Congenital dysfibrinogenaemia presented with preterm premature rupture of the membranes and vaginal bleeding.

A 26-year-old woman was found to have congenital dysfibrinogenaemia after presenting to our hospital with premature rupture of the membranes and vaginal bleeding. Given the absence of clear guidelines for the management of pregnancy complicated by dysfibrinogenaemia, we followed expert consensus that exists among published works, with some modifications. This case was managed by a multidisciplinary team of obstetrics-gynaecology, haematology and paediatric haematology. Here we review how the patient presented, the investigations that led to the diagnosis and the treatment options.

Exacerbated mini-puberty of infancy in an ex-extreme preterm girl.

Vaginal bleeding can occur shortly after delivery in 3%-5% of newborns as a consequence of placental hormone withdrawal . Although usually benign, its differential diagnosis includes central precocious puberty, tumours and other pathological conditions. A girl born at 26 weeks of gestation presented with five episodes of vaginal bleeding, each lasting less than a week, initiated at 4 months of age. Luteinising hormone and oestradiol levels were in the pubertal range. Later, she exhibited breast development, with no other pubertal signs. An ultrasonography test revealed an impregnated endometrium and a right ovarian cyst with 43 mm of diameter. A cranioencephalic MRI was unremarkable. Clinicians adopted expectant management and there was clinical, hormonal and radiological resolution in 3 months. The spontaneous resolution suggested mini-puberty of infancy. This is usually an asymptomatic condition, but to date, four cases of an exacerbated form in extremepremature infants have been reported. Long-term follow-up data are missing.A girl born at 26 weeks of gestation presented with five episodes of vaginal bleeding, each lasting less than a week, initiated at 4 months of age. Luteinising hormone and oestradiol levels were in the pubertal range. Later, she exhibited breast development, with no other pubertal signs. An ultrasonography test revealed an impregnated endometrium and a right ovarian cyst with 43 mm of diameter. A cranioencephalic MRI was unremarkable. Clinicians adopted expectant management and there was clinical, hormonal and radiological resolution in 3 months. The spontaneous resolution suggested mini-puberty of infancy. This is usually an asymptomatic condition, but to date, four cases of an exacerbated form in extremepremature infants have been reported. Long-term follow-up data are missing.

Expression of matrix metalloproteinase enzymes in endometrium of women with abnormal uterine bleeding.

OBJECTIVES: Abnormal uterine bleeding (AUB) is caused by derangement of physiological processes of tissue growth, shedding and regeneration. It is known that interplay between metalloproteinases (MMP's) and tissue inhibitors of metalloproteinases (TIMP's) may play a crucial role in its occurrence. AIM: To define if expression of proMMP-2, MMP-2 and TIMP-1 in endometrium of women with AUB is dependent on steroid sex hormone concentration and histopathological picture. MATERIALS AND METHODS: Endometrial scraps were taken from 21 women with AUB and 19 controls. Samples were evaluated in light microscopy by a certified pathologist. Activity of proMMP-2 and MMP-2 proteins levels were evaluated by gelatin zymography and TIMP-1 by reversed zymography. The results has been correlated with serum estradiol and progesterone concentrations in linear regression model. RESULTS: Expression: of proMMP-2 in endometrium of women with AUB is correlated with estradiol concentration and inversely correlated with progesterone levels. It was significantly higher in women with dysfunctional endometrium (p<0.001). Expression of MMP-2 was highest in women with endometrial polyps and longer bleeding (p<0.01), while expression of TIMP-1 was independent from hormone concentration. CONCLUSION: Lack of correlation between proMMP-2 and MMP-2 levels suggest different pathway of their activation in AUB. ProMMP-2 is up regulated by estradiol and down regulated by progesterone while MMP-2 levels increase with the length of bleeding.

CA 125 is a better marker to differentiate endometrial cancer and abnormal uterine bleeding.

BACKGROUND: Incidence of endometrial cancer in India is increasing due to lifestyle changes and obesity. As 5 year survival rate of cancer confined to uterus is good, there is need for serum tumor marker for early diagnosis. This study was designed to identify a tumor marker which differentiate endometrial carcinoma and abnormal uterine bleeding (AUB) because common presentation of endometrial carcinoma is AUB. OBJECTIVES: To estimate and compare serum prolactin, Cancer Antigen 125 (CA-125), Cancer Antigen 15-3 (CA15-3), and Carcino embryonic antigen (CEA) levels in patients with endometrial cancer and abnormal uterine bleeding; To evaluate the role of these markers in diagnosing endometrial cancer. METHODOLOGY: Thirty eight patients with endometrial cancer and 40 patients with AUB were recruited in this study. Serum prolactin, CA 125, CEA, and CA 15-3 levels were estimated in both groups. RESULTS: The levels of CA 15-3, CA 125, CEA, and prolactin were increased in endometrial carcinoma patients, on comparison with AUB patients. CA 125 alone was found to be a better marker to detect endometrial cancer with 52.63% sensitivity, 80.00% specificity. CONCLUSION: As individual tumor marker, serum CA 125 has the ability to detect endometrial cancer in patients with abnormal uterine bleeding.

Predictive value of some hematological parameters for non-invasive and invasive mole pregnancies.

AIM: The aim of this study was to discriminate mole pregnancies and invasive forms among cases with first trimester vaginal bleeding by the utilization of some complete blood count parameters conjunct to sonographic findings and beta human chorionic gonadotropin concentration. MATERIALS AND METHODS: Consecutive 257 cases with histopathologically confirmed mole pregnancies and 199 women without mole pregnancy presented with first trimester vaginal bleeding who admitted to Zeynep Kamil Women and Children's Health Training Hospital between January 2012 and January 2016 were included in this cross-sectional study. The serum beta HCG level at presentation, and beta hCG levels at 1st, 2nd and 3rd weeks of postevacuation with some parameters of complete blood count were utilized to discriminate cases with molar pregnancy and cases with invasive mole among first trimester pregnants presented with vaginal bleeding and abnormal sonographic findings. RESULTS: Levels of beta hCG at baseline (AUC = 0.700, p < 0.05) and 1st (AUC = 0.704, p < 0.05), 2nd (AUC = 0.870, p < 0.001) and 3rd (AUC = 0.916, p < 0.001) weeks of postevacuation period were significant predictors for the cases with persistent disease. While area under curve for mean platelet volume is 0.715, it means that mean platelet volume has 21.5% additional diagnostic value for predicting persistency in molar patients. For 8.55 cut-off point for mean platelet volume, sensitivity is 84.6% and specificity is 51.6%. Area under curve for platelet/lymphocyte ratio is 0.683 means that platelet/lymphocyte ratio has additional 18.3% diagnostic value. For 102.25 cut-off point sensitivity is 86.6% and specificity is 46.2. CONCLUSIONS: Simple, widely available complete blood count parameters may be used as an adjunct to other risk factors to diagnose molar pregnancies and predict postevacuation trophoblastic disease.

The effect of blood staining on cervicovaginal quantitative fetal fibronectin concentration and prediction of spontaneous preterm birth.

OBJECTIVE: Spontaneous preterm birth is the leading cause of neonatal morbidity and mortality. Cervicovaginal fetal fibronectin (fFN) has enhanced prediction of preterm birth and, more recently, quantified results have become available so that management can planned more effectively and targeted to individual women. Manufacture guidelines stipulate that fetal fibronectin (fFN) samples should be discarded in the presence of moderate to heavy vaginal bleeding but there hasn't yet been any formal investigation into the effect of blood staining on fetal fibronectin concentration and subsequent preterm birth prediction. The objective for this study was to determine the impact of blood stained swabs on quantitative fetal fibronectin (qfFN) concentration and prediction of spontaneous preterm birth (sPTB) in asymptomatic high-risk women. STUDY DESIGN: Predefined blinded sub-analysis of a larger prospective study of qfFN in asymptomatic women at high-risk of preterm labour. Women with and without blood stained swabs were matched for gestational age at testing and delivery, risk factors and cervical length measurement. RESULTS: Median fFN concentration in blood stained swabs (n=58) was 66ng/ml vs. 7.5ng/ml in the controls (n=58) (p<0.0001). At ≥50ng/ml threshold the false positive ratio (FPR) in blood stained was 25/33 (75.8%) vs. 8/15 (53%) in controls, (risk difference 22.4; -6.8 to 51.6, p=0.18). At ≥50ng/ml threshold the false-negative ratio (FNR) in blood stained was 2/25 (8.0%) vs. 1/43 (2.3%) in controls (risk difference -5.7; -17.2 to 5.9, p=0.55). At each threshold 10, 50 and 200ng/ml blood stained swabs had higher sensitivity but lower specificity for predicting preterm birth. Receiver Operating Characteristic (ROC) curve, the strongest global measure of test performance, for prediction of delivery at <34 weeks gestation was similar in blood stained vs. control groups. (0.78 vs. 0.84) in blood stained vs. control groups respectively. CONCLUSION: Blood stained swabs have elevated qfFN concentrations but may still have predictive value, and clinical utility. Very low fFN values (<10ng/ml) are especially reassuring and indicate lower risk of delivery than non-blood stained swabs. The higher false positive rate must be noted and explained to the patient.

Single-dose intravenous iron for iron deficiency: a new paradigm.

Iron-deficiency anemia is the most common hematologic problem in the world. Although oral iron is often viewed as front-line therapy, extensive published evidence has accumulated that IV iron is superior, in both efficacy and safety, to oral iron in many clinical situations and should be introduced much sooner in the treatment paradigm of iron-deficient patients. In this chapter, we will review the formulations of IV iron that allow total complete replacement doses in 1 or 2 sessions including practical tips for administration. We realize safety concerns abound and therefore will analyze evidence based overstated concerns regarding serious adverse events highlighting unnecessary interventions for minor, self-limiting infusion reactions, which infrequently occur with intravenous iron administration. Recent data for the use of IV iron in a variety of clinic situations will be reviewed including women with heavy uterine bleeding, pregnancy, bariatric surgery, inflammatory bowel disease, and restless legs syndrome. Briefly discussed is the new frontier of IV iron's use in the prevention of acute (high altitude) mountain sickness. It is clear that in many clinical situations IV iron is a new and improved standard of care offering advantages over oral iron in efficacy, toxicity, and convenience to patients and health care providers.

Interferon beta-1b-induced postmenopausal bleeding in a patient with multiple sclerosis.

OBJECTIVE: Postmenopausal bleeding must always be evaluated to rule out endometrial carcinoma, although there are many benign etiologies. There have been rare reports of premenopausal bleeding with interferon beta-1b, used to treat multiple sclerosis, but no prior reports in postmenopausal women. METHODS: Literature searches were performed using PubMed and Medline for articles with content related to premenopausal and postmenopausal bleeding while taking interferon beta-1b. The searches were restricted to the English language. Search terms included interferon beta-1b and/or uterine hemorrhage and/or vaginal bleeding and/or postmenopausal and/or menopause. RESULTS: The literature review found no related articles for postmenopausal bleeding while taking interferon beta-1b. We present a case of a patient with postmenopausal bleeding attributed to elevation of serum estradiol in association with interferon beta-1b therapy. CONCLUSION: It is important for patients and providers to be aware of the association between postmenopausal bleeding with the use of interferon beta-1b therapy which could be due to elevated serum estradiol levels.

Hormone replacement therapy affects iron status more than endometrial bleeding in older US women: A role for estrogen in iron homeostasis?

High iron levels in women of post-reproductive age may be related to their increased risk of chronic disease as they become older, but the causes of this rise in iron in late life is unclear. Recently estrogen has been implicated in non-human models of iron homeostasis. Studying iron in women who take hormone replacement therapy (HRT) may provide insight into the relationship between iron status and hormonal status in older women. This study examines the association between HRT and iron status in women aged 50+ who took part in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). Data were analyzed using multiple imputation, which corrects for missing data, and complex survey regression, which adjusts for NHANES sampling. Current HRT use was associated with lower ferritin (ß=-34.13, p=0.0002), controlling for potential breakthrough bleeding with a hysterectomy variable. HRT was associated with lower iron stores in women of post-reproductive in the absence of uterine blood loss, indicating potential homeostatic hormonal control of iron status. This research demonstrates the utility of studying clinical hormonal therapy to advance new understandings about the basic biology of iron homeostasis in women.

Risk factors for intra-operative haemorrhage and bleeding risk scoring system for caesarean scar pregnancy: a case-control study.

OBJECTIVES: To investigate risk factors associated with excessive intra-operative haemorrhage during evacuation operation, and to develop a bleeding risk scoring system in patients with caesarean scar pregnancy (CSP) to guide treatment. STUDY DESIGN: A case-control study was conducted. Excessive intra-operative haemorrhage was defined as active bleeding during dilation and suction evacuation (blood loss ≥200ml). The bleeding group consisted of patients who experienced excessive intra-operative blood loss. Patients with less intra-operative blood loss were included in the control group. RESULTS: In total, 458 admissions from 2009 to 2014 were included in this study. Compared with the control group, the bleeding group had higher serum ß-human chorionic gonadotrophin (hCG), higher gestational age, larger CSP mass, richer peritrophoblastic perfusion and thinner myometrial layer before evacuation (all p<0.05). Risk factors with p<0.05 on multivariable logistic regression analysis included serum ß-hCG >20,000mIU/ml [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.0-3.2], gestational age >8 weeks (OR 2.1, 95% CI 1.1-4.0), maximum diameter of gestational sac or CSP mass ≥5cm (OR 7.4, 95% CI 3.4-16.1), myometrial thickness ≤0.15cm (OR 3.6, 95% CI 1.9-6.9) and significant peritrophoblastic perfusion (OR 9.8, 95% CI 4.1-23.2). These risk factors formed the final bleeding risk scoring system by conversion of their OR values into corresponding points. A total of 10 points was identified as the optimal cut-off on the receiver operating characteristic curve. Thus, patients with scores ≥10 points were identified as being at high risk of bleeding. The final bleeding risk scoring system had an area under the curve of 0.86, sensitivity of 86.8% and specificity of 73.2%. CONCLUSIONS: Gestational age, serum ß-hCG, size of gestational sac, thickness of myometrial layer and peritrophoblastic perfusion were found to be associated with excessive intra-operative haemorrhage during suction evacuation of CSP. A bleeding risk scoring system was constructed to help guide the management of patients with CSP. Patients with total scores ≥10 points were identified as being at high risk of bleeding, whereas patients with total scores ≤5 points were identified as being at low risk of bleeding.

Are neutrophil/lymphocyte and platelet/lymphocyte ratios associated with endometrial precancerous and cancerous lesions in patients with abnormal uterine bleeding?

BACKGROUND: An easy, reproducible and simple marker is needed to estimate phase of endometrial pathologic lesions such as hyperplasia and endometrial cancer and distinguish from pathologically normal results. We here aimed to clarify associations among neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), endometrial hyperplasia and cancer in patients with abnormal uterine bleeding. MATERIALS AND METHODS: Patients (n=161) who were admitted with abnormal uterine bleeding and the presence of endometrial cells on cervical cytology or thick endometrium were investigated. The study constituted of three groups according to pathologic diagnosis. Group 1 included endometrial precancerous lesions like hyperplasia (n=63), group 2 included endometrial cancerous lesions (n=38) and group 3 was a pathologically normal group (n=60). Blood samples were obtained just before the curettage procedure and the NLR was defined as the absolute neutrophil count divided by the absolute lymphocyte count; similarly, PLR was defined as the absolute platelet count divided by the absolute lymphocyte count. RESULTS: The white blood cell count was significantly higher in patients with cancer than in those with hyperplasia (p=0.005). The platelet count and neutrophil to lymphocyte ratio were significantly higher in patients with cancer than in control patients, but there was significantly no difference between patients with hyperplasia and other groups (p=0.001 and p=0.025 respectively). PLR was significantly lower in control subjects than in other groups (p<0.001), but there was no significant difference between patients with hyperplasia and those with cancer. CONCLUSIONS: PLR was significantly lower in control subjects than in other groups. Thus both hyperplasia and cancer may be differentiated from pathologically normal patients by using PLR. White blood cell count was significantly higher in patients with cancer than in those with hyperplasia and pathologically normal patients. Therefore white blood cell count may be used for discriminate hyperplasia to cancer. By using multiple inflammation parameters, discrimination may be possible among endometrial cancer, endometrial precancerous lesions and pathologically normal patients.

[Efficiency of modern technology in obstetric practice].

Bleeding is one of the key components of critical states in obstetrics. The fight against obstetric hemorrhage related to the following aspects: the organization of care, qualifications of medical personnel, the availability and quality of the protocol. The introduction of modern technologies to reduce the frequency of massive postpartum hemorrhage and disability among women of reproductive age.

Vaginal examination does not improve diagnostic accuracy in early pregnancy bleeding.

OBJECTIVE: The study aims to determine if a vaginal examination improves diagnostic accuracy when assessing women who present to the ED with vaginal bleeding in the first trimester of pregnancy. METHODS: One hundred and thirty-five women with first trimester bleeding were randomised to have a vaginal examination (n = 61) or not (n = 74). They were given a provisional diagnosis, and then a final diagnosis after ultrasound, beta-human chorionic gonadotropin and gynaecological follow up. The provisional diagnosis was considered accurate if it matched the final diagnosis. RESULTS: The provisional and final diagnoses matched in a little over half of the cases, and there was no statistical difference between the two groups (χ(2) = 0.005, P = 0.94). CONCLUSION: In a stable patient presenting to the ED with first trimester bleeding, clinical diagnosis is highly inaccurate and is not improved by vaginal examination. Routine vaginal examination is not necessary as part of the initial patient assessment.

Serum angiopoietin-2 and ß-hCG as predictors of prolonged uterine bleeding after medical abortion in the first trimester.

OBJECTIVE: The combination of mifepristone and misoprostol is an established method for induction of early first trimester abortion, but there is no consensus about the best evaluation of treatment outcome. We evaluate serum Angiopoietin-2 (Ang-2) and ß human chorionic gonadotropin (ß-hCG) in women who had undergone a medical abortion as markers of prolonged uterine bleeding (PUB). METHODS: Prospective trial involving 2843 women attending an gynecology outpatient clinic who following a medical abortion with mifepristone and misoprostol, the study cohort was divided into women with duration of uterine bleeding >14 days (PUB) and women with duration of uterine bleeding ≤14 days (normal uterine bleeding, NUB). Serum determinations of Ang-2 levels by ELISA and ß-hCG levels by electrochemiluminiscence immunoassay. Receiver Operating Characteristics (ROC) analyses were calculated and plotted for the diagnostic accuracy of serum ß-hCG and Ang-2 concentration to discriminate PUB and NUB. RESULTS: Baseline characteristics for both groups were similar, Only duration of bleeding showed a significant difference between the PUB group and NUB group. Ang-2 serum levels moderately correlated with serum ß-hCG levels with statistically significant correlation coefficients of 0.536. Serum ß-hCG and Ang-2 levels on day 7 and on day 14 after medical abortion were signifcantly higher in PUB group than in NUB group. Plotted as ROC curves, ß-hCG area under curve (AUC) was 0.65 (95% CI, 0.53-0.76) on day 7, rising to AUC = 0.83 (95% CI, 0.75-0.92) on day 14. Using Ang-2 on day 7 and day 14 as predictive parameter resulted in an analogous AUC (AUC = 0.61 on day 7, AUC = 0.78 on day 14). CONCLUSIONS: Both parameters are clinically useful as a diagnostic test in predicting PUB after medical abortion, and can be helpful in uncertain clinical situations, but should be considered as supplementary to a general clinical evaluation.

Curative effects of two new endometrial ablation procedures using radiofrequency thermocoagulation for the treatment of severe abnormal uterine bleeding.

Severe Abnormal Uterine Bleeding (SAUB) is a common gynecological disorder. The clinical characteristics include disordered menstrual cycle and massive bleeding that can cause anemia or secondary infection. Current treatment mainly relies on drug therapy or surgical removal of the uterus, each having its significant disadvantages. How to preserve the uterus, reduce the pain from surgery, and achieve better treatment effects have been well known but remaining as unresolved issues. This study aims at evaluating two types of radiofrequency (RF) thermocoagulation procedures for the treatment of SAUB: the RF-A procedure group included 25 SAUB patients ≥45 years of age treated for amenorrhea; the RF-B procedure group included 51 patients at <45 years of age treated for the control of excessive bleeding. Post-treatment ratings of menstrual satisfaction and pre-/post-treatment menstrual scores-pictorial blood loss assessment chart (PBAC)-and hemoglobin levels were collected; and the mean length of follow-up was 72 months. Also, 38 SAUB patients treated with standard drug regimens served as a control group. The results of the study showed that following RF treatment, the average long-term patient menstrual satisfaction was greater than 92 %. In both the RF groups, PBAC scores and hemoglobin levels were significantly improved from baseline (p < .05). Compared with the control group, PBAC scores and hemoglobin levels were also significantly better for the RF groups at 6-24-month post-operation. Patients experienced no hysterectomy in association with the RF procedures. In conclusion, this pilot study suggests that the novel RF procedures are both safe and effective in treating patients with SAUB. Further investigation is necessary to evaluate their application in broader clinical indication.

Reevaluation of discriminatory and threshold levels for serum ß-hCG in early pregnancy.

OBJECTIVES: To reevaluate both discriminatory and threshold levels associated with visualization of gestational sacs, yolk sacs, and fetal poles in patients presenting with vaginal bleeding, pain, or vaginal bleeding and pain in the first trimester of pregnancy using current ultrasonographic technology. METHODS: We reviewed the records of patients with first-trimester vaginal bleeding, pelvic pain, or both who were evaluated with a serum ß-hCG level and a transvaginal ultrasonogram within 6 hours of each other and had a known pregnancy outcome. Discriminatory and threshold ß-hCG levels for visualization of a gestational sac, yolk sac, and fetal pole were identified for all ultimately viable pregnancies. Logistic regression was used to model the predicted probability of visualizing these structures as a function of ß-hCG values using fractional polynomials. RESULTS: Six hundred fifty-one pregnancies met inclusion criteria; 366 were viable. Discriminatory ß-hCG levels at which structures would be predicted to be seen 99% of the time were 3,510 milli-international units/mL, 17,716 milli-international units/mL, and 47,685 milli-international units/mL for gestational sac, yolk sac, and fetal pole, respectively. In our population, threshold values for ß-hCG levels at which these structures could be seen were 390 milli-international units/mL, 1,094 milli-international units/mL, and 1,394 milli-international units/mL, respectively. CONCLUSIONS: Improvements in ultrasonographic technology have led to lower threshold ß-hCG values for ultrasonographic visualization of early intrauterine gestational structures. However, discriminatory levels for serum ß-hCG levels were higher than values currently used in practice. LEVEL OF EVIDENCE: II.

The Th1/Th2/Th17/Treg paradigm induced by stachydrine hydrochloride reduces uterine bleeding in RU486-induced abortion mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The Th1/Th2/Th17/Treg paradigm plays an important role in achieving maternal-fetal immunotolerance and participates in RU486-induced abortion. Excessive uterine bleeding is the most common side effect of RU486-induced abortion; however, its etiopathogenesis has not been fully understood. Therefore, elucidating the correlation between the Th1/Th2/Th17/Treg paradigm and the volume of uterine bleeding may offer novel therapeutic target for reducing uterine bleeding in RU486-induced abortion. Leonurus sibiricus has been used in clinics to reduce postpartum hemorrhage with low toxicity and high efficiency; however, the effective constituents and therapeutic mechanism have not been described. Stachydrine hydrochloride is the main constituent of L. sibiricus, therefore L. sibiricus is regarded as a candidate for reducing uterine bleeding in RU486-induced abortion mice by regulating the Th1/Th2/Th17/Treg paradigm. AIM OF THE STUDY: The purpose of this study was to determine the Th1/Th2/Th17/Treg paradigm in uterine bleeding of RU486-induced abortion mice and to elucidate the immunopharmacologic effects of stachydrine hydrochloride on inducing the Th1/Th2/Th17/Treg paradigm in reducing the uterine bleeding volume in RU486-induced abortion mice. MATERIALS AND METHODS: To investigate the Th1/Th2/Th17/Treg paradigm in uterine bleeding during RU486-induced abortion mice, pregnant BALB/c mice were treated with high- and low-dose RU486 (1.5mg/kg and 0.9 mg/kg, respectively), and the serum progesterone (P(4)) protein level, uterine bleeding volume, and proportions of Th1/Th2/Th17/Treg cells in mice at the maternal-fetal interface were detected by ELISA assay, alkaline hematin photometric assay, and flow cytometry, respectively. To determine the regulatory effect of stachydrine hydrochloride on the Th1/Th2/Th17/Treg paradigm in vitro, splenocytes of non-pregnant mice were separated and treated with P(4,) RU486, and/or stachydrine hydrochloride (10(-5)M, 10(-4)M, and 10(-3)M, respectively). The proportions of Th1/Th2/Th17/Treg cells were analyzed using flow cytometry. To evaluate the effect of stachydrine hydrochloride in reducing uterine bleeding via regulation of the Th1/Th2/Th17/Treg paradigm, pregnant mice were treated with RU486 (1.5mg/kg) and/or stachydrine hydrochloride (2.5mg/kg, 5mg/kg, and 10mg/kg). The serum P(4) level, uterine bleeding volume, and proportions of Th1/Th2/Th17/Treg cells at the mice maternal-fetal interface were detected. Moreover, the protein levels of cytokines (IL-12 and IL-6) and the cytokine soluble receptors were analyzed by ELISA assay, and the mRNA expression of transcription factors (T-bet, GATA-3, RORγt, and Foxp3) were detected by RT-PCR assay. RESULT: Th1- and Th17-biased immunity was observed in RU486-induced abortion mice. The volume of uterine bleeding during RU486-induced abortion was negatively related to the proportions of Th1 and Th17 cells, as well as the ratios of Th1:Th2 cells and Th17:Treg cells, and positively related to the proportions of Th2 and Treg cells. Stachydrine hydrochloride promoted the protein expression of IL-12 and IL-6, as well as the mRNA expression of T-bet and RORγt, while inhibiting the mRNA expression of GATA-3 and Foxp3. Therefore, the Th1/Th2/Th17/Treg paradigm in RU486-induced abortion mice shifted to Th1 and Th17 after stachydrine hydrochloride administration. The volume of uterine bleeding during RU486-induced abortion was reduced significantly after stachydrine hydrochloride administration. CONCLUSION: The Th1/Th2/Th17/Treg paradigm is closely related to the volume of uterine bleeding in RU486-induced abortion mice. The Th1/Th2/Th17/Treg paradigm induced by stachydrine hydrochloride contributed to the reduction in uterine bleeding in RU486-induced abortion mice.

Adiponectin to leptin index as a marker of endometrial cancer in postmenopausal women with abnormal vaginal bleeding: an observational study.

OBJECTIVES: To evaluate the correlation between endometrial cancer and adiponectin plasma concentration, leptin plasma concentration as well as adiponectin to leptin index in the population of postmenopausal women with abnormal vaginal bleeding. DESIGN: An observational study SETTINg: Department of Gynecology and Obstetrics, Specialist Teaching Hospital in Tychy, Poland. Population. 99 women between 47 and 88 years old, in postmenopausal state. METHODS: The cases (54 women) were females hospitalized due to postmenopausal vaginal bleeding in whom dilation and curettage (D&C) was performed and endometrial intraepithelial neoplasia (EIN) was diagnosed in anathomopathology. Hysterectomy was then performed in all cases and the endometrial cancer diagnosis was confirmed. The controls (45 women) consists of females with no postmenopausal uterine bleeding in whom endometrial thickness in transvaginal ultrasound was greater than 5 mm. D&C was than performed and no endometrial neoplasia was detected in any of the subjects. Adiponectin and leptin plasma concentration was measured in both groups. Mein outcome measures. The area under the curve, sensitivity, specificity and cutoffs for adiponectin, leptin and adiponectin to leptin index. RESULTS: Adiponectin, leptin and adiponectin to leptin index were statistically correlated with the risk of endometrial cancer. At the suggested cutoffs, corresponding to the highest accuracy (minimal false-negative and false-positive results), adiponectin to leptin index resulted in the highest sensitivity and specificity compared to adiponectin and leptin alone. CONCLUSIONS: Adiponectin to leptin index due to the highest sensitivity and specificity may be used as a marker of endometrial cancer in postmenopausal women with abnormal vaginal bleeding.

[Clinical value of combined detection of serum human epididymal secretory protein E4 and CA(125) in the diagnosis of endometrial carcinoma].

OBJECTIVE: To explore the clinical value of combined detection of serum human epididymal secretory protein E4 (HE4) and CA(125) in the diagnosis of endometrial carcinoma. METHODS: From Jan 2010 to Apr 2011, the serum specimens were collected from 124 cases of endometrial carcinoma, 97 cases of benign disease of uterus and 109 cases of healthy women. HE4 levels in the serum were detected by ELISA, and CA(125) levels in the serum were detected by the electro-chemiluminescent immunoassay. Those results were shown with median level. Accuracy of the diagnosis was evaluated by the area under the receiver operating characteristic curve (ROC-AUC). RESULTS: The median levels of HE4 and CA(125) were 78.09 pmol/L and 33.43 kU/L in serum of endometrial carcinoma group. The median levels of HE4 and CA(125) were 46.37 pmol/L and 18.26 kU/L in serum of benign disease of uterus group. The median levels of HE4 and CA(125) were 31.75 pmol/L and 12.64 kU/L in serum of healthy women group. The HE4 and CA(125) levels in serum of endometrial carcinoma group were significantly higher than those of benign disease of uterus group or healthy women group (all P < 0.05). Compared with that benign disease of uterus group, the ROC-AUC of HE4 and CA(125) in endometrial carcinoma group were 0.913 and 0.801, respectively. When the specificity was 95.0%, the sensitivities of HE4, CA(125), and combined detection of HE4 and CA(125) in endometrial carcinoma group were 41.1%, 22.6% and 46.0%, respectively. The positive rates of HE4 and CA(125) were 31% (27/86) and 12% (10/86) in stage I-II of endometrial carcinoma, while the positive rates were 63% (24/38) and 47% (18/38) in stage III-IV of endometrial carcinoma, in which there were significant difference between patients in stage III-IV and stage I-II (P < 0.01). CONCLUSIONS: The combined detection of serum HE4 and CA(125) is helpful to the diagnosis of endometrial carcinoma. The sensitivity, specificity and early diagnosis of HE4 are better than that of CA(125). The positive rates of HE4 and CA(125) in endometrial carcinoma are related to the clinical staging.

Ovarian volume assessment in relation to histologic findings and sex hormone levels in women with postmenopausal bleeding and thickened endometrium.

BACKGROUND AND OBJECTIVES: In postmenopausal women, ovarian stromal hyperplasia and endometrial cancer are often identified concurrently. The aim of the present study was to verify the association of ovarian volume with histologic findings and sex hormones levels in women with postmenopausal bleeding and thickened endometrium. DESIGN AND SETTING: Prospective observational study conducted in a teaching hospital between March 2008 and February 2010 PATIENTS AND METHODS: Ninety women with postmenopausal bleeding and thickened endometrium (>=5 mm) were enrolled. They underwent vaginal sonography for ovarian volume measurement. Blood samples were collected for sex steroid hormones assay. In addition, endometrial sampling was done for definitive histologic diagnosis. RESULTS: According to histologic results, 18 cases (20%) had endometrial adenocarcinoma, 24 cases (26.7%) had endometrial hyperplasia with or without atypia and 48 cases (53.3%) had benign histologic findings. Large ovaries were significantly associated with higher body mass index (BMI>=30) (P=.002) and endometrial adenocarcinoma (P < .001). After adjustment for age and BMI, increased ovarian volume in adenocarcinoma was associated with high serum level of estradiol (P < .001), serum total testosterone (P=.04) and serum free testosterone (P < .01) compared with other histologic findings. CONCLUSIONS: Large ovaries among women with postmenopausal bleeding and thick endometrium were associated with elevated serum sex steroid hormones and represent a marker of risk for endometrial adenocarcinoma.