乳酸菌阴道胶囊辅助治疗在行ART反复着床失败患者中的应用CSCD

目的 探究行辅助生殖技术(ART)反复着床失败患者应用乳酸菌阴道胶囊辅助治疗对子宫内膜容受性(ER)和阴道微生物的影响。方法选取2020年5月至2022年5月本院收治ART反复着床失败患者100例,根据治疗方式分为观察组(n=50)和对照组(n=50)。对照组采用常规治疗,观察组采用常规治疗联合乳酸菌阴道胶囊。比较两组的性激素水平(雌二醇、孕酮),内膜容积、子宫内膜厚度、血管血流指数(VFI)、内膜血流指数(FI)和阻力指数(RI)等子宫内膜容受性指标,阴道pH值、阴道菌群检出率和乳酸菌数量。结果 两组治疗前后血清雌二醇、孕酮水平比较,差异无统计学意义(P>0.05)。两组治疗前子宫内膜厚度、内膜容积、血管血流指数、内膜血流指数和阻力指数比较,差异无统计学意义(P>0.05)。治疗后观察组子宫内膜厚度、内膜容积和血管血流指数均高于治疗前(P<0.01)和对照组(P<0.05)。治疗前两组菌群检出率差异无统计学意义(P>0.05),治疗后两组菌群检出率均低于治疗前(P<0.05),治疗后观察组菌群检出率低于对照组(P<0.05)。两组阴道pH值均低于治疗前(P<0.001),治疗后观察组阴道pH值低于对照组(P<0.001)。两组阴道乳杆菌正常率均高于治疗前(P<0.05),治疗后观察组高于对照组(P<0.05)。两组胚胎着床率、临床妊娠率、早期流产率和持续妊娠率差异无统计学意义(P> 0.05)。结论 乳酸菌阴道胶囊治疗ART反复着床失败患者可以改善子宫内膜容受性和阴道菌群。     

冷冻胚胎移植周期中内膜形态及内膜厚度对妊娠结局的预测价值分析

目的:评价内膜厚度及内膜形态对于体外受精-胚胎移植中冷冻胚胎解冻复苏移植的临床妊娠结局的预测价值。方法:回顾性分析1521个冷冻胚胎解冻复苏移植周期,将患者按子宫内膜厚度分为4组,子宫内膜≤6 mm、6.1-8.0 mm、8.0-12 mm、12.0 mm,根据子宫内膜形态分为A型内膜、B型内膜、C型内膜。分别比较不同内膜厚度分组及不同内膜形态分组患者的年龄,移植胚胎数目、内膜准备方案构成比、移植胚胎类型(卵裂期胚胎、囊胚)构成比及各组间的临床妊娠率和活产率。采用ROC曲线分析子宫内膜厚度、形态对临床妊娠结局的预测价值。使用逐步回归分析内膜厚度、形态、年龄及移植胚胎类型与妊娠结局的相关性。结果:纳入1521个解冻复苏周期中按内膜厚度分为4组,各组周期数分别为96周期、454周期、893周期、78周期,各组间平均年龄分别为34.1±5.5岁、33.3±5.4岁、32.5±5.2岁、33.7±6.0岁(P0.05)。内膜厚度≤6 mm组临床妊娠率为31.3%,子宫内膜≤6mm、6.1-8.0 mm、8.0-12 mm、12.0 mm组临床妊娠率分别为48.5%、51.8%、47.4%(P0.05)。子宫内膜≤6 mm、6.1-8.0 mm、8.0-12 mm、12.0 mm组间活产率分别为18.8%、37.7%、44.6%、39.7%(P0.05)。A型、B型及C型内膜组周期数分别为920周期、189周期及412周期,三组间平均年龄分别为32.3±5.1、33.0±5.7、34.2±5.5岁(P0.05)。A型/B型及C型内膜组临床妊娠率分别为51.2%、46.6%及46.4%,三组间活产率分别为42.1%、36.0%及37.1%,三组间差异无统计学意义(P0.05)。子宫内膜厚度ROC曲线下面积为0.534(95%可信区间0.505-0.564),子宫内膜形态ROC曲线下面积为0.526(0.476-0.955)。逐步回归分析纳入内膜厚度、内膜形态、年龄、胚胎类型4个可变量,女方年龄(OR=0.929,P0.001),移植胚胎中囊胚比例(OR=1.595,P0.001)与临床妊娠率明显相关,内膜厚度(OR=1.054,P=0.05)及内膜形态(OR=0.864)与临床妊娠率无相关性。结论:虽然子宫内膜薄临床妊娠率下降,但是子宫内膜厚度与内膜形态不能够预测体外受精-胚胎移植解冻复苏周期临床妊娠率,患者年龄以及移植胚胎的发育潜能才是预测临床妊娠率的参考指标。     

通元针法对IVF-ET反复种植失败患者妊娠结局、性激素和焦虑抑郁影响的前瞻性随机对照研究

摘要 目的：观察通元针法对体外受精-胚胎移植（IVF-ET）反复种植失败（RIF）患者妊娠结局、性激素和焦虑抑郁影响。方法：前瞻性选取广州中医药大学第一附属医院2019年5月到2021年4月期间收治的IVF-ET RIF患者122例，采用随机数字表法将其分为对照组（61例，常规治疗）和研究组（61例，对照组的基础上接受通元针法治疗）。观察两组临床妊娠率、胚胎种植率，记录治疗期间不良反应发生情况，观察治疗前后子宫内膜厚度和子宫内膜血流参数、性激素和焦虑抑郁的变化情况。结果：研究组的临床妊娠率、胚胎种植率高于对照组（P<0.05）。治疗后，研究组孕酮、雌二醇水平高于对照组（P<0.05）。治疗后，研究组的子宫内膜血流搏动指数（PI）、子宫内膜血流阻力指数（RI）、子宫内膜血流收缩期最高血流速度/舒张末期血流速度（S/D）较治疗前降低，且低于对照组，子宫内膜厚度较对照组更厚（P<0.05）。治疗后，研究组Zung焦虑自评量表（SAS）、Zung抑郁自评量表（SDS）评分低于对照组（P<0.05）。两组不良反应发生率组间对比，无统计学差异（P>0.05）。结论：通元针法用于IVF-ET RIF患者，可有效调节人体性激素，缓解焦虑抑郁心情，改善妊娠结局，安全可靠。     

MUC16 对子宫内膜容受性的影响及其意义

目的:多囊卵巢综合征(Polycystic Ovary Syndrome,PCOS)系由于体内复杂的内分泌和代谢环境影响了子宫内膜稳态,导致子宫内膜容受性下降,造成患者生育力减弱和不良妊娠结局.通过测定多囊卵巢综合征患者子宫内膜与正常生育力妇女增生期、分泌早、中、晚期子宫内膜中MUC16的相对表达量,本文探讨MUC16与PCOS患者子宫内膜容受性下降的关系,为临床上改善PCOS患者子宫内膜容受性,提高PCOS患者的妊娠率,降低流产率提供一条新的可能途径.方法:选择PCOS患者子宫内膜、正常生育力妇女增生期、分泌早、中、晚期子宫内膜各20例,用免疫组化SP法检测MUC16在各组的表达情况.结果:(1)MUC16在月经周期各期均有表达,在分泌中期表达最强.(2)PCOS组MUC16的表达较分泌中期组弱,差异有显著性(P＜0.05).结论:(1)在子宫内膜中的表达呈周期性变化.(2)PCOS患者子宫内膜中MUC16表达异常可能使子宫内膜容受性下降,推测其与胚胎不能正常着床或着床后发育不良、导致流产有关.     

联合子宫内膜厚度和类型对体外受精-胚胎移植临床结局的预测

为评估联合子宫内膜厚度和类型对体外受精-胚胎移植(in vitro fertilization-embryo transfer,IVF-ET)临床结局的预测价值,回顾性分析1 933个IVF-ET周期.按照HCG日子宫内膜厚度分3组(组1:≤7 mm;组2:>7 mm到≤14 mm;组3:>14 mm),每组按内膜类型再分为3个亚组(组1(2、3)-A、B、C型),分析各组的妊娠率和着床率.结果显示HCG日内膜厚度是影响妊娠的独立因素;组1和组3的3个亚组妊娠率及着床率无差异;妊娠率和着床率在组2的A、B、C中依次降低,各组比较有显著差异(P<0.05).提示子宫内膜厚度和类型都是影响妊娠结局的独立因素;当内膜<7 mm或>14 mm时,联合内膜厚度和类型更好地预测临床结局;当内膜厚度适中(7～14 mm)且内膜类型有三线征时,将预示很好的临床结局.     

IVF-ET时影响胚胎着床率的因素分析

胚胎移植成功的标志性事件是胚胎着床。着床是一个高度协调的事件,影响胚胎着床的因素主要有胚胎质量和子宫内膜容受性两方面。     

辅酶Q10联合金凤丸对体外授精-胚胎移植患者卵巢功能及子宫内膜容受性的影响

目的:探讨辅酶Q10联合金凤丸对体外授精-胚胎移植患者卵巢功能及子宫内膜容受性的影响。方法:选择2017年7月～2017年10月接诊的185例体外授精-胚胎移植患者进行研究,通过随机数表法将其分为观察组(n=95)和对照组(n=90)。对照组采用金凤丸进行治疗,观察组在对照组的基础上加用辅酶Q10进行治疗。治疗后,比较两组血清卵泡刺激素(FSH)、促黄体生成素(LH)、睾酮(T)、雌二醇(E_2)、胰岛素(INS)、子宫内膜厚度、孕激素(P)水平、获卵数、受精率及妊娠率。结果:治疗后,两组患者血清FSH、LH、T、E_2、INS水平均较治疗前明显下降,且观察组以上指标水平均显著低于对照组(P0.05);两组患者子宫内膜厚度和血清P水平均较治疗前明显升高,且观察组以上指标均显著高于对照组(P0.05);两组患者获卵数无明显差异,观察组患者受精率、妊娠率均显著高于对照组(P0.05)。结论:辅酶Q10联合金凤丸可明显增加子宫内膜厚度,提高妊娠率。     

通过体内基因转染改变Meis1在围着床期小鼠子宫中的表达影响胚胎着床

通过宫腔内脂质体转染改变小鼠子宫内Meis1基因的表达水平,研究其对子宫内膜容 受性的影响,从而推测Meis1基因在胚胎着床中的作用.选择8～12周龄昆明小鼠,于妊娠 第2 ｄ,通过向小鼠宫腔内注入Meis1基因表达质粒和siRNA表达质粒及其各自的对照质粒 ,在妊娠第5ｄ, 提取小鼠子宫mRNA 和蛋白质行半定量RT-PCR 和免疫组化分析,观察各组小鼠子宫内膜Meis1和整合素β3的表达变化.在妊娠第9 ｄ,观察Meis1基因上调组及其对 照组、Meis1基因下调及其对照组妊娠率和胚胎着床数的差异.结果显示,Meis1基因下调组胚胎着床率明显低于对照组（P<0.05）,Meis1基因上调组胚胎着床率略高于对照组,但无统计学意义（P>0.05）;Meis1基因上调组其整合素β3的表达高于其对照组,Meis1基因下调组 整合素β3的表达低于其对照组,差异均有显著性（P<0.05）.以上观察结果表明,Meis1基因表达下降可明显减少胚胎着床率,影响整合素β3的表达.Meis1基因表达提高则可促进整合素β3的表达. 因此,Meis1可能作为1种子宫内膜容受分子,在胚胎着床中发挥重要作用.     

麒麟丸联合炔雌醇环丙孕酮对多囊卵巢综合征致不孕症患者子宫内膜容受性、血清性激素和氧化应激水平的影响

摘要 目的：探讨麒麟丸联合炔雌醇环丙孕酮对多囊卵巢综合征（PCOS）致不孕症患者子宫内膜容受性、血清性激素和氧化应激水平的影响。方法：选取我院于2018年1月~2020年1月期间收治的PCOS致不孕症患者460例,符合要求的患者按照随机数字表法分为对照组和研究组,各为230例。对照组患者予以炔雌醇环丙孕酮治疗,研究组予以麒麟丸联合炔雌醇环丙孕酮治疗,对比两组疗效、子宫内膜容受性、性激素、氧化应激、排卵率、妊娠率和不良反应。结果：研究组的临床总有效率较对照组更高（P<0.05）。研究组治疗后子宫动脉搏动指数（PI）、子宫动脉血流阻力指数（RI）低于对照组,子宫内膜厚度大于对照组（P<0.05）。研究组治疗后促卵泡激素（FSH）和黄体生成素（LH）低于对照组,雌二醇（E2）高于对照组（P<0.05）。研究组治疗后丙二醛（MDA）、活性氧物质（ROS）低于对照组,过氧化物歧化酶（SOD）高于对照组（P<0.05）。随访6个月后,研究组的妊娠率、排卵率明显高于对照组（P<0.05）。两组不良反应发生率组间对比无差异（P>0.05）。结论：麒麟丸联合炔雌醇环丙孕酮治疗PCOS致不孕症患者,可以有效改善患者子宫内膜容受性、血清性激素和氧化应激状态,提高妊娠率、排卵率,安全有效。     

Decreased ANGPTL4 impairs endometrial angiogenesis during peri‐implantation period in patients with recurrent implantation failure

Insufficient endometrial angiogenesis during peri‐implantation impairs endometrial receptivity (ER), which contributes to recurrent implantation failure (RIF) during in vitro fertilization and embryo transfer (IVF‐ET). Angiopoietin‐like protein 4 (ANGPTL4) acts as a multifunctional secretory protein and is involved in the regulation of lipid metabolism and angiogenesis in various tissues including the endometrium. Herein, we found decreased ANGPTL4 expression in endometrial tissue and serum during peri‐implantation period in 18 RIF‐affected women with elevated uterine arterial impedance (UAI) compared with the pregnancy controls. ANGPTL4 and peroxisome proliferator‐activated receptor gamma (PPARγ) expression were up‐regulated upon decidualization on human endometrial stromal cells (HESCs). Rosiglitazone promoted the expression of ANGPTL4 in HESCs and human umbilical vein endothelial cells (HUVECs) via PPARγ. ANGPTL4 promoted the proliferation, migration and angiogenesis of HUVECs in vitro. Our results suggest that decreased abundance of ANGPTL4 in endometrial tissues impairs the endometrial receptivity via restraining endometrial angiogenesis during decidualization; while rosiglitazone‐induced ANGPTL4 up‐regulation in hESCs and HUVECs through PPARγ. Therefore, ANGPTL4 could be a potential therapeutic approach for some RIF‐affected women with elevated UAI.     

子宫内膜容受性检测技术在反复种植失败患者冻融胚胎移植中的应用价值及其临床妊娠的影响因素分析

摘要 目的：探讨子宫内膜容受性检测（ERT）技术在反复种植失败患者冻融胚胎移植（FET）中的应用价值,并分析其临床妊娠的影响因素。方法：回顾性分析2019年10月~2022年4月期间海南省妇女儿童医学中心收治的150例反复种植失败患者的临床资料,根据是否接受ERT技术分为ERT组（n=78,接受ERT技术）和无ERT组（n=72,未接受ERT技术）。按照反复种植失败患者是否临床妊娠分为临床妊娠组和未临床妊娠组。采用单因素和多因素Logistic回归模型分析临床妊娠的影响因素。结果：两组异位妊娠率组间对比未见统计学差异（P>0.05）。ERT组临床妊娠率、活产率高于无ERT组,移植日内膜厚度大于无ERT组,移植胚胎数少于无ERT组,流产率低于无ERT组（P<0.05）。所有患者按照是否临床妊娠分为临床妊娠组（n=85）和未临床妊娠组（n=65）。单因素分析结果显示：临床妊娠与年龄、移植胚胎类别、移植胚胎数量、总周期数、FSH、子宫内膜厚度、子宫内膜类型有关（P<0.05）,而与体质量指数（BMI）、不孕年限、不孕类型、胚胎冷冻保存时间无关（P>0.05）。多因素Logistic回归分析结果显示：年龄偏大、FSH偏高是临床妊娠的危险因素,而移植胚胎类别为囊胚、移植胚胎数量偏多是临床妊娠的保护因素（P<0.05）。结论：ERT技术用于反复种植失败患者FET中,可有效改善患者的临床妊娠。年龄、FSH、移植胚胎类别、移植胚胎数量是临床妊娠的影响因素。     

黄体酮对子宫内膜异位症在位内膜预处理与IVF治疗结局关系

摘要 目的：研究黄体酮对子宫内膜异位症在位内膜预处理改善IVF结局。方法：男性因素并卵巢子宫内膜异位囊肿168例,分两组：（1）实验组：IVF前自然周期月经第12天地屈孕酮30 mg/日、14天,3个月;（2）对照组：IVF前无干预。IVF前测血CA125,黄体期长方案促排卵,排卵后一周（垂体降调日）再测CA125并取子宫内膜行ER、PR、HOXA-10mRNA检测。HCG日测子宫内膜厚度、形态、血流。比较临床资料及结局、症状疼痛评分。结果：实验组胚胎种植率、临床妊娠率高于对照组（P<0.05）;HCG日对照组子宫内膜厚于实验组。实验组子宫内膜A型血流比率高于对照组（P<0.05）。实验组A型子宫内膜比率高于对照组,但无明显差异（P>0.05）;IVF前两组CA125均高于参考值,但无明显差异（P>0.05）。垂体降调日复查CA125,实验组明显低于对照组,实验组治疗后低于治疗前;实验组子宫内膜ER、PR、HOXA-10 mRNA表达量高于对照组,实验组分泌期子宫内膜比率高于对照组（P<0.05）;治疗后两组各项症状疼痛评分均较治疗前改善,且实验组优于对照组（P<0.05）。结论：IVF治疗中合并卵巢子宫内膜异位囊肿用黄体酮预处理在位内膜,可以降低血CA125,有利于转变子宫内膜组织类型、减小子宫内膜厚度、增加子宫内膜血流、增加子宫内膜ER、PR、HOXA-10 mRNA表达,改善在位内膜容受性,缓解症状疼痛,提高临床妊娠率。     

Correlation between three-dimensional power Doppler and morphometric measurement of endometrial vascularity at the time of embryo implantation in women with unexplained recurrent miscarriage

Power Doppler in combination with three-dimensional (3D-PD) ultrasonography has been used as a noninvasive tool to evaluate the vascularity. However, it is unclear whether 3D-PD can accurately reflect endometrial vascularization and replace the invasive endometrial biopsy. This study aims to investigate the correlation between 3D-PD and micro vessel morphometric measurement of endometrial vascularity. Twenty-five women with unexplained recurrent miscarriage were recruited for 3D-PD and endometrial biopsy on precisely day LH?+?7. Immunohistochemistry using vWF was employed to identify micro vessels in endometrial biopsy specimens followed by the use of morphometric technique to measure the mean vessel diameter and volume fractions. The vascularization index (VI), flow index (FI) and vascularization flow index (VFI) assessed by 3D-PD were calculated for both the endometrial and sub-endometrial regions. There were no significant correlations between any of the ultrasonographic measurements (endometrial thickness, endometrial volume, endometrial VI/FI/VFI, sub-endometrial volume, sub-endometrial VI/FI/VFI) and morphometric features (number of micro vessel, mean diameter of micro vessel and volume fraction measurement of vessel). This study indicates that endometrial vascularity assessed by 3D-PD could not be used to reflect changes in micro vessels of the endometrium at the time of embryo implantation in women with unexplained recurrent miscarriage.     

Potential innate immunity-related markers of endometrial receptivity and recurrent implantation failure (RIF)

The successful implantation of the embryo into a receptive endometrium is essential for the establishment of a viable pregnancy while recurrent implantation failure (RIF) is a real challenge in assisted reproduction. The maternal innate immune system, specifically the Toll-like receptors (TLRs), are involved in maintaining immunity in the female reproductive tract (FRT) required for fertility. In this study, we aimed to investigate the importance of innate immunity-related gene expression in the regulation of human fertility and as a prediction of potential outcome of in vitro fertilization - embryo transfer (IVF-ET), thus, we assessed the gene expression levels of TLR signalling molecules using quantitative real-time PCR between endometrial biopsies of healthy fertile women, and the patients experiencing RIF. Interestingly, our results showed that, TRIB2 and TLR9 genes were differentially expressed between the endometrial biopsies of healthy women and those with RIF. However, comparing expression levels of same genes between pre-receptive and receptive healthy endometrial biopsies showed different genes (ICAM1, NFKBIA, VCAM1, LIF, VEGFB, TLR5) had significantly altered expression, suggesting their involvement in endometrial receptivity. Thus, further investigations will enable us to better understand the role of these genes in the biology of FRT and as a possible target for the improvement of infertility treatments and/or development of non-hormonal contraception.     

Impact of endometriosis on embryo quality and endometrial receptivity in women undergoing assisted reproductive technology

ART is an important treatment method for infertile patients with endometriosis. However, the effects of endometriosis on embryo quality and endometrial receptivity remain unclear. Thus, we aimed to simultaneously investigate the impact of endometriosis and its stage on embryo quality and endometrial receptivity in women undergoing ART. We retrospectively analyzed the data from patients with and without endometriosis who underwent oocyte retrieval and/or high-quality embryos transfer between July 2015 and December 2020, including 1312 IVF cycles and 608 IVF or frozen-thawed embryo transfer (FET) cycles, respectively. The endometriosis group had a lower percentage of good cleavage-stage embryos and fertilization rates than those in the control group (p = 0.038 and 0.008, respectively). The number of retrieved oocytes, MII oocytes, cleavage, blastocysts, and blastulation rates was comparable between two groups. We found no significant difference in clinical pregnancy, implantation, live birth, miscarriage, or multiple pregnancy rates between the two groups among patients who transferred high-quality embryos. Stratification analysis showed that patients with stage III-IV endometriosis had fewer retrieved oocytes than those with stage I-II endometriosis (p = 0.012) and marginally fewer retrieved oocytes than the control group (p = 0.051). The stage I-II group had the lowest percentage of good cleavage-stage embryos, which was significantly lower than that of the control group (p = 0.043). In FET cycles, patients with stage III-IV endometriosis had a higher miscarriage rate than those in the control group (p = 0.023). Our results suggest that endometriosis does not alter endometrial receptivity but affects embryo quality, oocyte fertilization ability, and ovarian response.     

Immunolocalisation of phosphorylated STAT3, interleukin 11 and leukaemia inhibitory factor in endometrium of women with unexplained infertility during the implantation window

Background  

Uterine receptivity and embryo implantation are critical in the establishment of pregnancy. The diagnosis of endometrial fertility requires more precise measurements of endometrial receptivity. Interleukin (IL-11) and leukemia inhibitory factor (LIF) are essential for murine implantation and signal via intracellular phosphorylation (p) of STAT3 in the endometrium. Both cytokines are present in the endometrium of women duiring the receptive window. Endometrial IL-11, IL-11 receptor alpha (IL-11Ralpha), LIF and pSTAT3 in women with primary unexplained infertility was compared to normal fertile women during the implantation window.