Pre-IVF treatment with a GnRH antagonist in women with endometriosis - A prospective double blind placebo controlled trial 2/3

子宫内膜异位症女性 IVF 前使用 GnRH 拮抗剂治疗 - 一项前瞻性双盲安慰剂对照试验 2/3

• 批准号: 10025599
• 负责人: Nanette F. Santoro
• 金额: $ 27.21万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 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/10025599
• 关键词: Affect; Aftercare; Agonist; Alternative Therapies; Bioinformatics; Biological Markers; Biology; Birth Rate; Blood Circulation; Clinical Trials; Complication; Detection; Diagnosis; Disease; Embryo; Embryo Transfer; Estrogens; Etiology; Female infertility; 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; Placebos; Population; Pregnancy; Pregnancy Rate; Randomized Clinical Trials; Receptor Activation; Reporting; Research; Sample Size; Sensitivity and Specificity; Serum; Small RNA; Specificity; Testing; Time; Untranslated RNA; Woman; double-blind placebo controlled trial; endometriosis; endometriosis-related infertility; experience; implantation; improved; infertility treatment; innovation; microRNA biomarkers; novel; outcome forecast; parenteral administration; precision medicine; predicting response; predictive marker; primary outcome; prospective; protein biomarkers; randomized trial; 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.

抽象的 不孕是子宫内膜异位症的常见并发症； IVF 成功治疗子宫内膜异位症相关 与其他不孕原因相比，不孕不育的怀孕率会降低。我们的长期目标是 更好地识别和治疗子宫内膜异位症相关的不孕症。我们的中心假设是，在患有以下疾病的不孕女性中 子宫内膜异位症患者接受体外受精-胚胎移植（IVF-ET），活产率将会提高 与安慰剂相比，用 GnRH 拮抗剂预处理。促性腺激素释放激素（GnRH）的使用 有人建议在 IVF 之前使用激动剂可以提高成功率，但研究规模较小且很少 报告活产率。此外，该方法的使用受到所需长治疗时间的限制。最近的 口服 GnRH 拮抗剂治疗子宫内膜异位症的批准为患有子宫内膜异位症的女性提供了新的选择 正在接受体外受精的人。该药物避免了肠胃外给药和启动时间的延长延迟。 作用与 GnRH 激动剂相同。目前尚无关于 GnRH 拮抗剂治疗效果的研究 治疗子宫内膜异位症相关的不孕症。我们提出了一项口服 GnRH 的随机临床试验 对接受 IVF 的子宫内膜异位症女性进行拮抗剂预处理，其主要结果 活产率。我们最近还证明了患有以下疾病的女性循环中存在异常的 microRNA： 子宫内膜异位症，我们随后将其验证为具有高敏感性的生物标志物 检测活动性疾病的特异性。我们其次建议疾病生物标志物将识别 受益于 GnRH 拮抗剂预处理的女性，可采用精准医疗方法 子宫内膜异位症相关的不孕症。由于这两种不孕症的普遍发生，这项研究具有重要意义 和子宫内膜异位症以及诊断和治疗缺乏精确性。我们采用创新方法 识别子宫内膜异位症以及旨在改善子宫内膜异位症女性预后的新型干预措施 子宫内膜异位症正在接受 IVF。