4 failed transfers, what else can be done

[KH99]

I have had 4 failed transfers with day 5 blastocysts of grading 2-3BB, 1-2BB, 4AA and 3BB at 2 different clinics. I have one more left to transfer. As this point, I don't even see the grading makes any meaningful differences. It is really like fighting a losing battle. I just wonder what else I could do for the final round. I don't think I can continue after that. In a way, I just want to get this over with, move on with my life, cherish the family and child I already have. On the other hand, I also don't want to feel I missed something important in my treatment and wasted the opportunities and enormous cash spent on it.

Among the transfers, one was fresh and three were FET non-medicated. I used progesterone from day 0 of ovulation as well as 75mg aspirin. There was a progesterone blood test on day 4 in one of the cycles. Since the absorption was good, there was no further test afterwards. I had a recent thyroid test done too and it was good as well. Uterine lining thickness and blood flow were good. Doctors said they could prescribe medicine to lower immune system but in the context of COVID they did not recommend it. The thing was that they did not know if it was a problem since it was not tested. I also asked about embryo glue but doctor was also not keen on it citing it is not proven effective.

Apart from these, there was nothing much suggested from my doctor. In fact, my last two FET were exactly the same protocol. I don't know if my doctor would suggest anything new and the final round will go down the same protocol again.

The thing is that I don't know if the failure was due to embryo quality or environmental issues or both. There is not much to do about embryo quality so the only thing can be done is to eliminate environmental issues.

Should I considering anything to check the uterus so called Hysteroscopy and the immune system? I had a natural birth a long time ago and assume these aspects are fine. I don't know if these can change over time.

I also had a laparoscopy surgery a couple of years ago due to a very large cyst on the right tube and the right tube was damaged and had to be removed. I had hycosy afterwards and the result was block left tube. I recently read that if the block tube was due to hydrosalpinx it would negatively affect IVF result. Neither clinic mentioned it though. Should I get it checked although maybe it is not an obvious case as it is not a swollen tube?

I wonder if there is any point to do endometrial receptivity analysis? It is an expensive test. What kind of recommendations do you get from this test?

Anything else would be good to know.

I would investigate the hydrosalpinx before your transfer definitely. My clinic refused to transfer if it was present due to the lowered chance of successful implantation

There is also the scratch and embryo glue? I don't have any experience in those as my clinic didn't offer them but I've known people have them

Also assisted hatching?

Hi @KH99 I’m sorry to hear about the unsuccessful cycles. I’m pausing for investigations at the moment after two unsuccessful transfers, how old are you out of interest?

The first thing I did was PGT-A tested my frozen embryos, if you have 1 left them there probably isn’t much point to this, but if you had another collection and had a few then it can help with the selection.

The next thing to consider is endometrial receptivity, you mention the blood supply and thickness is good. In my case the specialist noted that my lining thickness had reduced substantially after I started progesterone. So I’m going to have a mock cycle so they can check it. During the mock cycle I’m going to have a ERA, EMMA, ALICE. My understanding is that ERAs are most helpful in medicated cycles, they determine the amount of time someone should be on progesterone, you could ask your specialist if this would help in your case. There is evidence that the good/bad bacteria can affect implantation and pregnancies which is what the EMMA and ALICE look at.

In relation to a hysteroscopy, the evidence suggests they should only be performed if there is some abnormality that needs further investigation, this is because there is a small risk of significant complications such as perforating the uterus. Given your previous issue it may be warranted though. When the embryo is transferred the environment needs to be as dry as possible, they only infuse the tiniest amount of liquid in the catheter when they do the transfer, if there is a hydrosalpinx releasing fluid then it makes it harder for the embryo to adhere to the endometrium in order to implant.

The next consideration would be recurrent implantation failure investigations, I’m having level 1 at the moment, a thombopholia screen (If anything flags up then I’ll be on aspirin and heparin) and autoantibodies (if anything flags up I’ll be on steroids).

In relation to embryo glue, the embryologist told me this can’t be used on hatching or hatched embryos, not sure if that’s the situation you’re in.

I think you need to ask yourself whether you want to investigate the situation and as you can see from above, there are a lot of investigations that could be considered, your specialist would be in the best position to advise on what is likely to be helpful in your case.

Your other option is to try to transfer the final embryo. If I was in your situation and did this without any further investigations, then I would have a scratch done, this is performed in the cycle before the transfer cycle. I have just read a book aimed at specialists on endometrial preparation and they speak about the research for seminal fluid around the time of transfer. I’m going to try this on my next transfer, the authors say the evidence suggest there could be an improvement in implantation and there aren’t risks. So me and DH plan to have sex the night before ET.

@KH99 just seen that you’ve had your right tube removed and your left is blocked, so you’d need to be safe to have sex during a natural cycle if you wanted to try the seminal fluid at the time of the transfer. If the sperm gets through the left tube and fertilizes an egg you would have a high risk of an ectopic, so definitely check that one with the specialist before doing it.

Sorry to hear about your failed transfers, OP. You've already had great and detailed advice. I just wanted to agree that hydrosalpinx would be something I would definitely want investigating given your tube is blocked. It is a potential explanation.

I had a scratch and embryo glue for my successful FET. Who knows if it made a difference but, apart from the additional cost, they're fairly simple and quick things to try.

Thanks all for your suggestions. I think it is best for me to pause and investigate more before another transfer. I went back to get the hycosy report yesterday and it was actually not conclusive. It said the dye did not go through. However it also stated it could be false negative as the dye not seen entering interstial portion of tube which may indicate tubal spasm. I want to speak to my GP as well as the clinic's doctor on this.

@Gardenlady543, I have been TTC for #2 for 4 years on and off and I just turned 40. Trying, investigating, waiting for nearly 1 year on NHS laparoscopy, trying again, investigating and IVF. I feel I am already running out of time and there is a high likelihood that there is no result at the end. Regarding the seminal fluid, does this contradict the rule that one cannot have unprotected sex before transfer?

@KH99 you know I wondered about the seminal fluid adding extra fluid as well, the two issues (dry environment needed and seminal fluid aiding implantation) were in 2 different chapters so I don’t know the answer. It’s also unclear when the best time would be, I’m going to ask my specialist what she thinks before I try it, but my hope is that if we DTD the night before the transfer then hopefully the liquid would mostly be dealt with before the embryo is transferred in. You’d need to make sure you check that you’re safe to do it as there is a slight chance that you will conceive naturally in a natural FET so having parent tubes would be important. I’m added a snippet from the book in case you want to look up the study they cite.

I think pausing for investigations is sensible, it’s what I’m doing, I just know there is something wrong in my case and I basically refused to do any more transfers until we assess what’s going on, it took my PGT-A tests to come back as 83% euploid (normal) for my specialist to get on the same page as me, at that point she said, ok there is something else going on here.

I think in your case the first step would be to address the hysteroscopy results and go from there.