Transplacental passage of cefazolin in the first trimester of pregnancy

The transfer of cefazolin, an antibiotic compound of the cefalosporin group, through the placental barrier was investigated in the first trimester of pregnancy. All cases were chosen from among women admitted for therapeutic abortion. The test group comprised 70 women, while there were 30 in the control group. The bacteriostatic activity was examined in the amniotic fluid, obtained by the vaginal route as well as in the maternal blood, following the i.m. injection of 500 mg cefazolin.Our results indicate that the antibiotic cefazolin crosses the placental barrier, even during the first trimester of pregnancy. However, the concentrations obtained were considerably lower than those observed in the 2nd and 3rd trimesters (Dekel et al., 1977; Goldman et al., 1980).     

生存素在正常子宫内膜、增生子宫内膜及子宫内膜癌中的表达研究

目的探讨生存紊(surviving)在正常子宫内膜、增生子宫内膜以及子宫内膜癌中的表达；并探讨生存紊与子宫内膜癌的临床分期、病理级别及浸润子宫肌层深度的关系。方法取正常周期、单纯增生、不典型增生子宫内膜各20例；萎缩性子宫内膜10例以及子宫内膜癌20例，应用人生存紊多克隆抗体，采用免疫组织化学SSCP法，观察其表达情况。结果生存紊在20例分泌期子宫内膜中全部表达，细胞浆呈均匀染色；20例增殖期子宫内膜，60％呈细胞浆均匀染色染色；10例萎缩型子宫内膜均不表达生存紊；20例单纯增生子宫内膜全部表达生存紊，细胞浆均匀染色；20例非典型增生子宫内膜全部表达生存紊，但问质细胞表达弱于腺上皮细胞；30例子宫内膜癌细胞100％表达生存紊，特点是100％浆表达，间质细胞表达明显弱于腺上皮细胞，同时43．33％核表达，且核表达率与临床期别、病理级别、侵犯基层深度有密切关系，统计学差异显著结论生存紊不是子宫内膜癌特有的标志蛋白，但可能是预后判断和监测治疗的指标。     

Polo-样激酶1在子宫内膜异位症患者在位和异位子宫内膜中的表达

目的探讨Polo－样激酶1（PLK1）在子宫内膜异位症发生发展中的作用。方法采用逆转录（RT—PCR）、蛋白免疫印迹法（Western blotting）及免疫组织化学的方法检测子宫内膜异位症患者的异位子宫内膜组织29例和在位子宫内膜组织20例及正常子宫内膜组织30例中PLK1的表达。结果PLK1蛋白在内异症组增殖期异位（2．19±0．63）和在位子宫内膜组织（1．78±0．59）上的表达量明显高于对照组子宫内膜组织（1．21±0．30）上的表达量（P〈0．05）。PLK1蛋白在内异症组分泌期异位（1．15±0．332）和在位子宫内膜组织（1．00±0．33）上的表达量明显高于对照组子宫内膜组织（0．82±0．24）上的表达量（P〈0．05）。内异症组增殖期和分泌期异位和在位子宫内膜组织上PLK1的表达量比较,差异均无统计学意义（P〉0．05）。结论PLK1蛋白的高表达可能与子宫内膜异位症的发生发展有关。     

The incidence of persistent functioning endometrial tissue following successful radiotherapy for cervical carcinoma

Sixty-three patients under the age of 50 years who were long-term survivors following radiotherapy for cervical cancer and had been placed on hormone replacement therapy (HRT) were identified. The median age at treatment was 37 years and the mean delay from treatment to the initiation of HRT was over 15 months. Fifteen of the 63 patients had experienced vaginal bleeding attributable to the effects of HRT on persisting endometrial tissue. The significance of this is discussed.     

Protein profile of the luteal phase endometrium by tissue microarray assessment

To investigate the luteal phase endometrial expression of leukemia inhibitor factor (LIF), insulin-like growth factor 1 (IGF-1), progesterone receptor (PR), claudin 4 (CLDN4), vascular-endothelial growth factor receptor 3 (VEGFR-3), bone morphogenetic protein 4 (BMP-4) and citokeratin 7 (CK-7), we obtained luteal phase endometrial samples from 52 women. Samples were dated and integrated using a tissue microarray (TMA). Samples were immunostained for LIF, IGF-1, PR, CLDN4, VEGFR-3, BMP-4 and CK-7. Frequencies of positive expressions at the early, mid and late luteal phases were compared by two proportions test. Concomitant expression of these proteins was assessed with Chi-square or Fischer's test. The frequency of LIF was positively correlated to the frequency of IGF-1 (r = 0.99; p < 0.05) and PR (r = 0.99; p < 0.05), and the correlation between IGF-1 and PR tended to be significant (r = 0.98; p < 0.1). The expression of PR was associated with the absence of CLDN4 (p < 0.001). Thus, expression of LIF, IGF-1 and PR are correlated during the luteal phase, and immunohistochemistry for these proteins might be used to assist in the assessment of endometrial maturation. In addition, the expression of CLDN4 and PR was not concomitant, warranting further investigation on the relationship of their endometrial expression.     

Measurement of endometrial tissue blood flow: a novel way to assess uterine receptivity for implantation

Objective: To assess endometrial receptivity in terms of endometrial tissue blood flow (ETBF) measured hysterofiberscopically by laser blood-flowmetry, and to examine the technique’s effectiveness in an in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) program.

Design: A prospective clinical study.

Setting(s): IVF program in a university hospital.

Patient(s): A total of 75 infertile women with normal menstrual cycles undergoing IVF/ICSI.

Intervention(s): ETBF, conventional ultrasonographic, endocrinologic, and histologic parameters for receptivity and immunoreactivity for vascular endothelial growth factor (VEGF) in endometrium were assessed between days 4 and 6 of the luteal phase in a spontaneous menstrual cycle. Then all patients underwent IVF/ICSI.

Main Outcome Measure(s): Achievement of clinical pregnancy by IVF/ICSI.

Result(s): ETBF, VEGF expression, and the number of embryos were significantly higher in the women who became pregnant than in those who did not. By stepwise multiple logistic regression, significant predictors of pregnancy were the number of embryos and ETBF but not conventional receptivity markers. The rate of pregnancy was significantly higher in women with ETBF values of at least 29 mL/min per 100 grams of tissue than in women with lower values (42 vs. 15% in 36 and 39 women, respectively). ETBF was significantly greater in morphologically normal than abnormal uteri. In normal uteri, ETBF was greatest in the fundus. Correspondingly, in normal uteri 85% of gestational sacs were implanted in the fundus.

Conclusion(s): ETBF is superior to conventional parameters for determining endometrial receptivity for implantation.     

Expression of claudin-3 and claudin-4 in normal, hyperplastic, and malignant endometrial tissue

To clarify the roles of claudins in endometrial tumorigenesis, we determined levels of protein and messengerRNA (mRNA) expression of claudin-3 and claudin-4 in human endometrial tissue (proliferative phase [PE, n= 25]; secretory phase [SE, n= 25]; simple hyperplasia [SH, n= 20]; complex hyperplasia [CH, n= 12]; atypical hyperplasia [AH, n= 15]; endometrioid adenocarcinoma [EEC, n= 30]) using immunohistochemistry, western blotting, and real-time polymerase chain reaction, respectively. Morphologic changes of tight junctions (TJs) were also observed in normal, hyperplastic, and malignant endometrial tissue. Absence or weak staining for claudin-3 and claudin-4 was observed in PE, SE, SH, and CH, while medium to intense staining was detected in AH and EEC. Staining of claudin-3 and claudin-4 was predominantly localized to the glandular epithelial cell membrane. Expression of claudin-3 and claudin-4 was significantly increased in the groups of AH and EEC in comparison with the groups of CH, SH, and normal cyclic endometrium at both protein and mRNA levels. The highest expression was observed in EEC. Although no relevance was found with regard to FIGO stage and histologic grade, overexpression of claudin-3 and claudin-4, especially claudin-4, significantly correlated with myometrial invasion. Transmission electron microscopy analysis indicated morphologic disruptions of TJs may lag behind the increase of claudins expression. These results demonstrate that claudin-3 and claudin-4 are strongly expressed in AH and EEC, but less frequently in normal endometrium. The upregulation of claudins expression during endometrial carcinogenesis suggests their potential utility as diagnostic and prognostic biomarkers.     

Importance of endometrial quality in women with tubal infertility during a natural menstrual cycle for the outcome of IVF treatment

Purpose: The importance of endometrial maturation at estimated time of implantation for the outcome of IVF treatment in regularly menstruating women with tubal infertility was evaluated. Methods: FSH was measured on cycle day 3, on days 10–15 urine and blood were collected to estimate the day of the LH peak, and E₂ and P₄ were measured during the luteal phase, on cycle days 19–26. An endometrial biopsy was obtained on days LH + 3 to LH + 6. Results: The number of subjects with delayed endometrial maturation was larger in the group of infertile women who did not become pregnant compared to pregnant women and controls. Those infertile women who did not become pregnant after IVF treatment also presented with a higher basal FSH on cycle day 3 and lower E₂ and P₄ AUC in the luteal phase. Six infertile women and two controls presented with mid- and late-proliferative endometrium in the luteal phase on cycle days LH + 3 to LH + 6, in the presence of adequate E₂ and P₄ secretion. Six morphological characteristics were compared in the three groups: (1) 17 infertile women who became pregnant, (2) 18 who did not become pregnant, and (3) 28 controls. The pregnant infertile women did not differ from the controls. The numbers of glandular and stromal mitoses were significantly higher in those women who did not become pregnant (P<0.01) compared with those who became pregnant. Endometrial biopsies obtained on cycle days LH + 5 and LH + 6 showed significant differences in glandular epithelial height (P<0.05) and number of vacuolated cells among the nonpregnant women (P<0.01), the pregnant women (P<0.05), and controls. Conclusions: A higher frequency of retarded endometrial development in women who did not become pregnant following IVF treatment was found. In some cases, endometrial insensitivity could most likely cause retarded endometrial development and failure of implantation after IVF treatment, which could not be overcome by routine luteal-phase support. However, our results do not allow conclusions concerning its relative importance compared to preembryo quality; this has to be investigated further.     

Histological dating of timed endometrial biopsy tissue is not related to fertility status

OBJECTIVE: To assess the ability of histological dating to discriminate between women of fertile and infertile couples. The utility of histological dating of endometrium in the evaluation of infertile couples is uncertain. DESIGN: Prospective multicenter study, with subjects randomly assigned to biopsy timing. Criterion standard for infertility was 12 months of unprotected, regular intercourse without conception and for fertility at least one live birth within 2 years. SETTING: University-based infertility practices. PATIENT(S): Volunteer subjects (847) recruited at 12 clinical sites participating in the National Institutes of Health-funded Reproductive Medicine Network. Inclusion criteria included ages 20-39 years, regular menstrual cycles, and no hormonal treatment or contraceptive use for 1 month before the study. Fertile controls were excluded if they had a history of infertility, recurrent pregnancy loss, or recent breastfeeding. INTERVENTION(S): Subjects underwent daily urinary LH testing. After detection of the LH surge, subjects were randomized to biopsy in the mid (days 21-22) or the late (days 26-27) luteal phase. Pathologists at each site estimated the cycle day based on standard criteria. For the primary analysis, an out-of-phase biopsy was defined as a greater than 2-day delay in the histological maturation of the endometrium. MAIN OUTCOME MEASURE(S): The proportion of out-of-phase biopsies in fertile and infertile women was compared using logistic regression models with age at randomization as a covariate. Comparisons were also made between fertile vs. infertile at the midluteal or late luteal phase time points. RESULT(S): Biopsies were evaluated (301 mid and 318 late; N = 619). Out-of-phase biopsy results poorly discriminated between women from fertile and infertile couples in either the midluteal (fertile: 49.4%, infertile: 43.2%) or late luteal phase (fertile: 35.3%, infertile 23.0%). Results did not substantially differ using alternative definitions of "out-of-phase" or standardized cycle day. CONCLUSION(S): Histological dating of the endometrium does not discriminate between women of fertile and infertile couples and should not be used in the routine evaluation of infertility.     

Oral contraceptives suppress cell proliferation and enhance apoptosis of eutopic endometrial tissue from patients with endometriosis

Objective: To evaluate the effects of administering combination oral contraceptives (COCs) to patients with endometriosis on the regulation of cell growth in the eutopic endometrium.

Design: Prospective study.

Setting: Research institute and clinical fertility center.

Patient(s): Thirteen women with untreated endometriosis and 13 controls.

Intervention(s): Biopsy specimens of the eutopic endometrium were obtained from all subjects. Apoptosis, cell proliferation, and Bcl-2 and Bax expression were examined at the epithelial and stromal levels in the eutopic endometrium from patients with endometriosis before and after 30 days of daily exposure to COCs and from controls.

Main Outcome Measure(s): Apoptotic cells were detected by using the dUTP nick-end labeling assay; Ki-67, Bcl-2, and Bax expressions were assessed by using immunohistochemical techniques.

Result(s): After exposure to COCs, apoptosis was significantly increased in the eutopic endometrium compared with before COC administration, both at epithelial and stromal levels. Cell proliferation was significantly lowered by COCs.

Conclusion(s): COCs showed a positive effect on patients with endometriosis by down-regulating cell proliferation and enhancing apoptosis in the eutopic endometrium.     

Advanced endometrial adenocarcinoma following endometrial ablation: a case report and review of the literature

Endometrial ablation is an alternate method to hysterectomy when treating dysfunctional uterine bleeding (menorrhagia, metrorrhagia and postmenopausal) that does not respond to hormonal treatment or curettage among a carefully evaluated and selected patient population. Its safety and efficacy have been confirmed in large studies. We present a case of advanced staged endometrial carcinoma diagnosed after endometrial ablation that followed uneventful preoperative work-up.     

输卵管阻塞患者宫颈和输卵管衣原体、支原体的检测分析

目的 研究输卵管阻塞患者输卵管分泌物衣原体(CT)、支原体(UU)阳性率。方法39例经腹腔镜诊断为输卵管阻塞、要求行输卵管再通手术患者为实验组,26例因其他病因行手术治疗、输卵管正常患者为对照组,采用多聚酶链反应技术(PCR) 对实验组和对照组患者宫颈分泌物和输卵管分泌物CT和UU进行检测。结果 实验组宫颈分泌物CT、UU的检出阳性率分别为35.9%(14/39)、38.5% (15/39),输卵管分泌物的CT、UU检出阳性率分别为25.6％(10/39)、5.1％(2/39);与对照组比较,宫颈分泌物CT、UU感染无明显差异P>0.05);输卵管分泌物CT阳性检出率差异有显著性(P<0.05)。实验组CT阳性检出率高于UU检出率,差异有显著性(P<0.05)。39例术中输卵管不同程度增粗、管壁增厚,其中19条输卵管管壁增厚,僵硬,管壁纤维化,管腔消失。结论 宫颈和输卵管是CT、UU感染的好发部位,CT、UU能损害输卵管粘膜,造成输卵管阻塞,引起输卵管性不孕。     

The influence of hydrosalpinx on endometrial elafin expression

The endometrium of women with hydrosalpinx has an increased number of neutrophils and lower expression of elafin, an elastase inhibitor and natural antimicrobial molecule. These findings suggest that women with hydrosalpinx have a reduced antimicrobial and antielastase activity.     

Endometrial hyperplasia involving endometrial polyps: report of a series and discussion of the significance in an endometrial biopsy specimen

Objectives  Endometrial polyps are a common cause of abnormal uterine bleeding. Rarely, a hyperplasia, either complex or atypical in type, is identified within a polyp in a biopsy or polypectomy specimen. Currently, it is not known whether the hyperplasia is likely to be confined to the polyp or also involve nonpolypoid endometrium. We aim to assess the likelihood of hyperplasia being confined to an endometrial polyp.
Design  In this study, we identified 32 women from pathology archives in whom endometrial hyperplasia was present within a polyp. The number of endometrial polyps during the study period was 1031 and therefore 3.1% of all endometrial polyps diagnosed during the study period contained a hyperplasia.
Setting  A major teaching hospital in the UK.
Methods  The biopsies were retrieved from the pathology archives of Royal Group of Hospitals, Belfast, between 2000 and 2006. We traced any follow-up biopsy or hysterectomy specimens to evaluate the status of the surrounding endometrium.
Results  The hyperplasias were complex ( n = 23) or atypical ( n = 9) in type. In 14 of 27 (52%) women in whom nonpolypoid endometrium was available for histological evaluation, either on the original biopsy or in a follow-up specimen, hyperplasia involved the nonpolypoid endometrium, and in three other women, hyperplasia was present in a polyp in follow-up specimens. Women with atypical hyperplasia in a polyp were slightly more likely to have hyperplasia in the surrounding endometrium than those with complex hyperplasia.
Conclusions  Our study illustrates that the risk of endometrial hyperplasia in a polyp concurrently involving nonpolypoid endometrium is significant. We suggest a strategy for the management of women with hyperplasia identified within an endometrial polyp in a biopsy or polypectomy specimen.     

Surgical adhesives and tubal sterilization: an experimental study

AIM: Our aim was to assess the application of three currently used surgical adhesives in the tubal lumen of rabbits, to promote sterilization, using a transvaginal approach. METHODS: Fifty-seven female albino New Zealand rabbits (114 uterine tubes), which became pregnant and delivered before the experiment, were divided into four groups: GS (sham-24 tubes), GEFIBRI (0.25 mL of fibrin adhesive in 30 tubes), GE-GRF (0.25 mL of resorcin adhesive in 30 tubes) and GEBUTYL (0.25 mL of n-butyl-2-cyanoacrylate adhesive in 30 tubes). The animals were mated with proven fertile males after the experiment and observed over 30, 90 and 180 days. Pregnancy and patency were macroscopically evaluated. The tubal diameter, tubal mucosa, myosalpinx, total optical density and inflammatory process were microscopically evaluated. The statistical analysis was performed by McNemar and Wilcoxon tests for the subgroups, and Fisher's exact test and Kruskal-Wallis test for the groups, the differences identified by Dunn's multiple comparisons test (P=5%). RESULTS: GS showed patency and pregnancies in all subgroups. GEFIBRI showed patency and pregnancies in all subgroups. GE-GRF did not show patency or pregnancies, but was associated with severe inflammatory process and tubal morphology alterations. GEBUTYL did not show patency, pregnancies or morphological tubal mucosa alterations. CONCLUSIONS: The n-butyl-2-cyanoacrylate adhesive effectively promoted tubal obstruction, did not cause tubal morphological alterations, nor did it impair the rabbit pregnancy. The fibrin adhesive failed to cause the occlusion. The GRF adhesive, in spite of producing tubal occlusion, caused severe uterine tubes damage.