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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Microarray results from IVF #7

Sorry for the long silence - and thanks much to those who have checked in on me, both on this blog and by email. I'm finding the depot lupron extremely difficult to tolerate. Feeling pretty miserable with it, honestly. It's knocked me for a major loop. I just took the second dose a week ago, so am at least at the halfway mark. Here's hoping the endometriosis is disappearing as I type. I can't wait to be done with this stage of things and to start feeling like myself again.

We've received the microarray results and wanted to share with you all. The news is fairly unbelievable - as in, it is so good that I almost cannot process the information. Will, too, is incredulous.

Out of our seven blasts that were tested from this latest cycle, FIVE were chromosomally normal. We also had one no result, which could also be normal. So only one confirmed abnormal.

Incredible.

Also - and this makes my and Will's hearts rest a bit easier - four of the five normals this time are day 6 blasts. The other is a day 7 (across both cycles, ALL of my day 7s have been normal, crazy, huh?)

So...with two CCRM cycles under our belts, we have totalled eight chromosomally normal embryos. Four that developed on time and without in vitro maturation.

Bottom line, we've got multiple tries here in case we don't get pregnant with our first transfer, which is something I never thought I would be able to say. Not something Dr. Schl. thought we would ever be able to say either. He told us back at the one day work up that he would let us cycle, but that we should expect to learn that we needed an egg donor. We cycled that first time really for emotional closure. Then threw in an extra cycle to boot.

And here we are several months later with EIGHT priceless normals.

Way to knock it out of the park, CCRM. I think you guys may have just changed the course of our lives.

Now if only I can survive the rest of these lupron days.

Mo

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A little less broken

One of the things that Will and I have discussed as this infertility situation has gone from a seemingly minor problem to a saga of epic proportions is what it feels like emotionally to have not been able to have our own children.

Despite being educated and reasonable people, neither one of us can completely shake the irrational idea that we are somehow defective.

Other people have sex and accidentally get pregnant and have a baby.

Or they time intercourse and get pregnant and have a baby.

Or failing that, they do IUI and get pregnant and have a baby.

Or in the most difficult circumstances, do IVF - maybe two or three times - and have a baby.

But we've done all those things (except for IUI). Multiple times. We've even been pregnant five times.

But no live baby.

We have laughed sadly that we are "doubly defective." Not only have we not succeeded in the normal way, but in addition, all the intervention in the world has so far been unable to help us have the one thing we want most: a family.

As one IVF failure after another has unfolded, as baby after baby has died and so many have turned out to be chromosomally abnormal, we had begun to doubt that we could make an embryo with the proper ingredients to be a living baby, with all the chromosomes aligned on their spindles, the cells from me and Will touching in the right places to create a heart-beating, breathing child.

We have felt that we are broken, as individuals. Broken as a couple.

So what does it mean to us to find out that we can make a chromosomally normal embryo?

It means a lot, even if none of the three blastocysts results in a live baby.

After everything we have been through the past few years, we have begun to accept that we are no longer whole. We are no longer the couple we used to be.

But finding out we can create normal embryos makes us feel a little less broken. Before we move on to any next steps, to the hope of a pregnancy, we both want to honor this moment.

Because this, just where we are at right now, is something we are enormously grateful for.

Mo

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

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