Ovarian response to 150 µg corifollitropin alfa in a GnRH-antagonist multiple-dose protocol: a prospective cohort study

Abstract

The incidence of low (<6 oocytes) and high (>18 oocytes) ovarian response to 150 µg corifollitropin alfa in relation to anti-Müllerian hormone (AMH) and other biomarkers was studied in a multi-centre (n = 5), multi-national, prospective, investigator-initiated, observational cohort study. Infertile women (n = 212), body weight >60 kg, underwent controlled ovarian stimulation in a gonadotrophin-releasing hormone-antagonist multiple-dose protocol. Demographic, sonographic and endocrine parameters were prospectively assessed on cycle day 2 or 3 of a spontaneous menstruation before the administration of 150 µg corifollitropin alfa. Serum AMH showed the best correlation with the number of oocytes obtained among all predictor variables. In receiver-operating characteristic analysis, AMH at a threshold of 0.91 ng/ml showed a sensitivity of 82.4%, specificity of 82.4%, positive predictive value 52.9%and negative predictive value 95.1% for predicting low response (area under the curve [AUC], 95% CI; P-value: 0.853, 0.769-0.936; <0.0001). For predicting high response, the optimal threshold for AMH was 2.58 ng/ml, relating to a sensitivity of 80.0%, specificity 82.1%, positive predictive value 42.5% and negative predictive value 96.1% (AUC, 95% CI; P-value: 0.871, 0.787-0.955; <0.0001). In conclusion, patients with serum AMH concentrations between approximately 0.9 and 2.6 ng/ml were unlikely to show extremes of response.

The performance of the Elecsys® anti-Müllerian hormone assay in predicting extremes of ovarian response to corifollitropin alfa

“…To the best of our knowledge, this is the first study to analyse the ability of the automated Elecsys® AMH assay to predict ovarian response in a CFA antagonist protocol. The AUC for the prediction of low ovarian response in this study was 0.883, which is in line with previous studies reporting AUCs between 0.836 and 0.929 with other assays (Oehninger et al, 2015;Lerman et al, 2017;Baker et al, 2018;Scheinhardt et al, 2018;Jacobs et al, 2019). Similarly, the AUC for the prediction of high ovarian response was 0.865, which is in line with previous reports varying between 0.821 and 0.890 (Polyzos, et al, 2013;Oehninger et al, 2015;Lerman et al, 2017;Scheinhardt et al, 2018;Anckaert et al, 2019).…”

“…Regarding AMH optimal cut-off levels for the prediction of the extremes of ovarian response, the cut-off of 1.0 ng/ ml, identified as the value with maximal sensitivity and specificity for predicting low response, seems to be comparable with previous studies and close to the proposed cut-offs defined by the Bologna criteria (Ferraretti et al, 2011). Baker et al (2018) reported a cut-off of 0.93 ng/ml in the prediction of four or fewer oocytes retrieved, whereas Lerman et al (2017) and Oehninger et al (2015) described a cut-off of 0.91 ng/ml and 1.03 ng/ml, respectively, as the most accurate to predict six or fewer oocytes retrieved.…”

“…Therefore, a cut-off point with a higher specificity at the expense of a lower sensitivity was selected for high responders. The cutoff of 2.25 ng/ml is similar to the cut-offs of 2.24-3.52 ng/ml previously suggested using the manual assays (Polyzos et al, 2013;Oehninger et al, 2015;Lerman et al, 2017). As far as AFC is concerned, this biomarker also showed a good clinical performance in predicting low and high responders (AUC 0.879 and 0.822, respectively).…”

“…Anti-Müllerian hormone has proven its clinical utility in the prediction of ovarian response among different ovarian stimulation protocols (Anckaert et al, 2012;Baker et al, 2018). In patients stimulated with CFA, previous studies have also reported AMH as the best predictor of ovarian response (Polyzos et al, 2013;Oehninger et al, 2015;Lerman et al, 2017). These studies, however, were carried out with manual plate-based ELISA assays, with inherent variability within and between laboratories (Zuvela et al, 2013).…”

“…Therefore, a wide range of markers have been proposed as predictors of ovarian response. Antral follicle count (AFC) and anti-Müllerian hormone (AMH) are now recognized as the most accurate (Broer et al, 2011;Martínez et al, 2013;Polyzos et al, 2013;Lerman et al, 2017;Scheinhardt et al, 2018). The advantages of AMH include its low intraand inter-cycle variability (Van Disseldorp et al, 2010;Polyzos et al, 2013;Kissell et al, 2014;Gracia et al, 2018), as well as the fact that it is less prone to observer biases compared with AFC (Iliodromiti et al, 2015).…”