Expression of α4β1 and αvβ3 integrins in the endometrium of women using the T200 copper intrauterine device

Objective: To investigate the expression of α4 and β3 integrin subunit levels in the endometrium of healthy women and copper intrauterine device (IUD) T200 users.Design: Case control study.Setting: An academic teaching hospital and a primary care clinic.Patient(s): Thirteen copper IUD users and 13 normal fertile women.Intervention(s): Timed endometrial biopsies during the mid-secretory phase (days 20 to 24).Main Outcome Measure(s): Histologic dating of endometrium and immunohistochemical staining intensity of α4 and β3, using the semiquantitative immunohistochemical score (HSCORE).Result(s): All endometrial biopsies consistent with menstrual dates were examined for integrin expression (β3 and α4). No difference in α4 integrin expression was found between IUD users and controls in both luminal and glandular epithelium. In fertile controls, αvβ3 staining was present in 100% and 38.4% of glandular and luminal epithelium, respectively. In contrast, only 61.5% of the IUD users had any αvβ3 staining in the glandular epithelium and only 53.9% in the luminal epithelium. The intensity of immunoreactivity between the two groups (mean HSCORE) did not differ significantly.Conclusion(s): Proportionately, significantly fewer women using copper IUD had positive αvβ3 immunoreactivity in the glandular epithelium of mid-secretory endometrium.     

A study of the copper T intrauterine contraceptive device (TCu 200) in nulliparous women

A study of the effectiveness and complications associated with the Model 200 copper T intrauterine device in 471 nulliparous women ranging in age from 14-33 years is reported, including 6044 woman-months of device use. 128 of the patients had had 1 or more previous abortions. This T-shaped device is made of polyethylene impregnated with barium sulfate, wound with .2 mm diameter copper wire providing a copper surface area of 200 square mm, and is inserted easily without anesthesia and with minimal pain. Continuation and failure rates were calculated for the first 12 months of use by life-table analysis. The overall continuation rate of device use was 74.2 per 100 women, the expulsion rate was 5.4, removal rate for bleeding or pain was 10.7, and pregnancy failure occurred at a rate of 1.7 per 100 women per year. These discontinuation event rates are lower than those reported for other IUDs in nulliparous women and comparable to IUD rates in multiparas. In the past, other IUD designs have been very unsatisfactory in nulliparas because of high expulsion and removal rates, but this study indicates that the TCu 200 IUD model is well accepted by nulliparas with good safety and effectiveness, and provides a promising and highly desired contraceptive alternative to oral contraception for young women.     

Expression of alpha(v)beta3 and alpha4beta1 integrins throughout the putative window of implantation in a cohort of healthy fertile women

BACKGROUND: Blastocyst implantation is a dynamic process requiring a specific cascade of cellular interactions and endometrial changes. The aim of this prospective observational study was to investigate the endometrial expression of alpha(v)beta3 and alpha4beta1 integrins throughout the window of implantation in healthy fertile women. MATERIALS AND METHODS: Forty fertile women (mean age 29.7 +/- 6.2 years) were recruited for this study. All underwent two endometrial biopsies in a single menstrual cycle. The first biopsy was performed on postovulatory day 6, while the second was taken on postovulatory day 8. Histological dating and immunohistochemical assessments of alpha(v)beta3 and alpha4beta1 integrins were analyzed. Oestradiol and progesterone serum concentrations were also measured at the time of biopsy. RESULTS: Second endometrial biopsy could not be performed in two of the 40 women (5%) because their menses had started in advance. No inflammatory or reactive phenomena were observed after biopsy. All the samples showed an in-phase endometrium. alpha(v)beta3 integrin expression was found in 21 out of the 38 first biopsies and in all 38 second biopsies (55.2% vs. 100%, p < 0.001). alpha4beta1 integrin expression was not significantly different between first and second biopsies (68.4% and 76.3%, NS). Oestradiol and progesterone serum concentrations were similar throughout the implantation window. Twelve of the 38 women (31.6%) conceived within 12 months of completing the study. All these had significantly higher alpha(v)beta3 integrin expressions in mid-luteal phase biopsies compared with those who did not conceive. CONCLUSIONS: These immunohistochemical findings demonstrate that both alpha(v)beta3 and alpha4beta1 integrins have a spatial and temporal expression throughout the implantation window in the endometrium of fertile women. Moreover, the shortage of alpha(v)beta3 integrin expression during the mid-luteal phase results in a detrimental effect for blastocyst implantation.     

Immunohistochemical analysis of alphavbeta5 and alphavbeta6 integrins in the endometrium and endometriosis.

We performed a case-controlled study to study the immunoreactivity patterns and staining intensity of alphavbeta5 and alphavbeta6 integrins in ectopic and eutopic endometrium from women with endometriosis and compared them with those in normal control endometrium. Forty eutopic and ectopic samples from patients with endometriosis were compared with 12 control endometrial samples. Staining was evaluated using a computerized image analysis system by a blinded, independent observer. The immunoreactivity patterns for both alphavbeta5 and alphavbeta6 were very similar. In eutopic endometrium from women with or without endometriosis, the immunostaining intensity score for both integrins was stronger during the secretory than the proliferative phase. Immunoreactivity in endometriosis was greater than in eutopic endometrium. There were no significant menstrual cycle-related staining differences in endometriosis. The percentage of blood vessels immunolabeled was greater in endometriosis than eutopic endometrium from endometriosis patients and greater in eutopic endometrium from these patients compared with control endometrium. Ectopic tissue from patients with stages I and II endometriosis showed significantly higher staining intensity than ectopic tissue from patients with stages III and IV disease. Determination of the specific functional consequences of the differences observed in alphavbeta5 and alphavbeta6 integrin immunostaining may provide an increased understanding regarding the pathogenesis of endometriosis.     

放置IUD后宫腔微生物及子宫内膜病理学研究

研究ＩＵＤ与盆腔感染及子宫内膜恶变或其他病理改变的关系,探讨 ＩＵＤ长期使用的安全性。方法：将 ８８例分为 Ａ、Ｂ、Ｃ、Ｄ ４组,Ａ组 ２０例使用带尾丝活性 ＩＵＤ;Ｂ组２４例使用惰性 ＩＵＤ;Ｃ组 ２４例为正常对照组;Ｄ组 ２０例为盆腔感染组。所有病例取宫腔冲洗液进行需氧菌、厌养菌、解脲支原体、沙眼衣原体等培养,并取子宫内膜进行病理学检查,结果：Ａ、Ｂ组主要表现为正常增生期、分泌期或月经期子宫内膜,部分是单纯性或腺囊性增生,与Ｃ组、Ｄ组差异无显著性（Ｐ＞０．０５）,４组均未见不典型增生及恶变。Ａ、Ｂ、Ｃ３组子宫内膜均无慢性炎症改变,Ｄ组８例存在慢性子宫内膜炎改变,与Ａ、Ｂ、Ｃ组差异有显著性（Ｐ＜０．０５）。Ａ、Ｂ、Ｃ组淋巴细胞、浆细胞、中性白细胞、纤维细胞计数差异无显著性（Ｐ＞０．０５）,Ｄ组淋巴细胞、浆细胞、中性白细胞计数较以上３组明显增加（Ｐ＜０．０５）,间质细胞及纤维细胞计数与以上３组差异无显著性（Ｐ＞０．０５）。Ａ、Ｂ、Ｃ组宫腔微生物检出率分别为３０．０％,２９．２％,２０．８％,与Ｄ组（７０．０％）差异有显著性（Ｐ＜０．０５）。结论：使用ＩＵＤ５－１４年未增加子宫内膜癌、癌前病变及慢性子宫内膜炎发生率。Ｉ     

Synchronous expression of pinopodes and alpha v beta 3 and alpha 4 beta 1 integrins in the endometrial surface epithelium of normally menstruating women during the implantation window

OBJECTIVE: To use histology, scanning electron microscopy (SEM) and immunohistochemistry to examine the expression of pinopodes, and alpha v beta 3 and alpha 4 beta 1 integrins in the same endometrial biopsies. STUDY DESIGN: A prospective observational study. Fifteen consecutive regularly menstruating women with normal hormone profiles were followed for detection of ovulation and then biopsied twice, on postovulatory days luteinizing hormone (LH) +6 and LH +8. Measurements included abundance and development stage of pinopodes and a semiquantitative assessment of intensity of antibody staining for integrins. RESULTS: All biopsies observed under light microscopy showed an in-phase endometrium. Pinopodes were found developing mostly on day LH +6 and were fully developed on day LH +8. The expression of alpha v beta 3 dimer increased significantly from day LH +6 to day LH +8, while alpha 4 beta 1 dimer did not show any significant change during the same period. Fully developed pinopodes and strong intensity of alpha v beta 3 integrin were the most common findings. CONCLUSION: These results indicate a coordinated, synchronous change in morphology and adhesion molecule expression of endometrial epithelial cells on day LH +8 of a normal menstrual cycle.     

Osteopontin and alphavbeta3 integrin expression in the endometrium of infertile and fertile women

Osteopontin and its receptor alpha(v)beta(3) integrin have recently been proposed as a major complex to promote embryo attachment, and thus they would be useful as markers of endometrial receptivity. In the current study alpha(v)beta(3) integrin and osteopontin expression and co-expression in in-phase and out-of-phase endometrial biopsies from normal healthy women (n = 12) and infertile patients (n = 107) were investigated. Two endometrial biopsies (post-ovulatory day +6 to +8, and 4 days later) were performed during a single menstrual cycle in each subject. Oestradiol and progesterone serum concentrations were quantified on the same days as endometrial sampling. No statistically significant difference regarding alpha(v)beta(3) integrin and osteopontin expression and their coexpression was found between fertile controls and infertile patients irrespective of endometria being in-phase or out-of-phase, infertility factors detected or whether patients became spontaneously pregnant or not. Although a co-ordinate high concentration of both glycoproteins on post-ovulatory day 8 onwards was observed, there was an evident lack of temporal co-expression of these markers during the implantation window. It is concluded that the functional significance of the osteopontin:alpha(v)beta(3) integrin complex as a marker of endometrial receptivity and implantation potential in women seems to be untenable.     

Plasminogen activators in the endometrium of women using intrauterine contraceptive devices.

Plasminogen activators in the endometrium before and after the insertion of an intrauterine contraceptive device (IUCD) were studied; an increase in the concentration was found following IUCD insertion in 16 of the 20 women. This change will enhance endometrial fibrinolysis and may explain the increased menstrual bleeding which usually follows insertion of an IUCD.     

The peritoneal reaction to the translocated copper intrauterine device in women and female rats

The observation of a very severe peritoneal reaction to translocated copper-bearing devices in five women necessitated operative removal. Three Copper-T (Ortho Gyne-T, Ortho, Saunderton, High Wycombe, England) and two Copper-7 (Gravigard, Searle, High Wycombe, England) devices were involved. Similarly severe peritoneal reactions were noted in 90% of female rats who had small-sized modified copper devices inserted into their peritoneal cavities. In a control group of rats with the same device but without a copper wire, mild adhesions were observed in the majority (85%), and none had a severe peritoneal reaction. It seems evident that the severe peritoneal reaction is induced by the copper wire in both women and female rats.     

白细胞介素1α、β及γ干扰素mRNA在子宫内膜异位症患者异位和在位子宫内膜巨噬细胞中的表达

目的探讨白细胞介素(IL)1α、β mRNA和γ干扰素(IFN-γ)mRNA在子宫内膜异位症(内异症)患者异位和在位内膜巨噬细胞中的表达变化及意义.方法采用原位杂交技术检测40例内异症患者(内异症组)异位和在位内膜(增生期18例,分泌期22例)和15例子宫肌瘤患者(对照组)的内膜(增生期8例,分泌期7例)巨噬细胞中IL-1α、β和IFN-γmRNA表达水平.结果(1)内异症组患者异位、在位内膜及对照组内膜巨噬细胞中IL-1α mRNA阳性表达率分别为70%(28/40)、38%(15/40)和20%(3/15),表达水平分别为3.12±0.32、2.65±0.34、1.32±0.23;IL-1βmRNA阳性表达率分别为75%(30/40)、40%(16/40)和20%(3/15),表达水平分别为3.45±0.43、2.74±0.39、1.45±0.18;内异症组IL-1α、β mRNA的表达水平较对照组明显升高,内异症组异位内膜较在位内膜的表达水平也明显升高,差异均有统计学意义(P＜0.05).(2)内异症组在位内膜和对照组内膜巨噬细胞中IL-1α、β mRNA表达分泌期高于增生期,差异也有统计学意义(P＜0.05).(3)内异症组内膜巨噬细胞中IFN-γmRNA的表达水平与对照组比较,差异无统计学意义(P＞0.05),且无周期性变化.结论内异症患者在位内膜和异位内膜巨噬细胞IL-1表达明显增强,而IFN-γ表达则无明显变化,推测内膜巨噬细胞及其分泌的细胞因子,可能参与了内异症的发生、发展过程.     

Comparison of three different models of the copper T intrauterine contraceptive device.

A random sequential comparative study of three models of the Copper T intrauterine contraceptive device (IUD) was undertaken in 1,792 women. For 7 months, the TCu 300 and TCu 220C were randomly inserted, and then the TCu 380A and 220C were randomly inserted for the next 12 months. The log-risk method of life-table analysis of event rates was performed at the end of each of the first 3 years of use of each device. The TCu 380A had the lowest pregnancy rate during each year of use, although the difference was not significant. At the end of each of the first 2 years, the TCu 300 was removed significantly less than the TCu 220C and TCu 380A for bleeding and pain. At the end of three years, the rates of removal for bleeding and pain for the TCu 380A and TCu 300 were similar and lower than that for the TCu 220C, but the overall difference was not significant. There were no differences among the devices for any other relevant use-related reasons. The TCu 380A was removed for other medical reasons significantly more frequently than the other devices at the end of 2 and 3 years. Adjusting for parity did not alter the results. The findings of this study suggest that the copper sleeves along the horizontal arms together with copper wire on the vertical arm in the TCu 380A model provide greater protection against intrauterine pregnancy, whereas the copper sleeves along the vertical arm as in the TCu 220C caused increased removals for bleeding and pain. The TCu 380A should be studied in a larger number of patients for a longer period of time to determine its clinical effectiveness. It may become the IUD of choice for all women irrespective of parity.     

Changes in copper and zinc serum levels in women wearing a copper TCu-380A intrauterine device

Abstract

Objective To assess the effects of the copper intrauterine device (IUD) TCu-380A, on copper and zinc serum levels.

Material and methods This longitudinal study enrolled 121 women attending Health Centres in Tehran between November 2011 and August 2012. A blood sample was obtained before use and three months after insertion of a TCu-380A IUD. Serum levels of copper and zinc were measured for the 101 women who had completed three months with the device in situ. Analyses of change included paired t-tests, McNemar tests and linear regression.

Results Significant elevations in mean serum levels were found for both copper (170.22 μg/dl at three months vs.160.40 μg/dl at baseline, p = 0.034) and zinc (107.67 μg/dl at three months vs. 94.61 μg/dl at baseline, p < 0.001) three months after IUD insertion.

Conclusions A slight, but significant increase in copper serum levels, not reaching toxic levels, was observed three months after TCu-380A IUD insertion. Zinc levels too had risen significantly, which was quite unexpected, and warrants further investigation.     

Haematocrit and other haematological values in women using intrauterine contraceptive device

To determine the long-range effect of insertion of intrauterine devices on hematological factors, the blood test results of 50 women between 25 and 40 years of age who had had an IUD in situ for 6-24 months (Group A) were compared with the test results of 50 women of similar age distribution without the IUD, serving as controls (Group B). Blood tests revealed the following significant differences between the groups: The hemoglobin level in Group A averaged 11.14, while group B averaged 12.81. The mean hematocrit was 35.8% in Group A and 38.7% in Group B. The mean red cell count was 3.87 million/cu.mm in Group A and 4.63 million/cu.mm in Group B. The mean corpuscular hemoglobin was 28.6 mcg in Group A and 29.5 mcg in Group B. The mean corpuscular hemoglobin concentration was 31.6% in Group A and 33.3% in Group B. There was no significant difference between the groups in mean corpuscular volume. It is concluded that the use of an IUD for 6 months or longer leads to a significant fall in hemoglobin level, hematocrit value, and red cell count. These results should be considered in planning a population control program with the intrauterine device.