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Telemedicine, as a health service provided remotely, is increasingly becoming a common part of health care. Telemedicine is defined as "an umbrella term for health activities, services and systems operated remotely through information and communication technologies to promote global health, prevention and health care, as well as education, health management and health research". It also describes telemedicine as "the provision of services where distance is a critical factor, using information and communication technologies to exchange valid information for the diagnosis, treatment and prevention of disease and injury, for research and evaluation, and for the continuing education of healthcare providers to improve the health of individuals and communities". Both definitions imply that two of the hallmarks of telemedicine include the use of communication and information technologies to overcome distance as a critical factor, a factor that is well known to us, not least from the recent months of the COVID-19 pandemic. Distance medicine can thus act as a tool for improving access to health care and also complement health care itself in a very appropriate way.

Magnetic resonance imaging (MRI) provides a detailed display of the pelvic floor structures responsible for normal pelvic floor anatomy. The aim of the study is to assess the appearance of musculo-fascial defects in women with pelvic floor dysfunction following first vaginal delivery.Analysis of axial T3 (Tesla 3) MRI scans from a case control study of symptomatic (n = 149) and asymptomatic (n = 60) women after first vaginal delivery. Presence and severity of pelvic organ support and attachment system defects in three axial pelvic planes were assessed.In the symptomatic group, major muscular defects were found in 67.1% (for pubovisceral muscle complex) and 87.9% (for iliococcygeal muscle). Only 6.7% of major pubovisceral and 35.0% of major iliococcygeal defects were identified in the controls (p = 0.000). Prolapse patients had an odds ratio (OR) of 22.1 (95% CI 8.94-54.67) to have major pubovisceral muscle complex defect and OR of 4.9 (95% CI 1.51-15.71) to have major iliococcygeal muscle defect. Fascial defects were found in 60.4% and 83.2% the symptomatic group, respectively. Those with prolapse had an OR of 29.1 (95% CI 9.77-86.31) to have facial defect at the level of pubovisceral muscle complex and an OR of 16.9 (95% CI 7.62-37.69) to have fascial defect at the level of iliococcygeal muscle. Uterosacral ligaments detachment was associated with prolapse with an OR of 10.1 (95% CI 4.01-25.29). For the model based on combination on all MRI markers, the area under the receiver operating characteristic curve is 0.921.This study provides comprehensive data about first vaginal delivery-induced changes in the levator ani muscle and endopelvic fascial attachment system. These changes are seen also in asymptomatic controls, but they are significantly less expressed.

We evaluated the potential of cardiovascular-disease-associated microRNAs for early prediction of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Gene expression profiling of 29 microRNAs was performed on whole peripheral venous blood samples collected between 10 and 13 weeks of gestation using real-time RT-PCR. The retrospective study involved singleton pregnancies of Caucasian descent only diagnosed with HELLP syndrome (n = 14) and 80 normal-term pregnancies. Upregulation of six microRNAs (miR-1-3p, miR-17-5p, miR-143-3p, miR-146a-5p, miR-181a-5p, and miR-499a-5p) was observed in pregnancies destined to develop HELLP syndrome. The combination of all six microRNAs showed a relatively high accuracy for the early identification of pregnancies destined to develop HELLP syndrome (AUC 0.903, p < 0.001, 78.57% sensitivity, 93.75% specificity, cut-off > 0.1622). It revealed 78.57% of HELLP pregnancies at a 10.0% false-positive rate (FPR). The predictive model for HELLP syndrome based on whole peripheral venous blood microRNA biomarkers was further extended to maternal clinical characteristics, most of which were identified as risk factors for the development of HELLP syndrome (maternal age and BMI values at early stages of gestation, the presence of any kind of autoimmune disease, the necessity to undergo an infertility treatment by assisted reproductive technology, a history of HELLP syndrome and/or pre-eclampsia in a previous gestation, and the presence of trombophilic gene mutations). Then, 85.71% of cases were identified at a 10.0% FPR. When another clinical variable (the positivity of the first-trimester screening for pre-eclampsia and/or fetal growth restriction by the Fetal Medicine Foundation algorithm) was implemented in the HELLP prediction model, the predictive power was increased further to 92.86% at a 10.0% FPR. The model based on the combination of selected cardiovascular-disease-associated microRNAs and maternal clinical characteristics has a very high predictive potential for HELLP syndrome and may be implemented in routine first-trimester screening programs.

To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). A prospective European multicenter observational study included women with a singleton pregnancy, 32 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values. An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.ZIEL: Beurteilung der longitudinalen Variation der umbilikozerebralen Ratio (UCR) der Pulsatilitätsindizes bei später fetaler Wachstumsrestriktion (FGR). Eine prospektive europäische multizentrische Beobachtungsstudie schloss Frauen mit Einlingsschwangerschaft (32 856 Frauen hatten 2770 Messungen; 696 (81 %) hatten mehr als eine Messung (Median 3, IQR 2–4). Bei Einschluss hatten 63 (7 %) eine UCR ≥ 0,9. Diese entbanden früher und hatten ein niedrigeres Geburtsgewicht und eine höhere Inzidenz für einen unerwünschten Outcome (30 % vs. 9 %, relatives Risiko 3,2; 95 %-KI 2,1–5,0) im Vergleich zu Frauen mit normaler UCR bei Einschluss. Wiederholte Messungen nach abnormaler UCR bei Einschluss waren in 67 % (95 %-KI 55–80) erneut abnormal, aber nach einer normalen UCR betrug die Wahrscheinlichkeit, eine abnormale UCR zu finden, 6 % (95 %-KI 5–7 %). Das Risiko für einen kombinierten unerwünschten Outcome war ähnlich, wenn man den ersten oder den nachfolgenden UCR-Wert verwendete. Eine abnormale UCR ist wahrscheinlich bei einer späteren Messung wieder abnormal, während nach einer normalen UCR die Wahrscheinlichkeit einer abnormalen UCR bei wöchentlicher Wiederholung 5–7 % beträgt. Wiederholte Messungen sagen das Ergebnis nicht besser voraus als die erste Messung, was höchstwahrscheinlich darauf zurückzuführen ist, dass die am stärksten gefährdeten Föten nach einer abnormalen UCR entbunden werden.

We assessed the diagnostic potential of cardiovascular disease-associated microRNAs for the early prediction of gestational diabetes mellitus (GDM) in singleton pregnancies of Caucasian descent in the absence of other pregnancy-related complications. Whole peripheral venous blood samples were collected within 10 to 13 weeks of gestation. This retrospective study involved all pregnancies diagnosed with only GDM (n = 121) and 80 normal term pregnancies selected with regard to equality of sample storage time. Gene expression of 29 microRNAs was assessed using real-time RT-PCR. Upregulation of 11 microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-181a-5p, miR-195-5p, miR-499a-5p, and miR-574-3p) was observed in pregnancies destinated to develop GDM. Combined screening of all 11 dysregulated microRNAs showed the highest accuracy for the early identification of pregnancies destinated to develop GDM. This screening identified 47.93% of GDM pregnancies at a 10.0% false positive rate (FPR). The predictive model for GDM based on aberrant microRNA expression profile was further improved via the implementation of clinical characteristics (maternal age and BMI at early stages of gestation and an infertility treatment by assisted reproductive technology). Following this, 69.17% of GDM pregnancies were identified at a 10.0% FPR. The effective prediction model specifically for severe GDM requiring administration of therapy involved using a combination of these three clinical characteristics and three microRNA biomarkers (miR-20a-5p, miR-20b-5p, and miR-195-5p). This model identified 78.95% of cases at a 10.0% FPR. The effective prediction model for GDM managed by diet only required the involvement of these three clinical characteristics and eight microRNA biomarkers (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-100-5p, miR-125b-5p, miR-195-5p, miR-499a-5p, and miR-574-3p). With this, the model identified 50.50% of GDM pregnancies managed by diet only at a 10.0% FPR. When other clinical variables such as history of miscarriage, the presence of trombophilic gene mutations, positive first-trimester screening for preeclampsia and/or fetal growth restriction by the Fetal Medicine Foundation algorithm, and family history of diabetes mellitus in first-degree relatives were included in the GDM prediction model, the predictive power was further increased at a 10.0% FPR (72.50% GDM in total, 89.47% GDM requiring therapy, and 56.44% GDM managed by diet only). Cardiovascular disease-associated microRNAs represent promising early biomarkers to be implemented into routine first-trimester screening programs with a very good predictive potential for GDM.

Introduction: With the increasing number of caesarean sections, the number of cesarean scar pregnancies (CSP) is also increasing. This is a relatively new entity of an ectopic pregnancy, which is risky mainly because of its possible association with placenta accreta spectrum. CSP is thought to represent about 6% of the total number of ectopic pregnancies in all women who have a history of at least one caesarean section. The estimated incidence of CSP is about 1/1,688 of all pregnancies and about 1/ 2,000 of all caesarean sections. Material and methods: Retrospective analysis of individual cases of cesarean scar pregnancies managed in our health care facility in the years 2012–2021. Results: In total, we managed 16 cases of pregnancy in the caesarean scar in 15 women. In one woman, we recorded CSP twice. The mean age of the women was 36.6 years (27–41). The mean number of caesarean sections was 1.6 (1–3) and gestational week was 7 (4–10). The average time since the caesarean section was 3.6 years (2–11). The management was methotrexate administration once, hysteroscopic resection once and 11times primarily vacuum aspiration only, when in two cases we had to attach laparoscopic uterine artery ligation due to postoperative bleeding. We performed primary ligature of uterine arteries twice before performing vacuum aspiration. In pregnancies above 10 weeks of gestation, we observed more bleeding complications requiring surgical management. Bleeding complications were also related to the presence of fetal cardiac action. Conclusion: Early correct diagnosis is essential in the management of CSP. Pregnancies up to the 10th week of gestation are managed by simple vacuum aspirations under ultrasound guidance. If the pregnancy is over the 10th week of gestation and especially with cardiac activity, we add laparoscopic uterine artery ligation before vacuum aspiration. All patients are subsequently advised to undergo laparoscopic resuturing of the lower uterine segment. Key words: cesarean scar pregnancy – ultrasound – vacuum aspiration – uterine artery ligation – methotrexate

Introduction Thanks to shared circulation in monochorionic twins, single intrauterine fetal death (IUD) may lead to acute feto-fetal transfusion (aFFTR). The objective of the study was to describe our model of aFFTR simulation after IUD in monochorionic (MC) twins. Methods Prospective study analyzed 99 fresh MC placentas with the physiological course. A specially designed protocol was used for the preparation and analysis of the placentas. A pair of infusion sets fixed together using a mechanical mercury sphygmomanometer cuff was connected to the cannulated umbilical arteries. The tonometer was pressurized up to 30 and 40 mmHg. A positive finding of aFFTR was determined as the amount exceeding 1 ml of dye flowed out of the umbilical cord simulating a dead fetus. The number and types of anastomoses, types, and distances between cords insertions, and the size of the placental areas for each fetus were also statistically analyzed. The placental angioarchitecture with and without proven aFFTR was statistically compared, odds ratio (OR) and multivariable logistic analysis were performed. Results A total of 49/99 (49.5%) cases of aFFTR was proven, and the average transfusion time of 1 ml was 30 s (19–46 s). aFFTR was present in 49/78 (62.8%) of placentas with arterio-arterial (AA) anastomosis. The median diameter of AA anastomoses with the present, and absent aFFTRF was 2.0 mm and 1.0 mm, respectively. The proven interfetal transfusion was 8%, 31%, and 61% in AA anastomoses with a diameter below 0,5 mm, 0,5–1,5 mm, and above 1,5 mm, respectively (p 1.5 mm had OR of 44.2 (95% CI 5.54–352.39). In the case of coexistence of AA anastomosis and umbilical cord distance ≤5th percentile, the aFFTRF occurred in 90.9%. Discussion The potential risk of aFFTR in monochorionic twins is mainly due to the presence and nature of AA anastomoses. The diameter and length of the vessels play a crucial role, which is clinically related to the distance of the umbilical cords insertions.

Objectives: The study aimed to assess the relationship between urethrovesical junction (UVJ) descent and development of de novo stress urinary incontinence (SUI) and postoperative progression of preexisting SUI following surgery for pelvic organ floor prolapse using the method of sacrospinal fixation (SSF). This was a secondary analysis of the SAME prospective randomized multicentre study (reg. no. NCT03053479) comparing three approaches to surgery for apical defects – sacropexy, SSF and transvaginal mesh. Methods: The subanalysis included 81 patients with apical defects managed by SSF, either right-sided (N = 14, 17.3%) or bilateral (N = 67, 82.7%). Postoperative follow-up was assessed at 3 months (N = 59), 12 months (N = 47) and 24 months (N = 30). UVJ mobility at rest and with maximum eff ort, the Valsalva manoeuvre was determined using a standardized 3D/4D transperineal ultrasound protocol proposed by Dietz et al. De novo SUI and postoperative progression of preexisting SUI were ascertained from history. Results: Preoperative demographic data (N = 81) were as follows: BMI 27.3 kg/m2 (16.8–44.5), age 67.0 years (31–85), and parity 2 (1–6). Concomitant anterior repair was performed in 65.4%. Postoperative progression of SUI was 45.8% at 3 months, 21.3% at 12 months, and 23.3% at 24 months. There were significant differences between preoperative and postoperative UVJ descent values at 3, 12 and 24 months (P < 0.0001). Correlations between UVJ descent at 3, 12 and 24 months postoperatively and de novo SUI or progression of preexisting SUI at 3, 12 and 24 months postoperatively were not statistically significant (P = 0.051–0.883). Correlations between differences (preoperative UVJ descent minus UVJ descent at 3, 12 and 24 months postoperatively) and de novo SUI or progression of preexisting SUI at 3, 12 and 24 months postoperatively were not statistically significant (P = 0.691–0.779). Conclusions: The study showed significant changes in UVJ descent values preoperatively and at 3, 12 and 24 months after SSF. There were no significant correlations between UVJ descent and de novo SUI and postoperative progression of preexisting SUI following surgery for pelvic organ floor prolapse at 3-, 12- and 24-month follow-up. There were no significant correlations between differences (preoperative UVJ descent minus UVJ descent at 3, 12 and 24 months postoperatively and de novo SUI and postoperative progression of preexisting SUI following surgery for pelvic organ floor prolapse at 3-, 12- and 24-month follow-up. Key words: pelvic organ prolapse – stress urinary incontinence – sacrospinous ligament fixation – pelvic floor ultrasound – urethrovesical junction mobility

Objective: To summarize the current knowledge on pregnancy in a cesarean scar. Methodology: A literature review on the topic using the PubMed database. Results: Gravidity in a cesarean scar is a relatively new type of ectopic pregnancy that will be an increasingly common problem in an era of increasing cesarean section rates. It is still a relatively rare event, occurring in about 6% of the population. Diagnosis is based primarily on ultrasound examination and is essential early on in pregnancy. The pathogenesis of the disease is due to a disorder of the basal layer of the endometrium and can lead to conditions that we refer to as placenta accreta spectrum. The management is completely individualized and depends on hCG values, ultrasound findings, fetal viability, the wishes of the pregnant woman and the experience of the gynecologist concerned. Conclusion: This is still a rare occurrence of ectopic pregnancy but with increasing potential. The solution is completely individualized based on a precise and early ultrasound diagnosis. Key words: cesarean scar pregnancy – ultrasound diagnosis – placenta accreta spectrum – vacumaspiration – methotrexate – uterine scar resuture

Introduction and hypothesis: Er:YAG laser is frequently used in dermatology and gynecology. Clinical studies document high satisfaction rates; however, hard data on the effects at the structural and molecular levels are limited. The aim of this systematic review was to summarize current knowledge about the objective effects of non-ablative Er:YAG laser on the skin and vaginal wall. Methods: We searched MEDLINE, Embase, Cochrane, and the Web of Science. Studies investigating objectively measured effects of non-ablative Er:YAG laser on the skin or vaginal wall were included. Studies of any design were included. Owing to the lack of methodological uniformity, no meta-analysis could be performed and therefore results are presented as a narrative review. Results: We identified in vitro or ex vivo studies on human cells or tissues, studies in rats, and clinical studies. Most studies were on the skin (n = 11); the rest were on the vagina (n = 4). The quality of studies is limited and the settings of the laser were very diverse. Although the methods used were not comparable, there were demonstrable effects in all studies. Immediately after application the increase in superficial temperature, partial preservation of epithelium and subepithelial extracellular matrix coagulation were documented. Later, an increase in epithelial thickness, inflammatory response, fibroblast proliferation, an increase in the amount of collagen, and vascularization were described. Conclusions: Er:YAG laser energy may induce changes in the deeper skin or vaginal wall, without causing unwanted epithelial ablation. Laser energy initiates a process of cell activation, production of extracellular matrix, and tissue remodeling.

Objective: To describe effects of non-ablative erbium-doped:yttrium-aluminium-garnet (Er:YAG) laser on vaginal atrophy induced by iatrogenic menopause in the ewe. Design: Animal experimental, randomised, sham and estrogen-treatment controlled study with blinding for primary outcome. Setting: KU Leuven, Belgium. Sample: Twenty-four ewes. Methods: Menopause was surgically induced, after which the ewes were randomised to three groups receiving vaginal Er:YAG laser application three times, with a 1-month interval; three sham manipulations with a 1-month interval; or estrogen replacement and sham manipulations. At given intervals, ewes were clinically examined and vaginal wall biopsies were taken. Vaginal compliance was determined by passive biomechanical testing from explants taken at autopsy. Main outcome measures: Vaginal epithelial thickness (primary), composition of the lamina propria (collagen, elastin, glycogen and vessel content), vaginal compliance, clinical signs. Results: Animals exposed to Er:YAG laser application and sham manipulation, but not to estrogens, displayed a significant and comparable increase in vaginal epithelial thickness between baseline and 7 days after the third application (69% and 67%, respectively, both P

BACKGROUND Laser therapy is now being proposed for the treatment of pelvic organ prolapse (POP) and urinary incontinence (UI). OBJECTIVES To systematically review the available literature on laser therapy for POP and UI. SEARCH STRATEGY PubMed, Web Of Science and Embase were searched for relevant articles, using a three-concept (POP, UI, laser therapy) search engine composed as (concept 1 OR concept 2) AND concept 3. SELECTION CRITERIA Only full-text clinical studies in English. DATA COLLECTION AND ANALYSIS Data on patient characteristics, laser setting, treatment outcome and adverse events were independently collected by two researchers. There was a lack of methodological uniformity so meta-analysis was not possible and the results are presented narratively. MAIN RESULTS Thirty-one studies recruiting 1530 adult women met the inclusion criteria. All studies showed significant improvement either on UI, POP or both; however the heterogeneity of laser settings, application and outcome measures was huge. Only one study was a randomised controlled trial, two studies were controlled cohort studies. All three were on UI and used standardised validated tools. The risk of bias in the randomised controlled trial was low on all seven domains; the controlled studies had a serious risk of bias. No major adverse events were reported, mild pain and burning sensation were the most commonly described adverse events. CONCLUSIONS All studies on vaginal and/or urethral laser application for POP and UI report improvement, but the quality of studies needs to be improved. TWEETABLE ABSTRACT There is weak evidence that laser therapy is effective for urinary incontinence and pelvic organ prolapse #LASER#UI#POP.

Objective: This study aimed to obtain sexual and reproductive behaviour data of late adolescent women in the Czech Republic and to analyse the relationships between sexual behaviour and social, demographic, and behavioural factors. Methods: Data were obtained using the Computer-Assisted Web Interviewing method from 25 April to 2 May 2018 from a representative group of sexually active women aged 18-24 years. Results were statistically evaluated using sign schema on adjusted residuals. Results: A total of 525 women participated (median age of coitarche - 16 years, condom use with/without hormonal contraception - 65%, unprotected sex - 9.3% in the sexual debut). Anamnestic artificial abortion and sexually transmitted disease (STD) rates were 5.3% and 3.8%, respectively. Early coitarche, number of sexual partners, history of abortion, and STDs were positively correlated with current hormonal contraceptive use; the number of sexual partners and use of hormonal contraception were negatively correlated. Hormonal contraceptive users were more likely vaccinated against human papilloma virus (HPV) in comparison with women without any contraception. There was no correlation between risky sexual behaviour, contraceptive use, and socio-demographic factors. Conclusion: Women with early coitarche and a high cumulative number of sexual partners have more unwanted pregnancies and STDs; moreover, those with regular coital activity without contraception are less frequently vaccinated against HPV.

Background: Although fetal size is associated with adverse perinatal outcome, the relationship between fetal growth velocity and adverse perinatal outcome is unclear. Objective: This study aimed to evaluate the relationship between fetal growth velocity and signs of cerebral blood flow redistribution, and their association with birthweight and adverse perinatal outcome. Study Design: This study was a secondary analysis of the TRUFFLE-2 multicenter observational prospective feasibility study of fetuses at risk of fetal growth restriction between 32 +0 and 36 +6 weeks of gestation (n=856), evaluated by ultrasound biometry and umbilical and middle cerebral artery Doppler. Individual fetal growth velocity was calculated from the difference of birthweight and estimated fetal weight at 3, 2, and 1 week before delivery, and by linear regression of all available estimated fetal weight measurements. Fetal estimated weight and birthweight were expressed as absolute value and as multiple of the median for statistical calculation. The coefficients of the individual linear regression of estimated fetal weight measurements (growth velocity; g/wk) were plotted against the last umbilical-cerebral ratio with subclassification for perinatal outcome. The association of these measurements with adverse perinatal outcome was assessed. The adverse perinatal outcome was a composite of abnormal condition at birth or major neonatal morbidity. Results: Adverse perinatal outcome was more frequent among fetuses whose antenatal growth was

The aim of the study was to assess if cardiovascular disease-associated microRNAs would be able to predict during the early stages of gestation (within 10 to 13 weeks) subsequent onset of hypertensive pregnancy-related complications: gestational hypertension (GH) or preeclampsia (PE). Secondly, the goal of the study was to assess if cardiovascular disease-associated microRNAs would be able to detect the presence of chronic hypertension in early pregnancies. The retrospective study was performed on whole peripheral blood samples collected from singleton Caucasian pregnancies within the period November 2012 to March 2020. The case control study, nested in a cohort, involved all women with chronic hypertension (n = 29), all normotensive women that later developed GH (n = 83) or PE with or without fetal growth restriction (FGR) (n = 66), and 80 controls selected on the base of equal sample storage time. Whole peripheral blood profiling was performed with the selection of 29 cardiovascular disease-associated microRNAs using real-time RT-PCR. Upregulation of miR-1-3p (51.72% at 10.0% FPR) was observed in patients with chronic hypertension only. Upregulation of miR-20a-5p (44.83% and 33.33% at 10.0% FPR) and miR-146a-5p (65.52% and 42.42% at 10.0% FPR) was observed in patients with chronic hypertension and normotensive women with later occurrence of PE. Upregulation of miR-181a-5p was detected in normotensive women subsequently developing GH (22.89% at 10.0% FPR) or PE (40.91% at 10.0% FPR). In a part of women with subsequent onset of PE, upregulation of miR-143-3p (24.24% at 10.0% FPR), miR-145-5p (21.21% at 10.0% FPR), and miR-574-3p (27.27% at 10.0% FPR) was also present. The combination of microRNA biomarkers (miR-20a-5p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, and miR-574-3p) can predict the later occurrence of PE in 48.48% of pregnancies at 10.0% FPR in early stages of gestation. The combination of upregulated microRNA biomarkers (miR-1-3p, miR-20a-5p, and miR-146a-5p) is able to identify 72.41% of pregnancies with chronic hypertension at 10.0% FPR in early stages of gestation. Cardiovascular disease-associated microRNAs represent promising biomarkers with very good diagnostical potential to be implemented into the current first trimester screening program to predict later occurrence of PE with or without FGR. The comparison of the predictive results of the routine first trimester screening for PE and/or FGR based on the criteria of the Fetal Medicine Foundation and the first trimester screening for PE wo/w FGR using a panel of six cardiovascular disease-associated microRNAs only revealed that the detection rate of PE increased 1.45-fold (48.48% vs. 33.33%).

Introduction This study compared healing of the scars after cesarean section during the first postpartum year using a single‐ or double‐layer suturing technique. Scarring was assessed by a transvaginal ultrasound. We explored the appearance and localization of uterine scars with regard to the obstetric history. Our aim was to compare the position of the scar or defect, if present, its dimensions, and any residual myometrium with respect to the suturing technique during the cesarean section. Material and methods Women with uncomplicated singleton pregnancies indicated for elective or acute cesarean section were randomly allocated to the uterine closure technique group. During the first postpartum year, their lower uterine segment was examined with a transvaginal ultrasound in three consecutive visits at 6 weeks, 6 months and 12 months. Results 324 women attended the 12‐month visit; of these, 149 underwent single‐layer closure of the uterine incision and 175 double‐layer technique. A higher proportion of the defects is seen in the single‐layer closure technique of suturing. Defects in the single‐layer group were wider (0.002) and the residual myometrial thickness in the single‐layer group were thinner (0.019). Women who underwent cesarean section at the stage of full cervical dilation had scars that were closer to the external cervical os (0.000). The position of the uterus varies greatly between controls (0.000). The combination of uterine position and scar defect presence changed significantly between controls (0.001), and was significantly dependent on the suturing method (0.003). Defects with or without contact with the uterine cavity changed statistically between controls (0.017). Both types of defects were more common in the single‐layer closure technique group. Conclusions The findings of this study demonstrate that double‐layer technique with the first continuous nonlocking suture followed by a second continuous nonlocking suture is associated with better suture healing and greater residual myometrial thickness. No difference was observed between single‐ and double‐layer closure for the presence of maternal infectious morbidity, wound infection or blood transfusion.

Introduction and hypothesis First vaginal delivery severely interferes with pelvic floor anatomy and function. This study determines maternal and pregnancy-related risk factors for pelvic floor dysfunction (PFD), including urinary incontinence (UI), urgency, anal incontinence (AI), pelvic organ prolapse (POP) and levator ani muscle (LAM) avulsion. Methods This is a single-centre prospective observational cohort study on healthy women in their first singleton pregnancy. All underwent clinical and 3D transperineal ultrasound examination at 6 weeks and 12 months postpartum. Objective outcomes were POP-Q and presence or absence of LAM trauma. Functional outcomes were measured by the ICIQ-SF and PISQ 12. Multivariate regression was performed to determine birth and maternal habitus-related risk factors for UI, urgency, AI, dyspareunia, LAM avulsion and ballooning. Results Nine hundred eighty-seven women were included. Risk factors for UI were maternal age per year of age (OR: 1.09; 95% CI: 1.04–1.13; p = 0.0001) and BMI before pregnancy (OR: 1.08; 95% CI: 1.04–1.13; p = 0.001); for POP stage II+ maternal age (OR: 1.08; 95% CI: 1.08–1.14; p = 0.005). Avulsion was more likely after forceps (OR: 3.22; 95% CI:1.54–8.22; p = 0.015) but less likely after epidural analgesia (OR: 0.58; 95% CI: 0.37–0.90; p = 0.015) and grade I perineal rupture (OR: 0.50; 95% CI: 0.29–0.85; p = 0.012). Ballooning was more likely at increased maternal age (OR: 1.08; 95% CI: 1.02–1.13; p = 0.005), epidural (OR: 1.64; 95% CI: 1.06–2.55; p = 0.027) and grade I perineal rupture (OR: 1.79; 95% CI: 1.10–2.90; p = 0.018). Conclusion Though maternal characteristics at birth such as age or BMI increase the risk of PFD, labour and birth factors play a similarly important role. The most critical risk factor for MLA avulsion was forceps delivery, while an epidural had a protective effect. Electronic supplementary material The online version of this article (10.1007/s00192-019-04044-2) contains supplementary material, which is available to authorized users.

(1) Background: Preterm-born children have an increased cardiovascular risk with the first clinical manifestation during childhood and/or adolescence. (2) Methods: The occurrence of overweight/obesity, prehypertension/hypertension, valve problems or heart defects, and postnatal microRNA expression profiles were examined in preterm-born children at the age of 3 to 11 years descending from preterm prelabor rupture of membranes (PPROM) and spontaneous preterm birth (PTB) pregnancies. The whole peripheral blood gene expression of 29 selected microRNAs associated with cardiovascular diseases was the subject of our interest. (3) Results: Nearly one-third of preterm-born children (32.43%) had valve problems and/or heart defects. The occurrence of systolic and diastolic prehypertension/hypertension was also inconsiderable in a group of preterm-born children (27.03% and 18.92%). The vast majority of children descending from either PPROM (85.45%) or PTB pregnancies (85.71%) had also significantly altered microRNA expression profiles at 90.0% specificity. (4) Conclusions: Postnatal microRNA expression profiles were significantly influenced by antenatal and early postnatal factors (gestational age at delivery, birth weight of newborns, and condition of newborns at the moment of birth). These findings may contribute to the explanation of increased cardiovascular risk in preterm-born children. These findings strongly support the belief that preterm-born children should be dispensarized for a long time to have access to specialized medical care.

Introduction: This study aimed to determine the effect and clinical impact of physiological characteristics on the 95th/5th centile of the umbilical artery (UA) Doppler and the cerebroplacental ratio (CPR), at 36+ weeks. Methods: From the multicenter randomized trial “Ratio37,” we selected 4,505 low-risk pregnant women between June 2016 and January 2020. We registered physiological characteristics and the pulsatility indexes (PI) of the UA and middle cerebral artery (36–39 weeks). The 95th/5th centile of the UA PI and CPR was modeled by quantile regression. To evaluate the clinical impact of adjusting Doppler, we retrospectively applied gestational age (GA) and fully adjusted standards to 682 small for gestational age (SGA)-suspected fetuses (37 weeks) from a cohort of consecutive patients obtained between January 2010 and January 2020. Results: Several physiological characteristics significantly influenced the 95th/5th centile of the UA and CPR PI. The fully adjusted 95th centile of the UA was higher, and the 5th centile of the CPR was lower than GA-only-adjusted standards. Of the 682 SGA fetuses, 150 (22%) were classified as late fetal growth restricted only by GA and 112 (16.4%) when we adjusted Doppler. These 38 fetuses had similar perinatal outcome than the SGA group. Discussion: The 95th/5th centile of the UA and CPR PI is significantly influenced by physiological characteristics. Adjusting Doppler standards could differentiate better between FGR and SGA.

This prospective cross-sectional case-control study investigated the postpartal gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases in the peripheral white blood cells of women with anamnesis of preterm pre-labor rupture of membranes (n = 58), spontaneous preterm birth (n = 55), and term delivery (n = 89) by a quantitative reverse transcription polymerase chain reaction. After pregnancies complicated by preterm pre-labor rupture of membranes or spontaneous preterm birth, mothers showed diverse expression profiles for 25 out of 29 tested microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-499a-5p, and miR-574-3p). The earliest gestational ages at delivery and the lowest birth weights of newborns were associated with the highest postpartal levels of the previously mentioned microRNAs in maternal peripheral white blood cells. Administration of tocolytic drugs in order to prolong pregnancy, used in order to administer and complete a full course of antenatal corticosteroids, was associated with alterations in postpartal microRNA expression profiles to a lesser extent than in women with imminent delivery, where there was insufficient time for administration of tocolytics and antenatal corticosteroids. Overall, mothers who did not receive tocolytic therapy (miR-24-3p and miR-146a-5p) and mothers who did not receive corticosteroid therapy (miR-1-3p, miR-100-5p, and miR-143-3p) had increased or showed a trend toward increased postpartal microRNA expression when compared with mothers given tocolytic and corticosteroid therapy. In addition, mothers with serum C-reactive protein levels above 20 mg/L, who experienced preterm labour, showed a trend toward increased postpartal expression profiles of miR-143-3p and miR-199a-5p when compared with mothers with normal serum C-reactive protein levels. On the other hand, the occurrence of maternal leukocytosis, the presence of intra-amniotic inflammation (higher levels of interleukin 6 in the amniotic fluid), and the administration of antibiotics at the time of preterm delivery had no impact on postpartal microRNA expression profiles in mothers with a history of preterm delivery. Likewise, the condition of the newborns at the moment of birth, determined by Apgar scores at 5 and 10 min and the pH of cord arterial blood, had no influence on the postpartal expression profiles of mothers with a history of preterm delivery. These findings may contribute to explaining the increased cardiovascular risk in mothers with anamnesis of preterm delivery, and the greater increase of maternal cardiovascular risk with the decrease of gestational age at delivery. Women with preterm delivery in their anamnesis represent a high-risk group with special needs on a long-term basis, with a need to apply preventive and therapeutic interventions as early as possible.

Objective In sheep of reproductive age, we aimed to document decrease in epithelial thickness, glycogen amount, and other vaginal changes after castration and the effect of Er:YAG laser as used clinically. Methods On day 0, 16 sheep underwent ovariectomy. They were randomized to sham or three vaginal Er:YAG laser applications at monthly intervals. Primary outcome was vaginal epithelial thickness (d60, d71, d73, d77, and d160). Secondary outcomes included indicators of atrophy (vaginal health index = VHI), pH, cytology, morphology at the above time points, microcirculation focal depth (FD; d70 and d160), and at sacrifice (d160) vaginal dimensions and active and passive biomechanical testing. Results Menopausal changes between 60 and 160 days after ovariectomy included a progressive decrease in epithelial thickness, in VHI, FD, glycogen, elastin content and vasculature, and an increase in pH and collagen content. In lasered animals, the first day a few white macroscopic foci were visible and an increase in pH was measured. Both disappeared within 3 days. Seven days after laser the epithelial thickness increased. At sacrifice (d160), there were no differences between sham and laser group in vaginal dimensions, morphometry, mitotic and apoptotic activity, active contractility, vaginal compliance, except for a lower blood vessel density in the lamina propria of the midvagina in the laser group. Conclusions In reproductive sheep, ovariectomy induces vaginal atrophy evidenced in different outcome measurements. Vaginal Er:YAG laser induced visual impact, a short-term increase in epithelial thickness yet no long-term changes compared to sham therapy in menopausal controls.

Background/Aims: The ewe is increasingly being used as an animal model for pelvic floor disorders. The aim was to further characterize changes in the vaginal properties during its entire lifespan. Methods: Vaginal tissues were collected at different stages of reproductive life (neonatal, prepubescence, nulliparous, primiparous, multiparous, and menopausal; ≥6 ewes/group). Vaginal size, as well as active and passive biomechanics, was measured. Microscopy included thickness of glycogen, epithelium, lamina propria and muscularis thickness, densities of collagen, elastin, smooth muscle, and nerves. Results: Vaginal dimensions increase during adolescence, peak at reproductive levels, and decrease sharply after ovariectomy. One year after first delivery, the distal vagina gets more compliant, yet this is reversed later in life. The thickness of glycogen staining epithelial layers changed with puberty and menopause. The epithelium was markedly thicker after multiple deliveries. The thickness of lamina propria and muscularis increased in puberty and in nulliparous. Semi-quantitative collagen assessment demonstrated a lower collagen and higher elastin content after first and multiple deliveries. Conclusion: The changes in the ovine vaginal wall during representative moments of her lifespan parallel those observed in women.

Mothers with a history of gestational diabetes mellitus (GDM) have an increased risk of developing diabetes in the future and a lifelong cardiovascular risk. Postpartal expression profile of cardiovascular/cerebrovascular disease associated microRNAs was assessed 3–11 years after the delivery in whole peripheral blood of young and middle-aged mothers with a prior exposure to GDM with the aim to identify a high-risk group of mothers at risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases who would benefit from implementation of early primary prevention strategies and long-term follow-up. The hypothesis of the assessment of cardiovascular risk in women was based on the knowledge that a series of microRNAs play a role in the pathogenesis of diabetes mellitus and cardiovascular/cerebrovascular diseases. Abnormal expression profile of multiple microRNAs was found in women with a prior exposure to GDM (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and-miR-574-3p). Postpartal combined screening of miR-1-3p, miR-16-5p, miR-17-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-133a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p showed the highest accuracy for the identification of mothers with a prior exposure to GDM at a higher risk of later development of cardiovascular/cerebrovascular diseases (AUC 0.900, p < 0.001, sensitivity 77.48%, specificity 93.26%, cut off >0.611270413). It was able to identify 77.48% mothers with an increased cardiovascular risk at 10.0% FPR. Any of changes in epigenome (upregulation of miR-16-5p, miR-17-5p, miR-29a-3p, and miR-195-5p) that were induced by GDM-complicated pregnancy are long-acting and may predispose mothers affected with GDM to later development of diabetes mellitus and cardiovascular/cerebrovascular diseases. In addition, novel epigenetic changes (upregulation of serious of microRNAs) appeared in a proportion of women that were exposed to GDM throughout the postpartal life. Likewise, a previous occurrence of either GH, PE, and/or FGR, as well as a previous occurrence of GDM, is associated with the upregulation of miR-1-3p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-29a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p. On the other hand, upregulation of miR-16-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-103a-3p, miR-195-5p, miR-342-3p, and miR-574-3p represents a unique feature of aberrant expression profile of women with a prior exposure to GDM. Screening of particular microRNAs may stratify a high-risk group of mothers with a history of GDM who might benefit from implementation of early primary prevention strategies.

The aim of the study was to determine if aberrant expression profile of cardiovascular disease associated microRNAs would be able to predict within 10 to 13 weeks of gestation preterm delivery such as spontaneous preterm birth (PTB) or preterm prelabor rupture of membranes (PPROM) in the absence of other pregnancy-related complications (gestational hypertension, preeclampsia, fetal growth restriction, or small for gestational age). In addition, we assessed if aberrant expression profile of cardiovascular disease associated microRNAs would be able to predict preterm delivery before and after 34 weeks of gestation. The retrospective study was performed within the period November 2012 to March 2020. Whole peripheral blood samples were collected from 6440 Caucasian individuals involving 41 PTB and 65 PPROM singleton pregnancies. A control group, 80 singleton term pregnancies, was selected on the base of equal sample storage time. Gene expression of 29 selected cardiovascular disease associated microRNAs was studied using real-time RT-PCR. Downregulation of miR-16-5p, miR-20b-5p, miR-21-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-126-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, miR-221-3p and miR-342-3p was observed in pregnancies with preterm delivery before 37 (≤36 + 6/7) weeks of gestation. Majority of downregulated microRNAs (miR-16-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, and miR-342-3p) was associated with preterm delivery occurring before 37 (≤36 + 6/7) weeks of gestation. The only miR-210-3p was downregulated in pregnancies with preterm delivery before 34 (≤33 + 6/7) weeks of gestation. The type of preterm delivery also had impact on microRNA gene expression profile. Downregulation of miR-24-3p, miR-92a-3p, miR-155-5p, and miR-210-3p was a common feature of PTB and PPROM pregnancies. Downregulation of miR-16-5p, miR-20b-5p, miR-26a-5p, miR-126-3p, miR-133a-3p, miR-146a-5p, miR-221-3p, and miR-342-3p appeared just in PTB pregnancies. No microRNA was uniquely dysregulated in PPROM pregnancies. The combination of 12 microRNAs (miR-16-5p, miR-20b-5p, miR-21-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, and miR-342-3p, AUC 0.818, p < 0.001, 74.53% sensitivity, 75.00% specificity, cut off > 0.634) equally as the combination of 6 microRNAs (miR-16-5p, miR-21-5p, miR-24-3p, miR-133a-3p, miR-155-5p, and miR-210-3p, AUC 0.812, p < 0.001, 70.75% sensitivity, 78.75% specificity, cut off > 0.652) can predict preterm delivery before 37 weeks of gestation in early stages of gestation in 52.83% pregnancies at 10.0% FPR. Cardiovascular disease associated microRNAs represent promising biomarkers with very good diagnostical potential to be implemented into the current routine first trimester screening programme to predict preterm delivery.

Introduction The aim of our study was to retrospectively learn about the incidence of abdominal wall endometriosis (AWE) after caesarean section (CS) in our Perinatal Centre (Perinatal Centre of the Institute for the Care of Mother and Child), one of the largest in the Czech Republic. Methods This is a retrospective review of hospital records on 18,454 caesarean deliveries between 2003 and 2014. Results A total of 17 cases of caesarean scar endometriosis (also known as AWE) were identified. The median age was 36.0 (33.5-43.5) years. In 10 patients, the cyclic pain was present. The median interval between CS and first symptoms was 3.0 (1.0-6.5) years. Ultrasound supported the diagnosis by the identification of hypoechogenic lesions in all patients. The median interval between symptoms development and surgical excision was 1.0 year (1.0-4.0 years). Excision was the mode of treatment. Excisions with clear margins (15 cases) were curative to all those patients. Two patients with involved margins had recurrences at 6 and 8 months, respectively, and were treated with a second resection with no further surgery. No malignant transformation cases were identified. Conclusions Physicians should be highly suspicious of CS scar endometriosis, especially after uterine surgery. Complete excision is the only curative treatment.

Objective: To construct valid reference standards reflecting optimal cerebroplacental ratio and to explore its physiological determinants. Methods: A cohort of 391 low-risk pregnancies of singleton pregnancies of nonmalformed fetuses without maternal medical conditions and with normal perinatal outcomes was created. Doppler measurements of the middle cerebral artery and umbilical artery were performed at 24–42 weeks. Reference standards were produced, and the influence of physiological determinants was explored by nonparametric quantile regression. The derived standards were validated in a cohort of 200 low-risk pregnancies. Results: Maternal body mass index was significantly associated with the 5th centile of the cerebroplacental ratio. For each additional unit of body mass index, the 5th centile was on average 0.014 lower. The derived 5th, 10th, and 50th centiles selected in the validation cohort were 5, 9.5, and 51% of the measurements. Conclusions: This study provides methodologically sound prescriptive standards and suggests that maternal body mass index is a determinant of a cutoff commonly used for decision-making.