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Essure® has been tested as an alternative treatment for hydrosalpinx before embryo transfer (ET) in women undergoing assisted reproduction techniques. However, the persistence of a foreign body inside the uterine cavity might have a negative impact on the outcome of pregnancy. The present systematic review aimed at identifying, appraising and summarizing the available evidence regarding the effectiveness and safety of using Essure prior to ET for women with hydrosalpinx.We searched for studies in PubMed, Scopus, CENTRAL, Web of Science and ClinicalTrials.gov and the reference lists of eligible studies. All studies including at least 10 women with hydrosalpinx who received Essure, any other intervention or no treatment prior to ET were considered eligible. Study selection, data extraction and evaluation of the risk of bias were performed independently by two authors. Study outcomes were miscarriage per clinical pregnancy, singleton preterm birth per singleton live birth and live birth/ongoing pregnancy and clinical pregnancy per ET. The pooled results for each outcome and intervention were summarized as proportions with their respective 95% CIs, using a random-effects model.Our electronic search of databases was performed on 7 November 2015, and 26 studies with 43 study arms were considered eligible: eight study arms evaluating Essure; seven assessing tubal aspiration; seven appraising effects of no treatment; 12 evaluating salpingectomy; two assessing tubal division; and seven evaluating tubal occlusion. When compared with women who had no intervention, women with Essure had a higher clinical pregnancy rate per ET (36% (95% CI, 0-43%) vs 13% (95% CI, 9-17%)). When compared with women who had other interventions, women with Essure had a higher miscarriage rate per clinical pregnancy (38% (95% CI, 27-49%) vs 15% (95% CI, 10-19%)).The available evidence suggests that, although Essure prior to ET in women with hydrosalpinx improves the chance of achieving a clinical pregnancy compared with no intervention, it is associated with a higher rate of miscarriage when compared with the other interventions. Although this evidence is based on observational studies, we believe that salpingectomy should be the first option for women who are eligible for videolaparoscopy. However, it is still premature to make recommendations for women who are not eligible for surgery, and randomized controlled trials are needed to clarify which is the best treatment alternative in such a scenario. Copyright © 2016 ISUOG. Published by John WileySons Ltd.

To compare the effect of various oestrogen and oestrogen/progestin preparations on bone density over a 2-year follow-up period in early postmenopausal women.A retrospective study on 315 women followed in a menopause clinic.Antero-posterior lumbar spine bone densitometry was performed at baseline and between 18 and 24 months (mean 22 months) after initiation of hormone therapy. Participants were divided into six groups: women taking conjugated equine oestrogen (CEE) (n = 30); CEE plus sequential monthly medroxyprogesterone acetate (MPA) (n = 52); CEE plus sequential bimonthly MPA (n = 51); oral estradiol plus sequential monthly norethisterone acetate (n = 52); transdermal estradiol plus sequential monthly MPA (n = 30). A control group (n = 100) was composed of nonusers of hormones.Hormone users, as a whole (n = 215), increased their bone mineral density (BMD) by 2.9% (4.8) as compared to the controls who lost 3.5% (3.4; P0. 001). There were similar gains in BMD amongst the five study groups. Calcium supplementation was associated with better results in all women: users of hormones and calcium had a gain in BMD of 4.5% (4.8) compared to only 1.5% (4.5) in those on hormones but without calcium (P0.001); amongst the controls, women using calcium lost 1.4% (2. 4), whilst nonusers of calcium lost 3.7% (2.4; P0.001). A dose-response curve was found between basal BMD and the effect of hormone therapy: women with osteoporosis (T-score75%) demonstrated the largest increase in BMD - 6.3% (4.6), osteopenia (T-score 75-85%) was associated with a gain of 3.2% (5.6), low-borderline values (T-score 86-100%) gave a modest increase of 1.3% (4.3), and those with more than average BMD values (T-score100%) actually lost bone despite hormone treatment [-2.1% (4.1)].All hormone regimens had a similar bone conserving effect. Basal BMD value may serve as a predictor for the success of treatment. Calcium supplementation should be recommended in all postmenopausal women.

Hypothyroidism, which is a common disorder among postmenopausal women, may be associated with higher than average bone mineral content. Contrarily, treatment with L-thyroxine may cause a significant bone loss. The aim of our study was to evaluate the effects of hormone-replacement therapy (HRT) on bone density in women with subclinical hypothyroidism treated with L-thyroxine. A total of 73 postmenopausal women with thyroid-stimulating hormone (TSH) levels5 mU/l and normal free thyroxine values, who never used HRT or L-thyroxine, were divided into three groups according to the treatment given during a 3-year follow-up period: 34 women received only HRT; 20 women received HRT and L-thyroxine, and the remaining 19 women received neither medications. A euthyroid control group included 41 postmenopausal women with TSH levels between 0.5 and 1.5 mU/l, who were using HRT since the initial visit. Lumbar spine bone density measurements were performed at baseline and study termination. Taken as a whole, the hypothyroid women had a non-significant higher baseline bone mineral density (BMD) as compared to the euthyroid controls (1.068 +/- 0.19 g/cm2 vs. 1.024 +/- 0.15). After 3 years, both the euthyroid and hypothyroid women on HRT only had an increase in BMD (0.032 +/- 0.04 g/cm2 and 0.028 +/- 0.05 g/cm2, respectively; p0.001 for both, compared to baseline). Hypothyroid women using no medication had a decrease of 0.034 +/- 0.07 g/cm2 in BMD, and those receiving both HRT and L-thyroxine lost the most: 0.04 +/- 0.08 g/cm2 (p0.05 for both, compared to baseline). The addition of L-thyroxine thus prevented the beneficial effect of HRT on BMD. Thyroid hormone replacement is recommended only when overt symptoms of hormone deficiency occur. In such cases, a single bone-conserving treatment with HRT may not suffice.

The aim of this study was to evaluate how many patients with endometriosis have concomitant irritable bowel syndrome (IBS) and/or constipation according to the Rome III criteria. Furthermore, the value of an additional gastroenterological consultation with therapeutic advice was evaluated.Patients with proven endometriosis were included in a prospective, single-centre study. A questionnaire was undertaken regarding IBS and chronic constipation. Patients with symptoms consistent with the Rome III criteria for IBS were referred to our gastroenterological outpatient clinic.In total 101 patients were included. Endometriosis was diagnosed surgically in 97% and visually in the vagina in 3%. Fifteen per cent of the patients with endometriosis also had IBS and 14% of the patients with endometriosis had functional constipation without IBS. Of the 22 patients finally presenting to the gastroenterologist, five had a significant stenotic rectosigmoid lesion and were treated surgically. The remaining 17 patients were treated conservatively. Defecation symptoms improved in 86% and pain was reduced in 64%.In patients with endometriosis, 29% also had IBS or constipation. Referral to a gastroenterologist resulted in improvement of defaecation in 86%, and 64% reported a reduction in the degree of pain.

To analyse the incidence and mortality of melanoma in the province of Vojvodina - the north part of Serbia- from the epidemiologic and clinical point of view.In this retrospective study, we used databases of the Cancer Registry of Vojvodina, Oncology Institute of Vojvodina in Sremska Kamenica; Clinical Centre of Vojvodina in Novi Sad; Institute of Public Health of Vojvodina in Novi Sad; and Institute of Public Health of Serbia in Belgrade.The incidence and mortality of melanoma in Vojvodina is permanently increasing over the last three decades. The number of newly diagnosed and deceased patients was higher in men and in women in Vojvodina than in central Serbia. Considering the incidence rate, the region of Vojvodina would be placed in the middle of the European countries. The results are more unfavorable with mortality, especially in male population, similar to the range of higher mortality rates among European countries.These upsetting facts call for improvement of primary and secondary prevention. Education of the population, continuous efforts to recognize groups of population at high risk for developing melanoma and detection of early phases of the disease increases the chances for cure and significantly reduces treatment costs.

A 52-year-old woman with known endometriosis was treated with a levonorgestrel-containing IUD for irregular vaginal blood loss. Two weeks later she was admitted with signs ofpelvic inflammatory disease (PID) and was treated with antibiotics. As no clinical improvement ensued, laparoscopy was performed which demonstrated an infected endometriosis cyst in her right ovary. Ovariectomy was performed. In a 29-year-old woman with a symptomatic endometriosis cyst in the right ovary, PID was also suspected. After an initially good response to antibiotic therapy her condition deteriorated. Laparotomy revealed an infected endometriosis cyst. It was drained with subsequent cystectomy. A third, 43-year-old, woman with known endometriosis was admitted with signs of PID. Although she had a good clinical response to antibiotic therapy, her C-reactive protein (CRP) level remained elevated. Diagnostic laparoscopy demonstrated a large abscess in the right ovary. Ovariectomy was performed. Histology showed signs of an infected endometriosis cyst. All these women presented with PID and, in addition, a cystic adnexal mass on ultrasonography. The incidence oftubo-ovarian and ovarian abscesses is higher in the presence of an endometriosis cyst. Irrespective of the presence of an endometriosis cyst, antibiotics should be the first line of treatment. Reduction in the size of the abscess is not a useful parameter for monitoring conservative treatment when an infected endometriosis cyst is present. If it is decided to perform surgery on the infected endometriosis cyst, drainage of the abscess is usually not sufficient: excision of the endometriosis cyst is the only adequate therapy.

To investigate the effect of postmenopausal oral and transdermal hormone therapy on plasma levels of C-reactive protein (CRP), we performed a randomised, double-blind, double-dummy, placebo-controlled, 15-month study. One hundred and fifty-two healthy hysterectomised postmenopausal women received daily either placebo (n = 49), or transdermal 17beta-oestradiol (E(2)) 50 micro g (tE(2) group, n = 33), or oral E(2) 1 mg (oE(2) group, n = 37), or oral E(2) 1 mg combined with gestodene 25 micro g (oE(2) + G group, n = 33) for thirteen 28-day treatment cycles, followed by four cycles placebo for each group. Data were collected at baseline and in cycles 4, 13 and 17. In cycle 13, CRP was significantly increased in the oE(2) group compared to placebo (P = 0.004). The median percentage change from baseline versus placebo was +75% (P0.001). In cycle 17, significantly lower values were observed in the oE(2) group compared to cycle 13 and to the placebo group (-49%, P0.001). There were no significant changes versus placebo in the other groups. In conclusion, oral E(2) significantly increased CRP levels. This change was larger than the increase found during oral E(2) + G. Transdermal E(2) did not affect CRP levels.

Objectives: To look for possible association between past history of ovulation induction and age at menopause. Design: Women attending our postmenopausal outpatient clinic were asked to fill questionnaires with demographic data, obstetrical history (including treatment for infertility), and medical details related to menopause. Patients: The study group (n=31) consisted of women with a history of ovulation induction, and a control group (n=200) included women who did not experience such intervention. Results: The age at the final menstrual bleeding was 46.4±5 in the study group, and 50±4 for the control group (P

Beta human chorionic gonadotropin (beta-hCG) is expressed in human fetal tissue and cancer cells of various histologic types. It is degraded to the beta-core fragment (beta cf-hCG) which is concentrated in urine, and is known as urinary gonadotropin peptide (UGP). The objective of this study was to assess 1) the value of urinary gonadotropin peptide (UGP) as a single test and the combination of UGP with CA 125 as a diagnostic test in predicting the benign or malignant origin of gynecologic disease, 2) the influence of surgical removal of the tumor on the levels of UGP and CA 125, 3) the influence of the urinary concentration on the UGP levels in relation to the test results. PATIENTS, MATERIALS, METHODS AND STATISTICS: Serum and urine were collected from 31 gynecological patients with malignant and non-malignant disease, preoperatively, and 1 week and 6 weeks after surgery. Optimal cut-off levels were determined by Receiver Operating Characteristic-curves (ROC). Sensitivity (SENS), specificity (SPEC), positive (PPV) and negative predictive value (NPV) and overall test accuracy (ACC) for their ability to discriminate benign from malignant masses were calculated. Logistic regression analysis was performed to calculate the contribution of CA 125, UGP and UGP/creatinine (UGP/creat) to a model predicting malignancy.The optimal cut-off level for UGP was found 1 fmol/l, for UGP/creat 1.33 fmol/mg creatinine and for CA 125 100 kU/L. The distribution of the urinary creatinine values varied considerably (median = 8.3 mmol/l, range 0.6-25.8 mmol/l). The correlation coefficient (r) between log UGP and log CA 125 was 0.44 (p = 0.001) and between log UGP/creat and log CA 125 0.53 (p0.0001).UGP may be used as a tumor maker in gynecological disease. However, CA 125 as single test discriminates malignant from benign disease better than UGP or UGP/creat. In a logistic model the combination of CA 125 with UGP and UGP/creat predicts the benign or malignant character in 89% of the study population. Significant changes in UGP and UGP/creat levels were seen after removal of benign tumors, however, this was not found in ovarian cancer patients. Correction of the UGP values for the urinary concentration improved the results slightly.

Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis. Serum Lp(a) concentrations increase after menopause, and postmenopausal estrogen replacement appears to decrease Lp(a) levels. In a randomized, double blind study, we examined the effects of 6-month treatment with daily 17 beta-estradiol (E2; 2 mg, orally) continuously combined with one of four dosages [2.5 mg (n = 41), 5 mg (n = 38), 10 mg (n = 38), and 15 mg (n = 20)] of dydrogesterone on fasting serum Lp(a) concentrations in 137 healthy postmenopausal women. At baseline, no significant differences were noted among the four treatment groups. During the study period of 6 months the median serum Lp(a) concentration decreased significantly from 128 mg/L (range, 5-1660) to 110 mg/L (range, 1-1530) in the total population, corresponding to a reduction of 13% (P0.001). The percent changes in serum Lp(a) correlated positively with the percent changes in serum E2 at 3 as well as 6 months of therapy (r = 0.38; P0.001 and r = 0.35; P0.001, respectively). A dose response of dydrogesterone on serum Lp(a) was not found. In addition, serum lipids and (apo)lipoproteins improved significantly in all four treatment groups. In conclusion, oral E2 continuously combined with dydrogesterone has beneficial effects on the lipid and lipoprotein profile and is effective in lowering Lp(a) concentrations in postmenopausal women.

Aims The 4S-AF classification scheme comprises of four domains: stroke risk (St), symptoms (Sy), severity of atrial fibrillation (AF) burden (Sb), and substrate (Su). We sought to examine the implementation of the 4S-AF scheme in the EORP-AF General Long-Term Registry and compare outcomes in AF patients according to the 4S-AF-led decision-making process. Methods and results Atrial fibrillation patients from 250 centres across 27 European countries were included. A 4S-AF score was calculated as the sum of each domain with a maximum score of 9. Of 6321 patients, 8.4% had low (St), 47.5% EHRA I (Sy), 40.5% newly diagnosed or paroxysmal AF (Sb), and 5.1% no cardiovascular risk factors or left atrial enlargement (Su). Median follow-up was 24 months. Using multivariable Cox regression analysis, independent predictors of all-cause mortality were (St) [adjusted hazard ratio (aHR) 8.21, 95% confidence interval (CI): 2.60–25.9], (Sb) (aHR 1.21, 95% CI: 1.08–1.35), and (Su) (aHR 1.27, 95% CI: 1.14–1.41). For CV mortality and any thromboembolic event, only (Su) (aHR 1.73, 95% CI: 1.45–2.06) and (Sy) (aHR 1.29, 95% CI: 1.00–1.66) were statistically significant, respectively. None of the domains were independently linked to ischaemic stroke or major bleeding. Higher 4S-AF score was related to a significant increase in all-cause mortality, CV mortality, any thromboembolic event, and ischaemic stroke but not major bleeding. Treatment of all 4S-AF domains was associated with an independent decrease in all-cause mortality (aHR 0.71, 95% CI: 0.55–0.92). For each 4S-AF domain left untreated, the risk of all-cause mortality increased substantially (aHR 1.35, 95% CI: 1.16–1.56). Conclusion Implementation of the novel 4S-AF scheme is feasible, and treatment decisions based on this scheme improve mortality rates in AF.

STUDY QUESTION: Is there an increased prevalence of male microchimerism in women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, as evidence of fetal exposure to blood and anti-Müllerian hormone (AMH) from a (vanished) male co-twin resulting in regression of the Müllerian duct derivatives?SUMMARY ANSWER: Predominant absence of male microchimerism in adult women with MRKH syndrome does not support our hypothesis that intrauterine blood exchange with a (vanished) male co-twin is the pathophysiological mechanism.WHAT IS KNOWN ALREADY: The etiology of MRKH is unclear. Research on the phenotype analogous condition in cattle (freemartinism) has yielded the hypothesis that Müllerian duct development is inhibited by exposure to AMH in utero. In cattle, the male co-twin has been identified as the source for AMH, which is transferred via placental blood exchange. In human twins, a similar exchange of cellular material has been documented by detection of chimerism, but it is unknown whether this has clinical consequences.STUDY DESIGN, SIZE, DURATION: An observational case-control study was performed to compare the presence of male microchimerism in women with MRKH syndrome and control women. Through recruitment via the Dutch patients' association of women with MRKH (comprising 300 members who were informed by email or regular mail), we enrolled 96 patients between January 2017 and July 2017. The control group consisted of 100 women who reported never having been pregnant.PARTICIPANTS/MATERIALS, SETTING, METHODS: After written informed consent, peripheral blood samples were obtained by venipuncture, and genomic DNA was extracted. Male microchimerism was detected by Y-chromosome-specific real-time quantitative PCR, with use of DYS14 marker. Possible other sources for microchimerism, for example older brothers, were evaluated using questionnaire data.MAIN RESULTS AND THE ROLE OF CHANCE: The final analysis included 194 women: 95 women with MRKH syndrome with a mean age of 40.9 years and 99 control women with a mean age of 30.2 years. In total, 54 women (56.8%) were identified as having typical MRKH syndrome, and 41 women (43.2%) were identified as having atypical MRKH syndrome (when extra-genital malformations were present). The prevalence of male microchimerism was significantly higher in the control group than in the MRKH group (17.2% versus 5.3%, P = 0.009). After correcting for age, women in the control group were 5.8 times more likely to have male microchimerism (odds ratio 5.84 (CI 1.59-21.47), P = 0.008). The mean concentration of male microchimerism in the positive samples was 56.0 male genome equivalent per 1 000 000 cells. The prevalence of male microchimerism was similar in women with typical MRKH syndrome and atypical MRKH syndrome (5.6% versus 4.9%, P = 0.884). There were no differences between women with or without microchimerism in occurrence of alternative sources of XY cells, such as older brothers, previous blood transfusion, or history of sexual intercourse.LIMITATIONS, REASON FOR CAUTION: We are not able to draw definitive conclusions regarding the occurrence of AMH exchange during embryologic development in women with MRKH syndrome. Our subject population includes all adult women and therefore is reliant on long-term prevalence of microchimerism. Moreover, we have only tested blood, and, theoretically, the cells may have grafted anywhere in the body during development. It must also be considered that the exchange of AMH may occur without the transfusion of XY cells and therefore cannot be discovered by chimerism detection.WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to test the theory that freemartinism causes the MRKH syndrome in humans. The study aimed to test the presence of male microchimerism in women with MRKH syndrome as a reflection of early fetal exposure to blood and AMH from a male (vanished) co-twin. We found that male microchimerism was only present in 5.3% of the women with MRKH syndrome, a significantly lower percentage than in the control group (17.2%). Our results do not provide evidence for an increased male microchimerism in adult women with MRKH as a product of intrauterine blood exchange. However, the significant difference in favor of the control group is of interest to the ongoing discussion on microchimeric cell transfer and the possible sources of XY cells.STUDY FUNDING/COMPETING INTEREST(S): None.TRIAL REGISTRATION NUMBER: Dutch trial register, NTR5961.