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Endometriotic lesions are able to infiltrate surrounding tissue. This is made possible partly by an altered local and systemic immune response that helps achieve neoangiogenesis, cell proliferation and immune escape. Deep-infiltrating endometriosis (DIE) differs from other subtypes through the invasion of its lesions over 5 mm into affected tissue. Despite the invasive nature of these lesions and the wider range of symptoms they can trigger, DIE is described as a stable disease. This elicits the need for a better understanding of the underlying pathogenesis. We used the “Proseek® Multiplex Inflammation I Panel” in order to simultaneously detect 92 inflammatory proteins in plasma and peritoneal fluid (PF) of controls and patients with endometriosis, as well as in particular patients with DIE, in order to gain a better insight into the systemically and locally involved immune response. Extracellular newly identified receptor for advanced gycation end-products binding protein (EN-RAGE), C-C motif Chemokine ligand 23 (CCL23), Eukaryotic translation initiation factor 4—binding protein 1 (4E-BP1) and human glial cell-line derived neurotrophic factor (hGDNF) were significantly increased in plasma of endometriosis patients compared to controls, whereas Hepatocyte Growth factor (HGF) and TNF-related apoptosis inducing ligand (TRAIL) were decreased. In PF of endometriosis patients, we found Interleukin 18 (IL-18) to be decreased, yet Interleukin 8 (IL-8) and Interleukin 6 (IL-6) to be increased. TNF-related activation-induced cytokine (TRANCE) and C-C motif Chemokine ligand 11 (CCL11) were significantly decreased in plasma, whereas C-C motif Chemokine ligand 23 (CCL23), Stem Cell Factor (SCF) and C-X-C motif chemokine 5 (CXCL5) were significantly increased in PF of patients with DIE compared to endometriosis patients without DIE. Although DIE lesions are characterized by increased angiogenetic and pro-inflammatory properties, our current study seems to support the theory that the systemic immune system does not play a major role in the pathogenesis of these lesions.

Purpose Vacuum-assisted deliveries (VAD) are complex procedures that require training and experience to be performed proficiently. We aimed to evaluate if a more resource intensive practice-based training program for conducting VAD is more efficient compared to a purely theory-based training program, with respect to immediate training effects and persistence of skills 4–8 weeks after the initial training. Methods In this randomized-controlled study conducted in maternity staff, participants performed a simulated low-cavity non-rotational vacuum delivery before (baseline test) and immediately after the training (first post-training test) as well as 4–8 weeks thereafter (second post-training test). The study’s primary endpoint was to compare training effectiveness between the two study groups using a validated objective structured assessment of technical skills (OSATS) rating scale. Results Sixty-two participants were randomized to either the theory-based group (n = 31) or the practice-based group (n = 31). Total global and specific OSATS scores, as well as distance of cup application to the flexion point improved significantly from baseline test to the first post-training test in both groups (pall Conclusion A practice-based training program for conducting VAD results in comparable immediate improvement of skills compared to a theory-based training program, but the retention of skills 4–8 weeks after training is superior in a practice-based program. Future studies need to evaluate, whether VAD simulation training improves maternal and neonatal outcome after VAD.

Background Neonates and small infants with congenital cardiac disease undergoing cardiac surgery represent major challenges facing paediatric anaesthesia and perioperative medicine. Aims. We here aimed to investigate the success rates in performing ultrasound (US) guided central venous catheter insertion (CVC) in neonates and small infants undergoing cardiac surgery, and to evaluate the practicability and feasibility of thereby using a novel wireless US transducer (WUST). Methods Thirty neonates and small infants with a maximum body weight of 10 kg and need for CVC before cardiac surgery were included in this observational trial and were subdivided into two groups according to their weight: Results In total, CVC-insertion was successful in 27 (90%) of the patients and the first attempt was successful in 24 (78%) of patients. Success rates of CVC were 80% P = .07), whereas, the total time for catheter insertion and the duration of the whole procedure were similar in both groups (199 [167–228] vs. 178 [138–234] and 720[538–818] vs. 660 [562–833]s. In total, we report 3 (10%) cases of local hematoma as procedure-related complications. Assessments of the WUST revealed very good survey results for all parameters of practicability and handling (all ratings between 4.5 and 5.0). Conclusion Although difficulties in CVC-placement seem to relate to vessel size and patient’s weight, US guided CVC-insertion represents a valuable, fast, and safe intervention in neonates and small children undergoing cardiac surgery. Using the WUST is feasible for this clinical application and may aid in efforts aiming to optimize perioperative care. Trial registration Wireless US-guided CVC placement in infants; Clinicaltrials.gov: NCT04597021; Date of Registration: 21October, 2020; retrospectively registered.

The sFlt-1 (soluble fms-like tyrosine kinase-1), PlGF (placental growth factor), and their ratio are useful for predicting delivery because of preeclampsia in singleton pregnancies. Evidence on the utility of sFlt-1/PlGF ratio in twin pregnancies is lacking. We aimed to evaluate the predictive value of sFlt-1/PlGF ratio for delivery because of preeclampsia in twins. A retrospective data analysis of 164 twin pregnancies with suspected preeclampsia was performed. The sFlt-1/PlGF ratio, which was known to clinicians, was significantly higher in women who delivered within 1 and 2 weeks compared with those who did not (median: 98.9 and 84.2 versus 23.5 pg/mL, respectively; P P >0.100 for interaction). The area under the curve values of sFlt-1/PlGF were significantly higher than for PlGF alone (mean 0.88 and 0.88 versus 0.81 and 0.80) for predicting delivery because of preeclampsia within 1 and 2 weeks of blood sampling ( P =0.055 and 0.001, respectively). sFlt-1/PlGF ratio lower than 38 was able to rule-out delivery within 1 and 2 weeks with a negative predictive value of 98.8% and 96.4% for delivery because of preeclampsia within 1 and 2 weeks, respectively. A cutoff of 38 is applicable for ruling out delivery because of preeclampsia in twin pregnancies.

Endometriosis is a chronic inflammatory disease associated with an impaired immune response at the site of lesion implantation. The ability of macrophages to respond to changes in their environment is critical for an effective immune response. However, the existing knowledge of the peritoneal immune cell populations, their activation state and contribution to the immunological changes that occur in endometriosis are still controversial and inconclusive. In this study, we have examined the relative abundance of peritoneal macrophage subtypes, in women with (n = 21) versus without (n = 18) endometriosis and disease-associated changes in the adaptive T cell response. Using flow cytometry, we showed that peritoneal fluid monocyte/macrophages are composed of two populations of cells that exhibit major differences in the levels of the CD14 and CD68 markers, which we classified as the CD14+low/CD68+low and CD14+high/CD68+high subpopulations. Moreover, endometriosis-associated changes in the macrophage subtypes occurred only in the CD14+low/CD68+low subpopulation. In this subpopulation, we found an increased macrophage type 2 response that was coupled with an increase in peritoneal T-helper 2 and T-regulatory cell populations in women with endometriosis, compared with controls. In summary, this study resolves conflicting data in the literature regarding changes in the peritoneal immune cell population in endometriosis and identifies CD14+low/CD68+low macrophages as the subpopulation that changes in response to the disease.

Research question Are selected cell adhesion molecules useful as urinary biomarkers for diagnosing endometriosis? Design Prospective, longitudinal study (the Endometriosis Marker Austria) in patients who underwent laparoscopic surgery for benign gynaecological pathologies. A total of 149 patients not receiving hormonal treatment for at least 3 months prior to recruitment were included and preoperative urine protein levels of soluble vascular adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), E-selectin and P-selectin were measured using a magnetic bead-based multiplex assay, normalized to creatinine levels of each sample. Levels were correlated with endometriosis status, menstrual cycle phase, body mass index, cigarette smoking and severity and entity of the lesions. Results Urine levels of sVCAM-1, sICAM-1, E-selectin and P-selectin did not differ between women with (n = 84) and without (n = 65) endometriosis and among subgroups. Accordingly, receiver operating characteristic analysis to examine the value of using sVCAM-1, sICAM-1, E-selectin and P-selectin levels and sVCAM/sICAM ratio to diagnose endometriosis were not significant. Whether the serum sVCAM-1 levels correlated with the urine levels of the protein in the same women was also investigated, which revealed no significant correlations for sVCAM or sICAM. Conclusion Although a previous study had suggested that serum sVCAM is a promising biomarker for diagnosing endometriosis, no significant differences were found in urine levels of sVCAM-1, sICAM-1, E-selectin and P-selectin between women with and without endometriosis. Other markers should be studied in an effort to establish a truly non-invasive urinary test for diagnosing endometriosis.

To provide a video tutorial on vaginal transisthmic myomectomy in women with large submucosal fibroids.Stepwise demonstration of the technique, with a narrated video footage.Submucosal fibroids protrude into the uterine cavity and can cause numerous symptoms, including abnormal uterine bleeding, dysmenorrhea, subfertility, and obstetric complications. Over the last decades, hysteroscopic resection has become the preferred surgical approach for submucosal fibroids because it provides significant advantages regarding perioperative morbidity and postoperative recovery time when compared with laparotomy or laparoscopy with complete transection of the uterine wall. However, in large or multiple fibroids, longer surgery durations of hysteroscopic resection can lead to higher complication rates and incomplete resection. In some cases, hysteroscopic resection might even be impossible to perform. Furthermore, in many regions, special equipment for hysteroscopic myomectomy might not be available. Herein, we present a minimally invasive surgical alternative for approaching submucosal fibroids.A 26-year-old woman presenting with hypermenorrhea and dysmenorrhea (on a numeric rating scale from 0-10) caused by a recurrent International Federation of Gynaecology and Obstetrics (FIGO) type 0 fibroid measuring 5 cm in diameter.Vaginal transisthmic myomectomy performed with a longitudinal transection of the uterine cervix and isthmus, morcellation of the fibroid with a scalpel, and multilayer reconstruction.Vaginal transisthmic myomectomy is a fast and relatively simple, minimally invasive surgical technique suitable for large or multiple FIGO 0 and some FIGO 1 fibroids, necessitating the use of only basic surgical equipment.Vaginal transisthmic myomectomy provides an additional minimally invasive surgical approach for submucosal fibroids.This surgical option for selected patients may help prevent complications resulting from prolonged hysteroscopic surgery, repeated hysteroscopic procedures owing to incomplete resection, and the morbidity of transabdominal approaches for myomectomy. With this video, we aim to expedite the clinical learning curve of this technique, which should be investigated on a broader scale in the future.

Endometriosis is a benign disease, characterized by a wide range of symptoms and different degrees of severity, which is why therapy should be individually adapted to the patient's needs. Over the years, a lot of research has gone into finding new therapeutic approaches for this enigmatic disease.This review presents the latest advances in pharmacological management of endometriosis and is solely focused on studies published from 2010 to 2021.Clinicians and researchers are constantly searching for new therapeutic strategies for endometriosis patients. As there are well-established treatments, however, any new medication should fulfill at least one of the three criteria: increased efficacy, comparable efficacy but a better safety profile, or treatments that have a lack of accompanying contraceptive effects that are seen in most endometriosis treatments. While some new substances show promising results, further studies are needed to demonstrate the fulfillment of one of the above-mentioned criteria.

Endometriosis is a chronic gynecological disorder affecting the quality of life and fertility of many women around the world. Heterogeneous and non-specific symptoms may lead to a delay in diagnosis, with treatment options limited to surgery and hormonal therapy. Hence, there is a need to better understand the pathogenesis of the disease to improve diagnosis and treatment. Long non-coding RNAs (lncRNAs) have been increasingly shown to be involved in gene regulation but remain relatively under investigated in endometriosis. Mutational and transcriptomic studies have implicated lncRNAs in the pathogenesis of endometriosis. Single-nucleotide polymorphisms (SNPs) in lncRNAs or their regulatory regions have been associated with endometriosis. Genome-wide transcriptomic studies have identified lncRNAs that show deregulated expression in endometriosis, some of which have been subjected to further experiments, which support a role in endometriosis. Mechanistic studies indicate that lncRNAs may regulate genes involved in endometriosis by acting as a molecular sponge for miRNAs, by directly targeting regulatory elements via interactions with chromatin or transcription factors or by affecting signaling pathways. Future studies should concentrate on determining the role of uncharacterized lncRNAs revealed by endometriosis transcriptome studies and the relevance of lncRNAs implicated in the disease by in vitro and animal model studies.

Endometriosis is a common gynecological disorder characterized by ectopic growth of endometrium outside the uterus and is associated with chronic pain and infertility. We investigated the role of the long intergenic noncoding RNA 01133 (LINC01133) in endometriosis, an lncRNA that has been implicated in several types of cancer. We found that LINC01133 is upregulated in ectopic endometriotic lesions. As expression appeared higher in the epithelial endometrial layer, we performed a siRNA knockdown of LINC01133 in an endometriosis epithelial cell line. Phenotypic assays indicated that LINC01133 may promote proliferation and suppress cellular migration, and affect the cytoskeleton and morphology of the cells. Gene ontology analysis of differentially expressed genes indicated that cell proliferation and migration pathways were affected in line with the observed phenotype. We validated upregulation of p21 and downregulation of Cyclin A at the protein level, which together with the quantification of the DNA content using fluorescence-activated cell sorting (FACS) analysis indicated that the observed effects on cellular proliferation may be due to changes in cell cycle. Further, we found testis-specific protein kinase 1 (TESK1) kinase upregulation corresponding with phosphorylation and inactivation of actin severing protein Cofilin, which could explain changes in the cytoskeleton and cellular migration. These results indicate that endometriosis is associated with LINC01133 upregulation, which may affect pathogenesis via the cellular proliferation and migration pathways.

Study Objective Chronic endometritis (CE), which often presents asymptomatically, is associated with recurrent pregnancy loss, recurrent implantation failure after in vitro fertilization, and endometriosis. Data connecting CE with fallopian tubal occlusion are limited. The aim was to assess a potential association of CE, defined by the presence of syndecan-1 (CD138)–positive plasma cells in endometrial tissue samples, with fallopian tube patency and other factors for infertility, including endometriosis, adenomyosis, and hydrosalpinges. Design Prospective, monocentral pilot study. Setting Tertiary care center. Patients A cohort of 100 women who were infertile was enrolled from July 2019 to December 2020. Interventions Hysteroscopy with endometrial biopsy and laparoscopy with chromopertubation. Measurements and Main Results CE was found in 13 women (13.0%) and was associated with endometriosis (p = .034) and unilateral/bilateral fallopian tube blockage (p = .013). In women with endometriosis, the mean number of CD138-positive cells was positively correlated with the revised American Society for Reproductive Medicine score (r = .302, p = .028). In a binary regression model, the presence of a hydrosalpinx on one or both sides (odds ratio 15.308; 95% confidence interval, 1.637–143.189; p = .017) and the finding of CE in the endometrial tissue sample (odds ratio 5.273; 95% confidence interval, 1.257–22.116; p = .023) were significantly associated with fallopian tubal occlusion. Conclusion CE was significantly associated with blockage of the fallopian tubes and endometriosis. Endometriosis stage was associated with the number of CD138-positive cells in endometrial biopsies.

Endometriosis appears to share certain cancer-related processes, such as cell attachment, invasion, proliferation and neovascularization, some of which can also be found in other healthy tissues. In order to better understand the altered milieu of the peritoneal cavity, while acknowledging the reported similarities between endometriosis and neoplastic processes, we applied a multiplex oncology panel to search for specific biomarker signatures in the peritoneal fluid of women with endometriosis, women with deep-infiltrating endometriosis (DIE), as well as controls. In total, 84 patients were included in our study, 53 women with endometriosis and 31 controls. Ninety-two proteins were measured in prospectively collected peritoneal fluid (PF) samples, using the “Proseek® Multiplex Oncology I Panel”. We first compared patients with endometriosis versus controls, and in a second step, DIE versus endometriosis patients without DIE. Out of the 92 analyzed proteins, few showed significant differences between the groups. In patients with endometriosis, ICOS ligand, Endothelial growth factor, E-selectin, Receptor tyrosine-protein kinase erbB-2, Interleukin-6 receptor alpha, Vascular endothelial growth factor receptor 2, Fms-related tyrosine kinase 3 ligand, C-X-C motif chemokine 10, Epididymal secretory protein E4 and Folate receptor-alpha were decreased, while Interleukin-6 and Interleukin-8 were increased compared to controls. Looking at patients with DIE, we found Chemokine ligand 19, Stem cell factor, Vascular endothelial growth factor D, Interleukin-6 receptor alpha and Melanoma inhibitory activity to be increased compared to endometriosis patients without DIE. We have shown a distinct regulation of the immune response, angiogenesis, cell proliferation, cell adhesion and inhibition of apoptosis in PF of patients with endometriosis compared to controls. The specific protein pattern in the PF of DIE patients provides new evidence that DIE represents a unique entity of extrauterine endometriosis with enhanced angiogenetic and pro-proliferative features.

Reduced depth perception due to two-dimensional (2D) visualization of a three-dimensional (3D) space represents a main challenge in acquiring basic laparoscopic skills (BLS), 3D visualization might increase training efficiency. This study aimed to assess whether BLS training on a standard box trainer using 2D is at least equally effective compared to 3D. Medical students were randomized to training of Fundamentals of Laparoscopic Surgery (FLS) tasks using either 2D or 3D for four weeks. Baseline and post-training tests were performed using the assigned visualization modality. Data of 31 participants were analyzed (n = 16 2D, n = 15 3D). Baseline test scores did not differ significantly between groups, only at the peg transfer task and total scores, the 3D group performed better than the 2D group. All scores improved significantly in both groups, with post training scores not differing significantly between groups. Non-inferiority of 2D compared to 3D was demonstrated for total score improvement and improvement in all individual FLS tasks except for suturing with extracorporeal knot tying. Post training test performance did not change significantly when changing to the unfamiliar modality. In conclusion, BLS training using standard 2D is at least equally effective as with 3D, without significant disadvantages when changing to the other modality.

Endometriosis is a chronic inflammatory disease associated with an impaired immune response at the site of lesion implantation. The ability of macrophages to respond to changes in their environment is critical for an effective immune response. However, the existing knowledge of the peritoneal immune cell populations, their activation state and contribution to the immunological changes that occur in endometriosis are still controversial and inconclusive. In this study, we have examined the relative abundance of peritoneal macrophage subtypes, in women with (n = 21) versus without (n = 18) endometriosis and disease-associated changes in the adaptive T cell response. Using flow cytometry, we showed that peritoneal fluid monocyte/macrophages are composed of two populations of cells that exhibit major differences in the levels of the CD14 and CD68 markers, which we classified as the CD14+low/CD68+low and CD14+high/CD68+high subpopulations. Moreover, endometriosis-associated changes in the macrophage subtypes occurred only in the CD14+low/CD68+low subpopulation. In this subpopulation, we found an increased macrophage type 2 response that was coupled with an increase in peritoneal T-helper 2 and T-regulatory cell populations in women with endometriosis, compared with controls. In summary, this study resolves conflicting data in the literature regarding changes in the peritoneal immune cell population in endometriosis and identifies CD14+low/CD68+low macrophages as the subpopulation that changes in response to the disease. Electronic supplementary material The online version of this article (10.1007/s43032-020-00211-9) contains supplementary material, which is available to authorized users.

STUDY QUESTION Are increased sVCAM-1 and sICAM-1 levels associated with tumor necrosis factor-alpha-converting enzyme (TACE) activity in endometriosis? SUMMARY ANSWER Here we provide the first functional evidence that induced TACE activity in human endometriotic epithelial cells is at least in part responsible for the enhanced release of sVCAM-1 from these cells. WHAT IS KNOWN ALREADY We and others have shown that serum-soluble (s)VCAM-1 levels are significantly higher in women with endometriosis, compared to disease-free controls. Experimental evidence exists suggesting a role of sICAM-1 and sVCAM-1 in the pathogenesis of endometriosis. TACE was identified as the protease responsible for phorbol 12-myristate 13-acetate (PMA)-induced VCAM-1 release in murine endothelial cells. Additionally, it has recently been shown that TACE is upregulated in the endometrial luminal epithelium of the mid-secretory phase in infertile women. STUDY DESIGN, SIZE, DURATION This study was conducted at the Tertiary Endometriosis Referral Center of the Medical University of Vienna. Samples from a total number of 97 women were collected between July 2013 and September 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS After complete surgical exploration of the abdominopelvic cavity, 49 women with histologically proven endometriosis and 48 endometriosis-free control women were enrolled. Each participating woman contributed only one sample of eutopic endometrium and normal peritoneum, and some of the women with endometriosis contributed samples of diverse types of endometriotic lesions (in total 52 ectopic samples). Among the 49 women with endometriosis, 36 matched samples of endometriotic lesions and corresponding eutopic endometrium were collected. In order to detect sVCAM-1 and TACE protein by ELISA, peritoneal fluid (PF) samples were collected from 44 cases and 32 controls during surgery. Expression of TACE mRNA was analyzed by qRT-PCR in 111 endometrium tissue samples (28 eutopic control samples, 33 eutopic samples from women with endometriosis, 50 ectopic samples from lesions) and 37 healthy peritoneum samples. Immunohistochemistry was performed in 123 tissue samples (39 eutopic control samples, 42 eutopic samples from women with endometriosis, 42 ectopic samples from lesions) and the relation between tissue TACE protein levels and sVCAM-1 secretion was examined. PMA-induced sVCAM-1 release, and TACE- and VCAM-1-transcripts or proteins were measured in an immortalized endometriotic epithelial cell line (11Z) pre-incubated either with TACE inhibitors or following TACE siRNA knockdown. MAIN RESULTS AND THE ROLE OF CHANCE Here, we demonstrate that TACE protein is overexpressed in epithelium of tissue samples of both eutopic endometrium and ectopic lesions of women with endometriosis compared to disease-free controls (P < 0.001 both) and that the overexpression of the protein in the lesions is due to activation of TACE gene transcription (P < 0.001). Moreover, epithelial TACE protein was significantly higher in ectopic samples than in corresponding eutopic tissue of women with the disease (P < 0.001). High endometrial tissue TACE protein expression correlated with higher serum sVCAM-1 levels (P < 0.05) but not with sICAM-1 levels. Inhibition of TACE either by TACE inhibitors or by TACE siRNA knockdown resulted in decreased PMA-induced shedding of sVCAM-1 in vitro (P < 0.005 or P < 0.01, respectively), but the TACE inhibitors did not affect transcription of TACE or VCAM-1. Additionally, we observed an upregulation of TACE in proliferative endometrial epithelium of infertile (P < 0.005), compared to fertile women. TACE was increased in infertile women with endometriosis (P = 0.051) but not in infertile women without endometriosis. LIMITATIONS, REASONS FOR CAUTION Albeit well characterized, our control population included women with other gynecologic diseases, which may have impacted the levels of sVCAM-1 and tissue TACE expression levels, e.g. benign ovarian cysts or uterine fibroids. Thus, the results of our analysis have to be interpreted carefully and in the context of the current experimental settings. WIDER IMPLICATIONS OF THE FINDINGS The dysregulation of TACE substrate shedding represents a promising yet relatively unexplored area of endometriosis progression and could serve as a basis for the development of new treatments of the disease. STUDY FUNDING AND COMPETING INTEREST(S) This work was supported by the Ingrid Flick Foundation. The authors have no competing interests to declare.

Endometriosis is a prevalent gynaecological disorder with a still unclear pathogenesis. So far inflammatory mechanisms are associated with disease progression and critical reviews have discussed the so-called 'danger theory' related to endometriosis. Hence, we performed immunoassays to evaluate whether local inflammation is linked to the severity of the disease. In addition, we investigated the role of recently described cytokines IL-33, IL-32α and the 'alarmin' high mobility group box 1 (HMGB1). We confirmed a dysfunctional immune response in the local environment of women suffering from endometriosis. However, we found no direct evidence for a significant up-regulation of danger signals in endometriosis, irrespective of the severity of the disease.

Research question As microRNA (miRNA) are stable in circulation, this study tested whether they could serve as putative non-invasive biomarkers for endometriosis, and their expression differences between endometriosis patients and controls. It also addressed whether the combination of differently expressed miRNA together with clinical parameters in a statistical model could distinguish between endometriosis patients and controls. Design This prospective cohort study explored the possibility of using changes in extracellular miRNA spectra in plasma of 51 patients with endometriosis compared with 41 controls combined with clinical data as non-invasive biomarkers for the disease. The project was divided into three different phases for biomarker screening, discovery and validation. The differences in expression levels of plasma miRNA obtained from women with and without endometriosis were analysed with quantitative PCR-based microarrays. The diagnostic performance of the selected individual and/or combined differentially expressed miRNA candidates and clinical parameters was assessed using in silico bioinformatics modelling and receiver operating characteristic curve analysis. Results Data showed that a specific plasma miRNA signature is associated with endometriosis and that hsa-miR-154-5p, which alone or in combination with hsa-miR-196b-5p, hsa-miR-378a-3p, and hsa-miR-33a-5p and the clinical parameters of body mass index and age, are potentially applicable for non-invasive diagnosis of the disease. Changes in the levels of expression of certain circulating plasma miRNA also occurred within the phases of the menstrual cycle. Conclusions miRNA seem to be promising candidates for the non-invasive diagnosis of endometriosis. Further, other clinical parameters may help in distinguishing women suffering from endometriosis from healthy individuals.

Objective To explore whether a surgeon’s training level influences the rate of incomplete resections or the amount of resected cervical tissue in women treated with large loop excision of the transformation zone (LLETZ). Methods The present study is a retrospective analysis of the data of women who had undergone LLETZ for cervical intraepithelial neoplasia (CIN) within the years 2004–2008 at the Medical University of Vienna. Women were grouped according to the level of training of the operating surgeon (i.e, resident or staff gynecologist) and univariate and multivariable analyses were performed to identify independent risk factors for excessive cone volume, depth and incomplete resection (i.e., positive resection margin). Results Data of 912 women were analysed. Residents had a significantly larger cone volume [median 2681 (interquartile range 1472–4109) mm3] than staff gynecologists [2094 (1309–3402) mm3] (p = 0.001) in univariate analysis. The depth of resection and the rate of incomplete resection were comparable between both groups. In a binary logistic multivariable analysis, the level of training as well as patient’s age was significantly associated with a cone volume larger than 2500 mm3. Conclusion Conization performed by residents as opposed to staff gynecologists does not compromise the procedure’s effectiveness but may expose women to a potential additional risk for adverse obstetrical outcomes due to excessive resection of cervical tissue. Electronic supplementary material The online version of this article (10.1007/s00404-018-4761-1) contains supplementary material, which is available to authorized users.

Purpose To evaluate the effect of gestational diabetes on omentin-1 in maternal and cord plasma. As a potent mediator of insulin resistance, Omentin-1, an adipokine derived from human adipose and placental tissue, may be an important player in the pathophysiology of gestational diabetes. Methods This was a prospective case–control study. The study included 96 women with gestational diabetes and 96 pregnant women without. Omentin-1 was measured at the time of the oral glucose tolerance test, at 32 weeks in maternal plasma and right after delivery in umbilical cord blood by ELISA assay. Results Over a period of 2 years, 200 patients were enrolled. Omentin-1 levels did not significantly differ between both groups throughout the pregnancy: omentin-1 levels were 157 ± 83 ng/ml in women with gestational diabetes and 158 ± 93 ng/ml in women without gestational diabetes (p = 0.94) at time of the oral glucose tolerance test and 118 ± 77 ng/ml in women with diabetes and 150 ± 89 ng/ml in women without (p = 0.12) at 32 weeks, respectively. Both groups showed a decrease in omentin-1 levels throughout pregnancy, with a more pronounced decrease in diabetic women (13 ± 53 versus 4 ± 48 ng/ml; p = 0.5). Neonatal omentin-1 levels were significantly lower in offspring of diabetic mothers: 106 ± 61 versus 134 ± 45 ng/ml (p = 0.03). Conclusions There was no significant difference in omentin-1 levels between healthy and diabetic mothers throughout the pregnancy. However, we found significantly lower omentin-1 levels in offspring of diabetic mothers. This may indicate a risk for the development of insulin resistance in later life.

Purpose A modified application technique of intrauterine insemination (IUI) is slow release insemination (SRI), first described by Muharib et al. (Hum Reprod 7(2):227–229, 1992), who postulated higher pregnancy rates with a slow release of spermatozoa for 3 h. Methods To investigate this approach, two randomized controlled, cross-over pilot studies were performed from 2004 to 2006 in Israel and Germany to compare SRI with the standard bolus IUI. We aimed to present the results and perform a meta-analysis on available data for SRI. Univariate comparisons of pregnancy rates were performed using one-tailed z tests for method superiority. For meta-analysis, a fixed-effect Mantel–Haentzel weighted average of relative risk was performed. Results Fifty treatment cycles (IUI: n = 25, SRI: n = 25) were performed in Germany, achieving four pregnancies (IUI: 4%, SRI: 12%, p > 0.05). Thirty-nine treatment cycles (IUI: n = 19, SRI: n = 20) were performed in Israel achieving six pregnancies (IUI: 10.5%, SRI: 20%; p > 0.05). Meta-analysis of all eligible studies for SRI (n = 3) revealed a combined relative risk for pregnancy after SRI of 2.64 (95% CI 1.04–6.74), p = 0.02). Conclusions In conclusion, these results lend support to the hypothesis that the pregnancy rate might be improved by SRI compared to the standard bolus technique.

Background Destruction of the endothelial glycocalyx has been observed within lung and kidney grafts during ischemic organ preservation. We aimed to quantify glycocalyx damage within human liver grafts after organ preservation and correlate the results with graft injury and postoperative graft function in patients undergoing orthotopic liver transplantation (OLT). Methods Syndecan-1 (Sdc-1) was measured as indicator of glycocalyx degradation in effluents of 38 liver grafts and serum of patients undergoing OLT. Effluent Sdc-1 concentrations were correlated with hepatic injury markers from the effluent. Furthermore, we assessed the association of Sdc-1 with early allograft dysfunction (EAD), 1-year graft survival, and 1-year patient survival. Results Effluent Sdc-1 concentrations correlated with effluent concentrations of hepatocellular injury markers, including alkaline phosphatase (R = 0.543, P = 0.003), aspartate aminotransferase (R = 0.420, P = 0.029), and lactate (R = 0.574, P = 0.002). Sdc-1 effluent concentrations were greater in patients who developed EAD compared with those without EAD (4720 [4374-5133] vs 3838 [3202-4240] ng/mL, P = 0.015). Furthermore, receiver operating characteristics analyses revealed that effluent Sdc-1 concentrations (AUC = 0.82, P = 0.017) and serum Sdc-1 concentrations (AUC = 0.84, P = 0.006) were associated with the development of EAD. These results were confirmed by regression analyses. No association was found between Sdc-1 and 1-year graft survival or 1-year patient survival. Conclusions Our data suggest that the glycocalyx is damaged within human liver grafts during preservation and the extent of glycocalyx damage correlates with the severity of hepatocellular injury. Recipients of livers grafts with greater glycocalyx damage might be at higher risk for development of EAD after OLT.

Background We investigated the dynamics and the predictive value of soluble syndecan-1 (Sdc-1), a biomarker of endothelial dysfunction, in uneventful pregnancies and pregnancies complicated by preeclampsia (PE). Methods Serum levels of Sdc-1 were measured at sequential time points during and after uneventful pregnancies (control, n = 95) and pregnancies developing PE (PE_long, n = 12). Levels were further measured in women with symptomatic PE (PE_state, n = 46) at a single time point. Results Sdc-1 levels increased consistently throughout pregnancy. In the PE_long group Sdc-1 levels were lower at all visits throughout pregnancy, and reached significance in weeks 18–22 (p = 0.019), 23–27 (p = 0.009), 28–32 (p = 0.006) and 33–36 (p = 0.008). After delivery, Sdc-1 levels dropped sharply in all pregnancies but were significantly elevated in the PE_long group. The predictive power of Sdc-1 was evaluated analyzing receiver operating characteristic (ROC) curves. A significant power was reached at weeks 14–17 (area under the curve [AUC] 0.65, p = 0.025), 23–27 (AUC 0.73, p = 0.004) and 33–36 (AUC 0.75, p = 0.013). Conclusions In summary, Sdc-1 levels were lower in women developing PE compared to uneventful pregnancies and Sdc-1 might be useful to predict PE. After delivery, Sdc-1 levels remained higher in women with PE. Additional studies investigating the link between glycocalyx degradation, Sdc-1 levels and placental and endothelial dysfunction in pregnancies affected by PE are warranted.

Objective Endometriosis is a benign gynaecological disease, affecting women during their reproductive years. Angiogenesis represents a crucial step in the pathogenesis of endometriosis, because endometriotic lesions require neovascularization. In this study several angiogenesis-related genes have been studied in the context of endometriosis. Some of the analyzed angiogenic factors as well as their interactions were studied the first time regarding a possible association with endometriosis. Study design This case-control study consisted of 205 biopsies of 114 patients comprising 61 endometriosis patients and 53 control patients. Among them in 29 cases paired samples were obtained. VEGFA, VEGFR2, HIF1A, HGF, NRP1, PDGFB, FGF18, TNFα, TGFB2, EPHB4, EPO and ANG mRNA expression was analyzed by qRT-PCR in ectopic tissue samples, in eutopic endometrium of women with and without endometriosis, and in unaffected peritoneum of women with and without endometriosis. Results VEGFR2, HIF1A, HGF, PDGFB, NRP1 and EPHB4 are overexpressed in ectopic lesions compared to eutopic tissues. VEGFR2, HGF, PDGFB, NRP1 , and EPHB4 showed highest mRNA levels in peritoneal implants, in contrast HIF1A showed the highest expression in ovarian endometriomas. Correlation analyses of angiogenic factors in ectopic lesions revealed the strongest associations between VEGFR2, PDGFB , and EPHB4 . We further showed a significant upregulation of VEGFR2, HIF1A and EPHB4 in eutopic endometrium of women with endometriosis compared to that of controls and a trend towards upregulation of HGF . Additionally, a significant downregulation for HIF1A, HGF and EPHB4 was observed in unaffected peritoneal tissues of women with endometriosis compared to controls. Conclusion We identified new genes ( EPHB4 and NRP1 ) that may contribute to angiogenesis in endometriosis beside known factors ( VEGFA, VEGFR2, HIF1A, HGF , and PDGFB ). Correlation studies revealed the putative importance of EBHB4 in association with endometriosis. Our analyses support preliminary reports that angiogenic factors seem to be differently expressed in peritoneal implants, ovarian endometriomas and deep infiltrating endometriosis. Our observation that angiogenic factors are differently expressed in the unaffected peritoneum of women with endometriosis compared to women without endometriosis underlines the importance of the peritoneum in the establishment of endometriosis.

Preeclampsia (PE) is a frequent pregnancy-related disease and a major cause of maternal and fetal morbidity and mortality. Despite that, exact mechanisms of its pathophysiology remain largely unknown. In pregnancies complicated by PE, changes in the regulation of apoptosis seem to result in increased apoptotic shedding of trophoblast particles (TPs) into maternal circulation. Since the number of TP in peripheral blood is low, their detection necessitates pre-analytical enrichment.In this prospective multicenter pilot study we aimed to analyze TP in peripheral blood of 29 women with PE and of 13 unaffected controls using the OncoQuick®plus system for cell enrichment. Using immunocytochemistry, slides were evaluated microscopically for TP. Statistical analyses were performed using Welch's t-test or Fisher's exact test.TP were detected in 10 (34.5%) women with PE and in two (15.4%) of unaffected controls. More than one TP were only found in PE. Comparing the mean counts of TP between groups, we detected significantly more TP in PE (p = 0.046).The OncoQuick®plus system can be applied to detect TP in both women with PE and in normotensive pregnancies. Longitudinal studies investigating the role of TP as a screening method for patients at risk for PE are warranted.

Endometriosis is a benign but troublesome gynecological condition, characterized by endometrial-like tissue outside the uterine cavity. Lately, the discovery and validation of noninvasive diagnostic biomarkers for endometriosis is one of the main priorities in the field. As the disease elicits a chronic inflammatory reaction, we focused our interest on two factors well known to be involved in inflammation and neoplastic processes, namely, soluble CD40 Ligand and CXCL1, and asked whether differences in the serum levels of sCD40L and CXCL1 in endometriosis patients versus controls can serve as noninvasive disease markers. A total ofn=60women were included in the study, 31 endometriosis patients and 29 controls, and the serum levels of sCD40L and CXCL1 were measured by enzyme-linked immunosorbent assay. Overall, there were no statistically significant differences in the levels of expression of both sCD40L and CXCL1 between patients and controls. This study adds useful clinical data showing that the serum levels of the soluble factors sCD40L and CXCL1 are not associated with endometriosis and are not suitable as biomarkers for disease diagnosis. However, we found a trend toward lower levels of sCD40L in the deep infiltrating endometriosis subgroup making it a potentially interesting target worth further investigation.

Lupus anticoagulant (LA) has been associated with pregnancy complications and pregnancy loss. Identification of predictive factors could aid in deciding on therapeutic management. To identify risk factors for adverse pregnancy outcomes in high-risk women with persistently positive LA, we prospectively followed 82 women of childbearing age, of whom 23 had 40 pregnancies within the Vienna Lupus Anticoagulant and Thrombosis Study. Pregnancy complications occurred in 28/40 (70%) pregnancies, including 22 (55%) spontaneous abortions (

Background International guidelines recommend that tocolytic therapy be restricted to a single 48-h application. However, multiple cycles of tocolytic therapy and maintenance therapy that exceeds 48 h appear to play a role in daily clinical practice. We aimed to evaluate current trends in clinical practice with respect to treatment with tocolytic agents and to identify differences between evidence-based recommendations and daily clinical practice in Austria. Methods A prospective multicenter registry study was conducted from October 2013 through April 2015 in ten obstetrical departments in Austria. Women ≥18 years of age who received tocolytic therapy following a diagnosis of threatened preterm birth were included, and details were obtained regarding clinical characteristics, tocolytic therapy, and pregnancy outcome. Results A total of 309 women were included. We observed a median of 2 cycles of tocolytic therapy per patient (IQR 1–3) with a median duration of 2 days per cycle (IQR 2–5). Repeat tocolysis was administered in 41.7% of women, resulting in up to six tocolysis cycles; moreover, 40.8% of the first tocolysis cycles were maintenance tocolysis (i.e., longer than 48 h). Only 25.6% of women received one single 48-h tocolysis cycle in which they received antenatal corticosteroids for fetal lung maturation in accordance evidence-based recommendations. Conclusions Here, we report a clear disparity between evidence-based recommendations and daily practice with respect to tocolysis. We believe that the general practice of prescribing tocolytic therapy must be revisited. Furthermore, our findings highlight the need for contemporary studies designed to investigate the effectiveness of performing maintenance and/or repetitive tocolysis treatment. Electronic supplementary material The online version of this article (10.1186/s12884-018-2078-5) contains supplementary material, which is available to authorized users.

Objective Oxidative stress and mitochondrial dysfunction may play a crucial role in preeclampsia (PE). The aim of this study was to investigate differences in maternal levels of serum-mitochondrial (mt) DNA, a proposed biomarker for mitochondrial dysfunction, in women with PE compared to healthy pregnant women. Study design Using samples obtained from the prospective Biobank study, we measured serum-mtDNA levels in pregnant women diagnosed with PE and in women with uneventful pregnancies, matched for gestational and maternal age, BMI, and smoking status. In a second step, we performed a generalized linear model to detect associations between mtDNA-serum-levels and certain conditions during pregnancy. Results Mean mtDNA levels were significantly higher in PE (n = 20) than in matched controls (n = 20) and were 0.00767 (SD 0.00255) U/L and 0.00513 (SD 0.00458) U/L, respectively (p = 0.038). We did not find a significant correlation between higher mtDNA levels and early onset PE, IUGR, maternal age, or maternal BMI. Interestingly, increased mtDNA levels were significantly associated with female fetal sex (p = 0.003). Conclusion Our findings strengthen the hypothesis postulating that oxidative stress and mitochondrial dysfunction are key factors in the pathophysiology of PE. More prospective studies are highly warranted to further investigate the role of mtDNA in PE and assess the usefulness as a possible biomarker for PE.

Objective To evaluate serum levels of the amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) in uneventful pregnancies and pregnancies complicated by preeclampsia (PE) and NTproCNP’s accuracy for prediction of PE. Study design Nested case control pilot study including women with uneventful pregnancy (Control, n = 100) and asymptomatic women who later developed PE (PE_long, n = 12). NTproCNP levels were measured in a maximum of ten sequential blood samples per patient (seven visits during pregnancy, three afterwards), which had been collected prospectively. Results In controls, NTproCNP decreased from weeks 11–13 on, reaching a nadir at the end of the second trimester (weeks 23–27), and subsequently reached the highest levels at the end of pregnancy. In comparison, the PE_long group showed a significantly different NTproCNP course (p = .042), including significantly elevated levels in weeks 18–22 (p = .034) and 23–27 (p = .016). Significant predictive power of single time point measurements of NTproCNP for predicting short-term occurrence of preeclampsia in asymptomatic women was found in weeks 28–32 (p = .023) and 33–36 (p = .014). Furthermore, an increase > −0.038 pmol/l per week between weeks 11–13 and 14–17 was also predictive for PE (area under the curve, AUC: 0.75; p 0.084 pmol/l per week between weeks 11–13 and 18–22 (AUC: 0.69, p = .048; sensitivity: 55%; specificity: 88%). Conclusions Measurement of NTproCNP in pregnancy might be useful to increase diagnostic awareness in women who will develop PE.

Background In view of the reported increase in obstetric anal sphincter injuries, the objective of this study was to evaluate the incidence of such injuries over time and the associated risk and protective factors. Methods This was a retrospective cohort study from a national database of 168 137 primiparous women with term, singleton, cephalic, vaginal delivery between 2008 and 2014. The main outcome measure was obstetric anal sphincter injury. A multivariate regression model was used to identify risk and protective factors. Results Age >19 years, birthweight >4000 g, and operative vaginal delivery were independent risk factors for obstetric anal sphincter injuries. Mediolateral episiotomy increased the risk for obstetric anal sphincter injuries in spontaneous vaginal birth (number needed to harm 333), whereas it was protective in vacuum delivery (number needed to treat 50). From 2008 to 2014, there was an increase in the rate of obstetric anal sphincter injuries (2.1% vs 3.1%, P

To evaluate the usefulness of Cytokeratin 19 as biomarker for the diagnosis of preeclampsia.Cytokeratin 19 protein fragment CYFRA 21-1 was measured by means of electrochemiluminescence immunoassays in urine and serum samples of 32 women with preeclampsia and 32 samples of normotensive healthy singleton pregnancies at random, matched for gestational age, as controls.The median serum concentrations of CYFRA 21-1 in controls and women with preeclampsia were 2.4 (range 1.3-6.6)ng/mL and 4.4 (range 2.1-16.2)ng/mL, respectively (p0.001). The median urine concentrations of CYFRA 21-1 in controls and women with preeclampsia were 13.7 (range 0.7-441.4)ng/mL and 11.8 (range 1.5-338.6)ng/mL, respectively (p=0.629). Calculation of a ROC curve to study the use of serum CYFRA 21-1 concentration as a predictor of preeclampsia revealed cut-off points with the highest sum of specificity and sensitivity of 3.2ng/mL, leading to specificity of 75% and sensitivity of 84%. A similar curve calculated for CYFRA 21-1 in urine showed an area under the curve of 0.536 meaning no predictive power. The correlation between urinary excretion of protein in 24h and serum concentrations of CYFRA 21-1 in the case group was r=0.26, which is not significant (p=0.258). The correlation between proteinuria and urine values of CYFRA 21-1 was r=0.10, which also is not significant (p=0.666).Serum levels of Cytokeratin 19 fragment are increased in women with preeclampsia. However this does not result in a significant difference in CYFRA 21-1 levels in maternal urine. Thus Cytokeratin 19 fragment may prove to be a valuable biomarker for preeclampsia in serum but not urine. We propose further longitudinal studies to investigate the role of Cytokeratin 19 in maternal serum of women with preeclampsia.

Endometriosis compromises the quality of life of countless women worldwide and is a leading cause of disability. Clinical symptoms of endometriosis can be very heterogeneous leading to a long interval between onset of symptoms and surgical diagnosis. A noninvasive, rapid diagnostic test is urgently needed. In this prospective study, we evaluated the usefulness of Cytokeratin-19 (CK19) as a biomarker for the diagnosis of endometriosis through urine and serum ELISA. 76 reproductive-aged women undergoing laparoscopy for benign conditions were included to this study and divided into two groups by the presence (n = 44) or absence (n = 32) of endometriosis. There was no statistically significant correlation between the concentration of CK19 in urine (p = 0.51) or in serum (p = 0.77) and the diagnosis of endometriosis. Assigning the samples to the proliferative or secretory cycle stage did not sufficiently lower the p values. In this study, the promising data reported in the recent literature about CK19 serving as a sufficient biomarker for endometriosis could not be verified when tested in a larger sample size. Further studies are warranted to explore the usefulness of CK19 in the diagnosis of endometriosis.

Oxytocin is crucially involved in the onset and maintenance of labor. We investigated the association between oxytocin receptor gene polymorphisms and preterm birth. The presence of four common oxytocin receptor gene polymorphisms (rs2254298, rs53576, rs2228485 and rs237911) was evaluated in one hundred women with preterm birth and one hundred healthy women using restriction fragment length polymorphism genotyping. No association was found between the presence of any individual oxytocin receptor gene polymorphism and preterm birth. In haplotype analysis, the haplotype combination of rs2254298 A allele, rs2228485 C allele and rs237911 G allele was found to be significantly associated with an increased risk of preterm birth (OR = 3.2 [CI 1.04–9.8],p= 0.043). In conclusion our findings suggest that a combination of three oxytocin receptor gene polymorphisms is associated with an increased risk for preterm birth. We propose further studies investigating the role of oxytocin receptor gene polymorphisms and preterm birth.

Study question Do cell adhesion molecules play a role in endometriosis, and can they be used as a biomarker for diagnosing endometriosis? Summary answer Altered expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in the endometrium and peritoneum may play a key role in endometriosis and the soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker. What is known already Cell adhesion molecules are cell surface proteins that mediate cellular adherence, inflammatory and immune responses, and cancer-related biological processes. Altered expression of VCAM-1 and ICAM-1 in women with endometriosis has been investigated previously; however, gene expression levels in tissues and protein levels in the serum have not been investigated in the same patients. Study design size, duration We performed a prospective, longitudinal study (the Endometriosis Marker Austria) in patients who underwent a laparoscopy for benign gynecological pathology in a university-based tertiary referral center for endometriosis. From a total of 138 women who were included in the study from July 2013 through September 2014, 97 had not received hormonal treatment for at least 3 months prior to recruitment and were included in the analysis; 49 (50.5%) of these women had endometriosis, and the 48 (49.5%) who did not have endometriosis served as a control group. Participants/materials setting methods During laparoscopy, tissue samples were obtained from ectopic and eutopic endometrium, and from normal pelvic peritoneum. In addition, serum samples were collected immediately before and 6-10 weeks after surgery. The mRNA levels of VCAM-1, ICAM-1 and epithelial cell adhesion molecule (EpCAM) were measured using quantitative real-time PCR, and serum protein levels of soluble VCAM-1 (sVCAM-1), ICAM-1 (sICAM-1) and EpCAM (sEpCAM) were measured using ELISA and correlated with endometriosis status. Main results and the role of chance The mRNA levels of both VCAM-1 and ICAM-1 were higher in ectopic endometriotic lesions than in eutopic endometrium (P < 0.001). Moreover, the mRNA levels of both VCAM-1 and ICAM-1 were higher in normal peritoneum samples obtained from women with endometriosis compared to those from controls (P = 0.038 and P = 0.009). The mRNA levels of VCAM-1 were also higher in the eutopic endometrium samples obtained from women with endometriosis compared to controls (P = 0.018). With respect to serum protein levels, compared to controls, the women with endometriosis had lower serum levels of sICAM-1 (P = 0.042) and higher levels of sVCAM-1 (P < 0.001). Our analysis revealed that the serum levels of sVCAM-1 were not affected by lesion entity, menstrual cycle phase or disease severity. An receiver operating characteristics curve, calculated to determine whether preoperative serum sVCAM-1 concentration can be used to predict endometriosis, found an AUC of 0.868 with 80% specificity and 84% sensitivity at a cutoff value of 370 pg/ml. This predictive performance can be further improved by calculation of the sVCAM-1/sICAM-1 ratio, leading to an AUC of 0.929 with 86.7% specificity and 90.3% sensitivity at a cutoff ratio value of 1.55. Large scale data Not applicable. Limitations reasons for caution The relatively small sample size in the expression analyses is a possible limitation of this study. Wider implications of the findings Our findings could contribute to an improved understanding of the pathogenesis of endometriosis and the role of cell adhesion molecules. In addition, the results may lead to the development of new, non-invasive tools for diagnosing endometriosis. The ability to diagnose patients by measuring serum sVCAM-1 levels or the sVCAM-1/sICAM-1 ratio would have considerable clinical value. Study funding/competing interest(s) The Ingrid Flick Foundation (Grant no. FA751C0801), which played no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors declare no competing interests.

Supplemental Digital Content is available in the text, Background: The aim of the study was to assess whether an inexpensive tablet-based box trainer (TBT) is at least equally effective compared with a standard box trainer (SBT) to learn basic laparoscopic skills (BLS). BLS training outside the operating room has been shown to be beneficial for surgical residency. However, simulation trainers are expensive and are not consistently available in all training centers. Therefore, TBT and other homemade box trainers were developed. Methods: Medical students were randomized to either a TBT or an SBT and trained 4 fundamentals of laparoscopic surgery (FLS) tasks for 1 hour twice a week for 4 weeks. A baseline test before the training period and a posttraining test were performed. All students then completed a questionnaire to assess their assigned box trainer. The primary outcome measure was the improvement in total test scores. Improvement in the scores for the 4 individual FLS tasks was chosen as a secondary outcome measure. Results: Thirty-two medical students were recruited. Baseline test scores did not differ significantly between the groups. BLS improved significantly in both groups for the total score and for all 4 tasks separately. Participants in the TBT group showed a greater improvement of total scores than those in the SBT group, although this did not reach statistical significance; noninferiority of the TBT compared with the SBT concerning the improvement of total scores could be demonstrated. Regarding the individual FLS tasks, noninferiority of the TBT could be shown for the pattern cutting and the suturing with intracorporeal knot-tying task. The acceptance of the TBT by the trainees was very good. Conclusion: Learning BLS on a homemade TBT is at least equally effective as on an SBT, with the advantage of being very cost saving. Therefore, this readily available box trainer may be used as an effective, flexible training device outside the operating room to improve accessibility to simulation training.

Objective To provide a review of the literature regarding this technique as well as a step-by-step description with the goal of increasing its use as a safe surgical option. Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by vaginal agenesis and a variety of mullerian duct anomalies. To date, a variety of procedures have been described for creating a neovagina, but the best treatment remains debated. The Wharton-Sheares-George method, a minimally invasive surgical approach for the creation of a neovagina, is remarkably simple to perform. Design Surgical video tutorial. Setting University hospital and referral center for pediatric and adolescent gynecology. Patient(s) A 20-year-old woman with MRKH syndrome who underwent Wharton-Sheares-George neovaginoplasty. Intervention(s) With the Wharton-Sheares-George neovaginoplasty the rudimentary mullerian ducts are dilated incrementally by pushing Hegar dilators in the direction of the pelvic axis, and the resulting median raphe is then intersected using diathermy. Subsequently a vaginal mold is inserted into the newly created cavity and held in position by two sutures. Main Outcome Measure(s) Discussion of the surgical steps according to the Wharton-Sheares-George method and review of the anatomic and functional results. Results Reviewing the existing literature shows that a mean vaginal length and width of 8.3 and 3.3 cm, respectively, can be achieved, and so far no major intraoperative or postoperative complications or prolapse of the neovagina has been reported. Patients can achieve a high degree of general well-being as well as sexual and psychosocial functioning. However, as with most other methods, the presented method requires diligent patient compliance due to the lifelong need to actively avoid contraction of the neovagina. Also, as revealed by vaginal cultures and biopsies, the neovaginas remarkably resemble natural vaginas with regard to type of bacterial colonization and structure of epithelium. The process of spontaneous epithelialization of the neovagina is not fully understood, but has been observed to begin at the vaginal orifice and take several months to reach the apex. This leads to the assumption that the nonkeratinizing, stratified squamous epithelium originates from the preexisting vaginal epithelium of the vaginal dimple and migrates in a cranial direction. Alternatively, epithelialization might arise from pluripotent stem cells located in the obliterated mullerian ducts. Conclusion(s) The creation of a neovagina using the Wharton-Sheares-George method does not require allogenic or autologous transplants, nor does it require traction devices or specialized surgical equipment. Furthermore, the procedure is comparatively simple to perform and easy to learn. By following our step-by-step description of this technique, surgeons can offer a minimally invasive, quick, and safe surgical option that provides long-term results that are both functionally and anatomically satisfying. We believe that this technique represents a valuable alternative for the creation of a neovagina in patients with MRKH syndrome and thus should be investigated on a broader scale in the future.

We hypothesized that the moon may have an effect on fetal circulation and the amount of fluid behind the fetus' neck in the first trimester of pregnancy. In the present study we investigated whether lunar position influences nuchal translucency thickness at first trimester screening for chromosomal abnormalities. The data of 1023 consecutive singleton fetuses measured between 11 + 0 and 13 + 6 gestational weeks at the four key lunar positions across 63 lunar cycles were retrospectively analyzed. To correct for gestational variation in nuchal translucency thickness, measurements were expressed as the difference from the normal median nuchal translucency at the measured crown rump length (Delta-NT). No significant difference between the mean Delta-NT at four key lunar positions (new moon, full moon, first quarter, last quarter) was found. There was also no significant difference between the mean Delta-NT on days with spring tide (new moon/full moon) and neap tide (first quarter/last quarter). Although effec...

Aim To investigate the difference in fetal heart rate of opioid-dependent mothers compared to non-dependent mothers in the first trimester of pregnancy. Design The data of 74 consecutive singleton pregnancies of mothers enrolled in a maintenance programme for opioid-dependent women was matched to 74 non-exposed singleton pregnancies by maternal age, crown–rump length, smoking status, ethnic background and mode of conception. Measurement Fetal heart rate measured as part of first-trimester screening by Doppler ultrasound between 11+0 and 13+6 gestational weeks was compared retrospectively. Findings The mean fetal heart rate in opioid-dependent mothers was 156.0 beats per minute (standard deviation 7.3) compared to 159.6 (6.5) in controls. The difference in fetal heart rate was significant (P = 0.02). There was a significant difference in mean maternal body mass index (P = 0.01) but not in mean nuchal translucency (P = 0.3), gestational age (0.5), fetal gender (P = 0.3) and parity (P = 0.3) between both groups. Fifty-five per cent (41 of 74) of cases were taking methadone, 30% (22 of 74) buprenorphine and 15% (11 of 74) were taking slow-release morphines throughout the pregnancy. Conclusions In fetuses of opioid-dependent mothers a decreased fetal heart rate can already be observed between 11+0 and 13+6 gestational weeks. The effect of opioid intake needs to be taken into consideration when interpreting fetal heart rate in opioid-dependent mothers at first-trimester screening.

Objective Gonadotropin releasing hormone agonists (GnRHa) decrease the expression of growth factors involved in the development of human endometriotic tissue. As endometriosis has been found to be associated with a mild increase in prolactin (PRL) serum levels, we aimed to evaluate changes in PRL serum levels as well as other hormones relevant to endometriosis and infertility during long-term administration of GnRHas in women with endometriosis. Study design In this prospective pilot study we obtained blood samples on the first day of leuporeline administration and then subsequently after 4, 8 and 12 weeks in 22 patients. Results Median PRL levels were unchanged after 4 weeks, but significantly decreased 8 and 12 weeks after the first leuporeline administration ( p 1 =0.085, p 2 =0.020, p 3 =0.001). There was no significant decrease in serum anti-Mullerian hormone (AMH) levels over the whole period of down regulation with leuporeline ( p 1–3 >0.05). Conclusion Our data support the hypothesis that the decrease of PRL levels might contribute to the known effect of GnRH treatment in patients with endometriosis via suppression of VEGF expression in endometriotic lesions. Moreover this study lends support to the thesis that AMH remains stable under GnRHa therapy and therefore can be also used as a marker of ovarian function prior to IVF-stimulation during down regulation.

To investigate the difference in fetal heart rate of opioid-dependent mothers compared to non-dependent mothers in the first trimester of pregnancy.The data of 74 consecutive singleton pregnancies of mothers enrolled in a maintenance programme for opioid-dependent women was matched to 74 non-exposed singleton pregnancies by maternal age, crown-rump length, smoking status, ethnic background and mode of conception.Fetal heart rate measured as part of first-trimester screening by Doppler ultrasound between 11+0 and 13+6 gestational weeks was compared retrospectively.The mean fetal heart rate in opioid-dependent mothers was 156.0 beats per minute (standard deviation 7.3) compared to 159.6 (6.5) in controls. The difference in fetal heart rate was significant (P = 0.02). There was a significant difference in mean maternal body mass index (P = 0.01) but not in mean nuchal translucency (P = 0.3), gestational age (0.5), fetal gender (P = 0.3) and parity (P = 0.3) between both groups. Fifty-five per cent (41 of 74) of cases were taking methadone, 30% (22 of 74) buprenorphine and 15% (11 of 74) were taking slow-release morphines throughout the pregnancy.In fetuses of opioid-dependent mothers a decreased fetal heart rate can already be observed between 11+0 and 13+6 gestational weeks. The effect of opioid intake needs to be taken into consideration when interpreting fetal heart rate in opioid-dependent mothers at first-trimester screening.

Background Cytomegalovirus (CMV) is the most prevalent congenital viral infection and thus places an enormous disease burden on newborn infants. Seroprevalence of maternal antibodies to CMV due to CMV exposure prior to pregnancy is currently the most important protective factor against congenital CMV disease. The aim of this study was to identify potential predictors, and to develop and evaluate a risk-predicting model for the maternal CMV serostatus in early pregnancy. Methods Maternal and paternal background information, as well as maternal CMV serostatus in early pregnancy from 882 pregnant women were analyzed. Women were divided into two groups based on their CMV serostatus, and were compared using univariate analysis. To predict serostatus based on epidemiological baseline characteristics, a multiple logistic regression model was calculated using stepwise model selection. Sensitivity and specificity were analyzed using ROC curves. A nomogram based on the model was developed. Results 646 women were CMV seropositive (73.2%), and 236 were seronegative (26.8%). The groups differed significantly with respect to maternal age (p = 0.006), gravidity (p

Introduction Modern medical science has to meet a series of challenges including the integration of new technologies and strategies to daily scientific routine. Biobanking is defined as ‘a collection of biological material and the associated data and information stored in an organized system for a population or a large subset of a population’ and plays a key role in these efforts. Objectives The study group obstetrics aims to establish a platform for efficient collaboration and networking in obstetrical science. Methods Based on existing resources, technologies and expertise, autonomous data and sample collection in local biobanks shall be processed with uniformed SOPs to guarantee quality and compatibility. Results The study group obstetrics has created harmonized standards for sample and data management in biobanks as well as ethical and legal frameworks. Internet – based data management with uniform documentation sheets guarantee high data quality. Material and data are administrated autonomously and can be combined in the context of specific co-operations. Conclusion Due to the outstanding dynamics over a limited period, the human pregnancy is an attractive field for biobanking and clinical case/control cohorts including disease focused cohorts. Harmonized standards and linkage in a network allow efficient scientific co-operations. Everyone interested is invited to join the study group obstetrics as an equitable member.

Background The ability to identify patients at risk for developing preeclampsia is important for preventing morbidity and mortality in both the mother and child. Although CYFRA 21–1 (a fragment of Cytokeratin 19) is considered a promising biomarker for diagnosing preeclampsia, little is known regarding the levels of CYFRA 21–1 during pregnancy. Here, we measured serum CYFRA 21–1 levels in women with an uneventful pregnancy and in women whose pregnancy was complicated by preeclampsia. Furthermore we evaluated whether maternal CYFRA 21–1 levels can be used to predict and/or diagnose preeclampsia. Methods Longitudinal, sequential blood samples were collected prospectively at seven predetermined visits during pregnancy. Maternal CYFRA 21–1 levels were measured in 50 women with an uneventful pregnancy (control group) and in 10 asymptomatic women whose pregnancy was later complicated by preeclampsia (PE_long group). In addition, CYFRA 21–1 levels were measured from a single sample collected from a separate group of 50 pregnant women with symptomatic preeclampsia (PE_state group). Results The CYFRA 21–1 levels were significantly higher in the PE_state group compared to the control group (p