AMH levels and diagnosis in PCOS phenotype D.

Purpose: Women with PCOS have higher levels of AMH than matched controls; however, the feasibility of using elevated serum AMH value as a criterion, in the diagnosis of PCOS, is still debatable. The goal of this study was to examine a population of women with elevated AMH (>5.0 ng/mL) and evaluate whether high serum AMH value can be predictive of four different clinical PCOS phenotypes (phenotype A (AOM, amenorrhea/oligomenorrhea + HA, hyperandrogenism + PCO, polycystic ovaries); Phenotype B: AOM + HA; Phenotype C: HA + PCO; and phenotype D: AOM + PCO, as defined by the Rotterdam criteria. Methods: This retrospective study included 227 women with one or more diagnoses of PCOS (ICD-9 256.4, ICD-10 E28.2) and 103 women without PCOS. All serum AMH levels were measured using Beckman Access-2 automated chemiluminescence assay and the age, BMI and AMH levels were analyzed using univariate analysis of covariance. Received operator curves were used to determine the AMH thresholds for predicting PCOS features and phenotypes. Results: Mean serum AMH levels were 9.96, 6.84, 6.43, 6.03, and 1.98 ng/ml in women with PCOS phenotype A, B, C, D, and control respectively. 101 (44.5%) patients were oligo/amenorrheic PCOS, 98 (43.2%) were hyperandrogenic PCOS, and 103 (45.4%) were PCO. Women with all three PCOS features had a significantly higher mean serum AMH compared to those with less of these features. The area under the curve (AUC) estimates of AMH showed high value ranging from 0.76 (95% CI, 0.71-0.81) in AOM group to 0.82 (95% CI, 0.79-0.88) in the PCO group. Conclusion: This study confirms the diagnostic opportunity of AMH test for discriminating between patients with PCOS phenotype and controls. High AMH accurately predicted PCOS in 92% (209 out of 227) patients diagnosed with PCOS. AMH value can predict PCOS in 78% women with oligo/amenorrheic PCOS, 77% with hyperandrogenic PCOS, and 79% with PCO. In keeping with the view that women with PCOS have a variety of phenotypic presentation that can be challenging to diagnose, using AMH test in combination with oligo/ amenorrhea or hyperandrogenism offers a non-invasive objective tool to screen patients with clinical features of PCOS.

Antimüllerian hormone as a predictor of controlled ovarian hyperstimulation outcome: comparison of two commercial immunoassay kits

Background: Polycystic ovarian syndrome (PCOS) is a frequently encountered endocrine disorders in women of the reproductive age. Various studies conclude there is no uniform correlation between the phenotypes of the PCOS and serum anti-Mullerian Hormone (AMH) levels. Aim and Objective: The objective of the study to estimate the association between different phenotypes of PCOS and the serum AMH level. Materials and Methods: This was a cross-sectional analytical study which included sixty subjects with PCOS according to Rotterdam's criteria. After procuring the detailed history, clinically examination and ultrasound scan subjects were classified into one of the phenotypes of PCOS. Auto-analyzer was used to measure serum AMH levels and was correlated with the various phenotypes of PCOS. Results: The study group categorized 28 patients under phenotype D, which was a predominant form. Serum AMH mean was 6.1 (±3.2) ng/ml. The mean serum AMH levels for phenotype A was 7.5 ± 3.0 ng/ml which was higher than the other phenotypes. Phenotype A had high mean body mass index which was significant (29.1 ±6.6) kg/m2 (P = 0.046). Phenotype B had significantly higher Hirsutism score 19.8 (±1.7). Phenotype A had significantly higher mean follicular count (19.7 ± 5.1). The difference of mean or median among the phenotypes was compared using Kruskal–Wallis test or ANOVA. P < 0.05 was considered as statistically significant. Conclusion: A positive correlation was seen between the serum AMH levels and the phenotypes of the PCOS. Thus, AMH levels can be used as an adjunct tool in the diagnosis and monitoring of PCOS.

Aims: To examine the link between serum anti-mullerian hormone (AMH) levels and homeostatic model assessment of insulin resistance (HOMA-IR) in different phenotypes of polycystic ovary syndrome (PCOS). Methods: This retrospective study included 120 patients aged 18-30 who visited our polyclinics between June 2021 and December 2022. Patients were divided into four groups based on the Rotterdam criteria for PCOS phenotypes. A control group of 24 individuals was also included. Clinical data, hormonal profiles, and metabolic parameters were obtained from medical records. Results: There were significant differences in AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH), and high-density lipoprotein (HDL) levels among the PCOS phenotypes and control group. AMH levels were highest in phenotype 1 (oligo/anovulation + hyperandrogenism + polycystic ovaries) and lowest in the control group. FSH were highest in phenotype 4 (oligo/anovulation + polycystic ovaries) and lowest in the control group. LH were highest in phenotype 2 (oligo/anovulation + hyperandrogenism). HOMA-IR was highest in phenotype 1. However, there were no significant differences in AMH or HOMA-IR levels among the PCOS phenotypes. Conclusion: Our study found hormone level differences among PCOS phenotypes but no significant differences in AMH or HOMA-IR. This suggests AMH may not distinguish between phenotypes and insulin resistance may not differ significantly among phenotypes.

Comparison of body mass index, anti-müllerian hormone and insulin resistance parameters among different phenotypes of polycystic ovary syndrome

Anti-Mullerian hormone (AMH) is one of the direct indicators of follicular pool but no standard cutoff has been defined for diagnosis of polycystic ovary syndrome (PCOS). The present study evaluated the serum AMH levels among different PCOS phenotypes and correlated the AMH levels with clinical, hormonal, and metabolic parameters among Indian PCOS women. Mean serum AMH was 12.39 ± 5.3ng/mL in PCOS cohort and 3.83 ± 1.5 ng/mL in non-PCOS cohort (P < 0.01). Out of 608 PCOS women, 273 (44.9%) women belonged to phenotype A, 230 (37.8%) women were phenotype D. Phenotypes C and B were 12.17% and 5.10% respectively. Among those with the highest AMH group (AMH>20ng/ml; 8.05%), majority belonged to phenotype A. Menstrual cycle length, serum testosterone, fasting total cholesterol levels, and follicle number per ovary had positive correlation with serum anti-Mullerian levels (P < 0.05). AMH cutoff for the diagnosis of PCOS was calculated as ≥ 6.06 ng/mL on ROC analysis with sensitivity and specificity of 91.45% and 90.71% respectively. The study shows high serum AMH levels in PCOS are associated with worse clinical, endocrinological, and metabolic parameters. These levels may be used to counsel patients regarding treatment response, help in individualized management and prediction of reproductive and long-term metabolic outcomes.

The role of anti-müllerian hormone in the classification of anovulation

Anti-Müllerian hormone (AMH) is produced by granulosa cells of pre-antral and small antral ovarian follicles. In polycystic ovary syndrome (PCOS), higher levels of serum AMH are usually encountered due to the ample presence of small antral follicles and a high AMH production per follicular unit which have led to the proposal of AMH as a serum diagnostic marker for PCOS or as a surrogate for polycystic ovarian morphology (PCOM). However, heterozygous coding mutations of the AMH gene with decreased in vitro bioactivity have been described in some women with PCOS. Such mutation carriers have a trend toward reduced serum AMH levels compared to noncarriers, although both types of women with PCOS have similar circulating gonadotropin and testosterone (T) levels. This report describes a normal-weight woman with PCOS by NIH criteria with severely reduced AMH levels (index woman with PCOS). Our objective was to examine the molecular basis for her reduced serum AMH levels and to compare her endocrine characteristics to similar-weight women with PCOS and detectable AMH levels. Twenty normoandrogenic ovulatory (control) and 13 age- and BMI-matched women with PCOS (19-35 years; 19-25 kg/m2) underwent transvaginal sonography and serum hormone measures including gonadotropins, sex hormone-binding globulin, total and free T, androstenedione, dehydroepiandrosterone sulfate, estrone, estradiol and AMH. The latter was measured by ELISA (Pico-AMH: Ansh Labs, Webster, TX, USA). Women with PCOS and detectable AMH had higher serum AMH (10.82 (6.74-13.40) ng/ml, median (interquartile range)), total and free T (total T: 55.5 (49.5-62.5) ng/dl; free T: 5.65 (4.75-6.6) pg/ml) levels and greater total antral follicle count (AFC) (46 (39-59) follicles) than controls (AMH: 4.03 (2.47-6.11) ng/ml; total T: 30 (24.5-34.5) ng/dl; free T: 2.2 (1.8-2.45) pg/ml; AFC 16 (14.5-21.5) follicles, P < 0.05, all values), along with a trend toward LH hypersecretion (P = 0.06). The index woman with PCOS had severely reduced serum AMH levels (∼0.1 ng/ml), although she also had a typical NIH-defined PCOS phenotype resembling that of the other women with PCOS and elevated AMH levels. All women with PCOS, including the index woman with PCOS, exhibited LH hypersecretion, hyperandrogenism, reduced serum estrogen/androgen ratios and PCOM. A homozygous Ala515Val variant (rs10417628) in the mature region of AMH was identified in the index woman with PCOS. Recombinant hAMH-515Val displayed normal processing and bioactivity, yet had severely reduced immunoactivity when measured by the commercial pico-AMH ELISA assay by Ansh Labs. In conclusion, homozygous AMH variant rs10417628 may severely impair serum AMH immunoactivity without affecting its bioactivity or PCOS phenotypic expression. Variants in AMH can interfere with serum AMH immunoactivity without affecting the phenotype in PCOS. This observation can be accompanied by discordance between AMH immunoactivity and bioactivity.

Characterization of women with elevated antimüllerian hormone levels (AMH): correlation of AMH with polycystic ovarian syndrome phenotypes and assisted reproductive technology outcomes

Reply of the Authors

Objective:To evaluate serum anti-Mullerian hormone (AMH) levels in adolescent and young adult (AYA) Turkish patients with Polycystic ovary syndrome (PCOS), and to determine whether it had a diagnostic value.Materials and Methods:A total of 90 AYA patients were recruited for this study. The study group consisted of 43 patients diagnosed as having PCOS, and the control group comprised 47 age-matched patients. The diagnosis of PCOS was made in accordance with the recent Amsterdam European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine PCOS consensus workshop group’s proposal that all three of the Rotterdam criteria for diagnosing PCOS in adolescents be present. In all patients, serum AMH levels were measured using enzyme-linked immunosorbent assay. Receiver operator characteristics (ROC) curve analysis was performed to reveal diagnostic potential of AMH.Results:Serum AMH levels were higher in the PCOS group compared with controls, but the difference was not statistically significant (10.1±6.9 ng/mL vs. 9.4±5.5 ng/mL, p=0.198). There was a significant age-related decrease in AMH levels in both the study and control groups (r=-0.331, p=0.001). There was also a significant inverse correlation between serum AMH and follicle-stimulating hormone levels in all patients (r=-0.227, p=0.031). ROC analyses demonstrated that the area under the curve indicative of AMH value for discriminating PCOS was 0.579 with a 95% confidence interval of 0.453-0.705 (p=0.198). The cut-off value according to the highest Youden index was calculated to be 14.0 ng/mL with a sensitivity of 48.8% and specificity of 77.1%.Conclusion:Serum AMH levels are slightly higher in AYA patients with PCOS than in controls. However, AMH is not a good marker for the diagnosis of PCOS in AYA patients.

To observe the effect of electroacupuncture (EA) at different acupoints on follicle development, expression of gonadotropins and their receptors and anti-Müllerian hormone(AMH), inhibin B(INHB) in polycystic ovarian syndrome (PCOS) rats, so as to explore its mechanisms underlying improvement of PCOS. Sixty female SD rats were randomized into six groups: control, model, Zusanli(ST36), Sanyinjiao(SP6), Guanyuan(CV4) and combination (ST36+SP6+CV4, n=10 rats/group). The PCOS model was established by gavage of Letrozole solution (1.0 mg/kg) once daily for 21 consecutive days. Rats of the control group were given 1% Carboxymethyl Cellulose (CMC, 1 mg/kg). EA (2 Hz) was applied to ST36, SP6, or/and CV4 for 20 min, once daily for 14 consecutive days. The number of follicles was counted, and the ovarian structure and follicular development were observed under light microscope after H.E. stain, and the contents of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), AMH, and INHB were assayed by enzyme-linked immunosorbent assay, and the ratio of LH/FSH was calcula-ted. The immunoactivity of LH receptor (LHR) and FSH receptor (FSHR) proteins was detected by immunohistochemistry. After modeling, the number of follicles at the growth stage, contents of serum LH, AMH and INHB, and ratio of LH/FSH were significantly increased, and serum FSH level and FSHR, LHR immunoactivity were remarkably decreased in the model group relevant to the control group (P<0.05, P<0.01). Following EA intervention, the number of follicles at the growth stage in the SP6, CV4 and combination groups, LH/FSH ratio and serum AMH levels in the 4 EA groups, INHB contents in the ST36, CV4 and combination groups were significantly reduced (P<0.05, P<0.01), while serum FSH contents in the 4 EA groups, FSHR immunoactivity at the early stage in the ST36 group and LHR immunoactivity at both early and late stages in the ST36 and CV4 groups were considerably increased in comparison with those of the model group (P<0.01, P<0.05). The therapeutic effect of SP6 was significantly superior to that of CV4 in down-regulating serum LH level (P<0.01), but significantly inferior to that of CV4 in up-regulating serum FSH content and in down-regulating LH/FSH ratio and serum AMH and INHB levels (P<0.05, P<0.01). The effect of CV4 was comparable to that of ST36 in up-regulating serum FSH, and in down-regulating serum LH/FSH ratio, AMH and INHB levels (P>0.05). EA of CV4, SP6, ST36 and ST36+CV4+SP6 can reduce the number of follicles at the growth stage and regulate the expression levels of gonadotropins in PCOS rats. The effects of EA of CV4 and ST36 are evidently better than those of EA of SP6 in up-regulating serum FSH content and in down-regulating LH/FSH ratio, and serum AMH and INHB levels, and EA of SP6 is evidently superior to EA of CV4 down-regulating LH level, but without synergistic effect among the 3 acupoints.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that significantly impacts reproductive health, quality of life, and increases cardiometabolic and oncological risks for women and their offspring. It also still poses a challenge for timely diagnosis and effective treatment.The objective: to determine the differences in anti-Müllerian hormone (AMH) level in women without obesity of early and active reproductive age with the most common form of PCOS (phenotype A), compared to normal ovulatory women matched for age, body mass index (BMI), and social and economic status.Materials and methods. It is a retrospective case-control study. Data from women aged 20–35 years with PCOS phenotype A (oligo-anovulation, hyperandrogenism, polycystic ovarian morphology according to the Rotterdam criteria, 2003) with a normal BMI (18.5–24.9 kg/m2), after excluding other causes, were analyzed (n = 40). The control group (CG) consisted of normo-ovulatory, normal androgenic women with normal ovarian morphology, matched for main parameters (n = 25). AMH level was determined using an automated, biotin-independent chemiluminescent immunoassay (Beckman Coulter DXI 800 analyzer) on the 3rd–5th day of the menstrual cycle in DILA laboratory. Statistical analysis included descriptive statistics, the Mann–Whitney U test, and Spearman’s (rs) and Pearson’s (rp) correlation coefficients. The study was approved by the Bioethics Committee.Results. The mean AMH level in the PCOS group was 10.53 ± 5.34 ng/mL, which was statistically significantly higher (U = 845.00; p ≈ 3.39 × 10−6) compared to the CG, in which the mean AMH level was 5.79 ± 2.47 ng/mL, this is consistent with literature data. No statistically significant correlation between AMH and age was found in the PCOS group (rs = −0.141; p = 0.386), whereas a moderate negative correlation was established in the CG (rs = −0.407; p = 0.043). In women with PCOS and normal BMI, a weak negative correlation between AMH and BMI was determined (rs = −0.272; p = 0.090); while in the CG group, the association was weak positive and non-significant (rs = 0.218; p = 0.295). Asymmetry in the distribution of AMH levels was found, especially in the PCOS group.Conclusions. The study confirmed significantly higher AMH levels in women with PCOS (phenotype A, normal BMI) compared to the CG and the absence of a typical negative correlation between AMH and age in these patients. A significant asymmetry in the distribution of AMH levels was found in the PCOS group. The obtained results underscore the potential value of AMH in the diagnosis and management of women with PCOS and indicate the need for further research to establish threshold AMH values for different PCOS phenotypes, considering BMI, age, and clinical severity of the syndrome. Expanding the accessibility of PCOS diagnosis is crucial, given its impact on the reproductive and overall health of women and their offspring, especially in today’s Ukrainian context.

Introduction: Polycystic Ovary Syndrome (PCOS) is the most prevalent metabolic disease affecting reproductive-age women and is often present with insulin resistance. Angiopoietin-like-protein-2 (ANGPTL2) is an angiogenic factor influencing insulin resistance in PCOS, manifesting in the anti-mullerian hormone (AMH). There are no previous studies regarding the relationship between ANGPTL2 levels and AMH in PCOS. The study aims to analyse the relationship between ANGPTL2 and AMH levels in PCOS and to compare ANGPTL2 and AMH levels between PCOS phenotypes. Methods: This cross-sectional study on 43 women aged 18-40 diagnosed with PCOS according to the Rotterdam criteria. Subjects were recruited consecutively and categorized into four PCOS phenotypes. Serum levels of ANGPTL2 and AMH were measured and analysed by correlation and comparison test using SPSS 26. Results: A total of 43 PCOS samples were included in the study within 4 months. Based on the severity, phenotype A (anovulation, hyperandrogenic and polycystic ovaries) showed the highest levels of ANGPTL2 and AMH. There was no significant difference in ANGPTL2 levels between the PCOS phenotypes. There was a significant difference in AMH levels between phenotypes, where the highest value was between phenotypes A and B. There was a positive correlation between ANGPTL2 and AMH levels. Conclusion: There is a positive relationship between ANGPTL2 and AMH serum levels. The ANGPTL2 serum levels were not significantly different. In contrast, the AMH serum levels significantly differed across the four PCOS phenotypes, with the highest level found in phenotype A.

Study question What is the optimal serum anti-Mullerian hormone (AMH) cut-off for diagnosing PCOS, and what factors influence AMH value variations in women with PCOS? Summary answer AMH cut-off for PCOS diagnosis was 5.055 ng/mL (sensitivity=85.4%,specificity=75.8%). In PCOS women, AMH levels declined more slowly with age and correlated with serum testosterone concentrations. What is known already Elevated serum AMH levels are a hallmark of PCOS, yet a widely accepted diagnostic cut-off remains controversial. PCOS is characterized by diverse endocrine and metabolic disorders, which can influence AMH concentrations. Study design, size, duration This case-control study included comprehensive sampling from medical records of women who visited our fertility clinics over the past five years (2019–2024) and underwent AMH testing (n = 8233). Participants were allocated into PCOS (n = 1200) and non-PCOS groups (n = 7233). PCOS was diagnosed following the Rotterdam criteria. Age and BMI were recorded for all patients. For women with PCOS, additional data on clinical characteristics, serum hormonal profiles, metabolic parameters, and polycystic ovarian morphology on ultrasound were routinely collected. Participants/materials, setting, methods Propensity score matching (PSM) in a 1:1 ratio was performed using age and BMI as covariates. Receiver operating characteristic (ROC) curve analysis and the Youden Index were used to determine the optimal cut-off point of AMH for the diagnosis of PCOS. Age-specific AMH values were compared between the two groups by analyzing difference in slope changes. Multiple linear regression analysis was conducted to identify factors associated with AMH distribution among PCOS women. Main results and the role of chance After PSM, 1162 PCOS patients and 1162 controls were included in the final analysis. Serum AMH levels demonstrated diagnostic relevance for PCOS (AUC=0.88, p &amp;lt; 0.05), with 5.055 ng/dL identified as the optimal cut-off (sensitivity=85.4%, specificity=75.8%). AMH levels decreased progressively with age in the study cohort, with a slope coefficient of -0.053 (95%CI: -0.103 to -0.003, p &amp;lt; 0.001). There were differences in age-specific AMH distribution between the two groups. The age-related decline in AMH levels was less pronounced in PCOS women compared to controls, as evidenced by a significant difference in slope coefficients (0.125, 95%CI: 0.044 to 0.205, p = 0.003). Multiple linear regression analysis was performed to identify factors influencing AMH levels in women with PCOS, using clinical characteristics, laboratory tests, and ultrasound findings as covariates. Serum AMH levels were positively associated with total serum testosterone levels (B-value=0.46, 95%CI: 0.07–0.85, p = 0.02). Prolactin concentrations (B-value=0.04, 95%CI: -0.07–0.85, p = 0.09) and the presence of polycystic ovarian morphology on ultrasound (B-value=1.16, 95%CI: -0.09–2.42, p = 0.07) showed a trend toward influencing AMH levels, albeit not statistically significant. Limitations, reasons for caution Older women constituted a small proportion of the PCOS population (n = 103 aged ≥35 years; n = 21 aged ≥38 years), potentially limiting the analysis of AMH-age correlations in this study. Wider implications of the findings These findings provide an AMH cut-off for PCOS diagnosis and suggest that endocrine disorders play a critical role in regulating AMH activity in women suffering from this condition. With advancing age, serum AMH levels appear to be better preserved in women with PCOS compared to their non-PCOS counterparts. Trial registration number No