Introducing Hallmark rejects...by Mo and Will

Inspired by the miscarriage e-card Mo found last week, we have decided to begin an occasional, off-color series of loss and infertility "cards," created by us. Who knew coming up with these could be so fun? Feel free to let us know if we take it too far.

Mo and Will

Meet the newest member of Mo and Will's family

We got a puppy this weekend! She's a girl! She has white paws and a white belly and a little wrinkled body and the most adorable floppy ears!

We are thinking we will name her Moxie, which according to the Merriam-Webster Dictionary, means 1.) Energy, pep. 2.) Courage, determination. 3.) Know-how. Per Wikipedia: This neologism has taken on the meaning of "courage, daring, energy, vision" in American English. As in, This girl's got moxie!

We are very busy (and a little sleepless!) helping Moxie settle in to her new home. It is wonderful for us to have someone to love.

Welcome home, little one!

Sick sense of humor

My husband Will and I are developing a twisted sense of humor. Maybe it's a way to cope with our five miscarriages, but over the past two years, our jokes have gotten increasingly dark. We laugh together quite a bit, but the jokes are getting to be a little off. I think it's actually a sign of progress that we can share a good chuckle, either making fun of our own horrid luck or using humor to express our exasperation with various family members (who always mean so well but sometimes say the gosh-darndest things.)

I've grown so comfortable with our increasingly weird shared humor that I've begun to lack good judgment about what others might find funny. You know, like normal people. I'm starting to notice that only those who are grappling with infertility seem to appreciate my IVF/miscarriage humor.

I had drinks earlier this week with a friend who after several canceled IVFs is about to move on to donor egg, and we had a grand ole' time, laughing our heads off about the ridiculously absurd moments with our feet in stirrups, the clueless things people say, our envy toward those with accidental pregnancies. The whole nine yards.

Then last night I had dinner with another friend, one who has known me for several years, and who knows my history of IVF and five pregnancy losses. And we had some real heart-to-heart moments, which was great.

And then I cracked a few really funny zingers about miscarriage and mangled chromosomes. We're talking practically stand-up material here.

Nothing. Not a single smile. Even though I know this friend shares my dry humor on other topics.

Hmm...perhaps she didn't get it?

I tried another one.

Nada.

She finally said, "Mo, I can't laugh with you about this. I just can't. What you say is really funny, but your situation is so awful that I just can't."

Oh. Right. Not funny. In fact, very, very sad.

Oops.

I acknowledged that I'd put her in an awkward position. Should she laugh? Not laugh? It must have felt very confusing. I promptly apologized.

And yet, I am still pulled to the dark side.

I just ran across this picture on a blog as an example of an e-card that never made it into print. And I howled with laughter:

I found it hilarious. Why? Because it touches on the fact that 1.) There is really no "good" side to loss and people's attempts to point out the silver lining are just doomed to piss you off and fail. And 2.) It highlights the point that there are no cards or other rituals to acknowledge pregnancy loss, just as there is no space to mourn miscarriage in this culture (unlike in say, Japan). And for that reason, our repeated losses are sometimes not acknowledged and have often created awkward silences in which both I and the other person feel badly.

So OK, OK! I get it. It is probably inappropriate to share this card with friends who haven't miscarried or struggled to conceive.

I will be a good friend and act with restraint.

Instead, I will share it with you.

Thanks for being there.

Mo

Fruit cake and Endometrial Function Testing

So I went in to see my RE yesterday and had an endometrial biopsy done so the tissue could be sent to the researcher at Yale who pioneered the Endometrial Function Test (click the link to see him compare the endometrial lining to a fruit cake.) I've pictured my endometrial lining looking like a lot of things. But never quite like this:

The biopsy hurt, but not too badly (about the same as the coculture biopsy), and it was over in a minute or two.

The idea of this latest test is to get a sense of my lining and whether it is a receptive place for a little embryo to grow. So a snippet of my uterine lining is now winging its way to the aforementioned Yale researcher so he can look for things like the progesterone receptor, and mouse ascites Golgi mucin, and cyclin E (which shouldn't be there), and also to check and see if leukemia inhibitory factor, αvß3 integrin, HOXA-10, and p27 ARE there, because they should be. Got that? Me neither. Totally confused.

Apparently results will take a couple of weeks, so we'll see what said researcher thinks soon.

I have to say, I'm not holding my breath. Instead I'm moping around a little bit.

I do hope that something informative will come out of this, I really do. But at the same time, this is starting to feel a little bit like an exercise in the absurd. Know what I mean?

Mo

Call from the geneticist

I finally spoke to the geneticist on the phone, and I want to cry.
She said the case conference was attended by staff from the cytogenetics lab, several geneticists, IVF folks, and at least ten genetics counselors.
You might think with all those smart people in one conference room, there would be some answers.
But if you're thinking that, you'd be wrong.
The consensus of all of this brain power? In terms of evidence based medicine's take on this, our risk of another aneuploidy is the same as the population risk for my age group (age 37), so something like a 1 in 150 or 1 in 200 chance. This is very hard to swallow and everyone seems to question whether this is or is not accurate, but it's as far as medical science can get us in terms of data-driven statistics at this time. Not very satisfying.
We have normal karyotypes, so that's not the problem. Any increased risk from radiation exposure secondary to all of the medical imaging I've had cannot be quantified (Direct quote: "No one knows"). Going back to the old tissue and making an attempt to determine the parental contribution of aneuploidy (i.e., was it the egg or the sperm in our three chromosomal losses) would apparently be getting pretty out there in terms of lab expertise, and although it can be done (we asked), it would be lengthy and expensive, and they really think the problem is with my eggs ("It would really be just an intellectual exercise").
Basically, the geneticist said that our problem could be just age-related and/or we could have a spindle problem (the spindle helps the chromosomes from the egg and the sperm line up so they touch in the right places), and/or a docking problem, and/or a problem with the gene that controls the spindle (and this gene has not been discovered yet - ha!), but these are all theoretical guesses and there is no way to test for them at this time.

"One of the big problems here," she said, "is the Why. And no one will be able to prove any of these hypotheses."
From her chart note: "There are several forces at play. One is the desire to understand the basis for their history of reproductive loss, which I think is reasonable. There does not really seem to be a satisfactory explanation" (emphasis mine).
And that's the rub. It feels like the bottom line is that we are not going to get an explanation. And we aren't going to know what our real risk is going forward.
Apparently, there were some at this conference who asked why we sought "more" genetic counseling. The geneticist defended us to them, saying that of course we need answers, that we are grieving and trying to make sense of why this keeps happening to us. And what is the harm in trying to get more information? Hear, Hear geneticist! You tell them!
The geneticist said she ran the information over and over in her mind during the weekend, trying to make sense of it. She said that she's only met us once, but our history is terrible, and that we need to think about how much more of this we can go through. She said she kept trying to think about us as human beings, not just an egg and a sperm. And that the financial, personal, and physical toll this must be taking on us is great. She said twice that she was amazed that we could tell our story without breaking down into crying, then said (both times) to herself, "You must cry at home. Your story is so sad." Believe me, geneticist, we have cried a lot.
She recommended that we begin moving toward a solution - pick a direction to head in and also pick a point at which we are going to stop. In the meantime, she suggested we begin pursuing other avenues to build a family concurrently, such as using a donor egg or adoption. She said we need a way out of this sooner rather than later and that we should really consider pursuing options simultaneously (e.g., try on own, but start looking for a donor or sign up to adopt) so that we can begin our family one way or another.
At the end of the call, she asked me to keep in touch and let her know what happens. "We are all really very interested," she said, "and we are hoping for a good outcome."
"Thank you," I said. "So are we," and hung up the phone with tears in my eyes.
I'm not sure why I am so sad, except that when she went over the options (1. try on your own; 2. do new IVF cycle with PGD; 3. do IUI), it sounded just like my own ruminative thoughts circling around and around with no answer in sight. And I think I'm now facing the fact that we're not likely to get any good answers. Ever.
More than that, it's hitting me like a ton of bricks that no one is going to give me permission to stop. I think that without realizing it, I've been unconsciously hoping that someone will be able to tell us that it just is not going to happen, so that I can stop with a clear conscience that I didn't give up too early, just when we were about to succeed. Somehow having to just make an arbitrary decision about when to stop feels like it makes all of this more my fault than it already feels. Without this "permission," I'm afraid I'll feel that not only are my eggs crap, but I'm a quitter too.
I really appreciated the time the geneticist took with us. And especially the fact that she tried to consider all of the issues comprehensively, including the reality that Will and I are two sentient beings, not just a clump of cells in a petri dish.
At the same time, I feel filled with longing and grief that we will probably never find an answer as to why we've had so many miscarriages, nor will we get a good read on what is the best direction to go in from here. Which feels like another loss. Nonsensical, I know, but there you have it.
Mo

Sisters

My sister was here this weekend for a visit and it was lovely one-on-one time (Will is in Europe for work this week). She and I are very alike from our looks, to our mannerisms, to our sense of humor. We look so similar that people comment on it, immediately recognizing the relation. Even here in NYC, where no one comments on anything, two people this weekend said, "That must be your sister! She looks SO much like you!" And she does. And I am grateful for this connection. She is much younger than me (8 years), which makes this even more flattering.

Something about having my sister with me all weekend was so centering, so healing. We spent the weekend laughing, talking, sharing. Having her here was like a breath of fresh air after not breathing for far too long.

The geneticist and I are playing phone tag but hopefully will catch up later today, and tomorrow, I am scheduled to have part of my endometrium removed for the Endometrial Function Test. So the quest continues, but for once this weekend, it felt like I could maintain the right perspective, and not be consumed. I only hope I can hang onto this newfound sanity.

Thank goodness for little sisters. I am so glad she's in my life.

Mo

It's not exactly hope, but it's something

The universe must have heard my despair over the past two days because this morning I received a surprise call from the geneticist's office that she had a cancellation and could see us today. So we went, grateful to get in before October and expecting a thirty-minute consult.
The M.D. attending, a resident, and a genetics counselor met with us as a group for 1.5 hours. The attending took an amazingly thorough history, explained a number of things, and seemed very interested in educating us and in getting to the bottom of our situation as much as possible and offering us tangible recommendations.
You could see the cogs turning in her mind as we told our story and produced our records. I was slightly embarassed (although she said it was extremely helpful), that one of the things I'd brought was a written summary of our pregnancies and IVFs (adapted from a link on this blog, no less). She asked a ton of questions, humored ours, and really validated where we are at emotionally.
And she broke things down into categories. The "what we know" and the "theoretical."
What we know: We've had two trisomies and one triploidy. We've had three failed IVFs, with many embryos transferred. Plus two other untested miscarriages.
Theoretical: We've been told to presume chromosomal problems for the lack of implantation and for the two untested losses. She said maybe, but maybe not.
One thing she cleared up right off the bat is how this latest triploidy is different from the trisomies. She explained that the mechanism that produces triploidy is unrelated to sequencing errors that cause the trisomies and is most likely two sperm fertilizing one egg. And in that case, the three sets of chromosomes were all in the right places, there was just an extra copy of all of them (hence XXX 69). That is why this latest miscarriage is truly not adding to our risk and is a bad luck event. It is not another disjunction during meiosis, it is entirely different. We finally understood this (or maybe Will had understood before, but *I* finally understood it). She took an incredibly thorough family history, going back to our grandparents, and seemed shocked that no one had done this before.
We also talked about my cancer history, and she seemed genuinely open to that having caused a chromosomal issue, but she expressed puzzlement as to what specific mechanism would have resulted in oocyte damage. She left the room and called a lymphoma genetics expert at Memorial Sloan-Kettering to consult with him and came back and said that there is no apparent linkage between recurrent aneuploidies and the chemotherapy regimen I had. The many CT scans, gallium scans, and PET scans I have had over the past ten years are potetentially another matter, but one that is hard to quantify. (She was slightly aghast that they used to give me neck, chest, abdominal, and pelvic CT scans every two months for the first year of my remission).
Ultimately, she said that she will present our case at an interdisciplinary team meeting later this week that will include obstetrics, IVF doctors, and other assorted genetics folks. She will then call us with a summary of their discussion and recommendations on next steps.
I'm trying to steel myself for the fact that there will almost certainly be no magic answers from this but it was so, so helpful to get to ask all of our questions and be able to talk to someone who is an incredible re searcher, excellent teacher, and gifted clinician. We'll see what the team has to say.
So for now, we wait. Today was a little bit of a gift. And it came just when I needed it most.
Mo

In the midst of it

It's official. I'm in a funk.

I have transitioned over the weekend from trying to obsessively problem-solve this miscarriage issue to a crashing sensation early this morning that hope is running out. All weekend, I tried to figure out, make a decision about PGD or CGH, but then in the middle of the night last night, I awoke and just thought, What's the point?

So we do PGD or CGH and the embryos are all abnorm

al. So then what? Does that mean that ALL of my embryos are abnormal? Probably no one can tell me that. Do we just stop then? Adopt? Find a donor? Or do we still think we need to try again, because hey, it's just 6 or 10 or 12 embryos, right? I've got lots more in there, and there's always that seductive (and increasingly sinister) thought creeping in, Maybe if we just keep going there's one good one in there somewhere...

Or we do PGD or CGH and one or more of the embryos are normal. So then what? We have had 14 embryos transferred and only two took. Two aneuploid ones. Were they ALL abnormal? Maybe, maybe not. So in this optimistic scenario, we transfer the normal one/s (now that we've damaged them with these procedures) and hope for the best. Except, thing is, I think the likelihood of pregnancy is almost nil. You see, I'm plumb out of hope. Five IVFs at a top clinic have gotten me nowhere but sad and strained and remarkably poorer. So I can't even imagine that I'd get pregnant and stay pregnant.

In the middle of the night, it felt like, who cares if all of our embryos are aneuploid or not? Whether the embryos are or are not chromosomally normal, IVF has decidedly NOT worked very well for us (not that natural pregnancy has either, but hey, at least it's free).

In my mind in either scenario, we're out $30k(ish), still have no baby and are left with dwindling financial and emotional resources to try to get one via adoption or donor. Like we're no closer to moving on and out of this sad and difficult place. A place I am so, so ready to move from.

I've also been having strange dreams.

I dream that I adopted my sister, who in real life is almost a decade younger than me, but in the dream was a four-year-old toddler. I had all of these baby clothes I kept trying to put on her and they didn't fit, baby gear that I wanted her to play with that she wasn't interested in. I was thrilled to have her and know that she was mine and yet, she was too big and bulky and not the little baby I was supposed to have. I awake, feeling unsettled and filled with longing.

Another night I dream that I am having strange gynecological procedures done. The goal is for me to get pregnant, but everyone on the medical staff is standing around looking sympathetically at me on the table, somber and sad. I know that I will not get pregnant, and I think they do too, and yet we were going through the motions with these uncomfortable procedures. I awake, anxious, depleted.

Will says I am paralyzed by too many options. And maybe he is right. Funny thing is, even though I know it's not true, I feel like I don't have any. I guess, if I were being more honest, I just am not wild about any of them. I'm not a gambling person, but the odds don't look good to me.

Mo

RE meeting: sticky wickets

We met with the RE today to discuss the genetic results from miscarriage number five. He wasn't in the best mood and pretty much said nothing has changed since the last time we met with him after our fourth miscarriage in May. That triploidy was a random event, not age-related, and not likely to repeat. He said we're in the same boat as before, faced with the same decisions as we were before. He seemed to want to leave it at that. So I asked if we could discuss all of the options again, and he said ok, not enthusiastically, but ok. I was hoping that talking about our options might help create some clarity.

Unfortunately, clarity can be hard to come by.

A few things that were decided:

Despite my longing for a miscarriage wizard, we currently feel that since everything tested is coming up chromosomal, we aren't going to pursue immune testing just now (although I have to say, Dr. Mary Stephenson in Chicago and Dr. Garcia at Penn did really peak my interest). We've already done a full recurrent miscarriage work up here and all was negative...I also spoke to a physician at the recurrent miscarriage clinic at Yale and told her the quick version of our situation, what's been done, and where we are receiving treatment, and she said Yale would not have much else to offer, except for one thing that you'll read about below (and from talking to a number of other academic OB peeps, it sounds like the academic miscarriage clinics tend to be similar in their offerings). Given that we have a clear idea of what went wrong for the three losses we were able to test, at this point we aren't going to look at more controversial, unproven tests and treatments (e.g., IVIG).

Based on one of your comments yesterday (and thank you for all of them!), we made an appointment with a geneticist M.D. here, which will be in early October. Just to get her take on our situation and to find out if there is anything else we can do or should consider. So we let the RE know about that. He seemed to think that was an ok idea (again, not enthusiastic, but didn't shoot it down).

And we did decide with the RE that I will have an Endometrial Function Test in a little over a week just to be sure there are no lining issues in addition to our other problems. This is one of those "just to be on the safe side for the future" sorts of moves. The physician who does this is a placental and endometrial pathologist at Yale (who even knew there was such a specialty?!). We've been considering this test for a while and it was the one thing the Yale program has to offer that we haven't already done.

Oh, and we're also both now taking high doses of folic acid. Low folate is associated with trisomy 21, in addition to neural tube defects, in some studies. So given that there is almost no risk of toxicity, we're adding this to both of our repertoires in the hope it might help and won't hurt.

So we did make a few decisions. But then we were left standing smack in the middle of the confusing morass of the bigger picture: the where to go from here. I'll tell you, it's a sticky wicket.

For the future, we discussed the following options:


1. IVF with PGD at our clinic
Pros: close to home/work. Good clinic. Comfortable here. Can test at day 3 so even if don't have blasts can get info. Transfers fresh embryos, so hopefully better.
Cons: Only tests 9 chromosomes (but would have caught all of our problems so far). Transfers fresh embryos while stim levels are still high (some docs say may hurt implantation).
Unanswered questions: Is PGD more or less traumatic to embryo than CGH/Microarray? How high is risk of mosaicism in a day 3 embryo?


2. IVF with CGH or microarray in Denver
Pros: Good clinic. New, potentially better treatment. Can test all chromosomes. Transfer several weeks after vitrification so body can return to more normal hormonal state (some docs say this can help with implantation)
Cons: Far away, inconvenient. More expensive. Emotionally taxing. Need to get to 5-day blast stage, so if that doesn't happen, whole cycle is a waste (this one really scares me as we haven't done so well on this front in the past). Cutting-edge, experimental treatment, so could turn out to be worse than standard of care. Uses vitrified embryos, which some docs say is worse than using fresh.
Unanswered questions: Is CGH/Microarray more or less traumatic to embryo than PGD? Is there lower or same risk of mosaicism in CGH v. PGD? Will I make enough blasts to make it worthwhile to test? Will we use up all of our financial and emotional resources this way? Will this be so taxing to do that after a single cycle we will feel we are burned out and just need to stop?


3. Highish dose stims and IUI at our clinic with goal of creating 4-6 follicles (I'd like to be stimmed even higher, but my RE said absolutely not because of risk of OHSS. No one is so worried about higher order multiples with us anymore...after 14 transferred embryos (and 37 embryos created in all), all we have to show for it are two dead, aneuploid babies)
Pros: Lower cost. Less invasive. No surgery. No transfer. So hopefully easier emotionally? No manipulation of embryos so some docs say lower risk of aneuploidy. Basically, the idea here is to just increase the numbers on the chance that one of them might be normal... looking for the needle in a haystack.
Cons: Can't test embryos.

And of course, maybe it goes without saying, but throughout all this, we will keep trying on our own. Hey, you never know. The RE encouraged this route as well.

And yes, at the same time, we are educating ourselves about adoption...reading, thinking, and feeling our way around about it. And yes, donor is still another possible option for down the line...

"This is so hard," I said to the RE as the meeting was winding down. And he said, humanity peeking through for a moment, "I know. I'm sorry. It's hard for me too. I want to be able to make it better. I want to be able to fix it." So maybe he feels almost as helpless and frustrated as we do?

Will and I dashed through the rain together and sat for a few minutes in my office after the appointment (my office is two blocks away) to regroup. We discussed the meeting and our thoughts. Apart from agreeing that our RE was not a happy camper this morning, we felt no more clarity about the situation.

The RE's parting words were: "Just tell me what you want to do, and I'll do it."

Ah, if only we knew. Around and around and around we go. We still don't know what direction to take. We're grateful that at least we have a few options.

Mo