Erm, what is going on?!?!?

That, gentle readers, is not a question that is likely to be answered anytime soon, if ever. After my IVF, when things had looked super weird, my RE and I concurred that maybe following my AFC  for the next few months would be a good idea. I finally rolled off the procrastination wagon and took myself off to get an antral follicle count (AFC) done. The results floored me.

To recap the madness, mostly for my own records: 

• August 2010: AFC = 34 (evenly distributed in both ovaries)
• November 2010 (post 1 pregnancy and 1 loss): discover AMH is paradoxically low and am Vitamin D deficient, correct vitamin D deficiency
• December 2010 ; AFC = 30 (evenly distributed in both ovaries) ; AMH = over 5 ng/ml
• December 2010-April 2011- Take around 4000 IU vitamin D daily
• April 2011: AFC = 16  (11 in one ovary and 5 in the other)
• April 2011-Feb 2011: Add prenatal with extra vitamin D, so total is 5000/day, start taking calcium (50 % of RDA) daily as well.
• Feb 2012: AFC = 16 (but now evenly distributed in both ovaries) AMH = 4.3.
• March 2012: IUI# 3 results in failure
• March-July 2012 - Drop vitamin D dosage to around 3000 IU/day
• June-July 2012- 3rd pregnancy and loss, due to Trisomy 4.
• August 2012-October 2012- drop Vitamin D dose 2500-3000 IU/day, continue calcium, however less regularly. Start Metformin
• October 2012: AFC = 13 (more or less evenly distributed in both ovaries); AMH= 1.6, then 2.6 on retest
• November2012-December 2011: Stop Metformin. Continue vitamin D at  2000 IU. Stop calcium almost completely.
• December 29th 2012: AFC = 25 (evenly distributed in both ovaries)! AMH still pending.

With the drastic drop in my AFC (from 30-13 in 2 years), my RE was afraid that it  was because of drastic ovarian aging. I was less afraid of this, and felt that it was an unexplainable response to physiological changes induced by varying levels of vitamin D and *maybe* calcium in my system. I had hoped that after I dropped it to 2000 IU/day, with no added calcium, things would change as far as AFC went eventually, but this big jump back up surprised the crap out of me.  I don't know what to make of any of this- the changes in my Vitamin D intake alone are not that drastic, and there are no good explanations. 

I've played around a lot with vitamin D. Not supplementing at all, and just relying on sunlight and diet is a joke, its been proven time and again that this will leave me in the deficiency range.  What does deficiency do for me? I also lost a chromosmally normal child in this period, and my luteal phase used to be far too short on occasion. Its not so great from a physiological viewpoint- my health overall has subtly but definitely been improved by bringing me into the sufficiency range. However, how sufficient should I be? 

Deficiency of vitamin D is something that has been proven to be a contributor to infertility.  But a too high blood level may be equally bad, or worse, in my case.

4000-5000 IU with added calcium was something I felt great on, but *may* have had unanticipated, adverse effects on my reproductive system, which is not surprising in theory, because hey,  Vitamin D has been shown without doubt, to be a powerful modulator of this system.

Two thousand IU, the dose I am on now, is a fairly conservative, play-it-safe dose, given all the hot debate on the Vitamin D RDA. The IOM's  2010 recommendation of 600 RDA/day is pretty controversial and has not been well received at all. Other, seemingly saner voices advocate in the 1000-2000 range. The vitamin D council recommends over 4000/day, I believe. Experts at endocrinology are all of differing opinions.  In my revised opinion, everybody needs to keep their blood levels around 30 ng/ml, and its best not to go much higher. The amount you may need to get your blood level to 30 may vary from person to person, some trial and error might need to go into how much you need.

So I'll stick with 2000 IU/month for a while and see how I do, longterm. I'm now also going to start the CCRM regimen (melatonin, argenine, myo-insoitol, coQ10 etc) and see how my AFC fares with that. I'm only wondering whether I should wait one more month to start it, to confirm this rise in my AFC. However, I want to be on this atleast for 3 months before we attempt another IVF, which may be necessary very quickly if the transfer to the surrogate next month fails.

But, hey, on the bright side, my issue does not look like ovarian aging.  If only I can figure out what exactly it IS, though.  Bloody, bloody biology.

Updated: Much, much later, I figured out that the issue is that my RE (Dr. Malpani's) machine is older and has poorer resolution. At the point of my second IVF, we checked in two different machines: my AFC was 16 when using the much older 2D machine, and 24 when using a fancy 4D ultrasound machine. All the scans that showed a high AFC (25-30) were done using the 4D machine. Facepalm moment, for sure.

In limbo..

I was so very low when I wrote my last post. About a day after that, I made up with the person I'd fought with, and no other awful thing happened, and within a few days, I was back to my usual even keel. If I'm truly, deeply thankful for anything, I think it is my natural tendency to be ok, no matter what.

Its been a very busy few weeks- my house got remodeled (we are talking painting, polishing, putting new windows and false ceilings in) followed by my brothers wedding- a fun, joyous, if completely exhausting event. We were all so tired that nearly everybody in my house was sick, mostly from our immune systems being hammered from overexertion.

After things came back to normal and most of the guests departed,I'm in limbo now on so many fronts. Waiting to see what happens with my green card application. Waiting for a surrogate to be recruited. Waiting to see what happens, on the career front (I'm working, but its mostly for shits and giggles, not a serious job, its a situation  where I'm just trying to learn new things that will make my resume more attractive to future employers).

Nothing in my life is decided. I've been battered by circumstances going south on me so many times- 3 pregnancy loses- it still is mind boggling. Especially when combined with that un-imaginable IVF result, I *should* be terrified for the future. The weird thing is, I'm not. I'm remarkably ok with the current state of uncertainty, which is a wonder in itself.

But the one thing I don't have in large supply is faith. Nothing really seems to work, and why should I hold out hope that this trend will reverse in the future? But  it can. The other day, I read such a lovely post by Mo, about  an email from her RE about her long term prognosis being excellent, shortly after her first loss. It took so many more losses and so many years for that RE's prediction to come true, but it did. I think that post is a must read for all of us still in the trenches, not to give up hope, and to keep going.

Update just in: a surrogate is close to being recruited. There is a part of me that does not want to know anything about her. I'm a painfully picky person in so many areas. i rejected almost every sperm donor I looked at, and I looked at over a 100 donors easily. And you can't control a surrogate and you have to be ok with whoever you get, whatever their background and habits are, and pray that they will take good care of the precious cargo entrusted to them, that their womb is fertile and they will faithfully swallow the vitamins you plan to give them and avoid chemicals during their pregnancy. I'm almost tempted to try with my own uterus,  then the remembrance of each loss hits me and I'm paralyzed and ready to do anything to avoid going through that again. So right now, I'm burying my head in the sand, and not calling my RE to get every last detail about whoever he has picked. Its so very unlike me.

But for now, I'm very ok. Out of my funk, still missing my cat. We rescued a tiny kitten off the streets. Had we had my old cat, we would not have considered doing this. Ah, the circle of life- one life splutters out, another living thing gets a shot at survival because of that.

A lone contender

Its been an incredibly tough few days. I'm still not over how my cat died- the violence and the wrongness of it. And I miss her so much-- I've had multiple pets in the past few years- I had a cat when I was a student, and when I moved, I found her a good home and kept tabs on her for a couple of years, but letting go of her, while not easy, was possible.I've lost an another dog and cat which were family pets and while those losses tore me up, it was nothing like this. I never bonded with any other creature the way I bonded with H. I could not imagine parting from her, so I never even considered trying to find her a good home when I left New York, even though bringing her across oceans was not easy, neither for her nor me. In the world of a gzillion cats and dogs, she was special. This is really, really hard.

 Now, to the part I'm sure some of you were wondering about--my IVF cycle. In the end, I only had 4 mature eggs. 3 of these fertilized to form 2PN embryos. One embryo arrested immediately, started up again, arrested at the 4 cell stage and stayed there. The second looked perfect (Grade 'A') on day 3, but started stalling on day 4. The 3rd, met all of its developmental benchmarks perfectly, compacted on day 3, morulated(??) on day 4 and was a 'gorgeous' 3AA blastocyst on Day 5, at which point it was frozen.

So---all that, and I end up with what I would have ended up with in an IUI anyway- one great looking embryo, my sole contender.  Since we had only one, we could not even think about comprehensive genetic screening- we have to transfer this one, and pray. We are currently on the surrogate recruiting portion of this program.

A detailed postmortem of my IVF cycle is badly needed, with all the following questions:
1) Am I a poor responder to superovulation or was it the combination and timing of drugs which was not optimal for my system? On CD9, I had 6 synched up follicles, which, I suspect, gave rise to my 4 M2 and 2 MI eggs.  At that point, we switched to from Foliraf (recombinant FSH) to menagon(Urine extracted FSH + LH), upped the dose of stims, and on paper, based on E2 and follicle size, I responded, but most of what came then were immature eggs. So all of that later stimulation, and waiting for the last follicles to respond, *may* have been futile. .As my doctor said, this is gambling to a extent- we did, and we lost. If we had aimed for just 6, and triggered me sooner, would these 6 eggs have been better?
2)My follicles were probably not synched up, whatever that means. Here is a question for you all- does a long lupron or BCP protocol help? I have to go back and look at my baseline ultrasound, but I remember thinking that the follicles in one of my ovaries (the right one) looked larger, and those just turned out to be cysts. 

Anyhow, all of these are things for the future. I pray I will not have to do another IVF and  my one blastocyst turns into a take home baby, But I have to say, my odds are much, much poorer than I thought they would be at this point. I'm so down, for so many reasons. The unimaginable result of this cycle. The massive fight I've had with somebody close to me that near shattered me yet again, just when I thought I'd started to recover from my poor cat's loss. Issues with living in India-that is what triggered that fight. And still, by far the most painful, the loss of my cat.  This is the roughest time I've had in a while, almost on par with the darkest period in my life, the weeks after my first loss. I have not been able to stop crying for the past 2 days and this morning, just in passing, I thought about anti-depressants. I NEVER think about anti-depressants, not even during the worst times of my life so far, so that was a shocker. But- if nothing more comes along, I will mend and get over this. I'm really praying for some kindness from the universe right now.

A time of horror

I had my retrieval last night. They got 11 eggs, so that did not seem too shabby.

I came home, was given Lyrica by my mom and went straight to sleep. Around 3 am, my parents woke me up. My cat, who likes to hang out in our garden (only at night, she is so contrary), which is gated and fenced, was attacked by feral stray dogs that came in through the gate somebody left slightly ajar. My dogs, who were inside the house started barking and my dad and housekeeper rushed out,chased the dogs away,  to find her mauled and barely alive. They bought her in and 10 minutes later she died.

This was a cat I'd rescued from a shelter. I  formed such a deep bond with her that when I left the country, I bought her with me, to keep her safe and give her a good life. It took her a while to get adjusted- which she finally did and now, this happened. I could not keep her safe, I feel so guilty and I'm such a mess emotionally, I can't believe she is gone, I have not been able to stop crying since I woke up this morning.

To add to the misery (that is all that seems to be on the menu for now), I got the fertilization report- out of the 11 eggs, only 4 were mature(in the M2 stage), and 3 out of the 4 fertilized.  None of the 2 M1s fertilized, and from the 4 immature eggs, which were put through in vitro maturation, one made it to M1 and was injected with sperm today.

So at the very best, I may end up with 4 blasts to freeze on day 5, but I doubt I will be that lucky.

My RE is baffled-my case is so, so weird. He says he will do another IVF only if something changes with my AFC or AMH, but right now, I am a shitty responder to superovulation, apparently.

The best thing for me would be to try again naturally- I've gotten pregnant 3 out of 4 times. But I'm done with that- I can't handle another loss.

I'll figure out what to do later, but right now, I'm shaken and saddened to my very core. Out of the two horrible things that have happened today- If I could make  the universe fix one of these 2 things, it would be what happened to my poor, poor cat.

When the universe hurls crap at you, boy is it generous.

Triggered!

I got the first piece of good news this cycle so far yesterday- my estradiol (E2)went up from 2200 (pg/ml) on CD12 to 3521 48 hours later. My ovaries are filled with largish follicles. We did not bother measuring anyway- we could tell that many had increased in size from 2 days ago, but there are no foolproof indicators based on size of whether a follicle has an egg, and a mature one at that.

An E2 of over 3000 is considered decent territory for an IVF response, but when I asked my doctor of how often E2 levels can predict mature follicle number (assuming each follicle produces between 200-300 pg/ml of E2)--he said--75 % of the time. So yeah, its always a crapshoot.

He did say that, barring my lowish AFC(13) for my age, my response has been 'textbook'.

So I triggered (with 5000 units HCG) this morning. And unfortunately, something happened. The injection is given IM, I asked my mom to give it in the hip area, bad call. As I was getting it I felt the muscles in my leg seize up. 4 hours later, I'm limping horribly and can't sit, and nor can I take any muscle relaxants/anti-inflammatories. Spending the day in bed---not as enticing as it sounds, unfortunately!

Minor issue though-egg collection is tomorrow evening, and I hope that brings good tidings. Wish me luck!

Day 12 scan results

First...I'm utterly blown away by what Sandy has wrought. It hits very close to home because had I still been in back in the US, I would have been at the epicenter of this clusterf*uck-  lets just say the building I lived and worked in has featured prominently in the news and a lot of my colleagues and friends have lost years of work. I was also reading about many, many women who had retrievals scheduled early this week--I really hope to god their clinics managed to make it happen. 

I'm thinking about all the people who lived in NYC/NJ area--I hope you all stayed safe, with your homes intact, and hopefully, managed to keep power. 

At my end of things, its looking slightly better, but definitely getting harder and harder to predict.  On day 12, I had my 3rd follie scan and  first E2 check. My estradiol levels were 2200 pg/ml, but since we are not testing regularly, it does not tell us much. maybe another version of me would have wanted more information and regular testing but right now, I'm content to wait till retrieval to see what will happen.

I had around 6 follicles so huge my RE did not know what to make of them---in the 18-25 mm range and a bunch of smaller follicles around 10-15 mm range. I have asynchronous follicle growth, with 2 groups, in other words, and my doc was not happy about that.  I'm going to be kept on my meds till day 14, with a trigger on day 15, with a hope of making some of the little guys grow.

I'm refusing to make a call of whether we should do the biopsy and CGH  microarray untill I have some inclination of  many Day 3 embryos I will end up with. 

But right now, I'm in pain. I've responded a little better (big maybe) to the menagon, which I restarted on day 9, but its turning my body into one big ache, whether given IM or SC.  I have to be reacting to a component in its preparation- the pain begins around 5 hours after the injection and settles into a deep sore ache which  has not gone away yet, even from my injections over 3 days ago.  My respect for the people who take shots, from time of IVF and continue taking them for months, with the PIO and the heparin, is now immense. It takes giant balls--I take my hat off to y'all!

CD 9 follie scan---MEH

I started out with 6 AFC on my right ovary--on CD9,  3 of these are appropriate size,synched up follicles and another 3 are giant (around 18 mm), looking like cysts. In my left ovary, out of 7 available AFC, only 3 are growing (correct size, synched up), one is a straggler, and nothing happening with the other 3. Its interesting-  at least 2 of my  3 pregnancies have come from my left ovary. The one time I failed to get knocked up, it was my right ovary in play.

Overall, this leaves me staring at 6 possible follicles which could yield eggs.  I'd go get a drink (or several), but there is no chance of that till egg collection, at which point I'm done for this cycle(YAY!). I'm coming really close to being called a poor responder (I looked up the definition, they also factor in estrogen production). I've been having mad EWCM since CD7, so hopefully, my E2 levels will not be shabby. Oh, please dear god, please.

The only thing I got a gold star on was something that will not even be in play, apparently, my lining (like every other time I've been examined by the dildo cam), was gorgeous. I'm like a shitty egg donor candidate, but with amazing surrogate potential, atleast till implantation point. Oh, the bloody irony.

I have not written this off yet---there is every flavor of IVF I've read about. The ones where you get a gzillion eggs and inexplicably end up with like 3 good embryos, the ones where you get 4 eggs and end up with the same, and then there are the perfect ones who make like 25 eggs and end up with like 10-15 freezable embryos. Right now, I'm hoping and praying with everything I've got that if I do end up with 4-6 eggs (super likely), they are atleast decent quality.

Surprisingly, I have not gone all gloom and doom--- I'm more like, MEH, whatever happens, happens. My doc asked me how I was doing and I told him I'm comfortably numb- which really is true. I should be more upset about all of this, but I can't bring myself to be, and that is a good thing, right? Why get upset about something you have zero control over?

My meds doses have been increased- I'm back to menagon  now since I was doing not so swimmingly with the Gonal-F equivalent (Brand name here is Foligraf). Problem with menagon, no matter how you give it(SC or IM)- the injection site keeps hurting. Otherwise, other than heartburn, I'm mostly fine. Aanybody have heartburn with IVF? Mine responds well to drugs, but I really hate taking them, given that I'm always illogically nervous about what they may do to my 6 precious possible eggs. But right now, ranitidine and Omeprazole are lifesavers.

Also---I'm just hearing about Sandy- stay safe, all my east coast friends!

IVF # 1---Not off to the most stellar of starts.

I'm on day 5 of my cycle and I had my first follie scan yesterday. It wasn't something that made anybody jump up and down with joy, my AFC was 13.

2 years ago, my AFC was 30 and above. Then I discovered I was vitamin D deficient and I started supplementing, which pushed my AMH considerably. But last year, I had already noted that my AFC had fallen, to around 16, and I also discussed the possible relevance and possible mechanism behind this drop in this post.

Back then, when I was not planning IVF, this was nothing to be bummed about-- I had assumed that my super high AFC for my age reflected my PCOSiness and any deviation from this was a GOOD thing- I thought, maybe decreased quantity might go hand in hand with improved quality, given the finding that women with PCOS have high AFC and can make many, many eggs, often of crappy quality. But since then, I've had one failure to achieve clinical pregnancy and another loss due to aneuploidy, so ummm, it does not look like things have gotten better???

Now that I'm staring IVF in the face, an AFC of 13 is 'not good news', especially when you've come from a much higher number--- it reflects a decreased potential, the best one could hope for is 13 eggs, and in reality you will get less, and you will have fewer than that number fertilize and even fewer that keep going till day 5.

My RE was pretty upset, he still had my AFC of two years ago in his head. While I'd gone in with a daydream of around 20, realistically, I knew I was going to get something in the vicinity of 16, and moreover, I was aware that the metformin I was taking could drop the numbers a touch-- there are a few studies that show that metformin can reduce AFC. So no surprises for me.

I started laughing when my RE finished the scan and he was shocked by my reaction-- he asked me why I was laughing-- I remember thinking it was a preferable reaction to crying.

The scariest part is, I really may have to give up on doing CGH microarray if we get only a few embryos that go past day 3,  for anybody who has done this- how many embryos did you have? My RE puts the cutoff number as 10, and that is a really tall order with an AFC of 13.

This presents so many dilemmas- if I can't do screening--then what? I don't know what percentage of my embies would be aneuploid, and its a very, very scary place to be in, for somebody who has lived with RPL.
Most people get around this by transferring multiple embryos---I really am terrified about transferring 2 embryos and the higher risk pregnancy of twins and the many, many higher risk scenarios that could occur.

Ironically, my number of 13 is in normal range for an Indian woman of 32, according to my RE. I've somebody who is SUCH a grey zone fertility-wise-- I've gotten pregnant out of 3 out of  4 attempts, by nothing more than un-medicated IUIs, which would make one think I'm a fertile frickin bunny till you realize I've managed to lose all of them.Then my AFC is all over the place--does my drop from 30 to 13  have nothing to do with weird vitamin D physiology and instead indicate a sharp drop in fertility?? I have no idea how I'll respond to superovulation inducers...and things have gotten off to a not good start.

Another thing that is an area of contention for me: My RE wanted me to try menagon (which is urine-extracted FSH with a little LH). I freaked out when it was given IM, and indeed, when I took it for the first time, 24 hours later, I still have injection site soreness. So instead my RE said I could take an equivalent of Gonal F(synthetic FSH), no LH, which is given subcutaneously, which was what I was looking for, being a wimp and all. I took that today, I tolerated it fine-- only thing I'm worried about, there is no LH. Here is a theory that some, but not all docs believe in, that a little LH makes follicle development better so they give Gonal F with luveris(synthetic LH). I'm wondering if I should ask for this, for my own peace of mind if nothing else....any opinions anybody?

Questions on IVF and supplements (updated at the end)

I begin IVF in roughly 10 days, on CD1.  I was going to take the CCRM cocktail (see below). This was the list I got by googling.

Folic Acid 5mg 
Myo Inositol, 2 grams, twice daily
Melatonin, 3 mg, bedtime
CoEnzyme Q10, 200 mg, twice daily
L-Arginine, 1000 mg, twice daily

Note: the original posted list also included DHEA for poor responders, which I'm refraining from, since my natural DHEAS levels are super high.

I'm already taking the folic acid, but I'm fuzzy on when to begin the rest. I know people are prescribed different IVF protocols, that complicates it even more.

Slightly veering off point: I've been trying to understand how lupron (GnRH agonist) is used, and my understanding is what you can achieve with it depends on the timing and duration of administration. If anybody wants to take a stab at explanation of the different ways in which lupron can be used in IVF, go for it!Also, if anybody knows of a good website/resource that explains the different IVF protocols available and what they can do, and who they are tailored for, that would be AWESOME. I've been confused by what I found, and that is rare for me!

In my case: I start Lupron from CD1-3, then followed by menagon (FSH with a dash of LH) from CD3-9, and eggs will be harvested a few days later, if all goes well.  Can anybody tell me what this protocol is called? Is it the micro flare?

I'm planning to start my cocktail on CD1. Should I be doing it before? If you were a CCRM patient, what instructions were you given?

I'm also being smart (or stupid) in taking a mini-holiday before starting this-- I head off to Singapore and Indonesia this week! And then, the games begin. I'm not really afraid, I'm excited. One way or the other, this is going to tell me a lot about myself, and that is information I really, really want.

Update: It turns out I've asked this question just a little too late, apparently, yes, CCRM does tell you to take melatonin and argenine PRIOR to the IVF, but tells you to stop during the IVF itself (ie, at the time of GNrH agonist administration). I'm confused if the same does hold true for CoQ10, there appear to be a lot of people who have taken it during medicated IUIs---will read up on IVF.

However,  just FYI, I've seen a study where patients which have prescribed melatonin + myo-inositol DURING the IVF itself. So it can be done. The rationale for melatonin is that it can help minimize free radical damage, which is perfectly plausible in theory.

Also, L-argenine administration may be detrimental during the actual ovarian hyperstimulation, according to this study, which makes sense, because it may result in increased nitric oxide (ie a free radical) buildup.

"You are hell bent on ruining your life"

I've been hearing a lot of that lately. Its coming from my mom and dad, when they talk about my insistence to have a baby as a single mom, and raising that child all by myself.

We've been doing the arranged marriage circuit(since I'm still open to either the Plan A or Plan B route of family building). We flew down to City X and met a guy my entire family literally drooled over- highly respected, very rich, very accomplished. and capable. I liked him too, he was nice, kind and easy to talk to. But I was not attracted to him in the slightest and he wanted to live in India, which, definitely, is not something I want to do for the rest of my life. I said nay, and basically, got the "You are hell-bent on ruining your life" spiel.

Its not like single mothers ruin their lives. They do have a difficult time of things though. But that lifestyle is utterly alien and terrifying to my parents. I can't even begin to convince my parents that everything will be ok, if I go that route because life comes with no such guarantees.

My parents keep telling me I can easily have it all...a father, grandparents for my baby, a superb support system, everything,while simultaneously reminding me of what I'm robbing my child of, by going the single parent route. Its the old argument, made new again, and I'm getting hit with it constantly. And its not even like I can dispute any of the above-- if I go with plan A, I can still give my child a better life than as a single mom.

But if I just agree to marry just anybody for the sake of avoiding single parenthood, it could end disastrously. My parents are convinced it would not be so, and they are coming from a culture where people married each other with little introduction, and in many cases, built successful marriages based on camaraderie and a mutual respect. It is not enough for me.  But who knows, if I forced myself down this path, it may even end well. 

The good (or bad) news is I can't force myself to marry just for the sake of marrying. And there has been so much arguing just to get me to do just that (as long as I can respect the guy!). Yet, to give my parents credit, they hate what I'm doing, but are helping me with it nonetheless.

Right now, its this cauldron of guilt, fear and whatifs I'm swimming in. I don't know what I should do, but I know what feels wrong--- I'm steering clear of that. But its not easy at all.

Aneuploidy as a cause of recurrent miscarriage

My RE sent me a study on aneuploidy (=abnormality in chromosome number) as a cause in recurrent pregnancy loss, and it was a fascinating, yet difficult to grasp read, as far as significance went.

They started with this statistic -- the prevalence of fetal aneuploidy in women in sporadic miscarriage (ie have loss(es) interspersed between live births) is around 76%. In women with recurrent loss, it is much lower-- around 50%.  This means that with recurrent loss, there is possibly greater contribution of factors other than a genetic abnormality in the embryo. Yet, fetal chromosmal abnormality still prevails as an important cause---around 50%.

They then subdivided by the patients based on presumed issue, such as as anti-phopholipid syndrome (APS), uterine abnormalities, abnormal karyotype in either partner, hypothyroidism/Diabetes/PCOS and then looked at incidence of fetal chromosomal abnormalities.

As expected, when either parent had a abnormal karyotype, they produced a very high number (over 75%) of aneuploid embryos.The APS and hypothyroidism/Diabetes/PCOS groups held steady with around 50 % of examined embryos being aneuploid. The uterine abnormality group had a much lower percentage of aneuploidy, around 17%.

The point the authors made conclusively- aneuploidy is a significant, but not sole,contributor to pregnancy loss, even of the recurrent variety.  But here is the question I want answered---do certain conditions or gene mutations predispose to a higher rate of aneuploidy?We all know advanced maternal age increases aneuploidy. However, the average age of women in this study was 32 years.  What are the other factors?  Does PCOS, for example, make the mother more prone to producing aneuploid eggs? Or do they just have 2 separate issues (the second of which-- the cause of the aneupolidy) is unknown?

I've done many pubmed searches trying to link issues found in me (such  PCOS, PAI4G and the MTHFR C677T) mutations and increased aneuploidy.  Turns out, there have been people trying to study the same.

The only semi-tangible thing to show up is the folate connection. The MTHFR 1298C mutation (but not the C677T) mutation has a link to an increased incidence of fetal aneuploidy. Interestingly, multiple other studies have reported the same, they see an association with the 1298C but not the C677T mutation and various single chromosome aneuploidies.

Furthermore, many, many studies show that low folate levels increases chromosomal abnormalities in cells of the immune system.  But what about germ (sperm and egg) cells?

A smart study looked at the effect of folate supplementation on aneuploidy in sperm (something that is so easily studied!), and basically found that increased folate intake decreased sperm aneuploidy. 2 important things: folic acid could possibly decrease risk of aneuploidy in eggs as well, and women, make your husbands take that 5 mg dose!

BUT--- whatever the road to it, aneupoidy is a major contributor to pregnancy loss. One statistic that knocked the carpet out under me was the finding that 40% of all IVF-generated embryos (even in younger women) are aneuploid. Is this true even of the natural process?  Is that why so few natural tries end in a clinical pregnancy?

I was recently pointed me to this study by a couple of people (thank you!)---Super-fertility’ may explain some miscarriages, BBC News has reported. It says that the wombs of some women are ‘too good at letting embryos implant’, even those that are of poor quality and so which should be rejected.   

Basically, if you take the assumption that the natural rate of aneuploidy is as high as that in IVF, and combine it with the above study, then, well, that would explain a lot, including what happened with me. Heck, maybe my aneuploidy rate is even higher than 40%, but my uterus is a champ at implanting any and all comers.  Or not. Who the heck knows?

Preparations..

Thank you all, everybody who responded to my last post, especially the final comment on surrogacy.

I've been a terrible blogger, so much so that I have not even been reading all the blogs on my list. As far as life goes, I feel like I'm on a treadmill I can't get off, I'm running, but am making little progress.

To catch you up on the TTC journey, a bullet list may be best

• If we can, we will go with CGH microarray for all generated embryos. Our only viable candidate for testing looks like it may be Bluegnome, based out of England, that offers this test for aneuploidy testing.  Bluegnome has developed the technology and is trying to distribute and train labs all over the world to use it. Here, there is the question to be pondered : I can try to ship frozen biopsy cells to England, or to somebody who now offers this test in India, an embryologist in Delhi.  Obviously, it would be far easier and cheaper to send the cells to Delhi, as opposed to shipping to England. But, I'd feel more secure if somebody who had done this test a gzillion times before does it. But then, this technology has been designed in such a way that using it, and obtaining interpretable results is easy. The scientist in Delhi has gone and trained at the Bluegnome facility in England.  Bluegnome's Indian partner offered me both options, but strongly pushed the Delhi choice. I have not decided what to do yet- right now, as long as I can test the embryos, I will rest relatively easy.
• I met with my doctor and got the details of the IVF protocol which will be used in my case- 3 days of suppression, using Lupron (a GnRH agonist), CD1-CD3,  followed by starting menagon (which is a mix of FSH and LH), on  CD3-9 (I think it ends on day 9). This was a very pleasantly short protocol, and I hope it works for me.
• I met with the lawyer to take the first first step of the surrogacy process. I want to recruit 2 surrogates, with a single embryo transfer per surrogate. Since I will be freezing the embryos down, this should be logistically simpler. I'm totally ok with ending up with 2 kids, as long as they did not undergo the risks that come with a twin pregnancy. I'm getting 2, because I fully anticipate that atleast 1, or both of them will fail, and I just want to move this process fast.
• I started metformin.I'm entirely unsure if I need it, but right now I'm going to go with the empirical method. I'm been on it for around 4 days now,  at a 1000 mg for the past 2 days. Apart from a slight headaches (god help me if I skip or even delay any meals) and the mildest of heartburn, no side effects at this dose. Interestingly, I've been having issues with acne (mostly on the body, rarely on the face), but both seem to be subsiding after I started it. I'm  contemplating going up to 1500, but the headaches are off putting.
• I've also finally started a high dose (5 mg) of folic acid. Since my homocysteine,which needs to be cleared either by folate or vitamin B12 had been low(and still was), I had never considered that therein lay a possible issue, but it may well have been, since I have one copy the C677T mutation. Note: The reason my homocysteine was not high may be attributable to my extremely high vitamin B1-2 levels. Everybody is worried about high folic acid supplementation masking a B-12 deficiency, I wonder if I had the reverse issue.
•  I have to get the swimmers shipped. While I still want to try with the donor I've used in the last tries, I'm wondering whether I should ship another donor, as backup if need be. But its so very hard for me to actually decide on another donor, lets hope I can find somebody else I feel comfortable with.  Also, lets face it, at this point, its all a game of russian roulette. My donor has been excellent at getting me pregnant, and seems to be very, very good with hordes of other women, none of whom have had issues with pregnancy loss. A new donor would be a completely unknown entity.

So much is being done, such drastic measures are being taken and yet, when I think of my chances for actually succeeding in all this, I have to be honest, I've lost all faith that anything will work. I think that is because I still can't understand why things have failed, over and over. How can they have failed? Will this trend ever reverse?

Is it my biology? Is the issue in my eggs, manifesting in a high rate of aneuploidy?I've got a big, speculation-filled post brewing in my head about the many roads that can lead to an increased rate of aneuploidy, which appears to be a prevalent cause of pregnancy loss. Good, if complicated paper on the subject, I'm still trying to fully understand it. Post coming up if I succeed.

It also comes down to faith. Does the universe not want me to succeed right now, not because it wants to punish me, but because it has an alternate plan for me? I honestly don't know anything anymore. 

I want to do IVF the next cycle- since I'm CD2, that is approximately 30 days away.  Exciting, yet terrifying times!

All about CGH microarray- part II

A continuation from my previous post, this discusses the pros and cons of CGH microarray. If there is anything I have missed out, please bring it up here.

2 kinds of embryo biopsies:
First a little background, and its going to get technical. You can biopsy a developing embryo at 2 points- around day 3, where you pull out a single blastomere, and on day 5-6, after the blastocyst has begun hatching- here you can get out multiple cells. The latter is called a trophectoderm biopsy.

A blastomere biopsy on day 3 is more harmful to the embryo, because "removal of one or two cells from a six- to eight-cell embryo on day 3 depletes the embryonic mass by 12.5%–25% or more, risking the inadvertent removal of critical cells from the embryo, especially if attempting to improve diagnostic certainty by taking more than one cell for testing." Also, with a single cell biopsy on day 3, you have a significant chance on missing out on mosaicism, a condition where chromosomal errors can be introduced during cell division after fertilization, at any point. The earlier the mosaicism is introduced, obviously, the greater impact it would have.  

A trophectoderm biopsy on day 6 appears to have 2 advantages over a blastomere biopsy on day 3-- a) it is potentially less damaging to the embryo (you remove a much lower percentage of the total number of cells, and one lab, who had done this a gazillion times and were now expert at this, clearly, reported that "after allowing for blastocele reconstitution" the majority of their embryos survived their freeze-thaw) and b) It has a  much higher chance (but is not a 100% reliable obviously), of catching out on mosaicism.

Ok- those technicalities being explained,  my RE wisely chose a trophectoderm biopsy, so lets move on to the pros and cons of that, with CGH micrroarray thrown in.

Cons

Damage to the embryo during biopsy: The more the lack of experience of the tech doing this, the higher the possibility of damage, or so i think--correct me if I'm wrong, it does not seem like a simple procedure, no idea what the learning curve is like. Additionally, there are different options of herniating the zona pellucida(?) prior to biopsy, and some may be safer than others, it depends on available technology.

Obviously, as stated above a trophoectoderm biopsy is better than a blastomere biopsy, because you take less from the embryo. But the risk remains that you can damage the embryo, worst case, none of your chromosomal normals might survive the thaw. Or they might be able to survive, but might have a lower chance of implanting. My mother had a unique worry: that there would be flawed development of the baby due to embryo biopsy.  Nothing I've read shows any indication of abnormalities in any children resulting from biopsy (there have been 700 children born from blastomere biopsy worldwide in 2005, apparently). There are plenty of logical reasons to think it decreases your chances of having viable embryos in itself, and based on the hardiness of the embryo and the skill/experience of the tech doing this delicate procedure, may even result in your IVF cycle producing zero clinical pregnancies. That, I think is the worst case scenario, and its one I've considered.I think my final decision will be made after considering the experience my clinic has had with this procedure. If I'm one the first people they try it with, I'll be aware before I decide, one way or the other. 

It does not eliminate the possibility of mosaicism: Obviously, a trophectoderm biopsy is your best chance of detecting this, while it is not foolproof. Again, it comes down to the luck of the draw and about overall risk reduction of pregnancy loss. My goal is to eliminate as many aneuploids as possible. I know that I may not be able to get them all.

Limitations of the technique itself:  My RE bought this one up- its a new-ish procedure, with limitations. In the very best hands with the very best luck, its limits of detection are possibly microdeletions/microinsertions. Still room for things to go wrong. But right now, I'm considering it only for its core ability- the ability to detect gross aneuploidy. Good enough for me.

Practical issues: I'm doing this in India, where CGH microarray is not offered as a procedure (I hope some enterprising individual comes across this and decides to start this as a business venture, sometime soon, though its not going to happen for me). So we are doing it in a clinic where this is not usually done (and I am deeply and utterly grateful for their willingness to take this on), then will be attempting to ship DNA across continents (So much can go wrong there), then I have to find a lab willing to do this, who accepts extracted, amplified DNA from another country as raw material for this procedure (anybody who has had this done, can you tell me the name of your lab?) CCRM girls, this is done in house (right?)
Right now, I just know of  24suretest (in England) and CCRM.

Pros:

It would definitely improve the chances of success. One study reported that after taking into account aneuploidy and mosaicism, over 50 % of the generated embryos of 'young women'  were chromosomally abnormal.  Clearly, age does not protect you fully.  And I'm young (in that I appear to have plenty of eggs left, with excellent FSH, AMH, estradiol and AFC--similar to that of any egg donor), and I make eggs capable of fertilization and implantation, and 2 out of my 3 eggs may have been chromosomally abnormal.

If 40 % of the embryos generated through IVF are aneuploid (and embryo grade is not much of an indicator of whether am embryo is euploid or not!) then I would need some serious luck to avoid having a surrogate go through loss. Both my RE and my mother were of the thought process that, if my surrogate went through one loss, or more, it would be something easily borne, because it is not me going through the pregnancy. I think everybody was startled when I burst into tears at the very thought of my surrogate losing the pregnancy--and the 20 week amnio time point was under discussion here. I think women who have lost babies will completely understand my horrified reaction, while others would think--- its not your body, so what is the matter? To that, I'm going to say, its still your child. So you will be devastated each and every time it happens, especially if you get to the point of 20 weeks, where your hopes have really been built up. For people having gone through the process of using a surrogate, if you could address how you felt at the thought of anything happening to the surrogate pregnancy in the comments section, that would be very useful.

It would potentially decrease time required for success: Lets start with the assumption that around 40% of my embryos will be aneuploid. I line up one surrogate. Transfer one embryo (I refuse to do multiple embryo transfers to one surrogate).  If its aneuploid, best case, we lose around 3 months.Worst case, its something that we don't detect for 20 weeks (again, bloody scary prospect for the mother, while the general audience thinks this is not a big deal). Then, we repeat the process again. If we get unlucky, it would really be a while before we hit on a winning combination. I want to stay in India around 3-4 years maximally. I also want any children I have to spend atleast the first formative 2 years of their lives around my family---which means, for my 2 plans to mesh, this has to work quickly. While IVF with PGS does not guarantee this---I could totally lose a chromosomally normal embryo, at 5 months, for multiple reasons, it reduces the overall risk of pregnancy loss.

A valuable learning experience: If we embark on this road, everybody involved could learn a lot, even if no pregnancy results from this IVF cycle.  I could learn more about the nature of my embryos. The person doing this should get valuable laboratory experience at this technique. If this entire IVF fails, the only commodity that would be definitively lost is money and time. The time would smart, but the money? We spend money on so many things, so many of them relatively inconsequential that I'm not going to feel bad about spending money on this, even if it fails utterly. My mom wants to get me a diamond set worth around a million rupees for the wedding. The possibility of a baby is definitely something priceless, and this venture may set us back around 1/5th of that price, so I'm not going to quibble about it.

This is a post utterly open to lively comment and debate. I hope there is some of that, and more importantly feedback on available facilities (in the US, or anywhere else) that do this routinely and are willing to accept samples and my $$$.  I know a lot of people, from everywhere, read this blog. I hope that will come in useful here!

All about CGH microarray---part 1

I had my visit with my RE yesterday, with my parents in tow. Coming back to India, with the difficult choices to be made, I had expected no step of this process to be easy, and that was proven right with a vengeance yesterday. And its not even a process that should be easy, these are extremely difficult decisions, with a great deal of grey area and a lot of room for arguing pros and cons for any particular fork in the road. Unexpectedly, the point I had expected to be the sticking one, surrogacy, was more easily settled, but another point provided a great deal of debate-- that of genetically testing the IVF-generated embryos.

First, lets segue to another point, that of treatment choice in itself. Both my RE and the MFM specialist I saw in the US gave me the impression that of all the treatment options they would offer as the first choice, an IUI conception (probably with ovulation-inducing drugs thrown in) would be a top choice, and possibly, many of you reading would also agree. This stems from the finding that even women who have had 5 losses have a good chance (is it 50%?) of carrying to term in the next round. This is where the patient and the doctor part ways I think. The patient looks at a 50% risk of going through the hell they went through previously, and may balk, for good reason, I should add. Nobody who has not experienced that reason, personally, (being a truly empathetic audience is not good enough), will  understand why.

I personally, am invested in making the risk of miscarrying/late loss lower. That is all I'm about. I'd love to eliminate that risk entirely, but I know all I can do is make the risk as low as practically and economically possible (and everybody's capabilities here are different), but I can never, ever, despite the best laid plans and all the plotting, planning, testing and novel approaches (IVF, PGS and surrogacy included), can I make that risk go away. Despite all you account for, things can go wrong in yet another way, I am so blindingly, painfully aware of that, far more so now, than 2 years ago.

My doctor proposed a novel  exercise, and its one that is pretty useful and logical- consider and write out the 'cons' of pre-genetic screening of embryos.  I'm doing that, but more for my parent's benefit (they need to understand why I'm proposing this, instead of following the doctor's advice), I'm also going to write a 'Pros' list. This list of pros and cons should be useful for anybody who is at the cusp of this difficult decision. This is coming up in the next post...stay tuned.

Meiotic non-disjunction strikes again

After a great deal of haranguing, I got the results.  Meiotic non-disjunction (which, in English means, the chromosomes did not separate properly during the process of making an egg or sperm) has happened again.

During my second pregnancy, it happened in the form of a monsomy of the X chromosome, which means either the egg or sperm had one less X chromosome that it should have. Monosomies are considered to be more likely a sperm error (a sperm that is missing a chromosome is lighter, can swim faster, yada, yada).

This time, it was most likely to be an egg error- a Trisomy, of chromosome 4. And it was a girl.

On googling, my blood ran cold- trisomy 4 appears be one of the rarer ones, and more often its a partial trisomy, (you have a 3rd copy of only one half of that chromosome) and the child can make it to birth, but obviously, with major, major issues. Thank god  my baby and I was spared that. Often, miscarriage is not about nature being cruel, its about nature being kind, and nature was kind here, but only AFTER the bloody trisomy had resulted. Bloody nature.

I'd had a bad feeling about this pregnancy from the time that the first beta and progesterone values had come in, because they were both far lower than my levels for the first 2 pregnancies (though, in normal range for the population) and the progesterone fell sharply by the 7th-8th week period-this was all in keeping  with the observation that some (but not all aneuploidies) can have lower progesterone and beta-HCG levels. Its fascinating, apparently trisomy 21 has higher HCG levels, but Trisomies 13 and 18 have lower progesterone and beta-HCG levels---wow, this suggests that complex mechanisms behind aneuploidy of different chromosomes, just because we don't understand it in the slightest, does not necessarily mean that its completely random. Chromosome 4 aneuploidy has not been studied, because its too rare, but my scenario also points to reduced hormone levels with this one.

What next? IVF with PGD obviously, but I'm trying to end up with a method more accurate than FISH, which does not analyze all the chromosomes, and would (probably?) have not caught this one.  The goal is to get microarray done with IVF in India-- this one has several logistical issues, lets see how they can get worked out. 

But as for now, I'm so very glad to have an answer. The point where we get grateful for small mercies is a sad one indeed.

The ability to cry

When I'm sad, or when I'm stressed and something gives out,  I cry.  Tears work in different ways for people. Some cry copiously, and feel no better. Others lack the ability to shed tears, and keep hoarding their negative emotions. In my case, crying works in precisely the way evolution probably intended it, as an exquisitely-designed mechanism to physically shed emotion and become free of it.

The most sensitive emotional barometer I possess is how much I've cried in any given situation. I cried copiously after my first loss, for days on end, for long periods of time. My second loss bought about far less frequent tears, I went to the numb and 'I'm ok' bits much more quickly. With this 3rd loss, while I cried infrequently through the pregnancy to expend the stress that was building, and plenty on the day of the loss, but afterwards, my tears just dried up.  They came maybe four times that coming week, in very short (like 1-3 min) durations, and afterwards, not all all. I also felt like life was almost normal, I was not even numb, most of the time, I just felt fine. That was bewildering in itself, I have to say.

There has also been very little grief with the loss of this particular life, and there is a little part of me that feels profoundly guilty about it. I never felt like this pregnancy was real, because my psyche, for whatever reason, solidly blocked it. There was no grief that I could identify over the loss of THIS life, this child. I felt sad that the pregnancy has failed. I cried because I'm so scared about the future, and that things were so hard for me.  But I never cried because this particular life was gone. And to this day, I wonder why it was. The easy and simple answer is, its a coping mechanism that my sub-conscious developed, after the back-to-back whacks of 2 pregnancy losses. But still, I'm not wholly satisfied with that explanation.

I want the results of my karyotyping back for multiple reasons-- one part is, that I want this lost pregnancy to become more real for me. I want to know what I had, so it finally becomes more tangible. Its been 21 days post D&C. When I left the country (17 days post-surgery), the results were not back yet. I called today, the receptionist was distinctly unhelpful. She would not inform me of the availability of results via email, she had no idea when they would become available, and her advice was to keep calling back until a) the results came back and b) a nurse practitioner was available to relay them to me. Yikes. That is a lot of international calls. And honestly, I'm just dying to know.

After talking to that woman, the dam finally cracked. I cried again, and I desperately needed to. Grief or the lack of it non-withstanding, these past few weeks have been enormously stressful. Like an idiot, I scheduled my flight out of the country 2 days after I had finished work. I decided the timing the day of the loss, on a day I should have been making no decisions, on a day that my primary priority was to run home to family. Two weeks after, when I was emotionally back to a completely even keel, when I was stressed and overworked with the burden of wrapping up my handover and packing to leave in a ridiculously short time, I seriously regretted it.  I managed it, finished everything I had to do and I'm back in India, but not without some serious stress and cost to myself. Its been rough. And I finally cried today, because of a rude receptionist. I just pray I get my results soon, and they don't end up tell me that they managed to lose all samples or the lab messed it up or something. Though my badly needed R&R has begun, I'm stretched very thin right now.  C'mon universe, tell me what I had.  

So, so boggy

During my pregnancy, I had a dream that I lost the baby. I remember being utterly unsurprised in my dream state and thinking, well, this had the lowest progesterone and HCG of any of my pregnancies, so yeah, this is no shocker that its over. I woke up, had a moment of disquiet, and dismissed the dream to my fears manifesting in my subconscious. After all, these 2 readings have proven to be very imperfect in predicting the fate of a pregnancy.

But my dream reasoning was probably dead on. Of all 3 of my pregnancies,this is has been the worst looking one and it ended the earliest too. 2 weeks have passed, and I still have no concrete idea why. I had them run a progesterone test after they discovered the loss, and it was interesting, my progesterone had dropped like a stone. It was around 25 ng/ml in the 15-21 DPO period. On the day of my loss, it was 11 ng/ml(!!), while my HCG was over 40,000.  You have to wonder, what came first, the chicken or the egg? Was my progesterone low because it was a bad. ie genetically abnormal pregnancy (those tend to have lower progesterone, though the correlation is not very good) or did my pregnancy end (partly) because of low progesterone?

I'm still waiting on the chromosmal analysis. Right now, my biggest fear is that they lose the sample, or can't test it. As long as I get an answer of what the embryo was, I'll be satisfied with that. Any day now, the doctor should call me.

I also got my bloodwork of my RPL panel in my hand, and I pored over every result, and I'm very glad I analysed it myself, because the doctor who was looking at it (who I had an RPL consultation with), was really not detail-oriented. AAARGGHH.

The doctor I spoke (not the one I consulted with) to said I had issues with 3 genes related to clotting issues. Not actually true-- i have semi issues with 2 of them.
This is how it goes
I'm actually normal for the anti-thrombin gene (very good news, the mutant variant confers pretty strong risk for various issues)
I'm heterozygous (ie have one copy) for the MTHFR C677T gene
I'm heterozygous for the PAI4G mutation- I'm 4G/5G (where 5G, I think, is the normal variant)

The immunological bloodwork should be taken with a giant grain of salt because yeah, the did not send to the best testing lab. Arghhhh. I asked my doctor why that was and he said, it was because 'the others are expensive'. At that point, I wanted to find a nice wall to bang my head against, I mean, why bother testing if you cannot trust the results?

So---I'm in grey zone territory for thrombophilias. This doctor (who according to his practice was 'aces' at treating RPL) gave the following verdict- I should try again,  preferably with clomid to improve egg quality (why do docs love clomid, and not femara, which has fewer side effects??) and once I got pregnant, add asprin, lovenox, Prednisone (10 mg, 2X/day) and progesterone to the mix. Basically, throw the empirical, basic RPL cocktail at me and see what happens.

Errm. Moving on from what that doctor (he was SUCH a name dropper, he just kept talking about his famous patients) thought- here is my biggest fear. There are 2 flavors of thrombophilias which can interfere with pregnancy-- maternal and fetal. If  both me and my donor are heterozygous(ie only one copy) for a bad version of the MTHFR or the PAI gene, any baby has a higher risk than either of us, because it could  get the bad copy from both of us and end up with much higher risk for developing clots. I asked the doctor when he thought fetal thrombophilias play out, and he thought it has a role in later (second and third trimester) pregnancy loss. Interestingly, all my losses have occurred after the fetus has developed a rudimentary blood circulation---so theoretically, fetal thrompbophilia could be in play. This issue would not, in theory, be fixed by using a surrogate, unless the surrogate was given lovenox as well.

To have a better idea of what is happening, I really want to talk to an RPL expert, even if just to brainstorm. Some of the best minds in the RPL field, are, as Adele pointed out in the comments section,  are in England, at St Marys. I can't go to England unfortunately. But ANY of you coming by this blog get to talk to anybody who is expert with RPL- can you ask about fetal thrombophilias-- when they think they play out? Btw, if any of you are heterozygous(ie, one copy) for thrombophilia-predisposing mutations(such as MTHFR C677T),  testing your husband for the same is a very good idea. Nobody wants to have a child that is homozygous (ie, 2 copies) for these mutations, that could predispose to a lot of health issues later. I wish I could frogmarch my donor to give some blood, but that, sadly is not an option. The only option I have is to test the embryos.

I know what I want to do- I want to do IVF. Then after we biospy that one blastomere, I want to expand the DNA so I can do a lot of testing with it, including running genetic tests for the MTHFR, PAI and anti-thrombin genes. This is going to be extremely technically and logistically challenging and is going to need a lot of money and initiative, but thankfully, money is the one commodity I do have to throw at this problem. After that-- I want to do surrogacy. There is a part of me that shudders at the thought of being pregnant again, I just don't ever want to go through a pregnancy, for so many reasons, though I most definitely want to be a mother. I don't trust my body anymore. I don't know if its immune issues or clotting issues, right now, its fair to say that with my history I AM higher risk for all the later term complications, such as placental abruption and IUGR and all that other good stuff. I can't keep gambling like this, not when I have an out. Even with this preset idea of what I want to do, its going to be an uphill task to figure out what I should do and to find a plan that everybody involved can make a degree of peace with.

In other news, I got done with work, I'm packing up to move back to India, and I'm really, shockingly fine, from a mental standpoint. There is a lot more to say there, but as of now, time is a commodity of which I am very short of.

Recovery

I had my D&C yesterday, and it was a huge releif to get that done. They did it under ultrasound guidance and the doctor assured me he was going to be 'very gentle' and he reiterated, after surgery that he had been and that everything looked fine. No doctor actually wants to give their patient Asherman's syndrome--so fingers crossed.

Emotionally, I'm recovering at warp speed from what happened. I measure how I'm feeling by 2 yardsticks- 1) how much time I spend crying, and 2) What my zest/enthusiasm for life in general is. In the past 5 days, if you added up all the time I had been truly emotionally upset or cried, I doubt it would be for more than a 15 minute period, which is amazing. My enthusiasm for life is well and truely there,I'm enjoying the olympics, I want to go out and shop, I'm eager to tick off items off my New York Bucket list,  this feels *almost*  like a normal week in my life. I'm gobsmacked by how well I'm doing, all in all.

But---I've definitely not gotten away scot- free from what happened, that is impossible. The thought of being pregnant again almost makes me feel ill. If I go the pregnancy route again, I think it would likely trigger feelings akin to PTSD. A number of you cautioned me to go easy on myself, not to blame myself for what happened.

The thing is, I definitely don't think anything I did caused the loss. It was not the cup of coffee I drank daily, it was not the beer I had 3 days past ovulation (baby not implanted yet, that was my rationale:)), It was not my 6 hour walks across Manhattan- Nothing I did caused it. But most certainly, something that I am  that is responsible for my 3 losses. I'm not really angry with myself for that , but its more like a deep embarrassment, that I'm failing where most people succeed without trying. As I've said, that comes down to ego. I've always enjoyed perfect health and a body that works well, and when you are used to thinking of yourself a certain way, learning otherwise is going to sting. There is also a little teeny tiny nugget of rage at everybody who has succeeded here. The first step to recovery is awareness, I've really been talking out how I feel with my mom, which helps.

I got a call from my doctor this morning- they got the results of my RPL panel back. No immunological issues whatsoever, which is nice, because that is the mildly harder thing  to fix, and also given that my Vitamin D levels were nice and high, I expected my immune system to be bitch slapped into submission. And yeah, it was.

But--3 flags on genes linked to coagulopathy. MTHFR (I have 1 copy of the 'bad' gene), Something with the thrombin gene, and something with  PAI4G.  I asked my doctor to email me the actual lab reports, since these are complicated, and you need the details to figure out what is going on.  Then, I'm going to read up on all of this myself, so I can asses risk independent of my doctor.  True risk aside, the treatment is simple, lovenox.

All in all, I have 4 factors that *might* elevate risk for RPL, anti-thyroid antibodies, and the 3 genetic risk factors for thrombotic abnormalities. Uhh, there is  a little smoke, and there has definitely been a fire. Are they related?

Einstein famously said insanity is doing the same thing again and again and expecting different results. Its not a 100 % true for infertility, sometimes, the 10th try may actually work. But I don't like such odds at all, and I refuse to keep gambling with them.  The next try is definitely going to be IVF, with PGD for all generated embryos. I"m seriously mulling adding surrogacy to the mix, for many, many reasons. Its around 20,000 $ in India- its very,very affordable.

But for now, I'm very, very ok.

How I'm faring..

I truly have the most amazing family. My mom is coming here on the 31st, and she will stay till the 12th. I leave the country just a few days after that, my ticket is booked.  I didn't go anywhere yesterday. Not to work, not to the birthday celebration of a friend, not to Philly to be with the friend who came down for the ultrasound (she really wanted me to be around people). Instead, I stayed home, holed up, read books, watched endless episodes of White Collar.  I did not even cry once, nor was I particularly sad. I was just  numb-- anybody familiar with that feeling where all of life comes at you in slow motion, like you are underwater? Today has been more of the same, though there was a bit of  a crying jag in the morning.  I am going to make myself to go out later, wear pretty clothes instead of ratty pajamas and hang out with actual people. I'm also in limbo.  I'm waiting to be rid of the physical presence of this pregnancy, and I'm eager to get karyotyping reports and the bloodwork, and then I just want to move on. Enjoy the silly, stupid things that make life colorful and fun.

I'm really looking forward to India. I'm looking forward to vegging out with family, I'm looking forward to not working,  I'm looking forward to getting seriously cute (and hot) outfits for my brothers wedding. Looking/feeling cute while you are knocked up is really not an option (since people would have looked at the unwed, visibly pregnant sister of the groom like they would a whore at church), and while I'd MUCH rather have been pregnant and scandalizing all and sundry and being the ultimate social rebel (I was planning to be open about the SMC route), I'm going to bloody enjoy the alternative since its been force-fed to me.

In my post titled 'Why does Miscarriage hurt so much' I'd expressed the desire to be more matter of fact and less attached during any particular pregnancy, so, if I had to go the distance and do this many, many times to have one healthy child, I would have the emotional where-withdrawal  be able to do so. I wanted a miscarriage "to be a stumble instead of a giant fall". The ghost of a silver lining is, I think my psyche has managed it. My first pregnancy loss hurt like crazy, the sheer unexpectedness of it knocked me for a six. I thought my second loss would finish me off, but surprisingly, the recovery was faster, which I attributed to being around family. This time, I'm actually recovering faster than even the second time--I'm getting desensitized to early pregnancy loss, for whatever that is worth.

The only things that are really bothering me:
a) The minor one: Feeling like such a screw-up. Other people have babies so easily and I've failed time and again. Its what has kept me from telling many people who I care about, but who manage to reproduce easily. I'm both proud and competitive. These are utterly pointless, foolish qualities, that keep one from truly evolving as a human being, and are utterly ridiculous applied to the area of biology, where none of us have any control about how we turn out and what issues we face. In this regard, what I'm going through may actually end up teaching me a valuable lesson, which might leave me a better person. That lesson is most definitely still a work-in-progress though- Being sad is fine, but I'm also pissed off and mainly, embarrassed that I keep screwing this up. Ugh. Stupid me.
b) The major one: I'm so, so very scared about what I might have to do, and how far and how difficult this road might be. I don't know what I'd do, if I could not have a child. I honestly just can't imagine it.

But for now-emotionally, I'm truly ok. Physically, I've started cramping a little though, no spotting yet. My mom is coming in Tuesday morning, I hope I can hang on and manage not to start miscarrying till that point.

Over

The 3rd time, is not the charm apparently. The baby measured 6w5d, with no heartbeat. I am so very thankful my friend from Philly was there, she literally held my hand through that and the staff of OB clinic was very kind. They immediately whisked me off for the full RPL panel, an eye popping 22 tubes.

I'm too chicken for a natural miscarriage, and it also makes it harder to collect the fetal material for karyotyping. So a D&C will be scheduled at the earliest, latest by next Thursday. I don;t want to wait too long, just in case they cannot make the fetal cells grow. Its imperative that I get that karyotype done. I really want a chromosomally abnormal verdict, the alternative points to a much harder to deal with scenario. 

Somebody called me resilient, and I most definitely am that. I will get through this, and I'm pretty determined to not let it bury me under a shadow for too long. I really, really want my mother, especially for the day of the D&C though, and for after. As I told my friend- its better to have people around you, but they have to be the right people, only the ones you love and trust to that degree, who you can allow to see you break down, temporarily. And my mother heads up that short list. But she is in India, she has a medical practice that she just can't abandon. We'll see, I'm really dreading telling them tonight.

And of course- what is going on as a refrain in my head- WTF is wrong with me? Why does this keep happening? And..the hardest one to face- can it EVER be fixed?

I'm don't have the problem of declining egg quality and I thought my *maybe* PCOS was tackled, or so I believed. Very boggy, scary ground indeed, but in a while, everything may be hopefully clearer than it is now.

95%

I'm sure some of you reading are wondering why I freak out when there seems to be no cause to freak out- my pregnancy so far looks pretty routine, with everything checking out, even the little lag in growth seems like no cause for alarm at this point.

I've seen my way through 2 textbook 'perfect' pregnancies so far. Great HCG rises, great progesterone. They say, after you see a heartbeat, your chances of success are 95 %. I had perfect ultrasounds at the 6-7 week point for both pregnancies, with strong heartbeats in both.   In the first pregnancy, by the end of the 7th week the baby was almost 6 days behind, and that was a red flag, but nobody was concerned, because hey, the bad stuff happens to other people. My second pregnancy was perfect almost to the end of the 9th week. With a predicted 95 % chance for sucess in both cases,  I miscarried twice.

I'm just trying to explain why I cannot relax, or trust the excellent odds I've been given. Augusta bought up a terrific point, that we just keep expecting the past to repeat itself, its human nature. But I also remind myself that each pregnancy is like a snowflake- truely unique. The problems that ended the first pregnancy were nothing like what ended my second pregnancy, and if I can be reasonably certain of anything, it is that this pregnancy is likely to be nothing like my first two. That is not any sort of guarentee that it will continue, only that it is likely different.

About how I'm feeling- OMG, do I have a baby bump now. There is no weight or mass gain, its just that internally, everything is redistributed and my belly is significantly distended. It probably is more apparent because I am super petite.  I think that old wives tale is true- you do show faster in subsequent pregnancies. Overall, I've lost a couple of pounds- I'm not even eating that much, just having small things throughout the day. I've also been feeling vaguely ill the past couple of days, its *almost* a queasy feeling, further limiting quantity of food consumed. I've also been feeling twingy & crampy in the uterus region today, which is new for this pregnancy.

Mildly twingy & crampy is ok, but around the time that my second pregnancy ended (on the day the heartbeat stopped), I had seriously strong, painful cramps that night. I was out with friends, we were playing boardgames, I remember this rush of adrenalin around the time the cramps began, my heart was almost trying to beat its way out of my chest, I was so very unsettled and did not know why. The timing of that with the stoppage of the heartbeat was an interesting coincidence, sometimes, you have to wonder whether your body registers it at a subconscious level. For now, there is none of that. Just mild twinges. Yay. One day at a time.

I wrote this post for one reason--Lots of new pregnancies everywhere, I see the excitement caused by good news at the early ultrasounds, the optimism, the hope. And that is what the people who come reading are comfortable with, I don't think most people know how to react to the darker, more pessimistic tone of the posts I'm putting out-- its like- why is she so afraid?  I hope this one goes towards explaining that.

But with the fear, intermingled in that, is beautiful, amazing hope. Right now she is kept tethered to my subconscious, with my conscious taking up a wait-and-see approach, but she is still there.

Ramblings from pregnancy brain

I've now entered that zone where time moves like molasses, and I'm far too preoccupied with the million dollar question: What is the Fate of this Pregnancy?

Although some my earlier posts sounded alarmist, for the most time, I was actually able to not obsess on this subject and life was fairly comfortable.But each ultrasound produces such upheaval.  Its literally like waiting for the Sword of Damocles to drop.

For the first 24 hours after the last one, it was awful, I could barely think of anything else. That night, I went out to a Broadway play (Newsies---review, its decent, not fabulous). This question was running in the background all the bloody way. I've done so many google queries on delayed growth, I'm now sick of the subject. The verdict is (drumroll please) it can go either way. DOH. Thank all of you who chimed in with stories. They really, really helped. I absolutely know that this can end well, its just that I also remain painfully aware of the alternate scenario.  But anyway, as predicted, I've calmed down now and am just going with the flow. Still time is moving by a bit too slowly. Should have a post on possible distractions.


This pregnancy remains completely abstract to me. I cannot possibly bring myself even to put up the pregnancy countdown widget, and find out what is developing in my baby at this very minute. I dug up some photos of how an embryo is supposed to look at this point, and compared it to my 2nd ultrasound pic, which is sharply defined, and its slightly reassuring when I play the utterly pointless game of comparing it to pregnancy #1, which was chromosomal normal, but with rapidly slowing growth between week 6-8 and looked entirely formless at both ultrasounds (yes, I am nuts and this is entirely illogical and ultrasounds are effected by the angle implanted, yada yada, but whatever makes me sleep better at night, right?). Is'nt it also amazing how different each pregnancy looks? I have not found 2 ultrasounds on the internet that look the same,even at the very same point.

I occasionally talk to my uterus, doing my best to let this baby know how much I love him/her and how I'd give anything for him/her to be ok, and how there is a world of people waiting to take care of him or her, but  that is it. I am utterly unable to process the likely miraculous potential of what is happening in me at all. I guess its an innate defense mechanism.

There is a part of me that is sadly envious of anybody who can get excited about a beating heart. I never even got excited and squealy like most people get on seeing that heartbeat, it was more been more like, been here, seen that, what is the next part?? It is painful (and sad) to lose that joy, to instead obsess about this process from the perspective of how many bloody millimeters the fetal pole has grown, and where you will be 2 weeks later.  I hope that this with this round, I get the privilege of reclaiming that simple wonder somewhere along the way. I think it can come back partly with new milestones crossed, lets see if I get to cross any of them.

This pregnancy is different in another way, this time, I have a friend with me always. Next week, the person who has been coming with me (love ya, V) is out of town. Another friend (instrumental in shoring up my sanity through this process) is traveling from Philadelphia for the day, just to be there for me. Words fail me as to how amazing that gesture and this person is. I hope we get good news, for her sake as well as mine. People other than me are going to be genuinely hurt if this one does not work out. I don't even want to think about how this might hurt my family.

Anyway, if I don't post again (like I can hold out that long), the ultrasound will be next Thursday, when I'll be 8 weeks and 2 days along. I'm not going to my RE (since he can see me only in the mornings), but I found an OB, which works better for my friend who will get here by afternoon. This practice sounds fancy, I'm excited!

On a side note: I had people email me that they were having issues commenting to discus- If you have problems, could you let me know?  If its a widespread problem, I'll have to look into deleting it. 

6w6d U/S

Well, the good news is the baby has clearly grown, and is still alive. Heartbeat was 110. Just on seeing it on the screen, I felt better. The part where everything in  me just sank was when the RE did a CRL- the fetal pole measured 6w2d. I'm 6w6d today, or rather, I'm at the start of the 6th day of the 6th week, since this was around 9:30 am. By that token, it is measuring at least 3 days behind, if not 4.  If I compare this to my 2nd pregnancy, by 6w6d, my baby was measuring 6w5d and the heartbeat was 130.  So its looking crappier than the last time, which looked almost perfect at this point.

Current pregnancy 6w2d,
 apparently measuring 6w1d(really?) by CRL

The good news is  that it visually appears like there has been growth. Its highly likely that the first measurement (of 6w1d at 6w2d) was rubbish given we could barely see anything. In the second ultrasound, the embryo looks a little curved to the right of the yolk sac (do you see it?) and I wonder if that could mess up the CRL too. Impossible to say, but please, throw in your inputs.

 Current pregnancy, 6w6d, 
apparently measuring 6w2d by CRL

I did some googling for delayed growth at similar timepoints. The results are very mixed- I found  a couple of instances where miscarriage occurred within a few weeks, and quite a few instances where things turned out to be just fine. Its really impossible to say, all options remain on the table, with a probably slightly raised risk for a unfavorable outcome within the next few weeks. Apparently, trisomies are supposed to show delayed growths. I've been mostly relaxed (or so I thought) before my first ultrasound and in the gap between this one and the last.  But when I came home and burst into tears, and cried for a good half hour, I realized the stress I'm under. Its insane. Nobody should have to go through this.

I'll be fine by tomorrow and will probably remain comfortably numb (with that tantalizing, beautiful flicker of hope still thrown in) for the most part, till the next terrifying ultrasound rolls around, which should be in the middle of the next week. It will be with my RE again- no graduation to OB yet. After realizing that it was behind, he called me in for round 3, mostly I think to reassure me. This scared me a little though because the nurse had said that if the RE deemed it was a good U/S, I'd be released to the OB at that point.

I know this can go south, in any number of ways. I know this could end well. If any of you have any anecdotal stories to share about being behind at this point ending well, then please, share. I really could use the momentary reassurance.

Like something the cat dragged in

Remember how I said I felt no symptoms of pregnancy? Well, I jinxed it, and I had had definite queasiness when I woke up 3 days in a row too. 2 days later (the evening of my 6w2d ultrasound), I ended up throwing up in a restroom in JFK when I went to pick up my cousin.  Then, the next day, it kind of faded away and its been gone 3 days, but I refuse to get worried by this. On balance, I'd rather I did not have nausea as a symptom to deal with. Despite the reassurance, you cannot possibly enjoy it (though I did feel a little happy while throwing up), and when it stops, you only get far more alarmed.  Women in my family often go through their entire pregnancy without feeling nausea, so its not even like its a requisite for a healthy pregnancy.

I've been exploring Manhattan like a fiend with my cousin. Both Friday and Saturday, we spent about 6-7 hours walking around the city. Saturday morning, I woke up with a sore throat, but I really did not let that stop me. Today, I woke up feeling like dog shit. My entire body hurts, it feels just awful. I've spent the day staying in with my poor cousin. This is my second infection in like 4 weeks since getting pregnant, I am most certainly immune-compromised. Gah.

So basically, between throwing up, feeling sick, feeling breathless, having what occasionally feels like hot flashes, I feel most definitely pregnant. My baby had better be hanging on, or its just another reason (like I would'nt have enough) to shake my fist at the universe. Ultrasound tomorrow morning, this is all effin terrifying.

6w2d U/S

It was most decidedly underwhelming, and not altogether reassuring, but nor was it a cause for alarm either. The gestational sac was visible, in the uterus, immediately and looked to be a decent size and was the prettiest part of the picture. It was really hard to see the fetal pole, but I definitely got glimpses of what could be the fetal pole as he kept moving the wand around, but it kept disappearing a second later. It was difficult to visualize because it was completely tucked into a corner of the gestational sac.

My heart stopped in the first few minutes, where we could not see the fetal pole. After we found it (he had to press down on my uterus to see anything), it was hard to see a heartbeat, I thought I could at times, but what do I know?  My RE said he saw a heartbeat too, but it was faint.  I asked him to do a CRL (difficult as we could barely see the thing) and it measured 6w1d, but the measurements were crude at best. The RE said he could see the yolk sac, but it was hardly the clear round thing of my previous pregnancy. The picture we got was god-awful. I don't have access to a scanner right now, but I took an iphone picture of the ultrasound.
 
I asked him if he thought things looked fine for this stage, and he said yes. He asked me to go back on Monday, which is what I will do.

I marvel at the change in myself. In the first ultrasounds in previous pregnancies (which were 2-3 days later in the 6th week), I saw better and more reassuring images, but I was still unsatisfied that things were not *perfect*, with the CRL lagging behind by like 2 days or something like that. Now, I just listened to the doctor, with a fetal pole I could barely see and a heartbeat that looked barely apparent, and left things to rest. I think the best way to describe me now is 'impassive'. The fate of this little one remains utterly unpredictable, and shrouded in fog, but que sera sera. I can get through this weekend, run around town with my cousin and have fun. That is the bottom line right now.  When I go back on Monday I have 2 people (my cousin and my friend) coming with me, can't ask for more.

I also spoke to my boss and told him I want to stop working by the middle of August. That conversation went surprisingly well. PIs (Primary Investigators, the nomenclature for professor at the head of a research lab in academia) can be unpredictable creatures, and there was a strong possibility that he would make life difficult for me after. But, so far, so good.   

Ultrasound tomorrow

I will be 6w2d tomorrow, and will be going in for an ultrasound with my RE.  I've seen heartbeats and  approximately age-appropriate growth in the past 2 pregnancies at the 6w3d and 6w4 timepoints respectively, so it should not too early.

I have barely any pregnancy symptoms-if this is indeed a healthy pregnancy, then its awesome as to how unaffected I am. I have no cramps, if I had not seen visual evidence of the HPTs getting darker till around 3 days ago (where the test line became as dark as control)  I would have been more worried. The only indications are the sore boobs from hell and  the definite expansion of my uterus, evidenced by the distention of my abdomen (I look like I'm already around 2-3 months along!). But there is absolutely no fatigue, which still amazes me, given how my last 2 pregnancies were. I can stay up late, I've been walking all over the city, in order to counteract my diet (my favorite and most often consumed meal is Cajun-spice tossed fries, butter, salt and nutella comprise my favorite food groups), with no ill effects, even the heartburn that plagued me (from 4-10 DPO) is almost gone.  I should qualify (before you think I'm utterly useless) that, in between the salt and the oil and the sugar, I do eat somewhat healthy (post coming up on that soon).

Another great thing- I'm not at all backed up (like I completely was) during pregnancy # 1. Interestingly, its a problem I have not had in pregnancy since taking thyroid hormone. Interestingly, constipation IS in the symptom list of thyroid insufficiency in pregnancy.

Although I've been looking at OBs, I'm far too afraid to call one before finding out where things stand. This can work. It *totally* could work. Yet, I find myself yet utterly unable to even make a prediction as to whether it shall or not. I had a sense, an intuition of sorts about 'Turbulence', my nickname for my second baby, about the day after conception, it just came to me that she was a girl, and indeed, she turned out to be  one. With this little one (I cannot even decide on a name for him or her), I'm completely in the fog in every way. It just does not seem real, in any way, other that the evidence of the changes in my body.

My cousin gets here tomorrow evening. The ultrasound is in the morning, a truly awesome  friend is coming with me to offer moral support. Going armed with sunglasses and eye-makeup remover, which I now never leave home without. If its bad, I'm determined to somehow put it out of my mind so I can somewhat enjoy my time with my cousin, we are so close and I've been looking forward to this visit for ages. The one thing the past 2 years have taught me: No matter what, life goes on, and it should. That is the only way one can last if one is in for the long haul. But hopefully, no such fortitude need be called upon, and I only get good news tomorrow. Its definitely possible.

The plan (for now)

I always marveled at anybody who can bang out a post or more per day, I could never find that much to say. Well, get pregnant after multiple losses, win a trip to the land of neuroses and you can find plenty to say. I'm so glad I have this outlet, it keeps me from appearing insane in real life.

After reading my post below (or rather the update), my friend IRL bawled me out,well basically for acting crazy. Getting nervous that shoulder pain mean a ruptured fallopian tube, if you have no other symptom of an ectopic is NOT rational in the slightest. If you google 'shoulder pain in early pregnancy' comfortingly, I found many women shared the same neuroses. Its nice to have company in cray-cray land.

It was also surprising to find out that the tubes rupture as early as 6 weeks in an ectopic pregnancy. Few women have ultrasounds to confirm uterine pregnancies by then, and the majority of pregnant women never check doubling betas or progesterone. A ruptured tube in an ectopic pregnancy is often fatal or life threatening, so why wait till 8 weeks to see a pregnant woman for the first time, as is the norm? I guess the thing is, most women do have symptoms of spotting or pain at least,which hopefully gets them to a doctor in time. There are a few unlucky ones who don't have these symptoms (a few ectopic pregnancies are reported to be absolutely symptom free, but hopefully some anomaly atleast shows up in the beta levels or the progesterone values), but still, as few in the population check these, and can often be oblivious to the fact that they are even pregnant, that is moving into dangerous territory.

It is mind boggling to me that many in the population are clueless--there was this article recently about women who go through the entire pregnancy without even realizing they are pregnant. Apparently, there are quite a few of these kinds of people. A friend of mine was telling me about somebody in her family who thought she was having food poisoning, they show up at the hospital, and voila, she is in labor with a  baby on the way. That poor child was born with cerebral palsy though- her mother's diet was supposedly awful and no prenatal folic acid was consumed. I asked my friend if her relative (the mother) felt guilty, but my friend replied that she probably has not even made the connection that one was responsible for the other yet. Facepalm moments, all of these.

Anyway, going off the topic of ectopic pregnancies and happy (moronic) oblivion, I spoke to another nurse in my RE's practice, and she said something different from the first person I talked to- I can come in anytime in the week, not merely on a Monday when my RE is around. So right now, the plan is to go in on 6w2d, which is Thursday, and pray that I can see stuff. I'm still torn about the timing, if I learn I'm in trouble, I will probably effectively destroy my cousin's weekend. But waiting 4 more days past Thursday may be a bit too much for me.