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.