Stamatina Iliodromiti1, Richard A Anderson2, Scott M Nelson3. 1. School of Medicine, University of Glasgow, Glasgow G31 2ER, UK. 2. MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, UK. 3. School of Medicine, University of Glasgow, Glasgow G31 2ER, UK scott.nelson@glasgow.ac.uk.
Abstract
BACKGROUND: Stratified (individualized) medicine has been recognized as a key priority for policy makers and healthcare providers. The main principle of individualized care depends on utilizing patients' characteristics and biomarkers to predict prognosis, tailor intended treatment and predict treatment outcomes. In reproductive medicine a wide variety of biomarkers have been proposed as predictors of ovarian response; of these, anti-Müllerian hormone (AMH) and antral follicle count (AFC) are purported as exhibiting the most favourable analytical and performance characteristics. Previously AFC and AMH have been considered essentially interchangeable; however, recent trial data have questioned this postulation. The aim of this review is to present an analysis of the strengths and weaknesses of these biomarkers as predictors of ovarian response, using both physiological and technical perspectives. METHODS: We have conducted a systematic search of the most recent (to May 2014) relevant literature and summarized the existing evidence. Articles written in a language other than English without an available English translation were excluded. RESULTS: Both AMH values and AFC can be influenced by comparable technical, physiological and exogenous factors. AMH displays some variation within and between cycles, consistent with its physiological role in follicle development, and there are growing data on the impact of pharmacological treatments and pathological conditions but cycle-independent measurement is appropriate for clinical purposes. A range of issues with manual AMH assays may be resolving with the development of fully automated assays. Despite described standardization of its measurement technique, AFC is subject to marked inter- and intra-operator variability and the effects of external influences are likely to be comparable. Outwith some highly specialist centres, the intracyclic variation in AFC requires its measurement between Day 2 and 4 of the cycle. Observational studies suggest comparable performance characteristics for AMH and AFC in predicting poor and high ovarian response, but recent RCTs suggest markedly better performance for AMH. CONCLUSIONS: The performance characteristics of both AMH and AFC for the prediction of ovarian response to exogenous gonadotrophins have been inflated by single site observational cohorts, resulting in the viewpoint that AMH and AFC exhibit equivalent performance characteristics. Large scale multicentre RCTs, with centralized assay performance, have demonstrated that AMH is substantially the more accurate and robust biomarker, probably reflecting difficulties with standardization of AFC determination. While AFC retains some advantages, particularly immediacy and accessibility, international standardization of AMH combined with a stable automated assay is likely to enhance its performance as the biomarker of choice in predicting the ovarian response in assisted conception.
BACKGROUND: Stratified (individualized) medicine has been recognized as a key priority for policy makers and healthcare providers. The main principle of individualized care depends on utilizing patients' characteristics and biomarkers to predict prognosis, tailor intended treatment and predict treatment outcomes. In reproductive medicine a wide variety of biomarkers have been proposed as predictors of ovarian response; of these, anti-Müllerian hormone (AMH) and antral follicle count (AFC) are purported as exhibiting the most favourable analytical and performance characteristics. Previously AFC and AMH have been considered essentially interchangeable; however, recent trial data have questioned this postulation. The aim of this review is to present an analysis of the strengths and weaknesses of these biomarkers as predictors of ovarian response, using both physiological and technical perspectives. METHODS: We have conducted a systematic search of the most recent (to May 2014) relevant literature and summarized the existing evidence. Articles written in a language other than English without an available English translation were excluded. RESULTS: Both AMH values and AFC can be influenced by comparable technical, physiological and exogenous factors. AMH displays some variation within and between cycles, consistent with its physiological role in follicle development, and there are growing data on the impact of pharmacological treatments and pathological conditions but cycle-independent measurement is appropriate for clinical purposes. A range of issues with manual AMH assays may be resolving with the development of fully automated assays. Despite described standardization of its measurement technique, AFC is subject to marked inter- and intra-operator variability and the effects of external influences are likely to be comparable. Outwith some highly specialist centres, the intracyclic variation in AFC requires its measurement between Day 2 and 4 of the cycle. Observational studies suggest comparable performance characteristics for AMH and AFC in predicting poor and high ovarian response, but recent RCTs suggest markedly better performance for AMH. CONCLUSIONS: The performance characteristics of both AMH and AFC for the prediction of ovarian response to exogenous gonadotrophins have been inflated by single site observational cohorts, resulting in the viewpoint that AMH and AFC exhibit equivalent performance characteristics. Large scale multicentre RCTs, with centralized assay performance, have demonstrated that AMH is substantially the more accurate and robust biomarker, probably reflecting difficulties with standardization of AFC determination. While AFC retains some advantages, particularly immediacy and accessibility, international standardization of AMH combined with a stable automated assay is likely to enhance its performance as the biomarker of choice in predicting the ovarian response in assisted conception.
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