[Anti-inflammatory and hemostatic effects of total extract, saponins, and flavonoids of Clinopodium chinense in female rats with abnormal uterine bleeding and mechanism].

This study aims to explore the anti-inflammatory and hemostatic effects of the total extract of Clinopodium chinense(TEC), total saponins of C. chinense(TSC), and total flavonoids of C. chinense(TFC) in female rats with abnormal uterine bleeding(AUB), and the possible mechanism. Mifepristone(i.g., 12.4 mg·kg~(-1)) and misoprostol(i.g., 130 µg·kg~(-1)) were used to induce AUB in SD female rats conceiving on the same day. Then the AUB rats were randomized into model group, TEC group, TSC group, TFC group, Yimucao Granules(LG) group, and estradiol valerate(EV) group, with 8 rats in each group. Another 8 non-pregnant female rats were selected as normal group. During the experiment, each group was given the corresponding drug by gavage once a day for 7 days. After the administration, blood and uterine tissue were collected. The uterine bleeding volume was measured by ultraviolet spectrophotometry and the pathological changes of endometrium were observed based on hematoxylin-eosin(HE) staining. In addition, the microvessel density of endometrium was determined by immunohistochemistry, and the content of thromboxane B2(TXB2), 6-keto-PGF_(1α), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in plasma and levels of lutenizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E_2), and progesterone in serum were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA and protein expression of estrogenreceptor α(ERα), progesterone receptor(PR), matrix metalloproteinase(MMP)-2, MMP-9, and vascular endothelial growth factor(VEGF) in uterine tissue was determined by Western blot. Compared with the model group, TEC, TSC, and TFC can reduce uterine bleeding volume, alleviate the pathological damage of endometrium, and increase the microvessel density in endometrium. Moreover, TEC and TSC can significantly raise plasma TXB2 level and ratio of TXB2 to 6-keto-PGF_(1α), and TEC and TFC can significantly reduce the levels of IL-6 and TNF-α. In addition, TEC significantly elevated serum progesterone level and TFC significantly increased serum levels of E_2, FSH, and LH. TSC can significantly raise serum progesterone and FSH levels. In addition, TEC can significantly down-regulate the protein expression of PR, MMP-2, and VEGF and TSC significantly reduced the expression of MMP-9. TFC significantly decreased the expression of PR, MMP-9, and VEGF, and up-regulated the expression of ERα. In conclusion, TEC, TSC, and TFC all show therapeutic effects on AUB, particularly TEC. TSC exerts the effects by enhancing the coagulation function and promoting endometrial repair, and TFC by regulating estrogen levels and reducing inflammatory response. This study reveals the mechanism of C. chinense against AUB and also explains the holistic characteristics of Chinese medicine.

Clinical Features, Management and Maternal-Infant Prognosis in Patients with Complete Uterine Rupture in the Second and Third Trimester of Pregnancy.

Objectives: Our study aimed to investigate the clinical features, management, and maternal-infant prognosis in patients with complete uterine rupture in the second and third trimester of pregnancy. Methods: A total of 15 patients with complete uterine rupture in their second and third trimester of pregnancy who were admitted to our hospital between January 2012 and December 2020 were included in our study. The patients enrolled were divided into the scar group (11 patients) and the non-scar group (4 patients) according to the existence or absence of a uterine scar. The general data, clinical characteristics and follow-up results in the 2 groups were compared. Results: There was no significant difference in age, pregnancy duration or delivery cycle between the 2 groups (P > .05). The incidence of original scar rupture in the scar group was significantly higher than in the non-scar group (P > .05). No significant difference was found in clinical characteristics between the scar and the non-scar groups (P > .05). The most common clinical features included abdominal pain, inability to lie flat, hemorrhagic shock, prenatal vaginal bleeding and uterine rupture, mostly occurring in the lower segments of the uterus and cervix. A total of 3 patients were misdiagnosed as having surgical disease. After completing relevant examinations, the uterine rupture was repaired surgically; the patients were discharged after blood transfusion, and their condition resolved. In all, 3 patients in the non-scar group and 1 patient in the scar group were transferred to the intensive care unit (ICU). All 15 patients were discharged after treatment. Follow-up was completed by all patients for 12 to 36 months, with an average follow-up time of 23.09 ± 2.19 months. Of the 15 patients, 2 underwent induced abortion after 24 months due to unplanned pregnancy. A 5-minute Apgar score of ≤7 in the scar group was higher than that in the non-scar group, but the difference was not statistically significant (P > .05). Perinatal mortality in the 15 patients was 40.00% (6/15). Conclusion: The most common clinical features in patients with complete uterine rupture in the second and third trimester of pregnancy included abdominal pain, inability to lie flat, hemorrhagic shock, prenatal vaginal bleeding and uterine rupture, mostly occurring in the lower segments of the uterus and cervix. In addition, a remarkably worse maternal-infant prognosis was seen in patients with complete uterine rupture in the second and third trimester of scarless pregnancy compared with patients with complete uterine rupture in the second and third trimester of scarred pregnancy.

Management and outcomes of vaginal bleeding and heavy menstrual bleeding in women of reproductive age on direct oral anti-factor Xa inhibitor therapy: a case series.

BACKGROUND: Observational data and results from post-hoc analyses in clinical trials suggest that direct oral factor Xa inhibitors might increase menstrual bleeding intensity in women of reproductive age, but the extent of this effect is unknown. We aimed to investigate the management and outcomes of vaginal bleeding complications during therapy with direct oral factor Xa inhibitors in a case series of women of reproductive age. METHODS: To identify individuals for inclusion in this case series, we searched two sources of prospectively collected data from women of reproductive age treated with direct oral factor Xa inhibitors: the non-interventional Dresden NOAC Registry (NCT01588119), which is based in the administrative district of Dresden (Saxony, Germany), and all locally archived data from phase 3 trials of direct oral factor Xa inhibitors done at University Hospital Carl Gustav Carus Dresden. Vaginal bleeding events were defined as any vaginal bleeding complications as reported by the patient. We collected data on type and dosage of anticoagulation; suspected or confirmed bleeding events, hospital admissions, and mortality; and pattern and management of vaginal bleeding events. For all cases of bleeding identified, we reviewed all available source data to identify examination results suggesting potential underlying anatomical causes of bleeding. FINDINGS: We identified 178 women of reproductive age who received direct oral factor Xa inhibitor therapy, of whom 57 had vaginal bleeding events, including 50 who received rivaroxaban, six who received apixaban, and one who received edoxaban. These 57 women had 72 vaginal bleeding events, including 59 cases of heavy menstrual bleeding and 13 bleeding events unrelated to the menstrual cycle. 51 (86%) of these heavy menstrual bleeding events (two major bleeding events, 17 clinically relevant non-major bleeding events, 32 minor bleeding events) were treated conservatively (eg, change of oral hormone therapy or reduction, temporary interruption, or discontinuation of direct oral factor Xa inhibitor) and the remaining eight (14%) events (three major bleeding events and five clinically relevant non-major bleeding events) required elective surgical or interventional treatment (hysterectomy, curettage, ovary excision, or excision of ovarian cysts). Of the 57 women, 13 (23%) had a second bleeding event and two (4%) had a third event. Nine patients had underlying anatomical abnormalities; compared with patients without abnormalities, these patients had more intense bleeding, more had recurrent bleeding (five [56%] of nine patients with abnormalities vs eight [17%] of 48 patients without abnormalities), and more needed surgical treatment for bleeding (eight [89%] of nine vs zero of 48). INTERPRETATION: Vaginal bleeding, particularly heavy menstrual bleeding, is a common complication in women of reproductive age on direct oral factor Xa inhibitor therapy. Most cases can be treated conservatively, but patients with severe or recurrent vaginal bleeding complications should be assessed for underlying anatomical abnormalities, which might require surgical or interventional treatment. Further data are needed to provide guidance on prevention and treatment of vaginal bleeding complications in this patient population. FUNDING: None.

Office diagnostic and operative hysteroscopy using local anesthesia only: an analysis of patient reported pain and other procedural outcomes.

STUDY OBJECTIVE: To evaluate the effectiveness of a multimodality local anesthetic protocol for office diagnostic and operative hysteroscopy. DESIGN: Retrospective cohort study (Canadian Task Force classification II-3). SETTING: Academic community-based institution. PATIENTS: Five hundred sixty-nine women undergoing 639 office-based diagnostic or operative hysteroscopic procedures. INTERVENTIONS: Multimodality local anesthetic protocol addressing vagina, cervix, paracervical region, and endometrial cavity. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were numeric pain scores and rate of premature termination because of pain. Secondary outcomes included procedure pain and parity, delivery route, menopausal status, procedure type, and cost effect on procedure delivery. The overall mean (SD) pain score across 535 evaluable procedures was 3.7 (2.5). Patients undergoing operative hysteroscopy had a higher mean maximum pain score than did those who underwent diagnostic hysteroscopy only (4.1 vs 3.2; p < .001). There was no difference among women in different age groups; however, those with both cesarean section and vaginal delivery had scores higher than the mean (4.7 [0.4]; p < .001). The estimated cost savings was almost $2 million. CONCLUSION: Using a multimodality approach to local anesthesia, a broad spectrum of diagnostic and operative procedures can be performed successfully, comfortably, and inexpensively in the context of an office procedure room, without the need for procedural sedation.

Blockade of tubal patency following transcervical administration of polidocanol foam: initial studies in rhesus macaques.

OBJECTIVE: To demonstrate the feasibility of polidocanol foam (PF) as a nonsurgical method of female permanent contraception using a nonhuman primate model. STUDY DESIGN: Four groups of adult female rhesus macaques underwent either transcervical treatment with 5% PF directly into the uterine cavity, treatment with inert (methylcellulose, MF) foam or no treatment followed by removal of the reproductive tract for histologic evaluation. Untreated animals were included in Group 1 (n=3). Group 2 animals (n=4) were treated once with MF. Group 3 (n=7) received a single, and Group 4 (n=5) received multiple monthly treatments with PF; in these 2 groups, baseline tubal patency was assessed either laparoscopically by chromopertubation (CP) or by hysterosalpingography. RESULTS: Group 1 (untreated) and Group 2 (MF) animals had normal tubal histology. In contrast, Group 3 and 4 females treated with PF showed evidence of tubal damage. In Group 4, bilateral tubal blockade was noted on CP after two (n=2) or three (n=3) treatments. Histologic analysis confirmed complete tubal occlusion (loss of epithelium, fibrosis) in three of these animals, and one showed significant tubal damage localized to the intramural segment. Nontarget (cervix, vagina, endometrium, ovary) reproductive tissues were unaffected. While similar tubal changes were observed after a single treatment (Group 3), endometrial hemorrhage was also noted as an acute change. CONCLUSION: PF is a promising candidate agent for nonsurgical permanent female contraception. The histologic features of PF occlusion are confined to the intramural portion of the tube. IMPLICATIONS: This study in rhesus macaques supports further development of transcervical administration of PF as a nonsurgical approach to permanent contraception. A nonsurgical method could reduce risks and costs associated with surgical female sterilization and increase access to permanent contraception.

Evaluation of a fibrin preparation containing tranexamic acid (Adhexil) in a rabbit uterine horn model of adhesions with and without bleeding and in a model with two surgical loci.

OBJECTIVE: To compare the efficacy of a fibrin preparation supplemented with tranexamic acid (Adhexil) with that of established devices, and to determine whether its effect is limited to the site of application. DESIGN: Rabbit uterine horns were abraded in nonbleeding and bleeding variants of an established adhesions model. In a separate study, a sidewall excision with approximation of the abraded cecum was added. Animals randomly received Adhexil at both, neither, or either loci. SETTING: Laboratory study. ANIMAL(S): Seventy-two female New Zealand White rabbits (Oryctolagus cuniculus). INTERVENTION(S): Adhexil, Seprafilm or SprayGel and Interceed. MAIN OUTCOME MEASURE(S): The extent of adhesions was evaluated 13 to 16 days after surgery. RESULT(S): Adhexil reduced adhesions (15 +/- 7%; 15 +/- 4%) compared with controls (74 +/- 13%; 78 +/- 9%) in the bleeding and nonbleeding models, respectively. The reductions resulting from the use of Seprafilm (39 +/- 17%; 34 +/- 14%) or SprayGel (61 +/- 18%; 43 +/- 14%) (n = 4) were not statistically significant. In the bleeding model, Interceed (48 +/- 15%) reduced adhesions only modestly. CONCLUSION(S): In the combined uterine and sidewall model, Adhexil reduced selectively the extent and incidence of adhesions. The absolute and relative performance of Adhexil in an established adhesions model and in the presence of bleeding justifies its further investigation.

[Uterine abnormalities in non menopausal women who received tamoxifen for breast cancer adjuvant therapy]. / Anomalies utérines chez la femme non ménopausée sous tamoxifène en traitement adjuvant du cancer du sein.

OBJECTIVE: To elaborate a strategy of endometrial follow-up for premenopausal women treated with Tamoxifen as adjuvant hormonal treatment of breast cancer. PATIENTS AND METHODS: Retrospective study of 152 premenopausal patients treated with Tamoxifen in Nantes Comprehensive Cancer Center for a breast cancer from January 2003 to December 2005. Vaginal sonography was used in the follow-up of 70 of them. RESULTS: Endometrial hypertrophy was found in 26 patients. Sonohysterography and hysteroscopy allowed to find 11 polyps and three hyperplasias in the 19 women who were investigated. In our study, endometrial pathology was found in 20% of premenopausal women treated with Tamoxifen (polyps or hyperplasia). Uterine bleeding was found in half patient of this group. DISCUSSION AND CONCLUSION: Vaginal sonography monitoring could be proposed to premenopausal women treated with Tamoxifen among whom endometrial pathology is usual.

[Clinical analysis of abnormal uterine bleeding treatment with Thermablate EAS].

OBJECTIVE: To study the two-year follow-up and contrast research for 182 patients by Thermablate EAS Uterine Balloon Therapy (UBT) or Transcervical Resection of Endometrium (TCRE). METHODS: We followed up 90 cases of UBT and 92 cases of TCRE between Oct. 2003 and June 2005. The mean age of UBT group was 49.4+/-9.4 (34-81) years, and that of TCRE group 46.6 +/-8.4 (35-74) years. The mean following-up for UBT group was 17.3+/- 5.0 (6-27) months, and that of TCRE group 17.5+/-4.1 (6-27) months. There was no noticeable difference of the high risk for complication between the two groups. The follow up happens twice a year one month after the operation. The follow up started in Dec. 2005. RESULTS: The chi(2) value of pain during operation between two groups is 12.744. The P value is 0.000. It has statistical significance. The pain of UBT group is heavier than TCRE. The chi(2) value of blood disappearance between two groups is 24.347. The P value is 0.000. It has statistical significance. The duration of the blood disappearance of UBT group is shorter than TCRE. The chi(2) value of discharge disappearance between two groups is 99.486. The P value is 0.000. It has statistical significance. The duration of the blood discharge of UBT group is shorter than TCRE. The chi(2) value of blood flow for two years after surgery between two groups is 4.708. The P value is 0.03. It has statistical significance. The blood flow of UBT group is much more decrease than TCRE. The chi(2) value of dysmenorrheal improved after surgery between two groups is 9.970. The P value is 0.002. It has statistical significance. The dysmenorrheal improved of UBT group is much better than TCRE. CONCLUSION: Thermablate EAS UBT is a new generation of endometrial ablation. Two years clinical observation shows that pain can be controlled by oral medicine for UBT group. The blood and discharge disappearance of UBT group is shorter than TCRE. Two years after the surgery the improvement of blood flow and dysmenorrheal released is much better than TCRE. However it probably will take longer time to show its long term effectiveness.

[Diagnostic hysteroscopy in abnormal uterine bleeding. Five-years' experience]. / L'isteroscopia diagnostica nel sanguinamento uterino anomalo. Cinque anni di esperienza.

BACKGROUND: Hysteroscopy has acquired a central role in the clinical diagnosis of intrauterine pathologies. This study evaluated the feasibility, procedure modality, tolerability, complications and diagnostic accuracy of hysteroscopy in the management of patients with abnormal uterine bleeding (AUB). METHODS: This retrospective study was carried out on 512 women (age range: 38-80 years, mean age: 63) with AUB who attended our hysteroscopy outpatient service from January 1996 to December 2001. After undergoing transvaginal sonography, the patients were referred for further diagnostic studies. Ambulatory hysteroscopy without premedication was performed using a Hamou hysteroscope and physiological solution or CO(2) as distension medium. Guided biopsy with a Novak cannula completed the examination. When focal lesions were found, the patients were referred for surgical treatment (hysteroscopic resection, hysterectomy, etc.). Hysteroscopic and histologic findings were then compared. RESULTS: Locoregional or general anaesthesia was required in only 9.3% of cases to complete the examination. Overall, the examination was well tolerated; one case of serious complications (vagal syndrome which resolved rapidly) and 18 cases of shoulder blade pain were recorded. The hysteroscopic picture was normal in 25% of cases, benign pathology was diagnosed in 58.6% and suspected malignant neoplasia in 16.4%. Correlation rates between hysteroscopic and histologic diagnoses are reported for the various hysteroscopic pictures. CONCLUSIONS: Ambulatory hysteroscopy was shown to be a simple, safe, well tolerated and reliable procedure in the diagnosis of AUB across all age groups. Its widespread use can drastically reduce the need for conventional curettage, thereby increasing patient satisfaction and lowering costs.

[Ambulatory hysteroscopy in evaluation of postmenopausal bleeding]. / Die ambulante Hysteroskopie in der Abklärung der postmenopausalen Blutung.

INTRODUCTION: Diagnostic hysteroscopy is the most precise procedure to evaluate diseases involving the uterine cavity. There is, however, only limited data concerning the use of hysteroscopy carried out as an outpatient procedure in patients with postmenopausal bleeding. MATERIALS AND METHODS: In this study we report on 360 postmenopausal patients with erratic bleeding, who were referred to our outpatient hysteroscopy clinic. 185 women had frank postmenopausal bleeding (PMB) and another 175 had abnormal uterine bleeding while taking hormone replacement therapy (AUB). The mean age was 57.9 years (range: 42-86). All hysteroscopies were performed using a standard 5-mm hysteroscope with a 30 degrees fore-oblique lens; the uterine cavity was generally distended with normal saline. RESULTS: Outpatient hysteroscopy was performed successfully in 339 patients (94.2%). In 166 cases (46.1%) cervical dilatation was necessary, and 138 required (38.3%) intracervical anaesthesia. Intrauterine pathology was diagnosed in 49.6% of cases, with endometrial polyps (20.9%) and fibroids (15.9%) being the most common abnormalities. While there was no difference in the incidence of intrauterine lesions between patients with AUB and those with PMB, endometrial carcinoma was more common in the latter group (PMB: n = 11 vs. AUB: n = 1; p < 0.002). CONCLUSION: Due to its high accuracy and patient acceptance, outpatient diagnostic hysteroscopy should become a first line investigation in postmenopausal patients with bleeding disorders.

The use of topical anesthesia in diagnostic hysteroscopy and endometrial biopsy.

STUDY OBJECTIVE: To determine whether the pain and discomfort of routine hysteroscopy with endometrial biopsy to diagnose infertility and endometrial pathology can be minimized by topical application of mepivacaine. DESIGN: Prospective, randomized, double-blind study. SETTING: The Department of Obstetrics and Gynecology at a teaching hospital in Rome, Italy. PATIENTS: Eighteen women undergoing diagnostic hysteroscopy. INTERVENTIONS: Hysteroscopy and endometrial biopsy were performed after transcervical injection of 5 ml 2% mepivacaine or 5 ml saline solution into the uterine cavity. MEASUREMENTS AND MAIN RESULTS: Difficulty introducing the hysteroscope was rated by the operator on a scale of 1 to 3. An observer scored visible signs of each woman's distress using a three-point scale. The patients reported their pain 15, 30, 60, 120 minutes after the procedure on a visual analog scale. Mepivacaine was more effective than placebo according to all measurements. CONCLUSIONS: Topical mepivacaine reduced the pain experienced during and after hysteroscopy and endometrial biopsy.