PDF(Pubmed)
Abstract：
Unexplained euploid embryo transfer failure (UEETF) is a frustrating and unanswered conundrum accounting for 30 to 50% of failures in in vitro fertilization using preimplantation genetic testing for aneuploidy (PGT-A). Endometriosis is thought by many to account for most of such losses and menstrual suppression or surgery prior to the next transfer has been reported to be beneficial. In this study, we performed endometrial biopsy in a subset of women with UEETF, testing for the oncogene BCL6 and the histone deacetylase SIRT1. We compared 205 PGT-A cycles outcomes and provide those results following treatment with GnRH agonist versus controls (no treatment). Based on these and previous promising results, we next performed a pilot randomized controlled trial comparing the orally active GnRH antagonist, elagolix, to oral contraceptive pill (OCP) suppression for 2 months before the next euploid embryo transfer, and monitored inflammation and miRNA expression in blood, before and after treatment. These studies support a role for endometriosis in UEETF and suggest that medical suppression of suspected disease with GnRH antagonist prior to the next transfer could improve success rates and address underlying inflammatory and epigenetic changes associated with UEETF.
摘要：
无法解释的整倍体胚胎移植失败（UEETF）是一个令人沮丧且未解决的难题，使用非整倍体的植入前遗传测试（PGT-A），占体外受精失败的30％至50％。许多人认为子宫内膜异位症是大多数此类损失的原因，据报道，在下一次转移之前进行月经抑制或手术是有益的。在这项研究中,我们对一部分UEETF女性进行了子宫内膜活检，检测癌基因BCL6和组蛋白脱乙酰酶SIRT1。我们比较了205个PGT-A周期的结果，并提供了GnRH激动剂治疗后与对照组（未治疗）的结果。基于这些和以前有希望的结果，接下来，我们进行了一项先导随机对照试验，比较了口服活性GnRH拮抗剂，elagolix,在下一次整倍体胚胎移植前，口服避孕药（OCP）抑制2个月，监测血液中的炎症和miRNA表达，治疗前后。这些研究支持子宫内膜异位症在UEETF中的作用，并表明在下一次转移之前用GnRH拮抗剂对可疑疾病的医学抑制可以提高成功率并解决与UEETF相关的潜在炎症和表观遗传变化。
