Things that go bump in the night

photo credit: tome chan

All is looking good. As good as good can be right now.

Our big hurdle - both real and psychological - is time. Just needing to get through the next few weeks or so - past the date of our latest loss, further into the pregnancy where things would be a bit safer. We're thinking that might make things start to seem more real, more likely to stick around.

And considering everything we've been through - the six losses, the five years getting to this point - I think we are holding up damn well. For the most part, I am not angst-ing too much or for too long.

There are some back-of-my-head worries, some middle-of-the-night worries, the type that you don't see so clearly, but maybe hear in the background sometimes, late at night bumping around in your head and your heart.

My main fear that I can pinpoint at this stage is a fear that this pregnancy is another triploidy. We've had beta numbers this high once before - during pregnancy number 5 - and it was a triploidy, 69 XXX. Actually, my beta numbers during that pregnancy were lower than my hcg numbers this pregnancy. Gulp. Which I'll be honest, does worry me some. (edited to add: I mean lower at the same day in time...much earlier than now - back in the beginning of a pregnancy when you usually get betas drawn....)

The embryos we transferred this time were tested ahead of time and were deemed normal by microarray analysis. Because the Denver clinic was worried about repeat triploidy in our case (usually a spontaneous, non-age related, not likely to repeat event), they also did FISH testing to specifically look for this. The FISH failed to work, however, on two of the three blasts we transferred this time. So we know there is no mismatch with the chromosomes - no trisomies - but there could be an entire extra set again, which is what triploidy is (microarray only looks for a mismatch between the chromosome numbers, not how many sets there are).

Cue the fear.

I talked to the OB about it last week and she reassured me some. She said that it's unlikely to be a triploidy, but that if it is, I'll miscarry in the next few weeks. If I don't miscarry in the next few weeks, and if the quad screen, nuchal, etc. comes back ok, we can pretty much rule that fear out.

May not sound like much reassurance, but it worked for me. Nothing I can do to change it if this is a triploidy, so it's a wait and see game at this point. OK. I can do that. I can wait and see.

I also contacted the genetic counselor in Denver, just to see if she could put my mind at ease at all. She also said triploidy is unlikely (which I know, but don't these folks realize that Mo and Will are especially prone to rare and unlikely events?). She affirmed what I thought, which is that because we did ICSI, we know only one sperm fertilized each egg, which is one way triploidy occurs. She also confirmed that the Denver clinic checks for the expulsion of the polar body from the egg, which is another way triploidy can occur (the egg doesn't shed its extra set of chromosomes, so you end up with 3 sets). I was also hoping to find out if the embryologists tried to visualize the 2PN stage that confirms fertilization (because I think in triploidy you'd have a 3PN, not a 2PN stage, but she didn't answer that part of my question...oh well).

So rationally, it seems unlikely this is another triploidy, except that my beta numbers are a little out of this world. And I realize to those without a crazy bad history, these thoughts and fears may seem crazy, or super negative or something. But I don't think so. I think this is what happens when you've rolled the dice as many times as we have and have come up wanting each time. It's hard to believe your luck may finally have changed. You keep looking for the catch. You keep looking for the asterisk. The "just kidding!" in small print at the bottom of the page.

Mostly I'm not thinking too much about this. Mostly I'm actually in the now...this fear is just a little niggling thought in the back of my mind sometimes. It helps so much to know that whatever is going on in there is out of my hands. I can't unmake a triploidy if that is what is growing. I also can't mess up a perfectly normal baby if that's what we're lucky enough to finally have.

It helps that I'm still feeling guarded, have not launched head over heels into this pregnancy with my heart wide open yet. I feel a little guilty about that, but am trying to be understanding of myself and Will. We are gun-shy. We are wounded. We are taking this a day at a time, and that's ok.

So these are some of the things that go bump in the night for us. If we can just get a bit farther along, these particular fears will be put to rest. And that will be a very good thing.

Mo

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FISH results are back: IVF #7

We received a call with the FISH results yesterday, which is the extra test we're having done just to look at the sex chromosomes in each of our blasts. We added this step at the advice of CCRM's genetic counselor who expressed concern that given our history of polyploidy and my history of cancer treatment, we might be more prone to a repeat polyploidy than the general population (usually there's a 1 in 1,000 chance). Since microarray doesn't show polyploidies, just trisomies and monosomies, we forked out some more cash to add this test to the mix.

Last time, this one pesky chromosome knocked out half of our sample. It was really disheartening, although things ended up ok and we got three normals.

And this time?

Well, so far we've got four with normal sex chromosomes!! And the other three? They only had one cell to test for each of the other three and they got no result. So We've got four with normal XY or XX and three wild cards, which will have their fates revealed with microarray. But we haven't lost a single blast yet! Unbelievable.

I felt my breath hitch in my throat when the genetic counselor Danielle identified herself on the phone. I had heard that the policy has changed since our first CCRM cycle and they are now typically sharing FISH and microarray news together once the microarray news comes in. So hearing her voice, I was worried that she was calling this soon because our embryos were ALL ABNORMAL and we could just begin grieving early.

I shared that fear with her and she said, "You know, this may be hard to believe, but maybe this time there won't be a lot of grief. Given your history, that is probably hard to imagine, but I'm really optimistic."

Huh. Not a lot of grief? Really optimistic? About us? Weird.

Here's the detailed rundown of our FISH results:

Embryo #05: 6BA NORMAL!!

Emrbyo #11: 4BB NORMAL!!

Embryo #14: 4BB NORMAL!!

Embryo #15: 3BB NORMAL!!

Embryo #17: 3BB No diagnosis

Embryo #20: 3BC No diagnosis

Embryo #21: 3AB No diagnosis

Three cheers for good news!!!

Only 22 more pairs of chromosomes to go!

The microarray result wait time of late has been 4.5 to 5 weeks...so...we should hear the final word on those results around the end of July. Right now that seems just fine. I can wait.

I pray the news is good.

Mo

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Microarray results are back

My husband, Will, and I were out walking little Ms. Moxie yesterday evening down by the Hudson River when Will's Blackberry rang. It was Danielle, the genetics counselor in Denver, calling to say that our microarray chromosomal testing results were in.

Will told me later that his heart leapt into his throat as soon as she identified herself, but that his apprehension eased a bit when she said to put her on speaker phone (I guess Will thinks you can't tell people devastating news via speaker phone?). Since too much ambient noise makes outdoor speaker phone usage infeasible in Manhattan, Will graciously handed the phone to me and we strained to listen together to the news.

Can't believe the results are back this fast.

The samples shipped to the lab on March 23 (so 15 days from shipping to results - amazing). Heck, the egg retrieval was less than a month ago, on March 12.

And the news? The news is good, folks. Can you believe it? Mo and Will get some actual good news for once! Hallelujah!

Three of our four remaining blastocysts came back as euploid. Euploid! All 23 pairs of chromosomes normal! Who would ever have thought?!!!!

You want to know what is the wildest thing? All three of our normals are embryos that never would have been considered contenders (and actually never would have even existed) at our New York clinic - #2 in the country.

That's because one of our normal embryos was harvested immature and matured in vitro, which my New York clinic doesn't do. And the other two normals are our day 7 blastocysts. Usually, you want to have your embryo develop into a blastocyst by day 5, day 6 tops. Day 7 is sort of unheard of, so these embryos in almost any other situation would have been discarded as nonviable. But they are chromsomally a-ok. We are considering these three our darkhorse embryos, because without a lot of finessing (and patience) in the lab, they would never even be here.

And all the rest of our blastocysts? The ones that developed appropriately, on time, and in the usual way? ALL ABNORMAL.

Huh.

So we are thrilled. Super thrilled. Cautious at the same time, because this still feels a million miles away from an actual dirty diaper. But rejoicing nonetheless.

At the same time, we are beginning to try to figure out what to make of the fact that all of our outliers are normal whereas all of the typical front runners are aneuploid. And trying to suss out what in vitro maturation or Day 7 blast status might mean in terms of implantation potential.

But this is undeniably, unbelievably good news!!

We are capable of making normal embryos!!! What an amazing thing!

We are so grateful we finally took the plunge and trekked out to Denver.

Is it possible that our lives could change?

That we could actually be parents?

One step at a time, but also completely...

Mindblowing.

Mo

P.S. See below for the the obsessive version, if it is of interest.

Embryo #03

Day 6 blastocyst, grade 4AA

Was immature when retrieved and fertilized with Day 2 ICSI after in vitro maturation:

FISH testing: No diagnosis

Microarray testing: NORMAL!!!

Embryo #05

Day 7 blastocyst (very unusual to culture this far), grade 4AB

FISH testing: Normal

Microarray testing: NORMAL!!!

Embryo #06

Another miracle Day 7 blastocyst, grade 6BB

FISH testing: Normal

Microarray testing: NORMAL!!!

Embryo #07

Day 6 blastocyst, grade 4BB

FISH Testing: Normal
Microarray testing: Monosomy 13

Embryo #10

Day 6 blast, grade 3BB

FISH Testing: XXX

Microarray testing: Monosomy 15 and Monosomy 21
(interestingly, the XXX didn't show up on the microarray, which means that either the FISH test was in error, OR that this one is triploid in addition to the two monosomies)

Embryo #15

Day 6 blastocyst, grade 4BB

FISH testing: XXY

Microarray testing: XXY

Embryo #18

Day 6 blastocyst, grade 3AB

FISH testing: Mosaic (6 cells normal, 1 cell XYY, 1 cell XXY). Two mitotic errors

Microarray testing: Monosomy 13

Another way to look at it: a.k.a. the silver lining

Will and I spent the evening moping and grieving on separate coasts (he's at a conference in California this week). As of this morning, I think we're both trying to pull ourselves back together, exhale, and find a bit of perspective.

And today's perspective on yesterday's not so great news?

Three abnormal blasts means three miscarriages we don't have to go through. Three babies we don't have to lose.

I wish those three blasts had been normal, but they weren't. While this news hits hard, it is much less painful than losing another pregnancy.

So there it is...ekeing out a silver lining.

And who knows? Maybe one or more of the other blasts will be euploid.

We are not banking on it. Not by any stretch.

But we are open to being surprised.

Thanks for all of your thoughts on the FISH results. We appreciated every one of them.

It's just amazing how much this all hurts, the continued losses, the cumulative disappointments.

We're ready for some good news already!

We aren't expecting it anymore, but we would welcome it.

Mo

FISH results are back

We got the FISH results back today from the Denver clinic.

This was the test looking just at the X and Y chromosomes, because the Denver clinic worried we may be more prone to polyploidy than, well, regular infertile people.

And while the results are not at all what we were hoping for, we are also not out of the running yet.

In sum, we got three normal, one no result, and three abnormal.

So in only 48 hours, and testing only one pair of chromosomes, we're down to (gulp) half of our blastocysts.

Here's the detailed version:

Embryo #03: Day 6 blast, 4AA: Fertilized with Day 2 ICSI: No diagnosis
Embryo #05: Day 7 blast, 4AB: NORMAL!
Embryo #06: Day 7 blast, 6BB: NORMAL!
Embryo #07: Day 6 blast, 4BB: NORMAL!
Embryo #10: Day 6 blast, 3BB: XXX
Embryo #15: Day 6 blast, 4BB: XXY
Embryo #18: Day 6 blast, 3AB: mosaic (6 cells normal, 1 cell XYY, 1 cell XXY). Mitotic error

All seven blastocysts will also be tested using microarray to check all chromosomes, so hopefully the no result will have a result that way.

There is no way to tell with the XXX or XXY if these are trisomies (just one extra X on each) or polyploidies (a full extra set of chromosomes, including the sex chromosomes). We'll have to combine these results with the microarray results down the line to determine that. But it doesn't matter; they are out of the running either way.

So how are we feeling? I want to tell you I'm happy with these results. That Will and I did fist pumps and are looking on the bright side and know that all will be ok.

But I'll be honest with you. Will and I were crestfallen at the news. We both (obviously, erroneously) thought that these results were going to be almost certainly good and that it would be when we got the the bulk of the chromosomes with the microarray that we would be facing longer odds. We hadn't discussed it ahead of time, but it turns out we were both expecting to get all normals, or maybe one abnormality in the bunch.

You gotta watch those expectations because they will come back to bite you in the ass every time. You would think we would know this by now, wouldn't you? Do we never learn?

As I listened to the genetics counselor's voice message detailing the news, I felt my face drain of color and tears well up in my eyes.

In a desperate attempt to avoid despair, I called her back and she reminded me that sex chromosome aneuploidies are among the most common aneuploidies. OK. Good point.

And she also reminded me that we're not really facing down the prospect of needing 22 more chromosome pairs to be normal (which seems impossible to Will and I since already just looking at one pair, we've lost half of our cohort). She said she's never seen chromosomes 1, 2, or 3 come up abnormal in the results, because these embryos would most likely not even make it to blast stage, so hey, at least there's only 19 more pairs that we need to hope we somehow beat the odds on. Ugh. Not so reassuring, really, but I guess it's something.

I'm extra worried because two of the three normals we got are the Day 7 blasts. While I am so, so appreciative that the lab went the extra distance and cultured and biopsied these (otherwise, we'd have ONE normal right now), I also can't forget that the head embryologist told me to really not count on those two because they were so slow growing and that they were likely abnormal and that even if they are normal, they are basically unknowns in his book (since even Denver doesn't work with Day 7 blasts), and probably less likely to implant after a transfer. Sigh. If that's true, then we're really down to ONE blastocyst that could be our golden child.

Strangely enough, the genetics counselor was actually pleased with the results. She told me that with our history, she'd expected we'd have a number of abnormalities crop up and is thrilled we still have three normals to work with (although she didn't know that two of our three normals were the day 7 blasts).

So despite my tears, I will try to see the world through her eyes. We are not out of the game yet.

All it takes is one. But damn, we are disappointed. Can't we catch a break already?

Mo

Final embryology news before heading off to microarray

I just heard from the director of the Denver embryology lab. None of our six frozen embryos from our second IVF cycle survived to blastocyst. The embryologist just said that it is so hard on them to be frozen and then thawed and cultured that he wasn't surprised. I am fairly strongly regretting sending them and wish we'd just done a blind transfer here in NY, where at least they could have been inside me. Probably none would have made it still, but it stings. Those embryos were three years younger than we are now. I've always held out hope that they might contain our magic bullet of a normal embryo, always seen them as an outstretched hope and safety blanket, that as long as they were there, we weren't completely at zero. But now they are gone. So I'm grieving their loss, more than I thought I would, and am filled with fear.

On the bright side, we have seven blasts from this 6th fresh cycle. The embryologist cautioned me that two of those, since they became blasts on day 7, are almost certainly abnormal. He said they cultured them out so we could at least get some information, which I deeply appreciate. And that if they aren't abnormal, the chances that they could implant are very low. That in fact, they have never transferred a Day 7 blast before, so it would be a total unknown for them. Weird that we're taking even the Denver clinic to places they've never gone before.

So...we've got 7, but somehow after talking to the head embryologist, it feels more like 5. Which I'll take, and please don't get me wrong, I'm really grateful for...but emotionally it's feeling like our chances are dropping right and left.

I started to ask the head embryologist how often this many blasts come back all abnormal, but then I stopped myself. The answer is that it doesn't matter how often. Even if he said that it rarely happens, having five miscarriages in a row rarely happens, but we've accomplished it. The somber tone of everyone we speak to there, all the calls from the head embryologist and the near daily contact with the genetics counselor, the taking our blasts to day 7, the attempts to expedite our sample - all speak to me that we are not being viewed by the Denver clinic as a typical case. So no comfort to be had there, whatever his answer on "typical" would have been. We will just have to wait it out.

So where are we at now? We have seven blasts frozen, each in an individual straw.

Let the testing commence. We will be doing two types of analyses:

We are doing sex chromosome FISH testing on all seven blasts and will get the results Weds. They *won't* tell us, though, what the sex of each blastocyst is, just that each one (hopefully) has both sex chromosomes present with no polyploidies or monosomies. Apparently there is a clinic policy against sharing the genders before transfer. The FISH testing is taking place in a lab in Maryland, so some of the cells from each blast are shipping off there today.

We are also doing microarray comprehensive chromosome screening, which will be looking at all 23 pairs of chromosomes, including sex chromosomes. This lab is in New Jersey.

We're doing both the microarray and FISH because apparently the microarray will not detect a polyploidy. And since we've won that lottery before, they don't want to tell us a blast is normal if it in fact is not. Usually the risk of a polyploidy is approximately 1 in 1,000, but because of my cancer history, they think I might be more likely to have repeat polyploidy than is typical.

The results from microarray generally take four to six weeks. I know the folks in Denver are trying to expedite things for us, because our history has been so dismal, which I appreciate. And I've read on IVFconnections that some folks have heard results back in as early as two and a half weeks. So we'll see how long it takes to get some news...

So, the waiting begins. Cells from each of the surviving seven blasts are shipping from Denver off to labs in Maryland and New Jersey as I type this.

A little bit of news coming on Wednesday.

And then the big reveal in the next month and a half or so.

Feels so tenuous, the hope. The waiting.

This is hard.

Mo