Wednesday, December 23, 2009

Today's lesson is brought to you by X, Y, and the number two.

When I first found out about III's chromosome inversion, but before we saw the doctor, I went to to try to find either information or others who had discussed in their blogs a similar situation. It's such a technical thing... so it was hard to find anything, or when I did I didn't understand it. So, one of the things I've been wanting to do is to give some more technical information about our inversion as I understand it so that if there are others who have a similar situation, they are able to get some info from our situation.

My disclaimer is that I am not a scientist; I am not a doctor. What I have posted here is a combination of what I remember the geneticist sharing with us, what she sent in her letter to my RE, and what I've found myself on based on what she told us. Don't take my information as "the word". All I can tell you is what is true, based on my own elementary understanding, in our situation.

My first search, before our genetic counseling session, resulted in this find. It is written for the layperson, so I found it helpful and informative:

PGD for patients that are carriers of chromosomal translocations

This is another rare situation in which a couple knows that one of them has a chromosomal arrangement called a balanced translocation. When someone (the husband or the wife) has a balanced chromosomal translocation they are normal - until they try to have a child. When their chromosomes join with those of their partner in the fertilized egg they make a high percentage of chromosomally abnormal embryos.

These embryos are at very high risk for miscarriage or could result in the birth of a child with birth defects. This is another situation where PGD can help. By having IVF and PGD, they can have chromosomally normal embryos transferred (if there are any) - greatly reducing their risk for miscarriage and birth defects.

PGD for aneuploidy screening (PGS) - checking the chromosomes (because they are having IVF and the wife is 38 or older, or because of multiple previous IVF failures)

Background: Human eggs are often chromosomally abnormal - and the percentage of eggs with a chromosomal abnormality increases with increasing female age. In general, it seems that about 25-40% of human embryos have some type of chromosomal abnormality. This increases to about 50% and higher as women approach or exceed age 40.

Theory: By testing the chromosomes of the embryos available for transfer, we can discard all embryos with abnormal chromosomal arrangements and pick the embryo(s) for transfer to the wife's uterus from those demonstrating normal chromosomes. This is fascinating technology, and the theory is logical as well. However, the data from studies on pregnancy outcomes after PGD testing of chromosomal normality does not appear to show any clear benefit at this time.PGD for aneuploidy is often referred to as preimplantation genetic screening, or PGS (instead of diagnosis).

III has an inversion, also called a "chromosomal translocation"*, of his chromosome 2. It is at the spot p23,q23. I don't really understand what that means- just that it's the location on the chromosome. It is a "pericentric inversion" which means it includes the center part of the chromosome (our geneticist called it the "waist"). So basically what that means is that part of the chromosome is flipped over.

During "meiosis" (the process which creates the sperm), each chromosome pair actually lines up and exchanges genes from one to the other. (So one half of the ch.2 exchanges genes with it's matching half.) Then they separate and one goes to one sperm, and the other goes to another sperm. When they line up, if there is an inversion, the chromosomes can loop around allowing the crossover to be balanced. There is also the possibility of an unbalanced crossover if they do not line up correctly.

The geneticist showed us a very basic picture of what that means. The first is what a normal person's chromosomes would look like- except I've drawn in red lines where the inversion might occur. The second picture is with the inversion. The last two are examples of what could result during meiosis.
Each person has 23 pairs of chromosomes. Through the process of conception, a potential fetus gets one chromosome from each pair from each parents. (The s.ex chromosomes are an easy explanation of this- a baby gets one of the mother's two x chromosomes, and then either the father's x chromosome or his y chromosome, determining what gender the baby will be.) III's translocation only affects one of the chromosomes in the 2nd pair.

Some good things:
  • Of III's pair of chromosome 2, one is normal. The process by which the pair is distributed to his sperm (each sperm carries one of each pair of each chromosome) is totally random. So it is possible to have sperm that are unaffected by the inversion.
  • Our geneticist told us III's is "rather large" inversion. The larger the section that is inverted, the more able it is to correct itself during conception.
  • Through the non-inverted ch.2 and through an inverted ch.2 that corrects itself during alignment (I don't know if that's the correct term), we could have a totally normal embryo.

Some negatives:
  • If an embryo is affected by the inversion, it could result in a miscarriage, in a baby with birth defects (though the severity is unpredictable), or it may not implant at all.
  • With "natural fertilization" there may be a lower incidence of having an embryo affected by the inversion since the sperm would likely be slower/less efficient swimmers. Since we have fertilization issues (possibly caused by the inversion), we have to do ICSI, increasing the chances of an embryo being affected.

Below is more information I found through Dr. It's pretty technical, but explains the occurrence of the chromosome "fixing" itself and has a pretty good picture of that.
Inversions involve two chromosomal breaks and rejoining, with the broken piece reincorporated in the opposite orientation from which it naturally occurs. When they include the centromere, they are called pericentric inversions... inversions arise in mitotic cells. If they arise in precursors of the gametes, they may produce abnormal genomes as they progress through meiosis. Recombination between homologous chromosomes is a necessary part of every normal meiosis. The probability for nondisjunction is greatly increased if there is no recombination. However, recombination between a chromosome with an inversion and its normal homolog may result in two abnormal chromosomes being produced. ...four different gametic products are produced, one normal, one has the inversion, and two have duplicated portions and deleted portions. The effect on the phenotype is almost always deleterious, but the magnitude of the effect depends upon the size of the duplications and deletions, and where they occur.

This picture from the above link shows the meiosis process and the different ways the pairs can crossover.

Another, more technical, picture.

I hope this information is useful, or at least interesting, to someone. We have decided to use PGD, and feel our clinic is experienced in this process. Clearly, I'll keep you all updated about how it goes. ;)

*ETA: After reading Julia's post on balanced translocation and then doing a little research myself, I wanted to clarify. While the geneticist used the term "chromosomal translocation", much of what is on the internet describes something different than what has happened with us. III's inversion only involves one chromosome, as opposed to a "reciprocal translocation" or a "Robertsonian translocations". In each of those, there are 2 different chromosomes involved. III's translocation is within only one chromosome.

Tuesday, December 22, 2009

"But that's a good thing, right?"

I have two friends who have really made an effort to keep up with where we are in this whole IVF process. Both of them called me after yesterday's doctor's appt.

After explaining, basically, what I explained here in yesterday's post to each of them, both of their responses were essentially "...those are good things!"

Yeah. I guess it is. Dr. Z seems pretty sure we're going to have a baby at the end of all of this. We have good enough insurance that it allows us these invasive and expensive treatments and we live in a state that requires insurance to pay for these treatments. We have not been told that our problems are too large to be overcome. We live in a time when science and medicine allows us, despite whatever crazy issues we have, to have (what our doctor assures us can be) a healthy baby.

So why am I not more excited? All I feel is the impatience of having to wait for my next period, and then through the necessary weeks of BCP. The anticipation of the shots and the bloating. The anxiety of scheduling all the appointments and procedures and the worry that it will all coincide with our vacation in February. The possibility of yet another failure.

Monday, December 21, 2009

No more dolls.

Dr. Z is optimistic.

He not only has Dr. N's report, but he contacted another geneticist who is the head of some program yada-yada who said that an inversion of the 2nd chromosome like ours can contribute to both miscarriage and infertility.

An interesting note- apparently PGD has come leaps and bounds in the last five years. In the past, FISH was the only method that was being used. The downside was that it really limited what they could look at. Now, at least in the labs my clinic is associated with, PCR is used. My limited understanding of this, based on our fifteen minute appointment with Dr. Z, is that with FISH they might be able to determine an issue in 3-8 chromosomes, but with PCR, they should be able to test all 23 chromosomes.

III told Dr. Z, "We feel like we're those Russian dolls. You open one, and you just find another." Dr. Z assured him that he's pretty sure we're on the smallest doll. He said not only does he feel like this could be the cause of all of our problems, but that it's possible we could learn more from the information we get through PGD. III asked "If there is another doll, what would it be?" and Dr. Z told us "This is pretty much as specific as it gets. And at this point, we've put so much time into you, we better near guarantee you a healthy baby!"

CD1 is likely going to be mid-January. That probably means a retrieval around the middle to end of February.

For my information...


What is PGD?
Preimplantation Genetic Diagnosis (PGD) is a technology used to screen embryos created from IVF with ICSI for genetic diseases, before they are transferred back to the female’s uterus. PGD is used to screen embryos for single gene defects such as Tay-Sachs, Huntington Disease, Sickle Cell Anemia and Cystic Fibrosis. It can also test embryos for chromosomal disorders such as Down’s Syndrome and for X-linked diseases like Hemophilia. Additionally, PGD may be used for women who suffer recurrent pregnancy loss from chromosomal abnormalities and advanced maternal age. Screening and transferring only unaffected embryos reduces the rate of miscarriage and may help to alleviate the decision to terminate a pregnancy due to a genetic defect.

What happens during the PGD process?
In this process embryos are created by using ICSI for insemination. The embryos that fertilize and begin to divide are cultured to Day 3 where they are 8-10 blastomeres (cells) in size. At this point a hole is made in the zona pellucida of the embryo, very similar to embryo hatching, but it is used for a different purpose. Once the hole has been made in the zona pellucida a biopsy micro tool is used to gently remove one or two blastomeres from the embryo. This does not harm the embryo because at this point the cells have not begun to differentiate. Differentiation means that certain cells will develop into certain tissues of the fetus. The 8-10 blastomeres are composed of identical genetic material, and will continue to divide and grow properly even if one or two cells are biopsied. The incident of embryo damage during this process is very low, but does exist as in any other micromanipulation. Once the blastomeres are biopsied, they are processed according to the testing to be performed, and sent to a laboratory specializing in PGD analyses for definitive results.

How are the results determined?
Results from the PGD are obtained, and the laboratory is able to determine which embryos are not affected by the genetic disease being screened for. At that point, generally on Day 5, the healthy embryos are transferred back to the patient in anticipation of creating a viable pregnancy. An HCG beta is drawn 2 weeks from the date of egg retrieval to determine if a pregnancy has been initiated.

What else do I need to know?
As with any diagnostic procedure, PGD is not 100% accurate. Some embryos have mosaicism which means that not all the blastomeres are comprised of identical genetic material. In this event embryos which have been determined healthy may in fact be affected by the genetic disease. Patients may undergo an amniocentesis or chorionic villus sampling (CVS) to confirm that the fetus is negative for the genetic disease.

Appt with Dr. Z today at 3pm...

Friday, December 18, 2009

Happy birthday to me.

It's been an awful year, and so, in kind, it's been a hectic, tiring day so far.

I can't believe I will likely reach my mid-thirties without a baby.

However... while my dad and I don't always get along, and we aren't as close as some daughters and fathers are, this message from him made me feel warm and fuzzy:

All I wish for you is that all your dreams come
true and that you are truly happy.

Thanks, Daddy. Me too.

Tuesday, December 15, 2009

A little lost.

I'm starting to think maybe I don't want to do this job anymore.

I don't know how much of it is being overwhelmed by everything else that is going on in my life. But I'm just too tired. I don't care enough right now. And that's bad in any job, but especially this one.

Last week I wrote the following to KB:
"I hate that I have to think about work and other people's children every day. Your kid doesn't like his seat in my class? She needs extra help but you don't want to bring her early for my set help times? He doesn't think the class is challenging enough?

Guess what.

I don't fucking care. "
Hmmm... Not a very good attitude. Not one you'd want your kid's teacher to have, right?

Don't get me wrong- it's not that I like nothing about my job. There are things I love. And parts that I'm really good at. It's just that the parts I like are lately outweighed by the parts that are crushing me under their weight.

I keep thinking of other jobs I might do. I have looked into training for a number of them. But really? I just feel like I need some time off. But I'm not even sure I could justify that to myself, not to mention my husband.

We have parent conferences today after school. And then tomorrow during the last two hours of the school day (which means I need to leave sub plans for the classes I'm missing). I'm dreading it. There is no major heavy hitters coming- I just can't imagine sitting down and having to be on for the parents for two and a half straight hours (not even a bathroom break).

Today is also our holiday party. Which I should be excited about. But really? I just want to go home, curl up with my Peanut and take a nap. But I paid $20, and III arranged to come home a little early to take care of the dogs so I can go. So I'll go. But a party shouldn't feel like something else I have to do, should it?

I'm just so damn tired.

Saturday, December 12, 2009

Retail Therapy: Part 2

Oh my. I can't believe I forgot the best one!

I bought myself a birthday present.

Going on my own the weekend of my birthday. :) So excited!!!!

Friday, December 11, 2009

Thursday, December 10, 2009

Missing my B every day.

"Until one has loved an animal, part of one's soul remains unawakened."

~Anatole France

Wednesday, December 9, 2009

Seeking PGD experience

I'd love to hear from/read about others who have experience with PGD- especially around chromosomal issues. If you'd like to share, or if you have a blog where you documented your experience, you can comment below or email me at the address on my profile.

Thanks. :)

Tuesday, December 8, 2009


I'd really like to share a lot of what we learned yesterday in more detail to potentially help anyone who finds themselves in a similar situation (while keeping in mind that I am not a medical professional and am relying on my perception and memory after talking to the doctor). However, I want to wait until we get the letter from her before getting into the technical nitty gritty.

But here's a rundown of what we talked about:

  • III has an inverted chromosome. The inverted section is fairly large, which is apparently good- it allows for more of a possibility that, in a conception, the chromosome would fix itself.
  • There is a possibility that the miscarriage was a result of the chromosome. But not necessarily.
  • There is a possibility that the chromosome inversion is hereditary. But not necessarily.
  • The chromosome inversion is unrelated to our fertilization problems.
  • There is no way to tell how much or little this could affect any potential fetus- no statistical numbers like we often get at the RE office. As I said to Dr. N- "It's kind of a crap shoot."
  • Doing ICSI may actually be increasing our chance of the embryo being affected by the inversion since in a natural conception there's the whole "survival of the fittest" thing going on. (Unfortunately, without ICSI we have no fertilization...)
Our options?
  • Donor sperm- certainly not ready to go there yet.
  • Keep doing what we're doing and hope for the best. (With a potential for more miscarriages or even a child with birth defects... though the latter is the smallest possibility of all of them. We could have a "normal" child without the inversion or even a "normal" child who may have the inversion and, like III, not be affected at all.)
  • Do IVF with PGD. (Meaning testing the embryos once they reach 8 cells for the chromosomal inversion)
I'm feeling very overwhelmed. I'm going to be thirty-four in a few weeks, and I feel like we've been doing this for so long and have done so much. And not only are we still here, but another wrench has been thrown in the mix. (Um... I think I'm mixing metaphors, but whatever...)

I'm just really, really sad and frustrated. :(

Monday, December 7, 2009

We didn't really learn anything new today at the geneticist's.

I want to go into more detail eventually, especially since I had trouble finding any info or others' stories on the internet when we first heard.

But right now I'm too busy feeling sorry for myself.

Sunday, December 6, 2009

For the moment...

...I am content.

Fire in the fireplace.

Snow in the yard.

Wine in my glass.

Dog in my lap.

Perfect for a December evening.

Friday, December 4, 2009

Appointments made

Yesterday at 11am I called Dr. N's office again. When C answered, I said "Look, I don't want to be a pest..." she apologized that it was taking so long, told me that Dr. N had looked at my file and put it on C's chair, but had not left instructions about what to do. ARGH. She promised me a call back by the end of the day.

On which she followed through. I have an appointment for Monday afternoon. Now that it's set up, I'm really scared about what she will tell us....

I then called Dr. Z's office. When we were given the referral, Dr. Z's nurse told me that when we had an appointment set up with Dr. N, to call and make an appointment to see Dr. Z and that it could even be on the same day. When I called to talk to Dr. Z's AA, she told me that he's in Asia for another week. *sigh* So I have an appointment with him on the tenth.

What that means in the immediacy is that, regardless of what we are told on Monday, it is unlikely we will be cycling until January. I anticipate CD1 to fall on or around the sixth. (Which I'm hoping is contributing to my dark mood... Yay PMS.) If we have to do a fresh cycle, we will probably be too far into the cycle to start BCP when we see Dr. Z. Since I don't know how the timing works for a frozen cycle, I don't know if we will be within an appropriate amount of time to do that, but I'm feeling it is very unlikely that they are going to tell us we are "all set" and can just keep going like we've been going.

I probably should feel positive about the fact that Dr. Z ordered this testing after my first m/c, instead of waiting to see if it was going to end up being an ongoing problem. But I'm having a hard time feeling positive about anything lately.

Thursday, December 3, 2009

Stop this ride....

We found out last night that my FIL's cardiac doctor is recommending that he have a heart transplant.

I don't know how much more we can take....

Wednesday, December 2, 2009

seeking more input...

Thanks for your suggestions yesterday. Much of that is the same as what I do. The hard thing is that there is usually an 8-9 hour work day to get through before I can do any of those things!!! I guess it's a one-foot-in-front-of-the-other time for me right now.

I'm interested in hearing your take on our current situation around our next step in our process. III is pissed off. I'm frustrated and nervous, but feel like it just goes with the territory.

Here's the run down:

8/09- positive beta after IVF#2 (though ICSI #1)
9/09- m/c at 8w
11/9/09- 3 day bloodwork + recurrent m/c bloodwork (though I've only had one)
11/11/09- sonohystogram: all clear
11/24/09- Attend appt with Dr. Z who hands us copies of our blood work results, which show normal for me and an inverted chromosome 2 for III. Tells us that we have to see a genetic specialist before we can proceed. Hands us the card for the specialist, who is in a different office, though right around the corner.
11/25/09- 10:15am- call specialist, am told I need to talk to the dr's secretary, C, who is on the phone and she'll call me back. 1:10pm- still haven't gotten a call and am leaving to go out of town for the holiday, so I call again. C's on the phone again, so the person I speak to takes a basic history and says I'll get a call back. 2:15pm- C calls to tell me they need all of the bloodwork results faxed to then from my RE, and then the dr has to look at it to "see if she can help" us and then C will call me to set up an appointment. 2:20pm- I call Dr. Z's nurse, who tells me she'll immediately print it out and send it to them.
11/26-29/09- Thanksgiving weekend. Everyone is closed.
11/30/09- I call and miraculously get to talk directly to C. I ask if they received my paperwork. She says "What's your name again... um, I think we did... um... yeah, I'm pretty sure we did. Yes, I gave it to Dr. N. She'll look it over and then I'll be calling you to set up an appointment."
12/1/09- no call. Pissed off III.
12/2/09- no call. Frustrated me.

What do you think? Is this reasonable? Could Dr. Z's office have done things differently? (<---III's opinion=yes) What should I expect from Dr. N's office? How long should this take-how long should I wait? When should I call again? This is the first time III has really reacted to any situation we've encountered, which is interesting. I'm definitely in a blue place, which lowers my expectations and hope. I'm just trying to get some perspective... lay it on me!

Tuesday, December 1, 2009

ISO blue day remedies...

Walking up the stairs to my classroom this morning, I thought "I'm having a cranky day." (already!)

Then I thought "Geez, I'm perpetually down lately, so if, at 7am, I can already identify this as a 'blue day' that's not a very good thing..."

I'm a doer. I want to be able to control what's going on with me. (That's part of what makes this IF stuff so hard.) I thought "What can I do to put myself in a better mood?"

So I'm here to ask my blog buddies: What do you do to cheer yourself up and help a bad mood improve? I need suggestions!