Associations of different molecular forms of antimüllerian hormone and biomarkers of polycystic ovary syndrome and normal women

Abstract

Objective: To study different antim€ ullerian hormone (AMH) isoforms in women with polycystic ovary syndrome (PCOS) and healthy regularly cycling women and to investigate whether levels of AMH isoforms combined with baseline characteristics can predict PCOS. Design: Cross-sectional study. Setting: Fertility clinic. Patient(s): Eighty-eight women with PCOS and 24 age-and body mass index (BMI)-matched normal control subject women recruited from April 2010 to February 2013. AMH isoforms were analyzed in biobanked serum samples collected at Holbaek Fertility Clinic, Denmark. All study participants went through a baseline examination including gynecologic history, objective examination, transvaginal ultrasound, and blood sampling. Each woman was characterized by measurement of total T, free T, SHBG, A, DHEAS, FSH, LH, E 2 , PRL, TSH, serum insulin, plasma glucose, and C-peptide. Interventions(s): None. Main Outcome Measure(s): Serum levels of three different AMH isoforms. Result(s): Levels of AMH measured with each of three AMH ELISAs were significantly higher in women with PCOS compared with control women. The ratio between AMH isoforms showed significant associations with metabolic parameters (BMI, SHBG, C-peptide, cholesterols, triglycerides, and the modified homeostasis-model assessment). Prediction of PCOS showed a high precision with areas under the receiver operating characteristic curve of 97% when AMH measurements were combined with androgens and BMI. Conclusion(s): Three ELISAs detecting different parts of the AMH molecule all detected significantly higher levels in women with PCOS compared with control women. The relative distribution of AMH isoforms did not differ between women with PCOS and control women. AMH isoforms alone and in combination with baseline characteristics predicted PCOS with close to 100% area under the receiver operating characteristic curve. (Fertil Steril Ò 2019;112:149-55. Ó2019 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

Anti-Müllerian Hormone and Ovarian Reserve: Update on Assessing Ovarian Function

“…This might indicate that AMH C is only generated after receptor binding of the AMH N,C isoform, as shown in vitro ( 40 ). In a recent study by Wissing et al ( 41 ), it was shown that the amount of uncleaved AMH (proAMH) in normoovulatory women is only 3% of the total promature isoforms (proAMH and AMH N,C ). This result was obtained using Ansh Labs ELISAs that either use a different antibody pair or sample treatment to distinguish the different isoforms ( 41 ).…”

“…In a recent study by Wissing et al ( 41 ), it was shown that the amount of uncleaved AMH (proAMH) in normoovulatory women is only 3% of the total promature isoforms (proAMH and AMH N,C ). This result was obtained using Ansh Labs ELISAs that either use a different antibody pair or sample treatment to distinguish the different isoforms ( 41 ). This suggests that the majority of serum AMH levels represents cleaved AMH.…”

High Variability of Molecular Isoforms of AMH in Follicular Fluid and Granulosa Cells From Human Small Antral Follicles

“…Other assays found normal concentrations of AMH corresponding to the number of follicles present (36,37), probably reflecting that the antibodies employed captured different epitopes. It is important to note that the concentration of AMH in FFs is a thousand times higher than it is in serum (38). Furthermore, some of the AMH isoforms present in FFs and GCs may be degraded in serum, explaining why we do not expect the isoform profiles detected in the follicular compartment to be reflected in serum.…”

Challenges in Measuring AMH in the Clinical Setting

“…It is now well recognised that serum AMH is elevated in women with PCOS ( 5 , 31 , 32 ). In a recent study, AMH exhibited high specificity:sensitivity based on the receiver-operating characteristic (ROC) curve in predicting PCOS compared with age-matched controls ( 32 ).…”

“…An international collaborative study ( 7 , 8 ) was thus undertaken by the World Health Organization (WHO) to produce a reference material purified from media from a stable human ovarian cancer cell line and available in ampoules (coded 16/190), and to derive an immunopotency evaluation for this human AMH preparation. The AMH preparation consisted of the full length 140kDa form with a modification of the internal cleavage site to ensure maximum cleavage between the pro-hormone and mature forms of the molecule ( 58 ) which represent the major forms of AMH in human serum ( 14 , 15 , 32 ). The WHO study involved the distribution the WHO reference preparation to participant laboratories, along with 21 human serum samples of varying origin.…”