Embryo Transfer Strategies for Women with Recurrent Implantation Failure During the Frozen-thawed Embryo Transfer Cycles:Sequential Embryo Transfer or Double-blastocyst Transfer?

Objective Both sequential embryo transfer(SeET)and double-blastocyst transfer(DBT)can serve as embryo transfer strategies for women with recurrent implantation failure(RIF).This study aims to compare the effects of SeET and DBT on pregnancy outcomes.Methods Totally,261 frozen-thawed embryo transfer cycles of 243 RIF women were included in this multicenter retrospective analysis.According to different embryo quality and transfer strategies,they were divided into four groups:group A,good-quality SeET(GQ-SeET,n=38 cycles);group B,poor-quality or mixed-quality SeET(PQ/MQ-SeET,n=31 cycles);group C,good-quality DBT(GQ-DBT,n=121 cycles);and group D,poor-quality or mixed-quality DBT(PQ/MQ-DBT,n=71 cycles).The main outcome,clinical pregnancy rate,was compared,and the generalized estimating equation(GEE)model was used to correct potential confounders that might impact pregnancy outcomes.Results GQ-DBT achieved a significantly higher clinical pregnancy rate(aOR 2.588,95%CI 1.267–5.284,P=0.009)and live birth rate(aOR 3.082,95%CI 1.482–6.412,P=0.003)than PQ/MQ-DBT.Similarly,the clinical pregnancy rate was significantly higher in GQ-SeET than in PQ/MQ-SeET(aOR 4.047,95%CI 1.218–13.450,P=0.023).The pregnancy outcomes of GQ-SeET were not significantly different from those of GQ-DBT,and the same results were found between PQ/MQ-SeET and PQ/MQ-DBT.Conclusion SeET relative to DBT did not seem to improve pregnancy outcomes for RIF patients if the embryo quality was comparable between the two groups.Better clinical pregnancy outcomes could be obtained by transferring good-quality embryos,no matter whether in SeET or DBT.Embryo quality plays a more important role in pregnancy outcomes for RIF patients.

Recurrent Implantation Failure and Low Molecular Weight Heparin

Implantation of the embryo into the endometrium is the first step in the establishment of pregnancy. This process is complex, and depends on many factors. Recurrent implantation failure is a source of distress to patients and specialists. It is defined as failure to achieve a viable pregnancy, following “>3 embryo transfers with high quality embryos or the transfer of ≥ 10 embryos in multiple transfers”. Thrombophilic conditions that contribute to recurrent implantation failure are the main concern in this review. The mechanism of implantation failure is believed to be due to decreased blood flow to the endometrium and placenta which can hinder normal endometrial receptivity leading to miscarriage. Defects in early placentation resulting in pregnancy failure, have focused attention on the therapeutic potential of low molecular weight heparin in the implantation process. Heparin has a role at all stages of implantation to improve pregnancy outcomes. There are controversies in literature regarding the association between thrombophilia and recurrent implantation failure and available literature regarding this issue is very heterogeneous. Various investigators, have shown that women with RIF are more likely to have a thrombophilia disorder, yet a clear cause cannot be acknowledged from these studies. Heparin treatment has been evaluated in several studies, showing conflicting evidence. However, several studies have pointed out that it may play a role in a subset of patients who presents a thrombophilia mutation, thus the group of patients that might benefit is needed to be identified. This review is dedicated to evaluate the published literature about the role of low molecular weight heparin in case of recurrent implantation failure with or without the presence of thrombophilia.

Ectopic Pregnancy in Cases of Recurrent Implantation Failure and Cases of Recurrent Early Pregnancy Loss

Objectives: To calculate the incidence of ectopic pregnancy in cases with recurrent early pregnancy loss and cases of recurrent implantation failure. Methods and materials: This is a retrospective cohort study. 200 women were recruited from the infertility clinic at shat by maternity university hospital seeking fertility. 100 of them were with history of recurrent implantation failure (RIF) and 100 with history of recurrent pregnancy loss (RPL). Revisiting their hospital files for the history of ectopic pregnancy was done. Results: 8% of cases of RPL had history of ectopic pregnancy while only 6% of cases of RIF had the history. There was no significant difference between the two groups (p = 0.579). There was significantly higher incidence of ectopic pregnancy in both groups if compared with the general population (p = 0.0001 and 0.043) in RPL and RIF consecutively. Conclusions: RPL and RIF may be considered as a risk factor for ectopic pregnancy.

Assessment of Sub-Endometrial Junction Zone by 3-Dimensional Transvaginal Ultrasound in Unexplained Recurrent Implantation Failure and Its Effect on ICSI Outcomes

BACKGROUND: Sub-endometrial junction zone (JZ) plays an important role in most of reproductive functions. OBJECTIVE: To find out the effect of the sub-endometrial JZ thickness assessment by 3-D trans-vaginal ultrasound (TVUS) on intracytoplasmic sperm injection (ICSI) outcomes in patients with unexplained recurrent implantation failure (RIF). SETTING: ART Unit of Obstetrics and Gynecology Department, Faculty of Medicine, South Valley University, Qena, Egypt. DURATION: From April 2016 to October 2018. STUDY DESIGN: A prospective observational study. METHDS: Fifty couples with history of unexplained RIF in previous ICSI cycles and prepared for another ICSI cycle (group I) and fifty couples with unexplained infertility prepared for ICSI for the first time (group II) had been included in this study. At time of ovum pick up, 3-DTVUS was done for all cases in both groups for assessment of sub endometrial junction zone thickness and correlated with ICSI outcome. RESULTS: There were statistically significant differences between group I and group II in JZ thickness in the 3 uterine regions (fundus, anterior and posterior walls) with p 0.001, but there were mildly statistically significant differences between both groups in chemical and clinical pregnancy rates with p < 0.01. CONCLUSIONS: The thickness of JZ in patients with history of unexplained RIF was higher than those with unexplained infertility scheduled for ICSI. The JZ thickness was inversely correlated with increased embryo implantation rates in ICSI procedures, the thinner the JZ thickness was associated with higher pregnancy rates (both chemical and clinical pregnancy rates).

Effect of heparin on recurrent IVF-ET failure patients

Objective:To elucidate the possible role of unfractionated heparin in patients with failed repeated in in vitro fertilization and embryo transfer(IVF-ET)and thrombophilia.Methods:This case control study evaluated the efficacy of the unfractionated heparin in increasing the pregnancy and implantation ratio in women with recurrent IVF-ET failures.Eighty-six women received in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)with a record of three or more previous IVF-ET failures.Participants were randomly distributed into two groups.Group A(n=43)received unfractionated heparin 5000 IU twice daily,and group B(n=43)did not take any antithrombotic drugs.Coagulation abnormalities such as factor桋Leiden(FVL)mutation,methylene tetra hydro folate reductase(MTHFR)mutation and prothrombin mutation(F栻)were evaluated.Age,body mass index,basal follicular stimulating hormone,basal estradiol,duration of infertility,and number of IVF-ET failures were compared between two groups.Results:45.0%and 17.4%of women were pregnant with and without MTHFR and prothrombin mutation,respectively,when they received unfractionated heparin treatment.The implantation rate was more in group A(12.5%)than group B(4.3%)and differences in the fertilization rate of the two groups were observed(27.7%vs.35.9%).The clinical pregnancy rate per cycle was remarkably more in group A(30.2%)than group B(14.0%).Conclusions:Heparin is a safe and valuable treatment for patients with repeated IVF-ET failures.The clinical pregnancy and implantation rates are higher in the heparin-treated group in contrast with the control group.

Immediate Effect of Electro-acupuncture on Endometrial Blood Flow in Patients with Recurrent Implantation Failure:A Randomized Controlled Trial

Objective To investigate the immediate effects of electro-acupuncture(EA)on endometrial blood flow among recurrent implantation failure(RIF)patients.Methods Eighty RIF patients,enrolled from March 2022 to December 2022,were randomly allocated into either the EA group(40 cases)or the waiting-list(WL)group(40 cases)by using a random number table.The EA group underwent acupuncture at points of Shenting(GV 24),Baihui(GV 4),Benshen(GB 13),bilateral Zigong(EX-CA 1),Huangshu(KI 16),Sanyinjiao(SP 6)and Xuehai(SP10),and electric acupuncture apparatus was connected to EX-CA 1,KI 16,SP 6,and SP 10 with disperse-dense waves at 4/20 Hz frequencies for 30 min after transvaginal ultrasound,while the WL group received no intervention.The primary outcome measured was the endometrial volume blood flow.The secondary outcomes included the bilateral uterine artery index,endometrial volume,endometrial blood flow type,vascular distribution index(VI^(MV))for endometrial and ovary,clinical pregnancy rate,and embryo implantation rate.Results In the EA group,there was a notable decrease in the bilateral pulsatility index and a significant improvement in the endometrial blood flow type post-EA(P<0.05).Both the endometrial blood flow type and VI^(MV) for the endometrium and right ovary were markedly higher in the EA group compared to the WL group post-treatment(P<0.05).Conversely,no significant disparities were observed in vascular index,flow index,vascular blood flow index,uterine arterial blood flow indices,endometrial volume,clinical pregnancy rate and embryo implantation rate between the two groups after treatment(P>0.05).Besides,no adverse events related to EA were observed.Conclusions EA can promptly ameliorate VI^(MV) for the endometrial and right ovary,and endometrial blood flow type.Future randomized controlled trials are warranted to investigate the long-term effects of EA on blood flow of RIF patients and its implications for pregnancy outcomes.(Trial registration No.ChiCTR2200057377).

Macrophage polarization disorder in the endometrial immune microenvironment may contribute to recurrent implantation failure

Objective:To investigate the role and mechanisms by which macrophages(MΦ)contribute to the immune environment of the endometrium in cases of recurrent implantation failure(RIF).Methods:Endometrial transcriptome data from women with and without RIF(control group)were collected.The CIBERSORT software was used to determine the abundance of immune cells within the endometrial tissue based on expression profiles.Weighted gene co-expression network analysis was used to identify crucial regulatory genes and pathways.Results:Application of CIBERSORT confirmed significant infiltration of macrophages in the RIF group.SOX6,TTC21A,KLHL31,NFIA,TNNT1,TPM1,CPVL,FUS,PEX5,and SLC43A3 were all closely correlated with M2 and M0 macrophages.Metascape and DisNor analyses revealed that these genes contribute to the regulation of macrophage polarization via the Wnt signaling pathway.Conclusion:This study identified dysregulation of macrophage polarization within the immune microenvironment of the endometrium in patients with RIF.A comprehensive analysis was conducted to investigate the potential mechanisms underlying this disorder.Dysregulation of macrophage polarization in the endometrium of patients with RIF is strongly associated with the Wnt signaling pathway.

Integrated bioinformatics analysis to identify key genes and pathways involved in the endometria of patients with recurrent implantation failure undergoing in vitro fertilization and embryo transfer

Objectives: Recurrent implantation failure (RIF) is a challenging clinical problem that occurs in approximately 10% of patients undergoingin vitro fertilization and embryo transfer. Because of the varied criteria for RIF, as well as differences in the time and methods of endometrial biopsy, previous studies have not reached an agreement regarding the key genes and pathways of RIF. In this study, bioinformatic analyses were performed in a homogeneous population with consistent biopsy conditions to explore the molecular mechanisms and identify key RIF-associated genes and pathways in the endometrium.Methods: Seven datasets from the Gene Expression Omnibus database were reviewed in detail, and GSE111974, GSE103465, and GSE26787 were included for further analysis. Common differentially expressed genes (DEGs) were identified using the GEO2R online tool. Gene Ontology and pathway enrichment analyses were performed and a protein–protein interaction (PPI) network was constructed. The RNA and protein expression files of the hub genes were obtained.Results: A total of 402 common DEGs were identified between patients with RIF and controls. The enrichment of these DEGs was mainly associated with tube morphogenesis, vasculature development, and positive regulation of cell migration. Pathway enrichment indicated that pathways involved in cancer, the vascular endothelial growth factor A-vascular endothelial growth factor receptor 2 signaling pathway, and cell cycle pathways were mainly involved. Moreover, a PPI network was constructed, and the three most significant submodules were mainly involved in rRNA processing and the regulation of proteolysis. The following ten DEGs with high degrees of connectivity were identified as hub genes:CDC42,VEGFA,MAP2K1,APP,CYCS,UBE2I,PLEK,LMNA,SMAD2, andATRX.Conclusion: Key genes and pathways identified in this study could improve our understanding of the underlying molecular events in RIF and be used as potential biomarkers and therapeutic targets. Further studies are required to confirm these results and explore the functions of hub genes in the endometrium during the implantation window in patients with RIF.

卵裂期胚胎复苏后培养至囊胚移植对RIF患者妊娠结局的影响

目的探讨对于反复种植失败(RIF)的患者,解冻卵裂期胚胎继续培养至囊胚移植能否改善患者的妊娠结局。方法回顾性分析2015年1月至2022年12月在我院生殖医学科接受冻融胚胎移植(FET)治疗的587例RIF患者的临床资料,根据不同的胚胎移植方案分为3组:解冻卵裂期胚胎继续培养至囊胚移植的为A组(n=45),解冻卵裂期胚胎移植的为B组(n=299),解冻囊胚移植的为C组(n=243);同时,将C组按解冻的囊胚发育时期分为移植第5天囊胚组(C-D5组,n=183)和移植第6天囊胚组(C-D6组,n=60),比较各组HCG阳性率、种植率、临床妊娠率、流产率、活产率等妊娠结局以及平均孕周和新生儿出生体重。结果选择解冻卵裂期胚胎继续培养至囊胚移植方案的患者初始有56例,11例患者(19.64%)因囊胚培养失败而取消周期。妊娠结局比较中,与B组相比,A组和C组的HCG阳性率(62.22%、57.61%vs.45.15%)、种植率(49.12%、44.48%vs.33.07%)及活产率(48.89%、44.03%vs.33.78%)均显著升高(P<0.05),3组间的流产率无显著差异(P>0.05);与C-D6组相比,A组和C-D5组的种植率(49.12%、48.70%vs.29.33%)、临床妊娠率(57.78%、56.28%vs.38.33%)及活产率(48.89%、49.18%vs.28.33%)均显著升高(P<0.05)。新生儿出生情况比较,A组的新生儿出生体重显著高于B组和C组(P<0.05),3组间的平均孕周无显著差异(P>0.05);A组和C-D6组新生儿出生体重显著高于C-D5组(P<0.05)。结论解冻卵裂期胚胎继续培养至囊胚移植可能在一定程度上能够改善RIF患者的妊娠结局。在FET周期中,若患者有D5囊胚冻存,建议优先解冻移植;若无冻存D5囊胚,可以尝试解冻卵裂期胚胎继续培养囊胚后移植,以获得较好的临床结局。

Sperm DNA fragmentation, recurrent implantation failure and recurrent miscarriage

Evidence is increasing that the integrity of sperm DNA may also be related to implantation failure and recurrent miscarriage （RM）. To investigate this, the sperm DNA fragmentation in partners of 35 women with recurrent implantation failure （RIF） following in vitro fertilization, 16 women diagnosed with RM and seven recent fathers （control） were examined. Sperm were examined pre- and post-density centrifugation by the sperm chromatin dispersion （SCD） test and the terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay. There were no significant differences in the age of either partner or sperm concentration, motility or morphology between three groups. Moreover, there were no obvious differences in sperm DNA fragmentation measured by either test. However, whilst on average sperm DNA fragmentation in all groups was statistically lower in prepared sperm when measured by the SCD test, this was not seen with the results from the TUNEL assay. These results do not support the hypothesis that sperm DNA fragmentation is an important cause of RIF or RM, or that sperm DNA integrity testing has value in such patients. It also highlights significant differences between test methodologies and sperm preparation methods in interpreting the data from sperm DNA fragmentation tests.

Advances in the Treatment of Recurrent Implantation Failure

Recurrent implantation failure(RIF)is a syndrome of complex etiology.Excluding the involvement of embryonic factors,RIF is characterized by women aged≤40 years who fail to achieve clinical pregnancy after at least four high-quality embryos transfer in a minimum of three fresh or frozen cycles.However,current methods in the treatment of RIF are controversial.So far,there are no reports of any criteria or guidelines,and the mechanism of RIF is still not clear.Herein,we summarize the pathogenesis of RIF and highlight recent methods in its treatment,to provide reference for the basic and clinical research on RIF.

RIF患者子宫内膜血流的络脉瘀阻理论研究

近年来,随着社会经济的高速发展及婚姻观念的改变,婚育年龄全面推迟,导致全球不孕症的发生率逐年上升。体外受精-胚胎移植(in vitro fertilization-embryo transfer,IVF-ET)是目前治疗不孕不育症的有效措施,但仍有部分患者经过多次优质胚胎移植后始终不能成功妊娠,使得患者面临巨大的心理负担和经济压力。因此,寻找更有效的治疗方法来帮助这些患者实现生育愿望迫在眉睫。当前,中医药的治疗贯穿辅助生殖全程,本文认为络脉瘀阻与微循环血流有互相耦合的作用,通过络脉瘀阻找到该病的症结所在,从而改善子宫内的血液灌注、促进子宫血液循环、降低子宫动脉阻力,提高胚胎种植率及临床妊娠率,为中医精准干预、精准治疗的临床应用与研究提供有力的依据。

RIF患者血浆外泌体源miRNA-183-5p通过靶向FOXO1影响蜕膜化

目的 探讨反复种植失败(RIF)患者血浆外泌体源性miR-183-5p通过靶向FOXO1影响子宫内膜基质细胞蜕膜化。方法 选取2021年8月1日至2021年12月31日在空军军医大学唐都医院生殖中心就诊的不孕患者,其中接受IVF治疗的20名RIF患者作为RIF组,20名同期无特殊病史的不孕患者作为对照组。采用实时荧光定量聚合酶链反应(qRT-PCR)检测两组不孕患者的血浆外泌体miR-183-5p的表达。从血浆中提取外泌体并与人子宫内膜间质细胞系(HESC)共培养48h后进行蜕膜化诱导,检测人胰岛素样生长因子结合蛋白-1(IGFBP-1)和催乳素(PRL)的表达。将miR-183-5p的agomir和antagomir转染HESC细胞并诱导蜕膜化后检测蜕膜化水平。通过qRT-PCR和免疫蛋白印迹(WB)实验检测miR-183-5p对于FOXO1 mRNA和蛋白表达水平的影响。结果 与对照组比较,RIF患者血浆外泌体能够抑制蜕膜化的子宫内膜基质细胞IGFBP-1和PRL的表达(t值分别为5.324、9.056,P<0.05)。与对照组比较,RIF患者血浆外泌体和子宫内膜组织高表达miR-183-5p((t值为-2.486、-4.821,P<0.05)。miR-183-5p能够抑制蜕膜化HESC细胞FOXO1的mRNA(agomir-NC vs agomir,t=3.120,P<0.05)和蛋白质的表达(对照组vs agomir,t=2.793,P<0.05)。结论 RIF患者血浆外泌体源性miR-183-5p能够抑制FOXO1表达,从而影响子宫内膜基质细胞蜕膜化。

基于网络药理学与分子对接技术探讨滋肾养血活血汤治疗胚胎反复种植失败作用机制

目的:通过网络药理学和分子对接技术探讨滋肾养血活血汤治疗胚胎反复种植失败(RIF)的作用机制。方法:利用中药系统药理数据库和分析平台(TCMSP)查找滋肾养血活血汤组成药物的化学成分,并筛选出有效活性成分及有效活性成分的作用靶点,通过GeneCards和人类在线孟德尔遗传(OMIM)数据库筛选RIF疾病靶点,将药物有效活性成分作用靶点与RIF疾病靶点取交集,借助String平台制作蛋白质-蛋白质互作(PPI)网络,然后利用Cytoscape3.9.1软件进行网络结构的拓扑分析筛选核心靶点,并构建中药-活性成分-靶点可视化网络图,利用DAVID在线数据库对核心靶点进行富集分析,采用AutoDock Vina软件对筛选出的主要药物有效活性成分和疾病关键靶点进行分子对接验证。结果:共获得122个药物有效活性成分和256个药物作用靶点,疾病相关靶点2215个,药物-疾病核心靶点36个。经筛选获得5个主要药物有效活性成分与9个疾病关键靶点。京都基因与基因组百科全书(KEGG)富集分析结果显示,滋肾养血活血汤治疗RIF可能主要通过调控缺氧诱导因子-1(HIF-1)、肿瘤坏死因子(TNF)、丝裂原活化蛋白激酶(MAPK)等多种信号通路发挥治疗作用。分子对接结果表明,β-谷甾醇与蛋白激酶B1(AKT1)、丹参酮ⅡA与HIF-1A、丹参酮ⅡA与TNF、槲皮素与HIF-1A对接活性较好。结论:滋肾养血活血汤可能通过槲皮素、山柰酚、木犀草素、β-谷甾醇、丹参酮ⅡA等与靶蛋白相互结合,调控多种信号通路发挥治疗RIF的作用。

玉屏风散加减颗粒联合分时间针刺治疗体外受精-胚胎移植反复移植失败的临床研究

目的分析玉屏风散加减颗粒联合分时间针刺治疗体外受精-胚胎移植(in vitro fertilization-embryo transfer,IVF-ET)胚胎植入前遗传学筛查(Pre-implantation Genetic Screening,PGS)反复失败(recurrent implantation failure,RIF)患者的临床治疗价值。方法选取2020年1月—2022年1月就诊于医院的RIF患者173例,采用随机数表法分为对照组(常规治疗)41例,观察组1(玉屏风散+常规治疗组)37例,观察组2(分时间针刺+常规治疗组)44例,观察组3(玉屏风散+分时间针刺+常规治疗)51例。对各组患者治疗前后子宫内膜容受性[子宫内膜厚度、血管化血流指数(vascu⁃larization-flow index,VFI)、血管化指数(vascularization index,VI)及血流指数(flow index,FI)]、汉密尔顿焦虑评量表-焦虑自评量表(Hamilton Anxiety Scale-Self-Rating Anxiety Scale,HAMA-SAS)评分及汉密尔顿抑郁量表(Hamilton de⁃pression scale,HAMD)评分和治疗后生化妊娠率、临床妊娠率、早期流产率、异位妊娠率及活产率结果进行分析。结果治疗后观察组3子宫内膜厚度、VFI、VI及FI高于对照组(P<0.05);各观察组HAMA-SAS及HAMD评分均低于对照组(P<0.05);观察组3生化妊娠率及临床妊娠率高于对照组,且各观察组产活率均高于对照组(P<0.05),但各观察组早期流产率与异位妊娠率与对照组相比差异无统计学意义(P>0.05)。结论玉屏风散加减颗粒联合分时间针刺治疗能显著提高RIF患者生化妊娠率、临床妊娠率及产活率,其作用机理可能是改善内膜厚度,增加子宫血流动力学参数,促进内膜生长,提高子宫内膜容受性且减低患者移植失败的焦虑抑郁情绪,调节舒畅情志,从而改善RIF患者妊娠结局。

反复种植失败与复发性流产的病因比较

目的了解反复种植失败(RIF)和复发性流产(RPL)患者的病因差异。方法选择2018年6月至2021年6月在中山大学附属第一医院生殖中心就诊的315例RIF患者和376例RPL患者为研究对象,进行一般资料及病因资料收集,比较其一般资料及病因构成差异。并采用多因素回归分析这两种疾病病因的相对风险度。结果RIF患者慢性子宫内膜炎、子宫内膜息肉、子宫内膜异位症、子宫内膜异位症合并子宫内膜息肉、卵巢储备功能减退病因比例均高于RPL患者,RIF患者不明原因病因比例低于RPL患者(P均<0.05)。多因素Logistic回归分析显示,RIF患者中病因为慢性子宫内膜炎(OR=3.044,95%CI 1.849~5.011,P<0.001)、子宫内膜息肉(OR=3.769,95%CI 1.670~8.510,P<0.001)、子宫内膜异位症(OR=3.812,95%CI 2.131~6.819,P<0.001)、卵巢储备功能减退(OR=2.175,95%CI 1.285~3.683,P=0.004)比RPL患者更为多见,RIF患者中抗米勒管激素水平低(OR=0.917,95%CI 0.864~0.973,P=0.004)的情况也较RPL患者多见。结论慢性子宫内膜炎、子宫内膜息肉、子宫内膜异位症、抗米勒管激素水平下降及卵巢储备功能减退等现象,在RIF患者中更为普遍,后续人工辅助生殖的工作实践中临床医师应强化对上述病变的筛查和监测。

反复种植失败患者种植窗期子宫自然杀伤细胞功能相关参数的分析及其临床意义

目的 探究种植窗期子宫自然杀伤(uNK)细胞的发育和功能状况与不明原因反复种植失败(RIF)的关联。方法 收集2021年9月至2023年8月在石家庄市第四医院生殖医学中心行IVF-ET助孕的61例患者的临床数据及其黄体中期内膜样本,根据移植周期结果分为RIF组(种植失败≥3个周期,n=39)和对照组(助孕1个周期即获得临床妊娠,n=22)。采用免疫组织化学(IHC)法检测uNK细胞并计算百分比,采用逆转录多聚合酶链式反应(RT-PCR)测定子宫内膜白介素15(IL-15)、成纤维细胞生长因子诱导分子14(Fn-14)、白介素18(IL-18)及肿瘤坏死因子样弱凋亡诱导因子(TWEAK)的mRNA水平,并计算IL-15/Fn-14 mRNA和IL-18/TWEAK mRNA比值,比较两组患者的一般资料和妊娠结局,分析uNK细胞功能参数间的差异。结果 RIF组和对照组间的年龄、体质量指数(BMI)、基础窦卵泡数(AFC)、移植日内膜厚度、不孕年限、不孕类型、抗苗勒管激素(AMH)和基础性激素水平比较,差异均无统计学意义(P>0.05)。RIF组的移植周期数及胚胎移植数目显著高于对照组(P<0.05);两组间的移植胚胎种类比较无显著性差异(P>0.05)。RT-PCR结果显示,IL-15、Fn-14、IL-18及TWEAK的mRNA水平在两组间无显著差异(P>0.05),但RIF组中的IL-15/Fn-14 mRNA及IL-18/TWEAK mRNA比值均显著高于对照组(P<0.05)。uNK细胞功能分析中,与对照组相比,RIF组黄体中期子宫内膜uNK细胞百分比显著升高(4.0%vs.3.0%,P<0.05),且IL-18/TWEAK mRNA比值紊乱比例显著上升(56.4%vs.45.5%,P<0.05),其中过度激活占51.3%,低激活占5.1%。结论 RIF可能与种植窗期uNK细胞的过度激活和激活不足有关。

复方玄驹胶囊治疗反复胚胎种植失败患者的临床效果及对子宫内膜的影响

目的探讨复方玄驹胶囊治疗反复胚胎种植失败(RIF)患者的临床效果及对子宫内膜容受性的影响。方法选取在本院生殖医学中心行体外受精-胚胎移植(IVF-ET)治疗,反复种植失败后经中医辨证属肾阳虚型,并拟再次行胚胎移植的116例患者,将其随机分为治疗组(55例)和对照组(61例)。治疗组采用复方玄驹胶囊联合人工周期内膜准备治疗,对照组采用人工周期内膜准备治疗。比较两组的治疗效果。结果治疗组的雌二醇(E_(2))水平及子宫内膜厚度高于对照组,差异具有统计学意义(P<0.05);两组的孕激素(P)水平及子宫内膜分型比较,差异无统计学意义(P>0.05)。两组的胚胎着床率、临床妊娠率、流产率及异位妊娠率比较,差异无统计学意义(P>0.05);治疗组的活产率高于对照组(P<0.05)。结论复方玄驹胶囊能够显著改善RIF患者的子宫内膜容受性指标,如E2和子宫内膜厚度,同时能使活产率提高。

基于阴道多普勒超声检查与临床资料构建不明原因不孕患者胚胎反复种植失败的预测模型

目的:观察不孕患者阴道多普勒超声检查结果与临床资料,构建预测模型分析其不明原因胚胎反复种植失败的影响因素。方法:选取2020年6月至2022年12月于本院不明原因胚胎反复种植失败的198例不孕患者为研究组,另取同期于本院胚胎种植成功的100例不孕患者为对照组,所有患者均接受阴道多普勒超声检查,对比两组阴道超声检查结果及临床资料,绘制受试者工作特征曲线(ROC)分析多因素预测不孕患者胚胎种植结果的价值,建立Logistic回归模型,识别不孕患者胚胎反复种植失败的影响因素,并进行模型验证。结果:研究组年龄大于对照组,AMH水平、自身免疫抗体异常率高于对照组,人工流产次数多于对照组(P<0.05);研究组移植日内膜厚度低于对照组,子宫动脉搏动指数高于对照组(P<0.05);绘制ROC曲线,结果显示,年龄、AMH、人工流产次数、自身免疫抗体、移植日内膜厚度、子宫动脉搏动指数对不孕患者胚胎种植结果具有一定预测价值(AUC=0.706、0.720、0.611、0.649、0.719、0.771);建立Logistic回归模型,结果显示,年龄大、人工流产次数多、自身免疫抗体异常、子宫动脉搏动指数高是不孕患者胚胎反复种植失败的危险因素(OR>1,P<0.05);AMH水平高、移植日内膜厚度高是不孕患者胚胎种植结果的保护因素(OR<1,P<0.05);根据Logistic回归模型得到回归方程,绘制ROC曲线发现,该模型预测不孕患者胚胎反复种植失败的AUC=0.928,P<0.05,模型可靠、稳定。结论:不孕患者胚胎反复种植失败可能与患者年龄、AMH水平、人工流产次数、自身免疫抗体、移植日内膜厚度、子宫动脉搏动指数等有关,临床可在胚胎种植前对患者进行阴道多普勒超声检查,结合临床资料综合评估患者胚胎种植结果,并采取针对性干预措施,以获得良好妊娠结局。

中医药治疗反复胚胎种植失败的现代研究进展

反复胚胎种植失败(RIF)是当今生殖医学研究的热点和难点问题,通过中医药辨证论治,取得较好疗效。文章将中医对RIF的认识从病因病机、中药及针灸治法方面进行梳理,总结RIF的主要病机为“本虚标实”,治法上补虚泻实,治疗上针药并用。现将近年来中医认识、治疗该病的相关文献综述如下,为今后RIF的治疗提供更多思路。