Background
Anti-Müllerian hormone (AMH), also known as Müllerian duct inhibitory hormone (MIH), is a member of the TGF-β superfamily, which acts through a specific type II receptor known as AMHR2, as well as through the type I receptor ALK2/ACVR1, ALK3/BMPR1A, ALK2/ACVR1, ALK3/BMPR1A, ALK6/BMPR1B, and SMAD1, SMAD5, or SMAD8 proteins (AMH has the same receptor as bone morphogenetic proteins (BMPs)) to transmit its effects. The Müllerian ducts are the analagen of the uterus, fallopian tubes, and upper part of the vagina in females, and AMH is secreted by the male fetal testes to inhibit the development of the Müllerian ducts. AMH is also expressed in the ovaries of females and regulates folliculogenesis. In clinical practice, serum AMH is a marker of follicular growth pools that correlates with the size of the primordial follicular pool and reliably reflects ovarian reserve function, which is significantly elevated in women with polycystic ovary syndrome (PCOS). Serum AMH is also a marker of a woman's response to gonadotropin-controlled ovarian stimulation.
The short arm of human chromosome 19 carries the AMH gene, which is 2.8 kb long and consists of five exons, the fifth of which encodes the C-terminal maturation domain of AMH. In addition, the gene includes a degenerate TATA box and several transcriptional start sites, with the major transcriptional start site located 10 bp upstream of the ATG codon in human fetal testes and granulosa cells (GCs), accounting for 88% of the AMH transcripts. The transcribed mRNA is approximately 2.1 kb in length and is subsequently translated into a 70 kDa monomer consisting of 560 amino acids, with the lowest homology between the N-terminal domain and members of the TGF-β family, while the C-terminal domain has approximately 30% homology. The AMH monomer contains two potential N-linked glycosylation sites and several cysteines conserved in the TGF-β family, and the 140 kDa AMH precursor is assembled from two disulfide-linked 70 kDa monomers. The 140 kDa AMH precursor is assembled from two disulfide-linked 70 kDa monomers.
Figure 1. The human AMH gene, mRNA, and protein processing
(Source: di Clemente N, et al. 2021)
In the ovary, AMH is produced by the GC, but its level of expression depends on the stage of the follicle. AMH synthesis begins in the primary follicle, is highest in the anterior follicle and the lesser anterior follicle, and then decreases in the larger follicles, except for the cumulus cells. AMH is undetectable in the corpus luteum and atretic follicles. Thus, AMH expression begins when the follicle begins to generate and continues through menopause. Serum AMH levels reflect the growth of the follicular pool, indicating that circulating AMH is predominantly of ovarian origin. Therefore, serum AMH levels decrease with age. During pregnancy, from the second trimester to the end of pregnancy, AMH levels gradually decline until they reach levels found in non-pregnant women with low ovarian reserve.
Alternative Names
Anti-Human Anti-Müllerian hormone monoclonal antibody
References
- 1. di Clemente N, et al. Anti-Müllerian Hormone in Female Reproduction. Endocr Rev. 2021 Nov 16;42(6):753-782.
- 2. Yuwen T, et al. Association between serum AMH levels and IVF/ICSI outcomes in patients with polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2023 Oct 23;21(1):95.
References
Can AMH levels predict the need to step up FSH dose for controlled ovarian stimulation following a long GnRH agonist protocol in PCOS women?
Reprod Biol Endocrinol
Authors: Huang H, Gao H, Shi Y, Deng B, He X, Lin J, Li P.
Abstract
Background: To explore the role of anti-Mullerian hormone (AMH) in predicting the need to step up recombinant FSH (rFSH) dose following long GnRH agonist protocol in IVF/ICSI cycles of polycystic ovarian syndrome (PCOS) women.
Methods: This is a retrospective cohort study of 825 PCOS women undergoing long GnRH agonist protocol enrolled from Jan 2019 to Dec 2021. The daily rFSH dose at which the first response to rFSH were recorded. The dose at which the first response to rFSH was based on folliculometry during follow up in which two or more follicles reached ≥ 11 mm. A receiver operating characteristic (ROC) curve analysis was done to investigate the ability of AMH to predict the need to step up initial rFSH dose.
Results: PCOS women who needed to step up initial rFSH dose had a significantly higher AMH compared with those didn't step up initial rFSH dose (11.37 ± 3.25ng/ml vs. 8.69 ± 3.16ng/ml, p < 0.001). In multivariate logistic regression analysis, increased AMH level was an independent factor for the need to step up initial rFSH dose in PCOS patients after adjusted for confounding factors. ROC curve analysis showed AMH could predict the need to step up initial rFSH dose (AUC = 0.738, 95%CI: 0.704-0.773), having 75.4% specificity and 63% sensitivity when the threshold AMH concentration was 9.30ng/ml. 58.8% PCOS women with AMH > 9.30 ng/ml required increased rFSH dose compared to 18.8% of women with AMH ≤ 9.30ng/ml (p < 0.001). Although the clinical pregnancy rate and live birth rate were not significantly different, there was a higher incidence of OHSS among women with AMH > 9.30 ng/ml vs. AMH ≤ 9.30ng/ml (20.8% vs. 15.3%, p = 0.043).
Conclusion: PCOS women with AMH > 9.30 ng/ml were resistant to rFSH stimulation and require increased dose for the cycle recruitment of ovarian follicles.
Seasonal AMH variability implies a positive effect of UV exposure on the deterioration of ovarian follicles
Steroids
Authors: Parikh R, Parikh S, Hemi R, Elkoshi N, Gepner Y, Levy C, Percik R.
Abstract
Anti-Müllerian hormone (AMH) is produced exclusively by granulosa cells of ovarian follicles and is an indicator of ovarian reserve which declines with age. Seasonality in AMH levels have been reported to be correlated with variations in Vitamin D levels, which is dependent on sunlight exposure. However, the effects of age and its association with solar radiation intensity with respect to AMH was never studied before. In this study, we investigated the relationship between AMH levels with season and with solar radiation intensity in a cohort of 2235 women aged 19-40 years undergoing hormonal work-up over a four-year period. Our findings revealed that among women aged 20-29 years, there was no significant association between AMH levels and either season or solar radiation intensity. However, for women aged 30-40 years, a seasonal pattern was observed, with higher AMH levels during spring and autumn months characterized by moderate solar radiation intensity. Women in their declining ovarian reserve age were found to be more sensitive to the effects of moderate solar radiation. Moderate solar radiation exposure positively impacted AMH levels, whereas low and high intensity exposure had a negative effect. Our findings indicate that age and solar radiation intensity must be considered when assessing AMH levels and provide valuable insights into the intricate relationship between AMH, seasonality, and UVB exposure in the context of reproductive health.
COA
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