Use of stimulated serum estradiol measurements for the prediction of hyperresponse to ovarian stimulation in in vitro fertilization (IVF)

Purpose: In ovarian stimulation an exaggerated ovarian response is often seen and is related to medical complications, such as ovarian hyperstimulation syndrome (OHSS), and increased patient discomfort. If it were possible to identify hyperresponders at an early stage of the stimulation phase, adaptation of the stimulation protocol would become feasible to minimize potential complications. Therefore, we studied the usefulness of measuring stimulated serum estradiol (E-2) levels in predicting ovarian hyperresponse. Methods: A total of 109 patients undergoing their first IVF treatment cycle using a long protocol with GnRH agonist was prospectively included. The E-2 level was evaluated on day 3 and 5 of the stimulation phase. Two outcome measures were defined. The first was ovarian hyperresponse (collection of greater than or equal to15 oocytes at retrieval and/or peak E-2 > 10000 pmol/L, or cancellation due to greater than or equal to30 follicles growing and/or peak E-2 > 15000 pmol/L, or OHSS developed). The second outcome measure comprised a subgroup representing the more severe hyperresponders, named extreme-response (cancellation or OHSS developed). Results: The data of 108 patients were analyzed. The predictive accuracy of E-2 measured on stimulation day 3 towards ovarian hyperresponse was clearly lower than that of E2 measured on stimulation day 5 ( area under the receiver operating characteristic curve (ROCAUC) 0.75 and 0.81, respectively). For extreme-response the predictive accuracy of E-2 measured on stimulation day 3 or 5 was comparable (ROCAUC 0.81 and 0.82, respectively). For both outcome measures the stimulated E-2 tests yielded only acceptable specificity with moderate sensitivity at higher cutoff levels. Prediction of extreme-response seemed slightly more effective due to a lower error rate. Conclusions: There is a significant predictive association between E-2 levels measured on stimulation day 3 and 5 and both ovarian hyperresponse and extreme-response in IVF. However, the clinical value of stimulated E-2 levels for the prediction of hyperresponse is low because of the modest sensitivity and the high false positive rate. For the prediction of extreme-response the clinical value of stimulated E-2 levels is moderate.