Clinical Applications of Serum Anti-Müllerian Hormone

During the fifth week of fetal life, formation of the genital ridges starts in the posterior abdominal wall, in response to colonization by primordial germ cells, migrating from the yolk sac. By the end of the sixth week, the male and female gonads are indifferent. Differentiation of the gonads is triggered by the sex-determining-region on the Y-chromosome. The first step in male gonadal development is differentiation of Sertoli cells, which produce anti-Müllerian hormone (AMH). Subsequently, between the eighth and tenth week, AMH induces regression of the Müllerian ducts. Thereafter, mesenchymal cells differentiate into Leydig cells, which produce testosterone. Further differentiation of the urogenital system into male derivatives is then ensured by testosterone. In absence of the sex-determining-region on the Y-chromosome, producing the testis determining factor, the gonad differentiates into a female genital system. In addition, production of AMH is lacking and Müllerian ducts, also called the paramesonephric ducts, continue to differentiate into fallopian tubes, uterus and upper part of the vagina. From the seventh week of fetal life onwards, germ cells differentiate into oogonia. Through mitotic cell divisions, the number of oogonia increases steadily and during the third month, the first oogonia begin to transform into oocytes. From the fifth month onwards, the oogonia enter meiosis. In addition, the oocytes are encapsuled by a single layer of pregranulosa cells, forming the primordial follicles. Meiosis is arrested during the first prophase of the first meiotic division, when the homologous chromosomes pair and the primordial follicles enter a dormant state

A genome-wide association study identifies risk alleles in plasminogen and P4HA2 associated with giant cell arteritis

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analysed in 2,134 cases and 9,125 unaffected controls from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, P = 1.94E-54, per-allele OR = 1.79; and rs9275592, P = 1.14E-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, P = 1.23E-10, OR = 1.28; and rs128738, P = 4.60E-09, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis

A functional anti-müllerian hormone gene polymorphism is associated with follicle number and androgen levels in polycystic ovary syndrome patients

Context: The common characteristic of polycystic ovary syndrome (PCOS) is a disturbance in the selection of the dominant follicle, resulting in anovulation. In PCOS women, serum anti-Müllerian hormone (AMH) levels are elevated. Because AMH decreases FSH sensitivity in mice, the elevated AMH levels may contribute to the disturbed follicle selection in PCOS women. Objective: The objective of the study was to investigate the role of the AMH signaling pathway in the pathophysiology of PCOS using a genetic approach. Design: The association of the AMH Ile49Ser (rs10407022) and the AMH type II receptor -482 A>G (rs2002555) polymorphism with PCOS susceptibility and phenotype was studied in a large cohort of PCOS women. Setting/Subjects: A total of 331 women with PCOS, 32 normoovulatory controls, and 3635 population-based controls were included. Main Outcome Measures: Ovarian parameters, serum AMH, FSH, androgen, and estradiol levels were measured. Results: Genotype and allele frequencies for the AMH Ile49Ser and AMH type II receptor -482 A>G polymorphism were similar in PCOS women and controls. However, within the group of PCOS women, carriers of the AMH49Ser allele less often had polycystic ovaries (92.7 vs. 99.5%, P = 0.0004), lower follicle numbers (P = 0.03), and lower androgen levels, compared with noncarriers (P = 0.04). In addition, in vitro studies demonstrated that the bioactivity of the AMH49Ser protein is diminished, compared with the AMH49Ile protein (P < 0.0001). Conclusions: Genetic variants in the AMH and AMH type II receptor gene do not influence PCOS susceptibility. However, our results suggest that the AMH Ile49Ser polymorphism contributes to the severity of the PCOS phenotype. Copyrigh

Anti-müllerian hormone as a marker of ovarian function in women after chemotherapy and radiotherapy for haematological malignancies

BACKGROUND: In female cancer survivors, the accelerated loss of primordial follicles as a result of gonadal damage may lead to premature ovarian failure (POF). However, the extent of the damage is unpredictable. Anti-Müllerian hormone (AMH) constitutes a sensitive marker of ovarian reserve. Serum AMH levels were measured to assess sub-clinical ovarian damage in patients treated with gonadotoxic therapy. METHODS: In 25 patients with haematological malignancies, serum AMH concentrations were measured prior to and after cancer therapy and were compared with normo-ovulatory controls. RESULTS: In all patients, AMH concentrations were lower than controls prior to treatment. Thirteen patients were treated with multi-drug chemotherapy. Although in most patients treated with chemotherapy menstrual cyclicity was restored, median serum AMH levels were lower than in controls. Twelve patients had stem cell transplantation (SCT) after total body irradiation. They all developed POF and their serum AMH concentrations were undetectable. CONCLUSIONS: Female cancer survivors treated with SCT all developed POF. Hence, in these patients fertility preservation should be considered. In patients treated with chemotherapy, ovarian reserve seems to be compromised as well

The phenotype of polycystic ovary syndrome ameliorates with aging

Objective: To assess the effects of aging on the features of polycystic ovary syndrome (PCOS). Design: Retrospective longitudinal follow-up study. Setting: Tertiary care center. Patient(s): Patients with PCOS, diagnosed according to the 2003 Rotterdam criteria, who visited the outpatient clinic on consecutive occasions with a minimum interval of 6 months. Intervention(s): Comparisons were made between the first visit and the consecutive visit grouped by intervals. Main Outcome Measure(s): Changes in clinical and endocrine characteristics. Result(s): A total of 254 women visited the outpatient clinic on 2 occasions each. Consecutive visits were grouped into 0.5 to 3.9 years (n = 172; mean follow-up, 2.6 years) and 4.0 to 7.0 years (n = 82; mean follow-up, 5.5 years). At their second visit, significantly more women had regained a regular cycle. The total antral follicle count was similar. Serum levels of testosterone, androstenedione, and dehydroepiandrosterone sulfate had decreased significantly. Plasma glucose levels had increased, whereas serum insulin levels and homeostasis model assessment score had significantly decreased. Conclusion(s): The PCOS phenotype changed with aging, suggesting an amelioration of the phenotype and ovarian dysfunction as indicated by the increase in number of regular menstrual cycles, decrease in serum androgen levels, and decrease in insulin resistance. (Fertil Steril (R) 2011; 96: 1259-65. (C) 2011 by American Society for Reproductive Medicine.