不明原因不孕患者着床窗期子宫内膜容受性分析

目的 对不明原因不孕患者着床窗期子宫内膜容受性进行评价.方法 对2005年10月至2008年8月在广东省计划生育专科医院就诊的71例不明原因不孕患者和16例正常生育妇女在着床窗期行阴道超声、宫腔镜检查及内膜活检,扫描电镜观察胞饮突,宫腔冲洗液和血清Glyeodelin水平测定,子宫内膜白血病抑制因子(LIF)及血管内皮生长因子(VEGF)测定,两组进行分析比较.结果 不孕组排卵期、着床窗期超声内膜厚度[(O.93±0.12)cm、(1.02±0.10)cm]均较正常生育组[(1.06±0.10)cm、(1.16±0.08)cm]薄(P<0.01),排卵期A型内膜比例(45.07%)较正常生育组(81.25%)显著减少(P<0.01).宫腔镜下不孕组佳型内膜比例(18.31%)明显少于正常组(81.25%).不孕组内膜发育不同步,子宫内膜胞饮突所占面积不足,且胞饮突的发育明显滞后于正常组.不孕组宫腔冲洗液glycodelin含量(116.34 ng/mL)较正常组减少(196.23 ng/mL)(P相似文献   

子宫内膜着床窗期血管生成状态及胞饮突表达对胚胎着床的影响

目的探讨子宫内膜着床窗期血管生成状态及胞饮突表达对胚胎着床的影响。方法选择2007年5月至2009年3月在广东省计划生育专科医院就诊的体外受精-胚胎移植(IVF-ET)失败患者53例作为着床失败组,正常已生育妇女18例作为正常生育组。比较两组着床窗期血清雌二醇(E2)、孕酮(P)的水平;以血管内皮特异标记物CD34抗体标记微血管内皮细胞并测定微血管密度(MVD)计数,免疫组织化学技术检测子宫内膜雌激素受体(ER)、孕激素受体(PR)、血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达;扫描电镜观察胞饮突的形态及数量。结果着床失败组MVD为(9.52±1.34)条/高倍视野(HP),正常生育组MVD为(21.71±3.97)条/HP,两组差异有统计学意义(P0.05)。两组血清E2、P水平及子宫内膜ER、PR的表达强度比较差异均无统计学意义(P0.05),着床失败组着床窗期子宫内膜CD34及VEGF的表达强度均明显低于正常生育组(P0.05)。子宫内膜MVD计数与内膜腺上皮VEGF的表达存在正相关关系(r=0.916,P0.01)。着床失败组子宫内膜胞饮突所占面积不足,且胞饮突的发育明显滞后于正常生育组(P0.01)。子宫内膜MVD计数与发育完全的胞饮突数量呈正相关(r=0.821,P0.01)。结论 (1)VEGF调控子宫内膜血管生成,促进胚胎着床。(2)IVF-ET失败妇女着床窗期存在血管生成不良和胞饮突表达不足,可能是导致其着床失败的原因之一。     

着床窗期宫腔镜下子宫内膜形态与性激素及其受体表达的研究

目的:探讨着床窗期宫腔镜下子宫内膜形态与性激素及其受体表达的关系.方法:对55例不孕患者及16例正常生育者在排卵后7～9天,行宫腔镜子宫内膜形态的检查,并检测血雌二醇、孕酮及内膜雌激素受体(ER)、孕激素受体(PR).结果:不孕组宫腔镜下子宫内膜血管及腺体发育较对照组差,差异有统计学意义(P＜0.05).内膜差组腺上皮细胞ER表达较内膜佳组弱,差异有统计学意义(P＜0.05);内膜差组间质PR表达较内膜佳组弱,差异有统计学意义(P＜0.05).结论:不孕患者子宫内膜ER、PR的低表达,可能是导致子宫内膜腺体和血管网发育不良的重要原因之一.通过宫腔镜观察子宫内膜腺体和血管形态是一种较好的、简单可行的评估子宫内膜容受性的方法.     

子宫内膜异位症不孕患者子宫内膜整合素av、β3表达的初步探讨

目的:探讨子宫内膜异位症是否影响子宫内膜容受性而造成不孕。方法:前瞻性研究我院2004年1月到2005年6月经手术病理确诊的子宫内膜异位症不孕患者胚胎种植窗期血清孕激素、雌激素浓度,组织学分期和子宫内膜整合素av、β3的表达,并与同期已育妇女的指标作比较。结果:15例子宫内膜异位症不孕患者中Ⅰ期和Ⅱ期共8例(研究1组),Ⅲ期和Ⅳ期共7例(研究2组),与16例对照组比较,血清孕激素和雌激素浓度差异无统计学意义。病理组织学确诊的黄体功能不足差异无统计学意义。子宫内膜整合素β3的表达差异无统计学意义,子宫内膜整合素av的表达差异有统计学意义(P<0.05),且仅Ⅲ期和Ⅳ期子宫内膜异位症子宫内膜整合素av的表达差异有统计学意义(P<0.01)。结论:初步证实Ⅲ~Ⅳ期子宫内膜异位症不孕患者子宫内膜容受性标记物-子宫内膜整合素av的表达下降,与其导致不孕和流产相关,值得进一步进行大样本的研究。     

胞饮突与子宫内膜容受性

胞饮突是在扫描电镜下所见宫腔被复上皮细胞膜预端出现的膜突起。在自然周期，它成熟的时间平均在月经周期的第２１天。激素治疗可使胞饮突的出现提前或延迟，在卵巢刺激周期，胞饮突比自然周期提前１～２天出现，相反，用雌激素和孕激素行人工周期治疗，胞饮突的形成推迟。由于它的出现不仅与鼠和人类子宫内膜容受胚胎着床的时间一致。而且有可能参与囊胚的着床过程，因此被认为是子宫内膜受性或着床窗的特异形态标记。     

GnRHa对改善他莫西芬诱发子宫腺肌病小鼠模型内膜容受性的作用

目的:探讨促性腺激素释放激素激动剂(GnRHa)对腺肌病模型小鼠种植窗期内膜容受性的影响。方法:新生ICR小鼠滴喂他莫西芬建立子宫腺肌病模型,随机分为GnRHa降调的模型鼠组(A组)、模型对照鼠组(B组),并取同龄正常小鼠作为对照组(C组),每组8只,于100~115日龄处死,HE染色检测小鼠子宫病理变化;免疫组织化学CD31染色计算小鼠子宫微血管密度;免疫组织化学法检测种植窗期子宫内膜LIF表达及扫描电镜下观察胞饮突发育情况。结果:①口服他莫西芬法建立ICR小鼠子宫腺肌病模型造模率为100%,B组小鼠子宫肌层微血管密度高于A、C组,差异有统计学意义(P<0.05)。②种植窗期子宫内膜LIF蛋白水平A组和C组明显高于B组,差异有统计学意义(P<0.05);A、C组间无统计学差异(P>0.05)。③B组可见较多退化的胞饮突,分布稀疏,呈局灶性分布;A组的胞饮突较B组丰富但大小略不均;C组胞饮突分布较丰富且发育完全。结论:新生小鼠口服他莫西芬法可高效建立子宫腺肌病模型,GnRHa降调节能改善子宫腺肌病小鼠子宫内膜中LIF表达及胞饮突发育,从而提高子宫内膜容受性。     

不明原因不孕症患者黄体中期子宫内膜E-钙黏素的表达及其与性激素关系的研究

目的:探讨不明原因不孕患者黄体中期E-钙黏素在子宫内膜中的表达与同期血清性激素的相关性。方法:选择不明原因不孕患者45例,随机分为研究组30例(A组)、对照组15例(B组),另选正常生育妇女17例为正常对照组(C组)。A组排卵后第2日起注射黄体酮7d,用药2个周期,B、C组不作治疗。用免疫组化法检测A组治疗前后及B组、C组黄体中期子宫内膜E-钙黏素的表达;用放射免疫法检测3组同期血清E2、P4水平。结果:A、B组黄体中期E-钙黏素的表达及同期血清E2、P4、P4/E2均明显低于C组(P<0.01);E-钙黏素的表达与P4和E2均呈正相关,与P4/E2无相关性;A组治疗后E-钙黏素、P4和P4/E2均高于治疗前(P<0.01);A组治疗后妊娠率高于B组;当P4>40nmol/L妊娠率最高,且妊娠率随P4/E2增高而提高。结论:不明原因不孕患者黄体中期E-钙黏素表达缺陷、P4不足、P4/E2比例失调是影响子宫内膜容受性的重要原因。孕激素干预治疗对E-钙黏素的表达有调节作用。     

GnRHa长方案超促排卵对围着床期小鼠子宫内膜溶血磷脂酸受体3(LPAR3)蛋白的表达及胞饮突发育的影响

目的:研究GnRHa/hMG/hCG控制性超促排卵对围着床期小鼠子宫内膜溶血磷脂酸受体3(LPAR3)蛋白的表达及胞饮突发育的影响。方法:雌性未孕昆明系小鼠72只,随机分为控制性超促排卵组(COH)和自然受孕组(NC),再按交配成功后天数每组分成4个亚组,接受相应的建模处理。用Western blotting检测性交后3~6 d(孕3~6 d)小鼠子宫内膜LPAR3蛋白的表达;同时用扫描电子显微镜观察子宫内膜胞饮突的发育。结果:COH组性交后3 d亚组LPAR3蛋白表达最强,NC组4 d亚组表达最强,但两者表达量无显著差异。COH组3~5 d亚组胞饮突发育不同步,大小不一,胞饮突数量较NC组相应时间明显减少,呈局灶性分布。NC组3 d亚组多为发育中的胞饮突,4 d亚组几乎均为完全发育的胞饮突,5 d亚组多为退化的胞饮突。结论:GnRHa控制性超促排卵可能通过改变小鼠子宫内膜LPAR3蛋白和超微结构的时序变化来影响子宫内膜容受性,从而影响胚泡着床。     

控制性超排卵周期的子宫内膜容受性研究

目的 研究控制性超排卵(COH)对子宫内膜容受性的影响。方法 扫描电镜观察COH后子宫内膜胞饮突的变化和免疫组化法检测整合素β3、TGFβl的表达；以正常月经周期分泌中期子宫内膜作对照。结果 COH周期，完全发展的胞饮突出现在月经周期的第18—19d，较正常周期提前l一2d出现和消失；整合素β3、TGFβl在正常月经周期第2l一23d的子宫内膜腔上皮和腺上皮细胞的细胞质高表达，而COH周期在第18—20d高表达。COH周期和正常周期，整合素β3和TGFβl在子宫内膜上皮细胞的高表达与完全发展胞饮突的出现在时期上存在着一致性。结论 COH可能通过改变子宫内膜与着床密切相关的粘附分子、细胞因子和超微结构的时序性表达来影响子宫内膜的容受性，使子宫内膜着床窗的开放与胚泡的发育不同步，这可能是影响IVF妊娠率的重要原因。     

子宫内膜整合素β_3和细胞外基质的变化及与不孕症的关系

对生育组３１例,原因不明不孕组３４例采用免疫组化方法检测整合素β３及细胞外基质纤维粘连蛋白（ＦＮ）、层粘连蛋白（ＬＮ）、Ⅳ型胶原纤维（ＣＬ）在分泌期子宫内膜上的表达,探讨其变化规律及在调控妊娠中的作用。结果显示整合素β３在生育组腺上皮细胞分泌中期出现,持续至分泌晚期,而不孕组分泌期无表达;细胞外基质在生育组分泌中期呈强表达,早期次之,晚期较弱;不孕组在分泌各期表达均高于生育组。结论认为整合素β３ＦＮ、ＬＮ和Ⅳ型ＣＬ在分泌期子宫内膜上呈周期性变化参与子宫内膜的功能变化及胚泡的着床环节,其异常表达可致着床失败而不孕。     

Altered expression of hormone receptor,integrin β3 and pinopode in the endometrium of luteal phase defect women

Objective: To invistigate estrogen receptor (ER), progesterone receptor (PR), integrin β3, and pinopode expression in luteal phase deficiency (LPD) women.

Methods: There were 52 nulligravidas consecutive infertile patients undergoing a routine assistant reproduction consultation included in this study. An endometrial biopsy sample was randomly obtained between days 4 and 10 of the luteal phase. Endometrial morphology was examined with scanning electron microscopy. Expressions of ER, PR, integrin β3 were determined in the endometrium of LPD patients with immunohistochemistry.

Results: The incidence of LPD was 15.3% (8/52) in this study. On day luteinizing hormone (LH) surge?+?9～LH?+?10, noted regressing pinopodes resembling a day LH?+?7～LH?+?8 in the endometrium of the control group. The expressions of ER and PR in glandular epithelium were significantly increased in endometrium of LPD than that in the control group (p?p?Conclusion: The altered expression of ER and PR may be associated with the expression variation of integrin and pinopode formation in endometrium of LPD women. This alteration may imply the association of low rates of cycle fecundity and high rates of embryonic loss in LPD women.     

黄体功能缺陷与子宫内膜效应不良患者的内分泌特征

目的：分析比较黄体功能缺陷（ＬＰＤ）和子宫内膜效应不良（ＩＥＲ）患者的内分泌特征。方法：采用放射免疫法和放射性配体饱和竞争、葡聚糖活性碳吸附分析法，测定ＬＰＤ、ＩＥＲ患者和月经周期正常者（对照组）的血清激素水平及同一月经周期子宫内膜组织中的雌、孕激素受体含量。结果：ＬＰＤ患者黄体期的雌、孕激素水平显著低于对照组（Ｐ＜０．００１），其子宫内膜雌、孕激素受体含量在整个月经周期中与对照组无差异（Ｐ＞０．１）；而ＩＥＲ患者整个月经周期的血清雌激素水平均低于对照组（Ｐ＜０．００１），但黄体期的血清孕激素水平与对照组无差异（Ｐ＞０．１），子宫内膜增生期的胞浆雌激素受体、胞核孕激素受体和整个月经周期的胞浆孕激素受体含量亦显著低于对照组（Ｐ＜０．００１，Ｐ＜０．００１，Ｐ＜０．０５）。结论：ＬＰＤ和ＩＥＲ是内分泌特征根本不同的两种情况，ＬＰＤ主要表现为黄体细胞分泌雌、孕激素功能下降，子宫内膜相应受体含量正常；ＩＥＲ则为整个周期的雌激素水平降低及相应受体合成障碍，而黄体分泌孕激素的功能正常。     

Endometrial Pinopode and αvβ3 Integrin Expression Is Not Impaired in Infertile Patients with Endometriosis

PURPOSE: To investigate endometrial receptivity in terms of pinopode formation and alphavbeta3 integrin expression in infertile women with endometriosis during natural cycles. METHODS: We investigated the expression of alphavbeta3 integrin and pinopode formation in the endometrium of 12 infertile patients with stage I or II endometriosis as the only cause of infertility, 12 infertile patients having unexplained infertility, and 12 fertile women who were undergoing tubal sterilization. Two endometrial biopsies (postovulatory day +7 to +8 and 4 days later) were performed during a single menstrual cycle in each subject. RESULTS: No statistically significant difference regarding alphavbeta3 integrin expression and pinopode formation was found between infertile patients with endometriosis and the two control groups. CONCLUSION: alphavbeta3 integrin expression and pinopode formation are not reduced during the window of implantation in patients with stage I-II endometriosis. Whether these results imply normal endometrial receptivity in such patients or add to the increasing uncertainty about the clinical value of assessing the endometrium with those markers of implantation, warrants further studies.     

Prolactin response to thyrotropin-releasing hormone in women with infertility and/or randomly elevated serum prolactin levels

Infertile women with normal serum prolactin (PRL) levels have been known to establish a pregnancy after the use of bromocriptine, a dopamine agonist. These data imply that there may be a group of women with a slight but significant increase in PRL secretion that may have resulted in their infertility. This study evaluates the thyrotropin-releasing hormone (TRH)-induced PRL and thyroid-stimulating hormone (TSH) response in normal women (NL, n = 6), women with anovulation and/or inphase endometrial biopsies (AN/IN, n = 12), and women with histologic evidence of luteal phase deficiency (LPD, n = 12). Most of these women were found to have elevated serum PRL values on random testing. There was a statistically significant increase in PRL response at all time intervals after TRH between the NL and AN/IN groups compared with the group with LPD on the basis of repeated measures analysis (P = 0.0013). There was no statistical difference in the TSH response between these three groups. Although the PRL response was statistically different, individual PRL response patterns were not diagnostic. It appears from these data that there is an increased PRL secretion in infertile women who have histological evidence of a LPD.     

不孕妇女黄体期子宫内膜与血清中微量元素的关系

目的 :探讨不孕妇女黄体期子宫内膜与血清中微量元素的相互关系。方法 :应用原子吸收分光光度法测定19例不孕和 14例已育健康妇女黄体期子宫内膜及血清中锌、铜、铁、锰水平。结果 :对照组子宫内膜锌与子宫内膜厚度呈正相关 (P <0 .0 1) ,且子宫内膜平均厚度明显高于不孕组 (P <0 0 5 ) ;不孕组子宫内膜铜与血清铜呈正相关 (r =0 .76 78,P <0 0 1) ,而子宫内膜锰与血清锰呈负相关 (r= 0 .5 5 95 ,P <0 0 5 )。结论 :微量元素在体内的异常分布可能与原因不明性不孕有关     

子宫内膜轻创对着床相关因子及IVF妊娠结局影响的研究

目的:探讨子宫内膜轻创术对提高子宫内膜容受性的价值及分子机理。方法:对120例不孕症患者行IVF140周期,随机分为行子宫内膜搔刮轻创术组60例(A组)及对照组60例(B组),采用内膜微活检的方法,在扫描电镜下观察胞饮突,免疫组化定位及半定量检测白血病抑制因子(LIF)、骨桥蛋白(OPN)。再将对照组未孕患者中的20例行轻创术(B2组),重复IVF,并进行相关因子测定。结果:A组和B组相关因子分别为:胞饮突丰富占63.33%和36.67%、LIF6.07±1.33和4.94±2.26、OPN6.36±1.49和5.28±2.06、单胚种植率27.8%和14.3%,组间比较差异均有统计学意义(P<0.05)。B2组行轻创术前后比,分别为:胞饮突丰富10%vs50%,LIF4.50±0.82vs6.33±1.25,OPN5.06±0.98vs6.83±1.46,轻创术前后差异均有统计学意义(P<0.05)。按妊娠与否分组后,妊娠组(n=62)与非妊娠组(n=78)相关因子分别为:胞饮突丰富54.84%和25.64%,LIF6.94±1.03和4.24±1.84,OPN7.31±0.85和4.52±1.65,差异有统计学意义(P<0.05),且LIF与OPN间呈正相关。结论:胞饮突、LIF、OPN是子宫内膜着床期重要的相关因子,它们的高表达与子宫内膜容受性紧密相关。而轻创术可增强3者的表达,从而提高胚胎种植率,改善IVF妊娠结局。     

Luteal function after delayed ovulation

Thirty-three infertile patients presenting spontaneous ovulatory cycles with long follicular phases (greater than or equal to 20 days) underwent a luteal function evaluation by basal body temperature, plasma progesterone (P), estradiol, and prolactin determination, and endometrial biopsy study. An endometrial luteal phase deficiency (LPD) was detected in 13 patients (39.4%), although in 10 of them (77%) P levels were normal. This study shows a high incidence of endometrial LPD among cycles with delayed ovulation and that in cases of LPD related to abnormal folliculogenesis, the endometrium is a better indicator than plasma P.     

A quantitative study of endometrial development in the luteal phase: comparison between women with unexplained infertility and normal fertility

Summary. This study compared endometrial development in the luteal phase of women with unexplained infertility ( n = 30) with that in women with normal fertility ( n = 70) by the use of quantitative histological techniques (morphometric analysis) on endometrial specimens which were precisely timed from the luteinizing hormone surge. When overall endometrial development (histological dating) was considered, the proportion of women with unexplained infertility who had retarded endometrial development (20%) was found to be significantly higher than for women with normal fertility (3%) (P<0·01). When individual histological features were considered, women with unexplained infertility were found to have significant deviation from the normal range established from fertile women in only five of the 14 histological features measured. All of these five features related to the glandular but not to the stromal component of the endometrium; four of these five features are related to glandular secretory activity.     

A quantitative study of endometrial development in the luteal phase: comparison between women with unexplained infertility and normal fertility

This study compared endometrial development in the luteal phase of women with unexplained infertility (n = 30) with that in women with normal fertility (n = 70) by the use of quantitative histological techniques (morphometric analysis) on endometrial specimens which were precisely timed from the luteinizing hormone surge. When overall endometrial development (histological dating) was considered, the proportion of women with unexplained infertility who had retarded endometrial development (20%) was found to be significantly higher than for women with normal fertility (3%) (P less than 0.01). When individual histological features were considered, women with unexplained infertility were found to have significant deviation from the normal range established from fertile women in only five of the 14 histological features measured. All of these five features related to the glandular but not to the stromal component of the endometrium; four of these five features are related to glandular secretory activity.     

种植窗口期宫腔镜检查对原因不明不孕症患者子宫内膜容受性及妊娠结局的预测价值

目的 探讨种植窗口期官腔镜检查用于预测原因不明不孕症患者子宫内膜容受性及妊娠结局的价值.方法 选择2007年10月-2009年3月在广东省计划生育专科医院就诊的原因不明不孕症患者93例,在排卵后7～9 d(即种植窗口期)行宫腔镜检查,将其中未发现官腔病变的79例患者根据宫腔镜下子宫内膜腺体开口和血管的形态分为佳型内膜组19例、差型内膜组60例.比较两组患者子宫内膜的形态、厚度、分泌情况、胞饮突形态及数量、血管分布等,以及两组患者的血性激素水平、宫腔冲洗液中白血病抑制因子(LlF)及妊娠相关子宫内膜蛋白glycodelin水平、妊娠结局等.结果 (1)佳型内膜组患者种植窗口期血雌二醇、孕酮水平分别为(518±176)pmol/L、(40±20)nmol/L,分别与差型内膜组[分别为(513±244)pmoL/L、(37±19)nmol/L]比较,差异均无统计学意义(P>0.05).B超检查显示,佳型内膜组排卵日、种植窗口期子宫内膜厚度分别为(1.06±0.10)cm和(1.16±0.08)cm,分别与差型内膜组[分别为(0.93±0.12)cm和(1.02±0.10)cm]比较,差异均无统计学意义(P>0.05);佳型内膜组患者排卵日内膜形态为A、B、C型者分别占63%(12/19)、37%(7/19)和0(0/19),差型内膜组分别占23%(14/60)、77%(46/60)和0(0/60),两组A、B型内膜百分率分别比较,差异均有统计学意义(P<0.05);两组患者种植窗口期内膜形态均为B型.(2)佳型内膜组患者中89%(17/19)子宫内膜分泌正常,差型内膜组患者中仅7%(4/60)子宫内膜分泌正常,两组比较,差异有统计学意义(P<0.01).(3)佳型内膜组患者中,胞饮突形态为成熟期者占84%(16/19),胞饮突数量丰富者占89%(17/19),均明显高于差型内膜组[分别为42%(25/60)和57%(34/60),P<0.05].(4)佳型内膜组内膜中CD_(34)表达水平及微血管密度(MVD)分别为(40.1±1.2)阳性单位(PU)和(21.7±4.0)条/高倍视野(HP),均明显高于差型内膜组[分别为(18.1±1.3)PU和(8.5±1.3)条/HP,P均<0.01].(5)佳型内膜组宫腔冲洗液中LIF、glycodelin水平分别为(72±54)ng/L和(196±20)μg/L,均明显高于差型内膜组[分别为(15±16)ng/L和(116±26)μg/L,P均<0.05].(6)佳型内膜组患者临床妊娠率、自然流产率、足月分娩率分别为74%(14/19)、0(0/14)和100%(14/14),差型内膜组分别为23%(14/60)、14%(2/14)和86%(12/14),佳型内膜组的临床妊娠率及足月分娩率均明显高于差型内膜组(P<0.01).结论 种植窗口期宫腔镜检查能反映子宫内膜血管及腺体的发育水平,是一种较好的评估子宫内膜容受性的方法,对预测妊娠结局有一定的价值.