Repeated clomiphene citrate challenge testing in the prediction of outcome in IVF: A comparison with basal markers for ovarian reserve

Background: The aim of this study was to investigate the predictive accuracy and clinical value of performing either a single or a repeated clomiphene citrate challenge test (CCCT) in predicting poor response in IVF, compared to that of currently used basal ovarian reserve markers. Methods: Sixty-three patients undergoing their first IVF treatment were prospectively included. After measurement of basal markers on cycle day 3 (cd3) [FSH, inhibin B and antral follicle count (AFC)], a CCCT was performed. FSH and inhibin B levels were measured on day 10 (cd10). A second CCCT was performed after a washout period of one cycle. In all patients the tests were followed by an IVF treatment. Poor response (< 4 oocytes or cancellation due to impaired (<3 follicles) or absent follicular growth) was used as primary outcome measure. Results: Both the single as well as the repeated CCCT markers had a rather good discriminative potential for the prediction of poor response (area under the receiver operating characteristic curve (ROCAUC): FSH cd10 = 0.79, inhibin B cd10 = 0.79, mean FSH cd10 = 0.82 and mean inhibin B cd10 = 0.88). This compared well with the performance of the basal markers (FSH 0.82, inhibin B 0.72 and AFC 0.83). In a multivariate analysis on only the basal variables, FSH cd3 and AFC were selected (ROCAUC 0.89). Only stepwise forward analysis on the repeated CCCT variables revealed a better discriminating potential for the prediction of poor response (ROCAUC 0.92). At a specificity level of ∼0.97, sensitivity and the positive predictive value were marginally improved in the CCCT models. Conclusions: Performing a CCCT (single or repeated) has a rather good ability to predict poor response in IVF. However, it appears that the predictive accuracy and clinical value of the CCCT is not clearly better than that of basal FSH in combination with an AFC. Therefore, the use of the CCCT as a predictor of outcome in IVF should not be advocated.

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