IVF and unexplained infertility

[DaddyinWaiting]

Hi all,

Full disclosure, I'm a bloke but desperately seeking your advice on IVF next steps.

My wife (32) and I (38) have been ttc for almost three years now. Not one single BFP at any point and essentially we're classed as "unexplained infertility".

My wife was on Clomid for 6 months and has had various tests (lap/dye, hysteroscopy, ovarian drilling, thrombophilia screening), I've had a semen analysis (low end of normal), we've both changed our diet (no red meat, no alcohol etc..), but to no avail.

We've now had three failed IVF cycles. The first cycle was TFF (lucky us being in that magic 1-3% club) and then next two cycles we were advised to go for ICSI.

The first ICSI yielded two embryos. One fresh transfer which failed and the other one now in the freezer. The second ICSI yielded four embryos with one fresh transfer that has just failed. So we're now left with four embryos in the freezer but seriously considering our next steps and bank balance.

We haven't been overly impressed with our current London-based clinic (lots of administrative cock-ups) and we are both left wondering why we've never even had one BFP. Hence why we're not sure how to proceed with our four frozen embryos. Should we keep going or should we go for more tests/procedures to increase our chances.

My questions are:

1. Does anyone have any advice on next steps with unexplained infertility after never getting a BFP, even after IVF/ICSI?
2. Can anyone recommend a specialist London/South East based consultant for a second opinion? As I mentioned above, we're not really sure our current clinic is doing everything it can for us and the back office function is often highly dysfunctional.

Thanks in advance!

Hi

Sorry to read about what you're both going through - infertility is horrible. My DH and I have unexplained infertility too, 7 years TTC (2 losses and 1 current pregnancy). We had ICSI eventually.

If you haven't already, it's worth trying to maximise egg and sperm quality by tweaking your diets and lifestyles (if you haven't already, I'd recommend reading It Starts With The Egg), taking supplements (I took Proceive Max), checking a sperm sample (including for DNA fragmentation) and possibly checking for any varicocoeles?

Some people choose to do PGS testing of their embryos, to make sure they're transferring chromosomally normal embryos. The thinking there is that abnormal or mosaic embryos are less likely to implant successfully and are more likely to result in non-viable pregnancies if they do implant. A chromosomally normal embryo has a better chance of implanting and becoming a successful pregnancy. There are different schools of thought about PGS though. We didn't do it in the end.

There's also the uterine environment to consider - a lot of factors can be at play there. An embryo is more likely to implant if it's being introduced into an optimal environment, and less likely if something about the environment is problematic. Your wife might want to consider additional investigations into her uterine anatomy (eg. a HyCoSy), receptivity (eg. an ERA) and microflora. There are a lot of threads on the forum about people having these investigations, and outcomes from them, so you both might want to read about the investigations and people's experiences, and ask questions of people who have had them.

I live quite a long way further north so can't help with clinic advice, I'm afraid, but I think quite a lot of posters are based in the South so hopefully someone can advise.

Thanks so much for your reply, Scirocco. And I'm so sorry to hear how difficult things have been for you. But I'm really pleased to hear of your pregnancy and wish you all the very best.

I've already had the fragmentation test and my wife had a HyCoSy but not an ERA, which is something we've been considering. We hadn't, however, heard of a microflora test, so that's something we will definitely consider. And thanks for the book recommendation as I'm sure there are many things we can still change in our diet.

PGS is a really difficult one. We're aware of the mixed evidence but the cost is eye-watering on top of all the other things associated with IVF.

Thanks once again :)

Try immune testing with your wife too. Gorgy and dr Shehata , best of luck

Hi @DaddyinWaiting ,
I am sorry about what you have been through. We had one failed ICSI (9 matured eggs, 4 embryos, none sticked). Just started our 2nd round 6 days ago. Our doctor will use PICSI and Calcium Ionophore methods to increase the fertilization rate this time.
We have also started to use some supplements that were mentioned in the book @Scirocco recommended.
I will keep you updated if we get better results so maybe you can also look into these.
Did they check your wife for natural killer cells?

Thanks so much @WakeuptoCake. The doctors do look expensive but then again there are some really positive reviews so we're definitely considering.

Also thank you @Cayandsimit and I'm sorry to hear you've been through similar. Best of luck for you both. Out of interest, have your doctors advised whether PICSI or calcium ionophore will help implantation or is it exclusively for increased fertilisation?

We were just checking the previous blood test forms and I can't see natural killer cells listed, so that's another one for us to look into.

Sounds like there are just so many possible causes for this and it's a bit of a minefield - I really do appreciate everyone's suggestions.

Lastly I wondered if anyone has any experience of an EMMA or ALICE test and whether you thin it's worth it?

@DaddyinWaiting PICSI and calcium ionophore to increase the fertilization and embryo quality.
PICSI costs around 300€ and Calcium ionophore costs around 150€ in Germany. I think they are significantly cheaper methods compared to genetic testing of the embryos.

Checking the natural killer cells (NK) is to improve the implantation. My doctor checked that through uterine biopsy. I have mildly elevated NK in the uterus so I will get Omegaven infusion.

In another thread someone mentioned that her clinic in the UK didn't check her prolactin levels. In Germany it is one of the standart things they check with blood test.

TUnfortunately I don't have any experience with genetic testing of the embryos since those stuff are highly regulated by an outdated embryo protection law in Germany...

Like you said, it is a bit of a minefield. I know our situation doesn't sound so bad compared to many other's, but I personally wanted to do whatever we can before our 2nd try. I

I'm also unexplained (but secondary) infertility and they have recently tested my endometrium with and ALICE and EMMA test. They sent husband for dna fragmentation.

I have unexplained secondary infertility and my age is an added bonus.

They gave us a lot of tests, both me and DH, and now we're in the middle of our 1st cycle.

Apart from being in mumsnet all day long -trying to keep sane-, I also plan a nutritional plan for us both, depending on our latest blood tests and where we need our vitamins and minerals to be. There are some amazing blogs about this, so maybe try this too.

The clinic I'm using atm offers free consultation with a video call, so if you want, DM to give you information.

Oh, also, which prenatal vitamins are you using?

Hi @DaddyinWaiting,
I thought I would give you an update since we got better results this time (even though I got OHSS in the end and we opted for not to transfer the best blastocyst). Since I am on bed rest and have a lot of time 😅, I write you in detail, what I think worked and what not.

So,
1st ICSI in May 2021- 150 Pergoveris, 10 days protocol:
•180 million sperm count, good motility, 1% morphology (5 days sample)
•11 eggs, 9 mature, 4 fertilized. One good quality, others are average.
•1 Day3 fresh transfer, 1 FET, none of the four embryos sticked.

3 months supplement use:
I (35): Femibaby prenatal vitamin, 300 mg vitamin C, 200 microgram methyl folate, 12 mg zinc, 100mg Q10 Ubiquinol, 100 ug selenium (due to hypothyroidism)

DH (36): 600 mg vitamin C, 400 microgram methyl folate, 25 mg zinc, 100mg Q10 Ubiquinol, 100 ug selenium, 1000mg Omega-3, 400mg Vitamin E, 500mg L-Arginine, 375 Magnesium, 1.6 mg Vitamin B, 3ug Vitamin B12 and 300 mg L-carnitin

Diet and life style:
We didn't change much in our diet because we were always eating healthy and bio food anyways. We don't eat pork but we didn't cut the lamb and beef. We increased chicken and fish intake. We use only olive oil for years now. We compliment the meat protein with brown rice, whole grain homemade bread. We always eat salad in all three meals. Fruits and nuts everyday as well.
We didn't do any HITT exercise. We usually walk 6-7 km per day and just continued with that. Also 7-8 hours solid sleep every night.
I think my thyroid values are also more stable ever since I have the correct dosage.

2nd ICSI in Nov-Dec 2021: 200 Pergoveris, 9 days protocol, moderate OHSS in the end:
•138 million sperm count, good motility, still 1% morphology (3 days sample)
•14 eggs, 10 are matured, 7 fertilized. 2 of them are frozen on the 1st day (due to stupid laws in Germany), 5 of them were put in Day 5 culture. We got good quality 3 blastocysts and 1 morula. Blastocysts are frozen.

So, with 30% increase in the fertilization rate, I would say the new methods our doctor used somewhat worked. Also I got bigger follicles evenly distributed this time. I think this time at least 7-8 of them were 17-21mm big whereas last time only 4-5 of them were that big. So, I think checking Pergoveris as a stim option, PICSI and Calcium ionophore make sense.

Oxidative stress is also ruining the sperm. I have read a few research papers suggesting that not ejaculating for 2-3 days instead of 5 days lowers the oxidative stress on the sperm. So this time DH saved it for 3 days, instead of 5. Maybe that also helped a bit.

However, all the supplements DH was taking in the last three months didn't increase his morphology... Maybe fixed the DNA damage a bit if he had but overall I think they were not useful at all. I can't really say if Q10 increased my egg quality either. Clearly it didn't hurt. But overall, I think such a vigorous supplement regime didn't give the improvement we hoped for. I think I good prenatal vitamin is more than enough. I feel stupid that we spent approx. 150€ every month to buy the best vitamins 🙄

In the end I got the morula transfered because I shouldn't get pregnant this month. OHSS can get worse otherwise.

PICSI and calcium ionophore are still seen as "experimental" methods by many doctors. I hope you can find an open-minded consultant to discuss these. Wish you and your wife good luck in your journey 🍀

Thanks so much everyone for your replies and sorry it's taken so long to get back to you.

@bmachine how did your EMMA and ALICE tests go, did they find anything useful?

@dutchessmom how is your nutritional plan going?

@Cayandsimit that sounds like great progress and thanks v much for your taking the time to write - so helpful. I hope the bed rest helped too! Interestingly we had two progressively better ICSIs, which I attribute to a combination of taking Proxeed Plus and having a holiday just before the treatment started - we were both much less stressed!

As for where we stand now... we had another embryo transfer last week, but this time frozen for the first time. And my wife is now taking daily lubion (progesterone) injections, prednisolone (immunosuppressants) tablets and inhixa (blood thinner) injections in the hope that we get our big fat positive after Christmas. The test date isn't until the 29th, so waiting is like torture for both of us. My wife hasn't had any symptoms at all (transfer was 4 days ago) but we're clinging to hope that not everyone does. We've also read that having cold feet is a big No-No, so wifey is wearing thick socks for most of the day!

Hi @DaddyinWaiting
Just to wish you the best of luck on your OTD this week. X

Thanks so much @Angeldelight21. We've been debating about POAS for a few days and have decided to do one tomorrow morning (12 days post FET), the day before the actual blood test. Keeping everything crossed!

Quick update - we have a faint pink line on the First Response test which we have never ever had before! Obviously need to wait for the blood test tomorrow but we're feeling hopeful!

This is the 12th day post frozen embryo transfer so hoping this can't be a false positive because there wasn't a trigger shot this round. And despite it being a faint line, it's still a line!

Everything crossed that it's your positive result. Hoping and hoping for you.

Quick update - we just had our 13dp5dt HCG result. It's 46.9 which is considered low and a risk of miscarriage/ectopic, but it could just be a slow pregnancy. We have absolutely no idea how to feel but have booked in another blood test in 2 days time and a scan in 7 days.

Does anyone have any words of wisdom to share?!

It's low but still positive. I think it's more about it doubling every 48 hours. Congratulations on your pregnancy x

It’s a horrible feeling being stuck in limbo. I had a HCG reading of 49 at 11dpt3dt in my first icsi cycle and sadly it turned out to be a chemical pregnancy. However I spent that weekend full of hope that it had worked and convinced myself it had, having thought previously it hadn’t. I even took another test which was positive. I found out on the following Monday and it had dropped again. It was worse having that false hope than if I’d just found out at the first test.

The only advice I would give is hope for the best but prepare for the worst. And try to resist the temptation to test again between now and your next blood test.

Hoping it is just a late implanter for you.

Thanks @Confused521 and @TheMagicDeckchair. We had our second beta today and we've more than doubled! Up from 46 to 99 which we're told is a really good sign and we're now booked in for a scan in 2 weeks time.

Obviously very early days but the nurses seemed really happy earlier so we're taking it as good news for now.

Thanks again all and wishing you all a very happy new year!

That's fantastic news. Happy New year!

@DaddyinWaiting that’s wonderful news, congratulations! Hoping everything goes well at your next scan. Happy new year to you too!

@daddyinwaiting great news! I hope you will give us more good news after the scan. Wish both of you best of luck 🤞🍀

Hi all, hope everyone's well. We were due to have our scan tomorrow but had to bring it forward to yesterday as wife had shooting pains and a bit of clotting, which was obviously quite concerning. But thankfully the scan went well! The doc was pretty sure he saw a heartbeat although couldn't be 100% sure, so we have another scan booked in for next week to be doubly sure. Being very cautious but for now it feels like good news!

@DaddyinWaiting Such a rollercoaster, isn't it?! I guess none of us would be fully convinced and relieved until we leave the hospital with a healthy baby... I wish you and your wife all the best in the next scan 🍀 Looking forward to hear good news 🤞

Thanks so much @Cayandsimit, that's exactly how we're feeling. Complete and utter paranoia!

I meant to ask how things are going with you? Hope the OHSS has subsided and sending you both lots of good luck too!

@DaddyinWaiting Thanks for asking! Physically all good. I got my scan and blood test results last week. Everything went back to normal. Frozen transfer is scheduled in the next cycle. We opted for single expanded blastocyst instead of two because all there are in the slightly different development stages. Hopefully the optimal one will survive the thawing process 🙏
Meanwhile my most beloved family member is in the ICU and recently got also Covid in the hospital. We had to travel to my country to visit my family. So, emotionally I feel like in a dark ditch...
I am really hoping that this transfer will bring a new member to our family. Finally something to look forward to...