Reproductive Medicine Collaborative Consortium: a randomized placebo-controlled trial of EGCG to improve fertility in women with uterine fibroids- Application 4/4

摘要 子宫肌瘤(子宫肌瘤)是全球妇女健康最重要的肿瘤威胁， 对有色人种妇女的影响不成比例，是不孕不育的重要原因。壁内和粘膜下 与未受影响的妇女相比，子宫肌瘤降低了怀孕的可能性。子宫肌瘤的手术切除是 具有高复发率和频繁的术后后果，如粘连。有一个 迫切需要创新有效的、非激素的、非手术的生育治疗方案 可能扭曲宫腔的子宫肌瘤。我们的长期目标是开发新的非激素治疗方法 子宫肌瘤。绿茶儿茶素，如表没食子儿茶素没食子酸酯(EGCG)在受孕和 怀孕了。EGCG通过调节细胞内信号通路抑制肿瘤生长的关键途径 增殖、转化、细胞凋亡和炎症。我们的团队评估了EGCG的疗效和安全性 在一项双盲、安慰剂对照的随机临床试验中，研究对象为有症状的子宫肌瘤妇女。在……里面 安慰剂组，肌瘤体积增加；然而，随机接受EGCG(800 mg/天)治疗的患者显示 肌瘤总体积显著减少。这些数据表明，EGCG减小了肌瘤的大小，并代表了 一种可能的非激素治疗妇女的子宫肌瘤追求怀孕。这项研究的目的是 进行一项随机临床试验，以确定EGCG对子宫肌瘤和后续妊娠的影响 寻求生育治疗的妇女。我们的中心假设是EGCG将缩小子宫肌瘤的大小并增加 怀孕的可能性。为了验证这一假设，我们提出了一项安慰剂对照临床试验来评估LIVE。 患有子宫肌瘤的不明原因不孕症妇女的分娩结局。受试者将被随机分配到 口服EGCG与安慰剂相比，为期7个月，磨合期为3个月，然后进行卵巢刺激 宫腔内人工授精最多4个周期。我们将在一项研究中确定EGCG的临床疗效 对654名寻求生育护理的妇女进行的随机研究；并确定寻求生育护理的妇女的妊娠结局 使用EGCG治疗的生育护理与安慰剂的比较。为达致招聘目标，督察已成立 财团。耶鲁大学将作为数据协调中心和临床站点，霍普金斯大学将协调单一 IRB并成为一个临床站点。伊利诺伊大学芝加哥分校的研究人员对 EGCG和临床试验，并将担任牵头PI。佛罗里达大学的调查人员有特殊的 有生殖医学经验的子宫肌瘤和不孕症临床试验方面的专业知识 网络。每个机构都有大量符合条件的患者和一流的生育中心。建议数 这项研究将对寻求生育护理的患有子宫肌瘤的女性产生巨大的积极影响。

Abstract Uterine leiomyomas (fibroids) are the most important neoplastic threat to women's health worldwide, disproportionately affect women of color and are a significant cause of infertility. Intramural and submucosal fibroids reduce the likelihood of pregnancy compared to unaffected women. Surgical removal of fibroids is afflicted with high recurrence rates and frequent postoperative consequences such as adhesions. There is a critical need for innovative effective, non-hormonal, non-surgical fertility treatment options for women with fibroids that may distort the uterine cavity. Our long-term goal is to develop novel non-hormonal treatments for uterine fibroids. Green tea catechins, such as epigallocatechin gallate (EGCG) is safe during conception and pregnancy. EGCG inhibits key pathways of tumor growth by modulating signaling pathways involved in cell proliferation, transformation, apoptosis and inflammation. Our team evaluated the efficacy and safety of EGCG in women with symptomatic uterine fibroids in a double-blinded, placebo-controlled randomized clinical trial. In the placebo group, fibroid volume increased; however, patients randomized to EGCG (800 mg/day) showed significant reduction in total fibroid volume. These data indicate that EGCG reduces fibroid size and represents a possible non-hormonal treatment for women with fibroids pursuing pregnancy. The objective of this study is to conduct a randomized clinical trial to determine the effect of EGCG on fibroids and subsequent pregnancy in women seeking fertility treatment. Our central hypothesis is that EGCG will reduce fibroid size and increase the likelihood of pregnancy. To test this hypothesis, we propose a placebo-controlled clinical trial to evaluate live birth outcomes for women with unexplained infertility who have uterine fibroids. Subjects will be randomized to either oral EGCG vs. placebo for up to 7 months with a 3-month run-in period followed by ovarian stimulation and intrauterine insemination for up to 4 cycles. We will determine the clinical efficacy of EGCG in a randomized study in 654 women pursuing fertility care; and determine pregnancy outcomes in women seeking fertility care treated with EGCG compared to placebo. To meet recruitment goals, the PIs have formed a consortium. Yale will serve as the data coordinating center and a clinical site, Hopkins will coordinate the single IRB and be a clinical site. Investigators at University of Illinois at Chicago have extensive experience with EGCG and clinical trials and will serve as lead PI. Investigators at the University of Florida have special expertise in clinical trials for fibroids and infertility treatment with prior experience in the Reproductive Medicine Network. Each institution has high volume of eligible patients and an excellent fertility center. The proposed research will have an immense positive impact on women with uterine fibroids that are seeking fertility care.