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BACKGROUND To review the accuracy of multivariate models for the prediction of ovarian reserve and pregnancy in women undergoing IVF compared with the antral follicle count (AFC) as single test. METHODS We performed a computerized MEDLINE and EMBASE search to identify articles published on multivariate models for ovarian reserve testing in patients undergoing IVF. In order to be selected, articles had to contain data on the outcome of IVF in terms of either pregnancy and/or poor response and on the prediction of these events based on a multivariate model. For the selected studies, sensitivity and specificity of the test in the prediction of poor ovarian response and non-pregnancy were calculated. Overall performance was assessed by estimating a summary receiver operating characteristic (ROC) curve, which was compared with the ROC curve for the AFC as the current best single test. RESULTS We identified 11 studies reporting on the predictive capacity of multivariate models in ovarian reserve testing. All studies reported on the prediction of poor ovarian response, whereas none reported on the occurrence of pregnancy. The sensitivity for prediction of poor ovarian response varied between 39% and 97% and the specificity between 50% and 96%. Logistic regression analysis indicated that cohort studies provided a significantly better discriminative performance than case-control studies. As cohort studies are superior to case-control studies, further analysis was limited to the cohort studies. For the cohort studies, a summary ROC curve could be estimated, which had a shape similar to that previously made for the AFC. CONCLUSIONS The accuracy of multivariate models for the prediction of ovarian response in women undergoing IVF is similar to the accuracy of AFC. No data are available on the capacity of these models to predict pregnancy, let alone live birth. On the basis of these findings, the use of more than one single test for the assessment of ovarian reserve cannot currently be supported.

The age-related decline of the success in IVF is largely attributable to a progressive decline of ovarian oocyte quality and quantity. Over the past two decades, a number of so-called ovarian reserve tests (ORTs) have been designed to determine oocyte reserve and quality and have been evaluated for their ability to predict the outcome of IVF in terms of oocyte yield and occurrence of pregnancy. Many of these tests have become part of the routine diagnostic procedure for infertility patients who undergo assisted reproductive techniques. The unifying goals are traditionally to find out how a patient will respond to stimulation and what are their chances of pregnancy. Evidence-based medicine has progressively developed as the standard approach for many diagnostic procedures and treatment options in the field of reproductive medicine. We here provide the first comprehensive systematic literature review, including an a priori protocolized information retrieval on all currently available and applied tests, namely early-follicular-phase blood values of FSH, estradiol, inhibin B and anti-Müllerian hormone (AMH), the antral follicle count (AFC), the ovarian volume (OVVOL) and the ovarian blood flow, and furthermore the Clomiphene Citrate Challenge Test (CCCT), the exogenous FSH ORT (EFORT) and the gonadotrophin agonist stimulation test (GAST), all as measures to predict ovarian response and chance of pregnancy. We provide, where possible, an integrated receiver operating characteristic (ROC) analysis and curve of all individual evaluated published papers of each test, as well as a formal judgement upon the clinical value. Our analysis shows that the ORTs known to date have only modest-to-poor predictive properties and are therefore far from suitable for relevant clinical use. Accuracy of testing for the occurrence of poor ovarian response to hyperstimulation appears to be modest. Whether the a priori identification of actual poor responders in the first IVF cycle has any prognostic value for their chances of conception in the course of a series of IVF cycles remains to be established. The accuracy of predicting the occurrence of pregnancy is very limited. If a high threshold is used, to prevent couples from wrongly being refused IVF, a very small minority of IVF-indicated cases (approximately 3%) are identified as having unfavourable prospects in an IVF treatment cycle. Although mostly inexpensive and not very demanding, the use of any ORT for outcome prediction cannot be supported. As poor ovarian response will provide some information on OR status, especially if the stimulation is maximal, entering the first cycle of IVF without any prior testing seems to be the preferable strategy.

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 approximately 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.