Evidence of time dependent degradation of polypropylene surgical mesh explanted from the abdomen and vagina of sheep.

The failure of polypropylene mesh is marked by significant side effects and debilitation, arising from a complex interplay of factors. One key contributor is the pronounced physico-mechanical mismatch between the polypropylene (PP) fibres and surrounding tissues, resulting in substantial physical damage, inflammation, and persistent pain. However, the primary cause of sustained inflammation due to polypropylene itself remains incompletely understood. This study comprises a comprehensive, multi-pronged investigation to unravel the effects of implantation on a presumed inert PP mesh in sheep. Employing both advanced and conventional techniques to discern the physical and chemical transformations of the implanted PP. Our analyses reveal a surface degradation and oxidation of polypropylene fibres after 60 days implantation, persisting and intensifying at the 180-day mark. The emergence and accumulation of PP debris in the tissue surrounding the implant also increased with implantation time. We demonstrate observable physical and mechanical alterations in the fibre surface and stiffness. Our study shows surface alterations which indicate that PP is evidently less chemically inert than was initially presumed. These findings underscore the need for a re-evaluation of the biocompatibility and long-term consequences of using PP mesh implants.

Approaches for hysterectomy and implementation of robot-assisted surgery in benign gynaecological disease: A cost analysis study in a large university hospital.

BACKGROUND: As a minimally invasive technique, robot-assisted hysterectomy (RAH) offers surgical advantages and significant reduction in morbidity compared to open surgery. Despite the increasing use of RAH in benign gynaecology, there is limited data on its cost-effectiveness, especially in a European context. Our goal is to assess the costs of the different hysterectomy approaches, to describe their clinical outcomes, and to evaluate the impact of introduction of RAH on the rates of different types of hysterectomy. METHODS: A retrospective single-centre cost-analysis was performed for patients undergoing a hysterectomy for benign indications. Abdominal hysterectomy (AH), vaginal hysterectomy (VH), laparoscopic hysterectomy (LH), laparoscopically assisted vaginal hysterectomy (LAVH) and RAH were included. We considered the costs of operating room and hospital stay for the different hysterectomy techniques using the "Activity Centre-Care program model". We report on intra- and postoperative complications for the different approaches as well as their cost relationship. RESULTS: Between January 2014 and December 2021, 830 patients were operated; 67 underwent VH (8%), 108 LAVH (13%), 351 LH (42%), 148 RAH (18%) and 156 AH (19%). After the implementation and learning curve of a dedicated program for RAH in 2018, AH declined from 27.3% in 2014-2017, to 22.1% in 2018 and 6.9 % in 2019-2021. The reintervention rate was 3-4% for all surgical techniques. Pharmacological interventions and blood transfusions were performed after AH in 28%, and in 17-22% of the other approaches. AH had the highest hospital stay cost with an average of €2236.40. Mean cost of the hospital stay ranged from €1136.77-€1560.66 for minimally invasive techniques. The average total costs for RAH were €6528.10 compared to €4400.95 for AH. CONCLUSION: Implementation of RAH resulted in a substantial decrease of open surgery rate. However, RAH remains the most expensive technique in our cohort, mainly due to high material and depreciation costs. Therefore, RAH should not be considered for every patient, but for those who would otherwise need more invasive surgery, with higher risk of complications. Future prospective studies should focus on the societal costs and patient reported outcomes, in order to do cost-benefit analysis and further evaluate the exact value of RAH in the current healthcare setting.

FERN: is it possible to conduct a randomised controlled trial of intervention or expectant management for early-onset selective fetal growth restriction in monochorionic twin pregnancy - protocol for a prospective multicentre mixed-methods feasibility study.

INTRODUCTION: Selective fetal growth restriction (sFGR) in monochorionic twin pregnancy, defined as an estimated fetal weight (EFW) of one twin <10th centile and EFW discordance ≥25%, is associated with stillbirth and neurodisability for both twins. The condition poses unique management difficulties: on the one hand, continuation of the pregnancy carries a risk of death of the smaller twin, with a high risk of co-twin demise (40%) or co-twin neurological sequelae (30%). On the other, early delivery to prevent the death of the smaller twin may expose the larger twin to prematurity, with the associated risks of long-term physical, emotional and financial costs from neurodisability, such as cerebral palsy.When there is severe and early sFGR, before viability, delivery is not an option. In this scenario, there are currently three main management options: (1) expectant management, (2) selective termination of the smaller twin and (3) placental laser photocoagulation of interconnecting vessels. These management options have never been investigated in a randomised controlled trial (RCT). The best management option is unknown, and there are many challenges for a potential RCT. These include the rarity of the condition resulting in a small number of eligible pregnancies, uncertainty about whether pregnant women will agree to participate in such a trial and whether they will agree to be randomised to expectant management or active fetal intervention, and the challenges of robust and long-term outcome measures. Therefore, the main objective of the FERN study is to assess the feasibility of conducting an RCT of active intervention vs expectant management in monochorionic twin pregnancies with early-onset (prior to 24 weeks) sFGR. METHODS AND ANALYSIS: The FERN study is a prospective mixed-methods feasibility study. The primary objective is to recommend whether an RCT of intervention vs expectant management of sFGR in monochorionic twin pregnancy is feasible by exploring women's preference, clinician's preference, current practice and equipoise and numbers of cases. To achieve this, we propose three distinct work packages (WPs). WP1: A Prospective UK Multicentre Study, WP2A: a Qualitative Study Exploring Parents' and Clinicians' Views and WP3: a Consensus Development to Determine Feasibility of a Trial. Eligible pregnancies will be recruited to WP1 and WP2, which will run concurrently. The results of these two WPs will be used in WP3 to develop consensus on a future definitive study. The duration of the study will be 53 months, composed of 10 months of setup, 39 months of recruitment, 42 months of data collection, and 5 months of data analysis, report writing and recommendations. The pragmatic sample size for WP1 is 100 monochorionic twin pregnancies with sFGR. For WP2, interviews will be conducted until data saturation and sample variance are achieved, that is, when no new major themes are being discovered. Based on previous similar pilot studies, this is anticipated to be approximately 15-25 interviews in both the parent and clinician groups. Engagement of at least 50 UK clinicians is planned for WP3. ETHICS AND DISSEMINATION: This study has received ethical approval from the Health Research Authority (HRA) South West-Cornwall and Plymouth Ethics Committee (REC reference 20/SW/0156, IRAS ID 286337). All participating sites will undergo site-specific approvals for assessment of capacity and capability by the HRA. The results of this study will be published in peer-reviewed journals and presented at national and international conferences. The results from the FERN project will be used to inform future studies. TRIAL REGISTRATION NUMBER: This study is included in the ISRCTN Registry (ISRCTN16879394) and the NIHR Central Portfolio Management System (CPMS), CRN: Reproductive Health and Childbirth Specialty (UKCRN reference 47201).

Experimental Induction of Complex Gastroschisis in the Fetal Lamb: Systematic Review.

We systematically reviewed experiments in the fetal lamb model of gastroschisis using PubMed, Embase, Web of Science, and Scopus, seeking for standardized surgical techniques to obtain complex gastroschisis. Eligible were studies where an abdominal wall defect was surgically induced and gross anatomical findings at birth were available. The primary outcome was complex gastroschisis, defined by the presence of bowel stenosis, atresia, volvulus, perforation, and/or necrosis. Secondary outcomes were fetal death and additional readouts reported. Of ten eligible studies, six included lambs that had no additional prenatal manipulations and were assessed at term (35 lambs). Gastroschisis was induced at day 70-80 (term = 140-145), typically (n = 4/6 studies) in the left lower abdomen with defect size ranging from 0.5 to 4.0 cm. Only one study, in which a 1.5 cm diameter silicone ring was utilized, resulted in complex gastroschisis in 100% of term survivors. Fetal loss was more frequent in studies where a silicone ring and/or a right-sided defect were used. No changes unique to complex gastroschisis were identified in additional readouts, including bowel histology. When gastroschisis becomes "complex" following induction is uncertain. This knowledge is essential in studying potential prenatal interventions that may change the natural course.

Diagnosis and management of selective fetal growth restriction in monochorionic twin pregnancies: A cross-sectional international survey.

OBJECTIVE: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. DESIGN: Cross-sectional survey. SETTING: International. POPULATION: Clinicians involved in the management of MCDA twin pregnancies with sFGR. METHODS: A structured, self-administered survey. MAIN OUTCOME MEASURES: Clinical practices and attitudes to diagnostic criteria and management strategies. RESULTS: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter-twin EFW discordance of >25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. CONCLUSIONS: There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management.

Tracheomalacia and tracheomegaly in infants and children with congenital diaphragmatic hernia managed with and without fetoscopic endoluminal tracheal occlusion (FETO): a multicentre, retrospective cohort study.

BACKGROUND: Temporary fetoscopic endoluminal tracheal occlusion (FETO) promotes lung growth and increases survival in selected fetuses with congenital diaphragmatic hernia (CDH). FETO is performed percutaneously by inserting into the trachea a balloon designed for vascular occlusion. However, reports on the potential postnatal side-effects of the balloon are scarce. This study aimed to evaluate the prevalence of tracheomalacia in infants with CDH managed with and without FETO and other consequences related to the use of the balloon. METHODS: In this multicentre, retrospective cohort study, we included infants who were live born with CDH, either with FETO or without, who were managed postnatally at four centres (UZ Leuven, Leuven, Belgium; Antoine Béclère, Clamart, France; BCNatal, Barcelona, Spain; and HCor-Heart Hospital, São Paulo, Brazil) between April 5, 2002, and June 2, 2021. We primarily assessed the prevalence of all (symptomatic and asymptomatic) tracheomalacia as reported in medical records among infants with and without FETO. Secondarily we assessed the prevalence of symptomatic tracheomalacia and its resolution as reported in medical records, and compared tracheal diameters as measured on postnatal x-rays. Crude and adjusted risk ratios (aRRs) and 95% CIs were calculated via modified Poisson regression models with robust error variances for potential association between FETO and tracheomalacia. Variables included in the adjusted model were the side of the hernia, observed-to-expected lung-to-head ratio, and gestational age at birth. Crude and adjusted mean differences and 95% CIs were calculated via linear regression models to assess the presence and magnitude of association between FETO and tracheal diameters. In infants who had undergone FETO we also assessed the localisation of balloon remnants on x-rays, and the methods used for reversal of occlusion and potential complications associated with balloon remnants as documented in clinical records. Finally we investigated whether the presence of balloon remnants was influenced by the interval between balloon removal and delivery. FINDINGS: 505 neonates were included in the study, of whom 287 had undergone FETO and 218 had not. Tracheomalacia was reported in 18 (6%) infants who had undergone FETO and in three (1%) who had not (aRR 6·17 [95% CI 1·83-20·75]; p=0·0030). Tracheomalacia was first reported in the FETO group at a median of 5·0 months (IQR 0·8-13·0). Symptomatic tracheomalacia was reported in 13 (5%) infants who had undergone FETO, which resolved in ten (77%) children by 55·0 months (IQR 14·0-83·0). On average, infants who had undergone FETO had a 31·3% wider trachea (with FETO tracheal diameter 7·43 mm [SD 1·24], without FETO tracheal diameter 5·10 mm [SD 0·84]; crude mean difference 2·32 [95% CI 2·11-2·54]; p<0·0001; adjusted mean difference 2·62 [95% CI 2·35-2·89]; p<0·0001). At birth, the metallic component was visible within the body in 75 (37%) of 205 infants with available thoraco-abdominal x-rays: it was located in the gastrointestinal tract in 60 (80%) and in the lung in 15 (20%). No side-effects were reported for any of the infants during follow-up. The metallic component was more likely to be in the lung than either outside the body or the gastrointestinal tract when the interval between occlusion reversal and birth was less than 24 h. INTERPRETATION: Although FETO was associated with an increased tracheal diameter and an increased probability of tracheomalacia, symptomatic tracheomalacia typically resolved over time. There is a higher risk of retention of metallic balloon components if reversal of the occlusion occurs less than 24 h before delivery. Finally, there were no reported side-effects of the metallic component of the balloon persisting in the body during follow-up. Longer-term follow-up is needed to ensure that no tracheal problems arise later in life. FUNDING: None.

Three-Dimensional Transperineal Ultrasound Assessment of the Anal Sphincter Immediately After Vaginal Birth: An Exploratory Study.

OBJECTIVES: To assess the feasibility of acquiring adequate transperineal ultrasound (TPUS) volumes of the anal sphincter (AS) immediately after vaginal birth, the reproducibility of its measurements, and detecting defects therein. METHODS: Secondary analysis of TPUS volumes of the AS, acquired immediately after vaginal birth with a transversely oriented convex probe. Two independent experts ranked off-line image quality as "inadequate," "adequate," or "ideal" using the Point-of-Care Ultrasound Image Quality scale. On "adequate" and "ideal" quality volumes, the length of the external AS at 6 and 12 o'clock, and the volume of the external and internal AS were measured. Additionally, volumes were screened for AS defects on tomographic ultrasound imaging. Subsequently, we rated the intra- and interrater agreement on those findings. RESULTS: Of 183 volumes, 162 were considered "adequate" or of "ideal" quality (88.5%). Reasons for "inadequacy" were shadow artifacts (16/21), poor resolution (3/21), incomplete acquisition (1/21), or aberrant AS morphology (1/21). The intrarater reliability of two-dimensional (2D) and three-dimensional (3D) measurements was excellent, whereas interrater reliability was fair to good for 2D measurements and good for 3D measurements. In those tomographic ultrasound imaging (TUI) sequences including AS defects, the intra- and interrater reliability of the defect measurement were excellent [intraclass correlation coefficient (ICC) = 0.92 (0.80-0.94)] and moderate [ICC = 0.72 (0.63-0.79)]. In this cohort, there were only few (4/48; 8.3%) AS defects. However, grading them was poorly reproducible between experts. CONCLUSION: TPUS of the AS immediately after vaginal birth yields adequate image quality and allows for reproducible measurements. In the few patients with AS defects, there was good agreement on the presence, but it was poor for the extent of defects.

Proposal for standardized prenatal assessment of fetal open dysraphisms by the European reference network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies (ITHACA) and eUROGEN.

Open dysraphisms, that is, myelomeningocele and myeloschisis, are rare diseases associated with a risk of severe disability, including lower limb motor and sensory deficiency, sphincter deficiency, and potential intellectual deficiency. Open dysraphism is diagnosed in Europe in 93.5% of cases. In case of suspicion of fetal open dysraphism, a detailed fetal morphologic assessment is required to confirm the diagnosis and exclude associated structural anomalies, as well as genetic assessment. In case of isolated fetal open dysraphism, assessment of prognosis is based on fetal imaging including the level of the lesion, the presence or not of a sac, the presence and nature of intra cranial anomalies, and the anatomical and functional evaluation of the lower extremities. Based on these biomarkers, a personalized prognosis as well as comprehensive information about prenatal management alternatives will allow parents to decide on further management options. Standardization of prenatal assessment is essential to compare outcomes with benchmark data and make assessment of surgical innovation possible. Herein, we propose a protocol for the standardized ultrasound assessment of fetuses with isolated open dysraphism.

Maternal "mirror" syndrome: Evaluating the benefits of fetal therapy.

OBJECTIVE: To evaluate maternal and perinatal outcomes following fetal intervention in the context of maternal "mirror" syndrome. STUDY DESIGN: A multicenter retrospective study of all cases of fetal hydrops complicated by maternal "mirror" syndrome and treated by any form of fetal therapy between 1995 and 2022. Medical records and ultrasound images of all cases were reviewed. "Mirror" syndrome was defined as fetal hydrops and/or placentomegaly associated with the maternal development of pronounced edema, with or without pre-eclampsia. Fetal hydrops was defined as the presence of abnormal fluid collections in ≥2 body cavities. RESULTS: Twenty-one pregnancies met the inclusion criteria. Causes of fetal hydrops and/or placentomegaly included fetal lung lesions (n = 9), twin-twin transfusion syndrome (n = 6), severe fetal anemia (n = 4), and others (n = 2). Mean gestational age at "mirror" presentation was 27.0 ± 3.8 weeks. Maternal "mirror" syndrome was identified following fetal therapeutic intervention in 14 cases (66.6%). "Mirror" symptoms resolved or significantly improved before delivery in 8 (38.1%) cases with a mean interval from fetal intervention to maternal recovery of 13.1 days (range 4-35). Three women needed to be delivered because of worsening "mirror" syndrome. Of the 21 pregnancies treated (27 fetuses), there were 15 (55.5%) livebirths, 7 (25.9%) neonatal deaths and 5 (18.5%) intra-uterine deaths. CONCLUSION: Following successful treatment and resolution of fetal hydrops, maternal "mirror" syndrome can improve or sometimes completely resolve before delivery. Furthermore, the recognition that "mirror" syndrome may arise only after fetal intervention necessitates hightened patient maternal surveillance in cases of fetal hydrops.

Self-reported respiratory and gastrointestinal outcomes in children with isolated congenital diaphragmatic hernia: A prospective multicentre study.

OBJECTIVE: To evaluate medium-term self-reported respiratory and gastrointestinal (GI) outcomes in children with congenital diaphragmatic hernia (CDH). DESIGN: Self-reported respiratory and GI outcomes correlated with prenatal severity indicators. SETTING: Prospective study at three fetal medicine units. POPULATION: Families of children prenatally diagnosed with isolated, left-sided CDH surviving for >1 year. METHODS: Families received validated questionnaires for GI outcomes (Infant Gastroesophageal Reflux Questionnaire Revised, I-GERQ-R, for infants aged <2 years, or Paediatric Gastro-oesophageal Symptom and Quality of Life Questionnaire, PGSQ, for children aged aged 2-8 years or >9 years) and respiratory outcomes (preschool respiratory outcome questionnaire, for children aged ≤5 years, or the International Study of Asthma and Allergies in Childhood asthma questionnaire, for children aged 6-8 years or ≥9 years). Prenatal data collected from the medical records included lung size (percentage observed/expected lung-to-head ratio, O/E LHR %), liver position, fetal endoluminal tracheal occlusion (FETO) gestational age (GA) at delivery, and perinatal data included birthweight, location, patch repair and respiratory support. MAIN OUTCOME MEASURES: The GI and respiratory scores were correlated with O/E LHR using linear and logistic regression models. Univariate analysis was used to evaluate associations with perinatal variables. RESULTS: We obtained 142 responses from 342 families (representing a response rate of 45%). The baseline characteristics of participants and non-participants were comparable. No correlations between perinatal variables and respiratory or GI scores were identified. Children aged ≤5 years with lower O/E LHR values reported higher respiratory scores (P = 0.0175); this finding was not reported in older children. Overall, the children who underwent FETO (n = 51) had GI (P = 0.290) and respiratory (P = 0.052) scores that were comparable with those of children who were expectantly managed. CONCLUSIONS: Families and children with prenatally diagnosed CDH reported fewer respiratory symptoms with increasing age. There was no correlation between O/E LHR or the use of FETO and self-reported outcomes.

Body image and pelvic floor dysfunction in pregnancy and postpartum: A prospective one-year follow-up cohort study.

OBJECTIVE: To determine the prevalence of pelvic floor dysfunction (PFD) among pregnant women, their clustering and their association with body image disturbance (BID) up to 1 year postpartum. DESIGN: Monocentric prospective cohort study. SETTING: University Hospitals Leuven. POPULATION: Pregnant women attending for pregnancy care, first assessed prior to 14 weeks of gestation and agreeing to follow-up until 1 year postpartum. METHODS: Standardised questionnaires reporting on PFD and BID at 12-14 and 28-32 weeks of gestation, and again at 6-8 weeks and 1 year postpartum. We calculated the prevalence of PFD, how the cases clustered and how the cases correlated with BID using a linear mixed-model analysis. A minimum of 174 women with complete follow-up were required. MAIN OUTCOME MEASURES: The questionnaires used were the International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF), St. Mark's Incontinence Score (SMIS), Patient Assessment of Constipation Symptoms (PAC-SYM), Pelvic Organ Prolapse Distress Inventory (POPDI), Pelvic Organ Prolapse/Incontinence Sexual Questionnaire IUGA Revised (PISQ-IR) and the Body Image Disturbance Questionnaire (BIDQ). RESULTS: Out of 208 women, 92.8% reported one or multiple symptoms of PFD at 28-32 weeks of gestation, dropping to 73.6% by 1 year postpartum. The most common symptoms were constipation (65.3% at 28-32 weeks of gestation and 42.8% at 1 year postpartum) and urinary incontinence (56.8% at 28-32 weeks of gestation and 35.1% at 1 year postpartum). After correcting for body mass index, parity and mode of delivery, the severity of BID was associated with the ICIQ-UI SF score (ß = 0.016, range 0.007-0.024), the PAC-SYM score (ß = 0.006, range 0.002-0.011) and the POPDI score (ß = 0.009, range 0.005-0.012), but not with the SMIS score (ß = 0.015, range -0.001 to 0.031) or the PISQ-IR score, in sexually active women. CONCLUSIONS: Urinary incontinence, constipation and symptoms of prolapse have a measurable impact on BID.

Urogenital cultures and preterm birth in women with cervical cerclage: a single center retrospective cohort study.

BACKGROUND: The leading hypothesis of the pathogenesis of cervical insufficiency suggests a role of cervical inflammation. Urogenital tract infections could play a causative role in this process. To test this hypothesis in women with a cervical cerclage, we aimed to retrospectively examine the relationship between gestational age (GA) at delivery and positive urogenital cultures. METHODS: This single center retrospective study reviewed the records of all women with a singleton pregnancy that underwent cervical cerclage (n = 203) between 2010 and 2020 at the University Hospital of Leuven, Belgium. Transvaginal cerclages were categorized as history indicated (TVC I, n = 94), ultrasound indicated (TVC II, n = 79) and clinically indicated (TVC III, n = 20). Additionally, ten women received transabdominal cerclage (TAC). Urogenital cultures (vaginal and urine) were taken before and after cerclage with 4-week intervals. Urogenital cultures were reported 'positive' if urine and/or vaginal cultures showed significant growth of a microorganism. Treatment decision depended on culture growth and clinical presentation. The primary aim was to evaluate the association between the urogenital culture results and the GA at delivery, for each of the cerclage groups. Secondarily, to investigate the effect of antibiotic treatment of positive cultures on GA at delivery. RESULTS: Positive pre-cerclage urogenital cultures were associated with lower GA at delivery in TVC III (positive culture 26w4d ± 40d vs. negative 29w6d ± 54d, p = 0.036). For TVC I, GA at delivery was longer when pre-cerclage urogenital cultures were positive (positive culture 38w0d ± 26d vs. negative 35w4d ± 42d, p = 0.035). Overall post-cerclage urogenital cultures status was not associated with a different GA at delivery. Treating patients with pre- or post-cerclage positive urogenital cultures did also not change GA at delivery. CONCLUSION: Positive urogenital cultures taken before clinically indicated cerclage intervention may be associated with lower GA at delivery. However, there seems to be no benefit of antibiotic treatment or routine urogenital cultures during follow-up of asymptomatic women after cerclage placement.

VaNoLaH trial: a study protocol-a multinational randomised controlled trial including two identical substudies comparing vaginal versus vNOTES (vaginal natural orifice transluminal surgery) hysterectomy or laparoscopic versus vNOTES hysterectomy.

INTRODUCTION: Hysterectomy is one of the most common surgeries performed in women. Minimally invasive methods are on the rise globally as they have been shown to decrease surgical morbidity compared with abdominal hysterectomy. Hysterectomy by vaginal natural orifice transluminal endoscopic surgery (vNOTES) is the latest innovation. It combines the vaginal approach and endoscopy via the vagina. Large pragmatic randomised controlled trials (RCTs) are lacking comparing outcomes after vNOTES, vaginal hysterectomy (VH) and laparoscopic hysterectomy (LH). METHODS: Multicentre pragmatic RCT aiming to recruit 1000 women aged 18-75 years undergoing hysterectomy for benign disease. The RCT includes two identical substudies (groups A and B). If VH is considered safe and feasible, the patient will be randomised within group A (VH vs vNOTES). If VH is not considered safe or feasible, patients will be randomised within group B (LH vs vNOTES). ANALYSIS: Primary outcome is the proportion of women leaving the hospital within 12 hours after surgery. Secondary outcomes are hospitalisation time, conversion rates, duration of the surgical procedure, intraoperative complications, postoperative complications and readmission. ETHICS AND DISSEMINATION: The Ethical Board Committee at Imelda Hospital, Bonheiden, Belgium, has approved the research protocol 230704 (principal investigator). Before including patients, all centres will require local or national ethical approval. The results of the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05971875.

Artificial Intelligence in Imaging in the First Trimester of Pregnancy: A Systematic Review.

INTRODUCTION: Ultrasonography in the first trimester of pregnancy offers an early screening tool to identify high risk pregnancies. Artificial intelligence (AI) algorithms have the potential to improve the accuracy of diagnosis and assist the clinician in early risk stratification. OBJECTIVE: The objective of the study was to conduct a systematic review of the use of AI in imaging in the first trimester of pregnancy. METHODS: We conducted a systematic literature review by searching in computerized databases PubMed, Embase, and Google Scholar from inception to January 2024. Full-text peer-reviewed journal publications written in English on the evaluation of AI in first-trimester pregnancy imaging were included. Review papers, conference abstracts, posters, animal studies, non-English and non-peer-reviewed articles were excluded. Risk of bias was assessed by using PROBAST. RESULTS: Of the 1,595 non-duplicated records screened, 27 studies were included. Twelve studies focussed on segmentation, 8 on plane detection, 6 on image classification, and one on both segmentation and classification. Five studies included fetuses with a gestational age of less than 10 weeks. The size of the datasets was relatively small as 16 studies included less than 1,000 cases. The models were evaluated by different metrics. Duration to run the algorithm was reported in 12 publications and ranged between less than one second and 14 min. Only one study was externally validated. CONCLUSION: Even though the included algorithms reported a good performance in a research setting on testing datasets, further research and collaboration between AI experts and clinicians is needed before implementation in clinical practice.

Length of hysterotomy for fetal spina bifida repair is associated with prematurity risk.

OBJECTIVE: To investigate whether prenatal repair of spina bifida aperta through mini-hysterotomy results in less prematurity, as compared to standard hysterotomy, when adjusting for known prematurity risks. METHODS: We performed a bi-centric, propensity score matched, controlled study, that is, adjusting for factors earlier reported to result in premature delivery or membrane rupture, in consecutive women having prenatal repair either through stapled hysterotomy or sutured mini-hysterotomy (≤3.5 cm). Matches were pairwise compared and cox-regression analysis was performed to define the hazard ratio of delivery <37 weeks. RESULTS: Of 346 meeting the MOMS-criteria, 78 comparable pairs were available for matched-controlled analysis. Mini-hysterotomy patients were younger and had a higher BMI. Mini-hysterotomy was associated with a 1.67-lower risk of delivery <37 weeks (hazard ratio: 0.60; 95% CI: 0.42-0.85; p = 0.004) and 1.72 for delivery <34 + 6 weeks (hazard ratio: 0.58; 95% CI: 0.34-0.97; p = 0.037). The rate of intact uterine scar at birth (mini-hysterotomy: 98.7% vs. hysterotomy: 90.4%; p = 0.070), the rate of reversal of hindbrain herniation within 1 week after surgery (88.9% vs. 97.4%; p = 0.180) and the rate of cerebrospinal fluid leakage (0% vs. 2.7%; p = 0.50) were comparable. CONCLUSION: Prenatal spina bidifa repair through mini-hysterotomy was associated with a later gestational age at delivery and a comparable intact uterus rate without apparent compromise in neuroprotection.

Single-cell guided prenatal derivation of primary fetal epithelial organoids from human amniotic and tracheal fluids.

Isolation of tissue-specific fetal stem cells and derivation of primary organoids is limited to samples obtained from termination of pregnancies, hampering prenatal investigation of fetal development and congenital diseases. Therefore, new patient-specific in vitro models are needed. To this aim, isolation and expansion of fetal stem cells during pregnancy, without the need for tissue samples or reprogramming, would be advantageous. Amniotic fluid (AF) is a source of cells from multiple developing organs. Using single-cell analysis, we characterized the cellular identities present in human AF. We identified and isolated viable epithelial stem/progenitor cells of fetal gastrointestinal, renal and pulmonary origin. Upon culture, these cells formed clonal epithelial organoids, manifesting small intestine, kidney tubule and lung identity. AF organoids exhibit transcriptomic, protein expression and functional features of their tissue of origin. With relevance for prenatal disease modeling, we derived lung organoids from AF and tracheal fluid cells of congenital diaphragmatic hernia fetuses, recapitulating some features of the disease. AF organoids are derived in a timeline compatible with prenatal intervention, potentially allowing investigation of therapeutic tools and regenerative medicine strategies personalized to the fetus at clinically relevant developmental stages.

Preterm membranes are mechanically more resistant than term membranes.

OBJECTIVE: To compare the biomechanical properties of fetal preterm membranes (20 + 0 weeks to 30 + 0 weeks) to those of the term (37 + 0 to 41 + 0 weeks). METHOD: Amnion and chorion were manually separated and samples were cut to the required geometry. Rectangular samples with (mode 1) and without (uniaxial) a notch, were tested for tearing energy, critical elongation, and tangent stiffness. Suture retention and inter-suture distance testing investigated the effect of suture placement. RESULTS: From the 15 preterm and 10 term placentas studied, no notable differences were observed in uniaxial testing. Mode 1 fracture testing showed a difference in tearing energy between the preterm and term chorion (0.025 ± 0.005 vs. 0.017 ± 0.005 J/m-1 ; p = 0.027) but not in the amnion (0.030 ± 0.017 vs. 0.029 ± 0.009 J/m-1 ; p = 0.895). Both preterm amnion and chorion showed a higher critical elongation compared with term (1.229 ± 0.057 vs. 1.166 ± 0.046; p = 0.019 and 1.307 ± 0.049 vs. 1.218 ± 0.058; p = 0.012). Preterm amnion had a higher suture retention strength than its term counterpart (0.189 ± 0.065 vs. 0.121 ± 0.031 N; p = 0.023). In inter-suture distance tests, no significant interaction was observed beyond 3 mm, but the preterm chorion showed less interaction at 1-2 mm distances. CONCLUSION: Preterm membranes have equivalent or superior tensile properties to term membranes. The chorion appears to contribute to the mechanical integrity of fetal membranes, particularly in preterm stages.

High-fidelity, low-cost synthetic training model for fetoscopic spina bifida repair.

BACKGROUND: Fetoscopic spina bifida repair is increasingly being practiced, but limited skill acquisition poses a barrier to widespread adoption. Extensive training in relevant models, including both ex vivo and in vivo models may help. To address this, a synthetic training model that is affordable, realistic, and that allows skill analysis would be useful. OBJECTIVE: This study aimed to create a high-fidelity model for training in the essential neurosurgical steps of fetoscopic spina bifida repair using synthetic materials. In addition, we aimed to obtain a cheap and easily reproducible model. STUDY DESIGN: We developed a 3-layered, silicon-based model that resemble the anatomic layers of a typical myelomeningocele lesion. It allows for filling of the cyst with fluid and conducting a water tightness test after repair. A compliant silicon ball mimics the uterine cavity and is fixed to a solid 3-dimensional printed base. The fetal back with the lesion (single-use) is placed inside the uterine ball, which is reusable and repairable to allow for practicing port insertion and fixation multiple times. Following cannula insertion, the uterus is insufflated and a clinical fetoscopic or robotic or prototype instruments can be used. Three skilled endoscopic surgeons each did 6 simulated fetoscopic repairs using the surgical steps of an open repair. The primary outcome was surgical success, which was determined by water tightness of the repair, operation time <180 minutes and an Objective Structured Assessment of Technical Skills score of ≥18 of 25. Skill retention was measured using a competence cumulative sum analysis of a composite binary outcome of surgical success. Secondary outcomes were cost and fabrication time of the model. RESULTS: We made a model that can be used to simulate the neurosurgical steps of spina bifida repair, including anatomic details, port insertion, placode release and descent, undermining of skin and muscular layer, and endoscopic suturing. The model was made using reusable 3-dimensional printed molds and easily accessible materials. The 1-time startup cost was €211, and each single-use, simulated myelomeningocele lesion cost €9.5 in materials and 50 minutes of working time. Two skilled endoscopic surgeons performed 6 simulated, 3-port fetoscopic repairs, whereas a third used a Da Vinci surgical robot. Operation times decreased by more than 30% from the first to the last trial. Six experiments per surgeon did not show an obvious Objective Structured Assessment of Technical Skills score improvement. Competence cumulative sum analysis confirmed competency for each surgeon. CONCLUSION: This high-fidelity, low-cost spina bifida model allows simulated dissection and closure of a myelomeningocele lesion. VIDEO ABSTRACT.

A Dempster-Shafer Approach to Trustworthy AI With Application to Fetal Brain MRI Segmentation.

Deep learning models for medical image segmentation can fail unexpectedly and spectacularly for pathological cases and images acquired at different centers than training images, with labeling errors that violate expert knowledge. Such errors undermine the trustworthiness of deep learning models for medical image segmentation. Mechanisms for detecting and correcting such failures are essential for safely translating this technology into clinics and are likely to be a requirement of future regulations on artificial intelligence (AI). In this work, we propose a trustworthy AI theoretical framework and a practical system that can augment any backbone AI system using a fallback method and a fail-safe mechanism based on Dempster-Shafer theory. Our approach relies on an actionable definition of trustworthy AI. Our method automatically discards the voxel-level labeling predicted by the backbone AI that violate expert knowledge and relies on a fallback for those voxels. We demonstrate the effectiveness of the proposed trustworthy AI approach on the largest reported annotated dataset of fetal MRI consisting of 540 manually annotated fetal brain 3D T2w MRIs from 13 centers. Our trustworthy AI method improves the robustness of four backbone AI models for fetal brain MRIs acquired across various centers and for fetuses with various brain abnormalities.