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.