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Objective: To evaluate the diagnostic performance of the antimüllerian hormone (AMH) level determined using the Access AMH assay for predicting poor ovarian response (POR) defined as ≤4 oocytes retrieved, including the validation of the predefined AMH cutoff of 0.93 ng/mL in both serum and plasma., Design: Prospective cohort study., Setting: Fifteen private and academic fertility centers (14 in the United States and 1 in Canada)., Patient(s): Women aged 21-45 years planning controlled ovarian stimulation for in vitro fertilization., Intervention(s): None., Main Outcome Measure(s): Number of oocytes retrieved, categorized as POR and normal-to-high ovarian response (non-POR). The correlation of AMH level and antral follicle count., Result(s): Data were available for 472 participants who completed the study (74 with POR and 398 non-POR). The mean AMH serum level among those with POR was 0.99 ng/mL (median 0.76 ng/mL) compared with 2.83 ng/mL (median 2.36 ng/mL) among the normal-to-high responders. For confirmation of the 0.93 ng/mL AMH level cutoff as a predictor of POR, a receiver operating characteristic analysis gave an area under the curve of 0.852, with corresponding sensitivity and specificity of 63.5% and 89.2%, respectively. The associated positive predictive value was 52.2% and the negative predictive value was 92.9%. The AMH plasma values demonstrated a strong correlation with AMH serum values with an r value = 0.9980. The previously established AMH cutoff of 1.77 ng/mL for antral follicle count >15 resulted in a sensitivity of 83.8% (95% confidence interval [CI] 77.7-88.5) and a specificity of 59.9% (95% CI 54.2-65.4)., Conclusion(s): This study validated the previously established AMH cut-point for the prediction of POR. Because this cut-point may vary depending on the assay used, the specific AMH assay should be reported in the literature whenever possible., (Copyright © 2021. Published by Elsevier Inc.)

Context: Recent studies have examined level and rate of change of anti-Müllerian hormone (AMH) for predicting time to menopause. Limited prospective, longitudinal data exists evaluating measures of ovarian reserve (MOR) in cancer survivors., Purpose: Determine the rate of change of MOR in survivors (15 to 39 years) compared with similar-aged controls and compared with late reproductive-aged controls (40 to 50 years)., Design: Prospective cohort., Setting: Quaternary university hospital., Participants: Survivors at least 1 year from therapy completion, similar-aged controls, and late reproductive-aged controls., Interventions: Annual visits with early follicular-phase hormone analysis and ultrasound., Main Outcome Measure: Changes in AMH and antral follicle count (AFC) were modeled using random effects linear regression., Results: Cancer survivors (170) and 135 similar-aged controls had annual visits for an average of 38 months; 71 late reproductive-aged controls were followed for an average of 24 months. In models adjusted for body mass index, time since cancer therapy (for survivors), and exogenous hormone use, the geometric mean AMH and AFC levels were lower in the survivors than similar-aged controls at all ages. After age 24.5 AMH and AFC declined in both groups at rates that were similar (P = 0.78 for AMH, P = 0.37 for AFC). Late reproductive-aged controls declined at a much more precipitous rate of 30% per year for AMH and 16% per year for AFC (P < 0.01 compared with survivors)., Conclusions: Although survivors had lower levels of AMH and AFC at the time of enrollment, the rate of change of AMH and AFC is not significantly different than similar-aged controls., (Copyright © 2019 Endocrine Society.)

Objective: To evaluate a new fully automated antimüllerian hormone (AMH) assay for prediction of poor ovarian response (POR) to ovarian stimulation defined as four or fewer oocytes retrieved., Design: Prospective cohort study., Setting: Thirteen private and academic fertility centers in the United States., Patients(s): A total of 178 women undergoing their first in vitro fertilization (IVF) cycle eligible for the study were consented and enrolled, with data available from 160 women for prediction of POR and 164 women for AMH correlation with antral follicle count (AFC)., Intervention(s): None., Main Outcome Measure(s): Cutoff point for AMH that predicts POR. Correlation of AMH with AFC, and cutoff point for AMH that correlates with antral follicle count >15., Result(s): The mean AMH among the poor responders was 0.74 ng/mL, compared with 3.20 ng/mL for normal to high responders. The AMH cutoff at 90% specificity for predicting POR with the use of the receiver operating characteristic (ROC) curve was 0.93 ng/mL, with an associated sensitivity of 74.1%. For prediction of POR, ROC analysis showed that AMH (area under the ROC curve [AUC] = 0.929) was significantly better than FSH (AUC = 0.615; P<.0001). AMH was positively correlated with AFC (Spearman rho = 0.756). The AMH at 90% sensitivity for AFC >15 was 1.75, with specificity of 59.1%., Conclusion(s): A fully automated AMH assay can be a useful biomarker for predicting POR in IVF cycles. Because AMH cutoff points vary depending on the assay used, future studies should continue to calibrate test results to clinically important outcomes., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: AMH is widely used for assessing ovarian reserve, and it is particularly convenient, because it is thought to have minimal variability throughout the menstrual cycle. However, studies assessing the stability of AMH over the menstrual cycle have been conflicting., Purpose: The purpose of this study is to determine whether AMH levels vary across the normal menstrual cycle., Design: A multi-center, prospective cohort study conducted at three US centers., Methods: Fifty females with regular menstrual cycles aged 18-45 underwent serial venipuncture every 3-5 days starting in the early follicular phase and lasting up to 10 collections. AMH was tested using the Access 2 immunoassay system., Results: Age-adjusted mixed-effect models utilizing data from 384 samples from 50 subjects demonstrated a within subject standard deviation of 0.81 (95% CI 0.75-0.88) with a coefficient of variation of 23.8% across the menstrual cycle and between subject standard deviation of 2.56 (95% CI 2.13-3.21) with a coefficient of variation of 75.1%. Intra-class correlation (ICC) of AMH across the menstrual cycle was 0.91., Conclusion: Overall, AMH levels, using the automated Access AMH assay, appear to be relatively stable across the menstrual cycle. Fluctuations, if any, appear to be small, and therefore, clinicians may advise patients to have AMH levels drawn at any time in the cycle.

Objective: To compare antimüllerian hormone (AMH) levels in women at high risk for hereditary breast and ovarian cancer compared with healthy low-risk control women., Design: Prospective cohort., Setting: Not applicable., Patient(s): Reproductive-age women with a uterus and both ovaries were analyzed in four groups: BRCA1 mutation carriers, BRCA2 carriers, BRCA-negative women, and low-risk controls., Intervention(s): Self-collected dried blood spot., Main Outcome Measure(s): AMH levels., Result(s): One hundred ninety-five women were included: 55 BRCA1 carriers, 50 BRCA2 carriers, 26 BRCA negative women, and 64 low-risk controls. After adjusting for confounders, BRCA2 carriers had AMH levels that were 33% lower than control women and an increased odds of having AMH <1 ng/mL. BRCA1 carriers and BRCA-negative women had AMH levels similar to control women. When analysis was restricted to regularly menstruating women younger than 40 years of age, BRCA2 carriers continued to demonstrate significantly lower AMH levels and increased likelihood of low AMH. Also, in this restricted group, BRCA-negative women demonstrated AMH levels that were 42% lower than control women. No difference in AMH was observed for BRCA1 carriers., Conclusion(s): We observed significantly lower AMH levels among BRCA2 carriers compared with low-risk control women. These results were stable across all models. BRCA-negative women also had lower AMH values, but only in models restricted to young regularly menstruating women. In contrast to earlier analyses, BRCA1 carriers had AMH values that were similar to low-risk control women, but this may be due to differences in the population studied., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the impact of hormonal contraception (HC) on markers of ovarian reserve, including antimüllerian hormone (AMH) and antral follicle count (AFC)., Design: Longitudinal prospective cohort., Setting: University hospital., Patient(s): Young adult female cancer survivors and healthy similar-age women., Intervention(s): None., Main Outcome Measure(s): Participants were followed annually to determine hormone levels and for transvaginal ultrasound. Subjects who used HC within the preceding 3 months were considered to be exposed. Linear mixed effects models were used to incorporate repeated measures and adjust for potential confounders., Result(s): A total of 249 women (126 survivors, 123 control subjects; average age 25.5 years) were followed for an average of 2.1 visits and 2.15 years. After adjusting for confounders, AMH was found to be 21% lower among survivors using HC and 55% lower among control subjects using HC (relative risk [RR] 0.79, 95% confidence interval [CI] 0.68-0.93; and RR 0.45, 95% CI 0.30-0.68; respectively). AFC was 20% lower among survivors and control subjects using HC (RR 0.80, 95% CI 0.69-0.93). When considering an individual subject, AMH was 17%-35% lower when a subject had recently used HC than when she had not (survivors: RR 0.83, 95% CI 0.75-0.93; control subjects: RR 0.65, 95% CI 0.55-0.78), and AFC was 11% lower (RR 0.89, 95% CI 0.82-0.96). Additive HC exposure across multiple visits was not associated with differences in AMH or AFC., Conclusion(s): AMH and AFC are significantly lower among women with recent exposure to HC. AMH and AFC should be interpreted with caution when measured in the setting of recent hormone use., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To identify factors associated with ovarian reserve impairment during and immediately after chemotherapy., Design: Prospective cohort study., Setting: Four university hospitals., Patient(s): Forty-six adolescent and young adult women with a new diagnosis of cancer requiring chemotherapy., Intervention(s): None., Main Outcome Measure(s): Measurements of ovarian reserve via levels of serum follicle-stimulating hormone, luteinizing hormone, estradiol, inhibin B, and antimüllerian hormone (AMH) as well as antral follicle counts and mean ovarian volume at 3-month intervals., Result(s): Changes in ovarian reserve were quantified for both the acute impact of treatment using linear regression and the longitudinal recovery after therapy using mixed-effects models adjusted for baseline ovarian reserve, use of alkylating agent, and hormone use. The women had at least one pretreatment and two posttreatment study visits (mean follow-up interval: 12 months). All measures of ovarian reserve demonstrated statistically significant changes during chemotherapy. Alkylating agent exposure and baseline ovarian reserve were acutely associated with the magnitude of impairment, and pretreatment AMH levels were associated with the rate of recovery of AMH after treatment. In adjusted models, participants with a pretreatment AMH level > 2 ng/mL recovered at a rate of 11.9% per month after chemotherapy, whereas participants with pretreatment AMH levels ≤ 2 ng/mL recovered at a rate of 2.6% per month after therapy., Conclusion(s): Baseline ovarian reserve and alkylating agent exposure effect the magnitude of acute changes in ovarian reserve from chemotherapy. The rate of recovery of AMH is impacted by pretreatment levels. This should be considered during pretreatment fertility preservation counseling., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the rate of change of antimüllerian hormone (AMH) level in the late reproductive years and its associations with time to menopause (TTM). We hypothesized that the rate of change between two measures of AMH reflects follicular atresia and varies among women independent of age., Design: A14-year follow-up., Setting: A randomly identified, population-based cohort (Penn Ovarian Aging Study)., Patient(s): Two measures of AMH were evaluated in survival analysis of 293 women., Intervention(s): None., Main Outcome Measure(s): Time to menopause., Result(s): The rate of AMH change was a strong independent predictor of TTM in multivariable analysis after adjusting for AMH baseline, age, and smoking (hazard ratio for 1 SD change = 1.82, 95% confidence interval 1.56-2.14). Among women with similar AMH levels, TTM differed by approximately 2 years when compared between a slow and fast rate of AMH change. A significant interaction of AMH rate of change and age indicated that a faster decrease in AMH level was associated with an increased risk of menopause in women aged 35-39 years (hazard ratio 6.97, 95% confidence interval 3.81-12.72), with less dramatic but significant associations in women aged 40-44 and 45-48 years., Conclusion(s): The AMH rate of change was independently associated with TTM in late reproductive-age women and increased the precision of estimates of TTM when included with an AMH baseline level and age. The rate of AMH change may be a more direct surrogate than age and increases the precision of estimates of TTM during this clinically important time period., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Biological markers of ovarian reserve have the potential to advance research on fecundability, infertility and reproductive aging. Anti-Müllerian hormone (AMH) has emerged as a clinically useful measure of ovarian reserve, but the requirement for venous blood is an obstacle to application in non-clinical settings. This paper validates a new method for quantifying AMH in dried blood spot (DBS) samples--drops of whole blood collected on filter paper following a simple finger stick., Methods: Matched serum and DBS samples were obtained from n=101 women of reproductive age, and AMH values were compared using regression analyses and scatter plots. The precision, reliability, linearity, recovery and lower detection limit of the DBS assay were evaluated, as well as the stability of AMH in DBS across a range of storage conditions., Results: There was a strong agreement between AMH concentrations measured in DBS and serum samples across the entire assay range. Analysis of within-assay (percent coefficient of variation, 4.7-6.5%) and between-assay (3.5-7.2%) variability indicated a high level of assay precision and reliability, respectively. The minimum detectable dose of AMH was 0.065 ng/ml. Concentrations of AMH remained stable in DBS samples stored for 2 weeks at room temperature, and for 4 weeks when refrigerated., Conclusions: The DBS assay performs at a level that is comparable to serum-based methods, with the advantage of lower burdens and costs associated with blood collection that may be advantageous for research in clinical as well as non-clinical settings on the causes and consequences of variation in ovarian reserve.

Context: Anti-mullerian hormone (AMH) has emerged as a marker of ovarian reserve and a possible surrogate measure of reproductive aging., Objective: The aim of the study was to evaluate the predictive value of AMH levels in determining the median time to menopause for late reproductive age women and the predictive ability of AMH compared to FSH and inhibin b., Design and Setting: A 14-yr follow-up in the Penn Ovarian Aging Study, 1996-2010, was conducted for a randomly identified population-based cohort., Subjects: A total of 401 late reproductive age women participated in the study., Main Outcome Measure: Observed time to menopause was measured., Results: All participants were premenopausal, with a mean (SD) age of 41.47 (3.52) yr and a median AMH level of 0.68 ng/ml at baseline. AMH strongly predicted time to menopause; age further improved predictions. Among women with a baseline AMH level below 0.20 ng/ml, the median time to menopause was 5.99 yr [95% confidence interval (CI), 4.20-6.33] in the 45- to 48-yr age group and 9.94 yr (95% CI, 3.31-12.73) in the 35- to 39-yr age group. With higher baseline AMH levels above 1.50 ng/ml, the median time to menopause was 6.23 yr in the oldest age group and more than 13.01 yr in the youngest age group. Smoking significantly reduced the time to menopause (hazard ratio, 1.61; 95% CI, 1.19-2.19; P = 0.002). AMH was a stronger predictor of time to menopause than FSH or inhibin b., Conclusions: AMH is a strong predictor of median time to menopause in late reproductive age women. Age and smoking are significant and independent contributors to the predictions of AMH.

Background: In late reproductive-aged breast cancer survivors, there is a need for real-time biomarkers of postchemotherapy ovarian function. The objective was to determine whether antimullerian hormone (AMH) and inhibin B are such biomarkers. The authors tested whether AMH and inhibin B were impacted by breast cancer treatment by comparing cancer survivors to age-matched control women and determined the association between these hormones and postchemotherapy menstrual pattern., Methods: Breast cancer patients (n = 127) with American Joint Committee on Cancer stage I to III disease who were premenopausal at diagnosis were enrolled postchemotherapy and observed. The primary endpoint was chemotherapy-related amenorrhea (CRA) (> or = 12 months of amenorrhea after chemotherapy). Matched pair analyses compared AMH, inhibin B, and follicle-stimulating hormone (FSH) levels between cancer and age-matched control subjects. Associations between hormones, CRA status, and change in CRA status over time were assessed., Results: The median age of the patients at chemotherapy was 43.2 years (range, 26.7-57.8 years). At enrollment, median follow-up since chemotherapy was 2.1 years, and 55% of subjects had CRA. Compared with age-matched controls, cancer subjects had significantly lower AMH (P = .004) and inhibin B (P < .001) and higher FSH (P < .001). AMH (P = .002) and inhibin B (P = .001) were found to be significantly associated with risk of CRA, even after controlling for FSH. AMH was significantly lower (P = .03) and FSH was significantly higher (P = .04) in menstruating subjects who developed subsequent CRA., Conclusions: AMH and inhibin B are 2 additional measures of postchemotherapy ovarian function in late reproductive-aged breast cancer survivors. With further research and validation, these hormones may supplement limited current tools for assessing and predicting postchemotherapy ovarian function., (Copyright 2009 American Cancer Society.)

Objective: To examine the association between obesity and serum and ultrasound measures of ovarian reserve in late reproductive age women., Design: Cross-sectional study of 36 healthy women, ages 40 to 52 years. Women were recruited in a 1:1 ratio of normal weight (body mass index <25) to obese women (body mass index >or=30). Early follicular phase blood draw, anthropometric measurements, and a transvaginal ultrasonography were performed. Outcome measures were serum antimullerian hormone, inhibin B, estradiol, follicle-stimulating hormone, ultrasound ovarian volume, and antral follicle count., Results: Mean antral follicle count was 7.6 for normal weight and 6.3 for obese women (P = 0.35). Proportions of normal weight (17%) versus obese women (22%) with antral follicle count less than 4 were similar. Ovarian volumes did not differ by body size. In adjusted models, antimullerian hormone levels in obese women were 77% lower on average than those in normal weight women (P = 0.02). Inhibin B levels were 24% lower in obese women compared with normal weight women (P = 0.08). Follicle-stimulating hormone and estradiol were not associated with body mass index., Conclusions: Although antral follicle count did not differ by body size, antimullerian hormone was lower in obese compared with normal weight late reproductive age women. These data suggest that lower antimullerian hormone levels in obese late reproductive age women result from physiologic processes other than decreased ovarian reserve.

Objective: To describe anti-mullerian hormone (AMH) levels in healthy late reproductive age women and test the hypothesis that AMH levels are lower in obese compared to non-obese women. Design: Cross-sectional study of AMH levels. Longitudinal analysis of a subgroup with 10 AMH measures over 8 years to support the cross-sectional results. Setting: A population-based cohort of healthy late reproductive-age women. Participants: Selected from the cohort to provide comparisons of body mass index (BMI), menopausal status, age and race (n = 122). Interventions: AMH levels were determined from blood samples collected in the parent study. Main Outcome Measure: Serum levels of AMH. Results: AMH levels were 65% lower in obese women compared to non-obese women (0.016 ng/mL and 0.046 ng/mL, respectively). The geometric mean ratio was 0.35; 95% CI 0.13, 0.92, P=.034. AMH levels were significantly lower in the menopausal transition compared to premenopausal women and were significantly lower in all age groups ≥40 years compared to the 35–39 year-old women. BMI remained significantly associated with AMH levels in multivariable models that included adjustments for menopausal status, age, race and cycle day. In the longitudinal analysis of a subgroup, obese women had significantly lower mean AMH levels over the 8-year interval compared to the non-obese women (0.459 ng/mL; CI 0.28, 0.75 and 0.566 ng/mL; CI 0.34, 0.94, respectively; P=.016), corroborating the cross-sectional study results. Conclusions: Obese women have lower AMH levels compared to non-obese women in the late reproductive years. The findings offer further evidence of the complex relationships between obesity and reproductive hormone levels in women. [Copyright &y& Elsevier]

Objective: To develop and internally validate a clinical predictive tool to assess the likelihood that a young cancer patient will experience diminished ovarian reserve (DOR) after chemotherapy.Design: Prospective cohort study.Setting: University hospitals.Patient(s): Postpubertal adolescent and young adult women with a new diagnosis of cancer requiring chemotherapy.Intervention: None.Main Outcome Measure(s): Diminished ovarian reserve after completion of and recovery from chemotherapy, defined as serum antimüllerian hormone (AMH) <1 ng/mL at 8-24 months after completion of chemotherapy.Result(s): A multivariable logistic regression model which includes age, cancer type, exposure to an alkylating agent, and baseline AMH value accurately predicts the diagnosis of DOR after chemotherapy with an area under the receiver operating characteristic curve of 0.89.Conclusion(s): Pretreatment information on age, cancer type, use of an alkylating agent, and baseline AMH levels make up a clinically useful predictive tool to identify which women are most at risk for DOR caused by chemotherapy. [ABSTRACT FROM AUTHOR]