Total fertilisation failure

[BlueBirdy]

Hello,

My husband and I have just gone through our first IVF (with ICSI - we have male factor issues - bad count and morph, motility is ok). At my final scan I was only showing 8 follicles (was on 150 units gonal f) 6 were a good size but two were smaller ones. I thought this was on the low side but the FC said they were happy with how I responded and pleased with the amount of follicles. Had pregnyl 1000 trigger shot on Saturday and went for egg collection yesterday (Monday). They collected 7 eggs but only 6 were mature. Got a call yesterday eve to say that of the 6 they injected, 2 didn't respond very well, so was usually an indication that those two did not have the best chance of fertilising, but overall there is a generally a 70% rate of fertilisation. Got a call this morning to say that sadly NONE had fertilised. They said this was very rare (I later googled it and apparently there is a 1 - 3% chance of it happening with ICSI) and said they could not tell why it happened (or rather, didn't happen) but could be down to either the sperm or eggs or drug regime I was on. I'm really gutted. This was our one and only NHS funded cycle.

I've got a follow up appointment on Thursday morning, not sure if I'll find out anymore then. Was just wondering if anyone else has experienced this, and if they had any success with further cycles?

Naty I know - and when they do change things around, it seems like it is more just to see if it would work that way, rather than because they have a solution for the problem. My first cycle was short protocol and only 150iu gonalF per day - I only had 8 follicles (including two 11mm ones). Second cycle was long protocol and double dose of gonalF, and I produced waaay more follicles. The thing that gets me, is that the first cycle 7 of 8 follicles produced mature eggs, so why did they feel they needed to change the trigger? Only 10 mature eggs out of more than 20 decent sized follicles! Anyway, rant over - so you are waiting to see if you can get past Saturday without any spotting? And OTD is next week Wednesday?

Eeeeek Shell - I so hope you are right! But can't get my hopes up! Just checked my paperwork, and after the first cycle egg collection (''ovulation' day) I started my next period at 11DPO. On an normal cycle I'd start on 14DPO, currently I'm 15DPO, and tomorrow is OTD, but I'm going to wait until Thurs morning to test as it's my day off, and if it's neg then at least I have the whole day to cry in peace. If I get that far without AF arriving!

Serenity hope you get some good answers tomorrow!

Sooo had my appointment with the new clinic.
The FS wants to start me on 175 gonal f and no ICSI.
My swingy bowel was behaving so both ovaries were playing the game.
AMH and FSH were ok.
So here we go again.

Far out Blue. I totally understand you not allowing yourself to get your hopes up but everything screams BFP to me. Your period is overdue!!!! I guess with your first egg collection you didn't take the progesterone so perhaps that is why you are 15 days past ovulation without a period instead of 11DPO/EC like your last IVF, or 14DPO in a natural cycle. I get my nerves up just clicking to open this thread as I expect to see you shout the words BFP!!!!

So that leaves you and me Serenity still on this side of the fence. Must have been a relief to hear your AMH and FSH were fine. So do you have any dates yet? I am starting next cycle which should be around the 23rd November depending on my cycle which always varies by a day or two.

Birdy do you know the follicle sizes on your cycles?
I also use ovidrel but surely if it was that the clinics wouldnt use it.
I have a couple of things that could contribute to poorer quality eggs
Hypothyroidism
Pcos with high lh and bmi 21
Very poor circulation so they fond it hard to get a vein.
Asthma and allergies

I was only 32 on first cycle so i cant see it being just age. Wondering if you have say good sperm it can compensate for not so good eggs and the other way round. As me and OH both have issues.
But it seens some couples the fertilisation can really vary.
I think though that for me if the was the protocol damaging the eggs it would have been unlikely for me to get a bfp with only 1 normally fertilised egg.
I think the icsi doesnt help as its interesting shell gets told when they disintegrate, but i only get told they havent fertilised.
I dont u derstand how i overrespond to the fsh/lh but the trigger doesnt work for me. Maybe because its similar to lh and ive been overexposed to it with my pcos

Birdy which day was OTD?

Shell haha, I haven't tested yet! I'm still on this side of the fence, too! I've gone through so many pregnancy tests in the past, and they have only ever shown 'negative'. When I got down to my last pregnancy test I vowed I would only ever use it if I was sure I could be pregnant. Normally in the past, even when AF was late, I'd test in the morning, get a negative, then AF would arrive that day. I don't want to temp fate! Anyway, guess I shouldn't put it off any longer, I'll test first thing tomorrow morning, so in about 12 hours time. Guess I need to know either way!

Naty Today was OTD, when is yours? Follicle sizes, I'm not sure exactly, but first cycle think 6 follicles were between 15 - 18mm ad two were at 11mm. I think they said only one was immature, so didn't ICSI it, and another one didn't survive the injection (disintegrated?). Out of the remaining six, none fertilised. This last time had around 30 follicles, and that was without counting a lot of ones less than 14mm (yet the previous time they included the 11mm ones in the count). There were a few (I think more than 4) that were going to be too mature by the time of EC (I recall one being 28mm). In the end I think she said that there were 23 follicles that would probably be the right size come EC. I wish I had written all the exact details down! I'll ask for them next time I'm in. Sounds like a possible theory with you being desensitised to LH. I'm hoping that next time I can be on the same protocol as last time, but with the pregnyl trigger. It will be private next time so hopefully I can get scanned more than once during the stim stage!

Serenity that sounds really good! Good luck!!!

Thats bad about only 1 scan.
I had several on nhs cycle - they couldnt not as i was high risk ohss so on low dose, could have eith had too many or not enough.
Ive found private exactly the same as nhs as at same clinic.
However
I was offered embryoglue this cycle but it may not have been avail in 2011, as i was also private jan 2014 and they didnt offer it.
Never been offered a scratch prob because i have implanted once.
Nor immunes or testing (despite the thyroid issue)

This cycle i did 3 scans wed, fri, sat.but wiuld have continued daily if id continued coasting.

Cancelled : wed, fri, mon, wed as still only 3 large follicles, they only ipped the dose on the mon though so that was prob too late

Jan wed fri sun

2011 nhs wed , fri mon wed

They dont usually do daily. So alt days.

Interesting your follicles were smaller last time bluebirdy

I think that mine not doing ops on weekend must affect some peoples outcomes but this last time it may have been in my favour as no matter what they couldnt trigger me on the fri (what they did in jan cut me off to stop rising e2 levels).

Good luck with the test.

My otd is wed 5th nov. Im not testing early, as my + was only really light on frer on day 15/16 (wondering if thats related to the fact the trigger doesnt work for me) so had to keep testing for days as it got darker.

I have no symptoms except very good sense of smell and that cant be related as it started 5dpo - before implantation starts day 6/7.
It must be the cyclogest.

Actually even the appts arent in favour of private as in 2011 we were offered an appt months away -like 3months and they tgen kept moving it further due to an error and cons was away. I said can i see him privately at clinic sooner. They said no everyone on same list. I saw same cons privately at his other location for about £200 signed the paperwork and started treatment weeks later. :)
I find all the waiting to see cons causes so much delay. Couldnt see anyone for 6 wks after failed feb cycle.
Not that it was much point anyway as they only let me grow follicles larger not change trigger or to gonal f.
They repeatedly say gonal f /vs menopur no difference.
And to changing trigger that theyve matured say 40 eggs with it so it shouldnt matter.
Oh and my clinic only offered menopur on nhs. Which is odd as they also tell me the cost is the same (and charged the same). I did waste some gonal f though due to fixed sized pens.

Well I'm not pregnant

Will phone them later to book follow-up consultation.

I completely forgot to ask about having a scratch, or about the glue. To be honest, judging by how badly all my other eggs/embryos performed, I doubt those two embryos even made it past day 3. Maybe next time I'll do what Shell does and ask for them to keep them in until blast - that way I know what happens to them. I read a study saying they don't do any better/worse if put back asap.

Hopefully going private and possibly going to a different clinic will give me better options.

Naty think my follicles were larger last time - think I waffled and my post was a bit confusing, but I'll get exact details at follow-up.

Good luck to the rest of you!!!

Oh Blue I am sorry to hear (read) that.

Shell I start on the 16th. We are moving for work so i begged to be squeezed in.

Blue, I am so sorry I led you up the garden path and got your hopes up.
I genuinely thought things sounded so promising with your period being late.
Yes, lots of women on here seem to be having the scratch.
Not so common in Australia and I hadn't even heard of it until women mentioned it on here.
I usually have very light periods and really noticed a difference after the scratch.
My lining was the thickest it has ever been during an IVF cycle after the scratch.
Do you know how thick your lining was on the day of your trigger?
I read that a lining between 9 or 10 to 14mm correlates with optimal implantation success.
Hope this gives you some hope for next cycle.

Yes, that's why I want a day 5 transfer too.
If they are put back at day 3 and you get a BFN, you are left wondering where things went wrong.
With a day 5, at least you know what went wrong if they don't make it, or you know they made it all the way to day 5 and just have to implant on day 6.

Interesting that you read a study saying they don't do any better/worse if put back ASAP.
I actually read a study showing that they do better when put back at day 5 as opposed to day 3.
The reason being that in a natural cycle they would still be in the fallopian tube at day 3 and not exposed to the progesterone filled uterus.
I am on my home PC but have the link to the study saved on my laptop if you want me to send you the link?

I truly hope that if you too have a light cycle, perhaps the scratch will give you hope for next time and possibly requesting only day 5 transfer might also feel like something positive to try for next time.
Although when I had my one lone embryo and I waited til day 5 but it died just before transfer, I wondered if it would have survived better inside me if put back at day 3 - despite the study I read about progesterone. So you just can't win sometimes!

Oh no blue. :(. I was also hopeful for you as i started spottting on 12dpo with my bfn last cycle.

As to 3d vs5d. I read a dr saying they 'manipulate' customers feelings by putting them back early when they are still growing. Rather than seeing them arrest and thinking its the lab.

Actually in a business sense it makes sense to put them back as if say
Cycle 1 i had
1 a/b 8 cell and my b/c and grew them to day 5 well i likely only had the a/b as a blast so wouldnt feel very positive.

Cycle 2 8b and 6b/c these probably didnt get to blast.
Now would i have kept trying (or with them) if i dont get anything to put back.

Cycle 3 8a/b and 10a/b
Well the 10 cell is growing a bit fast (shells one didnt go past day 4)

My clinic has about 60% pregnancy with set. Which of course doesnt include some day 3 transfers, although they did last time try to say single embryo.
When they include everything its much lower, maybe 40%.

I hope you get some answers at your review. I didnt learn much at mine cons just said chance failure.

Not all embryos are genetically normal. Only about 50% even of young women.
I only was ok with putting them back day 3 because i know it increases my chances. Because if i went to day 5 i could only put back 1 blast which would have 50% chance. Leaving the other embryo which may be frozen but may not defrost and cost me ~£2k for freezing and using.
Whereas putting both back i could be lucky and both make blasts and then the chance of implantation of 2 blasts would be double.

You would think clinics would be interested to find out why some people have only a couple of embryos.

Hopefully they can work out why you did better this cycle and further improve it next time

You could ask how the eggs and sperm looked.
More info on the fertilisation, so did the eggs activate, divide at all

Thanks guys, your posts are really helpful and have made me feel more positive, or at least like I know what I want to happen next time. I really appreciate all the info you share, and I'll respond properly when I'm not feeling so miserable.

When I called they said if my period still hasn't arrived in two days then I must test again. I said 'ok' but even as I was saying it I knew I wouldn't. I hate pregnancy tests and the way they make me feel - I hate having to go out and buy them, and I never want one in my house again, I'd rather just wait for AF to arrive. I'm sure I'm over emotional about it now, but that's just how I feel at the moment. They said I'd get a letter for a debrief consultation but it will only be in a few weeks time. I'd rather move on to the next clinic as soon as possible, though - I don't want to waste any more time.

Blue, please feel free to rant away whatever you are feeling even if you feel you are in an over emotional state and it's just how you feel now. I find typing on here is helpful and I hope you find it the same. I only wish I could do more for you as I know how utterly miserable this period after a failed IVF is.

To be honest, I was suprised that he was starting Bruselin earlier and upping the dose as the Drs solution. I mean, great to produce more eggs but it didn't address the blaringly obvious issue from your first cycle 0% fertisation. You definitely have the potential to produce lots of eggs. It's just the fertilisation and I hope your new clinic can give you some renewed hope as they address this issue. Please do consider the calcium injection. Mr Dr recommended it as I don't produce many eggs, and it would just up the chance of the few I do produce fertilizing. I went away and could only read great things about it. So when you are feeling better, please do some reading on it and I hope that gives you more faith for next time.

Do you know which clinic you want to change to? Perhaps you are able to ask in advance if they are familiar with calcium injection (or whatever else you decide to address the issue) so that you can start to feel positive about next time.

I am so sorry you are feeling miserable. You are bringing back my own negative emotions from my previous IVF's and making me feel like I am insane putting myself through this emotional torture again!

Hi Shell! I'm finally back, feeling back to normal now (ie not thrilled to be on this roller coaster, but strapped in and ready for the next round, anyway!). I had my de-brief today, and had kind of felt it pointless posting before now anyway. RE your last paragraph - don't feel like that!! You have made me feel like even if it takes up to 10 rounds, I can do it! I guess your are starting your next one in just over a week? Hope everything is running smoothly!

So today I learnt that they don't count on getting any eggs out of follicles larger than 22mm. My problem was that a lot of my follicles had gone way past this. I had 16 follicles the 'right' size, ie good potential to have an egg. They collected 11 eggs, one was immature, so only injected 10. Three didn't survive the injection, and one died shortly after. Two had 3 pro nuclei, two had zero pro nuclei, and 2 fertilised normally. So really, 6 out of 10 fertilising isn't so bad, just most didn't fertilise normally. The two that did fertilise, at day 2: one '2-' 5 cell and one '2+' 4 cell. I'm guessing '1+' is ideal, but she said the two I had were really good quality, so not to sure how far the scale goes.

I mentioned AOA with calcium, but she said the problem isn't that they are not fertilising (had kinda just figured that out) but she did say that at egg collection I was 36.25 hrs past trigger, and that my eggs were probably 'too ready' to activate, hence their pro nuclei confusion and not surviving the injection. Also when I asked about IMSI (greater magnification to choose better sperm) she said that while it did provide a better fertilisation rate, it didn't improve pregnancy rates. She did say that next time they would want to do the endo scratch, put me on no more than 225iu gonal f per day and scan me on day 8 as opposed to day 10. Also to do egg collection 34 hrs after trigger. She said that the pregnancy rate does not differ when the use pregnyl vs ovitrel, but even so, I'm going to make sure my next trigger shot is with pregnyl.

My next step is to write a letter to my CCG (the local group that decides how to spend the NHS money for this region - they are the ones that have decided that the NHS will provide 1 cycle here, even though the guidelines are that they should provide 3 cycles). Basically I'm just going to plead with them - beg them to fund one more cycle. I worked out that if/when we pay for our next cycle, it'll cost us about 6 grand. Not looking forward to that. If that doesn't work, we are planning on putting the house on the market (to move up the propery ladder, luckily something we were always going to do) so after we get the new mortgage deal we'll get out another loan for the IVF (we didn't want to get ourselves into more debt BEFORE apply for a new mortgage deal) so we're looking at waiting another 3 months at east before we can try again. That kind of sucks.

I've probably dropped of the radar by now, but if you do come across this, I really wish you all the best for this next cycle of yours!! Also hoping all went well with Naty, I'm off to snoop the threads to find out!

I'm guessing you found the other thread and that Naty did indeed get pregnant from a day 3 transfer.

I had two eggs break apart from the ICSI process and my Dr said that it would have been eggs from the larger follicles. And your Dr says they don't count on getting eggs from follicles larger than 22mm. So while our Dr's gave different reasons, it's the same conclusion that larger/over mature follicles is bad for eggs.

That's very, very interesting what your Dr said about egg collection being at 36.25 hours post trigger being the cause of the pro-nuclei confusion. It's a relief in a way to know that my eggs with this issue was not the result of my age and bad eggs, but frustrating in another way that the clinic are not more specific with EC timing if it is this critical. Definitely going to keep an eye on time of EC next round.

Yep, I agree with the trigger decision. And if she thinks there's no difference, then there's no harm in which one you choose. Frustrating that it will be a bit of a wait while you write to the CCG... or should I say, while you wait to get a response from the CCG. From the others I speak to on here, they seem so inefficient and frustrating.

Yes, you are correct (what a memory amidst your own disaster over there) - today is day 21 and I have started estrogen tablets yesterday in prep for IVF next cycle. I have been pretty darned perfect with my high protein low carb diet so I really hope that helps 50% of my embryos make it to blast, just as the study showed. The problem with me is producing enough eggs in the first place, and then not all fertilising, some break apart, some are abnormal and when I already only start with so few eggs... so I just want to be past that hurdle instead of this long anxious wait.

I am taking Puregon only instead of the Puregon / Menopur mix after reading a study that shows Menopur creates dominant follicles. So according to that research, I should have more co-ordinated follicle growth on Puregon alone, but I will be relieved when I actually see that working on a scan.

Id lost the thread. Yes it is a bfp for me, very anxious with my thyroid issues etc.
Very interested in what your clinic said about the over 36 hrs after trigger. I know this time i had ec at around 11 after 1015 trigger. As previously lots immature i thought a bit longer might help.
But like you i had lots of odd fertilisation. Some 0pn and 1 pns (no 3pn) this time. At least 4 abnormal ones.
I did want to go in first as i felt that they hadnt given the eggs the time in the lab to mature that they needed on ivf 2 but in the end didnt push for it.
As ive always been towards end of schedule i prob always go in late.
I wont get a review appointment so wont know what clinic thought went wrong.
I think if imsi could get you more embryos though that could only help.
On day 2 i had 2 4 cell, a 5, and a 2 cell.
Which went on to 2 6 cell and 8 and a 10, where 8 and 10 were put back.
I have consistently had low fert and abnormal fert, so if its the trigger timings my clinic dont know that.
Though i do think its likely something with the eggs as ive not read this about low sperm count or pcos
Its like mine dont know theyve been fertilised and then go asynchronously.
I cant remember did you say youre changing clinic

Oh hooray for Naty!! :) I didn't have time to look around the other threads and only just checked back in now - so pleased to hear it worked for you! Gives us hope, too!

When they say that there is probably an egg quality issue, I've always just assumed that the eggs are bad quality due to the type of regime, rather than because I naturally produce bad eggs. Not sure if that is the case or not, but all other tests I've had show I'm in the normal range. Guess they can only tell if they could test a naturally produced egg (which isn't really going to happen).

Good to hear your diet is going well, Shell. Hopefully this, and the new regime, will make all the difference! When is your first scan?

Yeh, I'd have thought that IMSI could only help, not sure whether my FC only say this as they don't have the equipment to preform IMSI? And her argument against using IMSI could equally be applied to the merits of an endo scratch, so not really sure what to believe. (Guess I better go google!)

Funded cycle or not, I'm torn between staying at this clinic (which at least has a new plan of action and is only half an hour away) or going to a very successful clinic in Bristol that offers a bundle of three ICSI cycles for just under £10 000 (obviously not including drugs and extra bits) or going to one in Cambridge that provides IMSI. The other clinics are 4/5 hrs away, though, so will need a whole day off to go to appointments, rather than just going in in an afternoon. Will have to speak to the other clinics before I can decide.

Good luck both of you for your first scans!!

An interesting read that kind of sums up what we have already gathered: haveababy.com/fertility-information/ivf-authority/ivf-trigger-shot-important-determinant-egg-quality

More detail on follicular size and egg quality: www.ncbi.nlm.nih.gov/pubmed/24189964

My clinic is bristol (bcrm)
They seem to mainly do long protocol, ovitrel.
Though i guess they may be ok with pregnyl (cons i saw said i should stick with ovitrel as it worked with dD.)

Ive had 2 bfps out of 3 EC.
Looking at the article its not that surprising i had low fert rates according to the follicles sizes.
Ivf 1 1*20mm rest smaller =1 ab grade embryo and 1 0/1pn embryo
Ivf 2 218 and 315
= 1 b grade, 1 bc grade and 1 3pn
Bfn so prob only the 2 18s fertilised

Ivf3.
4 20mm 2 18mm lots of other small ones
2ab grade 2 that didnt make blast like 4 0/1pn embryos

So it correlates with the link below. Except why i didnt have 4 good embryos on ivf 3.
Looks like i get 0 normal fert from anything under 18mm. And poor quality from the 18s
I think this must be extreme. And could be that such small ones cant cope with the poor quality sperm.
It makes me think ivf2 was done very badly i should have been allowed to grow on to 20mm (as estrogen wasnt that high) i still would have had 2 embryos but quality could have been better. I mean if id got to the ideal 22mm even the 3 smaller might have been 19. This risk of hyperstim is very annoying.
I mean if i had the fert rates in the article for those sizes
Which is around 50% even for the smallest id have had
3-4 embryos ivf 1
Still 2 ivf 2
6 ivf 3 so a lot better.

Its cost around 10k for 2 icsi and 1 cancelled.
With the success rates on the site it lists SET at 50-60% success. But they are allowing 2 embryos put back if the quality is lower/previous failed cycles etc and of course its probably blast transfers.
But you can see why its set for blast transfer as so many would be twins. Oh and not sure if thats per cycle or per transfer.

Blue, that second link is very interesting that not only are larger follicles more likely to produce a mature egg (which I already would logically assume), but that eggs from more mature follicles are more likely to fertilise and to fertilise normally. On the contrary, I do also remember reading that the first maturing follicles often contain the best egg (as they are the ones your body is naturally trying to select) and should not be allowed to over mature for the sake of allowing the smaller ones to catch up. So it's a tug of ware between going ahead with trigger when the first few are mature because they contain the best egg, or allowing them to over mature for the sake of the smaller follicles being at the right size so that they have a higher chance of fertilizing too!

There is one very interesting study which showed taking FSH at the time of the trigger drastically increased fertilisation rates. In a natural cycle, the FSH surges along with the LH before we ovulate, so it makes perfect sense that they should mimic this in an IVF cycle too. What's more, unlike the studies about follicle sizes which can be a bit out of our control and sometimes just stress us out more when our cycle doesn't go according to all the studies we have read, this is totally within our control. My Dr wasn't familiar with this, but I totally intend to inject my last FSH dose along with my trigger this upcoming cycle based on this article...www.medscape.com/viewarticle/731842

Just re-reading that article, it says the participants took 6 amps of FSH along with the trigger to produce the higher egg retrieval and better fertilisation rate.

Do either of you know how much FSH 6 amps is???

Interesting ivf 1&2 i took trigger at 10.15 with menopur either 6pm or 8pm.
Last 1 i was coasting 2 days so no injection at all.
In the study i would have been excluded.
Not sure why my clinic was making me take the last inj so early. Maybe the theory it makes them grow then they can focus on maturing.
But i guess as well it could depend on the time of op so if you are 9am wonder when my clinic say to do last inj

Yay for collaborative learning! I feel a lot more hopeful about how things can go right when we've figured out how things could have gone wrong.

Good to hear the info on BCRM Naty! I am tempted to try there, especially if we'll be paying!

Shell I think a standard ampoule of gonal f is 75iu? So maybe 450iu? Didn't check what FSH they used, though.

My first cycle I took 150iu of gonal f at 9pm and the trigger at 9:45. Second cycle I took last gonal f of 50 iu around 5:30 am (was coasting) and trigger at 9:45 pm. But then I think those aren't the best cycles to be gauging anything on, they were messed up already at that point. I think my clinic also had me coasting just to fit in with their schedule - they won't do EC on a Sunday. Maybe that is something I should check with potential clinics, as I want to be triggered when it's best for my follicles, not when it's best for them!

So thanks ladys, I'll be checking back in with any new info I find - please let me know how you get on!

Mine only do EC mon - fri.
Interesting you said some follicles were too big at EC.

I think for 6k and really it is 5k the op they should do it 7 days a week. But i think the rest of hosp being on weekend also influences it. As in if it went wrong and get a but of bowel better for patient its mon-fri.
Though wonder how much difference surgeon and embryologist makes.
I read the 3pn can be where the spindle is in the wrong place when injecting.
Though also that with icsi you can get parthenogenisis of the egg where it divides by itself because of the action of injection and then they divide up to 8 cells (think this was the 0 and 1 pn maybe)
If imsi doesnt affect pg rates then they cant pick the genetically best sperm by looking.