Access anti-Müllerian Hormone Research Articles

B-030 Performance evaluation of Siemens Atellica® IM Anti-Müllerian Hormone Assay

Abstract Background Anti-Müllerian hormone (AMH), a glycoprotein dimer, is produced by ovarian granulosa cells and its levels have been shown to directly correlate to the number of eggs remaining in the ovaries (ovarian reserve). Thus, measurements of AMH are widely used as an aid in the assessment of the ovarian reserve in women presenting to fertility clinics. This study aimed to evaluate the performance of the Siemens Atellica® IM AMH assay and compare it to the Beckman Access AMH assay. Methods The Atellica AMH assay is a fully automated chemiluminescent monoclonal sandwich immunoassay, while the Beckman Access AMH assay is also an automated chemiluminescent monoclonal sandwich immunoassay. Precision and linearity were assessed for the Atellica AMH assay using manufacturer-provided standards. Inter-laboratory correlation studies were completed using deidentified patient samples collected from 120 reproductive-age women undergoing fertility outpatient evaluation at Yale New Haven Health. Blood was drawn on the first office visit for fertility workup. AMH values were initially performed at Yale University using the Beckman Access AMH assay. Serum samples were then frozen (-20°C) and shipped on dry ice to the laboratory at the Ohio State University where they were thawed and analyzed using the Siemens Atellica AMH assay. Linear regression was employed for data analysis. Overall percent agreement using an AMH cut-off value of 1.77 ng/mL was calculated. AMH values >1.77 ng/mL were classified as positive and values ≤1.77 were classified as negative. Results The Siemens Atellica AMH assay exhibited good performance across the measuring range, with intra-assay and inter-assay coefficients of variation (CVs) ranging from 1.4% to 3.2% and 2.5% to 6.0%, respectively. The assay demonstrated linearity over the four recommended ranges (0.043-24.0 ng/mL) without significant bias observed. The Access and Atellica AMH assays demonstrated good overall agreement of 97% and were well-correlated with a R2 value of 0.9721. Conclusions The AMH assay was validated and routinely measured in-house using the Atellica automated assay. The Siemens Atellica AMH assay performs well across its measuring range and shows good agreement with Beckman Access AMH at the AMH cut-off of 1.77 ng/mL.

A-306 High Sensitivity Capability of an Anti-müllerian Hormone Assay on the Beckman Coulter DxI 9000 Immunoassay Analyzer*, a Next Step Toward Enabling Ovarian Failure Staging?

Abstract Background Measurement of anti-müllerian hormone (AMH) has proven value in the evaluation of ovarian reserve using assays such as the Beckman Coulter Access AMH assay. If improved sensitivity of AMH measurement can be achieved, enhanced clinical utility during the assessment of reproductive aging and ovarian response to enable staging of ovarian failure is possible (Practice Committee of the American Society of Reproductive Medicine 2020, Cappola et al. 2023). The Beckman Coulter DxI 9000 Immunoassay Analyzer* has been designed with new technology that can be leveraged to improve assay sensitivity. Such technological advancements include the new Lumi-Phos PRO chemiluminescent substrate which yields markedly increased signal-to-noise, a new luminometer with increased dynamic range, and improved low-volume pipetting capabilities. Data herein summarize results from analytical verification studies of the Access AMH assay on the DxI 9000 Immunoassay Analyzer. Results demonstrate an example of DxI 9000 technologies enabling sensitivity claims that are up to 20-fold improved. * The official name is DxI 9000 Access Immunoassay Analyzer. Methods A method comparison study was performed based on CLSI guideline EP09c, 3rd ed. to compare results for the Access AMH assay on DxI 9000 to the predicate device, the Access AMH assay on the Access 2 Immunoassay System. Within-laboratory precision was also evaluated following CLSI EP05-A3. Finally, performance at low analyte levels was evaluated following CLSI EP17-A2, and linearity was evaluated following CLSI EP06-Ed2. Results Method comparison of the Access AMH assay on DxI 9000 compared to the Access AMH assay on the Access 2 yielded excellent agreement with a Passing-Bablok slope of 1.02 for N=126 samples. Further, bias estimates for a number of key medical decision points suggest minimal bias (≤ 2%) across the assay range, and minimal non-linearity was observed. 20-day imprecision studies yielded CV’s between 2 and 5% across a broad range of concentrations evaluated. Sensitivity studies yielded estimates of limit of quantitation (LoQ) between 0.001 and 0.003 ng/mL. This represents an approximately 10- to 20-fold improvement in sensitivity claims compared to the AMH assay on the Access 2 and other commercially available automated immunoassay analyzers. Conclusions The data herein present performance data for the Access AMH assay on the DxI 9000 Immunoassay Analyzer. The assay demonstrates excellent accuracy relative to the predicate device, while showing good linearity and imprecision. Of note, the Access AMH assay exhibits exceptional low-end performance on the DxI 9000 analyzer as demonstrated by the ability to enable sensitivity claims that are up to 20-fold improved in comparison to existing immunoassays for the measurement of AMH. The sensitivity capabilities of the Access AMH assay on DxI 9000 suggest an opportunity for the addition of further intended uses for scenarios where extremely low AMH measurements can provide additional value of clinical significance. Further studies are needed to fully understand additional clinical utilities of the Access AMH assay with high sensitivity capability on DxI 9000, including the assessment of reproductive aging for menopause diagnosis or ovarian response for fertility treatment.

The Stability of the Anti-Müllerian Hormone in Serum and Plasma Samples under Various Preanalytical Conditions.

The anti-Müllerian hormone (AMH) is a glycoprotein that plays an important role in prenatal sex differentiation. It is used as a biomarker in polycystic ovary syndrome (PCOS) diagnostics, as well as for estimating an individual's ovarian reserve and the ovarian response to hormonal stimulation during in vitro fertilization (IVF). The aim of this study was to test the stability of AMH during various preanalytical conditions that are in accordance with the ISBER (International Society for Biological and Environmental Repositories) protocol. Plasma and serum samples were taken from each of the 26 participants. The samples were then processed according to the ISBER protocol. AMH levels were measured in all the samples simultaneously using the chemiluminescent kit ACCESS AMH in a UniCel® DxI 800 Immunoassay System (Beckman Coulter, Brea, CA, USA). The study proved that AMH retains a relatively high degree of stability during repeated freezing and thawing in serum. AMH was shown to be less stable in plasma samples. Room temperature proved to be the least suitable condition for the storage of samples before performing the biomarker analysis. During the testing of storage stability at 5-7 °C, the values decreased over time for all the plasma samples but remained stable in the serum samples. We proved that AMH is highly stable under various stress conditions. The anti-Müllerian hormone retained the greatest stability in the serum samples.

Development of a digital anti-Müllerian hormone immunoassay: ultrasensitive, accurate and practical strategy for reduced ovarian reserve monitoring and assessment

Anti-Müllerian hormone (AMH) is an ideal biomarker for the assessment of ovarian reserve. However, its application in determining ovarian reserve reduction is restricted due to the low sensitivity of existing AMH assays. Herein, a homebrew ultrasensitive digital AMH assay (UD-AMH) was established based on a single-molecule array (SiMoA, HD-X platform), and the analytical performance of UD-AMH was evaluated systematically. The limit of detection (LoD) and limit of quantitation (LoQ) of UD-AMH were 0.13 and 0.14 pg/mL, respectively, which is approximately 100-fold higher than that of the current reported general clinical AMH assay. A comparison study showed a high correlation, with r = 0.988 for the Beckman Access AMH assay and r = 0.945 for the Kangrun AMH assay. In addition, we found that the AMH concentrations of premature ovarian insufficiency (POI) patients were very low (2.59 (0.86, 31.79) pg/mL) and similar to those of perimenopausal women (2.37 (0.65, 35.88) pg/mL) but significantly higher than those of menopausal women (0.43 (0.28, 1.17) pg/mL). Furthermore, we observed that the AMH concentration of most hormone therapy (HT) treated POI patients decreased sharply, suggesting that the ovarian reserve of POI patients declines over time even under HT-treatment.

Validation study of the Access antimüllerian hormone assay for the prediction of poor ovarian response to controlled ovarian stimulation

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. Prospective cohort study. Fifteen private and academic fertility centers (14 in the United States and 1 in Canada). Women aged 21-45 years planning controlled ovarian stimulation for invitro fertilization. None. Number of oocytes retrieved, categorized as POR and normal-to-high ovarian response (non-POR). The correlation of AMH level and antral follicle count. 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). 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.

The interchangeability of two assays for the measurement of anti-Müllerian hormone when personalizing the dose of FSH in in-vitro fertilization cycles

Objective Study the interchangeability of Roche Elecsys and Beckman Coulter Access anti-Müllerian Hormone (AMH) assays to select the gonadotropin starting dose in IVF cycles. Methods Patients’ AMH was measured using both Elecsys and Access automated assays. AMH values were then used to calculate the FSH starting dose. The main outcome is the percentage of women that would have been stratified to a different dose of gonadotropin due to differences in AMH values from the two tests. Results The Access assay systematically gives higher values compared with the Elecsys assay (slope = 0.88). For Follitropin Alfa, the difference in starting dose was > 15% in 2/113 patients, when Access AMH was used instead of Elecsys. For Follitropin Delta the difference in the starting dose was >15% in 21/113 patients when using Access AMH. When considering women with high ovarian reserve, only 4/51 would have received a Follitropin Delta dose that exceeded a 15% difference using Access AMH as a substitute for the Elecsys value. Conclusions The use of the Roche Elecsys or Beckman Coulter Access leads to modest differences in AMH values, which seem to little affect the calibration of FSH dose used for ovarian stimulation.

Age-specific reference ranges of serum anti-müllerian hormone in healthy women and its application in diagnosis of polycystic ovary syndrome: a population study.

To establish the age-specific centiles of serum anti-müllerian hormone (AMH) levels in Chinese women, and to explore the use of multiples of median (MoM) AMH levels for the diagnosis of polycystic ovary syndrome (PCOS). An observational study. University-affiliated hospitals and community clinics. We included 3137 healthy women aged 20-44years recruited prospectively or who had archived serum samples from previous research projects. Another validation cohort of 751 women with PCOS as well as ovulatory controls, which was a convenient sample of women attending for infertility or menstrual disorders, was also studied. The serum samples were assayed for AMH by the automated Access AMH assay. Age-specific reference ranges were constructed on the primary cohort with the Lambda-Mu-Sigma method. The MoM AMH of each subject in the validation cohort was calculated. Centile curves of serum AMH level against age were established. MoM AMH was significantly higher in women with PCOS than in controls (P<0.05). The area under the ROC curve was 0.852 (95% confidence interval [CI] 0.825-0.877) (P<0.0001) for discriminating women with PCOS from ovulatory controls by MoM AMH. We established a set of year-by-year age-specific reference ranges of serum AMH levels in Chinese women. The MoM AMH derived from this set of reference ranges is a promising tool to replace antral follicle count in the diagnosis of PCOS. A set of age-specific reference ranges of AMH levels was established in Chinese women. Multiples of median AMH may be used to diagnose PCOS.

Comparison of Automated Anti-Müllerian Hormone Assays and Antral Follicle Count in Predicting Ovarian Response During Ovarian Stimulation

Objective: Various parameters had been used to predict ovarian response. Among them, Anti-Müllerian Hormone (AMH) and antral follicle count (AFC) demonstrate the most favourable analytical and performance characteristics. In this pilot study, we aim to determine the cut-off levels of AMH using automated AMH assays and AFC in the prediction of poor and high responders. Study Design: Prospective study of 43 women between 21 to 45 years old scheduled for assisted reproduction. AMH levels on day 3 of menstruation were analysed using two immunoassay kits, namely the Beckman Coulter Access AMH and the Roche Elecsys AMH on the two automated analysers Beckman Coulter DxI 800 and Roche Cobas e602 respectively. AFC was also assessed on day 3 of menstruation prior to in vitro fertilization (IVF). These were compared with the number of oocytes retrieved after controlled ovarian stimulation. Results: AMH (Beckman Coulter Access AMH and Roche Elecsys AMH) highly correlated with AFC and the number of oocytes retrieved after ovarian stimulation. Beckman Coulter Access AMH was the better predictor for poor ovarian response with ROC [Formula: see text] of 0.83. For the prediction of a high response, AFC had a higher ROC [Formula: see text] of 0.95. Through ROC, the AMH cut-off level for poor ovarian response was 2.23 ng/ml with Beckman Coulter Access AMH and 2.02 ng/ml with Roche Elecsys AMH, while the AMH cut-off for a high ovarian response was 5.19 ng/ml with Beckman Coulter Access AMH and 4.60 ng/ml with Roche Elecsys AMH. For AFC, the cut-off for poor ovarian response was 18 and for high response was 34. Conclusion: AMH and AFC are reliable predictors of ovarian response. Establishment of specific levels may improve individualised controlled ovarian stimulation and optimise the oocyte yield. Larger studies are required to establish these findings.

Anti-müllerian Hormone for the Prediction of Ovarian Response in Progestin-Primed Ovarian Stimulation Protocol for IVF.

Background: The ability of anti-Müllerian hormone (AMH) to predict ovarian response has been studied extensively in gonadotropin-releasing hormone agonist and antagonist treatments, but no information is available regarding its value in progestin-primed ovarian stimulation (PPOS) protocol.Methods: This retrospective data analysis included 523 patients without polycystic ovary syndrome who underwent their first in vitro fertilization/intracytoplasmic sperm injection cycle with PPOS protocol at our center between Jan. 2015 and Jul. 2018. Serum AMH measurements were acquired within 12 months prior to ovarian stimulation using the automated Access AMH assay.Results: AMH exhibited a significantly positive correlation with the number of retrieved oocytes (r = 0.744, P < 0.001). For the prediction of poor (<4 oocytes) and high (>15 oocytes) response, AMH had an area under the receiver operating characteristic curve (AUC) of 0.861 and 0.773, corresponding with an optimal cutoff point of 1.26 and 4.34 ng/mL, respectively. When stratified according to the dose of medroxyprogesterone acetate (MPA) (4 mg vs. 10 mg per day), AMH retained its similarly high predictive value for poor (AUC = 0.829 and 0.886, respectively) and high response (AUC = 0.770 and 0.814, respectively) in both groups. Amongst the 314 women who received their first frozen embryo transfer (FET) following PPOS protocol, no significant differences were observed on the rates of biochemical pregnancy, clinical pregnancy, implantation, early miscarriage, multiple pregnancy and ectopic pregnancy (all P > 0.05) across AMH quartiles (≤1.43, 1.44-2.55, 2.56–4.35, >4.35 ng/mL). In a multivariable logistic regression model, age was suggested to be the only independent risk factor for clinical pregnancy (P = 0.011).Conclusions: Our data demonstrated that AMH is an adequate predictor of both high and poor ovarian response in PPOS protocol regardless of MPA dose, but it does not associate with pregnancy outcomes in the first FET cycles in a freeze-all strategy.

Examination of different pre-analytical conditions on the values of anti-müllerian hormone (AMH) measured using the Access AMH Assay

To determine the association between ovarian reserve biomarkers and future fertility among late reproductive-age women.Cohort study of participants enrolled in Time to Conceive (TTC), a time-to-pregnancy cohort study of the ovarian reserve biomarkers.Community.Women aged 30–44 years without a history of infertility who provided a blood sample at enrollment in TTC and who agreed to future follow-up.Not applicable.The primary outcomes were probability of achieving a live birth >3 years after enrollment in TTC, diagnosis of infertility at any time, and time-to-pregnancy in future pregnancy attempts.Women with diminished ovarian reserve, defined as those with an antimüllerian hormone (AMH) level <0.7 ng/mL or follicle-stimulating hormone (FSH) level ≥10 mIU/mL, did not have low risk of future live birth (relative risk [RR], 1.32; 95% confidence interval [CI], 0.95–1.83 and RR, 1.28; 95% CI, 0.97–1.70, respectively) compared with women with normal ovarian reserve after adjusting for age at blood draw, race, obesity, use of hormonal contraception, and year of enrollment in original study. Among women in the cohort that attempted to conceive, there was not a significant association between diminished ovarian reserve, as measured by AMH or FSH, and risk of future infertility (RR, 0.65; 95% CI, 0.21–2.07 and RR,1.69; 95% CI, 0.86–3.31, respectively). Similarly, there was no association between AMH and FSH levels and future fecundability (fecundability ratio, 0.97; 95% CI, 0.59, 1.60; and fecundability ration, 0.86; 95% CI, 0.55–1.36, respectively).Diminished ovarian reserve is not associated with reduced future reproductive capacity. Given the lack of association, women should be cautioned regarding use biomarkers of ovarian reserve as predictors of their future reproductive capacity.Marcadores de reserva ovárica como predictores de la fertilidad futura.Determinar la asociación entre los biomarcadores de reserva ovárica y de la fertilidad futura en mujeres en edad reproductiva tardía.estudio de cohorte de participantes inscritas en Time to Conceive (TTC), un estudio de cohorte durante el tiempo hasta el embarazo de los biomarcadores de reserva ovárica.Comunidad.mujeres de 30 a 44 años sin antecedentes de infertilidad que proporcionaron una muestra de sangre al inscribirse en TTC y que aceptaron un seguimiento futuro.No aplicable.los resultados primarios fueron la probabilidad de lograr un nacido vivo > 3 años después de la inscripción en TTC, el diagnóstico de infertilidad en cualquier momento y el tiempo hasta el embarazo en futuros intentos de embarazo.Las mujeres con reserva ovárica disminuida, definida como aquellas con un nivel de hormona antimülleriana (AMH) <0,7 ng/mL o un nivel de hormona estimulante del folículo (FSH) R10 mIU/mL, no tenían bajo riesgo de futuros recién nacidos vivos (riesgo relativo [RR], 1,32; intervalo de confianza [IC] del 95 %, 0,95–1,83 y RR, 1,28; IC del 95 %, 0,97–1,70, respectivamente) en comparación con mujeres con reserva ovárica normal después de ajustar por edad en el momento de la extracción de sangre, raza, obesidad, uso de anticonceptivos hormonales y año de inscripción en el estudio original. Entre las mujeres de la cohorte que intentaron concebir, no hubo una asociación significativa entre la disminución de la reserva ovárica, medida por AMH o FSH, y el riesgo de infertilidad futura (RR, 0,65; IC 95 %, 0,21–2,07 y RR, 1,69; IC del 95 %, 0,86–3,31, respectivamente). De manera similar, no hubo asociación entre los niveles de AMH y FSH y la fecundidad futura (índice de fecundidad, 0,97; IC 95 %, 0,59, 1,60; e índice de fecundidad, 0,86; IC 95 %, 0,55–1,36, respectivamente).La reserva ovárica disminuida no está asociada con una capacidad reproductiva futura reducida. Dada la falta de asociación, se debe advertir a las mujeres sobre el uso de biomarcadores de reserva ovárica como predictores de su futura capacidad reproductiva.

Derivation of Russian reference intervals for anti-müllerian hormone (AMH) using access AMH assay

According to the European Regulation (EC) No. 1223/2009, cosmetic products should be safe for human health when used under normal or foreseeable conditions of use. To perform a safety evaluation, consumption data of finished cosmetic product are necessary to assess the corresponding consumer's exposure.The aim of this review was to highlight consumption (percentage of users, frequency of use, amount used, number of products daily used, types of products co-used …) and exposure data to cosmetic products available in the literature. A systematic approach was used following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. Literature search was performed in February 2018 using Pubmed and Scopus databases. The following information was collected for the 82 publications included in this review: type of study, characteristics of the population (number, age, sex, region of origin), period of data collection, types of products studied, method(s) of data collection, consumption and/or exposure parameters obtained. Because of the high number of quantitative results obtained in the different studies, these data are not presented here. Readers interested in one or more studies are invited to consult the results available in the original publication(s). This work could be very useful for safety assessors or other persons working in the risk assessment field.

Performance of anti-Müllerian hormone (AMH) levels measured by Beckman Coulter Access AMH assay to predict oocyte yield following controlled ovarian stimulation for in vitro fertilization.

PurposeWe evaluated the performance of anti‐Müllerian hormone (AMH) measured by the Beckman Coulter fully automated Access assay to predict oocyte yield following controlled ovarian stimulation (COS) for in vitro fertilization (IVF).MethodsThe correlation between the Access assay and the pre‐mixing method with Generation II ELISA assay (Gen II pre‐mix assay) was assessed using 230 blood samples. The relationship of AMH level measured by the Access assay and the actual number of oocytes retrieved following COS was assessed using 3296 IVF cycles. The performances of AMH, follicle stimulating hormone (FSH), and estradiol (E2) in predicting the responses to COS were also evaluated by constructing receiver operating characteristic (ROC) curves.ResultsThe AMH levels measured just before oocyte retrieval by the Access assay and the number of oocytes retrieved following COS showed a good correlation with R = 0.655. The ROC analysis revealed that the sensitivity of AMH was comparable with or lower than that of E2 but higher than that of FSH.ConclusionsWith the improved Access AMH assays, AMH was as sensitive as E2 and could become an accurate marker of ovarian response to COS in more than 3000 Japanese IVF patients.

Non-equivalence of anti-Müllerian hormone automated assays-clinical implications for use as a companion diagnostic for individualised gonadotrophin dosing.

STUDY QUESTIONCan anti-Müllerian hormone (AMH) automated immunoassays (Elecsys® and Access) be used interchangeably as a companion diagnostic for individualisation of follitropin delta dosing?SUMMARY ANSWERThe Access assay gives systematically higher AMH values than the Elecsys® assay which results in over 29% of women being misclassified to a different follitropin delta dose.WHAT IS KNOWN ALREADYFollitropin delta is the first gonadotrophin to be licenced with a companion diagnostic, the Roche Elecsys® AMH Plus assay. Alternative automated AMH assays including the Beckman Coulter Access immunoassay are considered to provide similar results, but clarification of their suitability as an off-licence companion diagnostic for follitropin delta is required.STUDY DESIGN, SIZE, DURATIONWe systematically searched the existing literature for studies that had measured AMH using both automated assays in the same cohort of women. Individual paired patient data were acquired from each author and combined with unpublished data.PARTICIPANTS/MATERIALS, SETTING, METHODSWe identified five eligible prospective published studies and one additional unpublished study. A 100% response from the authors was achieved. We collected paired AMH data on samples from 848 women. Passing–Bablok regression and Bland–Altman plots were used to compare the analytical performance of the two assays. The degree of misclassification to different treatment categories was estimated should the Access AMH be used as a companion diagnostic instead of the Elecsys AMH in determining the dosing of follitropin delta.MAIN RESULTS AND THE ROLE OF CHANCEThe Passing–Bablok regression shows a linear relationship (Access = −0.05 + 1.10 × Elecsys). The Access assay systematically gave higher values by an average of 10% compared with the Elecsys assay (slope = 1.10, 95% CI: 1.09 to 1.12). The average of the difference between the two assays was 2.7 pmol/l. The 95% limits of agreement were −11.7 to 6.3. Overall 253 (29.3%) women would have received an inappropriate follitropin delta dose if the Beckman Coulter Access assay was used. Specifically, a substantial proportion of women (ranging from 49% to 90% depending on the AMH category) would receive a lower dose of follitropin delta based on the Access AMH assay. Up to 10% (ranging from 2.5% to 10%) of women with high ovarian reserve would have been misclassified to a greater dose of follitropin delta based on the Access AMH assay.LIMITATIONS REASONS FOR CAUTIONWe compared the values of the two principal automated assays, extrapolation of our findings to other automated AMH assays would require similar comprehensive examination.WIDER IMPLICATIONS OF THE FINDINGSAn international standard for the calibration of the automated AMH assays is warranted to facilitate efficient use of AMH as a companion diagnostic. The variable calibration of alternative automated AMH assays may adversely impact on the performance of the follitropin delta dosing algorithm.STUDY FUNDING/COMPETING INTEREST(S)No formal funding has been received for this study. SI is funded by a UK Medical Research Council skills development fellowship (MR/N015177/1). SMN has received speakers fees, travel to meetings and participated in advisory Boards for Beckman Coulter, IBSA, Ferring Pharmaecuticals, Finox, Merck Serono, Merck and Roche Diagnostics. SMN has received research support from Ansh laboratories, Beckman Coulter, Ferring Pharmaceuticals and Roche Diagnostics.TRIAL REGISTRATION NUMBERN/A.

Performance characteristics of the Access AMH assay for the quantitative determination of anti-Müllerian hormone (AMH) levels on the Access* family of automated immunoassay systems

ObjectivesAnti-Müllerian hormone (AMH) measurement is useful as an aid in the evaluation of ovarian reserve. In the past, its conventional use was restricted by the low-throughput and variability of existing manual AMH assays. We developed the automated Access AMH assay for the quantitative determination of AMH levels on the Access family of immunoassay systems. The analytical performance of this new assay was evaluated. Design and methodsSensitivity, dilution linearity, assay imprecision, AMH sample stability, lot-to-lot comparison and correlation with AMH Gen II assay (Beckman Coulter, Inc.) were evaluated. Reference intervals for Access AMH were established in healthy females, males, newborns (≤60days) and pediatric males classified by Tanner stages. ResultsThe limit of blank and limit of detection were below 0.0077 and 0.0098ng/mL, respectively. The limit of quantitation was 0.010ng/mL. The total imprecision ranged from 2.4 to 5.2%. Linearity was observed up to 24ng/mL. Sample storage at room temperature up to 48h, at 2–8°C up to 7days and at −20°C up to 15months had no impact on measured AMH. The correlation study gave a coefficient between 0.99 and 1 and a regression slope between 0.89 and 0.92. Excellent lot-to-lot comparability was observed on controls and patient samples with a maximum bias of 3.7% between 2.81 and 15.03ng/mL. ConclusionsThe fully automated Access AMH immunoassay demonstrates excellent analytical performance. As a consequence, the availability of this assay will represent a robust, fast and precise alternative to manual AMH assay testing.

Assessment of the Access AMH assay as an automated, high-performance replacement for the AMH Generation II manual ELISA.

BackgroundThe manual Generation II (Gen II) ELISA method used to measure Anti-Müllerian Hormone (AMH) from Beckman Coulter has recently been superseded by a fully automated AMH immunoassay. The aim of this study was to evaluate the performance of the Access AMH assay and directly compare it to the modified Gen II ELISA method. A secondary aim was to verify that the fertile age-related AMH range previously established using the Gen II ELISA could be used to interpret results from the new automated Access assay.MethodsThe precision, stability, linearity, measurement range and detection limits were determined using recombinant AMH and patient serum samples. Different diluents and their effects on AMH concentration were compared. A correlation study was performed on patient samples to compare the Access AMH assay to the ELISA method on the Access2 and DxI800 analysers. The fertile AMH range was verified by comparing the 10th, 50th and 90th percentile values from both methods obtained from 489 natural conception pregnant women.ResultsThe Access AMH assay showed good performance across the measuring range for both intra-assay (CV 1.41–3.30 %) and inter-assay (CV 3.04–5.76 %) precision and acceptable sample stability. Dilution of the high concentration samples with the recommended diluent resulted in a small but significant downward shift in values. The assay was linear over the range of values recommended by the manufacturer, allowing for accurate reporting within the reported range. The two assay types were highly correlated (R2 = 0.9822 and 0.9832 for Access2 and DxI800, respectively), and the differences observed between the Access2 and DxI800 analysers were within clinically acceptable ranges, indicating that the methods are interchangeable. Furthermore, we demonstrated that results from the published reference range for the Gen II ELISA correlate with those from the automated Access AMH assay.ConclusionHere, we verified the published performance of the Access AMH assay and showed excellent correlation with the Gen II ELISA method. Moreover, we validated this correlation by confirming that the results from a fertile AMH reference range established using the preceding Gen II ELISA are interchangeable with the new automated Access AMH assay.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-016-0143-3) contains supplementary material, which is available to authorized users.