补肾助孕中药对促排卵后子宫内膜LIFmRNA表达的影响

目的探讨补肾助孕中药对多囊卵巢综合征（PCOS）不孕患者促排卵治疗后黄体中期子宫内膜白血病抑制因子（LIF）mRNA表达的影响及意义。方法随机给予患PCOS的不孕妇女两种不同的促排卵方案：克罗米芬（CC）／hCG或CC／hCG加服中药方案。选择促排卵周期中单卵泡成熟排卵的患者为研究对象,其中CC／hCG促排卵者26例,为A组;CC／hCG同时服用补肾助孕中药促排卵者28例,为B组。同期选择25例月经周期正常妇女为对照组,为C组。采用逆转录-聚合酶链反应技术（RT—PCR）对3组妇女黄体中期的子宫内膜LIFmRNA进行半定量分析。结果LIFmRNA在3组妇女着床期子宫内膜均有表达,组间比较有差异（P〈0．05）。B、C组均高于A组（P分别〈0．05、0．01）,差异有显著性;B组和C组间差异无显著性（P〉0．05）。结论单纯CC／hCG促排卵治疗降低了子宫内膜容受性,加服补肾助孕中药后改善了子宫内膜容受性,有利于胚胎着床和临床妊娠率的提高。     

多囊卵巢综合征患者着床窗口期子宫内膜容受性的改变

目的探讨正常妇女与PCOS妇女促排卵治疗后着床期子宫内膜容受性相关因子的改变,包括整合素αv、MMP9、TIMP1、VEGF和LIF的表达。方法12例正常妇女自然周期(对照组)和8例PCOS患者经过促排卵治疗后(P-COS组)均在着床期取子宫内膜进行integrinαv、MMP9、TIMP1、VEGF和LIF免疫组化染色,并进行统计学分析。结果PCOS组E2、P水平高于正常组,但E2/P比值变化幅度大,PCOS组着床期子宫内膜中integrinαv、MMP9、TIMP1、VEGF和LIF表达均弱于对照组。结论PCOS患者促排卵治疗后E2、P分泌不协调,导致着床期子宫内膜integrinαv、MMP9、TIMP1、VEGF和LIF表达减弱,进而影响着床过程中的多个环节,这可能是造成PCOS患者促排卵治疗后高排卵率、低妊娠率和高流产率的原因之一。     

pAKt在不明原因性不孕症妇女着床期子宫内膜的表达及意义

目的研究磷酸化AKt（pAKt）在不明原因性不孕症妇女着床期子宫内膜的表达变化及意义。方法收集18份原发性不孕症、不明原因性不孕症妇女黄体中期子宫内膜组织作为研究对象，并收集30份继发性不孕症、双侧输卵管阻塞患者黄体中期子宫内膜组织作为对照。用SP免疫组化法确定两组患者子宫内膜pAKt与白血病抑制因子（UV）的组织学定位及半定量表达。结果LIF在两组患者子宫内膜的表达均主要定位在腔上皮和腺上皮胞浆，pAKt在两组患者子宫内膜的表达主要位于间质细胞且呈胞浆强表达。两组患者子宫内膜LIF与pAKt蛋白表达半定量分析（sP免疫组化法）：不明原因性不孕症患者子宫内膜LIF与pAKt表达量较双侧输卵管阻塞患者明显降低（P〈0．05），两组患者中IVF／ICSI后未妊娠者子宫内膜LIF与pAKt表达量较妊娠者明显降低（P〈0．01）。结论子宫内膜容受性降低是不明原因性不孕症患者不孕原因之一，着床期子宫内膜pAKt表达降低可能是不孕症患者子宫内膜容受性降低的原因之一。     

PCOS与非PCOS患者在控制性超促排卵周期子宫内膜容受性差异的探讨

目的探讨PCOS与非PCOS患者在控制性超促排卵周期子宫内膜容受性的差异。方法选取8例PCOS不孕患者并行IVF-ET长方案超促排卵治疗,同期选择8例因输卵管因素或男方因素行IVF-ET长方案的非PCOS不孕患者为对照组,在取卵后7天取子宫内膜组织,用免疫组化法测定子宫内膜雌激素受体(ER)、孕激素受体(PR)、整合素αvβ3,用RT-PCR法测定同源框基因HOXA-10的表达。结果控制性促排卵后PCOS组着床窗口期子宫内膜ER、PR表达低于对照组,但差异无统计学意义;αvβ3及HOXA-10表达低于对照组,差异有统计学意义。结论 PCOS患者在控制性超促排卵后仍存在子宫内膜容受性下降的因素。     

GnRH antagonist治疗多囊卵巢综合征的IVF-ET结局

目的探讨GnRH antagonist治疗PCOS病人的IVF—ET结局。方法将2006年4月至6月42例临床诊断为PCOS的病人随机分为两组：GnRH antagonist治疗组18人和GnRH agonist长方案对照组24人，记录促性腺激素的用量及其用药天数，获卵数，受精率，卵裂率，HCG日子宫内膜厚度和雌激素水平，周期取消率，妊娠率，OHSS发生率等。结果两组促性腺激素的用量及其用药天数、获卵数、受精率和卵裂率相比较均无显著差异。在hCG日的雌激素水平明显降低，子宫内膜是增厚的，其差异有统计学意义（P均＜0．05），妊娠率和着床率经X^2。检验，结果差异有统计学意义（P＜0．05）。结论GnRH antagonist治疗PCOS妊娠率和着床率均升高的，而卵泡的发育、卵母细胞的受精率和卵裂率不受影响。E2水平明显低于对照组可能为影响着床率和妊娠率的主要因素，GnRH antagonist用药是安全和高效的，为促排卵提供了新选择。     

多囊卵巢综合征促排卵治疗临床研究

目的观察来曲唑（LE）和克罗米芬（CC）治疗多囊卵巢综合征（PCOS）排卵障碍的临床疗效。方法将符合PCOS排卵障碍及中医辨证属肾阴虚型的60例患者随机分为两组：LE组（LE＋中药,n=30）,CC组（CC＋中药,n=30）。1个月经周期为1个疗程,观察3个月经周期内两组的卵泡发育、排卵、子宫内膜和受孕的情况。结果排卵情况：两组的卵泡直径≥16mm,卵泡数、排卵率差异无统计学意义（P〉0.05）,均无卵巢过度刺激综合征（OHSS）发生;子宫内膜及宫颈粘液情况：LE组人绒毛膜促性腺激素（hCG）日子宫内膜平均厚度、A型内膜、宫颈粘液平均评分与CC组比较差异有统计学意义（P〈0.05）;受孕情况：LE组妊娠率为73.33%,CC组妊娠率为56.67%,两组比较差异有统计学意义（P〈0.05）。结论 LE与CC均有促卵泡生长作用,LE可作为CC反应不良患者促排卵的替代治疗,LE较CC有较高的妊娠率,可能与其不影响子宫内膜容受性有关。     

来曲唑与克罗米酚用于多囊卵巢综合征80例促排卵疗效观察

目的将来曲唑（LE）与克罗米酚（CC）分别用于多囊卵巢综合征（PCOS）共80例,比较LE及CC对卵泡发育、子宫内膜、生殖激素及妊娠率的影响。方法选择PCOS 80例随机分成两组,各40例,均于月经来潮或撤退性出血第3-5天口服LE2.5 mg与CC50mg共5天,超声监测卵泡发育,当最大卵泡平均直径≥18mm时,肌肉注射绒毛膜促性腺激素（hCG）5000-1000 IU诱发排卵,于hCG日取肘静脉血测定黄体生成素（LH）、雌二醇（E2）、睾酮（T）,并观察排卵率、子宫内膜厚度、生殖激素及妊娠率的变化。结果出现优势卵泡LE组30例,CC组17例（P〈0.05）;单卵泡发育LE组23例,CC组5例（P〈0.05）;HCG注射日子宫内膜厚度LE组（9.93±1.45）mm,CC组（5.83±0.86）mm（P〈0.01）;LE组在HCG日血清E2为（199.0±122.4）pg/m l,CC组为（762±287.8）pg/m l,差异有统计学意义（P〈0.05）。血清T和LH水平,在两组间差异无统计学意义（P〉0.05）。结论 LE促排卵效果好,单卵泡发生率高,降低卵巢过度刺激综合征、多胎妊娠的发生率。     

Survivin和CD44v6在子宫内膜异位症中的表达及意义

目的研究Survivin、CD44v6在卵巢子宫内膜异位症中的表达，以探讨二者与卵巢子宫内膜异位症发病的关系。方法用免疫组化S-P方法检测卵巢子宫内膜异位症31例异位内膜、5例在位内膜、15例正常内膜中Survivin和CD44v6的表达。结果Survivin蛋白在异位内膜中表达明显高于在位内膜、正常内膜（P〈0．05）；CD44v6蛋白在异位内膜组与增生期内膜比较有统计学意义（P〈0．05），与其他两组比较无统计学意义（P〉0．05）；二者的表达不随AFS分期的变化而变化；并且二者在卵巢子宫内膜异位症中的表达呈相关性（r=0．24），但无统计学意义（P〉0．05）。结论Survivin和CD44v6在卵巢子宫内膜异位症中的异常表达对卵巢子宫内膜异位症的发生及发展起着重要的作用.     

子宫内膜样腺癌中Maspin、VEGF—C的表达与肌层浸润程度的临床研究

目的检测maspin和VEGF—C在子宫内膜样腺癌中的表达及与肌层浸润程度的意义。方法采用免疫组化法检测49例子宫内膜样腺癌及15例正常子宫内膜中maspin、VEGF—C的表达及与肌层浸润程度的意义。结果（1）Maspin在子宫内膜样腺癌中表达阳性,肌层浸润深maspin阳性表达率增高,差异无统计学意义（P〉0．05）。（2）VEGF—C在子宫内膜样腺癌中表达阳性,肌层浸润深度〉1／2组阳性率（75．0％）高于肌层浸润深度≤1／2组（36．4％）,差异具有统计学意义（P〈0．05）。（3）子宫内膜样腺癌中maspin和VEGF—C呈正相关关系（P〈0．05）。结论maspin和VEGF—C表达上调可能共同促进了子宫内膜样腺癌的发生、发展、侵袭及转移,二者联合检测可能对临床诊疗、判断预后有指导意义。     

TGF-β1在子宫内膜异位症与子宫内膜癌中的表达及生物学行为相关性研究

目的研究转化生长因子β-（TGF-β1在子宫内膜异位症、子宫内膜癌中的表达，探讨其表达与子宫内膜异位症发生及子宫内膜异位症和子宫内膜癌生物学行为的相关性。方法采用免疫组织化学方法检测10例子宫内膜异位症在位内膜、异位内膜，10例子宫内膜癌，10例对照组正常子宫内膜TGF-β1表达。结果TGF-β1在子宫内膜异位症异位内膜组中的表达显著高于子宫内膜异位症在位内膜组及对照组（P〈0．05、P〈0．05）；TGF—β1在子宫内膜癌组中的表达显著高于对照组（P〈0．05）；TGF-β1在子宫内膜异位症异位内膜组中的表达与子宫内膜癌组中的表达差异无显著性（P〉0．05）。结论TGF-β1的异常表达可能与子宫内膜异位症的发生有关；且可能与子宫内膜异位症具有和子宫内膜癌相似的生物学行为有关。     

宫腔灌注人绒毛膜促性腺激素改善多囊卵巢综合征患者子宫内膜容受性

目的探讨宫腔灌注人绒毛膜促性腺激素(hCG)对多囊卵巢综合征(PCOS)患者子宫内膜容受性、雌孕激素及其受体的影响。方法对照组(n=23)为健康女性,研究组为PCOS患者。研究组1(n=25)给予口服来曲唑;研究组2(n=20)口服来曲唑同时于排卵前2日及排卵日分别给予hCG 500 IU/mL宫腔灌注1次。各组均于排卵后第6~8天抽取子宫内膜,行免疫组织化学染色检测雌激素受体(ER)及孕激素受体(PR)的表达;扫描电镜(SEM)观察子宫内膜胞饮突;于取内膜当日用化学发光法检测血清雌激素(E2)和孕激素(P)的浓度;于排卵后16 d计算各组妊娠率。结果研究组1成熟期胞饮突的表达率低于对照组,研究组2成熟期胞饮突的表达率高于研究组1(P<0.05)。研究组1着床窗期P水平、子宫内膜PR阳性表达率均低于对照组,研究组2着床窗期P水平、子宫内膜PR阳性表达率均高于研究组1(P<0.05)。研究组1妊娠率低于对照组,研究组2妊娠率高于研究组1(P<0.05)。结论PCOS患者着床窗期胞饮突发育不良;宫腔灌注hCG可能使成熟期胞饮突数量增加,改善子宫内膜容受性,其机制可能与P水平升高、PR表达增加有关。     

Ovarian stimulation with GnRH agonist, but not GnRH antagonist, partially restores the expression of endometrial integrin beta3 and leukaemia-inhibitory factor and improves uterine receptivity in mice

BACKGROUND: The impact of different ovarian stimulation (OS) protocols on endometrial receptivity remains controversial. In this study, the effects of different OS on the expression of endometrial integrin beta3 subunit and leukaemia-inhibitory factor (LIF) during the implantation window and the implantation rate in mice were investigated. METHODS: Three OS protocols were used, involving either pregnant mare's serum gonadotrophin (PMSG) alone, PMSG plus GnRH agonist or PMSG plus GnRH antagonist. Uterus samples were collected at 48 h after OS or ovulation and were detected with immunohistochemistry, Western blot and RT-PCR analyses. Normal embryos at gestation day 4 were transferred into the uteri of mice in the control and OS groups. RESULTS: All OS groups showed a significant decrease in the expression of both the endometrial integrin beta3 subunit and LIF during the implantation window and the implantation rate. Among the three OS groups, GnRH agonist-treated mice showed a higher endometrial integrin beta3 subunit and LIF expression and a higher implantation rate. No significant difference was found in the measured indices between the GnRH antagonist and PMSG groups. CONCLUSIONS: OS may inhibit the expression of endometrial integrin beta3 subunit and LIF and impair endometrial receptivity in mice. OS with GnRH agonist, but not GnRH antagonist, may partially restore the endometrial physiological secretion and improve uterine receptivity.     

Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study

BACKGROUND: The aim of this work was to evaluate the efficacy of adding dexamethazone (DEX) (high dose, short course) to clomiphene citrate (CC) in CC-resistant polycystic ovary syndrome (PCOS) with normal dehydroepiandrosterone sulphate (DHEAS) in induction of ovulation. METHODS: Eighty infertile women with CC-resistant PCOS were randomly assigned into two groups. Group I: Clomiphene citrate 100 mg/day was given from day 3 to day 7 of the cycle and DEX 2 mg/day from day 3 to day 12 of the cycle. Group II: Same protocol of CC combined with placebo (folic acid tablets) was given from day 3 to day 12 of the cycle. The main outcome was ovulation. Secondary measures included number of follicles >18 mm endometrial thickness and pregnancy rate. Ovarian follicular response was monitored by transvaginal ultrasound. HCG 10,000 U was given when at least one follicle measured 18 mm, and timed intercourse was advised. RESULTS: There were no statistically significant differences between groups as regards age, duration of infertility, BMI, waist-hip ratio (WHR), menstrual pattern, hirsutism, serum DHEAS or day of HCG administration. The mean number of follicles>18 mm at the time of HCG administration and the mean endometrial thickness were significantly higher in the DEX group than in the placebo group (P<0.05). Similarly, there were significantly higher rates of ovulation (75 versus 15%) (P<0.001) and pregnancy (40 versus 5%) (P<0.05) in the DEX group. Dexamethazone was very well tolerated as no patients complained of any side effect. There was a significant difference between the responders and non-responders in the presence of oligomenorrhea, amenorrhea or hirsutism. CONCLUSION: Induction of ovulation by adding DEX (high dose, short course) to CC in CC-resistant PCOS with normal DHEAS is associated with no adverse anti-estrogenic effect on the endometrium and higher ovulation and pregnancy rates in a significant number of patients. Induction with DEX appears to be independent on age, period of infertility, BMI or WHR.     

Uterine effects of metformin administration in anovulatory women with polycystic ovary syndrome

BACKGROUND: Metformin has been shown to improve fertility in anovulatory patients with polycystic ovary syndrome (PCOS), inducing not only a high ovulation and pregnancy rate but also reducing the incidence of miscarriages. The aim of the present study was to evaluate the uterine effects of metformin in patients with PCOS who ovulated under metformin. METHODS: Thirty-seven non-obese primary infertile anovulatory patients with PCOS and another 30 age- and body mass index-matched healthy women (control group) were studied. PCOS patients were treated with metformin (850 mg twice daily) for 6 months, whereas the control group did not receive any treatment. In these PCOS patients who ovulated whilst under metformin treatment (PCOS group) and in controls, uterine, sub-endometrial and endometrial blood flow, and endometrial thickness and pattern were evaluated using serial ultrasonographic assessments. RESULTS: Before treatment, uterine, sub-endometrial and endometrial blood flows were significantly lower in patients with PCOS than in the control group. All indexes of uterine vascularization were significantly improved in the PCOS group with metformin treatment and were not different from the controls. Nor was any difference in endometrial thickness and pattern detected between PCOS and control groups. After grouping the data of PCOS patients who ovulated under metformin for cycles with favourable/unfavourable reproductive outcome, no difference in any parameter was observed. CONCLUSIONS: Metformin improves all surrogate markers of endometrial receptivity in PCOS patients, without difference between patients who had favourable or unfavourable reproductive outcome.     

宫腔内人工授精97个周期临床分析

目的 选择84对患者97个周期的宫腔内人工授精(IUI)进行临床疗效分析。方法 按自然周期、克罗米芬(CC) 补佳乐 HCG、克罗米芬(CC) HMG HCG分为三组进行围排卵期IUI技术比较。结果 84对患者进行97含属期IUI，自然周期11个，有1例妊娠，妊娠率0．09％；克罗米芬(CC) 补佳乐 HCG组57个周期，有8例妊娠，妊娠率14．04％：克罗米芬(CC) HMG HCG组29个周期，有6例妊娠，妊娠率20．69％。结论 使用促排卵药物，尤其克罗米芬(CC) HMG HCG组，诱发排卵数目多，子宫内膜厚。妊娠率高。     

Removal of hydrosalpinges increases endometrial leukaemia inhibitory factor (LIF) expression at the time of the implantation window

BACKGROUND: The presence of hydrosalpinges is associated with lower implantation and pregnancy rates in women undergoing IVF-embryo transfer, while salpingectomy improves these parameters. Although the mechanism by which hydrosalpinges affects fertility is not entirely understood, an adverse effect on endometrial receptivity has been postulated. In this study, we hypothesized that the adverse effects of hydrosalpinges on fertility may be in part mediated by inappropriate endometrial expression of leukaemia inhibitory factor (LIF), a cytokine implicated in implantation. METHODS: In order to test our hypothesis, we prospectively examined the expression of LIF during the window of implantation in the endometrium of infertile women (n = 10) with hydrosalpinges prior to and following salpingectomy and of fertile controls (n = 10) by Western blotting and immunohistochemistry. RESULTS: LIF expression was significantly lower in infertile women with hydrosalpinges compared with fertile controls (P < 0.05). Salpingectomy resulted in an increase in LIF expression in eight out of 10 women with hydrosalpinges. LIF levels were increased by 231 +/-49% (mean +/- SEM) following salpingectomy. Immunohistochemical analysis confirmed the Western blot findings. The increased LIF immunoreactivity was predominantly localized to luminal and glandular epithelial cells. CONCLUSIONS: Our findings suggest that observed benefit from salpingectomy in infertile women with hydrosalpinges may be in part mediated by the up-regulation of endometrial LIF expression.     

Hydrosalpinges adversely affect markers of endometrial receptivity

While in-vitro fertilization (IVF) was initially developed in women with tubal factor infertility, recent clinical studies have suggested that the presence of hydrosalpinges lowers implantation and pregnancy rates. We postulated that these hydrosalpinges cause impaired endometrial receptivity. A total of 103 women with hydrosalpinges were prospectively evaluated, and compared with 55 infertile and 44 fertile controls. All women had endometrial biopsies during the window of implantation, analysed by conventional histological criteria, and also stained for three integrin markers of endometrial receptivity (alpha1beta1, alpha4beta1 and alpha vbeta3). Women with hydrosalpinges (cases) expressed significantly less of the alpha vbeta3 integrin compared with controls. There was no difference in expression of alpha1beta1 or alpha4beta1 among groups. A significantly greater number of cases had out of phase histology and missing alpha vbeta3 (type I defects) and absent integrin expression despite normal histological maturation (type II) defects, compared with controls. Of 20 women with impaired endometrial receptivity who were also biopsied after hydrosalpinx surgery, 70% demonstrated increased alpha vbeta3 expression. Seventy-seven percent of type I and 57% of type II defects were corrected postoperatively. Using markers of endometrial receptivity, this study demonstrates that inflammatory hydrosalpinges have an adverse effect on endometrial receptivity, which in some cases may be overcome by surgical treatment of the hydrosalpinx.