ChiCTR2200057985 版本V1.4 版本创建时间2022/11/29 10:54:10 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2200057985 

最近更新日期：

Date of Last Refreshed on：

 2022-11-29 10:48:30 

注册时间：

Date of Registration：

 2022-03-25 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

经皮穴位电刺激联合腔内理疗对肾阳虚薄型子宫内膜患者冻融胚胎移植周期子宫内膜容受性及S100A11表达的影响

Public title：

Effect of percutaneous acupoint electrical stimulation combined with endovascular physiotherapy on endometrial receptivity and S100A11 expression during freeze-thawing embryo transfer period in patients with thin endometrium with kidney-yang deficiency

注册题目简写：

English Acronym：

研究课题的正式科学名称：

基于卵泡液蛋白质组学的痰湿型PCOS不孕中医证候学研究

Scientific title：

Study on TCM Syndrome of Phlegm-Dampness PCOS Infertility Based on Follicular Fluid Proteomics

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

ChiMCTR2200005778

申请注册联系人：

夏芳丹 

研究负责人：

连方 

Applicant：

Xia Fangdan 

Study leader：

Lian Fang 

申请注册联系人电话：

Applicant telephone：

 +86 17862969233

研究负责人电话：

Study leader's
telephone：

+86 13706403122

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

 fancy_xfd@163.com

研究负责人电子邮件：

Study leader's E-mail：

 lianfangbangong@163.com

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

山东省济南市历下区文化西路42号

研究负责人通讯地址：

山东省济南市历下区文化西路42号

Applicant address：

42 Wenhua Road West, Lixia District, Jinan, Shandong

Study leader's address：

42 Wenhua Road West, Lixia District, Jinan, Shandong

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

山东中医药大学

Applicant's institution：

Shandong University ofTraditional Chinese Medicine

研究负责人所在单位：

山东中医药大学附属医院

Affiliation of the Leader：

Affiliated Hospital of Shandong University of Traditional Chinese Medicine

是否获伦理委员会批准：

是

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

 2019(044)

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

山东中医药大学附属医院生殖医学伦理委员会

Name of the ethic committee：

Reproductive Medicine Ethics Committee, Affiliated Hospital of Shandong University of Traditional Chinese Medicine

伦理委员会批准日期：

Date of approved by ethic committee：

 2022-02-28 00:00:00

伦理委员会联系人：

孙金龙

Contact Name of the ethic committee：

Sun Jinlong

伦理委员会联系地址：

山东省济南市历下区文化西路42号

Contact Address of the ethic committee：

42 Wenhua Road West, Lixia District, Jinan, Shandong

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 13256704356

伦理委员会联系人邮箱：

Contact email of the ethic committee：

研究实施负责（组长）单位：

山东省中医院

Primary sponsor：

Shandong Hospital of Traditional Chinese Medicine

研究实施负责（组长）单位地址：

山东省济南市历下区文化西路42号

Primary sponsor's address：

42 Wenhua Road West, Lixia District, Jinan, Shandong

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

山东

市(区县)：

济南

Country：

China

Province：

Shandong

City：

Jinan

单位(医院)：

山东省中医院

具体地址：

山东省济南市历下区文化西路42号

Institution
hospital：

Shandong Hospital of Traditional Chinese Medicine

Address：

42 Wenhua Road West, Lixia District, Jinan, Shandong

经费或物资来源：

国家自然基金面上项目：基于卵泡液蛋白质组学的痰湿型PCOS不孕中医证候学研究

Source(s) of funding：

General project of National Natural Science Foundation of China: Study on TCM Syndrome of Phlegm-Dampness PCOS Infertility Based on Follicular Fluid Proteomics

研究疾病：

薄型子宫内膜  

Target disease：

Thin endometrium

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 I期临床试验 

Study phase：

1

研究设计：

病例对照研究 

Study design：

Case-Control study 

研究目的：

不孕症是指夫妻有正常性生活未避孕1年而未孕者，或曾孕育过，而后无避孕1年未孕者，前者为原发性不孕，古称“全不产”；后者为继发性不孕，古称“断绪”[1-2]。其病因尚未完全明确，目前学术界认为不孕症的发生受内分泌、感染、解剖、免疫、遗传、子宫内膜容受性等各方面因素影响[3]。 辅助生殖技术的广泛开展，解决了部分不孕夫妇孕育难的问题，大量研究表明，女性子宫内膜厚度在8～12mm时，适合妊娠，因此薄型子宫内膜是导致其受孕失败的重要原因，成为所有临床医师面临的非常棘手的问题。在所有进行体外受精-胚胎移植的患者群体中，薄型子宫内膜患者约占2.4%［4］。结合现有研究，多数专家划定子宫内膜厚度＜7mm作为薄型子宫内膜的阈值，薄型子宫内膜对女性生育的影响非常显著，目前国内外观察一致显示，无论是在新鲜周期还是复融移植周期中，薄型子宫内膜患者的妊娠率较正常人群显著降低［5-6］。然而令人极为困扰的是，目前关于薄型子宫内膜尚无行之有效的治疗办法。 中医学中虽然并未有关于“薄型子宫内膜”的病名及临床症状等相关记载，但根据本病的临床表现可归属于中医学中“月经量少”、“闭经”及“无子”等疾病范畴，中医学认为月经及生殖有赖于“肾-天癸-冲任-胞宫轴”的正常运行。肾主生殖，肾精是人体胚胎发育的原始物质，有促进生殖机能的成熟、繁衍后代的重要作用。肾气是血的化生与运行的原动力，肾又是五脏阴阳之本，为冲任之本，冲为血海，任为阴脉之海，任通冲盛，月经以时下，故肾在月经生理中起主导作用，若肾气受损，精血亏乏，冲任虚损，则血海不足，子宫内膜失养而生长不足，进而导致月经稀少，形成薄型子宫内膜。年轻女性多爱生冷饮食，在月经过少患者中肾阳虚是比较典型的证型，薄型子宫内膜患者黄体期具有“宫寒”代谢特点且曾有研究指出薄型子宫内膜患者的好发体质以阳虚质、气虚质为主[7]。 自古以来便有肾虚导致不孕以及薄型子宫内膜的论述，正如《女科经纶》所说：“妇人不孕，亦有六淫七情之邪伤冲任。或宿疾淹留，传遗脏腑，或子宫虚冷，或气旺血衰，或血中伏热。又有脾胃虚损，不能荣养冲任。”《傅青主女科》所言：“妇人有素性恬淡，饮食少则平和，多则难受，或作呕泄，胸膈胀满，久不受孕。人以为赋禀之薄也，谁知是脾胃虚寒乎。夫脾胃之虚寒，原因心肾之虚寒耳。盖胃土非心火不能生，脾土非肾火不能化。心肾之火衰，则脾胃失生化之 权，即不能消水谷以化精微矣。既不能化水谷之精微，自无津液以灌溉于胞胎之中，欲胞胎有温暖之气以养胚胎，必不可得。”《圣济总录》曰：“妇人所以无子，由冲任不足，肾气虚寒故也。” 2.国内外研究进展 2.1薄型子宫内膜研究进展 薄型子宫内膜的病因多样、发病机制复杂，是不孕的常见病因，约有60%的胚胎种植失败与子宫内膜过薄密切相关[8]。子宫内膜损伤通常是由于宫腔内手术操作、子宫内膜感染、激素类药物作用、放射线、不明原因等多种因素造成的子宫内膜受损，导致子宫内膜变薄、再生困难，从而形成薄型子宫内膜，如宫腔部分或完全纤维化、宫腔缩窄、扭曲甚至消失，进一步可发展为宫腔粘连[9]，降低子宫内膜容受性，影响胚胎着床及发育，最终导致女性不孕，甚至影响IVF-ET成功率，难以维持妊娠。目前临床上多认为子宫内膜≤7mm即可影响正常妊娠，需临床干预，故大多将子宫内膜厚度≤7mm定义为薄型子宫内膜[10]而将子宫内膜厚度＜5mm者作为重度薄型子宫内膜的诊断标准，薄型子宫内膜的病理是指重度的炎症反应或子宫基底层受到损伤时，可使子宫内膜上皮及间质组织中的细胞及腺体数量骤降，失去内膜生理性分泌作用，炎性因子入侵子宫内膜并吞噬其表面的上皮细胞，导致间质外露，间质细胞弹性减少、纤维活性增加，子宫内膜功能层和基底层之间的正常界限模糊难以辨认，甚至完全消失，最终上皮细胞再生障碍，数量匮乏，上皮层对激素刺激无应答，炎性因子促使纤维组织粘连，间质中血管受损缺乏，子宫动脉血流高阻力，最终形成难治性薄型子宫内膜[11]。 目前，多认为形成薄型子宫内膜的原因有4个：1.宫腔手术：反复的宫腔操作损伤子宫内膜，这是目前临床上公认的最主要的病因之一其中最多见的是人工流产，包括刮宫术和清宫术等；2.宫腔感染：各种因素引起的病原体入侵宫腔，造成宫腔局部或完全感染，如累及内膜基底层，即可损伤子宫内膜并造成子宫内膜的再生困难；3.药物因素：Kodama等[12]发现口服某些避孕药5年以上即可对子宫内膜厚度造成负面影响,也有研究证实，不孕患者在接受促排卵治疗时，临床常用的促排卵药物及方案将影响子宫内膜的发育与厚度。4.原发性因素：当临床上除外了所有病理性因素后，仅表现为子宫内膜菲薄、反应性低下，可诊断为原发性薄型子宫内膜，有学者研究发现，这类患者可能与机体内血管内皮生长因子（VEGF）下调ERα的基因多态性有关[13]。 2.2子宫内膜容受性与S100A11蛋白 子宫内膜容受性是指子宫内膜对胚胎的接受能力即允许胚胎在子宫腔内进行定位、粘附、侵入等过程的能力。在每个月经周期中子宫内膜只有在一段特殊时期才具备良好的容受性这个时期通常被称为种植窗。良好的子宫内膜状态是成功妊娠的关键。据报道约2/3的植入失败或妊娠丢失病例可归因于子宫内膜的因素[14-16]。子宫内膜容受性不佳不仅影响胚胎的着床，还会影响胚胎远期的发育和胎盘的形成,因此良好的子宫内膜容受性是影响体外受精-胚胎移植结局的重要原因同时也是成功妊娠的关键。 S100A11属于蛋白家族成员,S100蛋白是一类多基因家族的低分子量蛋白,参与多种不同类型细胞和组织的多种生物行为[16-17]。包括S100A11在内的众多该家族成员的编码基因均位于1号染色体2区1带。这个区域编码众多与生长和分化有关的蛋白质的基因,S100A11在细胞增殖和分化中的作用因此倍受关注。 子宫内膜细胞中S100A11是胚胎种植的重要调节蛋白。能够调节胚胎种植的过程,原因在于：一方面,它能够控制一批跟子宫内膜容受息息相关的基因的表达,从而影响到子宫内膜容受状态的形成；另一方面,它参与调控子宫内膜细胞中型和型细胞因子的合成,使内膜细胞处于一种向性细胞因子偏移、而型细胞因子受抑的状态,这对于子宫内膜形成免疫耐受状态十分有益。子宫内膜S100A11通过影响滋养细胞球的粘附能力、子宫内膜容受的形成、子宫内膜免疫耐受的形成三个方面对胚胎种植产生影响。子宫内膜细胞中S100A11分布于内质网中,其中一个重要意义在于它能作用于内质网钙库上关键的钙离子摄取和释放的通道,从而维持子宫内膜细胞中钙离子的稳态。而外源性EGF对于子宫内膜细胞的重要作用在于,它能够促进钙离子的摄取和释放,使细胞产生钙振荡,这对胚胎着床意义非凡。更为重要的是,这个重要过程必须是在子宫内膜细胞中S100A11表达不受损的情况下才能够发生的[16-17]。 2.3经皮穴位电刺激与腔内理疗 经皮穴位电刺激与腔内理疗是基于传统中医药文化和现代医药生物物理科技的创新疗法。早在医圣张仲景《金匮要略·妇人杂病》中有:“蛇床子散方温阴中坐药”，开创了妇科阴道纳药治法的先河。古代阴道纳药是以性味辛热之药入于阴中，更好的发挥药物的作用。经皮穴位电刺激与腔内理疗系借鉴针灸体穴，结合阴道腔内红外波、微波与振动波理疗技术的创新型技术，使用腔内多功能治疗仪单电极和腹部双电极加速血液循环，改善盆腔局部营养状况促进新陈代谢，激活免疫功能。此过程为无创操作，简单且安全。且多项研究显示，腔内理疗对于IVF-ET患者的周期结局可产生良性影响[18-22]。传统中医学认为，血得热则行，配合取穴双侧子宫、双侧天枢、关元、气海、双侧三阴交，汇聚三阴经与阳明经气血，激发胞脉胞络血气，温通经脉，全息周流，以促进子宫卵巢血运与新陈代谢，?宫助孕。对卵巢功能衰退、薄型子宫内膜、反复种植失败等具有良好的疗效。  

Objectives of Study：

Infertility refers to the husband and wife have normal sexual life without contraception for 1 year and not pregnant, or had been pregnant, and then no contraception for 1 year not pregnant, the former is primary infertility, ancient said "not to produce"; The latter is secondary infertility, known as "broken thread" in ancient times [1-2]. The etiology of infertility has not been fully clarified, and the current academic community believes that the occurrence of infertility is affected by endocrine, infection, anatomy, immunity, genetics, endometrial receptivity and other factors [3]. The extensive development of assisted reproductive technology has solved the problem of infertility in some infertile couples. A large number of studies have shown that when the thickness of female endometrium is between 8 and 12mm, it is suitable for pregnancy. Therefore, thin endometrium is an important cause of pregnancy failure, which has become a very difficult problem faced by all clinicians. In all patients undergoing IN vitro fertilization-embryo transfer, patients with thin endometrium account for about 2.4% [4]. Combining with the existing research, most experts designated endometrial thickness < 7 mm as threshold of thin endometrium, thin endometrium influence on female fertility is very significant, consistent shows at home and abroad, in both fresh cycle and cycle, after melting transplantation thin endometrium in patients with pregnancy rate than normal population significantly reduced (5-6]. However, it is extremely disturbing that there is no effective treatment for thin endometrium. Though in TCM is not about "thin" of the film inside the uterus disease and clinical symptoms and related records, but according to the clinical manifestations of the disease attributable in traditional Chinese medicine "menstrual quantity is little", "menopause" and "no children" disease categories, traditional Chinese medicine thinks menstruation and the reproductive depends on "kidney - menstruation - blunt ren - cell palace shaft" normal operation. Kidney is the main reproductive, kidney essence is the human embryonic development of the original material, has the important role of promoting the reproductive function of maturity, reproduction. Kidney is a motive force of the blood of im and run, kidney and five zang-organs, Yin and Yang to blunt Ren Zhiben, rushed to blood, as for the sea of Yin meridians, ren tong sheng, menstruation to nowadays, so the renal physiology play a leading role in the menstrual cycle, if the kidney damage, JingXie kui, ren is deficient and blood deficiency, endometrial alongwith the growth, leading to menstruation is scarce, form a thin endometrium. Young women prefer raw and cold diet, and kidney-yang deficiency is a typical syndrome type in patients with little monthly passage. Patients with thin endometrium have the metabolic characteristics of "palace cold" during luteal phase, and studies have pointed out that patients with thin endometrium tend to have Yang deficiency and qi deficiency [7]. Since ancient times, there have been kidney deficiency leading to infertility and thin endometrium discussion, just as the Female section of the Economy and lun said: "women infertility, there are six erotic and seven feelings of evil injury chong Ren. Or lingering disease, transmission of internal organs, or uterine deficiency cold, or qi wang blood failure, or blood heat. He also has spleen and stomach deficiency and cannot nourish and chong ren." "Fu Qing main female" said: "women are well-conditioned and calm, eating less is peaceful, more is uncomfortable, or nausea, chest and diaphragm bulging, long time no conception. People think endowed with thin also, who knows is spleen and stomach deficiency cold. The deficiency of spleen and stomach caused by the deficiency of heart and kidney. Cover stomach soil without heart fire can not be born, spleen soil without kidney fire can not be changed. When the fire of the heart and kidney declines, the spleen and stomach lose biochemical function Right, that is, can not eliminate water grain to change the essence. We have no body fluid to irrigate the babies, so that they will have warm air to nourish them." The General Record of The Holy Economy says, "The woman had no children because of her lack of energy, and her kidney qi was deficient and cold." 2. Research progress at home and abroad 2.1 Research progress of thin endometrium Thin endometrium has various etiologies and complex pathogenesis, which is a common cause of infertility. About 60% of embryo implantation failure is closely related to thin endometrium [8]. Endometrial lesions are usually due to intrauterine operation, infection of endometrium, hormonal drugs, radiation and unknown reason caused by many factors such as endometrial damage, cause thinning of the film inside the uterus, regeneration is difficult, to form a thin endometrium, such as uterine, uterine cavity narrow, partial or total fibrosis distorted or even disappeared, Intrauterine adhesion can further develop [9], which reduces endometrial receptivity, affects embryo implantation and development, and ultimately leads to female infertility, and even affects the success rate of IVF-ET, making it difficult to maintain pregnancy. At present, a lot of clinical thought endometrial 7 mm or less to affect the normal pregnancy, to clinical intervention, so most of the endometrial thickness of 7 mm or less is defined as [10] thin endometrium and endometrial thickness < 5 mm as severe thin endometrium diagnostic criteria, thin endometrium pathological refers to severe inflammation or lesions in the basal layer of the uterus, Can make the endometrial epithelial and mesenchymal cells and glands Numbers have plummeted in the organization, and loss of endometrium physiological secretion, inflammatory factor invasion of endometrial epithelial cells on the surface of the swallowing its, lead to interstitial exposed, mesenchymal cells reduce, fiber activity increase elasticity and endometrial function layer and base layer, it is difficult to identify the distinction between the normal fuzzy even disappear completely, In the end, epithelial cell regeneration was impaired and the number was insufficient, the epithelium did not respond to hormone stimulation, inflammatory factors promoted adhesion of fibrous tissues, impaired and lack of blood vessels in the interstitium, and high resistance of uterine artery blood flow, resulting in the formation of refractory thin endometrium [11]. At present, it is believed that there are 4 reasons for the formation of thin endometrium: 1. Uterine surgery: repeated uterine operation damage to the endometrium, which is currently clinically recognized as one of the main causes of abortion, including curettage and uterine clearance; 2. 2. Intrauterine infection: pathogens caused by various factors invade the uterine cavity, causing local or complete infection of the uterine cavity, such as involving the endometrial basal layer, can damage the endometrial and cause endometrial regeneration difficulties; 3. Drug factors: Kodama et al. [12] found that oral administration of some contraceptives for more than 5 years can have a negative impact on endometrial thickness. Some studies have also confirmed that when infertility patients receive ovulation induction therapy, commonly used ovulation induction drugs and regimens will affect the development and thickness of endometrial. 4. Primary factors: When all pathological factors are excluded clinically, only thin endometrium and low response can be diagnosed as primary thin endometrium. Some scholars have found that such patients may be related to the down-regulated ERα gene polymorphism of vascular endothelial growth factor (VEGF) in the body [13]. 2.2 Endometrial receptivity and S100A11 protein Endometrial receptivity refers to the ability of endometrium to accept embryos, that is, to allow embryos to locate, adhere to, invade and other processes in the uterine cavity. During each menstrual cycle, the endometrium is receptive only during a specific period commonly referred to as the planting window. A good state of the endometrium is key to a successful pregnancy. It is reported that about 2/3 of implant failure or pregnancy loss cases can be attributed to endometrial factors [14-16]. Poor endometrial receptivity not only affects the implantation of embryos, but also affects the long-term development of embryos and the formation of placenta. Therefore, good endometrial receptivity is an important reason affecting the outcome of in vitro fertilization-embryo transfer and the key to a successful pregnancy. S100A11 is a member of protein family, and S100 protein is a low molecular weight protein of multi-gene family, which is involved in a variety of biological behaviors of different types of cells and tissues [16-17]. The encoding genes of many members of this family, including S100A11, are located in zone 1, region 2 of chromosome 1. This region encodes genes for many proteins involved in growth and differentiation, so S100A11's role in cell proliferation and differentiation is of particular interest. S100A11 is an important regulatory protein of embryo implantation in endometrial cells. It can regulate the process of embryo implantation for the following reasons: on the one hand, it can control the expression of a number of genes closely related to endometrial tolerance, thus affecting the formation of endometrial tolerance state; On the other hand, it is involved in regulating the synthesis of medium and type I cytokines in endometrial cells, making endometrial cells in a state of tropism and type I cytokines inhibition, which is very beneficial to the formation of endometrial immune tolerance state. Endometrium S100A11 affects embryo implantation by affecting the adhesion ability of trophoblast globules, the formation of endometrium receptivity and the formation of endometrium immune tolerance. In endometrial cells, S100A11 is distributed in the endoplasmic reticulum. One of the important significance is that S100A11 acts on the key calcium uptake and release channels in the calcium pool of the endoplasmic reticulum, thus maintaining calcium homeostasis in endometrial cells. The important role of exogenous EGF for endometrial cells is that it can promote the uptake and release of calcium ions, and make cells produce calcium oscillations, which is of great significance for embryo implantation. More importantly, this important process can occur only when the expression of S100A11 in endometrial cells is not impaired [16-17]. 2.3 Percutaneous acupoint electrical stimulation and endovascular physiotherapy Transcutaneous acupoint electrical stimulation and endovascular physiotherapy are innovative therapies based on traditional Chinese medicine culture and modern medicine biophysical technology. As early as in "Synopsis of golden Chamber · Miscellaneous Diseases of Women" written by the medical legend Zhang Zhongjing, "Cnithol Powder prescription to warm Yin and sit medicine in the middle", which pioneered the treatment of gynecological vaginal medicine. In ancient times, vaginal medicine was put into Yin with a sexual taste and hot medicine to better play the role of medicine. Transdermal acupoint electrical stimulation and intracavitary physical therapy refers to acupuncture body point, combined with the innovative technology of infrared wave, microwave and vibration wave physical therapy in the vaginal cavity, using single electrode and double electrode in the abdomen to accelerate blood circulation, improve the local nutritional status of the pelvic cavity to promote metabolism and activate immune function. This process is non-invasive, simple and safe. Moreover, a number of studies have shown that endovascular therapy can have a benign effect on the cycle outcome of IVF-ET patients [18-22]. Traditional Chinese medicine believes that blood heat line, with acupoint bilateral uterus, bilateral Tianshu, Guan Yuan, Qihai, bilateral sanyin intersection, convergence of Sanyin meridian and Yangming meridian qi and blood, stimulate cell veins cell collaterals blood gas, warm meridians, holographic circulation, to promote uterine ovarian blood transport and metabolism, ? uterine aid pregnancy. It has a good effect on ovarian function decline, thin endometrium and repeated implantation failure.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

（1）连续两次子宫内膜厚度<7mm而取消移植周期；
（2）年龄在25-35周岁之间；
（3）基础激素水平正常；
（4）月经周期正常，多周期B超监测排卵正常；
（5）近两个月内无宫腔操作史；
（6）冻融胚胎移植周期中至少1个Ⅱ级以上的优质胚胎

Inclusion criteria

(1) The transplantation cycle was cancelled when the endometrial thickness was less than 7mm for two consecutive times;
(2) Aged between 25 and 35;
(3) Normal basal hormone levels;
(4) Normal menstrual cycle and ovulation monitored by multi-cycle B-mode ultrasound;
(5) No history of intrauterine operation in the past two months;
(6) At least one high-quality embryo of grade ⅱ or above in the freeze-thaw embryo transfer cycle

排除标准：

（1）女方生殖内分泌异常；多囊卵巢综合征、子宫内膜异位症等；
（2）女方生殖道解剖结构异常不具备妊娠功能；
（3）输卵管重度积水；
（4）其他影响子宫内膜微环境的因素（内膜息肉、子宫内膜炎、子宫腺肌病等）；
（5）女方患有严重躯体或精神疾病不可以妊娠者；
（6）在治疗过程中因各种原因中断治疗，最终未能进行胚胎移植者。

Exclusion criteria：

(1) abnormal reproductive endocrine; Polycystic ovary syndrome, endometriosis, etc.;
(2) Abnormal anatomical structure of female reproductive tract does not have pregnancy function;
(3) severe hydrocephalus of fallopian tubes;
(4) Other factors affecting the endometrial microenvironment (endometrial polyps, endometritis, adenomyosis, etc.);
(5) if the woman is suffering from serious physical or mental disease and cannot conceive;
(6) Those who failed to carry out embryo transplantation due to various reasons during the treatment.

研究实施时间：

Study execute time：

从 From 2022-04-01 00:00:00至 To 2023-06-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2022-04-22 00:00:00 至 To 2023-04-30 00:00:00

干预措施：

Interventions：

组别：

理疗组

样本量：

 20

Group：

Therapy Group

Sample size：

干预措施：

腔内理疗

干预措施代码：

Intervention：

Cavity therapy

Intervention code：

组别：

非理疗组

样本量：

 20

Group：

Control Group

Sample size：

干预措施：

-

干预措施代码：

Intervention：

-

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 山东 

市(区县)：

 济南 

Country：

China

Province：

Shandong

City：

Jinan

单位(医院)：

 山东省中医院 

单位级别：

 三甲 

Institution
hospital：

Shandong Hospital of Traditional Chinese Medicine

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

钙结合蛋白

指标类型：

主要指标

Outcome：

S100A11

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

子宫内膜动脉血流

指标类型：

主要指标

Outcome：

Endometrial artery blood flow

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

子宫内膜厚度

指标类型：

主要指标

Outcome：

Endometial thickness

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

子宫内膜类型

指标类型：

主要指标

Outcome：

The type of endometrium

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

周期取消率

指标类型：

主要指标

Outcome：

Cycle cancellation rate

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

生化妊娠率

指标类型：

主要指标

Outcome：

Rate of biochemical pregnancy

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

临床妊娠率

指标类型：

主要指标

Outcome：

Rate of pregnancy

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

子宫内膜

组织：

子宫内膜

Sample Name：

Endometrium

Tissue：

Endometrium

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

标本中文名：

血液

组织：

子宫动脉

Sample Name：

Blood

Tissue：

Uterine Artery Blood Flow

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 25 岁 years
最大 Max age 35 岁 years

性别：

女性

Gender：

Female

随机方法（请说明由何人用什么方法产生随机序列）：

由实验主要实施人夏芳丹使用电脑随机抽样产生随机序列

Randomization Procedure (please state who generates the random number sequence and by what method)：

The main executor of the experiment, Xia Fangdan, used computer random sampling to generate random sequences

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：

Blinding：

是否共享原始数据：

IPD sharing

否No

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

无

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

no

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

SPSS

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

SPSS

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2022-03-25 00:17:14