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.