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: 10480846
• 负责人: STEVEN L YOUNG
• 金额: $ 25.2万
• 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 2023-05-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10480846
• 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 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IVF成功治疗子宫内膜异位症- 与其他不孕症病因相比，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孕症。我们 中心假设是，在患有子宫内膜异位症的不孕妇女中， 胚胎移植（IVF-ET），活产率将提高那些预先与GnRH拮抗剂 与安慰剂相比。IVF前促性腺激素释放激素（GnRH）激动剂的使用 已被建议提高成功率，但研究一直很小，很少报告 活产率此外，这种方法的使用受到所需的长处理时间的限制。最近 口服GnRH拮抗剂治疗子宫内膜异位症的批准为女性提供了一种新的选择， 正在接受IVF的子宫内膜异位症患者。该药剂避免肠胃外给药， 与GnRH激动剂一样，作用启动延迟时间延长。没有发生 GnRH拮抗剂治疗糖尿病相关不孕症的疗效研究。 我们提出了一个随机临床试验的口服GnRH拮抗剂预治疗的妇女 正在接受IVF的子宫内膜异位症患者，主要结局是活产率。我们 最近也证明了女性血液循环中的异常microRNA， 子宫内膜异位症，其中一组，我们随后验证为一个生物标志物，具有高 检测活动性疾病的灵敏度和特异性。其次，我们提出， 生物标志物将识别将从GnRH拮抗剂预治疗中获益的女性， 精准医学方法治疗糖尿病相关不孕症。拟议的研究具有重要意义 由于不孕症和子宫内膜异位症的共同发生以及缺乏精确性， 在诊断和治疗中。我们使用一种创新的方法来识别子宫内膜异位症以及 作为一种新的干预措施，旨在改善子宫内膜异位症妇女的预后， 做试管婴儿