Low AMH: Diminished ovarian reserve or a Vit D deficiency?

I received this email a few days ago. This post is to address this question and as well as the many people  who have come across my blog doing Google searches for "low AMH" or "AMH and Vitamin D."

"I came upon your blog while googling for information about low AMH levels, which I'm sure you know, is very difficult to find.  I'm curious whether you've found any other information about increasing AMH levels other than Vitamin D.  I was diagnosed with low AMH (all else normal) and my RE told me there is no way for it to increase and that it would only decrease.  He was pretty doom and gloom about everything.  I'm currently using royal jelly, acupuncture, Chinese herbs, sprirullina, and a general prenatal multi-vitamin.  I haven't had my Vitamin D level checked yet but am considering doing that and asking about DHEA next time I go to the doctor as I'm hesitant to add anything else to the mix right now.  Thanks for sharing your story online."

In addressing the question asked of me, I have to point out one important fact that I think falls between the cracks with most people.

AMH is a surrogate marker. Why it is considered a good indicator of your ovarian reserve is because it tells you how many antral follicles are present in your ovaries each cycle. The antral follicles actually make your AMH. So more the antral follicles you have, the more your AMH, or at least, that is the logical stream of thought. Women with a failing or low ovarian reserve have very few follicles left, so their AMH is low. In other words, the problem is not that their AMH is low, but it is that they have few follicles left.

The question is, can your AMH be falsely low? To find this out, you must have an antral follicle count done. AMH alone, or AMH + FSH/E2 cannot give you the full picture.

If you have a low AMH and very few follicles left, then the probability, sadly, is indeed that you do have a case of diminished ovarian reserve.However, if your antral follicle count is normal/good/high and your AMH is too low, then something may be wrong.

One of two possibilities may account for this:

1) The lab messed the test up
2) The tantalizing Vitamin D theory: Now----I came up with the theory only based on the finding that the AMH gene is turned on by Vitamin D. This is solid, irrefutable science here.  What is still unclear is whether a vitamin D deficiency leads to suboptimal AMH production in the antral follicles. My findings imply that it did, but we cannot rule out that the first lab really messed up my AMH test. It needs to be studied clinically.
Updated 2 years later: Yes, this has been studied, and it is now fairly certain that your vitamin D level affects your AMH level. If your AMH level is too low when compared with your AFC, Vitamin D may be the culprit.

Overall, if you have a low AMH, then your plan of action must be to test for both vitamin D and your antral follicle count.

If your vitamin D is normal and your antral follicle count is low, then that just means you do have few eggs left.  DHEA seems to have some little success at improving the success rate in cases of diminished ovarian reserve, but its horribly unclear as to what is happening. Is it increasing recruitment of antral follicles from the diminished supply left? Is it improving egg quality as well? There was a study which actually showed that DHEA decreases the rate of aneuploidy. I don't know how solid the data is, but that is tantalizing if it is indeed so.

When you truly have DOR, then it is what it is. There is no way to fix it. You can, however, improve your chances with supplements (look for the CCRM cocktail).

I'll end on this note, and this is purely an informed opinion on my part: If  you want to have a baby, it is folly not to investigate your vitamin D3 levels. Its not just to treat infertility, but it is also proving to be very relevant in preventing pregnancy-related complications stemming from infection, autoimmunity, or pre-eclampsia. Just taking supplements is not the best way to go, because you don't know how much to take: you could end up taking too little, or in rare cases, too much.  

ICLW

Welcome! I had put myself on the last ICLW, only to discover that my baby had died 2 days into it.  Needless to say, not much commenting got done. This time I want to actually participate.

To sum up, I started 2010 eager to become a mommy. Given my age (30), my family history (a bunch of bunnies all) and initial testing results, I confidently thought it would be a breeze. Well, the good news, I got pregnant both times I tried. The bad, I lost both my angels, late in the first trimester.  Two pregnancy losses in less than 6 months can either shatter you or make you stronger and tougher than you were before. Thankfully, the latter has happened. I'm facing demons I never thought I'd never have to face, or more to the point, never could face; recurrent pregnancy loss, the possibility that I might never have biological children, and I'm still standing. 

The other thing, I'm a science geek. I'm an immunologist and am intimately familiar with human biology to start with. Now, after countless hours of reading, inventive google searches, trawling of message boards etc  I've learned enough about reproductive science to give REs a run for their money.   A lot of this blog is about the science and the mechanics of it all, and if any of you want to wade thorough it, there is a lot of discussion on things like PCOS, thyroid issues, egg quality etc. Though I'm really scared, I'm also fascinated by the biology and love talking about diagnosis, treatments, clues, both my own and anybody else's!

So welcome, and I look forward to reading your stories!
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The rest of this post is actually about science stuff (indulge me and read if you feel upto it!)

On Vitamin D and AMH

It looked like I might have PCOS which was compromising egg quality.  To investigate this further, we tested AMH, a hormone that seems to be elevated in women with PCOS. To my utter horror, AMH levels came back low, similar to that of a 37 year old's.  Interestingly, I had also found that I was Vitamin D3 deficient (I think every woman who has undiagnosed fertility problems and is not a lifeguard or something similar should get this one checked out).

On a hunch, I decided to look whether there was any link between VitaminD3 and AMH.  A google search yielded one single clue, this article (which basically says that vitamin D3 is capable of stimulating AMH production) written by a group at Stanford University.

I wrote to the scientists explaining my situation of low AMH and vitamin D3, and asked them if they knew of any studies correlating the two, and whether they were planning to do any.    This is the response I got back:

Thanks for your message which I will forward to Dr. Malloy.
The original connection of AMH and PCOS we made was not based on a study but an unusual finding we made in a child with a mutation in his vitamin D receptor. In other subsequent work it is clear that in some organs of the body, vitamin D stimulates AMH. There is no proof that vitamin d deficiency causes AMH deficiency. In any case, you should have your vitamin D deficiency treated. If it turns out that your AMH rises after treatment, I hope that you will let me know. We have considered such a study but to my knowledge no data bearing on this point are yet available.

It was definitely my POA to restore D3 to normal levels and then retest AMH. It is kind of exciting to know that if AMH goes up,  my story might assist in starting a new study which might end up identifying a major problem, if D3 indeed regulates AMH.  Its a pretty long shot, but at this point, a logical one.

Plus, I'm praying AMH goes up, I do not want to be saddled with a rapidly falling ovarian reserve at age 30 , that would really, really suck. So I'm praying Vitamin D is the answer that will fix all my problems, because right now, I have no other candidates to play biological white knight.

Disclaimer: I've had many theories, always inventive and sometimes even logical in the past few months.  Each and every one of them has been shot down by the evil universe.  The mental image I have of the process is Peeves the Poltergeist zooming over my head, laughing maniacally as he drops dung bombs on my theories.  One day, I will be right about something- looking forward to it!

Another post on AMH, AFC, and Vitamin D

Biology is complicated.  X sets off Y which sets off Z. Z  can positively or negatively regulate X or Y, and any or all of them can be regulated by A, B, C, or D.  It is a crazy, multi-layered, mind-boggling system in other words. Yet, when perfectly balanced,  perfect health results.

Trying to understand it is like trying to untangle a Texas-sized jumble of wool, yet we solider on gamely, trying to do exactly that. After I took Vitamin D, a number of things changed: my antral follicle count went down, and my luteal phase got longer.  In this post, I wanted to talk about certain studies which may offer explanations for the first.  

After my second miscarriage, it came to light that I may have certain presentations of PCOS: primarily, a very high antral follicle count (AFC), and high levels of the hormone, DHEAS.  My AFC was consistently very high (30 and 34 when measured by 2 independent operators over 3 months apart).  Between these two counts, we also found out that, paradoxically, my AMH was low. I realized that this might be because I was vitamin D-deficient, and indeed, after increasing my Vitamin D, my AMH also went up 4-fold.

One of the things that concerned me from the getgo was my high AFC. Another TTCer (Tiara), who had one pregnancy loss, also presented with a high AFC. Her doctor, in what may have been a very prudent move, put her on metformin, which is supposed to combat insulin resistance.  She was alarmed that, the next cycle, her follicle count dropped sharply, but that IUI resulted in a healthy, beautiful baby girl.  Interestingly, her anecdotal finding of decrease in AFC after start of metformin correlates with this study, which also showed a drop in both AFC and AMH after starting metformin.  Nobody knows how metformin accomplishes this,  but its main mode of action appears to be combating insulin resistance.

Vitamin D also helps to correct insulin resistance, although a lot of studies seem to think it mainly helps that subset of women who are overweight because of PCOS (I don't belong to this subgroup).  Nonetheless, because Vitamin D and metformin share this property, I was hoping my AFC would go down. The conversation I had where I tried to explain this to my nurse, so I could just have an AFC recount ordered, was kind of funny, although, on the whole, a firmly closed mind does not amuse me in the slightest. 

Anyway, I turned out to be right in predicting the result, though I think I was wrong in the mechanism behind it. My AFC went down from 32 (average of 2 cycles) to around 16 ish (average of 2 cycles).  People have said that AFC can vary with different cycles,  and this is true, but in my case the variation, if nothing has changed, is less than +/- 5.

For the longest time I presumed my drop in AFC was *probably* because vitamin D did something similar to metformin. Recently, somebody left a comment on Dr. Malpani's blogpost on AMH , that gave a really smart, and plausible alternate explanation. Apparently, AMH has this really interesting property- it inhibits recruitment of primordial follicles into the pool of developing (or antral follicles). This property of AMH provides an explanation why women with PCOS, who usually have higher AMH levels, may hit menopause later, because the recruitment of primordial follicles is lower, and hence their ovarian reserve lasts longer.

Coming back to my case, in addition to a *maybe* case of PCOS,  I had an additional confounding factor of Vitamin D deficiency (though this is also shared by around 40 % of women with PCOS). If everything in the previous paragraphs is considered correct, the broad possible explanation is this- when I was vitamin D deficient, my AMH was low because this gene needs to be 'turned on' by Vitamin D.  Once my Vitamin D levels went up, my AMH level went up. Over time, that increased AMH decreased the recruitment  of primordial follicles, so my AFC went down.

My numbers are still respectable, my total AFC is now around 16. God knows what this means but 16 is a reassuring number. However, even if you do have PCOS and your AFC goes to a number you don't like, I would hold off the alarm. One should remember this: quantity does not necessarily equal quality. This is best exemplified by women with PCOS who make a TON of eggs in an IVF cycle, and the majority are not good quality. So, on the whole, for women with PCOS,  the moral of the story is, both metformin and vitamin D have a good chance of helping you. I had the option to take metformin, but I chose not to do it, thinking that just Vitamin D would be enough.  It looks like I may be right, I hope the facts bear it out eventually.

I'll end on this note- while the role of vitamin D in pregnancy is open-shut good, its role in fertility itself is a bit murky. Overall, being deficient is bad for you.  But a few studies show that going too high may also be non-optimal, especially if you have endometriosis....you can read an entire review on the role of Vitamin D in female reproductive states here.   I'd say, while trying to get pregnant, maintaining your blood levels at around 30 ng/ml seems like the best course. After you get pregnant, your vitamin D requirements are going to rise- making sure you are taking enough to maintain around 40 ng/ml  may be best.

WOW (edited)

For those of you who are following the vitamin D3- AMH story, here is the latest.

3 weeks ago, I was in the deficiency/low range for both Vitamin D3 and AMH.
Vitamin D3= 16 ng/ml, AMH= 1.1 ng/ml.

The low AMH sparked off an avalanche of fears about diminished ovarian reserve. Then I took gigantic doses of Vitamin D (60000 IU weekly) for 2 weeks

Then I gave blood again,  and tested both Vitamin D3 and AMH.
Vitamin D3 = 70 ng/ml (perfect) and most amazingly AMH= 5.18 ng/ml  (high and now in PCOS range)

Overall, a four fold increase in AMH levels (going from 'low fertility' to 'optimum fertility' in the lab classifications), which I found just incredible. Its always possible the first lab really messed up the test, but I think that there is really a fair chance (based on the study I posted about) that AMH went up because Vitamin D did. Anyway, I've let the group at Stanford studying this know and maybe one day a formal study might be launched. 

Right now, the primary emotion is  massive relief that I'm not dealing with a case of low ovarian reserve here.

Interestingly, my testosterone levels also changed dramatically, they went from being fairly high in the Vitamin D deficient state to being low after my deficiency was corrected.

Currently, my theory (derived from combining very few facts with a lot of speculation and intuition) is that my problem could be two-fold,  first low vitamin D3 (found in about 40 % of cases with PCOS ) and a possible undetectable issue with insulin resistance, which could be addressed with metformin.

Other than the now corrected Vitamin D deficiency, my only PCOS parameters are lots of antral follicles and now high AMH and slightly high DHEAS- The million dollar questions are:
1)  is this messing up egg quality and thus responsible for my two losses?
2) Is it tied to sugar metabolism and be fixed by metformin?

I have a very strong family history of type 2 diabetes (practically everybody in my father's side develops this), though I could find no indication whatsoever of insulin resistance in me. But still, metformin has been shown to help even when there is no overt insulin resistance. Nothing is a sure-fire fix. Last time I attempted conception I was praying the thyroid hormone would be the magic fix I needed. The next time, I will be hoping its all of this.

In which I pat myself (and you) on the back

Along this crazy, rollercoasterish journey, I've had theories up the wazoo. I'm constantly thinking about things, speculating away like mad and most of time I'm probably several miles off the mark.

But, just sometimes, I may be right, and it is so, so very sweet when I find out that it is so. A long time ago, when I first checked my AMH, it was low, resembling that of a woman almost a decade older.  But sometimes, I do believe the universe does look out for you, because, the day I had that blood draw, I also threw in a vitamin D test, based on an off-hand remark that the guy who was drawing that blood made. How is that for serendipity? Anyway, my vitamin D was low too, and I decided to look for a connection between the two and I found it, in a study which said the AMH gene can be 'turned on' by vitamin D, suggesting that the Vitamin D level could influence the AMH level. Based on that, I took massive doses of Vitamin D to correct my deficiency and retested both after 2-3 weeks.

I found that, coincidence or not, AMH went up 4-fold after vitamin D went up 4-fold. A few days ago, I got an email from a grad student who just had her paper accepted- its the first scientific confirmation of what I'd found, that if you are vitamin D low, your AMH is likely to be inaccurately low, and you can get a 'good' reading only after you get your vitamin D deficiency corrected.

The study is here

http://www.ncbi.nlm.nih.gov/pubmed/22508713

I remember how I felt when I was grappling with the possibility that based on my low AMH, I was a contender for diminished ovarian reserve. I think about what might have happened if that technician had not suggested the vitamin D test, or if I had not gone looking for a connection between the two things, and I have to shudder.  I don't think anybody else was going to put these 2 things together- I've been educating doctors about this, it has not been in the opposite direction, so really, I fixed the issue myself, and if I had not done it, nobody else would have.

It is National Infertility Awareness week. And I'm going to give myself a hand. I'm  also applauding the many, many, many women who have shown up on this blog doing Google searches for "AMH and Vitamin D." They fixed their own problem too. Most often, the only person we can rely on to save us is ourselves. And that is not just limited to doing a clever Google search- this is for anybody who has pulled themselves up by the bootstraps after their umpteenth BFN, or their miscarriage, or their stillbirth. We are all bloody amazing, and we need to take a moment to acknowledge that. 

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.

It looks like things may proceed as planned.....

Since my last attempt at conception, where I tried in what I thought was an awful cycle, got pregnant, and lost it to a chromosomal abnormality, I've decided that the next time I conceive I was I want it to be in a *very* good looking cycle.

The cycle before this was like.....Chris Pine. Crazy pretty-looking, in the pre-ovulatory phase.  This cycle is kind of like... Ewan Mcgregor. Its solid, its kind of nice-looking, but cannot compare to the few Godzilla-like fertile cycles I've had, wherein, even in the days I was blissfully unaware of anything fertility-related, I would have noticed that something was brewing below. Unfortunately, those cycles have shitty timing.
 
I've been having just the creamy CM for days, just enough to let me know that the estrogen rise is happening, but not hitting me on the head with it, like in the last cycle. EWCM is not here yet, and I'm atleast 72 hours (hopefully) away from ovulation. Today, I used my Clearblue fertility monitor for the first time this cycle- I was so expecting to see the 'Low fertility' (= low estrogen), instead I got 'High Fertility' (= high estrogen). A happy dance happened :)

 The reason I had utterly hated the last cycle I conceived in was that I went directly from 'Low fertility' to 'Peak fertility'(= high estrogen + LH surge) --- there were no days of high fertility, where your uterus and ovaries bathe in estrogen before the surge begins. This cycle, I have that, hopefully for 2 full days of that before my surge begins. If my OPK gets positive later today or even tomorrow, I'll have to bench myself, though I'd be on the fence about tomorrow.

Onto bloodwork results:  I had gone to see an endocrinologist 1 week ago, who is awesome and definitely gets a review written up in the 'good doctors section'. He ordered every test I wanted, and a few extras, and we got the results back.

The salient points:

• I should have been taking my own advice of getting Vitamin D levels regularly tested when you supplement. To be fair, I had tested twice and it looked like 4000 IU/day was kept my levels at around 35-40 ng/ml,which was just about prefect IMO. Maybe there is an accumulatory effect over time, and quite likely, the 8 days I mostly spend bikini-clad on a ship (slathered in sunblock, but still managing to tan meaning UV rays WERE getting through) had an effect too- my D3 (1,25 hydroxy version) was 86. Ack!!!! WAY too high. I'm going to cut down now and start retaking the same dose once pregnancy establishes.
•  TSH is nice and super-duper low at 0.65 mIU/DL, and my T4 levels were just over the high end of the normal range. Perfect for conception.
•  Anti-TPO antibody titer is slightly down, from 107 around 16 months ago to 90 now. I've been taking selenium (80 mcg/day), plus a nearly equivalent amount in my prenatal. Many studies show that which is supposed to lower Anti-TPO levels. This is an excellent link for anybody who has thyroid issues, I urge you to visit it.
•  AMH is down a bit, from 5.6 to 4.3. I had expected this, because my AFC has gone down in half, from 30 + to around 16 ish, so its logical that AMH (that is made by the follicles) would go down too.  I'm happy with just this slight drop.
•   DHEAS is still high, and has gone up to 331 from around 250 in the last tests. This is the only part I cannot understand.

Interpretation: My thyroid function is now as well behaved as it ever is going to be. I believe that becoming vitamin D replete- see above link- as well as the selenium intake had much to do with this slight change.  Over 1 year ago, the following tests suggested PCOS (High AFC (30+), High AMH (5+), high DHEAS). Now, the only thing that is left is the high DHEAS, which, in itself may not be a bad thing necessarily.  Also, I used to get annoying skin breakouts, which is a PCOS-related issue, every now and then. Interestingly, for the past few months (hammering on wood), my skin has looked as good as it ever has- no breakouts for months. Praying that typing this out here does not bring them back, just to prove me wrong.

Things look good. Right now, its a go for early next week.

I had my first acupuncture session- thank you everybody who came up with recommendations- I went to the first name suggested, and so far, so good. Liz Carlson (of Clarity point Healthcare) was very nice. Its too soon to say if it has worked, but hey, I did wake up to high estrogen today. I have another appointment on Monday, just to play it safe.

She also suggested that I take wheatgrass. I've been reading up on this and so far it seems like a good idea- I really like the fact that its supposed to help detoxify heavy metals from your body. I need advice- pills or juice shots? How disgusting do the shots taste? I kind of like pills because you don't have to go looking for a juice bar or a farmers market on a regular basis. For any of you who took wheatgrass,  what form did you take it in, and how regularly did you take it?  Plus, did any of you continue to take it into pregnancy?

I'd also promised a writeup on Thyroid and fertility/pregnancy, I'll add that directly to the 'Science of Infertility section'.

I noticed commenting is a little wonky today, it takes a while for comments posted to become listed- are people also having issues using Disqus?

Craziness all around

I get a call back about my AMH, with the lab informing me that they have to retest it. I used my 'Dr.' title to make them give me the preliminary result- its apparently OVER 6.9, and out of range probably.

An explanation of the reference ranges used by a testing lab in India

WTF?

2 years ago, I was looking definately PCOS-ish, with an AMH of 5.6 and an AFC of 30.

3 months ago, it was 1.9 one month, rose to 2.6 the next month, at which point my AFC was 13.

Fastforward 2 more months, now my AMH may be over 6.9, with an AFC of 25- back to looking PCOS-ish.

Like I've said, all I can monitor that has truly changed in my body are my vitamin D levels. My doctor, playing devil's advocate pointed out there could be a lot more changing that you could be aware of. Theoretically, that is a perfectly valid point. What confounds me is the timing- when my vitamin D levels stay within a range, say, deficiency, nothing changed over many months monitored. When my levels were really high, things changed and then stayed constant for a while. Now that they are lower again (but, above my original levels), things have changed again- we will need to monitor for many more months before drawing conclusions of any sort. 

What is my diagnosis? I have fertility issues sure, but the underlying causes are damned near indecipherable. Most people can get a clear label- of 'PCOS' or 'Diminished ovarian reserve'. With all my knowledge and recall of all the minutiae of my case, I have no idea how to label myself. I lean towards PCOS, but I'm not quite there.

So what I'm wishing for in 2013, aside from a baby-- enlightenment. Also, for concrete and viable solutions to counter gun violence and  violence against women, but sadly, there is a much higher chance of me actually having a baby than meaningful progress being made in those directions. 

Happy new year everybody. I hope this one is a kind one, on the whole.

Also, please go offer a shoulder to MN, as she faces the unthinkable, yet again.

'There is more to life than reproduction'

This is what my mother (in exasperated mode) said to me this morning. We were getting ready, and I was talking about testing and logistics. She turned to me and said, you don't really think about anything other than this, do you? I truthfully replied that that is kind of correct- no matter what else I'm doing or pursuing, this is always at the back of my mind.  I've never really pursued anything this vehemently and determinedly.

My mom let it go but she hates what this journey is doing to me, and her view of all of this is so very removed from mine. She does not want her baby to suffer, and she sees this process primarily as one that has hurt me more than anything else ever has and so she wants me to ease up and step back, for my own sake. Me, I'm incapable of it for the most part.

In addition to fighting infertility, you also have to fight the perceptions that others have. Not blaming them for those perceptions, but boy, its exhausting.

On the test front: This journey is littered with clues that may well be red herrings. Another such one has come up. I had Vitamin D3 checked- my levels are low (16 ng/ml for anybody interested). This vitamin is low in PCOS. I also spent a while asking Dr. Google in creative ways if AMH and Vit D3 are linked, and lets just say I found one tantalizing paper saying they were (Vitamin D binds to the AMH promoter and stimulates its production).

So I'm starting Vitamin D supplementation (that part is fine and sensible, 16 ng/ml is clinically too low)  the part that irks me is that I'm looking at this issue and hoping and projecting it to be the magic fix for all my problems, just like I did with the thyroid.  I'm so tired.

PCOS or not?!?!

On the medical front, I'm still ridiculously confused, I'm still pondering that million dollar question, do I really have PCOS? There are cases of PCOS that go undiagnosed for years because nobody runs the right tests. In my case, I've run all of them (sometimes in triplicate) and I'm still left scratching my head. This disease is COMPLICATED!!!

My San Diego RE( Dr. G) who first remarked that my ovaries looked polycystic, does not really think that I have PCOS. He thinks my ovaries look 'multi-cystic'. Translation- I have about a gzaliion follicles in each.

Courtesy of Google Images

My antral follicle count has consistently been in the 30s. My repeat AMH (because I never believe in just one test reading) was even higher, at 5.6 ng/ml.  You can look at these results from 2 different angles- from one angle I'm just blessed with a pretty abundant ovarian reserve, above average for age 30.  Look at it from another angle, and yeah, it looks like PCOS.

I've read some crazy complicated papers on how to diagnose PCOS.  There are 3 big players here-

• The ovarian parameters (high AMH and follicles) ---- big check mark here

• Ovulatory disturbances -----none. Ovulate beautifully, and in ridiculously reproducible patterns, every month.

•  Hyperandrogenism (greek for too much male hormone):  3 things to check here- DHEAS/ DHEA, testosterone and physical characteristic of hirsutism. 2 out of 3 qualifies you, I think.

Overall, you have to have at least 2 out of these 3 (ovarian parameters, inability to ovulate and hyperandrogenism) to qualify for a PCOS diagnosis. I have the first and definitely don't have the second. And as far as the 3rd goes......that is where I'm in limbo, awaiting a decision.

About hyperandrogenism:
I don't have high testosterone. I've tested this 6 ways to Sunday- conclusion- my testosterone is at the lowest end of the normal range.
I DO have high DHEAS (over 200 in 2 seperate tests)
The tie breaker is......hirsuteness. That is the condition where you are hairy like a man.  I'm sure everybody has seen somebody suffering from a really bad case of it one time or the other and knows what I'm talking about.  I'm NOT like that, not by a long shot, so if you had asked me a year ago whether I was hirsute, it would have been an absolute no-brainer to say no.

However, I recently came across this way to 'score' if you are clinically hirsute. Its called the Ferriman-Gallway score and it looks at body hair patterns not just on the face, but all over your body.

A picture speaks a 1000 words, so go here to see what it is all about. 

The papers say that if you have a Ferriman-Gallway score above 6, you might be considered hirsute. If you are above 8, you most definitely ARE hirsute. I looked at my own body hair patterns and I was like gee, I might just be in the 6-8 range, or maybe even higher but its really hard to evaluate one's self. If this comes through then we can conclude, yes, I just may have PCOS.

But right now, I'm waiting to pick an insurance, and then just find a doctor who will help me determine if I qualify for hirsutism. I usually get rid of body hair on a very regular basis, now I'm forced to keep it till I see a doc. UGH.

Quite a few medical professionals (including Dr. G) have asked me: how does it matter even if I DO have the mildest form of PCOS in the world, since its clearly not affecting my ability to conceive??? Well, because even in its mildest form, it CAN potentially be deadly.  It can stick a foot out and hamper fertility in MANY different ways.  PCOS can not only interfere with your ability to conceive, but can mess things up well after conception- ridiculously complicated post on that will be written one day in the future.

Phew

About 3 days ago I finally became negative on the urine beta HCG tests. Having gotten this green flag,  I finally went in for my antral follicle count today.

And...phew. AFC is 15 follicles per ovary(!!!).  Ovaries look polycystic but thankfully, ovarian volume looked normal. Most reassuringly, this definitely does not correlate with low ovarian reserve, which was my one gigantic fear since I found AMH was low.   I also gave blood to retest for AMH and (for good measure), Vitamin D3 since I've been on massive doses of the latter for the past two weeks. Testing in India is cheap so I go nuts. Off topic, but I'm also getting Vitamin B12 tested (nothing to do with fertility that I know of), but Vitamin B12 deficiency is really common in the Indian population and has also cropped up in my family. Interestingly, severe deficiency of this vitamin seems to cause some mental issues (periods of rage, stress etc).

   
So, overall,  it looks like I might have ovulatory PCOS (which according to my Indian RE may be compromising egg quality) but the jury is still out of the diagnosis. I'd be glad to have a confirmation, at least we would have something to treat.

Shattering my preconceived notions (karyotyping results)

I got the karyotyping results back and they were what I had been praying for since I heard my child's heart had just  stopped- a chromosomal abnormality, Turners syndrome (45 X0).   It does not seem that way, but I actually got lucky. Turners is a genetic condition with wide variation. In the least severe cases,  the child can survive, but have some serious physical issues, including heart defects and sterility.  Chances are, had this loss not occurred, I would have detected it in  the 5 month ultrasound and would have been faced with the agonizing decision whether to terminate or not. I thank god, the universe, whatever, that it did not take me to that place.

I would put this down to really crappy luck, except, though, as an effort to determine the PCOS diagnosis, we finally tested my AMH.  To my absolute amazement, it came back  on the low end, at 1.1 ng/ml. The reference range for the testing lab is 1.23- 8 ng/ml. AMH is touted to be the most accurate predictor of your ovarian reserve. The lower it is, the fewer eggs you have and the closer you are to menopause. My value, while not abysmally low, indicates that my ovarian reserve may not be as good as I thought it to be.

What this has told me- don't have preconceived notions about your own biology. I always thought that I had plenty of good reproductive years left. My grandma gave birth to my dad, her 9th child, at 45.  My cousin conceived her one and only child (a perfectly healthy boy) at the age of 43!  My mom got pregnant every time she wanted to, and produced 3 healthy children. Reproduction is NOT an issue with my family. When I had confessed my plans to that cousin who reproduced  (by accident) at 43, she tore into me for not waiting any longer, because according to her, I could have have done this comfortably even when I was skimming 40, given our history. At that point, I thought I could too. Now I don;t know anything anymore.

We have not yet confirmed that its a failing reserve we are dealing with here.  Overall, my test results can be summed up in one word- confounding. I'm baffled, nothing seems to add up.Adding weight to the PCOS diagnosis,  I have high-ish male hormones (though still within normal reference ranges). PCOS is associated with insulin resistance, with fits with my family history of type 2 diabetes. Because the universe has decreed that nothing should ever add up, I have the opposite,  insulin sensitivity- low insulin, normal sugar in fasting levels. With respect to ovarian reserve too I'm scratching my head.  At the last test around 4 months ago, the other good indicator of ovarian reserve, antral follicle count came back ridiculously high at 34. So we don't have the full picture yet, we need to determine if I have PCOS, or a close-to-failing reserve. Of the two problems, I'd pick PCOS I think, though its choosing between the devil and the deep sea.

Sometimes, things happen that really make you wonder if there is a gran plan to things, even if  a particularly perverse, slightly evil one. The day Turbulence was conceived, something told me it was a girl. After the loss,I've been praying it was a boy because then I thought, for some weird reason it would not hurt so much. It also it takes the guesswork out- if your karyotyping results are a chromosomally normal female, you will always be left a little in doubt, it might have been your cells they examined by mistake. But all in all, I was really anticipating an answer that would definitively give me the gender of my child. I've even been very mildly obsessive about this point.  When I got this result, I started laughing (the alternative was to cry). With an XO genotype, my child was essentially genderless.  Talk about the universe telling you, in a creative, slightly evil way of course, that sometimes, there are no answers.

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?

Understanding my infertility: four years in retrospect

When I had my first miscarriage and then my second in rapid succession, I had no idea what was going on, and I made truly valiant efforts to understand. I went off on a lot of tangents, and some of them (the Vitamin D deficiency, understanding the connection between Vitamin D and AMH, the thyroid autoantibody issue) yielded a lot of valuable information. There were some indicators that all of these (the vitamin D deficiency combined with the TPO antibodies, often seen in women with PCOS) may be indicative of a very low level of autoimmunity that may have interfered maybe oh-so-slightly with the progress of a pregnancy, but at the end of the day, I think these things were not my central problem.

There are two aspects to egg quality, both of which decline with maternal age. One is the state of the egg cytoplasm, which has all the mitochondria and the nutrients required to survive, divide, and thrive for the first 8 days of life by itself. The second is the chromosomes itself, and this is governed by the meiotic division process where your 46 chromosomes are divided into two sets of 23 chromosomes each. I talk about how one or both of these may be affected in the "Science of Infertility" section.

What was my problem? My cytoplasm quality was, by all accounts, really gosh darned good. It may be that I have an issue with the meiotic chromosomal division process, as a result of which a high number of my eggs are aneuploid, and I may have come into this problem (which is usually seen in women in their 40s) ten years or so too early. Compounding the problem may have been my "superfertility," which may have caused my rather stupid uterus to implant embryos that a "normal" person's uterus may have rejected. I have come to these conclusions based on the following statistics:

• My pregnancy rate was 75% (3 out of 4 unmedicated cycles), which is FAR higher than the figure (20%) reported in "normal" women. Two of my three embryos were shown to be aneuploid, and one of these aneuplodies was a Trisomy 4, which is extremely rare because embryos with a trisomy of this ginormous chromosome almost always fail to make it to the blastocyst stage, or after, fail to implant or grow. 
• Normally, the implantation rate for high-grade blastocysts is around 40-50% (i.e., 1 out of 2 blasts is likely to implant). The implantation rate for my high-grade blasts in women with "normal" fertility (the two surrogates) was far lower (1 out of 5 blasts, from 3 transfers).  

This suggests that most of my embryos were abnormal, and I kept implanting them anyway. This pregnancy may have come about because J's uterus could perform the selection that mine could not.

Had I not the "superfertility" issue, I may have just taken much longer to get pregnant, but may have stayed pregnant when I finally got knocked up. That would have been so much better, but as I gaze at my baby girl, I'm still fine with this version of events.

Now WHY I had the meiotic division problem is really the gzillion dollar question, that remains completely unknown. There appear to be no biomarkers or tests to indicate this. One has to wonder if the common problems seen in infertile women (The MTHFR mutation, the PAI variant, various autoantibodies) are biomarkers (indicators) for this issue, or are linked to it in some way, but nobody has ever looked at these particular questions, I think.

The other thing I wonder if there is a "cross talk" between my embryos and uterus that was messed up, and a developmental "brake" that malfunctioned in my embryos. Each time I ever got pregnant, it was an ovulation from my left ovary. The one time I failed to get pregnant was a right ovary ovulation, and honestly, I fail to see how that embryo could have been more messed up than the left ovary-derived Trisomy 4 embryo that implanted in my next attempt.

During IVF, I asked the embryologist to culture the eggs from my right and left ovaries separately, and the results were interesting. Normally, around 40% of fertilized eggs become blasts, and I saw this in my right ovary eggs. In contrast, over 70% of the fertilized eggs from my left ovary became blasts, which is far higher than normal. My daughter (feels SO amazing to say that), came from a right ovary egg. All this makes me wonder if the fault (for the messed up crosstalk between the uterus and the embryos) is a problem that is a problem specifically in the eggs of my left ovary. Of course, this last bit is wild speculation (even more so than the first bits, which are a lot more likely). 

There...the last 3 paragraphs will probably give everybody a headache, but I had to put down my thoughts for posterity. There is a part of me that wants to go back and do research on this issue, because I feel so passionately about it. I've actually been thinking about whether there are openings at RMA-NJ (because they are such a research-oriented fertility group).

Anyway...all is well that ends well, and I hope this recounting will be of use to somebody someday.

Grand plans

I met with this RE in India who came up with an interesting potential cause for my losses: PCOS that was affecting egg quality.  My regular RE had thought my ovaries looked slightly polycystic (~17 antral follicles in each ovary), and he had checked DHEAS and testosterone. DHEAS was in PCOS range (over 200) but testosterone was low, so the PCOS diagnosis had fallen by the wayside. This new guy now wants to recheck antral follicles and also LH and AMH (both of which are elevated in PCOS, and have never been examined in my case).  This offers a possible answer and the fix would be metformin both before and during pregnancy.

I know that there is still a higher than normal risk for miscarriage with the next pregnancy. This is, after all, only an emperical treatment. On suggesting gestational surrogacy, he flatly refused. He told me by all accounts, that I had a healthy uterus, and using surrogates just because I could would be premature and wrong at this point. In all fairness, I have to agree with him. But, I'm not ready to face the prospect of another short lived pregnancy and loss, while back in the States and alone.  I need a good support system and I can get this only if I  a) magically find Mr. Right and get hitched or b) come back to India and try here while being with family. All in all, I've reached the end of my tether as far as going-it-alone is concerned.

Setting the stage for short term return to India will take one year.  I'm willing to put off babymaking for that long. I''ll be only 32 at that point, and by all indicators, would have plenty of eggs left. The only real hurry has always been in my own head. To stay sane, I need plans with contingencies upon contingencies, so here goes.

The Plan 

1)Check genetics (mine and babies) and run every RPL test under the sun. If all is normal, then do nothing for 1 year. Enjoy life and return to the the person I used to be before pregnancy loss.

2) Return to India, start TTCing with unmedicated IUIs after 3 months on metformin.

3) If a loss occurs, then do IVF using 2 different donors ( including my original, who I just don't want to give up on yet) and THEN (with  this RE's blessing),  go to gestational surrogates. This is the part which can be repeated again and again, if need be. 3 losses would be when I'd stop using myself a s a guinea pig, its just too much. With surrogates and a shitload of dough though, its a different thing. I'm really lucky to have these options,.

4) If multiple tries here fail too, then that implies the issue is genetic and with my eggs.  At this point, go to donor embryos and use my body to carry them (hoping that all parts are still functional at the end of this and the issue was never with my uterus in the first place)

5) if this fails too-adoption in India. 

I can deal with the prospect of short-lived pregnancies and more losses, but I need to choose my battleground wisely. Having lived through the last few days mostly easily, I know being at home will do it.  But importantly, finding real peace requires preparing myself  for the final 2 options which involve letting go of a biological child. Once I become ok with this concept (its going to take work) then who cares how long it takes to get there? Life is making me work for a child, I have faith that it has something good (even if its not what I originally envisaged) waiting for me.

My super secret life (and results of the RMA-NJ consult)

It is funny how much I have going on, and so few people know about it. I'm currently in Canada, visiting family, and they have no idea what I'm going through. I sent my medical history (a mind-boggling total of 70 pages) to RMA-NJ, and nobody knows I've shed so much blood. Almost nobody I see on a daily basis knows about my D&Cs, my attempts to have babies, the fact that I have a blog visited by people from all over the world, that has made me over a 100 bucks in advertising (thank you, Google ads). When people talk about their problems, I kind of am amazed as to what I handle on a day-to-day basis without ever talking about it anymore. Anybody who leads this secret double life and goes about with a smile on their face regularly deserves applause, and I know a lot of you do so.

Anyway, getting to the meat of things:

Next transfer to the surrogate is set for Monday the 12th.

I had my phone consult with a doctor at RMA-NJ today, and it was a fun talk (I'm the only crazy person who thinks a breakdown of my problem is fun). We talked solely about the science of things, and it  is obvious that he would be the best informed and forward-thinking of any of the REs I have been to ( I seem to be collecting them, this would be my fifth RE!). RMA-NJ has a ton of studies going on, and some of them tackle questions that I've spent a while pondering, which is pretty cool.

Here are the salient points of our discussion
Turns out there are 2 roads to infertility as far as the egg goes:
Biochemical aging: Herein, the egg has metabolic issues; it divides poorly and and often does poorly in IVF. People with this issue hit menopause earlier. Importantly, this problem is correlated with the antral follicle count, and women with this issue present with diminished ovarian reserve.
Ovarian aging: Herein, the eggs may have no metabolic issues, even at an advanced maternal age. They may grow well in IVF, and women with this issue can have an abundant ovarian reserve with perfect FSH, and are often found to hit menopause much later. Yet, something is wonky with the meiotic process, and they produce eggs with aneuploidy. Importantly, this does not correlate with the antral follicle count.

The doctor concluded, based on our conversation, that my case may be one of ovarian aging, because, at a young age (early 30s) 2 out of my 3 naturally produced eggs have been aneuploid, and the first one (normal XY by karyotyping)  may have had genetic deficiencies as well, given the way the pregnancy progressed (slowing of growth between the 6th and the 7th week). So unless I'm insanely unlucky, I have an aneuploidy issue. The silver lining is that my eggs are, from a biochemical/metabolic standpoint, stellar. This my explain my family's crazy high fertility. I just have a problem that they did not have.

In other words, if you have decent AFC, decent FSH/E2, ovulate regularly, do well in IVF, get pregnant easily, but suffer from RPL, your issue may be ovarian aging. Here is the bad news: there is no biochemical test that can be done on you to diagnose it: there are no markers, nada. Since we do not know what causes this, we cannot fix this either.  The only way to sort of confirm that this is your issue is through CCS, and it will tell me if I need to go to donor eggs or adoption to have a baby.  So come early 2014, if all my transfers fail, I will pack my bags and return to the US.   

If I have to do IVF, they would put me on the antagonist protocol. The doctor expressed surprise that the microdose lupron protocol was chosen for round 1, given my AFC/AMH. Sigh...live and learn. It sucks to have done 2 IVFs though, and have to go through so much to get an answer. Had I a crystal ball, I would have gone to these people last year, and saved myself a ton of time (and money). Of course, if the surrogate gets pregnant, I'll sing a different tune! 

Miscellany

Life is progressing well in NYC. I think at this rate, my liver is going to be pickled (quite a change from the I-don't-touch-alcohol slogan which as the backbone of last year) but I'm slowly settling in and meeting new people.  Loads of fun!

I *finally* had my new RE appointment today (Dr. Licciardi, NYU). I walked out of it fairly pleased, on the whole.

The highlights
Finding out IUIs will be covered (or so I believe at this point)
No forking out 300 odd dollars for a new consult- only a flat small copay!
He agreed right off the bat to genotype me at the FMR1 locus (this is also the fragile X test)

The Plan Forward- do I really have a problem and can it be fixed??
We have no idea why the crapfest that was the last year really occurred.  I think the question to ask is- do lean/ovulatory PCO woman really have problems either conceiving or maintaining a pregnancy? There is a trend to suggest this, but really large, well designed studies have not been done. What I want is the opposite of the studies that are done- I want them to take women who conceive easily and have had multiple healthy pregnancies, and ask if THEY have lean PCO and thyroid autoimmunity and heightened NK cell activation and anti-phospholipid antibodies and all the million other vague problems that plague infertiles.   Sigh. 

Dr. L was willing to go with the theory that I might have lean/ovulatory PCO, but was completely noncommittal (as any sensible person would be) on whether this was the real cause of my losses and whether metformin would help me.  The way he put it- there are two types of PCO patients...The first category, that I fall into, which he referred to as 'New York PCO' (ha) wherein women are thin, are not visibly too hirsute and might even ovulate regularly. Then there is the second class of overweight women with overt glucose metabolism issues and ovulatory problems. In his opinion, metformin really helps the second category, but seems to not do so much for the first. I've read the studies, I've read the reviews discussing the studies, I can't really be sure metformin helps either, but nor can I discount it. There are studies which show it does seem to reduce the antral follicle counts and AMH levels, however bigger and better designed studies are needed IMO. So as it stands- we agreed I would start metformin about 3-4 months prior to my TTC cycle.  I think there would be significant debate about when to end it- I would probably atleast go to the end of the first trimester.

We are also getting my glucose metabolism investigated. I've had fasting glucose tests done and they are excellent- normal sugar levels and actually LOW insulin, indicating insulin sensitivity, not resistance. What we have not done though, is a glucose tolerance test. Given that I love to shock my system with an insanely sharp sugar spike atleast once a day (such a good idea for a girl coming from a family of type 2 diabetics...NOT), it will be interesting to see how my body responds.

More on vitamin D and BBTs and charting and follicle counts to come soon----and I've also got the doctor reviews to put up. Not that I have that many- but- my page is now the FIRST that comes up when you do a google search! Its even pulling up doctors mentioned in the comments- super cool!

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.

ICLW (quite a bit late)

Well, I’ve been meaning to write a post welcoming whoever came over for ICLW for the past 4 days, but my schedule has been nothing short of insane so nothing got written and worse, ICLW commenting did not get done.  I’ve had a lot of people who just jumped in there with the last disjointed, introduction-less entry and commented, I thank you for it.

Still, better late than never: To sum up my blog, I’m somebody who thought she would have absolutely no issues in the baby making department.  2 pregnancy losses later, I’m one hell of a lot tougher, and I think a whole lot wiser too.  Since I’m a scientist that studies how the body works for a living anyway, I’ve come a good way in understanding reproductive biology, and I’ve tried my best to share that knowledge with everybody.  I discovered I was Vitamin D deficient after my second loss, and intense reading on the subject of deficiency of this hormone in various disease states, including infertility has made me a very vocal advocate on the topic of testing for this, and making sure you have normal range blood levels, with a large portion of my blog being dedicated to this subject.

Sharing of knowledge aside, I’m awed at what a source of emotional support the blogsphere has proven to be. While nobody else in real life wants to spend more than 15 minutes listening to you, here, you have a network of people from all over the world, genuinely invested in everybody’s journey and willing to spend hours cheering others on, or crying with them in the horrible times.  Women going through infertility just a scant 10 years ago did not have this resource, yet, we today, do.  When we think about the unfair hands we are dealt, that is something to remember.

In other news, I'm gearing up for the next try. I finally got my act together and went to an endocrinologist.  I was lucky to find one at NYU with really good reviews, and thankfully, he more than lived up to them. He listened to me,  he was well versed on the topic of anti-thyroid antibodies and their potential role in pregnancy loss, as well as the studies (not terribly convincing, but still plausible) looking at correlations of higher levels of TSH during pregnancy and IQ of the resulting children. He was willing to re-test everything, which included the PCOS hormones (Testosterone, DHEAS, AMH, and LH), the thyroid hormones (TSH T4, T3) and the Anti-TPO/anti-thyro-globulin antibodies. I had a whopping 10 vials drawn, and I'm eager to find out what it will show. 

Detailed post on the PCOS + thyroid condition coming , but I have to say again what I will reiterate there- when you get your thryoid tests done, look at that TSH value.  The old normal range for TSH was about 0.4-4 mIU/ml, now  it seems to have been revised  to 0.3-3 mIU/ml, with studies suggesting being over 2.5 is bad in pregnancy.  If TSH  over 2.5 (but still in the normal range),  demand a test for anti-thyroid antibodies. Anybody who is TTC, with infertility issues, is best off maintaining their TSH at  around 1-1.5. 

Its a simple no-risk treatment that only asks that you take some amount of thyroid hormone (which is perfectly safe as long as you do not take too much) and get frequent monitoring done, and it *may* fix an issue which is kind of an ill-understood and murky threat.  I am of this opinion, my current RE is not, but thankfully, this endocrinologist definitely is.  My thyroid during pregnancy will be in good hands.

random musings from the fevered brain

I'm sick. I've got a noseful of snot, a fever of over a 100 degrees (thank god for anti-inflammatory drugs) and a really nasty sounding cough. Very happy I've got people to pamper the crap out of me. Unfortunately we also had a weekend getaway planned to see another large family cluster of cousins and nephews and nieces. Sucky timing, I was *really* looking forward to it.

Anyway, back to talking about baby-making. Currently, I'm grouching over the impossibility of predicting CD1, sans period.   I had my D&C 18 days ago, and I'm still showing up positive (though its almost gone to nothing) on pregnancy tests. I always figured that once the beta levels dropped to nothing, that would be when my true cycle began. The point of this exercise is repeating an antral follicle count and then AMH early on in the new cycle.

Right now I want to talk about uncertainty. The RE I consulted with told me,  I guarantee you, 100%, that you will have a baby one day.  I have none of his certainty. All of my confidence ( in making a biological child) is gone. I'm confident I'll still be a mother, by what route though, I now do not know. Oddly enough, I have faith in one thing- destiny. I believe that you will end up with only the child(ren) you were destined to have, period.  I see people suffering so much, with repeated losses, with years of infertility trying so hard to have that biological child, and failing. I keep thinking, do these failures occur because there is another child waiting for them, and they have to make their way to him/her?? Maybe its a child that somebody else has created. Maybe its from a donor embryo.  Or that  its not yet time to have the biological child, because the right combination of sperm and egg has not yet been achieved.

These are at the heart of philosophical debates- is everything that happens just an accident, or is everything by universal design?

Right now, I instinctively believe that everything is preordained. Its a belief that sustains me. My mom said to me, if Turbulence was meant to exist, if she was meant to have a rich life that touched so many others, it would have happened regardless of the Turners. I believe that, and it brings me peace. In this baby-creation game,  we can do whatever we can but we have no idea what the universal plan is, all that is in our power is to try and then accept whatever comes, no matter how painful or joyous.

If adoption or donor embryo are waiting at the end of the road for me, then I want to be at peace with that idea. Why am I concerned about either? Because I'm a control freak and its unfamiliar.  When choosing my donor, I looked at over 200 candidates, and I found ONE that made me happy. Because I spend so much time thinking about it, genetics IS important to me. But this fear I can deal with.  A part of me is aware that it does not matter, genetics is a crapshoot anyway and all people are unique and beautiful individuals, that nurture is about as important as nature.  The problem is, its the great unknown that I'm having issues with.. You don't KNOW the birth parents, while I know and I'm comfortable with the bagload of genetics I carry. I respect my family. I respect their intelligence, their values, their kindness, everything about them.  If my kids turned out to be like my mom or my dad, I'd be ecstatic. I'm deeply in admiration of my donor's genetics too. Overall, from both sides, the genetics are admired, but more importantly, they are familiar.  I'm afraid of adoption or DE because I have no clue what I'm dealing with in terms of parental genetics. The sensible thing, of course, is to cross these bridges only when you get to them. But this is one area of my life that I need resolution with, now, to be at peace.