Sunday, February 12, 2012

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 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.


  1. Thanks to all your research, I always make sure my PCOSers have normal vitamin D levels if they're considering TTC.  The whole theory about AMH is fascinating stuff.

    In all your reading, have you found anything about taking CoQ10 while breast feeding?  I'm thinking it's ok, it has a fairly high MW and so likely doesn't pass into breast milk, but I haven't found anything that says for sure.  

  2. Very interesting.  I love how you are doing all of this research on yourself!  I have to admit, some of your posts are over my head, but I followed what you were saying here.  

    What I found to be interesting/odd, is when I went to the MFM for my 12 week scan, the doctor was asking about my supplements.  When I mentioned VitD and Calcium, he asked me why I was taking those?  He said that there is no proven need/value for either during pregnancy.  I was shocked that he said that about VitD, as I've been low and supplementing to stay in normal ranges for years.  I didn't argue with him, but I also didn't change what I was doing.

  3. OMG, I think both my blood pressure and temper both spiked when I read what your MFM said. That a high risk OB is still clueless, especially given all the research on vitamin D and preeclampsia and gestational diabetes, is inexcusable.

    For the sake of the other hapless patients he treats- do you feel upto sending him a copy of the final link I posted? It's a pretty good review (written by his bloody peers) discussing the role of vitamin D in all areas of female reproductive health.I can send you a PDF copy to print out.

  4. Another very informative post...& just to note, I had also been taking VitD regularly prior to getting pregnant the 1st time & was encouraged by my RE to continue.

  5. Thanks for stopping by my blog earlier, Jay.  I find your blog very interesting and informative.  I have been supplementing with Vitamin D on advice of my clinic, and am now at 32 ng/ml, which sounds perfect for my transfer.  I will be continuing to supplement to keep my levels here, which my clinic said should be safe.  I'm really hoping this works, and hoping that you find success soon too!

  6. I don't know if CoQ10 passes into breast milk or not- Its molecular weight is 338.44 Daltons. Immunoglobulin molecules in breastmilk have molecular weights of 150 KILO daltons and over---they are much bigger, so its possible CoQ10 makes its way into breastmilk.This link suggests it does.. don't think there is any firm data on it one way or the other, sorry. Are you TTCing again?I think that it is great that you are making sure all women with PCOS are Vit D replete before pursuing pregnancy.  I think there is evidence that it helps women with weight control, so Vitamin D may be a good idea even when not TTCing. If you are deficient (37  % of women with PCOS are), then you are at an increased risk for so much crap anyway :(

  7. lol, I think I love your RE :) I remember from emails that you said you were taking around 400 IU daily.  Given everything, I think unless you get a lot of sun time or are one of those people who is naturally replete  (looks like a small % of the population), you probably would have still been in deficiency range. But then, most people are and most of the time nothing bad happens, but you remain at higher risk for many things.  Plus, I think the fact you took metformin- which probably has some overlapping functions with Vit D, as far as managing insulin resistance goes, probably helped!

    I read a really interesting paper which said that we use up around 4000 IU D3 on a daily basis- I think this (4000 IU/daily) is the dose that is now considered optimal for a singleton pregnancy.

  8. Thank you, once again, for sharing your sizeable wealth of knowledge with us, Jay. Even though my ovaries are completely offline, I am still intrigued by the relationship between AFC and AMH. And, as you know, I find the research on vitamin D to be super interesting. I now tell everyone I know (and I live north of the 40th parallel) to get their levels checked.
    I looked up the article you linked to and was fascinated to see the link between vitamin D and conception/pregnancy related factors.

  9. Thanks!  I am TTC again this summer-ish.  I'm considering starting at least a low dose CoQ10 once my period starts back, but can't decide if I should or not.

    I also check vitamin D in all my diabetics, too, given the suspected relationship between worsening insulin resistance and heart disease.  I always tell them that it's not proven, but the importance of vitamin D for bone health is a definite, so no matter what, they need to be replaced.  Such a fascinating little hormone, vitamin D is.

  10. I commented a while back on one of your other blog posts but I can't find which one :) I just wanted to share some good news with you regarding my vitamin D and amh levels. 5 months ago low vit D 41 nmol/L with AMH of 0.63 ng/ml. Then after supplementing Vit D daily since then now 1 months ago vitamin 79 nmol/L and amh 2.1 ng/ml - wow! I couldn't quite believe the 2nd test so I have taken a 3rd last week - 3.1 ng/ml. Thank you for your posts on this topic it certainly gave me inspiration.

  11. Wow, that is awesome.  I think you are the 3rd person to find AMH increasing after Vitamin D supplementation, including myself. But  3 cases do not a fact make, and controlled trials are really needed to address this question.  So glad things are working out for you!

  12. Really interesting post. A year ago I had low vit D, and AMH 11.8 pmol/L. I've been on vitamin D supplements since then, and when I had my AMH tested a few weeks ago it came back as 40.6 pmol/L! So very relieved, particularly since I have a whole heap of other signs of PCOS, so would expect my AMH to be high. Thanks for all the information on here - it was one of the reasons I asked for AMH to be tested again.

  13. Hi Sarah,

    Your right over 8 months having a rise no matter how small is still a great result as theoretically it should go down, nice one :)

    I have mixed feelings about AMH especially after even my fertility specialist said she couldnt exactly explain my results and they aren't entirely sure what it means, they think they know but are not 100% sure. Take any amh results in context with other testing.

    Vit D though I have a lot of time for well done on raising the levels. I have found I range in the 70's can't get higher but my Dr thinks this is still a very good place for me to be. I believe I did 2000ui per day for 3 months and now just 1000ui per day for good.

    Good luck.


    P.s. whatever I did a year ago worked, my baby is due in a couple of weeks :)