Complications and satisfaction in transwomen receiving breast augmentation: short- and long-term outcomes.

BACKGROUND: To achieve long-term improvement in health care of transgender women, it is necessary to analyze all aspects of gender-confirming surgery, especially the relation of risks and benefits occurring in these procedures. While there are many studies presenting data on the urologic part of the surgery, there are just few data about complications and satisfaction with breast augmentation. METHODS: This is a retrospective study using parts of the BREAST-Q Augmentation Questionnaire and additional questions for symptoms of capsular contracture and re-operations and analyzing archived patient records of all transwomen which were operated at University Hospital Essen from 2007 to 2020. RESULTS: 99 of these 159 patients (62%) completed the questionnaire after a median time of 4 years after surgery. Breast augmentation led to re-operations due to complications in 5%. The rate of capsular contracture (Baker Grad III-IV) in this population was 3%. Most patients (75%) rated high scores of satisfaction with outcome (more than 70 points) and denied to have restrictions due to their implants in their everyday life. All patients reported an improvement in their quality of life owing to breast augmentation. CONCLUSION: Breast augmentation by inserting silicon implants is a safe surgical procedure which takes an important part in reducing gender dysphoria.

Soluble endoglin versus sFlt-1/PlGF ratio: detection of preeclampsia, HELLP syndrome, and FGR in a high-risk cohort.

The angiogenic factors sFlt-1 and PlGF play an established role in the detection of preeclampsia (PE). Recent data suggest that sEng might contribute to the pathogenesis of PE. However, only a few studies so far have addressed its role.This monocentric cross-sectional study of high-risk pregnancies aims to compare the levels of sFlt-1/PlGF ratio and sEng depending on different placental-related adverse pregnancy outcomes. The statistical analysis takes into account Pearson's correlation coefficient between angiogenic factors, the area under the curve estimates (AUCs) for detection, and adjusted odds ratios (aOR) with 95% confidence intervals (95%-CIs). The analysis included 206 patients: 60 controls, 90 PE (59 EOPE, 35 LOPE), 94 FGR, and 35 HELLP cases. Some outcomes overlapped because FGR commonly complicated PE and HELLP syndrome. Serum levels of sFlt-1/PlGF and sEng correlated with each other. Higher levels were observed in HELLP syndrome and EOPE cases. AUCs for sFlt-1/PlGF ratio and sEng were, respectively, 0.915 (95%-Cl 0.87-0.96) and 0.872 (95%-Cl 0.81-0.93) in PE, 0.895 (95%-Cl 0.83-0.96) and 0.878 (95%-Cl 0.81-0.95) in HELLP syndrome, 0.891 (95%-Cl 0.84-0.94), and 0.856 (95%-Cl 0.79-0.92) in FGR.aORsfor sFlt-1/PlGF ratio and sEng were, respectively: 2.69 (95%-Cl 1.86-3.9) and 2.33 (95%-Cl 1.59-3.48) in PE, 2.38 (95%-Cl 1.64-3.44) and 2.28 (95%-Cl 1.55-3.4) in FGR, and 2.10 (95%-Cl 1.45-3.05) and 1.88 (95%-Cl 1.31-2.69) in HELLP syndrome. In addition, the aORs between sFlt-1/PlGF and sEng were very similar but higher for PE and FGR than HELLP syndrome.In conclusion,sEng performed similarly to sFlt-1/PlGF to detect placental dysfunctions.

Course of the sFlt-1/PlGF ratio in fetal growth restriction and correlation with biometric measurements, feto-maternal Doppler parameters and time to delivery.

PURPOSE: The study aimed to assess the course of the soluble Fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio in pregnant women with fetal growth restriction (FGR) and to evaluate potential associations between the sFlt-1/PlGF ratio and feto-maternal Doppler parameters, fetal biometric measurements and the time between study inclusion and birth ("time to delivery"). METHODS: This was a retrospective longitudinal single center study including 52 FGR cases. The serum levels of sFlt-1 and PlGF were measured by using the BRAHMS Kryptor Compact PLUS. Fetal biometric and Doppler parameters, as well as the sFlt-1/PlGF ratio, were obtained both upon study inclusion and upon birth. RESULTS: Various associations between the levels of the biomarkers in maternal blood upon study inclusion and upon birth and sonographic parameters were observed in FGR cases: umbilical artery (p < 0.01), uterine arteries (p < 0.01), ductus venosus (p < 0.05), cerebroplacental ratio (CPR) (p < 0.01), femur length (p < 0.01) and birth weight (p < 0.01). The higher the sFlt-1/PlGF ratio upon study inclusion, the shorter the "time to delivery" (p < 0.01). The multivariate regression analysis showed that the greater the daily percentage increase of the angiogenic markers, the shorter the "time to delivery" (p < 0.01). CONCLUSION: The fetal well-being, as measured by feto-maternal Doppler parameters such as CPR and the severity of the placental dysfunction, as measured by the urgency of birth and birth weight, is reflected by the level of the sFlt-1/PlGF ratio in the maternal serum. A rapid daily increase of the sFlt-1/PlGF ratio is significantly associated with the clinical progression of the disease.

MR-proANP, a cardiovascular biomarker to predict late-onset preeclampsia and intrauterine growth restricted fetuses.

OBJECTIVES: Midregional pro-atrial natriuretic peptide (MR-proANP) is a cardiac biomarker and the maternal serum levels could predict late-onset preeclampsia (PE) or intrauterine growth restriction (IUGR) at third trimester of pregnancy. METHODS: We measured MR-proANP between 32 and 37 weeks of pregnancy prospectively: 32 patients suffered from PE and 22 developed IUGR. 676 patients exhibited no pregnancy complications. RESULTS: The median MR-proANP showed significantly higher results in PE (64.9 pmol/l (interquartile range (IQR) 36.3-105.2) and IUGR (59.7 pmol/l (IQR 39.7-163.0) groups compared to controls (38.7 pmol/l (IQR 29.7-49.2). Linear regression analysis showed association between PE and MR-proANP levels (Exp(ß) = 1.56; 95% CI: 1.34-1.81). AUC showed a predictive value for PE (AUC: 0.72) and IUGR (AUC: 0.71). CONCLUSIONS: Measuring MR-proANP in maternal serum between 32 and 37 weeks of pregnancy could help predicting IUGR and PE diagnosed after 34 week in pregnancy. Thus, we assume that MR-proANP may be an additional biomarker which mirrors the maternal cardiosvascular status next to sFlt-1/PLGF representing the angiogenic status.

Recommendations for a standardised educational program in robot assisted gynaecological surgery: Consensus from the Society of European Robotic Gynaecological Surgery (SERGS).

BACKGROUND: The Society of European Robotic Gynaecological Surgery (SERGS) aims at developing a European consensus on core components of a curriculum for training and assessment in robot assisted gynaecological surgery. METHODS: A Delphi process was initiated among a panel of 12 experts in robot assisted surgery invited through the SERGS. An online questionnaire survey was based on a literature search for standards in education in gynaecological robot assisted surgery. The survey was performed in three consecutive rounds to reach optimal consensus. The results of this survey were discussed by the panel and led to consensus recommendations on 39 issues, adhering to general principles of medical education. RESULTS: On review there appeared to be no accredited training programs in Europe, and few in the USA. Recommendations for requirements of training centres, educational tools and assessment of proficiency varied widely. Stepwise and structured training together with validated assessment based on competencies rather than on volume emerged as prerequisites for adequate and safe learning. An appropriate educational environment and tools for training were defined. Although certification should be competence based, the panel recommended additional volume based criteria for both accreditation of training centres and certification of individual surgeons. CONCLUSIONS: Consensus was reached on minimum criteria for training in robot assisted gynaecological surgery. To transfer results into clinical practice, experts recommended a curriculum and guidelines that have now been endorsed by SERGS to be used to establish training programmes for robot assisted surgery.

Predictive value of sFlt-1, PlGF, sFlt-1/PlGF ratio and PAPP-A for late-onset preeclampsia and IUGR between 32 and 37 weeks of pregnancy.

OBJECTIVES: The aim of this study was to investigate, whether maternal serum levels of sFlt-1, PlGF and PAPP-A at third trimester of pregnancy are associated with late-onset PE and intrauterine growth retardation (IUGR) after 34 weeks of pregnancy. METHODS: This was a prospective study measuring the maternal serum levels of soluble tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 32-37 weeks of pregnancy: 730 patients were enrolled and 676 had neither intrauterine growth restriction (IUGR) nor preeclampsia (PE) or pregnancy induced hypertension (PIH) throughout the pregnancy. 22 patients developed IUGR, 32 PE and 24 PIH. RESULTS: Linear regression analyses after adjusting for maternal age, gestational age at the blood sampling and maternal BMI showed associations between PE and serum sFlt-1 levels (Exp(ß) = 3.29; 95% CI: 2.69-4.04), serum PlGF levels (Exp(ß) = 0.18; 95% CI: 0.13-0.24), sFlt-1/PlGF ratio (Exp(ß) = 15.59; 95% CI: 10.64-22.84) and serum PAPP-A (Exp(ß) = 1.48; 95% CI 1.15-1.89). sFlt-1, PlGF and sFlt-1/PlGF-Ratio showed comparable area under the curve (AUC) estimates with a predictive ability to discriminate pregnancies developing PE and IUGR from controls. The predictive ability of PAPP-A for PE was only slightly better than chance. CONCLUSIONS: This study supported the ability of a single measurement of sFlt-1/PlGF ratio at third trimester to predict PE and IUGR occurring after 34 weeks of pregnancy. However, larger multicentre studies are needed to replicate our results.

Time trends (2006-2015) of quality indicators in EUSOMA-certified breast centres.

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast centres to establish minimum standards and ensure specialist multidisciplinary care. Prospectively collected anonymous information on primary breast cancer cases diagnosed and treated in the units is transferred annually to a central EUSOMA data warehouse for continuous monitoring of quality indicators (QIs) to improve quality of care. Units have to comply with the EUSOMA Breast Centre guidelines and are audited by peers. The database was started in 2006 and includes over 110,000 cancers from breast centres located in Germany, Switzerland, Belgium, Austria, The Netherlands, Spain, Portugal and Italy. The aim of the present study is assessing time trends of QIs in EUSOMA-certified breast centres over the decade 2006-2015. MATERIALS AND METHODS: Previously defined QIs were calculated for 22 EUSOMA-certified breast centres (46122 patients) during 2006-2015. RESULTS: On the average of all units, the minimum standard of care was achieved in 8 of 13 main EUSOMA QIs in 2006 and in all in 2015. All QIs, except removal of at least 10 lymph nodes at axillary clearance and oestrogen receptor-negative tumours (T > 1 cm or N+) receiving adjuvant chemotherapy, improved significantly in this period. The desirable target was reached for two QIs in 2006 and for 7 of 13 QIs in 2015. CONCLUSION: The EUSOMA model of audit and monitoring QIs functions well in different European health systems and results in better performance of QIs over the last decade. QIs should be evaluated and adapted on a regular basis, as guidelines change over time.

Prognostic relevance of caspase 8 -652 6N InsDel and Asp302His polymorphisms for breast cancer.

BACKGROUND: The minor allele of two caspase 8 polymorphisms, namely CASP8 -652 6N InsDel (rs3834129) and CASP8 Asp302His (rs1045485), were repeatedly associated with reduced breast cancer susceptibility. Contrarily, the presence of the -652 6N Del or the CASP8 302His variant was reported to be an unfavorable prognostic factor in colorectal cancer or neuroblastoma. However, prognostic relevance of these genetic variants for breast cancer is completely unknown and is therefore adressed by the current study. METHODS: Genotyping was performed by pyrosequencing. Caspase 8 mRNA expression was quantified by comparative RT-qPCR. RESULTS: We observed an allele-dose dependent association between CASP8 -652 6N InsDel and caspase 8 mRNA expression in breast cancer tissue, with homozygous deletion carriers showing lowest relative caspase 8 expression (p = 0.0131). Intriguingly, the presence of the -652 6N Del or the 302His variant was shown to be a negative prognostic factor for breast cancer in terms of an allele-dose dependent influence on overall survival (OS, p = 0.0018, p = 0.0150, respectively). Moreover, both polymorphisms were independent predictors of OS after adjusting for co-variats (p = 0.007, p = 0.037, respectively). Prognostic relevance of both polymorphisms were confirmed to be independent from each other and combined analysis of diplotypes revealed an additive influence upon OS (p = 0.0002). CONCLUSION: This is the first report, showing negative and independent prognostic impact of the CASP8 -652 6N Del and the 302His variant for breast cancer. Our data provide rationale to further validate clinical utility of these polymorphisms for breast cancer and to extend this investigation to a broad scope of other malignancies.

Anti-Mullerian-Hormone during pregnancy and peripartum using the new Beckman Coulter AMH Gen II Assay.

BACKGROUND: AMH levels determined by the conventional AMH assay declined during pregnancy and postpartum. A new Beckman Coulter AMH Gen II assay removes the potentially assay-interfering complement which is activated in pregnancy. The aim of this study was to evaluate if the decline of AMH levels in the serum of pregnant women during the course of pregnancy and peripartum was assay-dependent and thus artificial. METHODS: In this cross-sectional study prepartal blood samples were collected from 62 patients (median age 30.6 years [interquartile range: 25.6 - 34.5]) in the third trimester of pregnancy and again 1-4 days after delivery between 2011 and 2012. In another cohort of 11 patients (median age 34.1 years [interquartile range: 32.6 - 37.8]) blood samples were taken in different trimesters of pregnancy between 1995 and 2001. The conventional and the modified AMH assay were performed in the same patient serum samples. We used the conventional and the modified AMH-Gen-II ELISA (Beckman Coulter, Immunotech, Webster, USA) for the assessment of AMH levels. The Wilcoxon signed rank test was used for determining differences between AMH levels pre- and postpartum. The method of Bland and Altman was applied for analyzing the agreement of both methods for determining AMH levels. RESULTS: AMH values peripartum were lower than those expected in fertile non-pregnant women of comparable age. An overall mean difference of 0.44 ng/ml was observed between the conventional and the modified assay. Measurements with the modified assay showed a significant decline of postpartal levels compared with prepartal levels which is consistent with values obtained using the conventional assay (both p < 0.00001). Compared to the longitudinal measurements of AMH levels determined using the conventional assay, AMH levels obtained using the modified assay suggest a steeper decline of values during the course of pregnancy. CONCLUSION: By comparing the conventional assay for AMH determination with the modified assay the present study confirmed that AMH levels decline during the course of pregnancy and early after delivery.

The effect of EUSOMA certification on quality of breast cancer care.

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast units to establish minimum standards and ensure specialist multidisciplinary care. In the present study we assess the impact of EUSOMA certification for all breast units for which sufficient information was available before and after certification. MATERIALS AND METHODS: For 22 EUSOMA certified breast units data of 30,444 patients could be extracted from the EUSOMA database on the evolution of QI's before and after certification. RESULTS: On the average of all units, the minimum standard of care was achieved for 12/13 QI's before and after EUSOMA certification (not met for DCIS receiving just one operation). There was a significant improvement of 5 QI's after certification. The proportion of patients with invasive cancer undergoing an axillary clearance containing >9 lymph nodes (91.5% vs 89.4%, p 0.003) and patients with invasive cancer having just 1 operation (83.1% vs 80.4%, p < 0.001) dropped, but remained above the minimum standard. The targeted standard of breast care was reached for the same 4/13 QI's before and after EUSOMA certification. CONCLUSION: Although the absolute effect of EUSOMA certification was modest it further increases standards of care and should be regarded as part of a process aiming for excellence. Dedicated units already provide a high level of care before certification, but continuous monitoring and audit remains of paramount importance as complete adherence to guidelines is difficult to achieve.

Impact of Age, Obesity and Smoking on Patient Satisfaction with Breast Implant Surgery - A Unicentric Analysis of 318 Implant Reconstructions after Mastectomy.

Aim: Breast reconstruction has become increasingly important for the body image of women with breast cancer. We conducted a study to investigate how patient characteristics correlate with surgical outcome after breast reconstruction with implant after mastectomy and to identify risk factors which could facilitate patient selection for reconstruction. Patients and Methods: For this case cohort analysis (n = 257 patients with 318 heterologous reconstructions), we analyzed BMI, smoking, pre-existing disease, chemotherapy and radiotherapy, one-stage/two-stage reconstruction, immediate/delayed reconstruction, antibiotic therapy and complications, partner interaction and adherence to the decision for reconstruction using a customized questionnaire. Results: 257 patients with 318 implant reconstructions (196 unilateral, 61 bilateral) were eligible for inclusion in the study. Median follow-up time was 3.1 years (range: 1 month to 10 years). Response rate to the questionnaire was 71.8 %. Median age was 49 years (range 24-79 years), median BMI was 22.44 (range 16.33-40.09). A BMI > 30 was inversely correlated with positive self-image (p = 0.004), and implant loss/rotation was more frequent in this group (p < 0.05). Smoking > 10 cigarettes/day had a negative impact on surgical outcome. A positive self-image had a positive impact on partner interaction (p < 0.001) and was correlated with a lower perception of pain. Aesthetic results did not vary with age (p = 0.054). Titanized polypropylene meshes were used to protect against implant rotation (p = 0.034). Rates of capsular fibrosis were low in our cohort (< 10 %), and implant loss rate was less than 2 %. Conclusions: This study offers a differentiated approach for the pre-surgical counselling of patients and shows that patients up to 80 years of age are highly satisfied with implant reconstruction. A high BMI and smoking > 10 cigarettes/day are unfavorable preconditions for implant reconstruction. The use of prophylactic antibiotics was confirmed as beneficial for surgical outcome. A positive self-image after reconstruction strongly influences partner interaction.

Translating the concept of intrinsic subtypes into an oncoplastic cohort of more than 1000 patients - predictors of recurrence and survival.

INTRODUCTION: A paradigm shift in breast cancer was introduced by Sørlie's concept of intrinsic subtypes [1]. We validated this concept - which was originally based on 84 individuals - in a large cohort study of 1035 patients with oncoplastic surgery and analyzed if early and late recurrences are linked to a specific intrinsic tumor subtype or resection margins. MATERIALS AND METHODS: 1035 patients with oncoplastic surgery (2004-2009) were analyzed with regard to treatment characteristics and patterns of early (<5 years) and late recurrence (>5 years) and survival related to the intrinsic subtypes. Data was retrieved from patient's charts, customized patients questionnaires and cancer registries. RESULTS: 944 patients with primary, unilateral breast cancer, median age 58 years, were eligible for analysis. At a median FU of 5.2 years, LRR was 4.0%, 5-year-OS 94.5% and DFS 90.9%. Intrinsic subtypes, but not T-size, nodal-status, resections margins nor histopathology, governed local control and survival. There was no signal for prevelance of unclear margins in any of intrinsic subgroups and no preference of any oncoplastic technique attributed to them. TNBC and Her2 non-luminal breast cancer had highest recurrence and lowest survival rates. Although sentinel involvement (SLN+) was prevailing in the Luminal-B-Her 2 negative subtype at 34.3%, this did not translate into a higher axillary dissection rate. CONCLUSION: This study confirmed the intrinsic subtype concept on a large clinical basis and describes the patterns of early and late recurrence in oncoplastic surgery, concluding that bigger risk may not be overcome by bigger surgery.

Evaluation of the prognostic significance of disseminated tumor cells in the bone marrow of primary, non-metastatic breast cancer patients after a 7-year follow-up.

PURPOSE: About 30% of primary, non-metastatic breast cancer patients show a relapse of the disease years after first diagnosis, probably due to early tumor cell spread to the bone marrow (BM). For disseminated tumor cells (DTCs) in the BM, tumor cell dormancy, stem cell-like features and discordant receptor status of DTCs as compared to the primary tumor have been described, explaining the failure of conventional therapies. Here, we demonstrate no prognostic impact of DTCs and explain these findings by early bisphosphonate intake. METHODS: Bone marrow aspirates of 394 patients with first diagnosis of breast cancer diagnosed between July 1997 and February 2003 were evaluated for DTCs, applying immunocytochemistry. In addition to the given therapy including chemotherapy, radiotherapy and anti-hormonal therapy, oral clodronate therapy was recommended for at least 2 years for all DTC-positive patients. BM results were correlated with clinical prognostic factors and overall survival (OS). RESULTS: Disseminated tumor cells were detected in 163/394 (41%) patients and significantly correlated with a histopathological lobular subtype (p = 0.032) and inversely with HER2 positivity (p = 0.01). After a median follow-up of 7 years, no significant differences with regard to OS could be demonstrated for DTC-positive patients as compared to patients with no DTCs in the BM at first diagnosis (p = 0.156). CONCLUSIONS: In this study, we demonstrate no prognostic impact of DTCs, contradictory to previous findings. We speculate that the lack of impact of DTC-positivity on OS might be due to early clodronate intake, but further studies will have to prove whether the observed effect can be confirmed.

Change of anti-Mullerian-hormone levels during follicular phase in PCOS patients.

Anti-Mullerian-hormone (AMH) does not seem to fluctuate significantly during the menstrual cycle in healthy women. However, little is known about cycle fluctuations of AMH levels in patients with polycystic ovarian syndrome (PCOS). The purpose of this study was to examine AMH fluctuations during the follicular phase in PCOS patients receiving antiestrogens or recombinant follicle-stimulating hormone (FSH). About 40 PCOS patients diagnosed according to Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2003 and 19 controls were prospectively enrolled. PCOS patients received either antiestrogens or recombinant FSH for monoovulation induction and controls received antiestrogens. AMH levels were determined (1) between the 2nd and the 5th day of follicular phase and (2) when a single large dominant follicle ≥18 mm had appeared. Our study shows that AMH levels do not change during follicular development in controls as well as in PCOS patients with AMH levels < 5 ng/ml, irrespective of antiestrogen or FSH therapy. However, in PCOS patients with AMH levels ≥5 ng/ml, AMH declines significantly during follicular development (p < 0.01). We conclude that AMH levels should be determined in the early follicular phase in PCOS patients without the influence of antiestrogens or exogenous FSH, because these interventions may lower AMH values in patients with high levels.

Anti-Mullerian Hormone: an indicator for the severity of polycystic ovarian syndrome.

PURPOSE: Features of polycystic ovarian syndrome (PCOS) including sonographic aspects, androgens, LH and LH/FSH ratio as well as Anti-Mullerian Hormone (AMH) were evaluated according to their diagnostic potency in detecting different degrees of PCOS severity. METHODS: 80 women with PCOS diagnosed according to the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2003 and 48 controls were enrolled between 2011 and 2013. PCOS patients fulfilling all Rotterdam criteria were defined as having severe PCOS (n = 59), while patients showing oligo-/amenorrhoea and polycystic ovaries but without hyperandrogenemia were defined as having mild PCOS (n = 21). All patients were treated at the University Hospital of Essen, Germany. RESULTS: The strongest group difference between controls and severe PCOS patients was observed for AMH showing an age-adjusted odds ratio of 2.56 [95 % confidence interval (CI) 2.00-3.27; p < 0.0001]. Age-adjusted receiver operating characteristic analysis showed that the area under the curve (AUC) of 0.88 (95 % CI: 0.80-0.95) for AMH and 0.94 (95 % CI 0.88-0.98) for antral follicle count did not differ significantly in their ability to discriminate between severe PCOS patients and controls. AMH showed higher AUC estimates than androgens, ovarian volume, LH and LH/FSH ratio and an AUC of 0.80 (95 % CI: 0.65-0.91) for detecting mild PCOS. CONCLUSIONS: To our knowledge, this is the first study comparing the diagnostic potency of AMH, sonographic aspects, androgens, and LH/FSH ratio according to different PCOS subgroups while accounting for the age-dependency of AMH. In cases where vaginal scans are not feasible or in patients without hyperandrogenemia AMH may be used as a surrogate parameter in PCOS diagnosis, superior to androgens and gonadotropins.

Predictive markers for the FSH sensitivity of women with polycystic ovarian syndrome.

STUDY QUESTION: Do parameters which are involved in pathogenesis of polycystic ovarian syndrome (PCOS) predict the dosage of recombinant FSH required to achieve monofollicular development for ovulation induction? SUMMARY ANSWER: Anti-Mullerian hormone (AMH) appeared to be an independent predictor of the required dosage of FSH to achieve monofollicular development for ovulation induction in a study sample of clomiphene-resistant PCOS patients. WHAT IS KNOWN ALREADY: AMH plays a key role in the pathogenesis of PCOS. This is the first study that has evaluated the association between AMH and the required FSH dosage to achieve the development of a large follicle of at least 18 mm, in the presence of additional predictors of ovarian responsiveness. In the few studies to date which have evaluated predictors of ovarian responsiveness in PCOS patients, fasting insulin has been shown to be a significant predictor. STUDY DESIGN, SIZE, DURATION: A total of 48 infertile PCOS patients aged 18-43 years were enrolled in this prospective, observational study between 2009 and 2013. Study participants received between one and six cycles of ovarian stimulation with recombinant FSH using a step-up protocol. The mean total FSH dosage per cycle for reaching a monofollicular development for ovulation induction was evaluated to investigate its association with AMH, LH, FSH, LH/FSH-ratio, sex hormone-binding globulin (SHBG), androstendione, testosterone, free testosterone index, antral follicle count, ovarian volume, body mass index (BMI) and the age of patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: We used AMH-Gen-II ELISA (Beckman Coulter, Immunotech, Webster, TX, USA) for the assessment of AMH levels. Crude and multiple linear regression models were fitted to explore potential predictors of the required FSH dosage. MAIN RESULTS AND THE ROLE OF CHANCE: An interquartile range (IQR) increase in AMH was associated with a 51.4% [95% confidence interval (CI): 24.7-79.0%; P = 0.0003] increase in the mean total FSH dosage per cycle (in IU) in a crude regression model, corresponding to a 7.2% increase in the mean total FSH dosage per cycle per ng/ml AMH. Adjustment for BMI augmented the effect of AMH, with a 58.3% (95% CI: 33.2-84.2%; P = 1.8 × 10(-5)) increase in FSH dosage per IQR AMH (corresponding to an 8.2% increase per ng/ml AMH) and a 46.2% (95% CI: 16.5-76.6%; P = 0.003) increase per IQR BMI (corresponding to a 3.7% increase per kg/m(2)). AMH was the only independent variable for which the effect on FSH dosage was statistically significant in the crude regression model as well as after adjustment for other promising predictors. The association of BMI with FSH dosage was statistically significant while adjusted for AMH, but not in the crude model. LIMITATIONS, REASONS FOR CAUTION: The impact of metabolic parameters such as insulin resistance on the reported association between AMH and FSH dosage was not assessed. WIDER IMPLICATIONS OF THE FINDINGS: Knowledge about the predictors of ovarian sensitivity to FSH can facilitate a physician's decision-making in providing the optimal infertility therapy for PCOS patients. STUDY FUNDING/COMPETING INTERESTS: Funding was provided by the University Hospital of Essen.

Early detection of maternal risk for preeclampsia.

Preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality. New molecular insights offer new possibilities of early diagnosis of elevated maternal risk. Maternal risk factors, biophysical parameters like Doppler examination of the uterine arteries and biochemical parameters allow early risk calculation. Preventive and effective therapeutic agents like acetylsalicylacid can be started in the early second trimester. This article reviews the diagnostic possibilities of early risk calculation to detect women having high risk for preeclampsia and the potential benefits for them, the offspring and health care systems. We provide risk calculation for preeclampsia as an important and sensible part of first trimester screening.

A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study.

BACKGROUND: Simultaneous adjuvant platinum-based radiochemotherapy in high-risk cervical cancer (CC) is an established treatment strategy. Sequential paclitaxel (Taxol) and platinum followed by radiotherapy may offer further advantages regarding toxicity. PATIENTS AND METHODS: An open-labeled randomized phase III trial was conducted to compare paclitaxel (175 mg/m(2)) plus carboplatin (AUC5) followed by radiation (50.4 Gy) (experimental arm-A) versus simultaneous radiochemotherapy with cisplatin (40 mg/m(2)/week) (arm-B) in patients with stage IB-IIB CC after surgery. Primary objective was progression-free survival (PFS). RESULTS: Overall, 271 patients were randomized and 263 were eligible for evaluation; 132 in arm-A and 131 in arm-B appropriately balanced. The estimated 2-year PFS was 81.8% [95% confidence interval (CI) 74.4-89.1] in arm-B versus 87.2% (95% CI 81.2-93.3) in arm-A (P = 0.235) and the corresponding 5-year survival rates were 85.8% in arm-A and 78.9% in arm-B (P = 0.25). Hematological grade 3/4 toxicity was higher in arm-B. Alopecia (87.9% versus 4.1%; P < 0.001) and neurotoxicity (65.9% versus 15.6%; P < 0.001) were significantly higher in arm-A. Early treatment termination was significantly more frequent in arm-B than in arm-A (32.1% versus 12.9%; P = 0.001). CONCLUSIONS: Sequential chemotherapy and radiation in high-risk CC could not show any significant survival benefit; however, a different toxicity profile appeared. This sequential regime may constitute an alternative option when contraindications for immediate postoperative radiation are present.