12/15/2008

I've been nominated...

**disclaimer**
I'm having a bad day.


I've been nominated by Nikki for the Brillante Weblog Award. I didn't prepare a 'thank you' speech, as I wasn't expecting this nomination. Oh gosh. Where do I start?

First of all, I'd like to take this opportunity to thank the driving force behind my blog - INFERTILITY. Without you kicking my ass all these years, I would not be the jealous and bitter person that I am today. Before you came into my life, I was a happy, go lucky kind of gal, skippidy-doo-dahing my way through life. And now, my life is like that of an addict - I can't wait for my next IVF fix. After all I am shooting up hormones, taking all kinds of meds, even getting some of the good stuff while they retrieve my eggs. I think I pay just about the same or even more than what an addict pays for a fix. The only difference is that I still have my house (at least for now). Thank you, Infertility, for making me a gambler. Each cycle, each egg, each embryo - I roll the dice hoping to get genetically normal embryos. But for the most part, we get mostly abnormals. I can't stop gambling. Perhaps, I should try another game like roulette. I might have better luck at spinning the big wheel and hoping it lands on my number. After all it is time that I win something back. I mean, after 3 IVFs, 1 OHSS, 3 FETs, 3 PGD/FISH, and 1 CGH - Isn't it about damn time? But until then, I just keep on bettin'.

Next, I'd like to give a special shout out to both MALE FACTOR and ROBERTSONIAN TRANSLOCATION. Male Factor, you were there from the beginning. You introduced us to the Translocation. Translocation, you are da bomb! Nobody can seem to by-pass around you. You're there whispering to us, after every PGS, to let us know just how screwed we really are. I mean, you can't mess with DNA. That's hardcore stuff there. Both of you have tried your hardest to break me. Sometimes, I even think you have a time or two or three. But that just made me even stronger and more determined.

I'd also like to thank my BIOLOGICAL CLOCK. Without you, I would not feel the pressure of each and every wasted cycle. I appreciate you for reminding me that my eggs are getting older every single day. And I may not be able to produce as many as before. So thank you for keeping count.

Next, I'd like to thank FALSE HOPE. Without you, I wouldn't be able to cry myself to sleep at night. And at my age, I need plenty of beauty sleep. Thank you for making sure I get plenty of that. You, False Hope, never disappoint me. You're always lurking in the corner, starting with my first injection; and you have stayed with me through it all.

I'd like to thank all the ASSVICE out there. Over the years, more and more of you have exploded onto the scene. When one appears two more show up as well. Sometimes, it seems that it is not possible to keep up with all of you who keep popping up. So let's break it down into the most popular categories. Let's start with Prayer. Yeah, that's a good one...Moving on. Next, there's Relax. Why don't you just shut the f-up? Next, there's Just Adopt. Um, yeah. Let's move on to Don't expect it. Oh another good one! Thank you, Assvice, for making me realize that you are all so ignorant!

I'd also like to thank all the FERTILE PEOPLE out there, who have control over when they get pregnant and how many children they want. Without your growing bellies and/or toddlers in tow, I wouldn't be reminded of the fact that your husband or significant other who may or may not be an abuser or an alcoholic or a drug user or even a deadbeat has the ability to knock you up. (Don't get your panties in a bunch. I'm just jealous.) Instead, I have to enlist a team of professionals and spend the equivalent of the FDIC insured amount, without the same guarantee of course, just to have a chance of having what you can get for free. Many of you know what it's like to just go have a drink and/or get drunk, then all of a sudden you are pregnant. Well I have kept my head on straight... no drinking, no smoking, no recreational drugs (not that I'm interested in the latter two). Perhaps I should throw caution to the wind and get drunk, do some drugs. I have enough leftover sterile needles and syringes after all. But the reality is that no matter how much alcohol I consume, it won't correct DNA. However, it may kill enough brain cells that I won't understand the concept of DNA and how hopeless our situation really is.

And last but certainly not least, I'd like to thank the UNIVERSE. I feel all the more special that you would take the time and energy, singling us out of the billions of people on earth. So an extra special thank you goes out to you, Universe, for weeding us out of the gene pool.

I know just where I'm going to put this award...right next to our 'SCREWED' trophy.



OMG, I need a drink. Hell, I need the whole damn bottle!

12/12/2008

Back in the chase...


As most of you know, we've been chasing that stork for our entire married life. We've never used any stork repellent or put out a sign that said "No Storks Allowed." Instead, we tried to attract it. We learned about the conditions that the stork likes and what would attract the stork. We learned about all the fertility signs and the most optimal time to entice the stork. We would even set out traps and hoped that we get lucky. Not once did the stork show up at our doorstep. After a while, it seemed like chasing the stork proved to be much more difficult than we first realized. So we enlisted the help of a local stork hunter. With his first attempt (IVF/ICSI/PGD-FISH), he shot me in the ovaries and I ended up hospitalized for 8 days (severe OHSS and almost lost both my ovaries). We realize that things happen that's not totally in our control but being the professional stork hunter that he claimed to be, he should've known better. However, we gave him the benefit of the doubt and gave him several other chances (3 FETs). After those failed attempts, we realized that the local stork hunter was more talk than results. He would keep stringing us along and taking our money (we're 100% out-of-pocket) until we finally realized that we had to hire another stork hunter...the best stork hunter in the United States. The best stork hunter came with a very steep price, but he has the reputation and stats to back that up. Even though there has been an empty trap (July's BFN) and unforeseen circumstances (the 7 CGH 'no result' blasts), we still have the utmost confidence that he has our best interest in mind and will do his best to catch our stork.

Before we made up our minds on what we're going to do with the 7 'no result' blasts, we spent the whole morning on the phone with a few people from CCRM. First, I spoke with John, our embryologist. Back in July, he did a re-biopsy on our blasts that were shipped to CCRM from the FL fertility clinic. Remember that he thawed the 5 frozen blasts... 3 died upon thaw (ugh, my FL RE used the old method of freezing) and 2 were re-biopsied for FISH analysis for the translocation...1 is normal and 1 is inconclusive. Both of them were vitrified and are still frozen in CCRM's lab. He told me that he personally will be doing a re-biopsy of these 7 'no result' blasts. Because the embryos were vitrified after the first trophectoderm biopsy and will be re-vitrified after the re-biopsy, he reassured me that the risk of damage to the embryos will remain at 1%. Apparently, vitrification makes a lot of difference (in addition to the skill of the embryologist). I asked him if he will re-grade the embryos after the biopsy, and he told me that the grade they were already assigned is pretty much the grade that they are even after another biopsy. He said that if we agree to have them re-biopsied, he will do the re-biopsy sometime next week and will call me afterward to let me know how things went. And we will have the results of the FISH analysis before Christmas.

Next, I spoke with our genetics counselor. She said that she doesn't have a written copy of the CGH report, but that she was told there were indeed abnormalities with 13 & 15, which we expected and there were no trisomy 21 in the 8 abnormals. I was thinking that maybe I should get the aneuploidy screening, but since she said that there were no trisomy 21 I felt more at ease. She reiterated that babies with trisomy 13, 18, and 21 can go on to have a live birth, but babies with trisomy 13 and 18 will die within a couple of weeks after birth. Those with trisomy 14, 15, 16, 17, 22, and 18 will all miscarry. Also those with monosomies (except XO - Turner's Syndrome) of any of the chromosomes will miscarry.

I asked for clarification on what 'no result' means. She reiterated that it has nothing to do with our embryos. She explained that sometimes when they amplify the DNA there is not enough DNA to test. And sometimes there is some signal but that signal is weak so they are not confident one way or the other. Now, I'm starting to get the picture. Apparently, glitches happen. She said that they happen in 10 - 15% of the cases, but that our case was unusual in that it resulted in 45%.

Then I spoke with my nurse. Our nurse Jen has been great throughout all of this. She was really upset at the number of no results. She told me that when she heard about our CGH results, she immediately ran to our genetics counselor's office. Anyway... we talked about the FET cycle and when we could start preparing for that. As we are expecting the results from the FISH analysis before Christmas, we could do the FET as early as January. I asked about the differently FET protocols, so she briefly explained them: (1) BCP & Lupron shots, (2) Lupron shots only, and (3) patches only. I told her that my regular doctor, upon knowing the results of my hypercoag panel, is concerned about my being on BCP, so she said that I will probably want to do the Lupron only protocol. She emailed me a sample FET calendar (Lupron only), and I am supposed to call her with my next AF to discuss which protocol and the date I want to do the ET. We briefly discussed about the FET schedule for February. Before we hung up the phone, she told me that once they get the results, she will schedule a re-group appointment for us to discuss things with Dr. Schoolcraft.

After the phone calls, Jerry and I discussed our options and what they recommend. After much thought and consideration, we're going to take their advice and choose Door # 1...To just do the FISH analysis for the translocation. We signed the consent form and FAXed it to them and put a hard copy in the mail. Sometime next week, John will call us to let us know about the re-biopsies. And hopefully before Christmas, we will get the results of the FISH analysis.

So our chase continues for our ever-elusive stork...

12/11/2008

So confused...


It doesn't seem like I'm ever going to be released from limbo-land. CGH was supposed to be our answer. But it looks like even the most high tech thing out there isn't even able to help us. I feel like I've been holding my breath all this time and thought I could start breathing again once we get the results. At least we would know one way or the other. But I was wrong. I don't even know if I could ever breathe again...

I received a phone call from our genetics counselor around lunchtime today. I so was not expecting a phone call from her at this time. Although my heart was excited for a very brief moment, I sort had a feeling that there's going to be bad news. She asked if we had time to discuss things. It cannot be good news if a genetics counselor is calling about CGH results and asks if you have a moment to discuss things. I asked her if it's bad news, and she said, "Complicated." Immediately, I knew that there was a problem. My first thought was that maybe our cells got lost in transit from Colorado to New Jersey. I was not prepared for what she was about to say.

The genetics counselor told me that Dr. Mandy Katz-Jaffe (CCRM's genetics research director) received our CGH report via phone from Reprogenetics, so she does not have a detailed, written report yet. Out of the 15 blasts biopsied, she said that 8 of them were abnormal. Ok, I guess that's to be expected. I was prepared for that. I wasn't prepared to hear what she was about to say next. The rest of the blasts were 'no results,' meaning that they aren't normal nor abnormal. Huh? She then went on to say that it has nothing to do with our embryos but that it's a limitation of the technology. Huh? I was confused. If CGH could determine 8 embryos as being abnormal, why can't they determine the rest one way or the other?

She said that Dr. Schoolcraft and Dr. Katz-Jaffe had a lengthy discussion about our situation, and she informed me that they never do that. They either defer it to one or the other, but I guess they wanted to discuss the best way to proceed given the circumstances. For the seven embryos with no result, Dr. Schoolcraft and Dr. Katz-Jaffe are recommending that Dr. John Stevens (CCRM's director of the embryology department) thaw the 7 embryos, re-biopsy them, and re-vitrify them. Then send the biopsied cells to Reprogenetics next week where they will perform FISH analysis for the translocation only (13 & 15). The genetics counselor emailed me papers that we will have to sign to have the 7 embryos re-biopsied and re-tested. Dr. Stevens would be able to re-biopsy them next week and we could get the results before Christmas.

Our second option is to do the re-biopsy and re-vitrify them. Instead of doing FISH analysis for only 13 & 15, they could also do aneuploidy screening (14, 16, 17, 18, 21, 22, X, and Y chromosomes). Because of my age, she said that I am not at an increased risk to produce eggs that have an abnormal number of chromosomes. Dr. Schoolcraft and Dr. Katz-Jaffe both agree that screening for aneuploidy (14, 16, 17, 18, 21, 22, X, and Y chromosomes) in addition to the translocation may reduce the number of normal embryos that would be available for transfer. As with any PGD (FISH and CGH), it is only 90% accurate and, therefore, it is possible that a normal embryo could erroneously be scored as having aneuploidy. They don’t want to risk that. Their goal is to eliminate the embryos with an unbalanced translocation, thereby preserving the embryos that are normal for the translocation and offering them for transfer.

Our third option is to do nothing and take our chances with the transfers. I asked her the consequences of transferring aneuploid embryos. Embryos with trisomy 13, 18, and 21 all could result in live-births; however, babies born with trisomy 13 and 18 would die within the first couple of weeks of life. Abnormalities with 14, 15, 16, 18, and 22 would always result in a miscarriage.

Before we decide what to do, I want more information on the 8 CGH abnormal blasts. Do all 8 have the translocation? If so, is there a pattern as to what other chromosomes are abnormal with the translocation? I still don't really understand why the 7 blasts had no results. She said that it has nothing to do with the embryos but with technology instead. But she said that CGH could screen for translocations. She said that ours is the first case using CGH to screen for translocations. I guess I'm just confused, just so confused.

12/09/2008

A thing about translocations...

Ok. So today is 3 weeks and 4 days. Gosh, it seems like forever already! I have been trying to keep myself occupied and not think about it, but it's nearly impossible for me to think of something else! People say that the hustle and bustle of the holidays are supposed to be a distraction, but I don't think it's working for me. Sigh.

Since I can't think of anything else but our 18 blasts -- 3 blasts that are PGD normal for 13 & 15 and 15 blasts waiting on CGH results -- I might as well not fight it and just blog about it.

We first heard the term Robertsonian Translocation from our first RE here in FL back in May '06. Because of the severity of the male factor (abnormal everything), the RE had Jerry karyotyped. We weren't opposed to it because every single exam that Jerry had to take (some of which were very painful like the trans-rectal ultrasound), everything came back normal. We just wanted answers. We were expecting his DNA to come back normal as well. I remember thinking, before we were told the results, that anything would be better than abnormal DNA. OMG, I was in shock and disbelief when we got the devastating news. We spoke with a geneticist in Boston, and I asked her how this could be. There really is no answer, as all of his siblings and his parents would have to be tested. All of his siblings and/or spouses are past the child-bearing age or had other issues going on, so the geneticist said that there would be no point in testing them. Only one of his siblings has a biological child. Two of his siblings resorted to adoption to complete their families. And one sibling chose not to have any children, as his spouse already has children from a previous relationship and doesn't desire any more. Upon hearing this, the geneticist told me that most likely the translocation could've been inherited. We spoke with 4 different geneticists, and they all said, after going over Jerry's family history, that it could most likely have been inherited rather than some random event.

If you click on the picture at the top of this post, you can see the translocation and how it affects the embryos. Before, it all seems so abstract. But after actually taking a look at the translocation, it gives me a better grasp on the whole thing. And when I study it further, it just makes me scared, scared at just how severe it really is. Because of the translocation, out of the six possible combinations, only 2 embryos would be viable - one completely normal embryo and one having the balanced translocation. Futhermore, we learned that about 65% of the sperm are affected. Our geneticist says that although it's good to know what we're dealing with, it doesn't mean that every cycle 65% of the embryos would be abnormal. Sometimes, there may be less abnormals and sometimes more abnormals. The 65% came from the sperm that was checked at that particular time (last June).

With our first two IVFs we did PGD, specifically the FISH testing. The FISH testing was used to screen for the affected chromosomes. With our first IVF (at the local FL clinic), we had 8 "normal" out of 17 embryos tested. However, we couldn't rely on the 8 being really normal. You see, the FL RE tested for 13, 18, 21, and the sex chromosomes, totally skipped testing for chromosome 15. While the additional chromosome testing information is useful, our situation didn't require 18, 21, or the sex chromosomes to be tested. Therefore, we couldn't trust if what he deemed "normal" is really normal in our case. So that's why we had the 5 remaining frozen blasts re-tested. (There were only 5 frosties left after the 3 failed FETs.)

With my 1st IVF/ICSI/PGD cycle at CCRM this past July, we had 23 embryos that were tested for chromosomes 13 and 15. And at the same time, Dr. Schoolcraft also tested the 5 frozen blasts from FL. Out of the 23 fresh embryos, only 7 were normal for both 13 and 15. And with the re-tested blasts, only 1 was normal and 1 was inconclusive. One 5AA and one 4AA blasts from the fresh IVF were transferred. BFN. Out of the fresh, only one made it to freeze and the re-tested blasts were also frozen. So at that time, we have 3 blasts on ice. With our November IVF/ICSI/CGH cycle, we have 15 blasts that we're waiting on on the results.

Because I've never even got so much as a BFP after transferring top quality blasts, there may even be a bigger problem with the chromosomes than expected. So that's why we're doing CGH, where it tests for all of the chromosomes. The FISH testing is limited to testing on a few chromosome pairs. Although it is great that chromosomes 13 and 15 could be tested with FISH, it doesn't test for the other chromosomes that might be affected due to the bulkiness of the translocation. Our CCRM geneticist told us that perhaps the translocation affected other chromosomes from pairing up correctly. So by doing CGH, hopefully we'll get some answers.

12/06/2008

While we're waiting...


So it's been 3 weeks and 1 day since the cells from our 15 blasts were sent to Reprogenetics in NJ for CGH testing. Our geneticist, a few days before my ER, informed us that it may take around 8 weeks to get the results back. So it looks like we've got a little while yet to go. I have always been very anxious during my 2 week wait, so this is having me on pins and needles for 4 times longer!

While we're waiting, let me give a quick overview of CGH (from what I understand). CGH stands for Comparative Genomic Hybridization and is used to analyze the full karyotype (23 pairs plus the sex chromosomes). It is used to identify an imbalance in chromosomal material such as Trisomy 21. It is until recently (within the past few months) that CGH can be used to screen for certain translocations (i.e., Robertsonian Translocation 13;15). We've been told that we're one of the first couples to use CGH to screen for Jerry's type of translocation. Before this, we could only do FISH analysis (tests only 9 to 12 pairs plus the sex chromosomes).

The process starts when the embryos are grown until they reach the blast stage (usually around 5 days in culture). Then the embryologist grades the embryos and decides which embryos to biopsy. The embryologist then biopsies the trophectoderm cells (outer cell mass of the embryo). The cells from each embryo are placed in its own test tube and shipped to Reprogenetics for analysis. Because the turnaround time for CGH, all of the biopsied blasts must be cryopreserved.

Once the samples are received by Reprogenetics, the DNA contained in the tubes is amplified. The sample DNA is tagged with a green fluorescent tag and then mixed with a sample of normal DNA, which is fluorescently labeled red. Then the sample DNA (green) and the normal DNA (red) are cohybridized to a slide, which takes approximately 71 hours. Then a microscopic analysis is done. The images images are collected and analyzed by the computer, which compares the intensities between the green and red of each chromosome. Thus, a molecular karyotype is generated. A 1:1 ratio of each chromosome is considered normal. Any other ratios are considered abnormal. A couple of examples of abnormal results include Trisomy 21 with a 3:2 ratio and Monosomy 21 with a 1:2 ratio. CGH has an accuracy rate of around 90%.

The chromosomes of interest to us are chromosomes 13 and 15. Those are the chromosomes affected with Jerry's Robertsonian Translocation. I will discuss the Robertsonian Translocation in further detail in another post. The reason we're doing CGH this time instead of the FISH analysis is because we've never gotten a BFP, even after transferring top quality PGD normal blasts. Remember, the FISH analysis only screens for up to 12 chromosomes. So there is a possibility that even though our previous blasts were considered PGD normal, the other chromosomes that weren't screen may be abnormal and we just didn't know it. Hopefully, CGH testing will be able to give us some much needed answers.