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: 10478236
• 负责人: Hugh Smith Taylor
• 金额: $ 123.22万
• 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/10478236
• 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; Placebo Control; 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; 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; 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 不育症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 与其他不育的病因相比，不育，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的不育症。我们的核心假设是，在不育的女人中 子宫内膜异位症经历了体外受精 - 胚胎转移（IVF-ET），现场出生率将有所提高 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 建议在IVF之前激动剂来改善成功，但是研究很少，很少 报告了实时出生率。此外，使用这种方法受所需的长时间治疗时间的限制。最近的 对子宫内膜异位症的口服GNRH拮抗剂的批准为子宫内膜异位女性提供了一种新颖的选择 正在进行IVF的人。该代理避免肠胃外管理和长时间的延迟 GnRH激动剂所看到的行动。没有关于GNRH拮抗剂的功效的研究 与子宫内膜异位相关的不育症的治疗。我们提出了一项口服GNRH的随机临床试验 患有IVF的子宫内膜异位症女性的拮抗剂预处理，主要结果 活产率。我们最近还证明了在患有女性的循环中的异常microRNA 子宫内膜异位症，我们随后已将其验证为具有高灵敏度的生物标志物，并且 检测活性疾病的特异性。第二，我们建议疾病生物标志物可以识别 将受益于GNRH拮抗剂预处理的妇女，允许一种精确的医学方法 与子宫内膜异位有关的不孕症。拟议的研究很重要，这是由于两种不育的常见发生 以及子宫内膜异位液以及诊断和治疗中缺乏精度。我们使用一种创新的方法 确定子宫内膜异位症以及一种新的干预措施，旨在改善女性的预后 子宫内膜异位症患IVF。