Monday 15 September 2014

The Strategery Room

Husband declined to accompany me to my latest WTF appointment with Dr Somebody that I Used to Know. "You're the mastermind of this operation." He has made this comment on multiple occasions, and to which I remind him, that we haven't had much success with my brain power. Nonetheless, I prepped for this appointment as if I were preparing a presentation. I created an outline and referenced my sources.

To my surprise, Dr STIUTK started by discussing the transfer procedure itself. On his consolatory voicemail, after noting the lower success rates with a single transfer, he added, "I thought the transfer itself went well." In my more fragile emotional state, I heard this as 'you're to blame for electing a single embryo transfer, as I did my part.' Basically I have challenging anatomy, which makes it hard to gain access to the fundus of my uterus. As I had to partially empty my bladder on my prior transfer, I thought I had achieved the 'just right' level of fullness, but apparently not. He wants it "insanely" full next time, while acknowledging how much discomfort that will cause, the hope is that it will make for a quicker procedure. He'd also like to try laminaria. Laminaria are actually small sticks of seaweed that are used to promote cervical dilation for women who are having a second trimester D+C. The goal is that it may soften my cervical-uterine junction. He described that patients who were his most difficult transfers have still become pregnant, but a challenging transfer does have lower success rates (which was confirmed in my reading). After repeating the same recommendations at least three times and emphasising the need to improve the transfer procedure, I almost told him, "don't beat yourself up over it."

As infertility is often described as a journey, I feel like a whiney child asking "are we there yet?" So where are we now in terms of a diagnosis and prognosis?
I wanted to start by putting all the cards on the table. We're not yet stuck with the label of 'recurrent implantation failure' as technically, we've only failed with two quality embryos. My day 3s were of questionable quality and my second FET was a Hail Mary to try to avoid a second stim cycle. He still feels we have a favourable prognosis. I did mention that I'm viewing these embies as our endpoint, as I don't feel we'd do any better with another fresh cycle, but he jumped in to disagree, although he quickly added that he hopes we don't get to that point.

Are there any explanations in terms of embryo quality or endometrial receptivity. Is my lining too thick and would I benefit from a change in estrogen protocol? 
A normal embryo does not necessarily indicate that it is a high quality embryo, and there are still many limitations around embryo assessment. However, this embryo was a grade 1 and it performed as well as it could in terms of thawing and spontaneously hatching. He believes my other fro-yos are grade 1, as I recall from the embryo reports, but he will verify with the embryologist. Regarding my lining, he disputed that a lining can be too thick, but noted that a measurement approaching 20 mm would raise suspicion for a polyp. He was also quick to defend that the priming protocols were established by his partner, who has been in practice for almost thirty years. I pointed out that I suspect I'm a bit hypothalamic. When I cycle on my own, my flow is very light and short. Prior to my septum removal, I would use 3-4 light tampons per cycle. Post resection, I've upgraded to 1 or 2 medium tampons, but the duration is still about 2 days. After a failed FET, I'm soaking through a Kotex super plus tampon every three hours in what Co-worker calls my "big girl period." He some what reluctantly conceded that we could slow my priming, although this would be truly emperic as there is no evidence to support this approach. Yet the more we discussed, I could tell the idea was growing on him. As I have a longer proliferative phase and lower estrogen production, it may make sense to mimic my own physiology. I was mentally high fiving myself.

Are there any investigations to be considered?
My RE and I both agreed that the pre-test probability that I have a hydrosalpinx is pretty low, especially as I wasn't promiscuous enough to acquire an STI or PID, despite my best efforts, but I also doubt that I have endometriosis. So there is no need to repeat an HSG or discuss a laparoscopy, as it would be of limited value. Regarding the Klinman Endometrial Function Test or the Beta-3 Intergrin test... he didn't completely dismiss them, but commented "I don't think we're at that point yet." The provider in me would agree. The patient in me just wants an answer. Some answer. Any answer. You can make something up because I'll feel comforted just by having an explanation.

Take a good long look at yourself in the mirror, young lady...
"Jane, I've been meaning to talk to you about your blood pressure..." Of all the uncomfortable conversations that I anticipated when I was drafting my outline, this was not one of them. I felt as if I were being scolded. I could feel my blood pressure start to rise at the mere mention of my blood pressure issues. "During both of your retrievals and during your hysteroscopy, the anesthesioloigsts informed me of your high blood pressure. I think it's time for you to be honest with yourself and admit that you have mild hypertension." My initial reaction was, no, I have labile hypertension! ...which proved his point... I am exhibiting signs of denial. Whenever I encounter a patient who tells me she has 'pre-diabetes', I translate it to 'no, you actually have diabetes, you're just not addressing it'. I can argue the difference between a manual and automated cuff reading, or home versus clinic readings, but I can't hide under propofol. "High blood pressure can negatively impact implantation," he continued "I think you should restart your Labetalol."

I sighed silently. Since I have a low resting heart rate, a beta-blocker is not a good choice for me. In fact, I actually had to reduce my dose in half as I was experiencing light headed episodes. Plus, it was really hindering with my swim training leading into Championships and Nationals, which is probably when I stopped it. A diuretic would be much more suitable, but I convinced my primary care doctor to start Labetalol as it's the drug of choice in pregnancy, and the presumptive idiot that I was, I needed it as I'd be pregnant soon... It's still a hard pill to swallow, but I run, swim and cross-fit... When I arrived home, Husband joined my RE in this intervention. "Jane, age and genetics are catching up with you. Think about how much worse it could be if you weren't this fit." I don't eat processed foods, I go to the Farmer's Market and make everything with fresh ingredients. I'm paleo-ish! Okay, now I'm sounding like my patients who insist they can't have gestational diabetes if they're vegetarians. Plus a food movement whose mascot is a caveman eating meat on a stick while professing his love for bacon, is really not making my case.

Are there any other interventions to consider? Should I injure my endometrium again?
Dr STIUTK reported that he recently read some studies with this tactic and noted that the data is really interesting, but he reminded me that not every intervention is appropriate for every patient. In short, because it did not work this past time, he would not recommend repeating it. Although ASRM advises against the emperic use of aspirin or prednisone, would either medication pose potential for harm? He didn't believe that they would, but conceded that adopting these approaches is going down the path of accepting immunology or hypercoaguable theories. I revealed that I received a prednisone protocol, but it was such a low dose, it was hard to determine if it would offer any benefit. Aspirin, on the other hand, I felt I could make a stronger argument, especially in light of our previous conversation.

There used to be only two options for treating high blood pressure in pregnancy; Methyldopa, an alpha-adrenergic agonist and Hydralazine, a smooth muscle relaxant. The limitations with these drugs is that Methyldopa isn't that effective at lowering blood pressure and Hydralazine requires frequent dosing, which presents issues with compliance and is associated with rebound tachycardia. Beta blockers were thought to be contraindicated as they would impair blood flow to the uterus, but Labetalol is distinct in that it is a mixed alpha and beta adreneric antagonist. Studies were able to demonstrate that it could effectively lower blood pressure, without any negative effects to the fetus. After all, it is more of a case that it is the elevated blood pressure which is compromising perfusion, thus arguing that untreated hypertension is more harmful than potential medication effects.  Even in the absence of a coagulation disorder, aspirin has been demonstrated to improve uterine blood flow. It has been recommended to start a baby aspirin prior to twenty weeks in women who are at risk for developing pre-eclampsia, which I am, since I have mild hypertension. I did admit that I am possibly looking for a placebo effect. I can accept that there is an element of randomness, but if you finally achieve success after so many failures, it's hard not to be convinced that what you ate for breakfast that morning had an effect. "Exactly," agreed Dr Somebody that I Used to Know.

Number to transfer...
I saved this for the end, as I presumed it would represent the bulk of our discussion. I figured based on his voicemail, his agenda for this meeting would be: convince Jane to transfer two embryos... I called him out right away; even with the advantage of hindsight, would he have recommended transferring two embies? To my surprise, he replied "No." (I did point out that his message suggested otherwise) Furthermore, he does not recommend transferring two with our upcoming attempt. "Jane, you have made your feelings about twins perfectly clear from day one..." he added. Oh. I was prepared to present my case again ending, with an impassioned plea; I resent having to chose between having none and having twins! He commented that the 74% success rate with a single euploid transfer that is listed on XYZ's website reflects a relatively small sample size and more larger scale studies are needed, but instinctively he feels a 60% success rate can be expected. Transferring two euploid embryos can be associated with more than a 50% twin rate (there was the stat I hadn't managed to find). Nonetheless, he feels it is reasonable to proceed with a single transfer.

The last issue addressed was timing. I'm going to be away for a week in October and my RE is gone for three weeks in November. I was planning to manipulate myself with a Nuva Ring in order to coordinate my transfer time, but after our discussion of being more respectful to my body's normal physiology, I'm going to go au natural and let the chips fall where they may. If the dates do not work out, then I'll accept that it simply wasn't meant to happen at this time.

16 comments:

  1. I would be compelled to do some imaging of your uterus, be it, HSG, SHG, or hysteroscopy. It's been a long time since your resection and you had a miscarriage early in the year. I would want to be certain that the uterine environment is on the up and up. Is there scar tissue, polyps, etc.? But, I agree with your doctor regarding the endometrial function test, even if it shows limited receptivity, there's no proven method for improving it. Furthermore, you've been pregnant before, that seems proof enough that it's not a molecular issue. I think an endometrial injury (scratch) is so simple to do, why not do it? The data I read supports it. I say take the baby aspirin and prednisone. Why not? Aren't we at the "throw the whole kitchen sink" in there level of treatment now? I did the scratch, the steroids, the aspirin, and I topped it off with a side of Lovenox. All of which could be classified as voodoo medicine, but I'm pregnant. If you know you're on the tail end of intervention, don't leave any room for second guessing. Your hypertension is unfortunate, but it sounds like it's time to formally address it.

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    1. I did a sonohystogram just before my prior transfer and I think we'll do another one after my laminaria insertion.
      I may still throw in the prednisone
      As I did one transfer after my D&C, and the scratch didn't offer any benefit this last time, I think it's worth skipping. Perhaps my endometrium has a more hostile reaction.
      I've been checking my blood pressure multiple ways, and it's not that bad high 120-130/ high 80s to low 90s. The Labetalol doesn't make too much of a difference.

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  2. "The provider in me would agree. The patient in me just wants an answer." This is SO interesting and so refreshing to know, but I have to admit I'd love to sit in on your follow up appts... I'm guessing your chats with your RE are on another level entirely.

    I like the plan, and I'm hoping the dates work out for your next transfer!

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  3. I agree with Amanda- your conversations wtih your RE are on another level. But i can definitely sympathize with the patient who just wants some freaking answers. I am right there with you. I'm hoping my decisioin to do the hysteroscopy is the right one. But I feel like I'll be disappointed if they DO find something or if they DON'T. So basically I'm a hot mess. It sounds like you did get all of your questions and concerns answered or at least addressed. And you gave your doctor some things to consider as well. I'm praying that the dates work out for you and that this next transfer is it. You are in my thoughts!

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  4. Sounds like a thorough meeting. I wonder about the thickness of the lining. My university/clinic will cancel a cycle if the lining is thicker than 15. I so hope you find the "right" protocol!

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    1. I always struck me as odd, they would measure around day 10, increase my estrogen from two patches to three then back to two once I start my PIO, but never checked the lining again before the transfer which was 2 weeks after my last lining check.

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  5. Is it terrible for me to say (with all of the high-faluting science talk in this post) that I love the fact that you used the word "strategery"? Cracks me up every time. Dubya! Anyway, you and your RE have covered so much ground here, it sounds like you have a solid plan in place going into your next FET. And now that I'm thinking about it, I think your RE is right that the EFT isn't for you. After all, you've had pregnancies before which demonstrates that embryos CAN implant. I never had implantation until after the EFT and the Lupron treatment.

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  6. Well it sounds like your RE really takes the time to cover everything you need to discuss. Have you ever thought of doing a natural cycle transfer? That's what I would have tried next if we didn't go ahead with the donor. I don't mean to give annoying advice, I was just thinking...

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    1. No advice is annoying! I've been thinking similar thoughts! The challenge is that I'm inconsistent with ovulation !

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  7. took me 4 normal embryos for one to stick (after years of other things including a transfer of 2 non tested embryos that ended in a single miscarriage). 18 1/2 weeks preg now. I did a 2nd hysteroscopy (with saline) before the transfer that worked. I really do think there is validity to a "trauma" to the uterus prior to transfer. I am also with your RE that these embryos shouldn't be the end of the line and you could possibly benefit from another retrieval. But after 5 retrievals myself, i know that is easier said than done. so tough.... you have a crowd of people rooting for you.

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  8. It's interesting that he has changed his tune a little about transferring one vs. two embryos, especially since you had your argument all prepared! I hope that the timing works out and you can go forward with your plan, but I love that you have a great attitude about waiting if the need arises.

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  9. I had the "are we there yet" feeling after 3 months of trying on our own, so I admire you for plugging through this.
    My blood pressure rises at the thought of being measured, I think. Which is a little inconvenient as it makes my doctor worry about missing developing real problems. It's too bad if the drug of choice doesn't work for you though. Is anything known about the relationship of (high-ish) blood pressure and implantation/early pregnancy?
    I really, really hope that the thorough strategic (strategeric?) planning from both yourself and your RE brings you a baby.

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    1. He implied that it has been noted that lower implantation rates with higher blood pressure, I didn't ask him to elaborate, as I resigned that I would be a good girl and take my medicine. However, my readings with and without Meds are about the same, high120/low 130s over high 80/low-mid 90s, so my BP is not THAT bad and the Meds are having much affect. I'll ask more at my next visit

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  10. Toooootally agree with the patient in you. Answers. Now. PLEASE?!?! I'm hopeful that everything will work out for you with timing!!

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  11. My RE had me take aspirin as part of his standard protocol and I think I took it for most of the first trimester. It's only recently that I read about it possibly helping to prevent pre-eclampsia and now I wonder if I had continued to take it through the entire pregnancy if I could have avoided it.
    Sounds like a good meeting. Though we never really do get any definitive answers at these things. I'm glad your RE didn't try to talk you into transferring 2 embryos. I hope the timing works out so you can do your next transfer soon.

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  12. "Big Girl Period" cracked me up. Thank you for providing so much detail about your WTF appointment. I always learn so much from your posts. 4 years ago, I had blood pressure readings similar to yours along with a family history. I was told by one PCP that I HAD to go on Labetalol. My new PCP was willing to let me lose a few more pounds and exercise, which has resulted in readings of 110/70. I've done research online and I couldn't find any information on BP and fertility. In fact, what I found stated that it was only a concern during pregnancy itself. I worry that my BP spikes on occasion when I am stressed, even though I have no proof. I tried a low dose aspirin and I felt light headed. During my retrievals, my BP was good. Should I still consider the possibility that my blood pressure could be affecting implantation?

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