Characterization of gene expression profile during the implantation phase in IVF cycles in endometrium of women with recurrent implantation failure. Homo sapiens

With the rapid development of assisted reproductive techniques (ART), the number and quality of embryos have been optimized, but the embryo implantation rate has not been significantly improved yet. Recurrent implantation failure (RIF), a condition that is typically diagnosed in patients who fail to achieve clinical pregnancy after having undergone at least 3 times of embryo transfers (including a total of ≥4 good-quality embryos), is a challenging problem in ART treatment. Previous studies about RIF are limited to clinical trials and the detection of limited biomarkers within peripheral blood, but few about gene expression within local endometrial tissue and RIF, the key factors involved in RIF remain unclear. Our study was designed with an aim to compare the gene expression profile of RIF women with that of healthy proven fertile controls to explore the influence factors of endometrial receptivity and the mechanisms of RIF. Overall design: Two groups of 6 women were selected: women with RIF (n=3) and fertile control women (n=3). Patients were suffering from tubal obstruction (tubal obstruction factor on hydrosalpinx, salpingitis, etc. were excluded) or unexplained infertility. Women recruited in the RIF group had a history of implantation failure from at least three consecutive IVF attempts (including a total of ≥ 4 good-quality embryos). Specimens were obtained via pipe suction curettage from the patients on day LH + 7. Tissue samples were washed thoroughly with sterile normal saline to remove excess blood and mucous and then snap-frozen in liquid nitrogen for microarray analysis.

随着辅助生殖技术（Assisted Reproductive Techniques，ART）的快速发展，胚胎的数量与质量均得到优化提升，但胚胎着床率仍未实现显著提升。复发性着床失败（Recurrent Implantation Failure，RIF）是辅助生殖治疗中的棘手临床难题，该病症通常指至少接受3次胚胎移植（累计移植优质胚胎≥4枚）后仍未获得临床妊娠的患者群体。
既往针对RIF的研究多局限于临床试验及外周血有限生物标志物的检测，针对子宫内膜局部组织基因表达与RIF关联的研究相对匮乏，RIF相关的关键调控因素仍未明确。本研究旨在对比复发性着床失败患者与已证实生育能力的健康对照女性的子宫内膜基因表达谱，以探索子宫内膜容受性的影响因素及RIF的潜在发病机制。
总体实验设计：本研究纳入两组受试者，每组各6名女性，分别为RIF组（n=3）与可生育健康对照组（n=3）。所有受试患者均因输卵管阻塞或不明原因不孕入组，且排除合并输卵管积水、输卵管炎等继发性梗阻因素的病例。RIF组受试者均有至少连续3次体外受精-胚胎移植（In Vitro Fertilization and Embryo Transfer，IVF-ET）周期的胚胎着床失败史，且累计移植优质胚胎≥4枚。所有受试者均于黄体生成素（Luteinizing Hormone，LH）峰值后第7天（LH+7）接受宫腔吸刮术采集子宫内膜标本。采集的组织标本经无菌生理盐水充分冲洗以去除残留血液与黏液，随后置于液氮中快速冷冻，用于后续基因芯片分析（microarray analysis）。