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

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 4/4

• 批准号: 10251322
• 负责人: STEVEN L YOUNG
• 金额: $ 25.67万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 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/10251322
• 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; Prognosis; 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; parenteral administration; precision medicine; predicting response; predictive marker; pregnant; 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 endometriosis 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；而试管受精成功地治疗了子宫内膜异位症-- 与其他不孕症原因相比，伴发不孕症、妊娠率降低。 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不孕症。我们的 中心假设是，在患有子宫内膜异位症的不孕妇女接受体外受精- 胚胎移植(IVF-ET)，使用GnRH拮抗剂预处理的人的活产率将会提高 与安慰剂相比。促性腺激素释放激素激动剂在体外受精前的应用 已经被建议提高成功率，然而研究规模很小，很少有报道。 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 口服促性腺激素释放激素拮抗剂的批准为患有子宫内膜异位症的妇女提供了一种新的选择 正在接受体外受精的子宫内膜异位症患者。该代理避免了肠外给药和 与GnRH激动剂一样，作用的启动延迟了很长时间。一直没有 促性腺激素释放激素拮抗剂治疗子宫内膜异位症不孕症的疗效研究 我们建议对女性口服促性腺激素释放激素拮抗剂前治疗进行随机临床试验。 接受体外受精的子宫内膜异位症患者，主要结局是活产率。我们 最近也显示出在患有癌症的妇女的循环中存在异常的microRNA 子宫内膜异位症，我们随后证实它是一个高水平的生物标志物 检测活动性疾病的敏感性和特异性。我们第二次提出这一疾病 生物标记物将识别将从GnRH拮抗剂预治疗中受益的女性，允许 子宫内膜异位症相关性不孕症的精准医学治疗。这项拟议的研究具有重要意义 由于不孕不育和子宫内膜异位症的共同发生以及缺乏精确度 在诊断和治疗方面都是如此。我们也使用一种创新的方法来识别子宫内膜异位症。 作为一种旨在改善子宫内膜异位症患者预后的新型干预措施 正在进行试管受精。