I'm under 35, the embryos weren't particularly chaotic and there was no pattern to the abnormalities, it looked like bad luck with the batch. As IMSI should have overcome sperm problems, it was thought that this was the eggs on that particular cycle. I felt ill at times during the down-regulation and stimulation during that protocol, however, and I wonder if that had any effect.

So, now to our fourth cycle, with a smooth, short protocol on Menopur and Cetrotide. 17 eggs retrieved, 11 mature, 9 fertilised with IMSI. We had day-5 CGH testing on 4 blastocysts (and are awaiting results of 2 more which weren't ready for biopsy until day 6). This time, all 4 came back normal. This seems to confirm that it had been rotten luck last time. We transferred a day-6, hatched blastocyst (grade 6AB) and froze the others. The doctor said when doing the procedure that "IVF transfers don't get better than this." We were so optimistic.

But here we are. Another BFN. I really thought, after our two 'wasted' non-IMSI cycles and the terrible shock with the CGH results last time, that we were actually going to get a break. And I don't know how we find answers as to why this wouldn't have worked...

If you have got to the bottom of this, I appreciate your reading and time so much – thank you. I think I partly just wanted to get it all down. But has anyone been in this position? Has anyone else failed again and again with an apparently 'great' prognosis? What would stop a seemingly genetically competent, hatched blastocyst from successfully implanting? An implantation problem on my side, as well as the male factor? Just more bad luck? What else / more can we do? How do you cope when you reach a point where you feel it will simply never work? Donors don't seem to be the way forward for us – I don't think they would dramatically increase our chances of success – so I just feel we are trapped; doomed to try and try and try, when we are now just so physically and emotionally exhausted by it all.

I would love to hear from anyone who has been in this position and we are open to any advice at this stage. Thank you again for reading.

Kate x


Me: 34. DH: 36.
IVF 1, April 2014 – BFN
FET 1, June 2014 – BFN
IVF 2, September 2014 – BFN
IVF 3, March 2015 – all day-5 embryos tested abnormal through CGH, no transfer.
IVF 4, June 2015 – BFN


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## Blondie71 (Oct 26, 2011)

Hi darling a very difficult journey for you so far pls have a look at the immunes section particularly agates "learning from your failed cycles" my clinic (serum Athens) deals with alot of complicated cases with great success so that could be something to research into x


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## Deferred Dreams (Jun 23, 2015)

Thank you for responding, Blondie x

The immunes side of things has been nagging me, so will definitely ask about this at our review app. Congratulations on your boys - identical twins are great!  

Kx


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## Tbird1 (Jun 4, 2014)

Hi, so sorry for unsuccessful attempts it's horrible and very painful. Let's look at the positives you are getting the eggs and they are getting to blactytost stage which is really fab!! Have you had the level two testing done, that has been advised  for me as i have been unsuccessful twice. The test are quite expensive though.


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## angelica_wales (Oct 10, 2012)

So sorry for the rotten time you've had   

I agree with blondie - check out Agate's guide. 

Have you had clexane or steroids during your cycles? Some clinics treat impirically so you can avoid the expensive testing....

I wish you all the luck in the world

Angelica
xx


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## Bubbles88 (Apr 18, 2013)

Hi,I'm sorry to read about your failed cycles,I'd had some myself and couldn't understand why they wouldn't implant,it's so frustrating isn't it,I also did a lot of lurking on this website and trying to gather information on why it wasn't working for me,after reading a lot of good things about serum in Greece I decided that was the route I wanted to go,so I got in touch and filled in a questionaire and had a consultation over the phone (which is free)after the consultaion I was emailed a sperm improving protocol for my partner,which was antibiotics and a couple of different vitamins which he had to take for 30days I think(his sperm was great after the protocol although it wasn't too bad to start with but there was a big difference in results still) I then went over there for a hysterscopy even though I had already had one here but was told the one they do in Greece is a lot better as they actually give you a good clear out and implantation cuts which are thought to improve implantation. My partner also done a sample to freeze so he didn't have to come with me when I done my fresh cycle.Then I done a fresh cycle on low dose of stims and ended up getting the best quality embryos is ever had.unfortunately that cycle didn't work even though I had been having intralipids and steriods (even though I'd had no immune testing they will treat you just incase) I was really losing hope now,I had kept a note of symptoms I had been having everyday since transfer and spoke to penny about what symptoms I had,with the information i gave  her she decided to up my steriods as she said it sounded like my body had rejected the embryos due to an immune response,I didn't have much hope for the fet but it worked so im so glad I followed my gut instinct as went to serum as I'm now expecting twins due the end of July.i understand serum and going abroad isn't for everyone and they can't solve everything but I think they do have a really good reputation for solving difficult cases,the prices are good too.just thought I'd give you my story.I like how they don't put everyone on the same protocol the treatment is completely tailored to you,I really hope you find some answers and wish you lots of luck x


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## Bluebell82 (Jan 24, 2015)

Deferred dreams,

Wow, your case sounds like my nightmares. I'm gearing up for third cycle, also unexplained, never had a positive pregnancy test. I'm also cnsidering genetic testing of embryos next time round.

I have seen people have singleton pregnancies from two chromosomally normal embryos, so sometimes good embryos do fail and I'm not sure why ... Maybe something related to non-chromosomal ingredients such as  mitochondria or how they were placed in uterus?

If you repeatedly fail implantation and they can't find a reason, you could check for Hidden infections (Greek test), I'm personally not convinced that it makes a difference but maybe it does.

Have you had your thyroid function tested? I have an appointment with GP next week, this is because I have some other symptoms such as pins and needles, recurring unexplained thrush and low energy and often ill. So thyroid might be underactive. This could be caused by autoimmune reaction, so your twin sister may not have it.

Otherwise I would at some point consider a host surrogate if you can find someone. Surrogates should fix implantation issues (if they are not due to the embryo), but it's obviously a huge step.

The best clinics in the country for tricky cases is ARGC with 75-80% pregnancy rate for your age bracket, but the treatment is intense and expensive.


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## Deferred Dreams (Jun 23, 2015)

Thank you so much for all your replies. I have so much admiration and sympathy for women struggling through this and find it very touching that anyone takes the time to read and reply. It is really helpful hearing about your experiences. MY DH and I are very, very grateful.

Agate's guide is brilliant - I hadn't seen it before; so much information! Thanks for the tip.

*Tbird* - yes, trying to be positive, and I know we are in a better position than many (even if it can up the frustration at times!). I think I did have the level 2 testing done after our second failed fresh cycle. I certainly had blood tests which involved taking about 14(!) vials in one go and were eye-wateringly expensive! All were normal, except for this 2% elevation in blood level of CD56, which I understand relates to NK cells. Because the elevation is small and relates to blood level rather than levels in the endometrium (where I think NK cells need to work slightly differently), both doctors I've asked weren't quite sure how to interpret this. But I will certainly ask about it again at the review.

*Angelica* - one of my frustrations this time, is that in the last round the approach was more empirical. I was put on Clexane and had an endometrial scratch on day 21 of the cycle before. But there was no transfer because of the CGH results, so it didn't matter anyway. Because the sperm was shown to be a problem in cycle 3, I think the doctor felt that that was where the issue was and I was taken off anything other than the progesterone suppositories, and I regret/wonder about that now.

In my head, our next step should be a FET, but throwing more at it - hysteroscopy, endo scratch, Clexane, etc. One of the things I find particularly painful this time is the feeling that we may have 'thrown away' a viable embryo. In the last cycles, the blastocysts hadn't been optimum, so I felt the failure was probably down to abnormalities with the embryos. This time I feel sad and confused when wondering about what else we could have done.

*Bubbles* and *Bluebell* - thank you for your responses. I think I could do another fresh cycle if it came to it and Serum and ARGC (actually about 15 minutes walk from where I work) would definitely be contenders. The intensity and expense of ARGC is what put has us off until now. I might try and get a consultation/second opinion from both in the meantime anyway. Congratulations on your twins, Bubbles - that is wonderful news and I wish you the absolute very best for the birth. You will be exhausted but happy!  I also got my best embryos this time, so think a lower dose protocol is the way forward for me.

*Bluebell* - I'm so sorry that you are in a similar boat. The 'unexplained' diagnosis seems relatively positive to begin with but turns into a curse! I hope you're not too filled with dread for number 3 - I think it tends to be better once you're underway. Have you considered IMSI for your next one? This seems to have been quite a big step forward for us in that it was diagnostic. It is expensive (surprise!) and I'm not sure there's much in it when compared with ICSI for results, but looking at my DH's sperm under the mega-microscope showed that quality was a problem, so IMSI had been worth doing for us. Average sperm can fertilise eggs in IVF, but the resulting embryos won't develop well. All his parameters/semen analyses came back normal, so this would have remained hidden without the IMSI. We also had the expensive sperm DNA fragmentation test, for which he had borderline results. Just a thought.

CGH can obviously be very helpful and diagnostic too. Though beware small sample sizes! After our third cycle we were talking about donors and thinking there may be a fundamental problem with my eggs and/or the embryos we make together. Completely different story the next round, so we are in better shape than we were in some ways.

I will ask about the Greek test, thank you. My thyroid has been tested and all normal I think. A good friend and my sister have both said they would be surrogates if it came to it (amazing how generous people are), though I think I would need to feel more confident that there was an incurable problem with my uterus/receptivity before going down that route. Definitely an option we would consider. Something else I've heard from an embryologist is that some women do better with a FET (even though rates are a bit lower in general), particularly if their estradiol levels are high. Apparently fresh cycles are something of a sledgehammer preparation to maximise eggs at retrieval, and the endometrium may prefer a more nuanced environment/preparation for implantation. One of my ovaries was still quite enlarged at transfer. It would be lovely if it turned out to be something as 'simple' as that and a FET with euploid embryos worked for us.

Anyway, thank you so much again for all your responses. They have lifted and informed me, and I feel better than I did yesterday (though, er, a little hungover - it doesn't take much when you've been so good for months!). And good luck - I hope you all find a way through this, and the difficult times are a memory soon.

Kate xxx


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## Blondie71 (Oct 26, 2011)

Kate the NK cell activity certainly sounds a key player, I had raised nk cell activity but the Greek Dr who ran the tests could only tell me I had inflammation somewhere in my body and he didn't know where, the culprit turned out to be my fallopian tubes leaking fluid and killing off embryos, tubes were both removed and my first FET worked, so if you haven't had an HSG it might be worth doing in case problem lies there x


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## Bluebell82 (Jan 24, 2015)

Hi Kate,

Thanks for reply and glad that you are feeling better. My DH had DNA fragmentatio test, it came back at 11% which is considered good. We will get husband's karyotype tested. My karyotype was tested for the egg-sharing cycle and is normal. Also not sure that abnormal karyotype would prevent pregnancy for almost 4 years, but it could make things worse and indicate that we have to use chromosome screening. We will stop using IV fertilisation and switch to ICSI (I'd pick IMSI but I don't think ARGC uses IMSI) to exclude stressful events caused by eggs being surrounded by millions of sperms for several hours. Don't know if this will make a difference, I hope it will.

Chromosomal abnormalities in our embryos may be a problem for us. Our embryo development hasn't been that great, which could be due to sperm but also egg chromosomal abnormalities. Your story gives me hope that getting away from the standard long protocol may give us better egg and hence embryo quality. I think the stimulation hormones can negatively affect the chromosome alignment and separation. some ladies seem to have eggs which are more sensitive to the hormone levels than others and get low blastocyst quality as a result. I'm hoping that ARGC monitoring will get this right for me. ARGC is more expensive and involved but then you also get the success rate of two Lister cycles in one ARGC cycle (and 3 UK average cycles).

FET might be better for implantation, indeed, so definitely worth trying with your frozen embies. I keep all fingers crossed for you that it will work this time and you don't have to change clinics.

It's amazing and generous indeed that you have people offering you help with carrying your baby. You will know when the time has come to pick them up on the offer, I'm sure, hopefully you won't have to.


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## Deferred Dreams (Jun 23, 2015)

I wanted to update this thread, in case people are still stumbling on it and find themselves in a similar position (I received a message about it today).

Following our fourth failed fresh cycle, we did another frozen cycle, transferring one of our CGH-normal blastocysts. It was a natural cycle, with Clexane and Cyclogest. Unfortunately, it resulted in another BFN.

We went directly into another frozen cycle, again a natural cycle with Clexane and Cyclogest as a precaution. I was nervous about doing this, as we didn't have a review appointment beforehand – but the doctor was keen for us to have one more go with an euploid blastocyst, which would give us enough to suggest an implantation problem (in addition to male factor) and before moving onto steroid treatment/further intervention. This cycle gave us our first ever BFP! I'm now 11 weeks pregnant, and everything has looked great on our 6-week and 10-week scans.

I still can't believe how difficult it has been to get to this stage. But I found the information and support in people's responses extremely helpful, and hope it may help others in a similar boat, as well as offering a dose of hope.

K xx


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## angelica_wales (Oct 10, 2012)

Lovely to hear a happy ending  

Congratulations! 

xx


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## Bluebell82 (Jan 24, 2015)

Hi deferred dreams,

Great to hear that the FET worked for you guys. Such a journey!

I had the lot of immune tests and my cytokine levels have come back high and are being stubborn, so I'm still waiting for my third cycle to start. I hope tackling the cytokines will mean that the next IVF will work.


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## RB76 (Jul 27, 2011)

Oh I'm so pleased, I just read your first post with sadness, not realising it was from June.
Wonderful that you're now pregnant, congratulations! X


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## 2boys (Jul 18, 2014)

Hi deferred dreams, congratulations on your pregnancy, I can see from your sig that you had a little boy, that is lovely news  You may not even see this, but I just wanted to ask a quick question in case you do read it. I have just had bfn from a blast transfer with euploid embryo. Our 6th attempt, 4 miscarriages and one bfn on a fresh transfer. I have had immune testing, was on IVIG, steroids, cleaner, aspirin. It was a natural cycle FET as my lining didn't respond to medicated and always had fluid as well as thin lining (5 cancelled cycles). So we have one final euploid blast left. It's our last chance as DH has said enough now. And he's right. I just wondered what else I can do? Did you have a hysteroscopy at all? I have had one when having a post-miscarriage d&c and all looked fine except for endometriosis but that was over two years ago now so maybe worth doing again. I had an endometrial receptivity test too and that was normal. I'm thinking of requesting low dose stims for next FET to plump lining up a bit but other than that I'm all out of ideas. 
Any suggestions more than welcome!!


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## Blondie71 (Oct 26, 2011)

2Boys give penny a ring at serum clinic, she'll give you free advice on what options there are for best outcome with your history, she's happy to talk to people regardless if you're a patient or not, she is passionate about helping women/couples get pregnant ❤


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## Blondie71 (Oct 26, 2011)

Private message agate on here she is a mine of information, not sure how frequently she's on though as just had twins herself x


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## 2boys (Jul 18, 2014)

Thanks so much Blondie71 and congratulations on your gorgeous twins xx


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## Blondie71 (Oct 26, 2011)

❤


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