子宫内膜异位症患者瘦素检测及临床意义

目的检测子宫内膜异位症(EMS)患者血清和腹腔液瘦素(Leptin)水平的变化及在子宫内膜表达情况,探讨其在内异症发病中的作用。方法放射免疫法测定40例内异症患者和40例非内异症患者妇女(对照组1)血清和腹腔液Leptin的水平。抗生物素蛋白-过氧化物酶(SP)法检测瘦素在子宫内膜表达情况,并与R-AFS分期进行相关分析。同期检测50例健康妇女(对照组2)血清Leptin水平。结果 EMS患者血清瘦素水平与对照组间比较无差异;腹腔液中瘦素水平明显高于对照组;EMS患者和对照组子宫内膜中均有瘦素表达,EMS患者与对照组表达上存在差异(P<0.05)。结论内异症患者腹腔液中瘦素水平明显升高,并随疾病的严重程度而改变,同期影响瘦素在子宫内膜中的表达,这可能是瘦素在内异症的发生发展中起作用的机制。     

抗子宫内膜抗体在子宫内膜异位症诊断中的评价

本文采用纯化了的人子宫内膜抗原以间接酶联免疫法检测经手术或腹腔镜证实了的子宫内膜异位症患者62例，单纯子宫肌腺病者8例及正常对照组30例的血标本，结果发现子宫内膜异位症组抗宫内膜抗体阳性率为58．6%，子宫内膜异位症之不育患者抗宫内膜抗体阳性率为72．22%，均明显高于对照组6．67%及子宫肌腺病组12．5%，并且发现子宫内膜异位症组中抗内膜抗体的阳性率随其分期的升高而下降，Ⅳ期子宫内膜异位症之阳性率已与对照组无差异。认为：抗子宫内膜抗体的检测不失为一种对子宫内膜异位症患者无捐伤的，经济方便的辅助诊断方法，尤其对轻度子宫内膜异位症患者更具价值。     

黄体中期子宫内膜活检在诊断黄体功能中的意义

目的 对原因不明的不孕症及反复流产患者的黄体期行不同时间子宫内膜活检,寻找患者不孕的原因,并观察内膜活检在诊断卵巢黄体功能上的意义。方法 对５３例不孕症患者进行了黄体中期血孕酮检测和黄体中,晚期子宫内膜活检。结果 ５３例患者中２４例子宫内膜分泌延迟都发生在黄体中期、其中９例内膜分泌延迟一直持续到晚期,这些患者的平均血孕酮值较正常组明显偏低（Ｐ〈０．０５）。另１３例晚期内膜分泌转为正常,其平均血孕酮     

galectin-3在子宫内膜异位症患者在位内膜中的表达及意义

目的：探讨galectin-3在子宫内膜异位症（内异症）患者在位子宫内膜中的表达及意义.方法：分别采用免疫组化和实时定量逆转录-聚合酶链反应（Real-time RT-PCR）检测内异症患者在位内膜及正常对照中galectin-3蛋白及mRNA的表达,比较其表达差异.结果：galectin-3蛋白定位于子宫内膜的腔上皮细胞、腺上皮细胞和间质细胞.与正常对照相比,galectin-3 mRNA及蛋白在内异症在位内膜中的表达显著下降（P＜0.05）.其表达在分泌期高于增生期.结论：内异症患者在位子宫内膜galectin-3低表达可能与其子宫内膜容受性的改变有关,从而导致了内异症不孕.     

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。     

端粒酶逆转录酶和c-myc基因在子宫内膜样癌及子宫内膜增生中的表达

目的　探讨端粒酶逆转录酶 (hTERT)及c myc基因在子宫内膜增生及癌变过程中的作用、意义及二者相关性。方法　所用标本包括 14例子宫内膜单纯增生 ,8例复合增生 ,10例不典型增生 ,42例内膜样癌 ,用原位杂交法检测hTERT和c mycmRNA表达。结果　 (1)hTERT在子宫内膜单纯、复合、不典型增生病变和内膜样癌中阳性结果分别 2 / 14、4/ 8、8/ 10和 92 9% (3 9/ 42 ) ,前两组均为弱阳性表达 ,后两组多为中度和强阳性 ,统计分析表明不典型增生病变和内膜样癌中hTERT表达高于单纯和复合增生 (P <0 0 5)。c myc在子宫内膜单纯、复合、不典型增生病变和内膜样癌中阳性结果分别 3 / 14、1/ 8、5/ 10和 54 8% (2 3 / 42 ) ,后两组c myc阳性率显著高于前两组 (P <0 0 5) ;不典型增生病变的c myc阳性水平高于单纯及复合增生 (P <0 0 5)。(2 )hTERT阳性水平与内膜样癌分化相关(P <0 15) ;c myc阳性率随内膜样癌浸润深度增加而递增 (P <0 0 5)。 (3 )子宫内膜增生和内膜样癌各组中hTERT与c myc表达均不相关 (P >0 0 5)。结论　hTERT及c myc基因过表达与子宫内膜不典型增生及恶性转化相关 ,并与内膜样癌演进以及不良预后有关 ,但其两者表达之间无相关性     

子宫内膜异位症患者的免疫功能变化

本研究对４４名经腹腔镜手术或剖腹手术证实为子宫内膜异位症患者进行免疫功能的研究，并与正常健康育龄妇女作对照。结果发现子宫内膜异位症患者体液免疫指标异常增高，外周血ＩｇＡ，Ｃ３及Ｃ４含量明显高于正常生育组。体内产生了抗子宫内膜抗体及抗磷脂抗体，显示出子宫内膜异位症患者出现自身免疫现象。而患者细胞免疫功能明显下降，表现在外周血ＣＤ３＋和ＣＤ４＋细胞及ＣＤ４＋／ＣＤＳ＋比值明显低于对照组，这种机体免疫调节失衡参与了子宫内膜异位症的发生与发展。临床应用手术＋丹那唑治疗后，ＩｇＧ、子宫内膜抗体及磷脂抗体水平均明显下降，调节了患者紊乱的免疫功能，使增强的体液免疫反应受到抑制，且有效地清除了循环系统的自身抗体。但未能有效地改善患者的细胞免疫功能。     

GnRHⅡ蛋白在子宫内膜异位症患者中的表达及意义

目的：检测GnRHⅡ蛋白在子宫内膜异位症患者异位子宫内膜、在位子宫内膜和正常子宫内膜中的表达情况,同时分析其表达是否与子宫内膜月经周期有关。方法：采用免疫组织化学SP法检测GnRHⅡ蛋白在异位内膜、在位内膜及正常子宫内膜组织中的表达情况,并分析和比较其表达是否有差异。结果：GnRHⅡ蛋白在子宫内膜异位症患者异位、在位子宫内膜及正常子宫内膜中均有表达,阳性表达定位于子宫内膜腺体及间质细胞的细胞质;GnRHⅡ蛋白在异位内膜、在位内膜及对照组正常内膜的表达依次增强,两两比较差异有统计学意义（P＜0.05）;GnRHⅡ蛋白在正常子宫内膜分泌期表达强于增生期（P＜0.05）,且以分泌早中期最强,显著强于增生期和分泌晚期（P＜0.01）,而异位组或在位组的分泌期与增生期比较,差异无统计学意义（P＞0.05）。结论：GnRHⅡ蛋白在子宫内膜异位症的发病中以及在人类月经生理方面可能起重要作用。     

\"种植窗\"时期人类子宫内膜组织差异蛋白质表达谱的初步研究

目的:建立\"种植窗\"时期人子宫内膜组织蛋白质差异表达的研究方法,探讨差异蛋白质表达与子宫内膜对胚胎接受性的关系。方法:采用荧光差异凝胶电泳比较\"种植窗\"前期[黄体生成素(LH)+2d]和\"种植窗\"时期(LH+7d)子宫内膜组织差异表达的蛋白质,并进行蛋白质功能聚类分析并探讨其与胚胎着床关系。Westernblotting检测差异蛋白膜联蛋白IV的表达以确认结果。结果:在pH3~10NL的双向电泳上显示的胶内差异图像经分析测到(2555±98)个蛋白质斑点。经鉴定、检索、查找和确认差异表达蛋白质共31个,其中17个上调表达,14个下调表达。查阅文献发现31个差异表达的蛋白质功能涉及到细胞迁移与融合、酶活性改变、信号转导与基因调控、免疫调节、血管生成和凝血纤溶等6个系统,与胚胎着床高度相关。膜联蛋白IV在蛋白质组学和Westernblotting表达趋势一致。结论:\"种植窗\"时期人子宫内膜上皮组织差异表达蛋白质的研究,发现与胚胎着床活动密切相关的6个功能组群蛋白质表达的动态变化,提示它们是参与子宫内膜向接受态转化的重要蛋白质,为探讨\"种植窗\"时期子宫内膜组织功能变化的研究提供了新的思路和途径。     

米非司酮在子宫内膜异位症患者腹腔镜手术中的应用研究

目的 观察促黄体激素释放激素类似物与米非司酮联合治疗,子宫内膜异位症腹腔镜手术患者的血清性激素水平的变化情况。方法 选取我院2019年5月~2020年10月收治的116例子宫内膜异位症患者,根据住院尾号奇、偶数分为两组,各58例,对照组给予促性腺激素释放激素治疗,观察组促性腺激素释放激素联合米非司酮,比较治疗前、结束时血清相关指标[促卵泡激素（FSH）、雌二醇（E2）、睾酮（T）、黄体生成素（LH）、血管内皮生长因子（VEGF）水平,基质金属蛋白酶-9（MMP-9）、脂氧素A4（LXA4）]及不良反应。结果 治疗结束时,观察组FSH、LH、E2、T低于对照组,差异有统计学意义（P＜0.05）;观察组VEGF、MMP-9水平低于对照组,LXA4高于对照组,差异有统计学意义（P＜0.05）;两组患者治疗期间失眠、潮热、阴道干涩等不良反应总发生率对比,差异无统计学意义（P＞0.05）。结论 子宫内膜异位症患者腹腔镜术后给予促黄体激素释放激素类似物联合米非司酮治疗,可改善机体血清性激素水平,缓解炎症状态,利于子宫内膜异位症腹腔镜手术患者恢复。     

CA-125 secretion by luteal phase endometrium in vitro

The source of CA-125 in normal women and the mechanisms which control CA-125 production remain to be defined. This study was initiated to examine the pattern of secretion of CA-125 from luteal phase endometrium. Endometrial samples were obtained during the early luteal phase (histological days 16-18) and late luteal phase (histological days 25-27) from ovulatory women with a laparoscopically normal pelvis. The tissue was maintained in explant culture using Trowell's T-8 medium with either no additions (NA), progesterone (P), oestradiol (E2), or E2 + P. The concentration of CA-125 in spent media from the second day in culture was determined by immunoradiometric assay. In early luteal endometrium, the concentration of CA-125 in spent media from the NA treated wells was significantly higher than when the endometrium was exposed to either P or E2 + P. Similar differences were noted between treatments for the late luteal endometrium. Within each treatment, there was a higher concentration of CA-125 in the spent media from the late versus the early luteal endometrium. We conclude that the endometrium is a potential source of serum CA-125 and that endometrial CA-125 is suppressed by P in both the early and the late luteal phase. Further, there appears to be an increase in endometrial CA-125 secretion from the early to the late luteal phase.     

The sonographic and endocrinologic evaluation of the endometrium in the luteal phase

Follicular development and the endometrial thickness were determinedsonographically in 19 outpatients with different causes of sterility,treated during natural or stimulated cycles. The estimates ofthe endometrial thickness, assessed by ultrasound in the mid-lutealphase, and the levels of 17-oestradiol and progesterone in thesame patients sampled on the day of sonography were compared.Five patients became pregnant (group 1) and showed good progesteronevalues. Eight patients who were not pregnant showed progesteronevalues above 15 ng/ml in the mid-luteal phase (group 2). Theprogesterone values of group 3 were below 15 ng/ml by definition.The mean endometrial thickness in group 1 (= 11.3 mm) and group 2 ( = 11.8 mm) weresignificantly higher than that of group 3 (= 8.3 mm). The sonographic measurement of the mid-luteal endometriumthickness serves as an additional criterion for the evaluationof the secretory phase of the menstrual cycle.     

The artificial cycle as an effective treatment of persistently retarded endometrium in the luteal phase

The objective of this study was to examine the results of twohormonal treatment modalities on subjects who had persistentlyabnormal endometrial development in the luteal phase. A prospectivestudy design was used to investigate 14 women who had persistentlyretarded endometrium associated with infertility (n = 11) orrecurrent miscarriage (n = 3). Treatment A consisted of progesteronesupplementation in the form of i.m. progesterone at a dailydose of 25–50 mg starting on day luteinizing hormone (LH)+1for 14 days. Treatment B consisted of artificial cycles producedafter down-regulation of the hypothalamic-pituitary-ovarianaxis with Goserelin (3.6 mg s.c.) followed by the administrationof a standard hormone replacement therapy. Endometrial biopsywas taken on day 19 of the artificial cycle or days LH +5 to+7 in the progesterone supplementation cycle. A histologicalstudy was made of the endometrial specimens by standard datingcriteria and morphometry. The artificial cycle resulted in normaldevelopment in all subjects (n = 11), whereas progesterone supplementationrestored normal endometrial development in only seven of 11(64%) subjects. We conclude that persistently retarded endometriumcould be treated more effectively with the artificial cyclethan with progesterone supplementation.     

Changes in basement membrane thickness in the human endometrium during the luteal phase of the menstrual cycle

We have examined aspects of the fine structure of the basal laminae associated with the luminal and glandular epithelium and small blood vessels in the human endometrium. Four short studies are presented and reviewed. Study 1 examined biopsies from 20 fertile women taken on days after the luteinizing hormone surge (LH): LH +2, 4, 6, 8 and 10. The basal lamina (both lamina densa and lucida) increased in thickness over the period studied. Study 2 again studied the glandular epithelium and examined the effect of RU486 (a progesterone receptor blocker) administered on day LH +3 and biopsied on day LH +6. The basal laminae were found to be the same as LH +2 control group but thinner than LH +6 control. Study 3 documented increased thickness of the basal laminae between LH +6, 8 and 13 in the luminal epithelium. The within-group coefficient of variation was 16% and 27% for LH +6 and LH +13 groups but only 2 % for LH +8. Study 4 demonstrated an increase in basal lamina thickness associated with small blood vessels between LH +6 and LH +10 in normal fertile women. The basal lamina provides the interface between epithelial and mesenchymal environments; changes in its structure can alter the phenotypic expression of the epithelia. It is one of the maternal barriers that must be transgressed by the trophoblast during implantation. Together, these combined studies provide quantitative baseline structural information on the electron microscopical appearance of the basal lamina during the luteal phase of the menstrual cycle.     

Uterus and endometrium: Immunohistochemical localization of extracellular matrix proteins in luteal phase endometrium of fertile and infertile patients

The lack of expression of certain components involved in celladhesion and migration is believed to contribute to endometrialdysfunction and implantation failure. The purpose of this studywas to investigate whether luteal phase endometrium in womenwith unexplained infertility differs, with respect to specificextracellular matrix (ECM) proteins, from endometrium of normalfertile women. A panel of monoclonal antibodies to collagentype IV, fibronectin and laminin was used to characterize thelocalization of ECM components in the different endometrialcompartments. Precisely timed endometrial biopsies obtainedat 4, 7, 10 and 13 days following the luteinizing hormone surgewere obtained from 22 normal fertile women (group 1) and 24women suffering from unexplained infertility (group 2). Paraffin-embeddedsections were labelled using the streptavidin-biotin alkalinephosphatase technique. In group 1, collagen type IV, fibronectinand laminin were absent from the luminal epithelium but presentin stromal cells and the basement membrane of glands and bloodvessels. In group 2, these components were absent from all endometrialregions using equivalent titres of antibody to those used ingroup 1. This suggests that the endometrium of women with unexplainedinfertility demonstrates defects in the distribution of certainECM glycoproteins. A possible consequence of this defect maybe implantation failure.     

Morphological changes and protein secretion induced by progesterone in the endometrium during the luteal phase in preparation for nidation

Progesterone induces morphological modifications and protein secretion during the luteal phase to permit implantation/nidation. It acts through specific receptors which are regulated by oestrogens. The proliferative phase is thus a prerequisite for progesterone activity. Changes in morphology are first located in the glandular component, with peak secretion occurring during the implantation window. The various components of the stroma are involved during the second part of the luteal phase, resulting in decidualization and the formation of spiral arteries. The subsequent fall-off in progesterone leads to menstruation. The next cycle begins with a regenerative process in which oestrogens induce the modifications typical of the proliferative phase. The luteal phase is usually assessed on morphological criteria but should also be accompanied by protein secretion profiles of glands and stroma.     

The endometrium in natural and artificial luteal phases

The normal human endometrium reacts precisely and sen–sitivelyto any hormonal stimulation with predictable changes. If thecorpus luteum develops normally after ovulation, the progesteronesecreted induces specific changes in endometrial glandular andstromal cells that can be dated by dally fine–structuralalterations. With corpus luteum deficiency the endometrial differentationis delayed and remains incomplete. The defect in the differentiationof glands and stroma varies in their distribution and intensityand may be dissociated or coordinated depending upon the causeof the corpus luteum deficiency. The administration of naturalprogesterone in the second half of the cycle prolongs the lutealphase and may result in hypersecretion of glands. In contrast,therapy with synthetic gestagens depresses glandular secretion,induces glandular atrophy and decidualization of the stroma.The various synthetic gestagens differ both quantitatively andqualitatively in their action; depending upon the dosage giventhe endometrium remains in abortive or arrested secretion, domlphenedepresses normal secretion by its antioestrogenk effect whichcauses deficient oestrogen priming. On the other hand, clomiphenecounteracts excessive oestrogen and will normalize the secretionin a deficient luteal phase that was preceded by follicularpersistency. In the artificial cycle, depending upon the stateof endogenous hormonal stimulation, the patients will benefiteither from clomiphene or gonadotrophin to maintain or normalizetheir secretory endometrium.     

Evaluation of the luteal phase

The values of various methods used to evaluate the luteal phase, including basal body temperature, measurement of progesterone (P), endometrial biopsy, ultrasonographic measurement of endometrial thickness, and measurement of endometrial proteins, are reviewed. Luteal phase defect (LPD) is a controversial entity. The diagnosis of this condition is best based on a histological study of the endometrium. Methods to improve the accuracy of the diagnosis are discussed. LPD is more likely to be a result of an abnormal response of the endometrium to P, than to a subnormal production of P by the corpus luteum. Many methods of treatment for LPD have been proposed but none is based on a properly controlled clinical trial. Treatment designed to improve the response of the endometrium to P may be more rewarding than P supplementation.     

Placental protein 14 in endometrium during menstrual cycle and effect of early luteal phase mifepristone administration on its expression in implantation stage endometrium in the rhesus monkey

Placental protein 14 (PP14) is a glycoprotein which is secreted by secretory phase endometrium and decidua in women. Despite the suggestion that PP14 is involved in the process of endometrial maturation for blastocyst implantation, our understanding in this regard is poor. In the present study, the concentrations and distribution patterns of immunodetectable PP14 in the endometrium during proliferative and secretory phases of normal ovulatory menstrual cycles, as well as in implantation stage endometrium in naturally mated ovulatory cycles with or without early luteal phase mifepristone treatment, were investigated using the rhesus monkey as a primate model. Immunopositive PP14 was observed mainly in epithelial cells of glands and it was detected in one major immunopositive band at Mr 28 kDa in tissue homogenate and spent medium. The area of immunopositive precipitation of PP14 in glands was minimal in follicular phase endometrium, and was higher (P < 0.01) in early, mid- and late luteal phase endometrium compared with that in pre- and periovulatory phases of the cycle, but there was no change in its area profile in the glandular compartment throughout the luteal phase. Immunopositivity for PP14 in luminal contents of gland displayed an increasing profile from early to late secretory phases. Thus, the concentrations and the distribution of immunodetectable PP14 in luteal phase endometrium of the rhesus monkey showed marked similarity with those of human endometrium during the natural menstrual cycle. Although there was no marked change in the band characterstics for the protein in implantation stage endometrium following early luteal phase mifepristone treatment, it was markedly decreased (P < 0.01) in tissue homogenate and in vitro spent medium along with a lesser (P < 0.02) degree of immunoprecipitation in the glands in implantation stage samples of mifepristone treatment group compared with that in control group samples. Thus, the contragestional effect of early luteal phase mifepristone treatment appears to be associated with a decrease in the concentration of immunodetectable PP14 in implantation stage endometrial glands and its secretion in the rhesus monkey. It remains to be seen whether this decline is caused from direct antiprogesterone action on endometrial glands during progesterone dominance, or secondarily from associated retarded development of endometrium.      

The effect of RU 486 administered during the early luteal phase on bleeding pattern, hormonal parameters and endometrium

The purpose of the present study was to investigate the effect of a single dose of RU 486 administered very early in the secretory phase on endometrial development and levels of progesterone receptors, on plasma levels of gonadotrophins and ovarian hormones and on the pattern of menstrual bleeding. Twenty-four regularly menstruating subjects participated and were studied during a control, a treatment and a follow-up cycle. In the treatment cycle, a single dose of 200 mg RU 486 was given in the evening of the second day after the urinary LH peak. Plasma was collected from cycle day 10 until menstruation in both control and treatment cycles. The lengths of the control, treatment and follow-up cycles were equal. Three of the subjects had slight vaginal bleeding in association with RU 486 intake which, however, did not disturb their normal menstrual rhythm. Plasma levels of oestradiol, progesterone and FSH were not affected in the treatment cycle, whereas LH levels increased slightly. The elimination half-life of RU 486 was 28.6 h. An endometrial biopsy was taken 12, 36 or 84 h (LH + 3, LH + 4 and LH + 6) after drug intake (eight subjects in each group) and another biopsy was taken on the corresponding day in the control cycle. The specimens were assessed by morphometric analysis and for cytosolic progesterone receptor concentrations. Endometrial biopsies taken 12 h (on LH + 3) after RU 486 intake contained significantly (P less than 0.001) lower levels of cytosolic progesterone receptors than in the control cycle, but levels at 36 and 84 h were similar.(ABSTRACT TRUNCATED AT 250 WORDS)