aCGH results. Did you put your bets in?

aCGH, (array comparative genomic hybridization), is a type of genetic testing that allows for the detection of all 24-chromosome type aneulpiods.  In other terms, a test that looks at the cells of the embryos to see if an embryo is ‘normal’ or ‘abnormal’.  This technology is used with IVF, but is not part of an IVF unless recommended by the RE/embryologist or requested by the patient.  For women of older child bearing age they typically recommend PGD/CGH (unless an egg donor is being used) since the chance of abnormal embryos are higher after the age of 35, but for women in their 20’s and early 30’s, CGH/PGD is not typically something they urge you to do.  You will find couples opting to do genetic testing that have history of RPL (recurrent pregnancy loss), several failed IVF cycles, structural chromosome rearrangement, or couples that carry markers for certain genetic diseases (i.e.. Huntington Disease, Cystic Fibrosis, Muscular Dystrophy et.).  The purpose of CGH/PGD is used for the diagnosis of genetic disease prior to implantation so that you can ensure that the embryos you are transferring are healthy and have the ability to implant and survive.

Our first IVF we didn’t think twice about testing our embryos, I was only 27 and there was no reason to.  After the 2^nd & 3rd miscarriage we brought it up to our doctors but was told there was still no reason to, so we didn’t.  Then the 4^rd m/c … we asked if we genetic testing is something that we should really considering it but since our 4^rd pregnancy was a healthy baby girl we were still advised there was no real reason to.  5^th transfer came around and I really, really, reeeeeally wanted to do genetic testing, even sought a 2^nd and 3^rd opinion, but was again advised there was no need for genetic testing.  Granted it was our choice and we could have done it, we took the recommendations of all the doctors and opted out – worst decision we made.  Lesson: Always trust your instincts!!! So despite our better judgement we opted not to.  

What a slide of Trisomy 21 looks like.  (3) Chromosome 21's instead of 2

That was the cycle we had 2 textbook perfect embryos.  Then 5^th m/c  - our Trisomy 21 (Down Syndrome) daughter.  We would have done testing for our 6^th IVF, but because it was a FET (frozen embryo transfer) we were unable to since it would require the embryos to be thawed, biopsied, then re-cryopreserved (to wait on results) and thawed out again.  It would have been far too much trauma for the embryos to handle.  

When we finally switched over to Dr. Sher there was no questioning if we should do CGH, it was a given and a must, mostly due to my history of RPL, but also our history of aneuploid pregnancy. 

Last cycle we did mCGH (metaphase comparative genomic hybridization).  We started with 13 embryos being biopsied, but by Day 5 we only had 4 embryos left ( only 3 of them were able to be tested).  With our previous cycle the mCGH results were: 1 normal embryos, 1 abnormal and 1 incomplete.  An incomplete result just means that when they went to look at the DNA strand, part of the DNA was missing (either during the biopsy, transferring of the cell to the slide,  during shipping, or a million other reasons, pretty much just human error) and an incomplete results happens in (I believe) <10% of cases.

With mCGH one cell is extracted on Day 3, its done in a lab in Turkey and takes 5-6 weeks to get results.  It is also much more expensive.

This time around we did aCGH, similar testing (both look for genetic abnormalities) but with aCGH a few cells are removed from a Day 5 embryos and results only take 2 days.

Difference between aCGH vs. mCGH

This cycle around they were able to test 13 embryos on Day 5.

Results: 4 came back abnormal, 2 came back inconclusive and 7 came back normal.  For a total of 9 frozen embryos waiting in SIRM - Las Veas for transfer.  9!!!  

And for those questions flying though peoples minds - no, not all 9 will be transferred.  I did asked our Baby Baker if she wanted to be the next Octomom, but I guess that didnt sound too exciting to her!  I think she would have gone for it if I didnt tell her she would have to keep half of the litter if all 9 took.  But in all reality, most doctors will not transfer more than 2 genetically 'normal' embryos at a time, because of the higher risk of multiples.  Success rate of a genetical 'normal' embryo to implant is >60%.

Going through the waiting process of this cycle, I knew all we needed in the end was 1 healthy ‘normal’ embryos, but of course preferred 2.  My hope was that we could get 4, so we could have 2 on ice for future use, since this was the last fresh IVF attempt I will be doing.  What I kept saying my ideal of great news would be, was if we got 6 normal embryos.  I would be on cloud 9 and more if that new came, but knew that seemed pretty much near to impossible and knew my hopes were far too high for that.  Well God gave me that 'near-to-impossible' of what I wanted and then threw in some humor by adding in 1 more to that 'normal' embryo for the icing on the cake!  Never, ever, did I think we would have news of 7 normal embryos.  Crap, now wondering what they heck we will do with all of them.  

We do know the sex of all 7 embryos, and will share that news when we are ready. But of course if we tell everything at once, what would be the fun of that!

Blasts: Day 6 update

Well I'm still in shock.  Not quite sure how to take everything.  'Praise Jesus' is all that can come out of my mouth at the moment!  The hand of God was on this cycle for sure – and praise God for his faithfulness in all this!   I don’t want to give credit to all the supplements I was doing this cycle, or all the electro-stim I did, because I know that is not what made this cycle, but I will say I will recommend it to anyone who ask what I took to help with quality!  I can not thank my amazing Acupuncturist enough for all her help.  She has a list of the Top 3 hardest clients she has treated over the 19-20 years she has been doing this - I got to make that Top 3, luck me!!  In her amazingness and extremely generous heart, she saw me for almost 3 months leading up to this last ER ... all on her.  She was determined to make this cycle successful!  I am so grateful for her,  her determination and her heart, because I know it made a difference!! 

With that being said.  A little info on Day 5 Blastocysts.  Embryos on Day 5 are continuing to divide and the number of cells are continuing to increase and at this point and are doing so into specific cell types.  Embryos that have been grown out until Day 5 are now referred to as "Blastocysts", or "Blasts" because they have formed a cystic cavity called a blastocoel in it center.  A Blast has two tissue types, the trophectoderm (TE) and the inner cell mass (ICM). The trophectoderm is what develops and become the placenta, while the inner cell mass is the begning of the fetus.  Think of a balloon.  If you blow up a balloon and put a ping-pong ball inside, that is what a Blast looks like. The latex of the balloon is the TE and the ping-pong ball is the ICM.  

Blastocysts have survived an important "survival test."  During the first few days, the embryo relies on the egg cell (mom) for its growing nutrients, but to survive past day 3, or 4, the embryo must activate its own genes so that it can carry on growing and diving.  If an embryo is able to make it to the Blastocyst stage it is sort of a sign that those embryos are the product of "survival of the fittest."

There is a 3 list of Blastocysts: Very Early Blast, Expanded Blast and Hatching Blasts. 

--  Very Early Blastocyst: the cavity is just beginning to form in the embryo and the cell types are not yet distinguishable;

--  Expanded Blastocyst: the cavity is fully formed, the embryo contains 100 to 125 cells, but is still contained within the shell

--  Hatched Blastocyst: the embryo is outside of the shell (hatched), and contains upwards of 150 cells.

On Day 5 (yesterday) they biopsied all our embryos for aCGH testing, or in general terms - they are testing to see what embryos are genetically normal.  After they biopsied them, they then continued to grow them out though today, Day 6.  Those that didn't arrest and were Graded 1 or 2, where then frozen!  Anything that would be considered Grade 3 typically doesnt survive a thaw and make it to a successful pregnancy, which is why they don't freeze them.

Around 2:30p this afternoon, I got the call for the payment for our CGH testing and was very confused.  The financial lady was charging me for a lot of biopsies.  Too many in my opinion.  It’s a flat rate of $2250 to test up to 8 embryos, and the bill was for *a lot* more, so was that meaning I had more than 8 embryos on Day 6??  Couldn’t be!!  I ask the billing lady some questions in regards to the numbers and everything, but she was unable to give me any information, just told me "I got the paperwork, this is what it said and was calling for payment, any more than that you have to talk to Linda (my nurse) or Dr. Sher."  I figured she had the wrong information or they misunderstood and thought I was doing Day 3 testing (which we did last time around) because the charge was for embryos numbers I had on Day 3.   I asked her to hold the charge until tomorrow because I wanted to hear from my nurse first – it just didn’t sound right. 

I emailed my nurse this morning at 11:30a because I had still yet to hear from her, she replied promptly and said she had not heard from the embryologist and promised she would call me after the cryopreservation.  6pm rolls around and still no news, despite the 2:30p payment call, so thought I would send her another email to check in.  Just before sending it, the phone rang.  It was her.

 
I explained to Linda I had talked to the billing department earlier and had an idea of the news but told her it didn’t seem correct.  She laughed at me and said that she had to double, then triple check the papers before calling me tonight because she too thought they had given her the wrong patient information.  HAHA!
The news, well ... A bakers dozen!  Yes 13!  13 Blasts is what we currently have in the freezer. WHAT!!  I was shocked.

Pregnancy rates are the same with Grade 1 and Grade 2 Blasts.  She said its on the rarer side for her to see many Grade 1 embryos, although it does happen from time to time, but most everyone has Blasts that are Grade 2 -just means the Blast has minimal fragmentation. 

Ours?  4 of them are Grade 1 (meaning no fragmentation at all) and 9 of them are Grade 2 (minimal fragmentation.)   AH!  Double shocked is all I can say.  Utter double shock. 

Of course now we are anxiously waiting for the last report to come on Friday.  The aCGH news, which tell us how many of those 13 are normal, and how many are abnormal.  Typically they say to expect 50% to be normal, (however the older you are the lower that % goes) I was told due to my age (being on the younger end) to expect a little over 50% to be normal - of course cant help but be cautiously optimistic about that too.  Would love to get news of 6 being normal, but honestly that seems like we are asking and hoping for a lot, so at this point just praying for new of at least 4 being normal!  These next 48 hours are going to crawl.  Patients is not my virtue and I am having to learn it the hard way with all of this.  

  

The Lord has been faithful through this whole cycle and I am going to have faith He will continue to do so with the aCGH news, I am grateful we are only asked to have faith 'big as a mustard seed' because at times like this, when you want something so much, its hard not to dwell on the past - and the past, our past, doesn't show the best of numbers in all this.

Thank you Jesus for these 13 Bakers Dozen!  Unexpected to say the least, but not unwanted!  My mom has always said 13 is a lucky number, mostly due to the fact I was born on the 13th and she hated that everyone would say it was unlucky.  But I will agree with her now - it is lucky!!!      

Day 3 Update

Day 3 Update - June 23rd:

Life as in IVF patient means you pretty much live in a state of constant suspense.  Things are always moving and fluctuating and there is rarely, if ever, a flat-even road.  You are continually asking yourself; How well am I responding to the drugs?  Is the dosages high enough?  Is it too high?  Would I have responded better to a different protocol?  How many follicles are there?  Will I have EFS (empty follicle syndrome)?  How many eggs will/did they retrieve?  Will I have enough mature eggs?  How many will fertilize?  Then once you get past the ER, and after you get your Fert Report, then you start a new roller coaster of worrying about the embryos and add in even more questions/worry.  How good are my embryos?  How are they growing/dividing at a health rate? Is the quality going to be good enough?  What if they arrest?  Should I do a Day 3 or Day 5 transfer?  Assisted Hatching?  PGD? CGH?  On and on and on.  

Thankfully most clinics will call you with updates about every other day, and it helps put your mind a ease, at least for about 10 mins, then the worrying and wondering starts back up until you get the next update phone call. 

After retrieval you will get 3 – 4 calls with updates telling you how the embryos are doing.  1^st update is with the Fert Report, which happens on Day 1 (the day following retrieval), the 2nd update is on Day 3, and the last update (unless you are doing genetic testing) is on Day 5, which is typically transfer day.  If you are doing genetic testing you will also get a call on Day 6 or 7 with the results on the biopsy and how many embryos were able to be cryopreserved (freezing (in liquid nitrogen) and storing embryos for future use), if any.

Day 3 embryos, are graded on 3 criterias, the 1^st being the rate of cell division.  On Day 3 most healthy embryos will be between 6-9 cells (with an ideal embryos being 8 cells), some healthy embryos can be lagging behind 4-5 cells, or growing a bit faster 10 cells, but typically if they are slow/fast growers it’s a sign of an abnormal embryo!  Embryos that’s are growing too slow, or fast, by Day 3 have about 10-15% chance (half that of a 6-9 cell embryo), of implantation success. 

The next thing that embryos are checked for in the grading process is Fragmentation.  Fragmentation is when parts of an individual cell in the embryo break apart, or ‘fragment’.  Most embryos will have a slight degree of fragmentation but typically you want no-to-little fragmentation, it has been found that 25% or more fragmentation leads to poor implantation rates.

 And the last of the grading criteria is wither the cells are symmetrical in size and shape.  Not only does cell number and fragmentation matter, but so do symmetry.  Symmetry is assessing the cell in the embryo to see if they are all the same size, it is not as significant as cell numbers and fragmentation but helps determine the grade of the embryo and which ones would be better suited for transfer.  An embryo with same size cells is graded G (good), if a few of the cells are different sizes its scored F (fair), and embryos with all different size cells P (poor) and those graded poor will typically arrest if watched/cultured for another 1-2 days.

So in a nut shell, a text book “perfect” Day 3 embryo would be a 8-cell, no fragmentation, and all the cells of equal and symmetrical size.  But as we know embryos are so variable, and a healthy baby can come from an any cell number, size or fragmented embryos.  Sometimes those “perfect” looking embryos are far from good, and actually have additional or deleted chromosomes.  We know this by experience. Our 2 textbook perfect embryos which we transferred back in August 2011 ended up being our daughter who had Trisomy 21 (Down Syndrome).  So really in the end, you can never truly know … unless genetic testing is done, and even then that has its margin of error.  God can do anything despite the poorest, of poor looking embryo - so "perfect" embryo or "poorest" its nothing that is in our hands.

So after explaining a little about Day 3 embryos, here was our Day 3 update yesterday:

18 total embryos, 16 which are growing “beautifully” all 18 with minimal fragmentation.

(1) – 4 cell (slow grower)

(1) – 5 cell (slow grower)

(3) – 7 cell 

(8) – 8 cell (ideal)

(2) – 9 cell

(3) – 10 cell (fast grower)

So we currently have 13 embryos that are in healthy 3 day range, with 8 of them being ideal.  This is amazing new, but with that being said we are cautiously exciting and very guarded.

This has been a typically IVF for us, granted we have about 3-6 more embryos that we have in the past, but we have always had an amazing fertilization report, and amazing Day 3 update, its after Day 3 when things start to get a little hairy, and go downhill.  By Day 5 we get the call that most of our embryos pretty much stopped growing at a steady rate and by the Day 6 call, we find out the left over ones (that were not transferred) are starting to arrest. 

In the past, by Day 5 we have 2-7 embryos left out of the entire batch - and with the the last cycle we only had 4 left and after the results of the biopsy we had even less.

Tomorrow will be big day and we are very nervous about it.  We would love any and all prayers that the Lord would continue to breath life into our little ones, but in the end we know its in His hands.  All we really need is 1 healthy embryo to transfer, of course would like 2 but we will take what we are given.  If by some miracle we are able to have any left over, health embryos to freeze, we would be on cloud nine!!  If I could have it my way, I would like 6 'normal' embryos after its all said and done, but I know that is asking for A LOT and my exceptions are super duper high, so trying to reel that in and hope for 4, but at this point all we can do is wait and see what the Lord has planned for this cycle. 

Next update, tomorrow, Day 5.

Egg Retrieval & Fert Report

Sorry I am a few days late on updates. Been a busy week and haven’t had much time to sit and get things down on paper … well screen. 

Remember when I listed the stages of an IVF?  Well Thursday we hit Stage #3 – Egg Retrieval. 

Signing into the SHER INSTITUTE - Las Vegas for my ER

The egg retrieval went very well – minus my mom being a Nervous Nelly, you would have thought she was going in for open heart surgery.  I will never understand why people don’t like anesthesia , because I love it.  This was my 11^th surgery and I totally get why M.J. wanted a private doctor for his Propofol … if I could do it, I would too.  I love the fun cocktail of drugs, it’s like a legal high, and of course, the best nap one could ask for!

       

Talking to Jim while waiting for the Dr & Anesthesiologist

 Thursday, early morning, we checked out of the AFB lodge and headed to the clinic.  Surgery was at 10am but we needed to arrive around 915 to fill out paperwork, and get through all the pre-op stuff.   

Around 930, they walked me back, had me change, took my vials and started my IV.  Nothing of much excitement, then we just sat and waited for the anesthesiologist and Dr. to get in – they were quite a bit late.  But when you’re the first one on the table you want to make sure they had their coffee for the morning, so I will blame their lack of promptness on the Starbucks line.

They finally arrived around 1030 and I was instructed to use the restroom one last time before walking to the OR.  I hopped up on the table and got situated in the spread eagle position.  They were knocking me out as Dr. Sher was walking in, and next I knew I was waking up in recovery.

Most all of my ER's have been pretty low when it comes to pain level.  My very first one was unbearable and I would easily give it a 10 on the pain scale if you had to ask me, and my by death grip on the gurney rails and lack of ability to talk, let alone breath, was a clear sign they didn't even need to ask if I was in pain and drugged me up pretty immediately.  The rest of the retrievals were fairly easy, minor pain but nothing Oxi couldnt take care of after I got home.

This time around as not as bad as the first, but damn close in line.  All I remember was waking up and eventually rolling on my stomach with my bear ass hanging out of the blankets curled up in the fetal position moaning.  At this point in time I was *highly* regretting my joking to the nurses, in regards to my love of anesthesia/drugs, because I needed my pain meds and didnt want them thinking I was some crazy med seeker ... but thankfully after 2 doses of IV pain meds they gladly gave me, I was able to un-curl out of the fetal position.

Typically ER take about 30-45 minutes.  The doctor uses a transvaginal ultrasound to guide a needle through the back wall of your vagina, up to your ovaries.  Each follicle is a small fluid filled space in the ovary that contains one egg.  They use the needle to aspirate the follicle, gently suck the fluid and egg from the follicle to the needle and collecting it into a test tube.   These eggs are then promptly transferred to the embryology lab for fertilization.

On an average ER day, while the women is in surgery, they set up the guy in a room to leave his sample.  They prefer a fresh semen sample, unless they man is dealing with MFI (male factor infertility) then they may have the man leave a sample a few days prior, as well as a sample on the day of – just to make sure they have enough healthy sperm to use. 

In our case, since we knew Jim wouldn’t be here, we made sure to leave his sample before he deployed. 

After the eggs are transferred to the lab, they are then fertilized with ICSI (intracytoplasmic sperm injection).  Once-a-upon-time this used to be used only for men with low sperm count or motility, however it is now typically for RE's to use this process over the conventional fertilization because pregnancy rates are much higher with ICSI than those of conventional fertilization.  And after spending thousands of dollars to make it this far into the cycle , it only makes since to give yourself the best possible opportunity for fertilization, rather then risking low fertilization rates.   ICSI involves the embryologist selecting a single healthy sperm, and injecting it directly into each egg under direct microscopic vision.

Stage #4 – Fertilization. 
Just because ICSI is used, and a sperm is directly inserted into an egg, doesn’t meant you will get an embryo / fertilized egg.  After ICSI is performed it takes, approximately, 24 hours to see if fertilization has occurred.
The morning after an IVF ER they eggs are checked for fertilization.  If fertilization has occurred there will be 2 pronuclei (male & female genetic material) in the center of the eggs.  And then the l.o.n.g. dreaded wait to see what happens with those embryos between fert day and Day 5 (typical transfer day) begins.  Its the waiting to see which embryos will arrest along the way, and which one, if any, will make it to Day 5.

So with all that being said, I am sure you are just wondering my news.
ER : 25 eggs retrieved, 2 immature, 19 mature and 4 they were watching to see if they would mature up in the lab.

Day 1, Fertilization report: 18 embryos, and 3 of the 4 eggs they were waiting and watching, showing signs of fertilization.  18 for sure embryos, with a possibility of upto 21!

Next update will be on Day 3.