The Colorado genetic counselor rocks

Thanks for all of your blogoversary wishes. We are ready to look forward to the coming year - and hope that there are fewer disappointments and more successes - please! Loved your comments reminding us to focus on what's important - our love for each other, and to be mindful of the accomplishments the last year has contained. We're with you guys - may this be the last year that this is an infertility blog!
So, finally, to fill you all in on the rest of the Colorado visit...
Our last meeting of the day was with Danielle, the genetics counselor. I'll be honest - I really didn't want to go to this. I mean, I spent an hour and a half with an M.D. geneticist in New York just a couple of months ago. What could this counselor possibly add? That said, once we met Danielle, I liked her immediately. And what she had to say perked up my ears rather quickly as well. We were drawn to Colorado because of their microarray technology. She said, however, that after reviewing our files, she'd spent the day meeting with the scientific director and making calls on our behalf because she felt that microarray wouldn't be enough for us, given my cancer treatment history and the fact that our losses have included both trisomies and polyploidies (overachievers, us!).
Basically, she said that microarray can only detect trisomies. Apparently, the way the technology works, microarray looks for alterations in the patterns of chromosomes - so one more or one less of a particular chromosome, a heterogenous problem. Microarray does not pick up polyploidy - because in this situation, there is an extra set (or sets) of every chromosome. And so the test reads it as normal, since it's a homologous defect across the entire set.
Who knew?
But surely, we're not the first couple to ever cross the Colorado Clinic's threshhold who's had a polyploidy plus a trisomy? I asked this, and Danielle assured me that although it is unusual, we are not.
But she said in our case (lucky us!), they were worried the polyploidy problem (usually a 1 in 1,000 occurrence) might have a tendency to repeat.
Hearing this, part of me was like YES! Finally, someone agrees with us that there is something unusual here - that these silly population statistics may not apply to us! This part of the information was super validating and welcomed. At the same time, I also had a Oh no, we are so f*cked up sort of reaction.
Bottom line, according to Danielle, we will need to do both microarray and FISH screening (the type of screening they use in PGD) to look for both trisomies and polyploidies. Because they do not want me to transfer embryos back thinking they are normal and then find out that they aren't normal after all. So they want to do a single biopsy of each blast (should we be so lucky to get blasts), split the tissue from each blast and send half of it for FISH and half of it for microarray.
Sounds good, right? The only problem is that each of these tests costs approximately $5,000. So it would add an additional $10k on top of the usual ridiculous IVF fees.
Ha. Ha. Ha.
Before we both fainted, Danielle quickly said that the Colorado clinic would never expect us to carry all of this cost and that they were already negotiating with the labs involved to waive fees so that we could have both tests run for no additional cost. In fact, she waived her $150 fee that day to get us started down the road of savings and said they were going to figure out how to shave $5,000 out of things somewhere so we don't foot the bill.
This was our final appointment of the day and we after we finished speaking with Danielle, we got into our rental car and drove directly to the airport to catch our flight home. What a way to finish out the day.
Our final impression was Wow. They are really thorough and have thought about our specific situation and what would be best for us. They are really looking out for us. Needless to say, we were impressed.
We'll keep you posted on what they're able to work out for us.
Mo

Meeting with the Colorado wizard

The first thing that struck us as we walked in the front door of the Colorado clinic was the attention to detail - each magazine, every plant, every tile - down to those around the edges of the walls, was perfectly positioned. There was no clutter, not even on the receptionists' desks. Information flowed efficiently between staff members. It was obvious that someone had put a lot of thought into everything from the design of the building to the systems of how various levels of staff communicated and how patients were funnelled through the clinic to reach their appointments. It was quite something.

After meeting briefly with a nurse, we were led into a consultation room. One entire side wall was lined with copies of research articles available for patients to take. Immediately this gave the sense that this clinic desired us to be informed about our situation. In detail. Which is very different than my New York RE (who I love, but who tends to be rather vague on the details, leaving me to go dig them up myself in the medical library).

Dr. Schl. entered not long after we sat down, wearing scrubs beneath a lab coat. And he got right down to business. We filled him in on everything that had happened between the February phone consult and now. Two more IVFs, two more miscarriages, diagnosis and surgery for stage III endo, etc.

And he basically toed close to the line of what he had said before on the phone with us in February. Except he said now we have a bit more data from the two additional miscarriages. His basic message was that we probably don't make any normal embryos, and that whether this is due to my treatment for cancer or some other factor is something we’ll likely never know. He said that through cytogenetic testing, we've been able to demonstrate these abnormalities three times, but that the only way to know across the board for sure is to look at the embryos themselves.

He was complimentary of our clinic here in New York. Said he knows all of our doctors and has respect for them and that if we’ve done five cycles at the clinic we've been at with no baby to show for it then we probably won’t end up with a baby with him either, because they’re really good at my clinic. I appreciated the confirmation that our clinic is one of the top ones, but of course, hearing that we’re likely screwed was not exactly what I was hoping for.

He spoke calmly and in a low tone throughout the meeting. He seemed pretty unflappable. He wasn’t nervous, wasn’t trying to sell us. In fact, at first, Will and I thought he was trying to dissuade us. He said something to the effect of “You’ve done 5 IVFs. No one can say you didn’t try.” This meeting was the first thing scheduled in our day of appointments and we looked at each other and considered just calling it a day and catching an earlier flight back.

Ultimately, though, Dr. Schl. stated that it was reasonable to give things one more try and that this would give us very important data - and maybe a baby. He seemed to think it was much more likely that we would end up with data leading us to choose donor egg, but left open room for him (and for us) to be surprised. And basically he said we’ll have good information no matter what happens if we cycle. If we cycle and I don’t even make blasts, he says that’s our answer right there – go on to donor – our eggs are too damaged to even get to day 5. If we do get to blast, we can test them and then we’ll know what we’re dealing with. He also said that it was difficult in my case to know if I can get to blast because my clinic has only ever tried to go to blast the first time with my eggs (and that cycle I did transfer two blasts and get pregnant). Especially since we’ve done coculture the last two times, which can only grow embryos to day 3, we really don’t know what my embryos are capable of. Interesting. What I most liked to hear, though, was that if I have a good number of eggs and don’t make any blasts in the Colorado clinic, then we have our answer. Maybe not an answer we like, but an answer.

When we asked him his thoughts on doing a high dose IUI, he said he thought it was not a good idea. That if we didn't get pregnant, we wouldn't be able to pinpoint why and if we did get pregnant we were just rolling the dice again - and he suspected we would likely miscarry again and spend months in the getting pregnant, being pregnant, and becoming unpregnant process. He felt that with IVF with microarray, we can get a good batch of embryos, know that they've fertilized, and see what happens exactly. It was honestly helpful to hear his opinion on this. It was fairly convincing.

The other interesting thing that Dr. Schl. said was about our most recent loss, which was a triploidy (three full sets of chromosomes instead of two). Since this was most likely caused by two sperm fertilizing an egg, we were told here in New York by multiple sources that this is a totally random event that won’t recur and has nothing to do with our chances. Dr. Schl. disagreed, saying that it is still an egg issue and that my egg allowed two sperm to enter, meaning that it was defective. He also thought that given that this is coupled with our other aneuploidies, and given my cancer treatment history, we might be more prone to polyploidy than other patients. Great.

Throughout the meeting, Dr. Schl. only cracked a smile once. I told him that our clinic was aware we were headed out to see him and that they were willing to monitor my cycle in NY. And then, when I told him I thought they were probably more than happy to do the monitoring so that I could stop messing up their stats and instead start messing up his stats, he smiled. It was brief, but it was definitely there.

So that’s the what’s what. Not exactly hopeful. But it’s where we are at. It was sobering to hear Dr. Schl.'s take. Not as devastating as it was a year ago, and not unexpected. But it wasn't easy, either. The fact that we could even sit across a table from someone telling us that it is likely that we will not succeed and not burst into tears is amazing. Just a year ago, we were still so, so hopeful, and were devastated when we spoke to Dr. Schl. by phone. This time, we just nodded and sighed in resignation. What a difference a year makes.

Wow - this post turned out to be a lot longer than expected. Sorry about that.

More on the rest of the work-up soon, in particular the meeting with the geneticist.

Mo

Home again, home again: Back from the one-day work up

We've returned from the Rocky Mountain clinic, and I have much to say about our journey, which will likely trickle out over the course of a few posts.

While out west, we saw a brewery called "Rock Bottom" and I thought, that's fitting. That's why we're here - we've hit rock bottom in this Trying To Conceive business.


We're so close to our absolute nadir of hope that we flew halfway across the country for potentially our last shot at having a genetically related child. We have long heard of this fabled Colorado clinic and had done a phone consult with their director way back in Feb. 2009. At that point, he had been quite sobering in his opinion, but had recommended a comprehensive chromosomal screening called microarray as our best option if we wanted to try one more time with my eggs.

To recap everything between the phone consult and now, we've done two more IVF cycles at our NYC clinic, planned to go out to Colorado twice, but gotten pregnant both times, and subsequently miscarried both pregnancies. So it feels a bit crazy but really kind of cool to actually finally make it to the one-day work up. We brought all of our information with us, curious to see what this clinic and specifically their head doctor, Dr. Schl. would have to say.

What a whirlwind trip - there was really not a moment of downtime. Will and I were both pleasantly impressed with the Colorado clinic's professionalism and efficiency. And honestly, at this point, I'm a bit cynical and am almost looking for something to criticize. So it was quite something that consistently we found this clinic to be really on their game.

For example, throughout the day of appointments, everyone we encountered had read my chart and knew our history. This clinic definitely gives an impression of knowing what they are doing. And when we met with Dr. Schl., he was perfectly pleasant and very informed and articulate, despite his reputation for not having the best bedside manner. He didn't sugarcoat anything, not a morsel of it. But he wasn't overly harsh in the way he delivered what seemed to be his honest opinion either.

Below is our schedule for the day. It was pretty back-to-back and well-organized. Lots of information presented and many tests and some procedures done. I expected this to all be (yawn) redundant (and I therefore predicted I would be annoyed) and some of the things were redundant of course, but there were a number of interesting things we discovered (in bold below):

9:00 - 9: 30: (but it ran longer): met with Dr. Schl (will post details in a separate post. Very interesting chat).

9:30-10:00: met with laboratory people and signed many consents.

10:30-11:00: very detailed ultrasound for me, semen analysis for Will. Turns out I have three fibroids that won't affect anything. According to some kind of doppler scan, I also have blood flow resistance to my uterus - for which they recommended 8 sessions of electro-acupuncture before embryo transfer. Who knew?

11:00-12:00: met with IVF nurse for full hour of education on how things work at this clinic in terms of contact with staff, cycling, testing, etc. Cool to see how they do things as compared to my clinic (more on this later). Geesh - this clinic really wants us to be informed - they presented us with a full binder of materials and literature - this is more info than my clinic has ever given me across two years of treatments.

12:00-1:00: lunch (was supposed to be a half hour but they had mercy on us).

1:00-2:00: met with IVF nurse for another full hour for education on genetic testing required for heritable diseases, required communicable disease testing, medication administration, etc. Good Lord, these people are thorough in their written materials and presentations (hmmm...does someone on staff have obsessive compulsive personality disorder, perhaps? Across the board, the attention to detail was...actually a little scary...but also kind of comforting.)

2:00-2:30: lots of blood work, plus was offered and accepted the chance to get the H1N1 shot - cool! - it's not available at my hospital yet. Don't have it in front of me so can't remember everything that was ordered in terms of bloodwork, but at least two things were new: AMH testing and CMV antibody testing. Will be curious to see results.

2:30-3:00: office hysteroscopy with Dr. Schl. Hurt less than I thought it would. (Given that this cost $645, I was slightly annoyed that as expected, everything in ye ole' uterine cavity is normal). Structural problems are not our problem.

3:00-3:45: met with genetic counselor (thought this meeting would be totally redundant and annoying, but it turned out to be quite useful and surprising...so much so that I will tell you about it in a separate post).

We arrived home very late last night, picked up our puppy, and dropped like dead people into bed. Right now Will and I are trying to dig out from all that went on in our work while we were away and emotionally process everything we heard. As well as attend to Ms. Moxie who had to go to (gasp! she's just a puppy!) a pet sitter while we were away.

Everything we saw and learned gave us a lot to think about. I promise to post again soon when I can. Bottom line, at the moment, we are anticipating we will likely give this IVF with microarray thing a try. It may or may not help us, but at least we'll know. And maybe then we can move forward. Or, even better, although probably unlikely, maybe IVF with microarray will actually work and we'll end up with a baby. Wouldn't that be something.

Mo

Lap recovery and a second second opinion

Recovery continues slowly from the laparoscopy. My RE had said I would feel about 80 percent better by Monday, which unfortunately wasn't the case. I went into work, and during rounds in the psych ER, nearly passed out. I ended up first sitting on a patient's bed (a no-no, but thought I would fall if I didn't) and then crouching near the floor. I had a brief fear of contracting MRSA off of the psych ER hospital linoleum, but I didn't care at that point. I felt clammy, nauseated, lightheaded, had greyed vision, and was cold and sweaty. Chalk it up to hypotension, I think. Was a bit embarrassing to see the house staff spring into action taking my pulse and BP, offering fluid and crackers ("Look she's tremulous! Her pulse is weak and thready! See how pale she is!") Oops. Sorry, eager young physicians, I should have stayed at home one more day.

After crawling through the morning, Will picked me up and we went to see the head of the Other Great Fertility Center in NYC for what felt like our zillionth second opinion, but was actually only our second second opinion (so third?).

We'd seen this RE once in the past, before we even got married, just to get everything checked out. He remembered us and said, "It's been a while! How have you been?" Then he looked at our chart and said, "Oh, yeah. Oh." So things began on a somber note.

He seconded what the Colorado doctor had said a bit, stating "Given how things have gone, we really have to start to wonder about your health history and the impact it has had on you." We asked whether he'd seen others with my particular chemo treatment have this kind of problem, and he said that no, he hadn't, and that the literature didn't support it either, but that it was the most likely explanation for all of the chromosomal problems.

He said it was very unusual but not unheard of to have such a great response to the medications in terms of numbers of eggs and embryo quality (he called my response "textbook" and "beautiful"), but then to have such dismal results.

In fact, he described it as "puzzling." I have other words to describe it, but I'll keep them to myself.

We talked about PGD. At length. He was a big proponent. He does feel that we are in the small sample of people for whom it would offer additional benefit. He said he wasn't sure what he would do in our shoes but he thinks he would do PGD if it were him (we asked, as we know he's been down the IVF road himself in his personal life). He wouldn't say if he felt his clinic is better at PGD than our current clinic. He said they should both be pretty good at it. And he said microarray CGH is unproven. "Could be better than PGD, could be worse." He helped us interpret the data from a number of studies that we'd previously been reading as unsupportive of PGD. He pointed out some flaws in the study design of the articles and analytical methods that we hadn't appreciated before, which made the data in support of PGD appear a little more favorable overall. He also said that if we do PGD on a good number of embryos and all are abnormal, that we only have about a 30% chance of having anything turn up normal the time after that. So that was new information.

He spoke highly of Colorado and he spoke highly of our current clinic. Of course he was positive about himself as well.

Ultimately, he said "Because of your experiences and all of the reading and researching you have done, you know more about this field than most OB/GYNs and more than some reproductive specialists." And then he shook his head. He said that if we had come to him hoping for some answers, that we were out of luck, as he had none for us.

"The best I can tell you is that you are doing all the right things. Think of it this way: whatever path you choose - to stay at your clinic, to come to our clinic, or to go to Colorado - all are great choices. All are the RIGHT choice. I can't tell you if a baby will result from any of these paths, but I can tell you that they are all solid paths with no one substantially better than the others."

So no magic bullet, no identification of something that had been overlooked. I guess this shouldn't be surprising. If there is some peace to be found in this consult, it's in this RE's last statement. That we are facing multiple right choices and have done everything in our power to achieve a good outcome. Whatever happens, we've tried our very best. The rest of it is out of our hands.

This RE shook our hands as we left the consult and offered to speak to us by phone if we have any further questions. I wish I could come up with some questions that he would have the answers to.

Mo

Second opinion - Will's take

Mo and I often work late or have things going on in the evenings, so sometimes we don't have a quality block of time to sit and discuss. This morning we were both leaving for work at the same time, so we were able to walk and chat and get some seriously good conversation while heading our respective ways to work. There is something about a brisk walk or (even better) a jog that helps me clear my mind.

I, like Mo, had a twinge of guilt about requesting our records. More so than Mo, once I select a doctor I tend to put my trust in them and not look back. As a physician, I try to check my professional life at the door and just be a "patient." In truth, however, I recommend to everyone that they get a second opinion. I am happy when patients have second opinions - for me it is an honor that they entrusted me in the first place. And besides, a second opinion is just that - an opinion. I would hope that other physicians my patients consult with have a similar overall read on things, but I also hope they will have their own views on the patients issues. Medicine is an art.

After speaking with the CCRM doctor, I reminded myself that what we initially sought was a different opinion - not a different truth or different set of facts. We also were not seeking someone to tell us that what we have been doing is perfect, don't change anything. The facts are the facts and no matter who we consult they will not be able to provide "truth."

In the end, we learned that we are on the right course, with some additional angles to consider. A few things he reminded us: We have been able to get pregnant, both with and without IVF. Mo also has responded well to the stims in the past and there is no reason she will not in the future.

On the downside we have gotten blasts, but not as many as one would hope. We have also had miscarriages secondary to genetic abnormalities. This is the kicker, the lynch pin. The theory presented to us is that given Mo's history of chemo, these aneuploidies are most likely iatrogenic. This theory makes sense and should be considered, but at the end of the day we will never know what toll the chemo took on her ovaries.

Even though both Mo and I know (and have known) this intellectually, it is different to have it uttered from an MD's lips. It somehow made this possibility seem like a fact. It validated our fears.

The offer of microarray and vitrification is extremely appealing. However, many things in medicine are initially promised as the next-best-thing-since-penicillin. Any new technology should be seriously considered, but also contemplated carefully. I am obviously aware of our lack of positive results so far, but we need to be thoughtful in making any changes. Thus far we have been happy at our clinic and with our doctor and that counts for a lot.

In the end, we will continue our research and continue to cogitate on our options.

As Mo said to me last night, nothing has really changed in reality; whatever state her ovaries are in remains the same now as it was before this conversation. What's changed is our awareness of the possibility options has expanded.

I hope everyone has a great weekend. Mo and I are headed to a comedy club tonight with friends for a little relief.

Will

"It's not your clinic, it's YOU" - reflections on a second opinion

We spoke with the head of the Colorado clinic last night. I presented our clinical situation, beginning with my health history and including our forays thus far in IVF. He was a very nice, articulate man. He gave us a lot of time, and a lot of detailed information, which we really appreciated.

But his opinion was sobering.

Bottom line, he thinks the Hodgkin's chemotherapy treatment and subsequent radiation from all of the imaging I have had done (more than 30 CT scans, gallium scans, PET scans) have damaged my eggs and are the culprits behind our multiple chromosomal losses. He said that it was pretty unusual to have a double aneuploidy and then to have another consecutive aneuploidy (and in our case two more consecutive), so he didn't think that was just random bad luck, as it has previously been explained to me by my RE and OB/GYN.

He also cited as concerning the fact that we have made many eggs and embryos during the past three cycles (40 mature eggs and 31 fertilized embryos), but only two blastocysts - all while at a top clinic.

He seemed to think our male factor issues, although fairly rough on paper, were not such a big deal since we've gotten pregnant occasionally on our own. And that it is good we don't have any uterine or clotting or other issues (all tested negative in recurrent miscarriage work up).

He said our best chance going forward is donor egg, but that "if you're not yet there philosophically," we have a couple of other options:

1. We can continue the IVF method we have been using - which he likened to a scattershot approach - hoping that eventually we will produce a chromosomally normal embryo and happen to transfer it.

2. We can come to his clinic and use a technique that is under clinical development called microarray analysis to see if any of the embryos we produce are euploid. He thinks we may find out that most or all of our embryos are abnormal. Microarray analysis would involve another fresh IVF with aggressive stimulation and attempts to grow the embryos to blastocyst (a little concerned that we've only ever had two blastocysts...but he seemed confident he could get a decent number). They would then sample the polar bodies or take a few cells from the trophoblast (part of blast destined to become placenta) and test for all 23 chromosomal pairs. It takes several weeks to complete this testing so all blasts are frozen using vitrification and those that are chromosomally normal are then thawed and transferred later (he reported a 99% survival rate after thaw). So far they've had 85 patients - mostly those who have failed other cycles - and a pregnancy rate of 70%.

Using microarray, he gave us a 25-30% chance of success. We didn't even ask about the likelihood of success with traditional IVF.

We were a bit shellshocked after the conversation (me more than Will, since I'm the defective one) but everything he said makes sense. My RE's continued optimism ("Your prognosis here is fabulous!") despite how things keep turning out has been a bit puzzling, but I have just been chalking it up to my own pessimism.

If we decide to go with the Colorado clinic, the whole process will take approximately (gasp) 4 to 5 months, beginning with a day of testing (lose a month, possibly two depending on if they need more testing) and working through the whole process of stims (one month), microarray analysis (4-6 weeks), and then a medicated FET (another month).

Daunting. We have a lot to think about.

Note to self: be careful about looking under every stone - sometimes you may not like what you find.

Mo

Second opinion

We have a phone consult tonight with a clinic in Colorado to get a second look at our case.

Part of me wonders why we're going this route, because we're at an undisputably great clinic in NYC and I really don't have doubts about the care I've received here. I feel a little guilty getting another opinion, like it means we don't trust our RE or like we're cheating on him a little bit. But I'm hoping he would understand the desperation and anxiety we are beginning to feel. After all, we've been at IVF for over a year and a half with no baby to show for it. We also have only one more IVF left before we're out of insurance coverage (I do realize we've been very fortunate to have this much coverage in the first place).

When our NYC clinic couldn't fit me in last month for the endometrial co-culture, I started to panic. Within a few days, I'd requested my records and lined up this phone consult. This clinic in Colorado is supposed to be the best clinic in the country. We're currently receiving care at what is probably number 2. Is there a difference between the two clnics in outcome? Hard to say. But a fresh pair of eyes never hurts.

So the plan is to stay at our NYC clinic at least for IVF #4 and then see where to go from there. It feels a little weird to be going in to our next IVF cycle already preparing for #5, but that's where we're at. I am hopeful that #4 will result in a live baby but am also trying to be realistic and come up with a plan B (and also begin considering plan C - adoption/donor egg).

This is so different than where we were at emotionally when we started. We went into this IVF business excited and eager, disappointed that this was an expensive and stressful way to have a child, but really believing and expecting we would come out of this with a baby after 1 or 2 IVFs.

Those expectations have not proven to be true and we're left trying to come to terms with where things are at, to try to make sure we leave no stone unturned before we call it a day.

Tonight's talk is part of the process of looking under every stone, I suppose. Making sure we're not missing something that we should be considering while we still have the time and the financial and emotional resources to do something different. We'll see what they have to say.

Have any of you sought second opinions from another clinic? What questions should we be sure to ask?

Mo