Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China.
Front Endocrinol (Lausanne). 2023 Jan 20;14:1074347. doi: 10.3389/fendo.2023.1074347. eCollection 2023.
Reliable predictive models for predicting excessive and poor ovarian response in controlled ovarian stimulation (COS) is currently lacking. The dynamic (Δ) inhibin B, which refers to increment of inhibin B responding to exogenous gonadotropin, has been indicated as a potential predictor of ovarian response.
To establish mathematical models to predict ovarian response at the early phase of COS using Δinhibin B and other biomarkers.
Prospective cohort study in a tertiary teaching hospital, including 669 cycles underwent standard gonadotropin releasing hormone (GnRH) antagonist ovarian stimulation between April 2020 and September 2020. Early Δinhibin B was defined as an increment in inhibin B from menstrual day 2 to day 6 through to the day of COS. Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression with 5-fold cross-validation was applied to construct ovarian response prediction models. The area under the receiver operating characteristic curve (AUC), prevalence, sensitivity, and specificity were used for evaluating model performance.
Early Δinhibin B and basal antimüllerian hormone (AMH) levels were the best measures in building models for predicting ovarian hypo- or hyper-responses, with AUCs and ranges of 0.948 (0.887-0.976) and 0.904 (0.836-0.945) in the validation set, respectively. The contribution of the early Δinhibin B was 67.7% in the poor response prediction model and 56.4% in the excessive response prediction model. The basal AMH level contributed 16.0% in the poor response prediction model and 25.0% in the excessive response prediction model. An online website-based tool (http://121.43.113.123:8001/) has been developed to make these complex algorithms available in clinical practice.
Early inhibin B might be a novel biomarker for predicting ovarian response in IVF cycles. Limiting the two prediction models to the high and the very-low risk groups would achieve satisfactory performances and clinical significance. These novel models might help in counseling patients on their estimated ovarian response and reduce iatrogenic poor or excessive ovarian responses.
目前缺乏可靠的预测模型来预测控制性卵巢刺激（COS）中卵巢过度反应和反应不良。抑制素 B 的动态变化（Δ），即抑制素 B 对外源性促性腺激素的反应增加，已被证明是卵巢反应的潜在预测指标。
利用 Δ抑制素 B 和其他生物标志物建立预测 COS 早期卵巢反应的数学模型。
本研究为前瞻性队列研究，纳入 2020 年 4 月至 2020 年 9 月在一家三级教学医院接受标准促性腺激素释放激素（GnRH）拮抗剂卵巢刺激的 669 个周期。早期 Δ抑制素 B 定义为从月经第 2 天到第 6 天至 COS 日，抑制素 B 的增加量。采用 5 倍交叉验证的最小绝对收缩和选择算子（LASSO）逻辑回归构建卵巢反应预测模型。接受者操作特征曲线（ROC）下面积（AUC）、患病率、敏感性和特异性用于评估模型性能。
早期 Δ抑制素 B 和基础抗苗勒管激素（AMH）水平是预测卵巢低反应或高反应的最佳指标，在验证组中的 AUC 和范围分别为 0.948（0.887-0.976）和 0.904（0.836-0.945）。早期 Δ抑制素 B 在低反应预测模型中的贡献为 67.7%，在高反应预测模型中的贡献为 56.4%。基础 AMH 水平在低反应预测模型中的贡献为 16.0%，在高反应预测模型中的贡献为 25.0%。已开发了一个基于网络的在线工具（http://121.43.113.123:8001/），以便在临床实践中应用这些复杂的算法。
早期抑制素 B 可能是预测 IVF 周期卵巢反应的新型生物标志物。将这两个预测模型限制在高风险和极高风险组中，可以获得满意的性能和临床意义。这些新模型可能有助于对患者进行估计的卵巢反应咨询，并减少医源性卵巢低反应或高反应。
