# Failed second cycle (42)



## rothbard (Jan 24, 2016)

My wife (42) and I just tried having a baby using a frozen embryo transfer, after failing to obtain new ones. Late in 2014 we went to 92 Harley Street, where we saw Mr Geoffrey Trew, who recommended ICSI rather than IVF due to my low sperm count. The procedure was carried out at Boston Place, where they got 10 eggs of which only 1 fertilized and turned into a blastocyst. 

In March this year we decided to try and have a baby as soon as possible, and opted to get new embryos before transferring the frozen one. This time we decided to go to the Lister Hospital, where we saw Dr James Nicopoullos. We had IMSI, which is similar to ICSI, except for the use of a high-power microscope for sperm selection. Of 10 eggs, again only 1 fertilised, but it did not develop into a blastocyst and on day 5 we were told there was no point in transferring it. We chose to transfer the frozen blastocyst anyway. However, two weeks later that seems to have failed - my wife is bleeding heavily and a HPT just gave a negative result. 

What are the possible causes of such a low success rate in embryo collection? The embryologist who did the transfer suggested we investigate the possibility of DNA sperm fragmentation. 

For the record, here is a list of the medications my wife took during this cycle:

- Nafarelin (200 mcg per puff), two puffs twice a day for a week, one puff twice a day for two weeks, beginning one week before her period.
- Menotropine (375 ius), 12 doses, once daily, starting on day 7 after the beginning of her period.
- Ovitrelle (250 mcg) 33 hours before egg collection
- Progesterone (400 mg per suppository), twice a day, starting the day after egg collection. 

Her last tests in December 2015 showed clinically insignificant fibroid, otherwise no problems and an antral follicle count of 12. Her AMH was 8.0. Those were dropped from the previous figures of an AMH of 13.01 in October 2014 and an antral follicle count of 15, as expected due to her age. 

My wife and I would be most grateful for any advice.


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## EdnaAverage (Aug 11, 2015)

Hi Rothbard,

I don't have any advice to offer you but just wanted to wish you well and didn't want to read and run. You sound like a very caring husband and I'm almost the same age as your wife and in the middle of my own second fresh cycle.  Sperm fragmentation can be an issue if small numbers of embryos are fertilising or if embryos are not making it to blastocyst.  By it's nature, fertility treatment focuses on women and its hammered down our throats morning noon and night that we're too old when often we're only 50% to blame....  You mention that you have a low count, do you know why this is and have you had any other tests other than the standard analysis?  Karyotyping may be another angle to explore to check how genetically normal your sperm are, issues seem to increase with age and you haven't told us how old you are?

If you haven't already seen it, check out the male factors sub board, there's some really good advice there on male issues and tests which may be worth exploring.

What did your consultant think may have gone wrong, did your wife respond as expected to the drugs? I'm not familiar with her drugs but it sounds like long protocol rather than short and the Lister is well regarded so I'm sure they got it right based on her AMH/Age etc.  One issue with IMSI, great as it is for sperm, is that it can leave the eggs sitting around for a little while when the best sperm are being selected which can be detrimental to them.  As with everything to do with IVF, it's often a balancing act!

I really hope you both find some answers, can highly recommend Jonathan Ramsay for clinical know how in male issues and we'll find out in the next week if his advice has made any difference to our own blastocyst development this time round. All of our embryos fell by day 5 last time. This was attributed to sperm issues at the time but I think it may have been a mix of both as other than slightly higher than usual abnormality detected in a FISH test, there are no other major issues with my husband's sperm that can't be worked around with ICSI etc. 

Edna


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## rothbard (Jan 24, 2016)

Hi Edna, thanks for your reply and encouragement. My wife indeed used the long protocol. Today we saw Dr Nicopoullos again. He said that in terms of sperm count my last results were fine. The embryologist had raised the possibility of sperm DNA fragmentation, but he advised us against testing this because, even if that were the case, the only thing that could be done about it would be to use ICSI or IMSI, and we are already doing that. By the way, he said we had an "easy IMSI", meaning that they didn't have to wait long to find the right sperms.

In the last cycle we had 10 eggs, of which 4 matured, 1 fertilized but degenerated before reaching blastocyst stage. He said he would normally have expected 60-70% of eggs to mature, and 70% of these to fertilise. To try and improve the outcome of the next cycle he recommends the following:

1. More than double the amount of hCG from 6,500 units to the maximum 15,000 units. 
2. Stick to the long protocol, but push longer to improve maturity. They will wait at least one extra day for egg collection, in order to get the follicle to be slightly larger.
3. A possible issue with the low fertilisation rate might be that the sperm didn't release its fertilisation/activation factor (either that, or the eggs didn't respond to it). To improve this, he proposed to add calcium ionophore during the procedure. 
4. Switch from Menopur to Gonal F, which my wife had used during the first cycle early last year.

We are hoping for the best, even though I am feeling a bit down. We really need to increase the number of fertilised eggs in order to have a reasonable chance. 

I am sorry about the fact that your embryos didn't reach day 5. Are you currently doing your second cycle? What did your consultant recommend to change from the first one?


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## rothbard (Jan 24, 2016)

I just wanted to give an update. We did a third cycle, the eggs were collected on Wednesday. In addition to the changes mentioned in my previous post (more than double the dose of hCG, wait an extra day for collection, add calcium ionophore, use Gonal F), my wife took 75 mg of DHEA for several weeks up until collection. She also tried to avoid any kind of stress. 

On Thursday we heard that, out of 16 eggs, 14 had fertilized. This looks like an improvement over the previous cycles, when only 1 egg fertilized out of 10. We are now awaiting a second call from the embryologist.


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## rothbard (Jan 24, 2016)

We got another update from the embryologist this morning. All 14 embryos fertilized on Wednesday are still alive, and have now between 7 and 9 cells each. They are graded 1-2 in the scale used by the Lister hospital (1 being best, 5 worst). Hopefully on Monday at least one of them will be a blastocyst.


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## Mum2M (May 15, 2016)

wishing you the  best


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## rothbard (Jan 24, 2016)

Thanks


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## AngelJ (Jan 19, 2016)

What about using PICSI? Have you considered this?


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## rothbard (Jan 24, 2016)

I had never heard of PICSI until I read your post and googled it. I suspect that it's not offered at the Lister, otherwise the doctor would have mentioned it. 

Today, on the doctor's advice we transferred two blastocysts and had another one frozen. Two others may be formed soon, and if so then they will be frozen as well. Now the 2WW starts again.


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## RumPunch (Nov 17, 2015)

Very best of luck over next 2 weeks!


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## RumPunch (Nov 17, 2015)

Hi rothbard

Do you mind me asking about your first point on what you've changed this cycle:

1. More than double the amount of hCG from 6,500 units to the maximum 15,000 units. 

Is this the trigger shot? I am on Ovitrelle 250mcg what does that equate to in units....do you know why your consultant has made this change? Mine hasn't made any changes like that for this round but it would be great to know the reason behind it for you, it's all helpful the more information you can get!

Thanks, well done and best of luck!
RP


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## rothbard (Jan 24, 2016)

Feeling a bit discouraged since my wife doesn't seem to have any symptoms of pregnancy yet at 7dp5dt. Only some general tiredness and abdomen pains / headaches, which could either indicate pregnancy or that her period is coming.


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## maybebaybee (Apr 17, 2016)

Try not to get discouraged, rothbard. Some women have almost no symptoms early on.


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## rothbard (Jan 24, 2016)

Thanks, I am trying to stay positive, especially for my wife's sake. Today I took the day off to stay home with her. The pregnancy test is on Wednesday (not sure why the doctor scheduled it so early, at 9dp5dt). She is feeling optimistic.


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## rothbard (Jan 24, 2016)

This morning my wife did a HPT and there was a very faint second line. This is especially interesting since she had already gone to the bathroom about 30 minutes earlier. Tomorrow morning she'll do it again the proper way, and later in the day she has an appointment for a blood test at the hospital.


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## maybebaybee (Apr 17, 2016)

That sounds encouraging, rothbard.  Do you know if she had an HCG booster shot at any point after transfer? Fingers crossed for both of you!


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## rothbard (Jan 24, 2016)

maybebaybee said:


> That sounds encouraging, rothbard.  Do you know if she had an HCG booster shot at any point after transfer? Fingers crossed for both of you!


Thanks. No, she did have a much higher dose of hCG than the previous time (15,000 units), however that was on 2 July. By the way, I was wrong in my previous yesterday when I said we were at 7dp5dt. Actually the transfer was on Wednesday, so it's now 6dp5dt. I am not sure why the doctor scheduled the pregnancy test for a week after transfer instead of the usual two weeks.


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## rothbard (Jan 24, 2016)

Actually yesterday's message was correct, the transfer was Monday last week, so we are now 8dp5dt. Looks like I haven't been getting enough sleep.


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## Bahhumbug (Nov 30, 2014)

Reading and sending you both all the very very best, Rothbard


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## rothbard (Jan 24, 2016)

Thanks for all the good wishes. Looks like my wife is pregnant. Today she had a blood test and the hCG level, at 9dp5dt, was 51. She is going to do a second test on Monday, which, if positive, will be followed by a scan.

Does the fact that so far she has experienced no bleeding mean that both embryos have probably taken? Or is it possible for one of them not to stick, without any bleeding?


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## maybebaybee (Apr 17, 2016)

Rothbard that's amazing! Congratulations!!


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## Bahhumbug (Nov 30, 2014)

Delighted to read this! Here's to the next phase...
🎉🎉🎉


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## Blueestone (Feb 28, 2015)

Rum punch - are you still about on here? I had a lovely inbox from you but have been unable to reply as ur inbox is full!

Blue x


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## AngelJ (Jan 19, 2016)

Congratulations!! How wonderful - and such a turnaround!!  You wife might have 1 take without getting bleeding from the 1 that didn't take.....(that was the case for me, as I had 2 put back and 1 took).


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## rothbard (Jan 24, 2016)

Actually the outcome was not very good.. in the end we lost the baby, my wife had a miscarriage in mid-August  . We still have a frozen embryo but have decided to do another cycle before transferring that one. We'll probably do that in late October / early November, after my wife's next period starts.


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## rothbard (Jan 24, 2016)

Today my wife and I did IMSI again. This is a summary of our last two cycles:

1. May 2016: 10 eggs, of which 3 injected, 1 fertilised but died before reaching blastocyst stage.
2. July 2016: 16 eggs, all injected, 14 fertilised, 3 reached blastocyst stage. Transferred 2, froze 1. BFP, miscarriage at 7 week due to genetic defect (two copies of chromosome 8 were present). 
3. November 2016: 13 eggs, of which 7 injected so far. 

Our hope is to get a few more embryos we can use, together with the frozen one. In the worst case scenario we'll just transfer the frozen one next week. My wife turned 43 last August, by the way.


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## Efi78 (Jun 26, 2017)

rothbard said:


> Today my wife and I did IMSI again. This is a summary of our last two cycles:
> 
> 1. May 2016: 10 eggs, of which 3 injected, 1 fertilised but died before reaching blastocyst stage.
> 2. July 2016: 16 eggs, all injected, 14 fertilised, 3 reached blastocyst stage. Transferred 2, froze 1. BFP, miscarriage at 7 week due to genetic defect (two copies of chromosome 8 were present).
> ...


Hi rothbard
I found your posting interesting as we are on the same boat. How did it turn out eventually? Still cycling with Lister? Got your BFP?


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## rothbard (Jan 24, 2016)

Hi Efi, in the end we got 4 embryos, of which we transferred two. Unfortunately the same thing happened as in the previous cycle: my wife got pregnant and then had a miscarriage, most likely due to a chromosomal abnormality. Despite having three frozen embryos, we decided to do a batch of 3 cycles of IVF (instead of ICSI/IMSI) and try to harvest as many blastocysts as possible for genetic testing. We are now at the end of the second cycle and have collected 7 new blastocysts. Our next cycle will be late in July or early in August. 

Our hope is that the genetic testing, combined with IVF instead of ICSI, should help prevent another miscarriage. We saw a big improvement after the first cycle at the Lister, probably due to the DHEA and the increased dosage of the trigger shot. How are things going for you? Which clinics have you been using?


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## Efi78 (Jun 26, 2017)

We are still with Lister and will continue. I find them an excellent clinic. Same boat as you. Trying to collect as many blasts as possible and then test to avoid another miscarriage. However, before next cycle I will also have the thrombophilia and NK tests to ensure it is not an immune problem. You mention that you chose IVF instead of ICSI. Why is that? You believe natural selection brings better results?


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## Efi78 (Jun 26, 2017)

Rothbard
Apologies for bothering you again. Just a question. Did you go for the 3 cycle embryo batching at Lister? Did you do three cycles one behind the other or left intervals in between?


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## rothbard (Jan 24, 2016)

About IVF instead of ICSI, exactly: I was hoping it would avoid chromosomal abnormalities. As far as I know there is no evidence that this is the case; in fact our consultant said it shouldn't make any difference. However it's possible that not many people have looked into this (e.g., for an unpublished study they use at the Lister, showing the probability to get a normal embryo according to number of embryos and age of the woman, I understand they didn't look at IVF and ICSI separately). To me it seems common sense that natural selection should be at least as good as ICSI, but I don't know how much better it is, if at all. We originally tried ICSI because the results of my first sperm test were quite poor, however that seems to have been an isolated incident. When our consultant told us that in fact my sperm at our previous cycles would have been good enough for IVF, I decided to switch to IVF.

We are happy with the Lister as well. Right now it probably wouldn't make sense to change, since that would mean starting from scratch with someone who is not familiar with my wife's full medical history. 

I just read your next message as I was about to post. Yes, we went for the 3 cycle batch process at the Lister. It seems economically convenient, since the costs of the genetic test are to some extent absorbed by the fact that the freezing charges for each cycle (about £1000) are waived. The fee for the test covers a maximum of 8 blastocysts, but if you get more than that there is only an additional charge of about £150 each. Best of luck with your next cycle!


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## Efi78 (Jun 26, 2017)

Interesting. We will probably do the same. Sounds very economical indeed. 
With regards to IVF vs ICSI I would think natural selection is better, but on the other hand our first two conceptions were natural without IVF and ended in termination/miscarriage. Same with first ICSI cycle. We tried an IMSI cycle and although we had 100%  fertilization rate, we got only one bad quality blastocyst which we decided to not transfer and let go. Now two good quality frosties and thinking of banking a few more embryos for testing.


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## Efi78 (Jun 26, 2017)

Hi Rothbard
Sorry for bothering you again, our stories are so similar.
May I ask whether you have had recurrent miscarriage testing done? I am thinking of having these tests done to rule out immune/blood clotting issues. Keep thinking that it is not possible all these miscarriages to be chromosome abnormalities. It could be but maybe worth ruling out other causes?


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## rothbard (Jan 24, 2016)

Hi Efi, no problem at all  . Our first miscarriage was due a genetic abnormality (Trisomy 8 Mosaicism). This was the result of a genetic test we did right after my wife's first miscarriage last year. The first scan, just after 6 weeks, had found a much slower heartbeat than normal, and the second scan a week later found no heartbeat at all. We didn't do a genetic test after our second miscarriage, however since there was no fetal pole it's highly likely that this embryo was abnormal as well. Did you have any genetic tests done after your miscarriages? 

By the way, who is your consultant at the Lister? We are with Dr Nicopoullos.


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## Efi78 (Jun 26, 2017)

Hi Rothbard
We have Dr Nicopoullos as well. We really like him.
The first miscarriage wasn't a miscarriage as per se. It was a natural conception and TMFR due to T21. Huge heartbreak....
Second again natural conception and no heartbeat at 8 weeks. We didn't do testing as heartbreak and repeat of history was too much for us. Has surgery to remove remains
This one IVF conception and the same thing happened as in your first miscarriage. Opted for medical management of miscarriage and we didn't find the embryo as too small....


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## rothbard (Jan 24, 2016)

Sometimes miscarriages due to genetic disorders happen even to young women with no fertility issues. Three pregnancies of my wife's older sister, for example, ended up in a miscarriage (all natural conceptions). She went on to have four kids, all of them naturally.


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## miamiamo (Aug 9, 2015)

rothbard - good to know. I have always thought that genetic abnormalities make conception less likely.


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## Efi78 (Jun 26, 2017)

Rothbard

How are things with you guys? Haven't heard from you for a long time in the thread and wanted how you are getting on. How did it go with the embryo batching?


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## Tootles (May 9, 2017)

Hi, hope it's ok to pop on to this thread. 

Really interesting to read your journeys. Thanks so much for sharing.

I'm desperately trying to decide whether to have tests after having two miscarriages. I've been told by our clinic (Nurture) that it will mean delaying IVF by a month which is frustrating as, at our age, every second counts.

I'm looking at my treatment plan which lists all the options and can see a test has been ticked called: Recurrent Implantation without Karyotype (N8 profile - female).....I have no idea what that is!  Also, Nayral Killer Cell Biopsy.  These tests come to £1,000. 

I just wonder if it's worth it?  Interested to learn about tests on the embryos before they are transferred to see if there are genetic abnormalities. This sounds so sensible and could save in a lot of heart ache down the line.


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## rothbard (Jan 24, 2016)

Hi, we chose the "Rapid CGH" test for day 5-6 blastocysts. It's expensive at around 3000 pounds, however at the Lister Hospital if you combine it with a batch of IVFs then the embryo freezing fees (1000 pounds each) are waived. Unfortunately it didn't work very well for us, for two reasons: first, the number of blastocysts went down from 5 in the first cycle, to 2 in the second, to 0 in the third. It's possible that for my wife doing back-to-back cycles didn't work. All these embryos came back as abnormal.

We also tested our 3 frozen embryos from last year, and one of them, a 4CC we had had frozen in November, came back as normal. Unfortunately we got a BFN after the transfer. It's possible that the extra day it had to wait before the transfer caused this to fail, as it had been frozen on day 6. So, if instead of doing this batch/test procedure we had chosen to transfer all of our embryos early this year, we might be about to have a baby right now.

Finally, I would keep into account that genetic testing isn't 100% accurate. We were told there was a 1% probability of a single test giving no results or the wrong results. It sounds small, but if you are testing 10 embryos it's almost 10% probability, which is not negligible. Indeed, one of our embryos came back as "no result", and we'll transfer it next month. This article also indicates that sometimes "abnormal" embryos can produce normal babies.


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## miamiamo (Aug 9, 2015)

> This article also indicates that sometimes "abnormal" embryos can produce normal babies.


I come across similar opinions, as well.


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## Efi78 (Jun 26, 2017)

Hi Rothbard

Hope all is well. How did your transfer go? I had one FEt this month of a 3BB blasto and failed. Now thinking about transferring the last one in December. Another 3BB


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## rothbard (Jan 24, 2016)

Hi Efi, in the end the "no result" embryo did not survive the thaw. Our genetics counsellor had earlier suggested that this would likely be the case, since the lack of results often happens when the DNA in the biopsy has deteriorated.

We decided to transfer two of the embryos which had been found to be abnormal, hoping that the result was incorrect. If it was accurate, then the type of abnormality is such that they would not lead to a viable pregnancy in any case.


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