The DHEA and AMH paradox

I have seen many women who ask the following question in infertility bulletin boards – I have low AMH levels, what can I do to increase it? Since women with poor ovarian reserve have low AMH level they believe that increasing their AMH level might solve the problem of poor ovarian reserve. But this notion is not correct! Increasing your AMH level cannot increase your ovarian reserve. If it is that easy, the pharmaceutical companies will be producing and selling AMH at an enormous price. You just have to buy it and inject inside your body : ) On the other hand, can increasing ones ovarian reserve lead to an increase in AMH level? Theoretically the answer is YES, but, until now there are no proven ways to increase the ovarian reserve of women.

What is AMH and how is it connected to ovarian reserve testing? The AMH story is not yet clearly dissected out scientifically. But there are some well-known facts about AMH which I will try to summarize below: 

Anti-Müllerian harmone is secreted by the granulosa cells of primary, pre-antral and small antral follicles. Antral follicles are considered to be the primary source of circulating AMH as they contain a large amount of granulosa cells. AMH is preferentially and constantly secreted by the small  (4-6 mm) rather than large follicles (8mm and above). AMH expression disappears in follicle of increasing size and is almost lost in follicles larger than 8 mm (PMID:16388003) Small antral follicles are usually 4-8 mm in diameter and can be seen, measured and counted via vaginal ultrasound. Women with high ovarian reserve will have more AFC in their ovaries. Since these small antral follicles secrete the maximum amount of AMH into the blood stream, AMH testing is used as an indirect measure of our ovarian reserve. AMH can be measured at any time during the menstrual cycle due to insignificant intra-cycle variability which is a great advantage in clinical practice. Whenever you do an AMH test to measure ovarian reserve please insist that you should know your AFC counts too! AMH level is measured in blood and although this test is considered to be pretty accurate there can be chances of laboratory errors, so it is always wise to compare your blood AMH levels with your AFC count! A recent report suggested that, the method used to store the blood samples for AMH measurement can make a difference in the results obtained and they have suggested that caution should be exercised in the interpretation of AMH levels in the clinical setting (PMID:22777530).

High AFC count can contribute to increased AMH level but increasing the AMH level cannot increase our AFC count or ovarian reserve. Actually, increasing our AMH level via artificial means (for example injecting AMH in your body or using substances that can actually increase the AMH expression in your granulosa cells) can lower AFCs. Addition of AMH to neonatal ovaries invitro inhibited primordial follicle recruitment and thusby decreased the AFC count. When primordial follicle recruitment is inhibited there is less depletion of follicles from the ovaries – theoretically this means increasing the AMH level in our body artificially can preserve ovarian reserve. Slower recruitment of primordial folicles = longer reproductive period. Ovarian reserve preserving can become a therapeutic option for women, who wants to post-pone child-bearing and use of AMH for such purposes will be explored in the future.

What will happen if you decrease AMH level (decrease AMH signalling) artificially? Mice lacking AMH gene answers this question. AMH null mice showed increased rate of follicle recruitment from primordial follicle pool. This led to the premature exhaustion of their ovarian reserve. Since AMH null mice have low levels of FSH, and yet increased number of growing follicles, it has been hypothesized that follicles are more sensitive to FSH in absence of AMH. Does it mean women with dysfunctional AMH gene due to certain mutations can deplete their ovarian reserve sooner? I found a single study which talks about AMH and AMHRII polymorphisms in normo-estrogenic and normo-ovulatory women with unexplained infertility ( (PMID:19539910).

Do women with low AMH have poor egg quality too? AMH is not an indicator of egg quality but of egg quantity. But women with poor egg quality can have low AMH (aged women will have poor egg quality and they also have less ovarian reserve!). Egg quantity and quality are two different processes which are mutually exclusive. So younger women, with low AMH level doesn’t necessarily have to have bad egg quality. Women with high AMH level can also have poor egg quality too. As an example, consider women with PCOD, they have high level of circulating AMH (because of high AFCs) but not necessarily good quality eggs.

Now the DHEA and AMH story – DHEA has helped some women with diminished ovarian reserve to produce more eggs during IVF. I have used DHEA for 9 months and my AFC count increased significantly. I naturally expected my AMH levels to go up too. But my AMH level dropped from 3.5-4.7 ng/ml (different time point measurements; spanning over a period of one year) to 1.8 ng/ml (measured twice, the initial measurement is 1.8 ng/ml and the next in a different lab which showed an AMH level of 1.9 ng/ml). Yet I got 24 eggs out of that cycle. The mechanism by which DHEA increases egg yield is not yet known. Can DHEA decrease AMH production in granulosa cells and thus by increases the recruitment of follicles from primordial follicle pool? This can't be true because PCOD women have high DHEA levels and also have very high AMH and high AFC. There are studies which show that DHEA increased AMH levels in women who took it (PMID:20638339). Is anyone out there who took DHEA and had higher egg yields? Did your AMH level change (increase or decrease) after taking DHEA? I would be happy to hear from you. I did a brief search in google and found many women reporting that their AMH leve became worser after taking DHEA !!!

Points to remember

1)   AMH is an indicator of ovarian reserve. When doing test for ovarian reserve it is wise to interpret AMH levels along with our AFC count.

2)  Low AMH levels don’t necessarily mean you have poor egg quality too. If you are young womenwith low AMH and if your ovaries can produce some eggs in response to gonadotrophin stimulation, your chance of conceiving a baby via IVF is still bright.

3)  Artificially increasing your AMH level will not increase your ovarian reserve or egg quality.