Background
Anti-Müllerian Hormone (AMH), also known as Müllerian Inhibiting Substance (MIS), is a 140 kDa homodimeric glycoprotein released by the granulosa cells of developing folliculi. It is a member of the TGF-β superfamily. The AMH gene, which is located on chromosome 19 p13.3, is 275 bp long and contains 5 exons. The molecular structure of AMH consists of a large N-terminal pro-domain and a smaller C-terminal mature signaling domain. The N-terminal pro-domain regulates folding, dimerization, and secretion, whereas the C-terminal mature signaling domain is responsible for signal transduction. AMH signals through its specific type II receptor (AMHR2) as well as BMP type I receptors (such as ALK2, ALK3, and ALK6), activating BMP-like pathways, phosphorylating, and activating downstream Smad proteins. In rats, the expression pattern of AMHRII is similar to AMH, and the three types of AMH/BMP type I receptors are also expressed in the ovaries. However, their contribution to ovarian AMH signaling remains to be studied. The AMH signaling pathway plays a crucial role in regulating Müllerian duct regression and folliculogenesis, with abnormal AMH signaling potentially leading to Persistent Müllerian Duct Syndrome (PMDS) and Polycystic Ovary Syndrome (PCOS).
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Figure 1. Structural and Sequence Features of AMH and AMHR2 (Source: Howard JA, et al., 2022)
Clinically, AMH is widely used to assess ovarian reserve function, and predict, and treat infertility. Serum AMH levels are closely related to ovarian reserve function and can be verified by counting antral follicles measured by ultrasound (AFC). One study showed a significant correlation between serum AMH and the number of primordial follicles in the ovary, with an unadjusted correlation coefficient of r=0.72 and an age-adjusted correlation coefficient of r=0.48. AMH fluctuates little during the normal menstrual cycle and is usually not clinically significant, but more sensitive AMH immunoassays may be required in specific situations (such as after chemotherapy). Polycystic Ovary Syndrome (PCOS) is a highly prevalent heterogeneous disease in women, characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology. The diagnosis has been controversial for decades. AMH is closely related to PCOS, with significantly elevated serum levels in patients, often 2 to 3 times the normal level.
Currently, research applications of AMH are expanding into the field of oncology. Elevated levels of AMH in certain ovarian tumors (such as granulosa cell tumors) can serve as tumor markers for detecting or monitoring tumor recurrence. For example, AMH levels in cancer patients treated with gonadotoxic drugs are 140 pg/m after treatment, so AMH can be used to monitor the recovery of ovarian reserve function. Additionally, in assisted reproductive technology, serum AMH testing is widely used to obtain prognostic information, such as the chances of successful ovarian stimulation, subsequent embryo quality, and even pregnancy rates. AMH is also used as a tool to predict menopause, forecasting its occurrence within 12 to 36 months. Long-term assessments in women have shown that understanding the rate of AMH decline improves the accuracy of menopause prediction. In conclusion, while AMH cannot reliably predict female pregnancy, its value in managing and treating female infertility is significant, and its potential in oncology is worth further research and exploration.
Alternative Names
Anti-AMH antibody, clone 9D8
Anti-Müllerian Hormone antibody, clone 9D8
Anti-AMH (N-terminal) antibody, clone 9D8
References
- 1. Howard JA, et al. Molecular Mechanisms of AMH Signaling. Front Endocrinol . 2022;13:927824.
References
GnRH agonist and hCG (dual trigger) versus hCG trigger for final follicular maturation: a double-blinded, randomized controlled study
HUMAN REPRODUCTION
Authors: Haas, J.; Bassil, R.; Samara, N.; Zilberberg, E.; Mehta, C.; Orvieto, R.; Casper, R. F.
Abstract
STUDY QUESTION: Does co-administration of GnRH agonist and Human chorionic gonadotropin (hCG; dual trigger) in IVF cycles improve the number of mature oocytes and pregnancy outcome compared to hCG alone? SUMMARY ANSWER: Using the dual trigger for final follicular maturation increases the number of oocytes, mature oocytes and number of blastocysts (total and top-quality) compared to triggering with hCG alone. WHAT IS KNOWN ALREADY: hCG is used at the end of controlled ovarian hyperstimulation as a surrogate LH surge to induce final oocyte maturation. Recently, based on retrospective studies, the co-administration of GnRH agonist and hCG for final oocyte maturation (dual trigger) has been suggested to improve IVF outcome and pregnancy rates STUDY DESIGN, SIZE, DURATION: A single center, randomized controlled, double-blinded clinical trial between May 2016 and June 2018 analyzed by intention to treat (ITT). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: One hundred and fifty-five normal responder patients were randomized either to receive hCG or dual trigger for final oocyte maturation. Data on patients age, BMI, AMH, number of oocytes retrieved, number of metaphase 2 (MII) oocytes, zygotes and blastocysts, clinical pregnancy rate and live birth rate were assessed and compared between the dual trigger group and the hCG group. We performed a planned interim analysis after the recruitment of 50% of the patients. Based on the totality of outcomes at the interim analysis we decided to discontinue further recruitment. MAIN RESULTS AND THE ROLE OF CHANCE: One hundred and fifty-five patients were included in the study. The age (36 years versus 35.3 years P = NS), BMI (24 kg/m(2) versus 23.7 kg/m(2)) and the AMH (20.1 pmol/l versus 22.4 pmol/l) were comparable between the two groups. Based on ITT analysis, the number of eggs retrieved (11.1 versus 13.4, P = 0.002), the MII oocytes (8.6 versus 10.3, P = 0.009), total number of blastocysts (2.9 versus 3.9, P = 0.01) and top-quality blastocysts transferred (44.7% versus 64.9%; P = 0.003) were significantly higher in the dual trigger group compared to the hCG group. The clinical pregnancy rate (24.3% versus 46.1%, OR 2.65 (1.43-1.93), P = 0.009) and the live birth rate per transfer (22% versus 36.2%, OR = 1.98 (1.05-3.75), P = 0.03) were significantly higher in the dual trigger group compared to the hCG group. LIMITATIONS, REASONS FOR CAUTION: None. WIDER IMPLICATIONS OF THE FINDINGS: The enhanced response observed with the dual trigger might lead to better IVF outcomes were it used more widely.
Assessment of Anti-Mullerian Hormone and Anti-Mullerian Hormone Type II Receptor Variants in Women with Repeated Implantation Failures
REPRODUCTIVE SCIENCES
Authors: Fu, Yun-xing; Yang, Hui-min; OuYang, Xiao-e; Hu, Rong; Hu, Ting; Wang, Fei-miao
Abstract
Repeated implantation failure (RIF) is a common endocrine disease that causes female infertility and the etiology is unknown. The abnormal expression of key proteins and hormones at the maternal-fetal interface affected the maternal-fetal communication and leads to adverse pregnancy outcomes. The expression of anti-Mullerian hormone (AMH) and AMH receptor II (AMHRII) was observed in the endometrium. This study aimed to investigate the expression of AMH and AMHRII at the human endometrium, decidual tissue, and blastocyst. Furthermore, the expression of AMH and AMHRII were examined in the RIF patients using immunohistochemistry and quantitative real-time PCR to test the AMHRII expression. The results demonstrated that AMH and AMHRII were present in healthy endometrium and AMHRII was highly expressed in mid-luteal phase. In addition, AMHRII expression was detected throughout the pregnancy and AMHRII's highest expression was in the second trimester. AMHRII was expressed in the blastocysts; however, AMH was not observed. The positive expression rate for AMHRII was significantly higher in the endometrium from RIF. Estrogen receptor (ER), insulin-like growth factor binding protein 1(IGFBP1), and prolactin (PRL) were significantly less expressed in RIF with high expression of AMHRII. The apoptosis was significantly higher in patients with high expression of AMHRII than in patients with normal expression of AMHRII. Our data suggests that AMHRII had an effect on RIF via the AMH and AMHRII signaling pathway. It participated in the development of RIF by interfering with endometrial decidualization and apoptosis.
COA
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