The anti-Müllerian hormone: history and reality of a hormone essential for reproduction
The anti-Müllerian hormone (AMH) from a “technical” point of view is a member of the transforming growth factor-beta (TGF-β) family, and is produced by the granulosa cells of the small follicles, the so-called secondary and tertiary ones.
When a baby girl is born, she has a variable number of egg cells contained in very simple structures, called primordial follicles, made up of a single layer of ancillary cells, responsible for nourishing the egg, and the egg itself, stationary at an early stage of meiosis.
The primordial follicles are kept in a state of quiescence by a series of inhibitory factors, which prevent them from all starting to grow at the same time. During the fertile life of a woman, however, every day, in a non-cyclical way, some primordial follicles begin to grow, to secondary follicle, to tertiary, to pre- antral and then become small antral follicles. The latter are the follicles that can be stimulated monthly by the pituitary gland with the FSH hormone.
The anti-Müllerian hormone is mainly produced by small secondary and tertiary follicles. It therefore represents the measure of acyclic follicular activity.
From this it follows that the use of the AMH assessment as a measure of the ovarian reserve is not able to assess the presence of primordial follicles. The anti-Müllerian is therefore a measure of the functional ovarian reserve and not of the real reserve, which is why it has oscillatory values, which can also paradoxically increase.
Could the anti-Müllerian hormone be an infallible measure of the ovarian reserve?
In the literature there are quite conflicting data relating to the use of AMH in clinical practice. An individualised dosage of gonadotropins based on AMH does not change the predetermined number of oocytes, nor the cancellations due to poor response, nor the rate of hyper-stimuli. Furthermore, the number of oocytes and the rate of cancellations correlate with AMH, but not the pregnancy prognosis. However, it is true that women with low AMH have a high probability of cancellations, of not obtaining embryos and therefore worse pregnancy rates.
In conclusion, the evaluation of the anti-Müllerian hormone, which also presents technical problems for which sometimes the values found must be reconfirmed, is not a prognostic criterion for pregnancy. It does not indicate which patients to treat and which not, it is not a “death sentence” for the woman, it can change, even increase with androgenic therapies (e.g. DHEA). Finally, it is not strictly associated with the quality of the oocytes. It is only indirectly associated with the cause of failure to recruit the primordial follicles.
The anti-Müllerian hormone is part of a delicate balance that can be modified by various factors and many causes and the statement: “AMH = ovarian reserve” is false. Rather, it is the measure of a functional ovarian reserve, that is, of the follicles that are growing at that time. The utility of the evaluation of the anti-Müllerian hormone does not lie in establishing an absolute prognosis; the possibility of pregnancy must also be assessed on the basis of other factors, especially age.
However, the anti-Müllerian hormone is a useful tool that measures the capacity of the recruitment systems of primordial follicles, and can lead to interventions aimed at promoting the awakening of follicular recruitment, correcting thyroid dysfunctions or helping those who are deficient with androgens.
For clinical use it is above all an element that allows patients to be characterised in anticipation of treatment, helping the doctor to choose the type and doses of drugs to be used for ovulation induction.
Tran ND, Cedars MI, Rosen MP. The role of anti-müllerian hormone (AMH) in assessing ovarian reserve. J Clin Endocrinol metab 2011; 96 (12): 3609-14.
Magnusson A, Nilsson L, Oleröd G, et al. The addition of anti-Müllerian hormone in an algorithm for individualised hormone dosage did not improve the prediction of ovarian response-a randomised, controlled trial. Hum Reprod 2017; 32 (4): 811-9.
Koshy AK, Gudi A, Shah A, et al. Pregnancy prognosis in women with anti-Müllerian hormone below the tenth percentile. Gynecol Endocrinol 2013; 29 (7): 662-5.