Sunday, 28 September 2014

The Second Opinion

While I was in research mode after my latest FET, I contacted two other REIs in the area. One has visited our office a few times, and I have corresponded with him via email regarding some of my patients, as well as my personal situation. The other was Co-worker's RE, as we also have a few mutual patients. I was hoping that I could take some of their suggestions into my WTF appointment, but neither wrote back to me. Not even with an, "I'm sorry you're going though this, but you'll have to schedule a formal consultation." I shared with my colleagues how disappointed I was with their failure to respond. It makes you realise just how lonely and isolating infertility is when you receive this type of treatment from your infertility specialist associates.

The next day, after slagging them both off to my colleagues, I received a message from Co-worker's RE. He apologised for the delay and expressed his empathy for my frustrating situation. Very little information is available about Recurrent Implantation Failure (RIF). The issue is either the embryo or the endometrium. Even with a euploid embryo, his observation is that the implantation rate is only 50%. Mere chance does explain our failures. He then introduced a new test that identifies the window of implantation from an endometrial biopsy. If my endometrium is found to be out of phase, I could pursue another single transfer after correction. If the endometrium is in sync, then we should consider transferring two embies. "Being responsible to limit twins is respectable, but I think you need to be more aggressive."

They say you shouldn't ask a question, if you don't want to hear the answer. I wanted a second opinion, just not after I had already established a plan. I needed some information on this new test, so I typed the name into The Google, which led me to the company's website. 'Recurrent Implantation Failure? We can help!' Okay...I'm intrigued. The test involves performing an endometrial biopsy 7 days past the LH surge in a natural cycle, or 5 days after starting progesterone in a medicated cycle. Apparently, 20% of women with RIF are found to have a displaced implantation window. The results will either indicate that the endometrium is receptive, and the transfer should occur at that time, or it will reveal that the lining is not receptive and the analysis will offer a recommendation on when the transfer should take place.

So, this was another test to assess endometrial capacity. We had dismissed two other testing methods for lack of reproducibility and ambiguous implications. However, this one could offer feedback on my endometrium, which seemed pertinent given our plans to alter my estrogen priming. Suddenly my head was spinning. I had to do this test! If my next transfer resulted in my fourth consecutive BFN, I'd be filled with regret. This could provide a possible answer for my failures as well as increase my chances for success! I can't risk wasting another embryo, not mention the cost of an FET. What did I have to lose? Besides the cost of the test, (~$1,000) there would be a loss of time. I could have the test done in October, but my RE is away in November and my parents are visiting in December, so I wouldn't be able to transfer until the new year. Although, there is the hypothetical loss that I could just proceed with my planned transfer, have it work, and possibly be done with this process without making things more complicated.

I read through the research article that was posted on this company's website. In the clinical trial, they evaluated 85 participants with RIF and 25 control patients. A receptive endometrium was found in nearly 75% of the RIFers and 88% of the control group. 29 RIF patients with a receptive endometrium went through a transfer and the pregnancy rate was 51.7%. A non-receptive endometrium was seen in 22 RIF participants, but only EIGHT went through a personalised transfer based on the recommendations from their analysis. Four became pregnant, yielding a 50% pregnancy rate. The author concluded that due to the low number of patients, these results should be considered preliminary.

I had become swept off my feet. The lonely and desperate infertile who was seduced by the latest theory promising answers and results. Yet, what if this was the one? I started stewing about how much I resent being in this position and needing to make these difficult decisions. "Just talk to Dr. Somebody that I Used to Know about it." advised Husband, who was keen to shut me up so that he could go to sleep. I already knew what we would say about it. Limited studies, lack of reproducibility, ambigious findings...Yet he'd be willing to go along with it if I felt so compelled. I reviewed the data and crunched the numbers again. 85 women entered this study and only 4 (less than 5%) benefited from the intended intervention. (15 women who had a receptive endometrium also became pregnant, so the pregnancy rate for the trial was 22%)

It feels like a rational decision, but there is something else contributing to the lingering doubts. At times, it just seems like every decision I make turns out to be the wrong one. A bit reminiscent of the episode of Seinfeld where George observes that every instinct he has is wrong, so Jerry deduces that the opposite must be correct. I shared with Husband that if we proceed with our transfer as planned, and it works, then our formula must have been right. "Yet, if it doesn't work, it doesn't mean that it was wrong" he quipped, displaying remarkable wisdom in his half asleep state. That is precisely what is so fucked up about this process.

Wednesday, 24 September 2014

A Day in My Life

0505  Wake up ten minutes before my alarm.
0506  Tyler senses that I am awake and begins to stir. He assumes that my first priority is to feed him.
0510  Drag myself out of bed.
0514  Feed Tyler, check Facebook to review Newsfeeds from England.
0515  I forgot to shut off my alarm, which wakes up a now grumpy Husband.
0535  Ready to leave the house.
0555  Arrive at the pool. No one has seen me yet. I could turn around and go home.
0635  It's an IM set. I should have bailed when I had the chance.
0703  Waiting for hot water in the showers.
0706  At last! Post work out shower feels so good!
0730  Locker room attendant has to leave, ushered to hurry up.
0740  Ready to depart from the pool with a little extra time on my hands.
          I could get a jump start on my day, or I could hit Starbucks.
0745  Starbucks it is!
0747  No eating or drinking in the new car rule is in effect for at least three months. Sit outside and overlook the Bay while drinking my coffee.
0810  Arrive at work.
1755  Day ends with giving a patient a diagnosis of herpes. I hate my job at times.
1825  Review Cross-Fit work out. Ugh. Burpees. Unfortunately, I've already been spotted. Too late to bail.
1955  Home at last after a minor car accident caused major traffic. Husband has already started dinner and notes that I am just in time to help him with laundry.
1956  A hungry Tyler is glued to my ankles as I set my bags down. Husband hasn't given him his  dinner as he "doesn't do wet food". Wonder how he'll handle baby related fluids if he can't deal with canned cat food.
1957  Feed the little bugger and concede that his food is pretty gross. Angus would only eat canned food that was in slices with gravy and it almost looked suitable for human consumption. Tyler prefers the pate. May try to change this
2000  Hang wet clothes on our drying rack.
2005  Make some zoodles by using a julienne peeler to produce zucchini noodles. Zoodles is much more fun to say.
2008  Look through mail. Misery sent me my prescriptions for next transfer. My surname is spelled wrong on one of them. Fucking A. I've been in and out of that office for the past two years and you can't spell my name correctly! Furthermore, I've pointed out to her that on multiple occasions I've discovered an incorrect spelling. Is this too much to expect? I am merely asking for sharks with freckin laser beams attached to their head!
2009  Glass of wine ends rant. Wonder if Misery is dyslexic.
2010  Dinner is served. Dine with Husband and his iPhone.
2035  Start to clear up plates.
2040  Husband accidentally turns off the kitchen lights while I'm washing dishes. I make a joke about how frugal he is. (Seriously, the guy is the electricity police) He gets insulted and announces that he's going to bed. Suspect his over-reaction is really a ploy to avoid clean up.
2100  Wash all the containers from my lunch box. Wonder if washing baby bottles will be as tedious.
2110  Throw wet swimming stuff in the tumble dryer.
2112  Pack lunch for tomorrow.
2125  Empty gym bag, hang up work clothes. Repack gym bag with workout clothes.
2130  Prepare consent forms for FET#4 at XYZ Fertility Centre. Prior to FET#2, I learned we had to sign a new set of forms with each transfer. Last time, I printed out four copies of the consent forms for each of our euploid embryos and I joked that we should sign a batch of these forms. This time, I decided to do it. I signed all three remaining three copies, but only dated one. If we have to face FET#5 or 6, we'll just have to note the date.
2200  Remove swim towel from the dryer. Select work clothes for tomorrow and pack into swim bag.
Double check to make sure I didn't forget to pack underwear. Arrange swimsuit and swim clothes for easy access in the morning.
2215  Plug iPhone into the charger
2220  Finally in bed at last. Husband is long been asleep, so I check in with email, Facebook and blogs.
~2300 Fall asleep.

Even before our experience with infertility, I was always annoyed with couples who would declare, "we're having a baby, but nothing is going to change!" Um, everything is going to change. Isn't that kind of the entire point? Nonetheless, my own parents told me, "we weren't going to be those parents who revolved their lives around their baby. We incorporated you into our life." I've become fascinated with these 'A Day in the Life' posts from new moms and I think they should be required reading for every expectant parents. Admittedly, they scare the shit out of me. Actually my own recount is pretty frightening, look how much organisation and effort it takes just to get me out of the house!

I haven't spent too much time thinking about how our lives with change with a little bundle of joy. After my second beta from IVF#1 Co-worker issued the warning on how much our life would change in the coming year. So far the only change is that now I'm prepping for a FET where I was stimming at this time last year. Yet, while not imagining any specific situations, I hold a few delusions that let me think I might be able to manage, you know, if this whole implantation and pregnancy thing is actually possible.

I'll want to do this!
I once told my mother that I had no desire to give up my precious sleep to tend to a crying baby, to which my mother countered "I loved you so much that I wanted to get up and take care of you." Effective way to induce a guilt trip. Will all our experienced make me appreciate these tasks and challenges more? Perhaps, but I can also see the novelty fading quickly.

It CAN be done!
In her book, Bossypants, Tina Fey described how irritated she gets when people ask 'how do you juggle it all?' While the question may sound complimentary, she feels the accusing eyes are really noticing 'you're fucking everything up, aren't you?' Still, I look for ways to make it seem possible. My swim group is going to start an evening session. While I was recently on an 8 mile run, not only did I see women and men with jogging strollers, I saw a woman in a boot camp class doing air squats with her baby snuggly attached to her chest.

I'll be MORE productive
I've heard some working mothers described that they've become more efficient at the office. When there's a task standing between you and your kids, or if your daycare centre charges by the minute for a late pick up, you don't waste any time. It's go in, get 'er done, and go home. Avoid the idle chit-chat in the break room. Pack a lunch and eat at your desk while you work. Presumably, this is after the sleep deprived state where one is napping under the desk...

I'll get some help
I know my options are very limited here as my parents live on the other side of the country and my in-laws are on the other side of the world. My aunt and uncle, who live nearby, are dealing with her breast cancer, and my cousins are busy dealing with their own kids. Although, in fairness, we didn't do anything to help with their arrivals, so we don't expect anything in return. However, my mother will be retiring next February, and my father is self employed, so they could come out for a good stretch of time, if they wanted. (Yikes, I feel old to describe my parents as retired).

I have some friends who expressed concerns about their partners' contributions prior to the newborn's arrivals...and then found their fears were confirmed. In particular, a few have commented that their husbands' lives didn't change much at all. I actually don't have such fears about Husband, and I'm not just writing that on the off chance that he's reading this. I know he'll be a very hands-on Dad, and will probably learn baby's patterns and routines quicker than I will. It's the remaining chores that give me concerns.

It has taken eight years of marriage for me to finally realise that Husband will never participate in meal planning. On time, I gave him a cookbook and asked him to select one entree, and I would shop for ingredients. He looked through the book and reported, "anything is fine." This led to a huge argument on whether or not he actually completed his assigned task. Earlier this summer, when I was extra busy preparing for a presentation, he offered to help with the cleaning. I figured he would identify something that is dirty and clean it. Apparently not. He had to be assigned specific tasks. I asked him just to vacuum and dust, but he decided to turn our kitchen inside and out to make it sparkle. I had to spend over an hour helping him finish, just so I could start dinner. I did appreciate all his efforts, but I couldn't stop thinking all you had to do was fucking vacuum and fucking dust... We've decided that our Christmas present to ourselves may be looking into getting a cleaning lady in 2015. Co-worker hired one after her twins were born. "She sucks, but at least she gets to the bathrooms!" She claims the $120 for her twice monthly services is worth every penny in terms of saved time and aggravation.

It gets better
Please tell me it does.

Friday, 19 September 2014

A Trigger for Negative Emotions

After my WTF appointment, I prepared to face heavy traffic on my drive home. I also decided that I would call Myrtle. As my new car has bluetooth capability, I thought it would be a good use of time. I hadn't spoken to Myrtle in a while and she had been trying to get in touch with me to offer condolences for my grandmother's death. Once we had exhausted every topic of conversation that wasn't asking about our fertility, she broke over six months of silence, by asking "so, how is that going?" I remembered her utter insensitivity  after my first FET failure, and simply answered with "still not pregnant, just came back from my doctor." I thought that would be enough to shut her up. Apparently not.

"So, do you even have any eggs left?" she asked. Those words hit like a slap in the face. I thought I might be over reacting, but when I told Co-worker she gasped and put her hand over her mouth. With all due respect to my friends with Premature Ovarian Failure and Diminished Ovarian Reserve, what was so insulting to me is that she doesn't understand that this isn't our issue! As a matter of fact, my ovaries were rockstars during our last stim cycle! (not that it mattered) As I started to explain that actually we have three euploid embryos available, it occurred to me that she has absolutely no idea what that means. Husband, who reacted with a palm to the forehead, was just as irritated. "I really broke everything down for her in the simplest of terms. It was the Idiot's Guide to IVF!" I think she meant to ask if we have any embyros left, but as she doesn't know the difference between an oocyte and an embryo, she has no clue how inappropriate it is to ask an infertile woman if she has any eggs left. It makes me feel as if I'm at the point of needing to search under the sofa cushions for loose coins, although when Husband heard that we had 20 oocytes retrieved, he asked my RE if that tactic were employed.

Although along those lines, she delivered another punch with her next question, "how are you able to afford these treatments?" Once again, I felt a bit insulted. I alone earn close to Myrtle and her husband combined, and Husband's salary is not too far behind mine (yeah baby, I'm the breadwinner). Not that it matters, as Myrtle is a trust fund baby, although most of her money is tied up in investments. That question was being asked by someone who decided against a second child, as up until four months ago, her husband didn't have a proper job. A job we're not sure how long it will last as he's unqualified for the position, as was only promoted because the manager likes him personally. That question was being asked by someone whose fertility related costs were less than twenty dollars. Myrtle spent a grand total of $17.99 for a digital pregnancy test. Just one expense that confirmed she was perfectly pregnant and her healthy gorgeous daughter was on the way. Let that sink in for a moment.

Admittedly, I was in a more sensitive state as I was recovering from her "do you even have any eggs left" comment, but for the first time I truly felt as if I were being judged. As if I were frivolously spending or being irresponsible with our money. I could almost hear Myrtle thinking, you're not going to be able to afford a baby if you ever do have one! Among my irrational concerns is that she'll treat us like a charity case if we ever get to that point. More so, I felt that she was criticising us for being on this path; All Jane has to do is just go home and relax! I know so many people who became pregnant after they stopped trying so hard. Or why doesn't she just adopt -that's free! 

So many potential responses entered my head. Most of them involved a combination of the words 'fuck' and 'you' and 'none of your business'. Rather, I decided to invite her into the mindset of an infertile woman. I told her about how I learned I would be receiving a small inheritance from my grandmother on the night before my beta test. Instead of thinking 'oh, that will be great as we'll be having a baby!', my thinking went to 'that will cover further treatments'. Unfortunately, this just gave Myrtle an opening, "I know you're not religious, but don't you believe your grandmother's death will lead to new life?" Actually Myrtle, we already ran that play. Twice. Didn't work. Thanks for trying.

I know it's so hard for Myrtle (or anyone) to find any comforting words in this situation, and I know don't make things easy for her. Yet it never ceases to amaze me; how is it that she knows nothing about infertility but she has mastered saying all the wrong things? I guess I answered my own question.

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.

Monday, 8 September 2014

The more I learn; the less I know...

The morning after our most recent BFN, I woke up with my arms and legs feeling sore from Cross-Fit, and my head was slightly throbbing from drinking a bit too much wine. As I've done on prior occasions, I had a moment of wondering if my negative results were part of a dream. Maybe I didn't actually test yet and there was still a chance... "Well it's another day, another failed IVF transfer" Husband announced to pull me out from under the fog of my hangover. As the kettle started boiling water for some much needed tea, I sat down with The Google and typed the words 'recurrent implantation failure'.

I found a rather comprehensive review article that was published in Reproductive BioMedicine in 2013. The author began by noting that there still is not a universally accepted definition on what constitutes Recurrent Implantation Failure (RIF), but for the purpose of her article, she included any women under the age of 40 who fails to achieve a clinical pregnancy after 3 fresh or frozen transfers with 4 good quality embryos. So, I'm not sure if I meet that criteria, but I decided to continue reading as she defined that treatment should focus on improving embryo quality and endometrial receptivity.

Regarding embryo quality, she cites that only 30% of embryos will implant. I am presuming this is a global average, as it doesn't account the higher success rates with donor eggs, but we all know that implantation rates with donor gametes will only reach 60-70%. She also noted that as embryologists select the best embies first, lower success rates can be expected with subsequent transfers as the embryos will be of reduced quality. Rather disheartening to see that in print. It's also humbling to accept that despite the top grade and euploid status of my embryos, they may have quality issues. Nonetheless, this is what we have with which to work.

Uterine factors can include congenital findings such as a septum, (been there, fixed that) or acquired pathology such as a fibroid, polyp or adhesions. The presence of fluid in the fallopian tube, a hydrosalpinx, can negatively impact the endometrium and make it unfavourable for implantation. Pregnancy rates are improved once the tube is isolated from the uterus, which creates the irony that fertility is enhanced by sterilisation. She deferred the issue of immunologic factors by commenting that it's "an interesting area worth a separate in depth review" and summarised that there is no consensus on whether or not immunological investigations and treatments are useful. Somewhat similar, some studies have demonstrated a benefit with thrombophilia evaluations and appropriate treatments, while others have not.

The work up should start with a sonohystogram and/or a hysteroscopy. A hystersalpingogram is more sensitive than an ultrasound for detecting a hydrosalpinx, and any suspicious findings warrant further evaluation with a laparoscopy for possible intervention. Regarding the management, she describes "a multidisciplinary  approach should be adopted (interesting word choice) between an experienced fertility specialist, senior embryologist, reproductive surgeon and counsellor. This appointment should not be another 'routine' review." Regarding lifestyle factors, it's not surprising that the data finds smoking is bad, a healthy weight is good and alcohol intake should be limited to 1-2 drinks per week, if at all. Routine use of assisted hatching is not supported by the American Society for Reproductive Medicine (ASRM), but the author reports that it may benefit those with a poor prognosis or two or more failed cycles. The transfer procedure itself should be performed with ultrasound guidance, and a procedure that takes longer, invokes cramping, and requires changing multiple catheters or uses a tenaculum is associated with lower implantation rates. Good to know. I did take note that she did not address increasing the number of embryos at transfer.

Selfishly, I skipped the section on the thin endometrium, as actually, I am starting to wonder if my lining is too thick. More so, I question if my normal appearing endometrium is functional. About ten years ago I met Dr Harvey Klinman, as he presented his recently published article describing his method for testing cyclin E and p27 as a measure of endometrial competency. XYZ Fertility Centre (the site of my embryology lab) lists the Beta-3 Integrin test as a measure they employ (this analysis is also used at CCRM). When I previously asked my RE about Klinman's endometrial function test, he replied that the data isn't consistent. Some patients who lack said markers are able to achieve a pregnancy and others with the proper components still can't become pregnant or continue to miscarry. My case is interesting as I have been pregnant twice, although with the first, my uterus rejected the pregnancy rather early (I attribute my septum as the cause) and the second was due the trisomy, but we'll never know if I could have maintained that pregnancy if there had a normal set of chromosomes. Regarding the action of an endometrium biopsy, the process of inducing an injury and causing a release of cytokine did double pregnancy rates in a trial published back in 2003. This begs the question, do I undergo another scratch?

Based on his voicemail message, I have the feeling my RE is going to steer me in the direction of transferring two embies next time. I'm starting to accept that it's more likely to result in a waste of two normal embryos, than a twin pregnancy, but I've still seen this move too many times before. Couple fails single embryo transfer. Couple transfers two embryos. Boom. Twins. Plus, these are two grade 1 euploid embryos! I needed data, so I googled 'twin rates with two euploid embryos'. My search brought me to two articles that compared a single transfer with an known euploid embryo versus two untested blasts. The first study described that 39 singleton pregnancies were achieved with 60 women doing a single transfer in a fresh cycle (65%). 43 pregnancies were noted in the 61 women who transferred two blasts (70%) but 24 were singletons (55%) 18 were twins (42%) and there was one set of triplets. They also looked at women doing a frozen transfer, and found 15 single pregnancies from 27 women with single euploid transfers (55%) and 13 from 25 women with a double transfer (52%). The 13 pregnancies included 5 singletons and 8 twins.

The second study included number of days spent in the Newborn Intensive Care Unit (NICU) as one of their endpoints. Not surprisingly, they found that the twins born to couples who were in the two unknown blasts group had a five fold increase in NICU stay compared to the singleton babies born to women in the single euploid embryo intervention. (actually there was one baby in the singleton group who was in the NICU for over one hundred days, if he or she were excluded as an outlier, I think the ratio would be more than ten-fold.) The authors concluded, "enhanced embryo selection with a single euploid embryo was associated with high reproductive potential without compromised delivery rates and improves chances for a healthy term delivery after IVF." Dude, you're preaching to the choir... I still wasn't finding answers about transferring two euploid lasts, so I searched a little more an uncovered another article that was also comparing a single euploid blasts versus two unknowns. The author admitted that their study design initially included transferring two euploid blasts, but it was associated with an "unacceptably high twin risk." I'm presuming that intervention group was stopped early. Of course, the participants in these studies are IVF virgins, not three time losers such as myself.

Next, I took a look at the 2013 ASRM guidelines for the maximum number recommended to transfer, and noted that they do not specifically address euploid embryos, but they do make a distinction between "favourable" embryos and "all others". Presumably, my euploid embryos would fall in the 'favourable' category, but when I read the fine print of the foot note "favourable" was defined as "first IVF cycle, good embryo quality, excess embryos available for cryopreservation, or previous successful IVF cycle." So now I'm not sure if I'm considered 'favourable' or 'all others'. Anyway, for women in my age group, they recommend a maximum of  2 favourable blasts and 3 all others. Then, I saw a note that one additional embryo may be added to all age groups and all situations when a patient has two or more previous failed fresh cycles, or a less favourable prognosis.

That word fresh is the distinction. Technically, I haven't failed a fresh cycle. My RE admitted he didn't have any explanation as to why I scored with a fresh transfer, but failed with two frozen embies. Theoretically, conditions for implantation are more ideal with a frozen transfer. I revisited this notion with my RE when he called with my day 5 embryo report. He didn't feel a fresh transfer was indicated as my fro-yos had thawed well, and the risks for OHSS were too high. Yet, things aren't always what they seem. Maybe I could consider a minimally stimulative IVF cycle to gain a few embryos that could be employed in a fresh transfer.  Of course, this also involves surrendering any benefit from CCS testing, as well as sacrificing a single embryo transfer. Grrrr! 

I felt more depressed and discouraged after researching recurrent implantation failure, than I did after reviewing recurrent pregnancy loss. Unless, I happen to have a hydrosalpinx which could be clipped, there really isn't an identifiable explanation. Maybe, it's just as simple as I've just been really, really, really unlucky and the next one magically will work.  Oddly, I've been thinking about a clip from an interview with Jaime Foxx at the time of the premiere of his movie Ray. He described that while preparing for the role, he played with Mr Ray Charles and noted that during one session he became angry when Jaime missed a few notes. "Son," Jamie recalled him saying very sternly, "The right keys are underneath your fingertips. All you have to do is find them!" The actor felt that what Mr Charles was really trying to teach him, was that in life the right choices, the right directions are already there in front of us, and we just have to find them. So begins our quest: the right formula is out there -we just have to find it.

Tuesday, 2 September 2014

Elite Level Status

I believe that everyone who finds herself on this infertility journey must ask: how did I end up here? However some of us find ourselves asking: how did I end up here?

I remember when Myrtle first announced her pregnancy, I wasn't so much jealous of the fact that she was pregnant, it was that she made such quick work of it. After all, at that point in time, we had been trying for six long months! By the time we had a diagnosis of moderate male factor infertility, I wasn't bothered by her speed, but by the fact that she conceived without intervention.  I know my surprise spontaneous BFP  fostered some hapulosy from Co-worker as she had a negative home test 10 days after her planned final IUI. Ah, the dangers of testing too early, as her beta was 155 just four days later. In turn, I would become jealous of her IUI success as I went through five failures and knew I would be facing the dreaded IVF process. After my first transfer ended in a miscarriage, and my second two failed, I started to envy my cousin, who was a first time IVF success with a subsequent spontaneous conception. It feels like Alice in Wonderland, the further you fall down the rabbit hole, the more your perception changes.

I feel as if my membership in The Infertility Club has been upgraded to Elite Level status. I won't reveal the inclusion criteria; you know who you are if you're at this stage. The perks of getting to this point? A personal call from my RE expressing his disappointment. As usual, he presented the data, which is where he earns his money, but is not the most compassionate approach. Transferring only one embryo does reduce the risk of twins, but it's also associated with a higher failure rate. He added "don't beat yourself up about it." So is he subtly implying that I'm to blame for the failure because I elected for a single transfer, but that I shouldn't be too hard on myself? Was this an 'I'm sorry you're an idiot' apology? Husband listened to the voicemail message and thought that he seemed sincere, but is just very socially awkward. "The guy could talk his way out of getting laid" he observed. It's always interesting to learn a man's perspective.  

More than being disappointed, I feel frustrated. I'll ask again; how can my day 3 'your embryos seemingly suck, so your best chance is to just shove some up your uterus' desperation transfer result in a pregnancy with a lethal anomaly, and two grade 1 blasts (one proven eupliod) and one grade 2 blast with assisted hatching can't even generate a chemical pregnancy? I want answers, but I know that they may not exist. I feel as if there is something broken with my body. I'm not yet convinced that increasing the number of embryos on the next round is the answer. While we haven't had the gestational carrier conversation and I don't know if we're in a position to entertain the thought, I'm afraid to waste any more embryos in my uterus. More than anything else, I feel so discouraged right now.

I've been drawing inspiration from some fellow Infertility Elite members who have finally achieved their success, I still have some hope that I may join them, albeit fading. I do know how fortunate I am to have three more normal embryos (plus we have a bonus embryo with inconclusive testing). I also know that I sound like an asshole to lament that it's frustrating to know that donor gametes or embryos won't offer any advantage in my situation. This is it for us. It just feels like pursuing more transfers is representing Albert Einstein's definition of insanity: we're repeating the same actions and expecting a different result. While I'm still so terrified of transferring two or more embryos and achieving a twin pregnancy, it's starting to register that we may be too infertile to become pregnant with twins. I can imagine that my RE probably has the words unrealistically concerned about the potential for twins jotted in his notes. Again, I acknowledge that I sound like an asshole as some fellow infertiles would love to become pregnant with twins. As I never expected to have multiple miscarriages and repeated failures, I feel it is daft to merely hope that I wouldn't encounter the potential complications with a multiple gestation.  

At times I think back to my initial meeting with my RE, when he projected our odds with IVF to be "good" at 40%. I made a crack questioning how something with a greater failure rate could be considered good, but I don't think I understood the implications at that time. I really didn't see myself doing IVF. I guess a part of me thought it wouldn't come to that. Maybe I would be one of those lucky women who magically conceived after merely consulting with an REI. Well, I sort of was, but only for about five minutes. After miscarrying my spontaneous conception, I felt encouraged about my chances with assisted reproduction. When IUIs didn't work, I could fall back on the IVF option.  As my second cycle was so much more improved, it seemed reasonable to expect that it might actually work.  Now I wonder if I'll be that case that Misery and New Girl will always recall: Remember Jane Allen? 14 eggs retrieved, all fertilised -you almost never see that! Yet she still didn't become pregnant...

I'm starting to come to terms with the fact that it's statistically more likely that I'll be on the side of the 60% with failed treatment. I'm moving beyond my former OMG! I am never going to have a baby! overly dramatic self, to the more practical actually Jane, you may not be able to have a baby...and it will be okay. That's the other reward of Elite Level membership to the Infertility Club. A fabulous life still awaits.