Anti-Müllerian hormone (AMH) is emerging as the serum marker that provides the most accurate assessment of ovarian reserve and promising emerging clinical applications, explains Geralyn Lambert-Messerlian, PhD, FACB, in the January issue of CLN. The term “ovarian reserve” refers to the number of primordial follicles—oocytes—in the ovary. Ovarian reserve status can be used as an aid in predicting the onset of menopause, for family planning, or in treating infertility. The serum marker follicle stimulating hormone (FSH) has conventionally been used to assess ovarian reserve, but like age, it has significant limitations.
AMH is part of the TGF-beta family of growth factors, and like other members of this protein family, it is synthesized as a larger inert precursor protein (140 kDa), called pro-mature AMH. Post-translational processing of the molecule includes cleavage at amino acid 451, resulting in an N-terminal pro region and a C-terminal mature region. These peptide fragments stay in a tight non-covalent complex and circulate as a molecule called AMHN,C. The AMHN,C complex enhances receptor binding and bioactivity at target tissues.
AMH was discovered and named on the basis of its role in prenatal gender differentiation. The Y chromosome directs differentiation of the gonad into the testis. Sertoli cells secrete AMH, causing regression of the Müllerian ducts, which would otherwise develop into the female secondary sex organs: the fallopian tube, uterus, and vagina.
The ovaries do not secrete AMH in early prenatal development. However, by mid-gestation, the small developing follicles of the ovary begin to produce and secrete AMH. High levels of AMH mRNA and protein are observed in the granulosa cells of primary, secondary, and preantral follicles. AMH inhibits the recruitment of follicles from the primordial pool, and also inhibits the response of larger follicles to pituitary gonadotropin stimulation.
AMH has the advantage over other serum hormone markers for assessment of ovarian reserve in that it is directly produced by the small follicles of the ovary, which are most proximal to the primordial pool. This contrasts with other serum markers that are either not directly secreted by the ovary or are made by more developed follicles. For example, FSH is an indirect measure of ovarian reserve produced by the pituitary gland, not the ovary. Other candidate markers, such as inhibin B and estradiol, are produced from larger follicles after FSH stimulation, and are more distal to the primordial pool. Studies have shown that serum AMH has the highest correlation with ovarian primordial follicle number, among all serum hormones tested.
AMH has another important advantage over other biomarkers of ovarian reserve in that measuring it is more convenient for patients. AMH secretion is independent of gonadotropin regulation, with relatively stable serum levels throughout the menstrual cycle. As a result, samples can be collected without regard to cycle day. Again, this contrasts with other candidate markers like FSH, inhibin B, and estradiol that have variable patterns of secretion across the menstrual cycle. AMH has also proved to have the highest reproducibility between consecutive menstrual cycles.
Read more about AMH in the January issue of CLN.