无创性子宫内膜容受性评价体系的构建以及针刺干预治疗的研究

Although in vitro fertilization and embryo transfer (IVF-ET) has being widely used in infertility treatment, the chance to get pregnant after embryo transfer remains to be improved.To make a successful implantation, both embryo quality and endometrial receptivity are crucial,the latter even plays more important roles. In our previous study, we reported transfer of vitrified-warmed blastocysts yielded higher implantation and clinical pregnancy rates compared with fresh blastocys transfer on ovarian stimulation cyles due to better endometrial receptivity. Our studies also show that gene expression of endometrium changed under stimulation, adversely affecting endometrial receptivity. However, to study endometrium receptivity is invasive, therefore the clinical application is limited. To establish a clinically applicabe approach to determine endometrium receptivity, in this study, we collect exfoliated cervical cells rather than emdometrium tissue, to investigate marker genes expressed in cervical cells representing endometrium receptivity. Correlation between cervical cell marker genes with clinical outcome (implantation rate,pregnancy rate) will be studied, prospectively. on top of it, acupuncture applied in ovarian stumulation period is to be ivestgated to improve endometrium receptivity in this project.Molecular mechanism under biology between candidate marker genes and receptivity will be investigated well. This non-invasive approach might help to avoid embryo transfer to unfriendly endometrium therefore optional embryo transfer timing would be determined, which will improve efficiency of human IVF. This non-invasive technique could be applied to clinical practice.

体外受精-胚胎移植（IVF-ET）技术在不孕症治疗中被广泛应用，但妊娠率尚有待提高。在IVF治疗中，良好的胚胎质量和子宫内膜容受性是着床成功的关键。本课题组前期研究发现，在玻璃化冷冻保存的囊胚移植周期，更好的子宫内膜容受性显著提高临床妊娠率，促排卵治疗导致子宫内膜容受性不良是IVF治疗的重要障碍之一。但子宫内膜取样检测其容受性有创伤性，临床应用价值有限。本课题无创性采取IVF患者宫颈脱落细胞，研究其基因表达，与子宫内膜表达的容受性相关基因比对分析，探讨宫颈细胞标志基因与胚胎移植结局的相关性,探讨宫颈细胞标志基因与胚胎着床关系的分子生物学机制。同时评价卵泡期采用针刺治疗改善子宫内膜容受性的疗效，并探讨其可能机制。宫颈细胞容受性相关标志基因的发现能够指导胚胎移植时机，减少移植失败，能够提高体外受精胚胎移植的治疗效率。本无创性技术有广泛临床推广价值

体外受精-胚胎移植（IVF-ET）技术在不孕症治疗中被广泛应用，但妊娠率尚有待提高。在IVF治疗中，良好的胚胎质量和子宫内膜容受性是着床成功的关键。本课题组前期研究发现，更好的子宫内膜容受性显著提高临床妊娠率，但子宫内膜取样检测其容受性有创伤性，临床应用价值有限。本课题无创性采取IVF患者宫颈脱落细胞，研究其基因表达，得到上调基因2,193个和下调基因1,088个；其中上调基因中参与细胞粘附功能的基因显著富集；有18个下调基因与角质化有关，在参与角质化包膜形成的基因中成显著富集，另外还有与一些代谢通路等相关的基因。选择其中表达最显著改变的两个基因SLPI与FLT作为标志基因进行下一步的定量PCR验证和临床验证，同时探讨了标志基因的DNA甲基化改变，发现在未妊娠组样本中SLPI启动子区C位点的甲基化。.在针刺治疗中发现可提高子宫内膜转化日的激素水平，改善子宫内膜下血流，可能提高临床妊娠率。研究其基因表达，发现针刺治疗后，有高达16,520个基因发生了显著上调；而只有1,087个基因发生了显著下调。显著上调基因中，表达量上调最高的基因是GSGL1、microRNA MIR663B、MIR24-2、MIR663等，在非针刺治疗组中都没有表达，因此可以作为潜在的针刺治疗效果评判和优化疗效的marker。.以宫颈细胞容受性相关标志基因结合B超和生化检查等一系列评价方法，能够指导胚胎移植时机，减少移植失败，同时配合针刺治疗，更能够提高体外受精胚胎移植的治疗效率。本无创性技术进一步深化后有广泛临床推广价值。