Pre-IVF treatment with a GnRH antagonist in women with endometriosis - A prospective double blind placebo controlled trial 2/3

子宫内膜异位症女性 IVF 前使用 GnRH 拮抗剂治疗 - 一项前瞻性双盲安慰剂对照试验 2/3

• 批准号: 10259750
• 负责人: Nanette F. Santoro
• 金额: $ 26.67万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 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/10259750
• 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; 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.

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 以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， 子宫内膜异位症进行体外受精-胚胎移植（IVF-ET），活产率将改善那些 与安慰剂相比，GnRH拮抗剂预处理。促性腺激素释放激素（GnRH） 在IVF之前使用激动剂可以提高成功率，但研究规模较小， 报告的活产率。此外，这种方法的使用受到所需的长处理时间的限制。最近 批准口服GnRH拮抗剂治疗子宫内膜异位症为子宫内膜异位症妇女提供了新的选择 正在接受试管受精的人该药剂避免了胃肠外给药和开始给药的长时间延迟。 作用与GnRH激动剂相同。目前还没有关于GnRH拮抗剂对 治疗子宫内膜异位症相关的不孕症。我们提出了一项口服GnRH的随机临床试验 子宫内膜异位症妇女接受IVF的拮抗剂预处理，主要结局 活产率。我们最近还证实了在患有乳腺癌的女性的循环中存在异常的microRNA。 子宫内膜异位症，我们随后验证了其中的一组作为具有高灵敏度的生物标志物， 检测活动性疾病的特异性。我们其次提出，疾病生物标志物将识别 将受益于GnRH拮抗剂预治疗的女性，允许精确的医学方法， 子宫内膜异位症相关不孕症。由于不孕症的普遍发生， 以及缺乏精确的诊断和治疗。我们采用创新的方法 确定子宫内膜异位症以及一种新的干预措施，旨在改善妇女的预后， 子宫内膜异位症进行IVF。