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 abnormal. 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

Genetics are back

We would have had a girl. She had a triploidy: 69, XXX (yes, that's right. 69. XXX. Now, knowing my luck, I'm going to get a bunch of hits from people looking for porn. Sigh). But basically this means our little girl had three full sets of chromosomes instead of the usual two. The chromosomes would look something like this:



So far, my RE has said by email: "Random event. Not age-related. Not likely to repeat. Not compatible with life."
Wonderfully fast response time with the email, and the info is much appreciated. But he's kind of the king of brevity, no?
At the moment, I am relieved to find out there is nothing I could have done differently, nothing I did to harm the baby. That helps to know. Enormously. At the same time, I am stunned that we're having another random* and unlikely* bad event.
Just to review, here's the line-up of pregnancy disasters over the past two years:
Pregnancy number 1 (9 weeks, after IVF): monosomy x and trisomy 21
Pregnancy number 2 (7 weeks, natural): lab loses sample (aarrrgh!)
Pregnancy number 3 (5 weeks, natural): trisomy 16
Pregnancy number 4 (chemical, after IVF): too early to test
Pregnancy number 5 (9 weeks, natural): triploidy
Oh, and in addition: 5 IVF cycles with 14 good-looking embryos transferred. Fourteen!!!
Are we really unlucky or is it just me?
We meet with the RE tomorrow to discuss options. More to come.
As always, we welcome your thoughts. It helps to know you're out there. And maybe one of you will have an idea we haven't thought of.
Mo
*How often do "random, unlikely to repeat" things have to keep happening to not be random and unlikely anymore? And is it too much to ask for some random good things happen occasionally?

Where I've been

I've been away from the blog, burrowed down into myself, trying to remember what my life was like before we started trying to conceive, trying to reconnect with my husband Will, trying to reconnect with my former, happy self.

We've been in the midst of a lot of traveling, a lot of processing of our five losses, thinking about the future. Just sitting in the I-don't-know-where-to-go-from-here place we find ourselves in. I haven't been writing because so much of this has been on a not quite verbal level. And Will has not really been ready to move forward just yet. Truth be told, probably neither am I.

I have been moving toward a place of being more truly open, for the first time, to all possibilities. Depending on the day, I'm imagining adoption, imagining donor egg parenting, imagining trying again. I've also been doing my homework on recurrent miscarriage (more on this in future posts), trying to educate myself. If an answer is knowable, I want to know it. If it is NOT knowable, I want to know that too, so I can make peace with the not knowing.

As part of trying to reconnect with my former pre-trying-to-conceive self, I bought a bicycle yesterday - and today, I biked to work. It felt fun, active, slightly risky - ok, to be honest, fairly nervous-making - given the big city I live in. But I felt vibrant and alive. Like I'm not just waiting for something to happen, waiting for a baby to come into our lives. Like I'm out there living my life.

A brief reconnection with the woman I used to be. It was nice to catch a glimpse of her again.

Mo