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

项目摘要 不孕症是子宫内膜异位症的常见并发症；而体外受精成功地治疗了子宫内膜异位症相关的疾病 不孕症、妊娠率比其他不孕症的病因要低。我们的长期目标 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，在不孕妇女中 随着子宫内膜异位症接受体外受精-胚胎移植(IVF-ET)，活产率将在 使用促性腺激素释放激素拮抗剂的患者与安慰剂患者进行比较。促性腺激素释放激素的应用 体外受精前使用促性腺激素释放激素激动剂(GnRH激动剂)被认为可以提高成功率，但研究规模较小，而且 鲜有报道的活产出生率。此外，这种方法的使用受到所需较长治疗时间的限制。 最近批准口服促性腺激素释放激素拮抗剂治疗子宫内膜异位症，为患有以下疾病的妇女提供了一个新的选择 正在接受体外受精的子宫内膜异位症患者。该药避免了肠外给药和长时间的延误。 与促性腺激素释放激素激动剂一样，启动作用。目前还没有关于促性腺激素释放激素疗效的研究 用于治疗子宫内膜异位症相关性不孕症的拮抗剂。我们建议进行一项随机临床试验。 口服促性腺激素释放激素受体拮抗剂对接受体外受精的子宫内膜异位症患者的预治疗 活出生率的主要结果。我们最近还展示了异常的microoRNAs 子宫内膜异位症患者的血液循环，我们随后将其作为生物标志物进行了验证 对活动性疾病的检测具有较高的敏感性和特异性。我们第二次提出这一疾病 生物标志物将识别将从GnRH拮抗剂预治疗中受益的女性，从而实现精确度 子宫内膜异位症相关性不孕症的医学治疗。这项拟议的研究具有重要意义，因为 不孕不育和子宫内膜异位症的发生，以及诊断和治疗的精确度不足。 我们使用一种创新的方法来识别子宫内膜异位症，以及一种旨在改善 子宫内膜异位症患者体外受精治疗的预后

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.