Pre-IVF treatment with a GnRH antagonist in women with endometriosis - A prospective double blind placebo controlled trial (Pregnant) - Application 1/4

使用 GnRH 拮抗剂治疗子宫内膜异位症女性的 IVF 前治疗 - 前瞻性双盲安慰剂对照试验（怀孕） - 应用 1/4

• 批准号: 10700871
• 负责人: Hugh Smith Taylor
• 金额: $ 100.73万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-26 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10700871
• 关键词: Affect; Aftercare; Agonist; Alternative Therapies; Bioinformatics; Biological Markers; Biology; Birth Rate; Circulation; Clinical Trials; Complication; Detection; Diagnosis; Disease; Embryo; Embryo Transfer; Estrogens; Etiology; Fertilization; Fertilization in Vitro; Flare; Functional disorder; Gonadotropin Hormone Releasing Hormone; Gonadotropin-Releasing Hormone Receptor; Hormone Antagonists; Infertility; Inflammatory; Intervention; Live Birth; MicroRNAs; Modality; Molecular Profiling; Morphology; Oocytes; Oral; Pain; Patients; Placebo Control; Placebos; Population; Pregnancy; Pregnancy Rate; Prognosis; Receptor Activation; Reporting; Research; Sample Size; Sensitivity and Specificity; Serum; Specificity; Testing; Time; Untranslated RNA; Woman; antagonist; double-blind placebo controlled trial; endometriosis; endometriosis-related infertility; experience; implantation; improved; infertility treatment; innovation; microRNA biomarkers; novel; parenteral administration; precision medicine; predicting response; predictive marker; pregnant; primary outcome; prospective; protein biomarkers; randomized trial; randomized, clinical trials; secondary outcome; success; therapy design; treatment response

Abstract Infertility is a common complication of endometriosis; while IVF successfully treats endometriosis-associated infertility, pregnancy rates are diminished compared to other etiologies of infertility. Our long- term objectives are to better identify and treat endometriosis related infertility. Our central hypothesis is that in infertile woman with endometriosis undergoing in vitro fertilization-embryo transfer (IVF-ET), live birth rates will improve in those pretreated with GnRH antagonist compared to placebo. The use of gonadotropin releasing hormone (GnRH) agonist prior to IVF has been suggested to improve success, however studies have been small and rarely reported live birth rates. Further, use of this approach is limited by the long treatment time required. Recent approval of an oral GnRH antagonist for endometriosis provides a novel option for women with endometriosis who are undergoing IVF. This agent avoids parenteral administration and the prolonged delay in initiation of action as was seen with GnRH agonists. There have been no studies on the efficacy of GnRH antagonists for the treatment of endometriosis-related infertility. We propose a randomized clinical trial of oral GnRH antagonist pre-treatment for women with endometriosis who are undergoing IVF, with a primary outcome of live birth rate. We have also recently demonstrated aberrant microRNAs in the circulation of women with endometriosis, a panel of which we have subsequently validated as a biomarker with high sensitivity and specificity for the detection of active disease. We secondarily propose that disease biomarkers will identify women who will benefit from GnRH antagonist pre-treatment, allowing a precision medicine approach to endometriosis-related infertility. The proposed study is significant due to the common occurrence of both infertility and endometrioses as well as the lack of precision in both diagnosis and therapy. We use an innovative approach to identify endometriosis as well as a novel intervention designed to improve the prognosis of women with endometriosis undergoing IVF.

摘要 不孕症是子宫内膜异位症的常见并发症；而体外受精成功地治疗了子宫内膜异位症相关的疾病 不孕症、妊娠率比其他不孕症的病因要低。我们的长期目标是 以便更好地识别和治疗子宫内膜异位症相关性不孕症。我们的中心假设是，在患有不孕症的妇女中 接受体外受精-胚胎移植(IVF-ET)的子宫内膜异位症患者的活产率将会提高 GnRH拮抗剂与安慰剂的比较。促性腺激素释放激素的应用 体外受精前使用激动剂被认为可以提高成功率，然而这方面的研究很少，而且很少。 报告的活出生率。此外，这种方法的使用受到所需较长治疗时间的限制。近期 批准口服促性腺激素释放激素拮抗剂治疗子宫内膜异位症为子宫内膜异位症患者提供了一种新的选择 他们正在接受试管受精。该药避免了肠外给药和在启动时的长时间延迟 作用与GnRH激动剂相同。目前还没有关于促性腺激素释放激素拮抗剂的疗效的研究 子宫内膜异位症相关性不孕症的治疗。我们建议进行口服促性腺激素释放激素的随机临床试验 接受体外受精的子宫内膜异位症患者的拮抗剂预治疗，其主要结果是 活出生率。我们最近还发现，在患有癌症的妇女的血液循环中存在异常的microRNAs。 子宫内膜异位症，一个小组，我们随后验证为一个生物标志物具有高敏感性和 检测活动性疾病的特异性。我们第二次提出疾病生物标记物将识别 将受益于GnRH拮抗剂预治疗的女性，允许精准医学方法 子宫内膜异位症相关性不孕症。由于两种不孕症的共同发生，这项拟议的研究具有重要意义 以及子宫内膜异位症，以及在诊断和治疗方面缺乏精确度。我们使用一种创新的方法 确定子宫内膜异位症以及一种旨在改善子宫内膜异位症患者预后的新干预措施 接受体外受精的子宫内膜异位症。

项目成果

Pre-IVF treatment with a GnRH antagonist in women with endometriosis (PREGNANT): study protocol for a prospective, double-blind, placebo-controlled trial.

• DOI: 10.1136/bmjopen-2021-052043
• 发表时间: 2022-06-17
• 期刊: BMJ OPEN
• 影响因子: 2.9
• 作者: Taylor, Hugh;Li, Howard J.;Carson, Sandra;Flores, Valerie;Pal, Lubna;Robbins, Jared;Santoro, Nanette F.;Segars, James H.;Seifer, David;Huang, Hao;Young, Steven;Zhang, Heping
• 通讯作者: Zhang, Heping