Use of Stimulated Serum Estradiol Measurements for the Prediction of Hyperresponse to Ovarian Stimulation in in Vitro Fertilization (IVF)

Abstract

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 ≥15 oocytes at retrieval and/or peak E 2 > 10000 pmol/L, or cancellation due to ≥30 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 E 2 measured on stimulation day 5 (area under the receiver operating characteristic curve (ROC AUC ) 0.75 and 0.81, respectively). For extreme-response the predictive accuracy of E 2 measured on stimulation day 3 or 5 was comparable (ROC AUC 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.

Integrins β1 and β3 are biomarkers of uterine condition for embryo transfer

“…Our results showed that P4 attenuated the negative regulatory effect of E 2 on integrin β3. It is known that P4 can inhibit the proliferative effect of E 2 on endometrium by down-regulating the expression of E 2 receptors [24]. While this antagonistic effect of P4 on E 2 is generally believed to influence the completeness of the secretory transformation of endometrium [20]; during the embryo implantation process, a high E 2 level will cause the window of uterine receptivity to rapidly close [1].…”

Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline

“…Finally, serum estradiol concentrations were also significantly associated with OHSS (17)(18)(19)(20)(21)(22)(23)(24)33). In the majority of these studies, the mean estradiol value in patients with OHSS was >3,500 pg/mL.…”

Pre-hCG variables associated with occurrence of ascites in IVF/ICSI patients at moderate risk of developing OHSS: A pilot investigation

“…Many investigators have shown that an elevated concentration of estradiol during ovarian stimulation constitutes a risk factor for OHSS [3,5,22,23,35,37,38]. However, as mentioned above, patients presented with serum estradiol of ≥6000 pg/ml and/or more than 30 follicles, or where coasting or other preventive measures for managing OHSS had been applied, were not included in the present study cohort.…”