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.

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.

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.

Sorry for being MIA..

I rarely blog nowadays and the reason for that is twofold- first, there is nothing concrete to say and secondly, life is, in a word, frantic, with work during the week and a fairly hectic social life on the weekend.  The second part is surreal.  A year ago, I gave up my carefree existence to start TTC. I gave up drinking completely, I became a homebody, I completely lost interest in the opposite sex.  After my 2 losses and the move and having to shelve my TTC plans temporarily, I'm suddenly thrust into this 'Sex and the City' lifestyle which is all about having a good time and meeting new people.   Its just a completely different set of priorities. This change actually feels good. It feels weird thinking about giving all up to go to last years way of life,  but there would be no regrets. All of this is fun, but if I had to abandon this to stay home in sweats and watch TV while being pregnant, I would do it without a second thought, and with complete happiness. 

Things are changing so rapidly, I feel like Alice in Wonderland, not knowing what will happen next. I think its highly unlikely that I will meet somebody and abandon plan B, but at the same time, I have no idea how the future is going to unfold. I have just a feeling that this year has some tricks up its sleeve- I just hope they are ones that lift me up, not knock me down. But even if they are ones that knock me down, I have to say, what does not kill you only makes you stronger. Despite all my misgivings of whether I will be able to handle another catastrophe in the baby-making department, I know this- I have a far greater reserve of equanimity than when I first started out. I've started realize, and more importantly, accept that I have no power, so when life does not go my way, I  have a better chance at not fighting it and just accept and adjust to whatever comes along. There is nothing else to do.

Science stuff

My antral follicle counts- done twice last year, have been very high, in the 30s. At my appointment with Dr L, I was shocked to see that one ovary had 11 follicles (small decrease), while the other had only 4-5 (huge drop down), giving a total of about 15. My antral follicle count has decreased by half. I was flabbergasted. I don't know what it means.  As you all know, I tend to attribute everything to the change in my vitamin D levels (because that has been the only big change in my physiology). Metformin has been shown to decrease antral counts in women with PCOS,  but that data, as my SD RE put it, is not too good. It would be interesting if vitamin D could do this as well, because both things actually influence sugar metabolism, which is has mysterious, ill understood links to fertility and egg production.

I don't know if my decreased AFC is good for overall egg quality, we shall see. As my next TTC cycle will be completely unmedicated as well, the only thing I have to go on is quality of my natural cycle. This takes into account BBTs, length of luteal phase, number of days with egg white cervical mucus, number of days of high fertility, etc.  Following your fertility signs can tell you a lot about your own cycle- this doctor describes it well here. The problem is though, you are shooting in the dark. The last cycle I conceived in, was, in my own opinion, an absolutely crummy one. I was very concerned about egg quality. Nonetheless, the RE, looking at my uterus and ovaries the day of ovulation, thought things looked good and we proceeded. And it was all good enough to produce an embryo that implanted beautifully and thrived in the first 6 weeks even thought it had a gross chromosomal abnormality. What I would love to know is whether my egg was missing an X chromosome because it was produced in a cycle with less than one day of high fertility before the LH surge began, but I will never know, will I? And even though I understand my cycle far better than the average person, I haven't a hope of figuring out what works and what does not.