3/4: Pre-IVF treatment with a GnRH antagonist in women with endometriosis - A prospective double blind placebo controlled trial (PREGNANT)

3/4：子宫内膜异位症女性接受 GnRH 拮抗剂进行 IVF 前治疗 - 一项前瞻性双盲安慰剂对照试验（怀孕）

• 批准号: 10684216
• 负责人: Emily S Jungheim
• 金额: $ 24.67万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 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/10684216
• 关键词: Affect; Aftercare; Agonist; Alternative Therapies; Bioinformatics; Biological Markers; Biology; Birth Rate; Circulation; Clinical Trials; Complication; Detection; Diagnosis; Disease; Embryo; Embryo Transfer; Estrogens; Etiology; Fertilization; Fertilization in Vitro; Flare; 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; Receptor Activation; Reporting; Research; Sample Size; Sensitivity and Specificity; Serum; 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; primary outcome; prospective; protein biomarkers; randomized trial; randomized, clinical trials; secondary outcome; success; therapy design; treatment response

Project Summary 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 micoRNAs 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.

项目摘要 不孕症是子宫内膜异位症的常见并发症;而IVF成功地治疗了子宫内膜异位症相关的 不孕症，与其他不孕症病因相比，怀孕率降低。我们的长远目标 是为了更好地识别和治疗子宫内膜异位症相关的不孕症。我们的中心假设是不孕妇女 子宫内膜异位症进行体外受精-胚胎移植（IVF-ET），活产率将提高， 与安慰剂相比，接受GnRH拮抗剂预治疗的受试者。促性腺激素释放激素的应用 已经建议在IVF之前使用促性腺激素释放激素（GnRH）激动剂可以提高成功率，但是研究规模较小， 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。 最近批准的一种口服GnRH拮抗剂治疗子宫内膜异位症为患有子宫内膜异位症的妇女提供了一种新的选择。 子宫内膜异位症患者正在接受IVF。该药剂避免了胃肠外给药和延长的延迟给药。 如GnRH激动剂所见的启动作用。目前还没有关于GnRH疗效的研究 用于治疗子宫内膜异位症相关不孕症的拮抗剂。我们提出了一项随机临床试验， 接受IVF的子宫内膜异位症妇女的口服GnRH拮抗剂预治疗， 活产率的主要结果。我们最近也证明了在细胞中的异常microRNA。 子宫内膜异位症妇女的循环，我们随后验证了其中一组作为生物标志物， 检测活动性疾病的高灵敏度和特异性。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， 治疗糖尿病相关不孕症的药物。这项研究具有重要意义，因为 不孕症和糖尿病的发生以及诊断和治疗缺乏准确性。 我们使用一种创新的方法来识别子宫内膜异位症以及一种新的干预措施，旨在改善 接受IVF的子宫内膜异位症妇女的预后。