Sonographic assessment of the endometrium in osteopenic postmenopausal women treated with idoxifene.

Idoxifene is a novel selective estrogen receptor modulator that has shown beneficial effects on bone turnover and lipid metabolism in clinical studies. Preclinical studies have demonstrated that idoxifene has estrogen antagonist activities on the endometrium. This paper describes the results of a double-blind, placebo-controlled, and dose ranging study involving 331 osteopenic postmenopausal women who were treated with either placebo or idoxifene (2.5, 5, or 10 mg/day) for 12 weeks. In these women, endometrial assessment was carried out by transvaginal sonography and endometrial biopsy on selected patients at baseline and on all women at the end of treatment. Women with an endometrial thickness greater than 10 mm were excluded from the study. Aspiration endometrial biopsy was performed on women with an endometrial thickness between 6 and 10 mm at baseline and on all women after treatment. Of the 298 biopsies performed in the subjects at the end of treatment, 99% of the women were reported to have either a benign or atrophic endometrium (85%) or insufficient tissue for diagnosis (14%). Proliferative histologic features were reported in two cases (1%) (2.5 mg idoxifene) and atypical hyperplasia in one placebo patient. Even though idoxifene use was associated with a dose related increase in endometrial thickness as evaluated by transvaginal sonography, no relationship was established between endometrial histologic features and change in endometrial thickness. On histologic analysis, the increase in endometrial thickness seen on transvaginal sonography was not associated with proliferative or hyperplastic change in the epithelial (glandular) endometrial tissue. In 48 patients (16% of total) transvaginal sonography showed endometrial thickening of 5 mm or more over the study period. The endometrial histologic features were benign in all these patients. Nineteen percent of women developed intraluminal fluid, even though endometrial thickness was normal and unchanged and histologic features were normal. Our data show that after 3 months of treatment, no significant pathologic changes of the endometrium were observed. Our data indicate that measurements of endometrial thickness by transvaginal sonography may falsely suggest the presence of endometrial pathologic changes in some postmenopausal women treated with idoxifene. Additional testing using saline infusion sonohysterography is an important part of the transvaginal sonography protocol in equivocal or abnormal cases to exclude focal lesions such as polyps. In addition, our data indicate that pathologic changes of the endometrium are extremely rare in the treated group, indicative of its short term safety. Continued investigation such as this will be needed to establish long term safety.     

永川区1872例健康妇女子宫内膜经阴道超声检查结果分析

目的了解正常妇女子宫内膜回声及厚度情况，为建立中国妇女正常子宫内膜标准提供依据。方法对重庆市永川区1872例已婚健康妇女进行经阴道超声检查，观察内膜声像图并测定其内膜厚度，而后进行统计分析。结果绝经前不同年龄段的妇女从增生期、排卵期到分泌期其子宫内膜逐渐增厚，回声逐渐增强；在不同月经周期，其子宫内膜厚度差异有统计学意义（P〈0．05），但在同一月经周期不同年龄段妇女子宫内膜厚度差异无统计学意义；绝经前和绝经后妇女子宫内膜厚度差异有统计学意义。结论通过经阴道超声普查，建立大样本的数据库，将有助于建立中国妇女正常子宫内膜的标准，为鉴别异常子宫内膜提供依据。     

Clinical significance of endometrial fluid collections in asymptomatic postmenopausal women.

Routine vaginal ultrasonographic evaluation of pelvic organs was performed in asymptomatic postmenopausal women to evaluate the diagnostic significance of sonographic findings of endometrial fluid collections in the presence of a thin endometrium in postmenopausal women. The study included nine women aged 61 to 79 years who had been postmenopausal for 7 to 30 years, and in whom endometrial fluid collections were incidently demonstrated. Endometrial samplings followed the ultrasonographic examinations in all nine patients, and the correlation between the histologic report and the endometrial ultrasonographic thickness was evaluated. The diameter of the endometrial fluid collections varied from 3 to 12 mm. The thickness of the endometrium surrounding the fluid ranged from 1 to 3 mm. Of the nine endometrial samples examined, five revealed atrophic endometrium, three had insufficient material for histologic evaluation, and one specimen revealed well-differentiated adenocarcinoma. The woman in whom endometrial carcinoma was diagnosed underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and lymph node sampling. The pathologic examination confirmed the previous histologic finding, and deep penetration into the myometrium was noticed with intact lymph nodes. Endometrial fluid collections found in asymptomatic postmenopausal patients still may be associated with endometrial malignancy, even in the presence of thin endometrium.     

Sonographic depiction of postmenopausal endometrium with transabdominal and transvaginal scanning.

The thickness of the endometrium was measured in postmenopausal women by both the transvaginal and transabdominal ultrasound approaches in two separate groups of patients. The first group consisted of 90 women who received a transabdominal scan of the endometrium before dilatation and curettage or hysterectomy for either postmenopausal bleeding or uterine prolapse. The second group consisted of 111 women who underwent a transvaginal scan of the endometrium for similar postmenopausal conditions.Both methods suggested that an endometrial thickness of 5 mm may be used as a cut-off level in the conservative management of patients with postmenopausal bleeding or in a screening program for endometrial carcinoma.Patient acceptance and image quality were better in the group examined transvaginally. The proximity of the transvaginal probe to the endometrium, in the absence of a full bladder compressing the endometrium, revealed a unique group of patients with atrophic endometrium but thick endometrial cavity caused by intracavity fluid. In the presence of uterine fibroids distorting the uterine cavity, transvaginal scanning was better than transabdominal scanning for visualizing the endometrium. The transabdominal full-bladder technique can be of value in detecting asymptomatic bladder pathology.     

宫腔镜联合免疫组织化学法确诊子宫内膜癌的临床研究

目的 探讨宫腔镜及抑癌基因PTEN（phosphatase and tensin homolog deleted on chromosome ten）、P27的免疫组织化学法在子宫内膜癌及癌前病变诊断中的意义。方法 宫腔镜检查846例患者，免疫组织化学SP法检测其中10例正常子宫内膜，13例子宫内膜不典型增生，32例子宫内膜癌中PTEN和P27基因表达。结果 宫腔镜及病理检查确诊32例子宫内膜癌（3．78％）；3种组织比较，PTEN、P27阳性表达率明显降低，差异有显著性（P〈0．01）。结论 宫腔镜检查直观病灶，准确活检，宜于早期诊断；PTEN、P27表达异常对子宫内膜癌发生、发展及预后判定有重要意义。     

Combination of endometrial thickness and time since menopause in predicting endometrial cancer in women with postmenopausal bleeding

PURPOSE: This study was conducted to assess the combination of endometrial thickness, as measured by transvaginal sonography, and time since menopause, in predicting the presence of endometrial cancer in women with postmenopausal bleeding. METHODS: The study group consisted of 95 women with postmenopausal bleeding who underwent sonographic measurement of endometrial thickness followed by endometrial biopsy. No patient had ever received hormone replacement therapy. RESULTS: The mean endometrial thickness was significantly lower in the absence of endometrial carcinoma (6.9 +/- 4.3 mm) than in its presence (13.5 +/- 7.7 mm) (p < 0.005). The incidence of endometrial carcinoma increased with increases in endometrial thickness and the number of years since menopause. No patient had carcinoma when the endometrium was less than 5 mm thick, but 18.5% did when the thickness exceeded 9 mm. The incidence of cancer was 2.6% in women who had undergone menopause less than 5 years earlier but was 21.4% in women who had undergone menopause more than 15 years prior. Multiple logistic regression analysis showed that time since menopause and endometrial thickness were statistically significant predictors of endometrial carcinoma. CONCLUSIONS: Time since menopause and endometrial thickness together define cutoff points for the diagnostic biopsy of tissue samples for endometrial carcinoma; that is, within a particular time interval, sampling should not be performed if the thickness is below a given value. When using cutoff points of 6 mm of endometrial thickness for women experiencing menopause 5-15 years prior and 5 mm in those going through menopause 15 or more years prior, approximately 60% of invasive procedures may be avoided. In addition, models derived by multiple logistic regression can be used to calculate a patient's risk of cancer based on her age and endometrial thickness.     

Errors in the measurement of endometrial depth using transvaginal sonography in postmenopausal women on tamoxifen: random error is reduced using saline instillation sonography.

OBJECTIVE: The endometrium in women on tamoxifen is often made irregular by small cysts. The aim of this study was to assess the accuracy and precision of the measurement of endometrial depth by transvaginal sonography. METHODS: The endometrial depth from endometrial biopsies obtained with the resectoscope in 15 women receiving tamoxifen was compared to the endometrial depth measured by TVS. The inter-observer variability was measured in 58 women. RESULTS: In those biopsies of sufficient quality to allow a measurement, the corresponding depth measurement obtained by ultrasound was up to 3 mm greater than the histological measurement. The interobserver variability for the measurement of endometrial depth using TVS was assessed in 58 postmenopausal women on tamoxifen. The interobserver variability deteriorated as the mean endometrial depth increased, probably because the increase in depth resulted from greater morphological changes within the endometrium such as cyst formation which resulted in an irregular endometrial/myometrial boundary. This may, however, be improved by performing saline instillation sonography. In a prospective study of 10 postmenopausal women, the interobserver variability was significantly greater during tamoxifen treatment compared to pretreatment. CONCLUSIONS: On the basis of the above, if uterine surveillance using TVS were to be offered to postmenopausal women on tamoxifen, then the procedure should be augmented by saline instillation sonography if the endometrial depth is > 4 mm, as this will improve the measurement precision and also identify intrauterine pathology.     

A thin and regular endometrium on ultrasound is very unlikely in patients with endometrial malignancy.

OBJECTIVE: To evaluate the clinical and sonographic features in patients with endometrial malignancy in whom endometrial thickness on ultrasound examination had been recorded in our database to be < 5 mm. METHODS: This was a retrospective observational study on 187 consecutive patients diagnosed with endometrial malignancy in whom an ultrasound evaluation of the endometrium had been performed in our institution. The characteristics of those patients presenting with an endometrial thickness < 5 mm were analyzed. RESULTS: The median endometrial thickness was 15 mm: 12 mm for the women who underwent endometrial sampling before ultrasound examination vs. 17 mm in those who did not (P = 0.0086). In 13 women (6.9%), the endometrial thickness recorded in our database was < 5 mm. In 12 of these the measurement was compromised in some way: nine of these patients had undergone endometrial sampling (Pipelle biopsy in one and dilatation and curettage in eight patients) before the ultrasound examination, in two cases, focal malignant lesions were not included in the recorded endometrial thickness and in one, the endometrial thickness was visualized poorly due to myometrial distortion. In only one case was was the endometrium correctly measured to be < 5 mm; this woman had diffuse uterine and endometrial metastases of a breast cancer. CONCLUSIONS: A thin and regular endometrial line is very reliable for the exclusion of endometrial carcinoma. The suspicion of focal lesions as well as incomplete visualization of the endometrium on sonography should be considered abnormal. Recently performed endometrial sampling makes measurement of the endometrial thickness unreliable.     

In vivo evaluation of endometrium through dual-modality intrauterine endoscopy

Female infertilities are highly associated with poor endometrial receptivity. A receptive endometrium is generally characterized by the normal uterine cavity, intact endometrial surface, appropriate endometrial thickness, and echo pattern. Acquiring comprehensive structural information is the prerequisite of endometrium assessment, which is beyond the ability of any single-modality imaging method. In this paper, we introduce a custom-made intrauterine dual-modality (OCT/ultrasound) endoscopic imaging system and achieve in vivo imaging of rabbit uteri, for the first time to our knowledge. The endometrial features of the injured uteri in both ultrasonic and OCT images are consistent with their corresponding pathology. The quantified parameters, including uterine thickness and endometrial surface roughness, show the correlation with the endometrial injury degree but with poor performance for injury classification. The combination of these parameters was proved to assess the degrees of endometrial injury more accurately. Our work shows the potential of the dual-modality system to be translated into a clinical tool, providing multiple quantitative imaging information and helping evaluate the endometrial receptivity and diagnose infertility.     

An algorithm including results of gray-scale and power Doppler ultrasound examination to predict endometrial malignancy in women with postmenopausal bleeding.

OBJECTIVE: To determine if power Doppler ultrasound examination of the endometrium can contribute to a correct diagnosis of endometrial malignancy in women with postmenopausal bleeding and endometrium > or = 5 mm. METHODS: Eighty-three women with postmenopausal bleeding and endometrium > or = 5 mm underwent gray-scale and power Doppler ultrasound examination using predetermined, standardized settings. Suspicion of endometrial malignancy at gray-scale ultrasound examination (endometrial morphology) was noted, and the color content of the endometrium at power Doppler examination was estimated subjectively (endometrial color score). Computer analysis of the most vascularized area of the endometrium was done off-line in a standardized manner. Stepwise multivariate logistic regression analysis was carried out to determine which subjective and objective ultrasound and power Doppler variables satisfied the criteria to be included in a model to calculate the probability of endometrial malignancy. RESULTS: Endometrial thickness, vascularity index (vascularized area/endometrial area), and use of hormone replacement therapy (HRT) satisfied the criteria to be included in the model used to calculate the 'objective probability of endometrial malignancy'. Endometrial morphology, endometrial color score and HRT use satisfied the criteria to be included in the model to calculate the 'subjective probability of malignancy'. Endometrial thickness > or = 10.5 mm had a sensitivity with regard to endometrial cancer of 0.88 and a specificity of 0.61. At a fixed sensitivity of 0.88, the specificity of the 'objective probability of malignancy' (0.81) was superior to all other ultrasound and power Doppler variables (P = 0.001-0.02). The 'objective probability of malignancy' detected more malignancies at endometrium 5-15 mm than endometrial morphology (5/7 vs. 1/7, i.e. 0.71 vs. 0.14; P = 0.125) with a similar specificity (49/57 vs. 51/57, i.e. 0.86 vs. 0.89). CONCLUSION: Power Doppler ultrasound can contribute to a correct diagnosis of endometrial malignancy, especially if the endometrium measures 5-15 mm. The use of regression models including power Doppler results to estimate the risk of endometrial cancer deserves further development.     

经阴道超声综合评价子宫内膜容受性的研究

目的探讨经阴道超声（包括灰阶超声及彩色能量多普勒超声）检测内膜厚度、血流分布及内膜波状运动在综合评价子宫内膜容受性中的价值。方法对57例（157个月经周期）接受促排卵治疗的患者,在注射绒毛膜促性腺激素（HCG）日行经阴道超声检查,观测子宫内膜厚度、内膜及内膜下血流分型及内膜波状运动的类型和频率。按是否妊娠分两组,比较两组之间各指标的差异。结果子宫内膜厚度两组之间无统计学差异;内膜及内膜下血流分型两组之间有统计学差异（P〈0.05）;非妊娠组子宫内膜波状运动总频率及负向运动频率均高于妊娠组,两组之间有统计学差异（P〈0.05）。结论注射HCG日经阴道超声综合观测子宫内膜厚度、内膜及内膜下血流、内膜波状运动有助于评价子宫内膜容受性,预测妊娠结局。     

Transvaginal color and pulsed Doppler sonography of the endometrium: a possible role in reducing the number of dilatation and curettage procedures.

The objectives of the study were to establish color and pulsed Doppler sonographic characteristics of uterine vascularity in postmenopausal patients with pathologic endometrium in order to reduce the number of unnecessary diagnostic dilatation and curettage procedures. The prospective study involved 42 postmenopausal patients who were examined, prior to dilatation and curettage operation, with transvaginal color and pulsed Doppler sonography. Twenty patients had symptoms such as vaginal bleeding or clinically enlarged uterus and 22 postmenopausal women, from our screening group, were asymptomatic. Endometrial thickness (cut-off value of 8 mm), rates of visualization, and the density of uterine, myometrial (peritumoral) and endometrial (intratumoral) vessels were used, along with pulsatility and resistive indices of these vessels, to assess and correlate with endometrium pathology. Endometrial thickness was greater than 8 mm in all cases of endometrial carcinoma (14 of 14 cases), endometrial hyperplasia (eight of eight cases), and one endometrial polyp. In all cases of uterine myoma (nine cases) and in asymptomatic controls (11 subjects) the endometrium thickness was below 8 mm. Percentage of visualization of myometrial and endometrial vessels in cases of endometrial carcinoma was 93% and 43% respectively, which was significantly higher than for cases with benign endometrium (P < 0.05). RI and PI values of these studied vessels of endometrial carcinoma were significantly lower than those for endometrial hyperplasia (P < 0.05). In 80% of cases of endometrial carcinoma, dense vascularity was found in the myometrium (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Sonographic depiction of the endometrium during normal cycles

Pelvic sonograms were performed every 2-3 days in 10 volunteers in order to study changes in thickness and texture that occur in the normal endometrium. A total of 75 sonograms were performed. The accuracy of sonographic estimates of endometrial thickness was also evaluated in eight patients who underwent hysterectomy for reasons unrelated to the uterus. The majority of sonographic measurements of endometrial thickness in these patients were within 1 mm of the actual thickness as measured in the unfixed specimen. In all of the individuals studied, sonography was able to depict changes in the thickness and texture of the endometrium which corresponded to the various phases of its development. Specifically, the average thicknesses of the endometrium were greater in the secretory phase (3.6 +/- 1.4 mm) than in the proliferative phase (2.9 +/- 1.0 mm) (p less than or equal to 0.05). The texture of the endometrium varied throughout the cycle with the hypoechoic texture slightly more common than echoic in the proliferative phase, whereas the echogenic appearance was most common in the secretory phase. Those technical factors which optimized sonographic depiction of the endometrium are discussed, as well as the possible clinical applications of the sonographic depiction of normal and abnormal endometria.     

Vaginal ultrasonography in patients with postmenopausal bleeding.

Our objective was to define a subset of women with postmenopausal bleeding in whom the accepted practice of endometrial sampling could be safely omitted. Vaginal endosonographic measurements were compared to the histological findings of curettings following diagnostic dilatation and curettage in 129 women with post-menopausal bleeding who were not receiving hormonal therapy. Atrophy was diagnosed in 49%, slight proliferation in 10%, endometrial polyps in 11%, hypoplasia in 12%, and adenocarcinoma in 12%. Endometrial atrophy was associated with a mean sonographic thickness of 2.6 mm of the double layer (range 0-6.5 mm). Of the women with a final histological diagnosis of atrophy, 92% had an endometrial thickness of 3 mm or less. Furthermore, all women with a sonographic endometrial thickness of 3 mm or less had atrophic endometrium (p < 0.0001). An endometrial thickness of 3 mm or less would have reduced the number of dilation and curettage procedures by 45% and no cases of endometrial pathologies would have been missed. In women presenting with postmenstrual bleeding, meticulous scanning of the endometrium can select a group where endometrial sampling can be omitted from the protocol.     

Ultrasonography of endometrium

Abdominal and particularly vaginal sonography are useful diagnostic techniques for evaluating endometrium. Endometrial thickness can be measured and the echo pattern of the different parts of endometrium analysed. During normal cycles a triple line sign is typical for the late proliferative and periovulatory phase. In the secretory phase the endometrium is echogenic and posterior enhancement of echoes can be seen. It is also useful to control the effects of hormonal treatments or the endometrium using sonography. In postmenopausal women endometrial thickness of 4-5 mm or more is abnormal and further evaluations are indicated. In endometrial cancer sonography is a reliable way to estimate myometrial invasion.     

经阴道彩色多普勒超声对绝经后子宫出血疾病的诊断价值

目的　评价经阴道彩色多普勒超声（ＴＶＳ）对绝经后子宫出血妇女内膜疾病的诊断价值以及对子宫内膜癌肌层浸润的估测。方法　对１１１例绝经后子宫出血妇女进行ＴＶＳ检查, 观察其内膜厚度、内膜回声结构及血流。结果　ＴＶＳ测量内膜厚度＜ ５ｍ ｍ 时可不做诊刮, 定期进行观察; 内膜癌和良性病变的血流显示率及动脉ＲＩ值有显著性差异（Ｐ＜ ０．０５）; ＴＶＳ能较精确地判断内膜癌的肌层浸润, 与病理结果有极显著相关性（ｒ＝ ０．９８,Ｐ＜ ０．００１）。结论　ＴＶＳ可作为绝经后子宫出血患者的首选检查方法     

Effect of doxycycline on pre-menstrual syndrome: a double-blind randomized clinical trial

Thirty patients with well-defined symptoms of pre-menstrual syndrome were randomly treated with the antibiotic doxycycline or placebo. The antibiotic-treated group showed a highly significant reduction of symptoms. Subsequent antibiotic treatment of the original placebo group similarly diminished the symptoms in this group. A 6-month follow-up demonstrated that the improvement in symptom scores was permanent and independent from the presence of the antibiotic. Luteal phase endometrial biopsies showed a high incidence of out-of-phase endometrium. An unexpectedly high percentage of endometrial biopsy cultures yielded positive findings for mycoplasma, Chlamydia trachomatis and anaerobic bacteria. There were no characteristic hormonal changes in this study group. An infectious aetiology, possibly a sub-clinical endometrial or ovarian infection, behind certain cases of pre-menstrual syndrome is postulated.     

Transvaginal sonography of the endometrium during ovum pickup in stimulated cycles for in vitro fertilization

The endometrium of a series of 190 in vitro fertilization patients was investigated by transvaginal ultrasound. The endometrial pattern was related to the likelihood of implantation. No such relationship was found for the thickness of the endometrium. There was not a strong correlation between the endometrium and hormonal values. However, three endometrial patterns were detected after hormonal stimulation. The predominant pattern consisted of an outer hyperechogenic layer and an inner hypoechogenic layer. This pattern correlated in a positive fashion with subsequent implantation. It is concluded that the texture of the endometrium at the time of ovum pickup has a prognostic value for the likelihood of implantation to occur.     

子宫内膜厚度对IVF-ET妊娠结局的影响

目的探讨行体外受精-胚胎移植(IVF-ET)患者中,不同子宫内膜厚度对妊娠结局的影响。方法回顾性分析2016年1月至2017年12月在该院遗传与生殖研究所行新鲜胚胎移植的患者2981例。根据子宫内膜厚度分为5组:A组80例,子宫内膜厚度为7 mm;B组908例,子宫内膜厚度8~9 mm;C组1379例,子宫内膜厚度10~11 mm;D组542例,子宫内膜厚度12~13 mm;E组72例,子宫内膜厚度≥14 mm。比较各组胚胎着床率、临床妊娠率、异位妊娠率、临床流产率、分娩率、单胎率、双胎率等IVF-ET助孕结局。结果各组年龄、体质量指数(BMI)、促排卵药物(GN)用量、GN用药天数、平均获卵数、可移植胚胎数等比较,差异无统计学意义(P>0.05);不同组间妊娠率、异位妊娠率、临床流产率、畸形率比较,差异无统计学意义(P>0.05)。E组胚胎着床率、双胎率显著高于A组,单胎率显著低于A组,差异均有统计学意义(P<0.05);C组分娩率显著高于A组,差异有统计学意义(P<0.05)。各组患者妊娠结局比较,差异均无统计学意义(P>0.05)。结论改善子宫内膜厚度有助于改善妊娠结局,子宫内膜厚度越厚,此时胚胎着床可能性越大;子宫内膜厚度的变化不会增加IVF-ET出生婴儿的安全风险。