Glasgow Center for Reproductive Medicine

Glasgow, United Kingdom

Glasgow Center for Reproductive Medicine

Glasgow, United Kingdom

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Nelson S.M.,University of Glasgow | Messow M.C.,University of Glasgow | Wallace A.M.,Royal Infirmary | Fleming R.,University of Glasgow | And 2 more authors.
Fertility and Sterility | Year: 2011

Objective: To define an optimal model for the decline in circulating antimüllerian hormone (AMH) with age and develop a validated age-related nomogram. Design: Cohort study with validation of linear, biphasic linear, differential, power, and quadratic equations undertaken in two additional cohorts. Setting: United Kingdom infertility clinics. Patient(s): Training cohort of 4,590 infertile women. Two separate validation cohorts; 4,588 infertile women, and 423 women with confirmed ovulation and normal pelvic ultrasound who have a male partner with severe oligospermia. Intervention(s): Serum AMH measurement. Main Outcome Measure(s): Optimal fit and age-related AMH nomogram. Result(s): The linear model had the largest sum of absolute and squared residuals and provided a less adequate fit than the four nonlinear models. Of these, the R2 ranged from 19.45% to 19.48% in the training dataset, from 21.30% to 21.36% in the validation dataset, and from 13.29% to 13.75% in the partners of oligospermic males. The parameters of the differential model were difficult to estimate, and the goodness-of-fit of the power model was slightly inferior to the quadratic model. Conclusion(s): Circulating AMH concentrations decline with increasing reproductive age in a manner optimally described by a quadratic equation. This validated age-related AMH nomogram will enable counseling of infertility patients regarding reproductive performance. © 2011 American Society for Reproductive Medicine, Published by Elsevier Inc.


Khader A.,University of Glasgow | Lloyd S.M.,University of Glasgow | McConnachie A.,University of Glasgow | Fleming R.,Glasgow Center for Reproductive Medicine | And 3 more authors.
Journal of Ovarian Research | Year: 2013

Background: Chronological age and oocyte yield are independent determinants of live birth in assisted conception. Anti-Müllerian hormone (AMH) is strongly associated with oocyte yield after controlled ovarian stimulation. We have previously assessed the ability of AMH and age to independently predict live birth in an Italian assisted conception cohort. Herein we report the external validation of the nomogram in 822 UK first in vitro fertilization (IVF) cycles. Methods. Retrospective cohort consisting of 822 patients undergoing their first IVF treatment cycle at Glasgow Centre for Reproductive Medicine. Analyses were restricted to women aged between 25 and 42 years of age. All women had an AMH measured prior to commencing their first IVF cycle. The performance of the model was assessed; discrimination by the area under the receiver operator curve (ROC§ssub§AUC§esub§) and model calibration by the predicted probability versus observed probability. Results: Live births occurred in 29.4% of the cohort. The observed and predicted outcomes showed no evidence of miscalibration (p = 0.188). The ROC§ssub§AUC§ esub§ was 0.64 (95% CI: 0.60, 0.68), suggesting moderate and similar discrimination to the original model. The ROC§ssub§AUC§esub§ for a continuous model of age and AMH was 0.65 (95% CI 0.61, 0.69), suggesting that the original categories of AMH were appropriate. Conclusions: We confirm by external validation that AMH and age are independent predictors of live birth. Although the confidence intervals for each category are wide, our results support the assessment of AMH in larger cohorts with detailed baseline phenotyping for live birth prediction. © 2013 Khader et al.; licensee BioMed Central Ltd.


Nelson S.M.,University of Glasgow | Fleming R.,University of Glasgow | Fleming R.,Glasgow Center for Reproductive Medicine | Gaudoin M.,Glasgow Center for Reproductive Medicine | And 3 more authors.
Fertility and Sterility | Year: 2015

Objective To compare antimüllerian hormone (AMH) and antral follicle count (AFC) separately and in combination with clinical characteristics for the prediction of live birth after controlled ovarian stimulation. Design Retrospective development and temporal external validation of prediction model. Setting Outpatient IVF clinic. Patient(s) We applied the boosted tree method to develop three prediction models incorporating clinical characteristics plus AMH or AFC or the combination on 2,124 linked IVF cycles from 2006 to 2010 and temporally externally validated predicted live-birth probabilities with an independent data set comprising 1,121 cycles from 2011 to 2012. Intervention(s) None. Main Outcome Measure(s) Predictive power (posterior log of odds ratio compared to age, or PLORA), reclassification, receiver operator characteristic analysis, calibration, dynamic range. Result(s) Predictive power, was highest for the AMH model (PLORA = 29.1), followed by the AMH-AFC model (PLORA = 28.3) and AFC model (PLORA = 22.5). The prediction errors were 1% to <5% in each prognostic tier for all three models, except for the predicted live-birth probabilities of <10% in the AFC model, where the prediction error was 8%. The improvement in predictive power was highest for the AMH model: 76.2% improvement over age alone relative to 59% improvement for AFC and 73.3% for the combined model. Receiver operating characteristic analysis demonstrated that the AMH and the combined model had comparable discrimination (area under the curve = 0.716) and similar prediction error for high and low strata of live-birth prediction, with an improvement of 6.3% over age alone. Conclusion(s) The validated prediction model confirmed that AMH when combined with clinical characteristics can accurately identify the likelihood of live birth with a low prediction error. AFC provided no added predictive value beyond AMH. © 2015 American Society for Reproductive Medicine.


Fleming R.,Glasgow Center for Reproductive Medicine | Fairbairn C.,Glasgow Center for Reproductive Medicine | Blaney C.,Glasgow Center for Reproductive Medicine | Lucas D.,Glasgow Center for Reproductive Medicine | Gaudoin M.,Glasgow Center for Reproductive Medicine
Reproductive BioMedicine Online | Year: 2013

The new Gen II assay for anti-Müllerian hormone (AMH) shows good stability and reliability in serum, but analyses of stability in whole blood are lacking. Testing the effects of storage of whole-blood samples at room temperature revealed significant increases in the measured value of AMH of 31% over 4 days (P < 0.001). The effect is temperature dependent, with storage at 4°C showing markedly reduced increments. Further, samples collected into serum tubes with gel separators and centrifuged within 5 h (blood cells and serum physically separated within the collection tube) showed reliable stability over a period of more than 5 days. © 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.


Fleming R.,Glasgow Center for Reproductive Medicine | Seifer D.B.,Oregon Health And Science University | Frattarelli J.L.,Fertility Institute of Hawaii | Ruman J.,Ferring Pharmaceuticals Inc
Reproductive BioMedicine Online | Year: 2015

Oocyte number and quality decline with age; however, fertility varies significantly even among women of the same age. Various measures have been developed to predict response to ovarian stimulation and reproductive potential. Evaluation of ovarian reserve can identify patients who may experience poor response or hyper-response to exogenous gonadotrophins and can aid in the personalization of treatment to achieve good response and minimize risks. In recent years, two key methods, antral follicle count (AFC), an ultrasound biomarker of follicle number, and the concentration of serum anti-Müllerian hormone (AMH), a hormone biomarker of follicle number, have emerged as preferred methods for assessing ovarian reserve. In this review, a live debate held at the American Society for Reproductive Medicine 2013 Annual Meeting is expanded upon to compare the predictive values, merits, and disadvantages of AFC and AMH level. An ovarian reserve measure without limitations has not yet been discovered, although both AFC and AMH have good predictive value. Published evidence, however, as well as the objectivity and potential standardization of AMH level and the convenience of testing any time throughout the menstrual cycle, leans towards AMH level becoming the gold-standard biomarker to evaluate ovarian reserve and predict ovarian response to stimulation.


Fleming R.,Glasgow Center for Reproductive Medicine | Fleming R.,University of Glasgow | Kelsey T.W.,University of St. Andrews | Anderson R.A.,Queens Medical Research Institute | And 2 more authors.
Fertility and Sterility | Year: 2012

The changes in the relationships between circulating antimüllerian hormone, the size of the primordial follicle pool, and follicular recruitment before and through the reproductive years have now been clarified, and show dynamic changes through sexual development. The constant relationship between the number of follicles and circulating antimüllerian hormone exists only after the age of 25 years, implying that the association between follicular recruitment and follicular survival to the later stages of development is not constant across the reproductive life course. This commentary assesses the factors that may underlie these relationships and their clinical implications for reproductive health. Copyright © 2012 American Society for Reproductive Medicine, Published by Elsevier Inc.


PubMed | Fertility Institute of Hawaii, Oregon Health And Science University, Ferring Pharmaceuticals Inc and Glasgow Center for Reproductive Medicine
Type: Comparative Study | Journal: Reproductive biomedicine online | Year: 2015

Oocyte number and quality decline with age; however, fertility varies significantly even among women of the same age. Various measures have been developed to predict response to ovarian stimulation and reproductive potential. Evaluation of ovarian reserve can identify patients who may experience poor response or hyper-response to exogenous gonadotrophins and can aid in the personalization of treatment to achieve good response and minimize risks. In recent years, two key methods, antral follicle count (AFC), an ultrasound biomarker of follicle number, and the concentration of serum anti-Mllerian hormone (AMH), a hormone biomarker of follicle number, have emerged as preferred methods for assessing ovarian reserve. In this review, a live debate held at the American Society for Reproductive Medicine 2013 Annual Meeting is expanded upon to compare the predictive values, merits, and disadvantages of AFC and AMH level. An ovarian reserve measure without limitations has not yet been discovered, although both AFC and AMH have good predictive value. Published evidence, however, as well as the objectivity and potential standardization of AMH level and the convenience of testing any time throughout the menstrual cycle, leans towards AMH level becoming the gold-standard biomarker to evaluate ovarian reserve and predict ovarian response to stimulation.


PubMed | Univfy Inc., University of Glasgow and Glasgow Center for Reproductive Medicine
Type: Journal Article | Journal: Fertility and sterility | Year: 2015

To compare antimllerian hormone (AMH) and antral follicle count (AFC) separately and in combination with clinical characteristics for the prediction of live birth after controlled ovarian stimulation.Retrospective development and temporal external validation of prediction model.Outpatient IVF clinic.We applied the boosted tree method to develop three prediction models incorporating clinical characteristics plus AMH or AFC or the combination on 2,124 linked IVF cycles from 2006 to 2010 and temporally externally validated predicted live-birth probabilities with an independent data set comprising 1,121 cycles from 2011 to 2012.None.Predictive power (posterior log of odds ratio compared to age, or PLORA), reclassification, receiver operator characteristic analysis, calibration, dynamic range.Predictive power, was highest for the AMH model (PLORA = 29.1), followed by the AMH-AFC model (PLORA = 28.3) and AFC model (PLORA = 22.5). The prediction errors were 1% to <5% in each prognostic tier for all three models, except for the predicted live-birth probabilities of <10% in the AFC model, where the prediction error was 8%. The improvement in predictive power was highest for the AMH model: 76.2% improvement over age alone relative to 59% improvement for AFC and 73.3% for the combined model. Receiver operating characteristic analysis demonstrated that the AMH and the combined model had comparable discrimination (area under the curve = 0.716) and similar prediction error for high and low strata of live-birth prediction, with an improvement of 6.3% over age alone.The validated prediction model confirmed that AMH when combined with clinical characteristics can accurately identify the likelihood of live birth with a low prediction error. AFC provided no added predictive value beyond AMH.


PubMed | Glasgow Center for Reproductive Medicine
Type: Journal Article | Journal: Fertility and sterility | Year: 2012

The changes in the relationships between circulating antimllerian hormone, the size of the primordial follicle pool, and follicular recruitment before and through the reproductive years have now been clarified, and show dynamic changes through sexual development. The constant relationship between the number of follicles and circulating antimllerian hormone exists only after the age of 25 years, implying that the association between follicular recruitment and follicular survival to the later stages of development is not constant across the reproductive life course. This commentary assesses the factors that may underlie these relationships and their clinical implications for reproductive health.


PubMed | Glasgow Center for Reproductive Medicine
Type: Journal Article | Journal: Reproductive biomedicine online | Year: 2013

The new Gen II assay for anti-Mllerian hormone (AMH) shows good stability and reliability in serum, but analyses of stability in whole blood are lacking. Testing the effects of storage of whole-blood samples at room temperature revealed significant increases in the measured value of AMH of 31% over 4 days (P<0.001). The effect is temperature dependent, with storage at 4C showing markedly reduced increments. Further, samples collected into serum tubes with gel separators and centrifuged within 5h (blood cells and serum physically separated within the collection tube) showed reliable stability over a period of more than 5 days.

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