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: 10025592
• 负责人: STEVEN L YOUNG
• 金额: $ 26.67万
• 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/10025592
• 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; 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.

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 与其他不育的病因相比，相关的不孕症，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的不育。我们的 中心假设是，在子宫内膜异位症的不育妇女中 胚胎转移（IVF-ET），用GNRH拮抗剂预处理的人将有效出生率提高 与安慰剂相比。在IVF之前使用促性腺激素释放激素（GNRH）激动剂 有人建议改善成功，但是研究很小，很少报道 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 口服GNRH拮抗剂用于子宫内膜异位症的批准为患有的女性提供了一种新颖的选择 正在进行IVF的子宫内膜异位症。该代理避免肠胃外管理和 GNRH激动剂所见，作用开始的长期延迟。没有 研究GNRH拮抗剂治疗子宫内膜异位相关的不育症的疗效。 我们提出了针对女性口服GNRH拮抗剂预处理的随机临床试验 正在接受IVF的子宫内膜异位症，其主要出生率的主要结果。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，我们随后验证了其较高的生物标志物 对活性疾病检测的敏感性和特异性。我们第二提出了这种疾病 生物标志物将确定将从GNRH拮抗剂预处理中受益的妇女，从而允许 精密医学方法与子宫内膜异位相关的不育。拟议的研究很重要 由于不育和子宫内膜异位症的常见发生以及缺乏精度 在诊断和治疗中。我们也使用一种创新的方法来识别子宫内膜异位症 作为一种新的干预措施，旨在改善子宫内膜异位女性的预后 经历IVF。