Marianne Koch

Cut-off value of initial serum β-hCG level predicting a successful MTX therapy in tubal ectopic pregnancy: a retrospective cohort study

OBJECTIVE To determine the optimal serum β-hCG cut-off level to predict MTX treatment success in tubal ectopic pregnancy (EP). STUDY DESIGN Data of 240 women, who presented between 2003 and 2011 at the Department of Gynecology and Obstetrics, Medical University of Vienna, with tubal EP and who received MTX as primary treatment, were retrieved from the hospital information system (KIS). 198 patients could be included for final evaluation. Statistical analysis included area under the ROC curve, maximal Euclidean and Youden index, chi-squared and a five-fold cross validation. RESULTS The serum β-hCG level cut-off value was calculated at 2121mlU/ml with a specificity of 76.54% and sensitivity of 80.56% (AUC 0.789; p<0.001). Patients with an initial serum β-hCG level below 2121mlU/ml (n=131) experienced MTX treatment failure in 5.3% (n=7), compared to 43.3% (n=29) of patients with an initial serum β-hCG level equal to or above 2121mlU/ml (n=67). There was no statistically significant correlation between clinical symptoms and the MTX therapy outcome (p=0.580; likelihood quotient p=0.716). CONCLUSION The correct decision of therapy in patients with tubal ectopic pregnancy still represents a challenge. In this study we can conclude that, according to our results there is no endpoint of initial serum β-hCG levels, which can be clearly used as cut-off value for the optimal management of tubal EP. However, an initial serum β-hCG level of less than 2121mlU/ml seems to be a good value to expect a successful MTX treatment. Limitations are the retrospective study design and the inability of classifying clinical symptoms like pain as an objective parameter. Wider implications of the findings may include more detailed patient information and more accurate selection of suitable patients for MTX therapy.

The human urinary microbiome and how it relates to urogynecology.

Introduction and hypothesisRecent studies applying molecular techniques have demonstrated the presence of a urinary microbiota not detected by standard microbiological techniques. These have been found in the urine of healthy individuals and in those suffering from clinical symptoms. The present article reviews the findings of these studies to date, describing the molecular techniques, and specifically outlining any differences in microbiomes in relation to urogynecological disease. Further, the role of commensal bacteria in the lower urinary tract is considered.MethodsAn extensive literature search was conducted to identify articles on the microbiome of the female urinary tract in health and disease. We searched the electronic meta-databases Ovid MEDLINE® 1946–2015 and Embase 1974–2015. The keywords “microbiome, microbiota, bacterial colonization, microbiology, commensal bacteria, and bacteriuria” were searched in combination with “lower urinary tract symptoms, urogenital symptoms, urinary tract infection, overactive bladder and urinary incontinence.” A total of 426 papers were retrieved; 33 were included in this paper.ResultsThe microbiome of the female lower urinary tract shows variance between individuals and between age groups. There are significant differences between the microbiota in the lower urinary tract of individuals with urological symptoms and those without, relating to type and proportion of commensal Lactobacillus spp. There is only weak evidence to suggest that Lactobacillus might be applied as a therapeutic measure.ConclusionsIt is still unclear what role microbiota plays in female urinary tract health. The discovery of bacteria in the urine of healthy individuals may have implications for future therapies for lower urinary tract symptoms.

Urinary proteomic pattern in female stress urinary incontinence: a pilot study.

Introduction and hypothesisPrevious studies aiming to identify specific pre-defined urine protein biomarkers for stress urinary incontinence (SUI) have not identified clinically important differences. The hypothesis of our study was that the global distribution of urinary proteins, the proteome, differs between women with and those without SUI.MethodsIn this age-matched case–control study, we compared the urinary proteome of 20 women with SUI and 20 controls. Proteins were identified by applying high-performance liquid chromatography separation and tandem mass spectrometry detection. Data analysis was performed using Mascot 2.4.1 embedded in ProteinScape 3.1.ResultsWe identified 828 different proteins. The concentration of six of those showed a significant difference between urine samples of SUI patients and those of controls (q value < 0.25). Four proteins showed a higher abundance in SUI samples compared with controls: plasma serine protease inhibitor (logFC 1.11), leucine-rich alpha-2-glycoprotein (logFC 3.91), lysosomal alpha-glucosidase (logFC 1.24), and peptidyl-prolyl cis- trans isomerase A (logFC 1.96). We identified two proteins in lower abundance in SUI samples compared with controls: uromodulin (logFC −4.87) and TALPID3 (logFC −1.99).ConclusionsOverexpression of plasma serine protease inhibitor, leucine-rich alpha-2-glycoprotein, lysosomal alpha-glucosidase, and peptidyl-prolyl cis- trans isomerase A, and lower expression of uromodulin and TALPID3, in urine may be associated with female SUI.

The explicit mentioning of reporting guidelines in urogynecology journals in 2013: A bibliometric study

Poor reporting of research may limit critical appraisal and reproducibility, whereas adherence to reporting guidelines (RG) can guarantee completeness and transparency. We aimed to determine the explicit citing of RGs (CONSORT, PRISMA, STROBE) in urogynecology articles in 2013, the requirements of relevant journals and a potential difference between urogynecology and general gynecology journals.

Correlation of the volume of ectopic pregnancy and MTX therapy outcome: a retrospective cohort study.

OBJECTIVE To investigate a possible correlation between the volume of the tubal ectopic pregnancy (EP) measured by vaginal-ultrasound (VUS) and methotrexate (MTX) therapy outcome. STUDY DESIGN Data of EP volume measured by one expert-sonographer, viability, clinical symptoms, previous IVF/insemination, follow-up of β-hCG and progesterone levels, and treatment of EP was collected of 100 patients with sonographically diagnosed EP, who attended the Department of Obstetrics and Gynecology of the Medical University Vienna between March 2008 and September 2011. RESULTS The mean volume of EP (mVol.) in the group with successful MTX therapy (n = 38) was 5.11 ml, 95%CI [2.4; 7.8] with a median 3.2 ml, IQR [5.0], in the group with unsuccessful MTX treatment (n = 11) it was 15.24 ml, 95%CI [-2.6; 33.1], with a median 4.4 ml, IQR [11.4]. We could observe a trend towards a lower mVol. in the successful MTX group (5.11 ml vs. 15.24 ml). We could not show a significant correlation (u-test p = 0.208). CONCLUSION A clear tendency was observed towards a lower mVol. in the successful MTX therapy group, but we could not verify a statistically significant correlation of volume of EP and MTX therapy outcome most likely due to the small sample size. This was the first study investigating the correlation of volume of EP and MTX therapy outcome as principal question.

Risk Factors for De Novo Malignancies in Women After Kidney Transplantation: A Multicenter Transversal Study.

Objective Transplantation results in a 5-time elevated risk for a variety of malignancies (Kaposi sarcoma, skin, liver, lung, gastrointestinal cancer). A patient’s risk for malignancies could be of particular interest for the follow-up programs of patients and risk adaption after kidney transplantation. The aim of this study was to identify independent risk factors for de novo malignancies in women after renal transplantation. Methods and Materials This is a multicenter transversal study, conducted at the Medical University of Vienna and Hospital Rudolfstiftung, Vienna, Austria. We included female kidney graft recipients who were transplanted between 1980 and 2012 and followed-up at our institutions (N = 280). Clinical data of patients were extracted from hospital charts and electronic patient files. Patients were interviewed using a standardized questionnaire regarding their medical history, history of transplantation, and malignant diseases. Detailed information about present and past immunosuppressive regimens, rejection episodes and therapies, renal graft function, and information about primary disease was obtained. Diagnostic work-up and/or surgical exploration was performed if any presence of malignancy was suspected during routine follow-up. Histological specimens were obtained from all patients. Main outcome measures: the presence of de novo malignancy after kidney transplantation. Results Two hundred sixty-two women were included for statistical analysis. Median (interquartile range) follow-up period after transplantation was 101.1 (27.3–190.7) months. Thirty-two patients (12.2%) developed a malignancy: dermatologic malignancies (5.7%), breast cancer (3.4%), cervical cancer (0.8%), lung cancer (0.4%), gastrointestinal malignancies (1.5%), vulvar cancer (0.4%), and unclassified malignancies (1.9%). Median (interquartile range) time to malignancy after transplantation was 185.9 (92.0–257.6) months. Cumulative cancer rates were 4.9% (1 year), 14.4% (3 years), 16.4% (5 years), and 21.8% (10 years). Second transplantations were identified as independent risk factor for development of malignancy after transplantation. Conclusions Long-term risk of developing a malignancy after kidney transplantation is high, which might justify a follow-up of more than 10 years.

The primary outcomes and power calculations in clinical RCTs in urogynecology - need for improvement?

Background Except for studies where composite outcomes are chosen, a randomized controlled trial must have a primary outcome parameter. The primary outcome must be unambiguous, reliably assessable and clinically relevant. The estimated difference between the primary outcome in the study and control group(s) is used for the power calculation to determine the number of subjects needed for the trial.

Serum Human Chorionic Gonadotropin (β- hCG) Clearance Curves in Women with Successfully Expectantly Managed Tubal Ectopic Pregnancies: A Retrospective Cohort Study

Objective To establish clearance curves for serum β -hCG in women with successfully expectantly managed tubal ectopic pregnancies. Design Retrospective cohort study. Non- viable tubal ectopic pregnancy was diagnosed on transvaginal ultrasound. If initial serum β hCG was less than 5000 IU/L and patients were asymptomatic, expectant management was offered. Patients underwent serial β hCG measurements until serum β hCG was less than 20 IU/l, or the urine pregnancy test was negative. Setting Early Pregnancy and Gynaecology Assessment Unit, Kings College Hospital, London (December 1998 to July 2006). Patients We included 161 women with diagnosed non-viable tubal ectopic pregnancy who underwent successful expectant management. Main outcome measure Serum β hCG level. Results Mean initial serum β- hCG was 488 IU/L (41 - 4883) and median serum β hCG clearance time was 19 days (5 - 82). The average half-life of β hCG clearance was 82.5 hours (±SD 50.2) in patients with steadily declining serum β- hCG levels compared to 106.7 hours (±SD 72.0) in patients with primarily plateauing β-hCG levels in the declining phase. However, these differences were not significant (p>0.05). Conclusion We identified a median follow-up of 19 days until serum β hCG clearance in women with tubal ectopic pregnancy and successful expectant management. Although non- significant, women with initially plateauing serum β hCG showed a longer follow-up time until clearance compared to women with steadily declining β hCG levels. This information may serve as a guideline enabling clinicians to predict the length of follow-up for women with tubal ectopic pregnancy and expectant management.

Commentary on the paper titled: “Partially absorbable mesh or native tissue repair for pelvic organ prolapse: a randomized controlled trial”

This randomized controlled trial of 163 women with primary pelvic organ prolapse (POP) stage ≥2 aimed to compare the efficacy and safety of a partially absorbable mesh kit to native tissue repair at 24months postsurgery. The study was conducted in five teaching hospitals in The Netherlands from 2011 to 2013, and operations were exclusively performed by experienced surgeons in pelvic floor reconstruction and vaginal mesh insertion. Prolift +MTM was used in the mesh arm, a 50–50 blend of monofilament, nonabsorbable polypropylene mesh and absorbable polyglecaprone 25. Mesh insertion was performed via transvaginal trocar guidance, which does not permit resection of redundant vaginal tissues or simultaneous hysterectomies or T-incisions. It does, however, allow for additional native tissue surgery for restoration of level I support. Native tissue repairs were more heterogeneous, allowing vaginal hysterectomywith vault suspension, modifiedManchester Fothergill procedure, uterosacral vaginal suspension, and sacrospinous ligament fixation for the apical compartment in addition to anterior colporrhaphy. Gynecologists performing the 2-year follow-up assessments were not blinded to treatment allocation. The main outcome of this study was the overall anatomic success [defined as Pelvic Organ Prolapse (POP) stage < II] at 24 months postsurgery. Overall results showed no significant difference in anatomical or subjective benefit of partially absorbable mesh over native tissue repair at 24 months’ follow-up. Anatomic success was 45% inmesh and 32% in native tissue repair [relative risk (RR) 1.4]; composite success rates were 88% for mesh and 73% for native tissue (RR 1.1); global impression of improvement was 86% for mesh and 77% for native tissue (RR 1.1). There was no significant difference in benefit/risk ratio between procedures, including adverse events such as mesh exposure, de novo pain, and dyspareunia. One limitation of this study was the inability to reach the prespecified sample size (n = 176). In addition, of 81 women allocated to the mesh arm, 10% crossed over to native tissue repair. The authors speculate that a simultaneous television program on complications of vaginal mesh surgery may have complicated recruitment, highlighting the existing ambivalence toward mesh procedures in vaginal surgery. Results from this study showing equivalent outcomes of native tissue repair and partially absorbable mesh insertion may prospectively support a more accurate selection of patients to either treatment option. Long-term followup is definitely needed, as previous studies indicated higher mesh exposure rates after 24 months.

Association of uterine leiomyoma and overactive bladder syndrome

To assess associations between anterior and/or fundal uterine leiomyoma and overactive bladder syndrome.