First IVF cycle failed - what to do next?

[agesandages11]

Hope someone can give me some additional hope/encouragement. I know that IVF is a trial and error process with a lot of luck, and that having a failed first cycle is pretty normal, but I'm still a little down at the minute.

My husband (now 35) and I (now 34) started TTC in December 2019. We were successful within three months, but I started to have bleeding episodes on and off from about 6w, resulting in a MMC at 9w in April 2020 for which I had an ERPC. On recovering from the ERPC we were keen to start trying again ASAP, but the months went by with nothing...

About three months after my ERPC, I noticed that my periods had become drastically lighter. I feared Ashermans' as a result of the ERPC, and so went to Mr Lower. I ended up having a hysteroscopy and HSG at the end of October 2020 both of which were normal, but my cervix was very stenosed (narrowed) which had been affecting my menstrual flow, and possibly also the access of sperm. Mr Lower treated this via dilation, and said that he would expect us to conceive within 2-3 months.

In February 2021 after still no success, we went to IVF at Care Fertility. I was diagnosed with poly-cystic ovaries (although I seem to ovulate by myself and have regular menstruation) and put on a short protocol of Menopur/Fyremadel at the beginning of March. They retrieved 14 eggs, nine of which were mature, all fertilised (although only eight were viable as one was fertilised by two sperm), but only blasts on Day 5. Around Day 3, all of the eight embryos started to fragment quite badly, with most of them being Grade 3 fragmented and succumbing to arrest here. The two that did make it to blast were Grade 2 fragmented, and rated as 4BB and 3BB. The 4BB was a failed fresh transfer and the 3BB was tested as aneuploid. If I was a betting person, I would wager that the 4BB was possibly also chromosomally abnormal as well.

So, we we are back to the start. I am on a multi-package deal with Care, so have my consultation this week, and hope to start another round either in May (depending on when my period arrives and how quickly they can issue my protocol/I can buy the meds) or June latest. I won't deny that I was a little disappointed with Care, as on my first scan on Day 6, they discovered I had a cyst, but yet carried on with the stimulation meds. I never had any bloods taken, and they never even checked my lining prior to the transfer.

Can anyone provide any guidance as to what I should expect from this consultation? Are my results just bad luck? Will they put me on the same protocol again? I did seem to get a fair number of eggs (and likely would've gotten more had it not been for the cyst - the ovary affected only had five follicles, vs. the other which had 13) so I cannot see the benefit in suppressing me prior to a cycle.

I do already have a long list of questions to ask the clinic, but would be grateful to hear from anyone who has been here, and had a better result on their second attempt - what did you do different? Especially keen to hear from ladies with PCO(S).

Thank you!

I should add that my husband's SA is totally normal, and I would guess that with all the mature eggs retrieved being fertilised that there are probably no/fewer issues on his side, although I appreciate there is always DNA fragmentation which can be explored.

I am also on a long list of supplements including CoQ10, inositol etc.

I’d be interested to hear what your response is as well as we had a similar outcome, though slightly less eggs (9) and only one blast which I think was a 3 or 4 aa. Same protocol.
I did have lining check which was good and bloods which I think showed an lh surge prior to the fyramedel starting and I will ask if they think that affected quality.
What dose of menopur were you on?
We’re using donor sperm with proven donor so should not be any issues that side.
About to book follow up appointment.

@Aprilia123 Hi there, sorry to hear about your cycle, but that is a very well graded blast! Did you have a fresh transfer or have you had it sent for testing and/or freeze for a FET?

We initially said that we would only test if we got a fair number of blasts, but I'm glad we actually tested the remaining one, and actually wish we had tested both if I could go back. I won't be doing any more fresh transfers as the progesterone suppositories were a nightmare, and gave me thrush. We will be testing all embryos moving forwards with the hope of doing unmedicated FETs.

I started 187.5iu Menopur in the PM on the second day of my period (CD 2). The standard Fyremadel injections were introduced as an AM injection three days later (CD 5). They upped my Menopur to 225iu on CD 8 and I continued on at this dosage plus the Fyremadel until I triggered with 10,000 HCG on CD 12. I took a Menopur and Fyremadel on the same day that I triggered. In total, I was injecting for eleven days.

You said you had an LH surge prior to starting Fyremadel. If your protocol was the same as mine I would find that very unusual to have a surge so early in your cycle? Do you ovulate by yourself typically?

Hi @agesandages11 - sorry it has been such a tough journey. I don’t have PCOS but wanted to share that I have had 5 rounds of ivf and they have had wildly different outcomes. Medication has stayed largely the same - menopur all the way just at different doses (lower is better for me it turns out). Two different triggers used. Other than that identical protocols.

Best 2 outcomes I got 7 blastocysts from 16/15 eggs - rounds 1 and 5. Round 5 i genetically tested and 5 were good. Worst -
Round 4 - I got 1 blastocyst which was genetically tested as no good, from 14 eggs. Who knows why it is all so different.

I have found though that I need to get very clear on my expectations of my clinic and hold them to it. I even had a strong view on my medication levels in my final round based on how I knew I reacted previously etc. So keep lots of notes. Push them to scan, push them to measure your lining etc. There is nobody who cares more about your treatment than you: I learned that over the last two years and advocate heavily for myself now.

Hi @agesandages11 your case is very interesting and you have clearly read up on everything, are you medical by any chance? I’m a doctor and have approached IVF in a similar way to you.

A few things jump out to me

1. Why do they think you have PCOS? I presume you have a high AFC, but generally you need 2 of 3 of these and you say your periods are regular.

— Clinical Hyperandrogenism (Ferriman-Gallwey Score >8) or Biochemical Hyperandrogenism (Elevated Total/Free Testosterone) AND
— Oligomenorrhea (Less Than 6-9 Menses per Year) or Oligo-Ovulation AND
— Polycystic Ovaries on Ultrasound (>= 12 Antral Follicles in One Ovary or Ovarian Volume >= 10 cm3)

1. Why did you have a big drop off after day 3? My understanding is that this is to do with the sperm, what tests do they recommend to look into this further.

1. Is a natural cycle the best option in your case? I know you got thrush from the pessaries but there are other options: I use a combination of lubion (injection) and cyclogest (I use this rectally). In those with regular cycles natural FET can be a good option, but you the clinic may have to cancel if they are closed at the transfer time. In my case it’s not an option as I have thin lining.

I’m currently under investigation for Ashermans syndrome, I’ve never had surgery but had very light periods since I has an IUD removed. I ended up with 9 blasts in my fresh cycle, but I’ve had no success with 2 transfers. I only just realised that my lining is a problem as nobody told me it was only 5.4mm at 9dpo back in September 2020. I spoke with Mr Trew last week and have my HSG in 2 weeks time.

@Shamoo Thank you for sharing, and gosh, you are so brave to have gone through this five times. Did you stay with the same clinic throughout all of that? What is their explanation for keeping you on the same protocol? When I have spoken with US people about just being on a Menopur-only protocol, this is often met with shock or being very unusual (most often it's combined with Gonal F) but it seems to be quite normal over here. Were you always on a short protocol or have they ever had you suppress beforehand?

I have had a very very small stroke of luck in that my consult was originally scheduled for next week, and was with just one of the clinic doctors, but because I asked to be put on the cancellation list, I have been able to have it brought forward slightly, and it is now with the most senior individual at the clinic. I'm really really hoping that I'll be able to start another round in May rather than have to wait another month.

I will say that although I was disappointed with some aspects of Care, I found the staffing for the retrieval and transfer processes was excellent - everyone was very kind. That said, the primary reason we have gone with them is because we are in the Midlands and so options are limited here. If this second cycle doesn't work, then I would possibly consider going to somewhere in London, although I know you can find positive/negative reviews of pretty much everywhere.

@agesandages11 Oh that’s really interesting, very different regimen! I had 300 iu menopur from cd2, went in for first test cd6 and they called that evening and told me to do a double shot of fyramedel and drop the dosage to 225. I then stayed on 225.
It’s definitely the part of my protocol I’ll query at the follow up, other than that I found I had no issues with the meds in terms of side effects and the amount of eggs was decent for my ages, but the drop off was disappointing.
We did a fresh transfer, didn’t really see the point in testing unless we had a fair haul, and will probably do the same again as I was ok with the cyclogest too - we’ve set at limit at two full fresh cycles and then considering a natural or mild third cycle.

@agesandages11 - to be honest if you had told me it would be five cycles at the beginning, I probably would have had a breakdown 😂 - but once you are in it, you are! And I just sort of cracked on and it’s been ok. Lots of money but I’m ignoring that part.

I have been at Lister throughout. After the second fresh round I debated leaving. I did a lot of research and met with two other clinics, and did actually decide to move. But once I kicked off with the new clinic I realised I wasn’t comfortable with them for a couple of reasons (I didn’t agree with the protocol I was offered, or how they were trying to charge me for extra stuff) and I felt I couldn’t trust them. I have medically and financially always trusted Lister, I was annoyed with their admin but it has actually improved recently and overall I am happy with them. Better the devil you know, I guess.

The thing is I have always responded really well to the protocol. I have very regular periods, and my age combined with blood results meant they have always said I am better on short protocol (which I would prefer anyway). My first two cycles were, on paper, very successful - 7 and 3 blastocysts. I clearly don’t respond well to fresh transfers so have stopped them. I had MMCs and CPs, and they suggested genetic testing which was our next step.

@Gardenlady543 Hello there, I was hoping you might stumble on my thread as I know we are a similar age! I don't really post myself on this forum, but have been reading some of the IVF threads with interest, and saw your posts on a few occasions (hope that doesn't sound too creepy!).

I am not a medical professional, but funnily enough literally everyone I have spoken to asks me that (even Mr Lower with our first telephone consultation!) - I am just someone who is quite good at research, and have tried to turn that to my advantage here.

1. Why do they think you have PCOS?

I have never been clinically diagnosed with PCOS, but according to Care, I have polycystic ovaries as visualised on ultrasound, and personally I would not be surprised if I had some variant of PCOS, as I have always struggled with my skin/weight. I have never had any sort of hormonal panel done though. My AFC is somewhere around 24 (has differed a little on the two occasions I've had it done over the past six months) but interestingly, my AMH is actually normal for my age (2.1 ng/15.6 pmol) and not the extreme elevated figure you would expect to see in typical PCOS presentations. I also ovulate independently and have regular menstruation. It is still possible to have a variant of PCOS with my profile, but I'm not too fussed with getting a proper diagnosis seeing as now I'm at the stage of using ART, anything that would manifest as a result of having PCOS should be able to be resolved via the IVF process.

1. Why did you have a big drop off after day 3?

There is a bit of a debate amongst embryologists as to whether it is related to the egg or the sperm. PCO(S) individuals can often have problems with egg quality, so it could well be my crappy eggs which caused the fragmentation. On the sperm side, my husband's SA is totally unremarkable, but there are further tests which could be done to examine the level of DNA fragmentation (different from embryo fragmentation) he carries. From a non-andrologist's standpoint, as all the eggs that could be fertilised were, I would hope that there aren't any problems on his side, and it's most likely something to do with how my eggs reacted to the protocol on this occasion that resulted in the crappy quality and so few making blast.

1. Is a natural cycle the best option in your case?

One thing that I do normally have going for me is a thick lining (again something else that can be associated with PCO(S)) and I've been told historically that it was trilaminar as well (sometimes considered more important than thickness) although I have no idea whether it was the case for my fresh transfer, but I recall the u/s tech saying it was "nice and thick" when I had my last scan on CD 13. I totally agree concerning the possible frustrations of clinics not being open/only conducting procedures on certain days, but whereever I can (ironic considering I am undergoing IVF) I would like to reduce the amount of medications I am taking, so if they would support me with a natural cycle, I'd like to try it.

I saw your posts about your Ashermans' investigation, and I will keep my fingers crossed for your HSG coming up soon. As you know, Mr Trew/Lower are the experts in the UK, so you are in very safe hands.

I'm sorry to hear about the lack of success with your blasts so far, but getting nine out of one retrieval is awesome! What was the range of quality? Have you considered doing PGT on those that are left? That said, you might be a victim of 'soil' quality vs. 'seed' considering your lining though, so definitely having the investigations with Mr Trew are an excellent next step.

@Gardenlady543 Correction, my last scan was on the morning of the day I triggered, CD 12. I had the retrieval on CD 14, and then a fresh transfer on CD 19, so no idea what happened in between on that count!

@Aprilia123 Very different! I'm not sure of your age or profile, but when they found I had PCO, they were naturally erring on the side of caution to avoid overstimulating me. They seemed to be taking me low and slow at first, but then decided to up the doseage. The problem with Care is that they only do collections/retrievals on certain days, so I am a little paranoid that they manipulate the meds to fit their calendars sometimes. Had I not triggered when I had, I would have had to wait until the following week to have my collection, and I think they were worried about what might have happened over the weekend.

Clearly in your case, they thought you'd need a higher dose from the start, but then took you down once they realised your follicles were growing faster than they had anticipated, plus the double dose of Fyremadel to prevent ovulation.

My protocol was never properly explained to me (I presumed I was given a short protocol because of PCO, but never told why only Menopur, and not a combo of that and Gonal F, or any other sort of stim meds) so absolutely ask questions about that as I plan to as well. In a lot of cases, the first cycle is a bit of a 'suck it and see' - it could work out, but it's very normal if it doesn't I think. Glad you didn't have any side-effects, that is a good bonus to take!

@Shamoo That's wonderful that you've had faith in your clinic and been able to stay with them as long as you have. I have also heard good things about the Lister. Did you ever consider the super aggressive one (ARGC I think)? I had been doing some reading about the various London clinics though, and think they manipulated their stats in terms of live births - when you look on the HFEA website, apparantly they are the same as most places, but you do hear people raving about them because of the amount of attention in terms of blood/scans you'll get there. Apparantly they push an immune regime though which I wouldn't be keen on.

Really happy for you that you've found a protocol you feel works for you, and your clinic is supportive. I would definitely recommend PGT as a next step if you've got a good bank of embryos. I know it's a bit of a taboo thing in the UK, and red rated on the HFEA, but having had one MC (which I presume was due to chromosomal abnormality, although I'll never know) I want to avoid the chances of that happening again as much as I can. I think provided people don't see it as a guarantee, and just more of another tool in the ART arsenal that could reduce your chances of a loss (vs. increase your chances of a live birth), then it's very useful.

@agesandages11

It’s quite flattering to know I might be a bit famous on these threads! Lol! To be honest I spend huge amounts of time on here as I don’t feel able to go on social media/interact with many of my friends while I’m having IVF, this is a much safer space and I’ve learned so much that’s been helpful for my treatment.

The PCOS is interesting, I wonder if it might explain your situation at least a bit, those with PCOS seem to get large amounts of eggs and end up with quite a big drop off. I do think exploring the sperm might be useful as well though. Something to chat about with your specialist I reckon.

So far I’ve had
-PGT-A
-Autoantibodies and a thrombophilia screen
-ERA/EMMA/ALICE

In my case the PGT-A pointed towards recurrent implantation failure, the soil being the problem as you say!

I had 12 eggs, all mature, all fertilized and had 9 blastocytes. After the 2 transfers, I had the 7 remaining blasts PGT-A tested, 1 didn’t survive the thaw, of the rest 5 out of 6 were euploid, that’s a whopping 83%. I’m glad we got this done because this was when my specialist changed from “relax it will happen” to “ok something is wrong here”. She said she expects the 2 transfers were euploid as well. I’m hoping to get a treatable diagnosis, I’m feeling a bit in limbo at the moment. I’ll know more once the ERA/EMMA/ALICE results are back and I’ve had the HSG, Mr Trew said to book in for a review then, so in about 3 weeks time.

By the way I’m at Care and in the Midlands as well, when I had my heart set on natural FET I thought about Manchester Fertility, it seems to be the closest clinic that is open 7 days a week and seems to prioritise natural FET. I’ve had a few bad experiences at Care (a couple of insensitive nurses and a specialist who isn’t my specialist who asked me to tell him the pharmacodynamics of progesterone when I was in pieces asking for a progesterone blood test). I also find it quite annoying that they take on so many patients and then adjust protocols around their availability, rather than what’s best for the patient. But I get on well with my specialist who is happy to work with me, so I think I’ll stay put there for now, especially as natural FET isn’t an option for me right now.

I agree that reviews are variable, if someone goes through IVF and has a great outcome at the first attempt then I’d imagine they would be keen to write a glowing review. I think it’s far more important to know about the experiences of those who had multiple unsuccessful attempts.

I don’t know much about protocols, I was going through my fresh cycle with very little knowledge on fertility and ended up with a good outcome. But it sounds like something your specialist needs to focus on in your case, so definitely pick their brains on the options and what they think is best in your review appointment.

@agesandages11 - I actually had PGT on my final three rounds. The last round was by far the most successful and I got 5 good ones from 7 tested (and one without a result). So I have 6 good ones frozen now, 1 tested and unknown, and 3 untested. I couldn’t have asked for more. I think I am now done for harvesting. What will be will be from here!

I find clinics that don’t operate at weekends mind blowing. For PGT testing at lister you need collection to be from Wednesday to Sunday I think. This time around I was collected on the Thursday, and got taken in for egg removal exactly the right time after trigger. I can’t help feeling that that contributed to my positive outcome. In one of my previous rounds they definitely kept me on longer than they would have done otherwise, and I think that had an impact on my results. I can’t be sure though of course (and I know they would never admit it).

I looked at ARGC and did read some good things about them but I wasn’t sold. I actually decided on another big, similar London one based on all my research, but like I say it just didn’t feel right when I got there. But I have a friend there who loves them. So it’s probably just hit and miss like all clinics. For me trust and integrity is very very important and I didn’t trust that either would give me advice that was purely medical based, but that may well be completely unfair of me! The clinic I was going to move to wanted to medicate my periods to stop my cycle, which felt totally unnecessary given I had had no issues at all with my cycle at any stage, and when I challenged it they just said I could chose not to if that’s what I wanted. They had done no bloods or anything at this point so I thought it was very odd advice that felt money driven and not about my best interests. They were also charging loads more for a Covid test than Lister. I have nothing else really to base it on. I also really liked the look of Evewell but stayed with Lister in the end.

My good blasts are not amazing quality, which is the next thing for me to explore before I decide no more rounds for definite. A few BCs in there causing me concern. It never really stops!!

@Gardenlady543 I totally understand re. only feeling able to go certain places online! I actually think infertility communities actually end up 'feeling' quite small and everyone getting to know each other (or at least recognise usernames) pretty quickly. This is my first thread here, but I'm actually quite active on another US-centric website. It can be a bit frustrating posting as a UK based person because the vast majority are Americans (and things are totally different IVF-wise over there, with seemingly bloods and scans every day, which is totally unusual here), but I quite like the community as they are very protective around what/can can't be posted in terms of trigger-y sorts of things, so I find it helpful for my MH.

5 out of 6 embryos coming back as euploid is absolutely wonderful, congratulations! You are absolutely doing the right thing with all of your investigations re. lining and I will sincerely hope you get a result that points towards an easy fix to improve implantation chances.

Is your specialist Dr M.R...? She actually did my ER, so it felt a tiny bit like meeting a celeb (I'd seen her in the website vids, lol) and felt reassured that I was in very safe hands. I'm actually at a satellite clinic so I've just attended the main Midlands location for my ER and transfer.

I'm sorry to hear about the bad experiences - I think I can empathise with some of those re. off the cuff comments that were made and just attitude when I was attending for scans, but I tried to just suck it up and get on with it. Hoping I'll feel more encouraged after this consult as it's with the most senior person at the satellite.

I actually have some really useful lists of pre/post-IVF questions I was sent from a lady at Fertility Network UK, so am happy to share those with anyone if they are due to go into a consult and could do with a jumping off point. Also have some other really good resources online I can direct people to build their consultation question list as well.

@agesandages11 Maybe we’ll both end up in the middle on the same protocol!
It sounds like you’re well armed for your review - I’m the same as you, massive researcher - I understand so much more than when I started. The clinic tailoring you to them doesn’t sound awesome - I’m with the Lister as well and they seem to do collection whenever it’s needed, I was on a Saturday and there was quite a few of us there.
Very happy with them in general - some admin a little random but overall they’ve been great.
Best of luck, I hope they’ve learnt good things and you go on to have good results.

@Shamoo Congratulations, those are wonderful results, and I would similarly hope you won't need to go through a retrieval again! I think a PGT-euploid status embryo is widely considered more important than its quality in terms of grade, so even if they aren't the highest rankings, I'm sure you have some very solid chances in there.

Your experience at the Lister sounds pretty positive, and absolutely, I think that would raise a red flag for me at the other clinic if they wanted you to undergo suppression 'just because' without any clear medical benefit for you as a patient. Suppression's purpose is to quiet the ovaries prior to stimulation so that the largest possible cohort of follicles can be recruited and to encourage them to grow at the same rate - if you are achieving good numbers of eggs retrieved without suppression, then I don't see how there could be a case for it to be needed unless it's to suit someone's calendar!

I'm definitely open to moving clinics depending on how this next cycle goes - I'd prefer to be able to stay due to convenience, but am also aware that the London clinics do seem to have some really good results, so it might be more sensible to pay a bit more and be inconvenienced slightly in terms of travel for one really great cycle if that avoids many more rounds closer to home. Appreciate all of this is totally 'what if' and with hugely crossed fingers though!

@Aprilia123 You're with @Shamoo! I will say the Lister does seem to be very well regarded, and that's great that they're open 7 days a week. The London clinics do seem to have much more flexibility in that aspect. Thank you so much for the kind wishes; I'll similarly be sending good luck your way as well for what's next.

@agesandages11 I’m not with that doctor no, I didn’t realise Care had a celebrity doctor . One good thing about Care is that they have regular meetings to discuss complex cases, so you do get input from a number of specialists. I am sure I’m frequently discussed at these meetings!

What’s the USA discussion board that you’re on? I might join, since my situation seems to be getting more complicated. From what I’ve seen the USA have a completely different approach to IVf, in particular a lot more investigations from the outset. Rather than a standard protocol trial and error approach in the UK, with the HFEA traffic lights reflecting this. Saying that if sounds as if the USA is a lot more expensive.

Your lists of questions and resources sound really interesting, you might want to start a new thread. “Advice on what questions to ask after a unsuccessful IVF cycle” or something along those lines. That way it will be easier to find. One thing I’ve found helpful is being able to read through past threads, sometimes written a few years ago. Plus others might have questions to add to.

@Gardenlady543 I can definitely recommend the USA board - it's just the sub-reddit for infertility (www.reddit.com/r/infertility) as there are some super knowledgeable people on there who have been through many cycles and many different interventions/investigations, so they can certainly shed some light on what you're going through, and if there's anything else they can suggest.

Please note there are quite a lot of rules to protect posters though, so just make sure you check out the rules in the side-bar and the pinned post before posting! The best place to start with a question is in one of the Treatment threads (they are posted 2x a day, so just find the most current one by sorting by 'new' on the main sub-reddit page) as stand-alone posts are reserved for super-long or more complex topics. You'd be very welcome though!

Good idea, I'll make another post with a copy of the questions from FN, and links to the resources (lifted from the reddit!).

@agesandages11 that sounds complex! I might have to be a lurker for a little bit to get the hang of it!