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We developed an ex vivo model system to analyze the influence of relevant environmental and mechanical factors potentially affecting the integrity of fetal membranes during fetoscopic surgery. The set-up exposes amniochorion membranes to insufflation at predefined levels of gas pressure, flow, humidity, and temperature. Change in fetal membranes stiffness is quantified during the phase mimicking surgery through measurement of membranes' strain in response to cyclic overpressure. The trocar induced perforation creates a mechanical weakness whose stability is assessed by increasing the insufflation pressure until membrane rupture. Damage of the epithelial cells lining the amnion is assessed through live-dead staining. Initial experiments demonstrated the functionality of the new apparatus and the feasibility of the proposed protocols. Fetal membranes exposed to air with low humidity for approximately 1 h demonstrated significant embrittlement, while their mechanical integrity was maintained in case of gas insufflation at high humidity (air as well as CO 2 ). Under dry circumstances, there was a significant rate of epithelial cell death. Separation of amnion and chorion in the region of the trocar site was visible in all experiments. This new model is a versatile platform for analyzing the mechanical, histological, and biological implications of fetoscopic surgery on fetal membranes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: To estimate stresses and strains in the uterine wall and fetal membranes with single/multi-port fetoscopy, simulating either a percutaneous access or via exteriorized uterus., Study Design: Finite element models based on anatomical dimensions, material properties and boundary conditions were created to simulate stresses, strains and displacements on the uterine wall and fetal membranes during simulated fetal surgery either via exteriorized uterus or percutaneous approach, and with one or three cannulas. Clinically, we measured the anatomical layer thickness and cannula entry point displacement in patients undergoing single port percutaneous fetoscopy., Results: Simulations demonstrate that single port percutaneous fetoscopy increases stress on the fetal membranes (+105%, 128 to 262 kPa) and uterine wall (+115%, 0.89 to 1.9 kPa) compared to exteriorized uterine access. Using three ports increases stress by 110% (148 to 312 kPa) on membranes and 113% (1.08 to 2.3 kPa) on uterine wall. Finite Element Method showed 0.75 cm uterine entry point displacement from the cutaneous entry, while clinical measurements demonstrated displacement of more than double (1.69 ± 0.58 cm), suggesting modeled measurements may be underestimations., Conclusion: The stresses and strains on the fetal membranes and uterus are double as high when entering percutaneously than via an exteriorized uterus. Based on what can be clinically measured, this may be an underestimation., (© 2024 John Wiley & Sons Ltd.)

3D imaging technology is becoming more prominent every day. However, more validation is needed to understand the actual benefit of 3D versus conventional 2D vision. This work quantitatively investigates whether experts benefit from 3D vision during minimally invasive fetoscopic spina bifida (fSB) repair. A superiority study was designed involving one expert team ([Formula: see text] procedures prior) who performed six 2D and six 3D fSB repair simulations in a high-fidelity animal training model, using 3-port access. The 6D motion of the instruments was recorded. Among the motion metrics are total path length, smoothness, maximum speed, the modified Spectral Arc Length (SPARC), and Log Dimensionless Jerk (LDLJ). The primary clinical outcome is operation time (power 90%, 5% significance) using Sealed Envelope Ltd. 2012. Secondary clinical outcomes are water tightness of the repair, CO[Formula: see text] insufflation volume, and OSATS score. Findings show that total path length and LDLJ are considerably different. Operation time during 3D vision was found to be significantly shorter compared to 2D vision ([Formula: see text] vs. [Formula: see text] min; p [Formula: see text] 0.026). These results suggest enhanced performance with 3D vision during interrupted suturing in fetoscopic SBA repair. To confirm these results, a larger-scale follow-up study involving multiple experts and novice surgeons is recommended., (© 2023. The Author(s).)

Objective: To assess the safety of Partial-Amniotic-Insufflation-of-heated-humidified-CO 2 (hPACI) during fetoscopic spina bifida repair (fSB-repair)., Method: A simulated fSB-repair through an exteriorized uterus under hPACI was performed in 100-day fetal lambs (term = 145 days) under a laboratory anesthesia protocol (n = 5; group 1) which is known to induce maternal-fetal acidosis and hypercapnia. Since these may not occur clinically, we applied a clinical anesthesia protocol (n = 5; group 2), keeping maternal parameters within physiological conditions, that is, controlled maternal arterial carbon dioxide (CO2) pressure (pCO 2  = 30 mmHg), blood pressure (≥67 mmHg), and temperature (37.1-39.8°C). Our superiority study used fetal pH as the primary outcome., Results: Compared to group 1, controlled anesthesia normalized fetal pH (7.23 ± 0.02 vs. 7.36 ± 0.02, p < 0.001), pCO 2 (70.0 ± 9.1 vs. 43.0 ± 1.0 mmHg, p = 0.011) and bicarbonate (27.8 ± 1.1 vs. 24.0 ± 0.9 mmol/L, p = 0.071) at baseline. It kept them within clinically acceptable limits (pH ≥ 7.23, pCO 2  ≤ 70 mmHg, bicarbonate ≤ 30 mm/L) for ≥120 min of hPACI as opposed to ≤30 min in group one. Fetal pO 2 and lactate were comparable between groups and generally within normal range. Fetal brain histology demonstrated fewer apoptotic cells and higher neuronal density in the prefrontal cortex in group two. There was no difference in fetal membrane inflammation, which was mild., Conclusion: Fetoscopic insufflation of heated-humidified CO 2 during simulated fSB-repair through an exteriorized uterus can be done safely under controlled anesthesia., (© 2022 John Wiley & Sons Ltd.)

Gastroschisis (GS) is a congenital abdominal wall defect, in which the bowel eviscerates from the abdominal cavity. It is a non-lethal isolated anomaly and its pathogenesis is hypothesized to occur as a result of two hits: primary rupture of the 'physiological' umbilical hernia (congenital anomaly) followed by progressive damage of the eviscerated bowel (secondary injury). The second hit is thought to be caused by a combination of mesenteric ischemia from constriction in the abdominal wall defect and prolonged amniotic fluid exposure with resultant inflammatory damage, which eventually leads to bowel dysfunction and complications. GS can be classified as either simple or complex, with the latter being complicated by a combination of intestinal atresia, stenosis, perforation, volvulus and/or necrosis. Complex GS requires multiple neonatal surgeries and is associated with significantly greater postnatal morbidity and mortality than is simple GS. The intrauterine reduction of the eviscerated bowel before irreversible damage occurs and subsequent defect closure may diminish or potentially prevent the bowel damage and other fetal and neonatal complications associated with this condition. Serial prenatal amnioexchange has been studied in cases with GS as a potential intervention but never adopted because of its unproven benefit in terms of survival and bowel and lung function. We believe that recent advances in prenatal diagnosis and fetoscopic surgery justify reconsideration of the antenatal management of complex GS under the rubric of the criteria for fetal surgery established by the International Fetal Medicine and Surgery Society (IFMSS). Herein, we discuss how conditions for fetoscopic repair of complex GS might be favorable according to the IFMSS criteria, including an established natural history, an accurate prenatal diagnosis, absence of fully effective perinatal treatment due to prolonged need for neonatal intensive care, experimental evidence for fetoscopic repair and maternal and fetal safety of fetoscopy in expert fetal centers. Finally, we propose a research agenda that will help overcome barriers to progress and provide a pathway toward clinical implementation. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Open fetal surgery for spina bifida (SB) is safe and effective yet invasive. The growing interest in fetoscopic SB repair (fSB-repair) prompts the need for appropriate training. We aimed to develop and validate a high-fidelity training model for fSB-repair. fSB-repair was simulated in the abdominal cavity and on the stomach of adult rabbits. Laparoscopic fetal surgeons served either as novices (n = 2) or experts (n = 3) based on their experience. Technical performance was evaluated using competency Cumulative Sum (CUSUM) analysis and the group splitting method. Main outcome measure for CUSUM competency was a composite binary outcome for surgical success, i.e. watertight repair, operation time ≤ 180 min and Objective-Structured-Assessment-of-Technical-Skills (OSATS) score ≥ 18/25. Construct validity was first confirmed since competency levels of novices and experts during their six first cases using both methods were significantly different. Criterion validity was also established as 33 consecutive procedures were needed for novices to reach competency using learning curve CUSUM, which is a number comparable to that of clinical fSB-repair. Finally, we surveyed expert fetal surgeons worldwide to assess face and content validity. Respondents (26/49; 53%) confirmed it with ≥ 71% of scores for overall realism ≥ 4/7 and usefulness ≥ 3/5. We propose to use our high-fidelity model to determine and shorten the learning curve of laparoscopic fetal surgeons and retain operative skills.

Objective: To evaluate the neonatal outcome of fetuses with isolated right-sided congenital diaphragmatic hernia (iRCDH) based on prenatal severity indicators and antenatal management., Methods: This was a retrospective review of prospectively collected data on consecutive cases diagnosed with iRCDH before 30 weeks' gestation in four fetal therapy centers, between January 2008 and December 2018. Data on prenatal severity assessment, antenatal management and perinatal outcome were retrieved. Univariate and multivariate logistic regression analysis were used to identify predictors of survival at discharge and early neonatal morbidity., Results: Of 265 patients assessed during the study period, we excluded 40 (15%) who underwent termination of pregnancy, two cases of unexplained fetal death, two that were lost to follow-up, one for which antenatal assessment of lung hypoplasia was not available and six cases which were found to have major associated anomalies or syndromes after birth. Of the 214 fetuses with iRCDH included in the neonatal outcome analysis, 86 were managed expectantly during pregnancy and 128 underwent fetal endoscopic tracheal occlusion (FETO) with a balloon. In the expectant-management group, lung size measured by ultrasound or by magnetic resonance imaging was the only independent predictor of survival (observed-to-expected lung-to-head ratio (o/e-LHR) odds ratio (OR), 1.06 (95% CI, 1.02-1.11); P = 0.003). Until now, stratification for severe lung hypoplasia has been based on an o/e-LHR cut-off of 45%. In cases managed expectantly, the survival rate was 15% (4/27) in those with o/e-LHR ≤ 45% and 61% (36/59) for o/e-LHR > 45% (P = 0.001). However, the best o/e-LHR cut-off for the prediction of survival at discharge was 50%, with a sensitivity of 78% and specificity of 72%. In the expectantly managed group, survivors with severe pulmonary hypoplasia stayed longer in the neonatal intensive care unit than did those with mildly hypoplastic lungs. In fetuses with an o/e-LHR ≤ 45% treated with FETO, survival rate was higher than in those with similar lung size managed expectantly (49/120 (41%) vs 4/27 (15%); P = 0.014), despite higher prematurity rates (gestational age at birth: 34.4 ± 2.7 weeks vs 36.8 ± 3.0 weeks; P < 0.0001). In fetuses treated with FETO, gestational age at birth was the only predictor of survival (OR, 1.25 (95% CI, 1.04-1.50); P = 0.02)., Conclusions: Antenatal measurement of lung size can predict survival in iRCDH. In fetuses with severe lung hypoplasia, FETO was associated with a significant increase in survival without an associated increase in neonatal morbidity. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Purpose: Fetoscopic laser photocoagulation is a minimally invasive surgical procedure used to treat twin-to-twin transfusion syndrome (TTTS), which involves localization and ablation of abnormal vascular connections on the placenta to regulate the blood flow in both fetuses. This procedure is particularly challenging due to the limited field of view, poor visibility, occasional bleeding, and poor image quality. Fetoscopic mosaicking can help in creating an image with the expanded field of view which could facilitate the clinicians during the TTTS procedure., Methods: We propose a deep learning-based mosaicking framework for diverse fetoscopic videos captured from different settings such as simulation, phantoms, ex vivo, and in vivo environments. The proposed mosaicking framework extends an existing deep image homography model to handle video data by introducing the controlled data generation and consistent homography estimation modules. Training is performed on a small subset of fetoscopic images which are independent of the testing videos., Results: We perform both quantitative and qualitative evaluations on 5 diverse fetoscopic videos (2400 frames) that captured different environments. To demonstrate the robustness of the proposed framework, a comparison is performed with the existing feature-based and deep image homography methods., Conclusion: The proposed mosaicking framework outperformed existing methods and generated meaningful mosaic, while reducing the accumulated drift, even in the presence of visual challenges such as specular highlights, reflection, texture paucity, and low video resolution.

Objective: One of the drawbacks of fetal endoscopic tracheal occlusion (FETO) for congenital diaphragmatic hernia is the need for a second invasive intervention to re-establish airway patency. The 'Smart-TO' device is a new balloon for FETO that deflates spontaneously when placed in a strong magnetic field, therefore overcoming the need for a second procedure. The safety and efficacy of this device have not yet been demonstrated. The aim of this study was to investigate the reversibility, local side effects and occlusiveness of the Smart-TO balloon, both in a simulated in-utero environment and in the fetal lamb model., Methods: First, the reversibility of tracheal occlusion by the Smart-TO balloon was tested in a high-fidelity simulator. Following videoscopic tracheoscopic balloon insertion, the fetal mannequin was placed within a 1-L water-filled balloon to mimic the amniotic cavity. This was held by an operator in front of their abdomen, and different fetal and maternal positions were simulated to mimic the most common clinical scenarios. Following exposure to the magnetic field generated by a 1.5-T magnetic resonance (MR) machine, deflation of the Smart-TO balloon was assessed by tracheoscopy. In cases of failed deflation, the mannequin was reinserted into a water-filled balloon for additional MR exposure, up to a maximum of three times. Secondly, reversibility, occlusiveness and local effects of the Smart-TO balloon were tested in vivo in fetal lambs. Tracheal occlusion was performed in fetal lambs on gestational day 95 (term, 145 days), either using the balloon currently used in clinical practice (Goldbal2) (n = 5) or the Smart-TO balloon (n = 5). On gestational day 116, the presence of the balloon was assessed by tracheoscopy. Deflation was performed by puncture (Goldbal2) or MR exposure (Smart-TO). Six unoccluded fetal lambs served as controls. Following euthanasia, the lung-to-body-weight ratio (LBWR), lung morphometry and tracheal circumference were assessed. Local tracheal changes were measured using a hierarchical histologic scoring system., Results: Ex vivo, Smart-TO balloon deflation occurred after a single MR exposure in 100% of cases in a maternal standing position with the mannequin at a height of 95 cm (n = 32), 55 cm (n = 8) or 125 cm (n = 8), as well as when the maternal position was 'lying on a stretcher' (n = 8). Three out of eight (37.5%) balloons failed to deflate at first exposure when the maternal position was 'sitting in a wheelchair'. Of these, two balloons deflated after a second MR exposure, but one balloon remained inflated after a third exposure. In vivo, all Smart-TO balloons deflated successfully. The LBWR in fetal lambs with tracheal occlusion by a Smart-TO balloon was significantly higher than that in unoccluded controls, and was comparable with that in the Goldbal2 group. There were no differences in lung morphometry and tracheal circumference between the two balloon types. Tracheal histology showed minimal changes for both balloons., Conclusions: In a simulated in-utero environment, the Smart-TO balloon was effectively deflated by exposure of the fetus in different positions to the magnetic field of a 1.5-T MR system. There was only one failure, which occurred when the mother was sitting in a wheelchair. In healthy fetal lambs, the Smart-TO balloon is as occlusive as the clinical standard Goldbal2 system and has only limited local side effects. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Purpose: Twin-to-twin transfusion syndrome (TTTS) is a placental defect occurring in monochorionic twin pregnancies. It is associated with high risks of fetal loss and perinatal death. Fetoscopic elective laser ablation (ELA) of placental anastomoses has been established as the most effective therapy for TTTS. Current tools and techniques face limitations in case of more complex ELA cases. Visualization of the entire placental surface and vascular equator; maintaining an adequate distance and a close to perpendicular angle between laser fiber and placental surface are central for the effectiveness of laser ablation and procedural success. Robot-assisted technology could address these challenges, offer enhanced dexterity and ultimately improve the safety and effectiveness of the therapeutic procedures., Methods: This work proposes a 'minimal' robotic TTTS approach whereby rather than deploying a massive and expensive robotic system, a compact instrument is 'robotised' and endowed with 'robotic' skills so that operators can quickly and efficiently use it. The work reports on automatic placental pose estimation in fetoscopic images. This estimator forms a key building block of a proposed shared-control approach for semi-autonomous fetoscopy. A convolutional neural network (CNN) is trained to predict the relative orientation of the placental surface from a single monocular fetoscope camera image. To overcome the absence of real-life ground-truth placenta pose data, similar to other works in literature (Handa et al. in: Proceedings of the IEEE conference on computer vision and pattern recognition, 2016; Gaidon et al. in: Proceedings of the IEEE conference on computer vision and pattern recognition, 2016; Vercauteren et al. in: Proceedings of the IEEE, 2019) the network is trained with data generated in a simulated environment and an in-silico phantom model. A limited set of coarsely manually labeled samples from real interventions are added to the training dataset to improve domain adaptation., Results: The trained network shows promising results on unseen samples from synthetic, phantom and in vivo patient data. The performance of the network for collaborative control purposes was evaluated in a virtual reality simulator in which the virtual flexible distal tip was autonomously controlled by the neural network., Conclusion: Improved alignment was established compared to manual operation for this setting, demonstrating the feasibility to incorporate a CNN-based estimator in a real-time shared control scheme for fetoscopic applications.

Antimicrobial prophylaxis during surgery aims to prevent post-operative site infections. For fetal surgery, this includes the fetal and amniotic compartments. Both are deep compartments as drug equilibrium with maternal blood is achieved relatively late. Despite prophylaxis, chorio-amnionitis or endometritis following ex utero intrapartum treatment or fetoscopy occur in 4.13% and 1.45% respectively of the interventions. This review summarizes the observations on two commonly administered antimicrobials (cefazolin, clindamycin) for surgical prophylaxis during pregnancy, with emphasis on the deep compartments. For both compounds, antimicrobial exposure is on target when we consider the maternal and fetal plasma compartment. In contrast, amniotic fluid concentrations-time profiles display a delayed and much more blunted pattern, behaving as deep compartment. For cefazolin, there are data that document further dilution in the setting of polyhydramnios. Along this deep compartment concept, there is some accumulation during repeated administration, modeled for cefazolin and observed for clindamycin. The relative underexposure to antimicrobials in amniotic fluid may be reflected in the pattern of maternal-fetal complications after fetal surgery, and suggest that antimicrobial prophylaxis practices for fetal surgery should be reconsidered. Further studies should be designed by a multidisciplinary team (fetal surgeons, clinical pharmacologists and microbiologists) to facilitate efficient evaluation of antimicrobial prophylaxis., (© 2020 John Wiley & Sons, Ltd.)

Objective: The Management of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida aperta (SBA). Recently developed alternative techniques may reduce maternal risks without compromising the fetal neuroprotective effects. The aim of this systematic review was to assess the learning curve (LC) of different fetal SBA closure techniques., Methods: MEDLINE, Web of Science, EMBASE, Scopus and Cochrane databases and the gray literature were searched to identify relevant articles on fetal surgery for SBA, without language restriction, published between January 1980 and October 2018. Identified studies were reviewed systematically and those reporting all consecutive procedures and with postnatal follow-up ≥ 12 months were selected. Studies were included only if they reported outcome variables necessary to measure the LC, as defined by fetal safety and efficacy. Two authors independently retrieved data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effects model when heterogeneous. To measure the LC, we used two complementary methods. In the group-splitting method, competency was defined when the procedure provided results comparable to those in the MOMS trial for 12 outcome variables representing the immediate surgical outcome, short-term neonatal neuroprotection and long-term neuroprotection at ≥ 12 months of age. Then, when raw patient data were available, we performed cumulative sum analysis based on a composite binary outcome defining successful surgery. The composite outcome combined four clinically relevant variables for safety (absence of extreme preterm delivery < 30 weeks, absence of fetal death ≤ 7 days after surgery) and efficacy (reversal of hindbrain herniation and absence of any neonatal treatment of dehiscence or cerebrospinal fluid leakage at the closure site)., Results: Of 6024 search results, 17 (0.3%) studies were included, all of which had low, moderate or unclear risk of bias. Fetal SBA closure was performed using standard hysterotomy (11 studies), mini-hysterotomy (one study) or fetoscopy by either exteriorized-uterus single-layer closure (one study), percutaneous single-layer closure (three studies) or percutaneous two-layer closure (one study). Only outcomes for standard hysterotomy could be meta-analyzed. Overall, outcomes improved significantly with experience. Competency was reached after 35 consecutive cases for standard hysterotomy and was predicted to be achieved after ≥ 57 cases for mini-hysterotomy and ≥ 56 for percutaneous two-layer fetoscopy. For percutaneous and exteriorized-uterus single-layer fetoscopy, competency was not reached in the 81 and 28 cases available for analysis, respectively, and LC prediction analysis could not be performed., Conclusions: The number of cases operated is correlated with the outcome of fetal SBA closure, and the number of operated cases required to reach competency ranges from 35 for standard hysterotomy to ≥ 56-57 for minimally invasive modifications. Our observations provide important information for institutions looking to establish a new fetal center, develop a new fetal surgery technique or train their team, and inform referring clinicians, potential patients and third parties. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Purpose: Fetoscopic laser photocoagulation is a minimally invasive surgery for the treatment of twin-to-twin transfusion syndrome (TTTS). By using a lens/fibre-optic scope, inserted into the amniotic cavity, the abnormal placental vascular anastomoses are identified and ablated to regulate blood flow to both fetuses. Limited field-of-view, occlusions due to fetus presence and low visibility make it difficult to identify all vascular anastomoses. Automatic computer-assisted techniques may provide better understanding of the anatomical structure during surgery for risk-free laser photocoagulation and may facilitate in improving mosaics from fetoscopic videos., Methods: We propose FetNet, a combined convolutional neural network (CNN) and long short-term memory (LSTM) recurrent neural network architecture for the spatio-temporal identification of fetoscopic events. We adapt an existing CNN architecture for spatial feature extraction and integrated it with the LSTM network for end-to-end spatio-temporal inference. We introduce differential learning rates during the model training to effectively utilising the pre-trained CNN weights. This may support computer-assisted interventions (CAI) during fetoscopic laser photocoagulation., Results: We perform quantitative evaluation of our method using 7 in vivo fetoscopic videos captured from different human TTTS cases. The total duration of these videos was 5551 s (138,780 frames). To test the robustness of the proposed approach, we perform 7-fold cross-validation where each video is treated as a hold-out or test set and training is performed using the remaining videos., Conclusion: FetNet achieved superior performance compared to the existing CNN-based methods and provided improved inference because of the spatio-temporal information modelling. Online testing of FetNet, using a Tesla V100-DGXS-32GB GPU, achieved a frame rate of 114 fps. These results show that our method could potentially provide a real-time solution for CAI and automating occlusion and photocoagulation identification during fetoscopic procedures.

Fetal myelomeningocele (fMMC) closure (spina bifida aperta) has become a care option for patients that meet inclusion criteria, but it is clear that fetal intervention, while improving outcomes, is not a cure. This review will: (1) focus on the rationale for fMMC surgery based on preclinical studies and observations that laid the foundation for human pilot studies and a randomized controlled trial; (2) summarize important clinical outcomes; (3) discuss the feasibility, efficacy, and safety of recent developments in fetal surgical techniques and approaches; and (4) highlight future research directions. Given the increased risk of maternal and fetal morbidity associated with prenatal intervention, accompanied by the increasing number of centres performing interventions worldwide, teams involved in the care of these patients need to proceed with caution to maintain technical expertise, competency, and patient safety. Ongoing assessment of durability of the benefits of fMMC surgery, as well as additional refinement of patient selection criteria and counselling, is needed to further improve outcomes and reduce the risks to the mother and fetus. WHAT THIS PAPER ADDS: High-quality prospective studies are needed to broaden the indication for fetal surgery in the general myelomeningocele population. Innovative minimally invasive approaches have had promising results, yet lack comprehensive and robust experimental or clinical evaluation. Important information to help families make informed decisions regarding fetal surgery for myelomeningocele is provided., (© 2019 Mac Keith Press.)

Introduction: Congenital head and neck pathology may cause direct postnatal airway obstruction. Prenatal diagnosis facilitates safe delivery with pre- and perinatal airway assessment and management and Ex-Utero-Intrapartum-Treatment (EXIT) if necessary. Fetoscopic airway evaluation can optimize the selection of patients in need of an EXIT procedure., Methods: Description of 11 consecutive fetuses, born with a potential airway obstruction between 1999 and 2011 and treated at the University Hospitals Leuven, with a long-term follow-up until 2018. An algorithm including fetoscopic airway evaluation is presented., Results: In utero imaging revealed seven teratomas, one fourth branchial pouch cyst, one thymopharyngeal duct remnant, one lymphatic malformation and one laryngeal atresia. A multidisciplinary team could avoid EXIT in eight patients by ultrasonographic (n = 2) or fetoscopic (n = 6) documentation of accessible airways. Three patients needed an EXIT-to-airway-procedure. Neonatal surgery included tracheostomy during EXIT (n = 2) and resection of teratoma (n = 7) or branchiogenic pathology (n = 3). All patients do well at long-term (minimum 54 months) follow-up., Conclusions: Combining prenatal imaging and perinatal fetoscopy, EXIT-procedure and neonatal surgery yields an optimal long-term outcome in these complex patients. Fetoscopy can dramatically reduce the number of EXIT-procedures., (Copyright © 2019. Published by Elsevier B.V.)

Objective: To establish maternal complication rates for fetoscopic or open fetal surgery., Methods: We conducted a systematic literature review for studies of fetoscopic or open fetal surgery performed since 1990, recording maternal complications during fetal surgery, the remainder of pregnancy, delivery, and after the index pregnancy., Results: One hundred sixty-six studies were included, reporting outcomes for open fetal (n = 1193 patients) and fetoscopic surgery (n = 9403 patients). No maternal deaths were reported. The risk of any maternal complication in the index pregnancy was 20.9% (95%CI, 15.22-27.13) for open fetal and 6.2% (95%CI, 4.93-7.49) for fetoscopic surgery. For severe maternal complications (grades III to V Clavien-Dindo classification of surgical complications), the risk was 4.5% (95% CI 3.24-5.98) for open fetal and 1.7% (95% CI, 1.19-2.20) for fetoscopic surgery. In subsequent pregnancies, open fetal surgery increased the risk of preterm birth but not uterine dehiscence or rupture. Nearly one quarter of reviewed studies (n = 175, 23.3%) was excluded for failing to report the presence or absence of maternal complications., Conclusions: Maternal complications occur in 6.2% fetoscopic and 20.9% open fetal surgeries, with serious maternal complications in 1.7% fetoscopic and 4.5% open procedures. Reporting of maternal complications is variable. To properly quantify maternal risks, outcomes should be reported consistently across all fetal surgery studies., (© 2019 The Authors. Prenatal Diagnosis Published by John Wiley & Sons Ltd.)

Partial amniotic carbon dioxide insufflation (PACI) involves insufflating the amniotic sac with carbon dioxide (CO 2 ) and, in some cases, draining some of the amniotic fluid. The creation of a gaseous intra-amniotic compartment improves visualization, even in the presence of limited bleeding, and creates the work space required for complex fetoscopic procedures. Clinically, PACI is mostly used to perform fetoscopic myelomeningocele (MMC) repair, enabling a minimally invasive alternative to open fetal surgery. However, evidence of the fetal safety of PACI is limited. Previous animal experiments in sheep demonstrate that PACI induces fetal hypercapnia and acidosis with largely unknown short and longer term implications. In this review, we examine the literature for the physiological effects of intrauterine insufflation pressure, duration, humidity, and the role of maternal hyperventilation on fetal physiology and well-being., (© 2018 John Wiley & Sons, Ltd.)

Aim: To establish the provision of fetal surgery for myelomeningocele (MMC) worldwide., Methods: Through the International Society for Prenatal Diagnosis (ISPD) Fetal Therapy Special Interest Group and the North American Fetal Therapy Network (NAFTNet), fetal therapy centres were surveyed (September 2017-June 2018) regarding availability of fetal MMC surgical repair, patient inclusion criteria, repair techniques, number of cases, and outcome reporting. Responses were summarised on an interactive map on the ISPD website., Results: Forty-four of 59 centres responded (74.6%) of which 34 centres (77.1%) currently offered fetal surgery for MMC and seven centres (15.9%) were awaiting a first case after service set up. Patient inclusion criteria were similar and based on the Management of Myelomeningocele (MOMS) trial. Five centres (14.7%) operated beyond 26 weeks' gestational age, outside the MOMS criteria. Open fetal surgery was provided in 23 centres (67.6%), fetoscopic surgery only in five (14.7%), and six centres offered both types (17.6%). Neurosurgical closure was similar for open surgery but highly variable in fetoscopy surgery. The median number of cases per centre was 21 (range 1-253)., Conclusions: Fetal surgery for MMC is now offered globally. Two thirds of centres offer open repair via hysterotomy using criteria based on the MOMS trial., (© 2018 John Wiley & Sons, Ltd.)

Spina bifida aperta (SBA) is one of the most common congenital malformations. It can cause severe lifelong physical and neurodevelopmental disabilities. Experimental and clinical studies have shown that the neurological deficits associated with SBA are not simply caused by incomplete neurulation at the level of the lesion. Additional damage is caused by prolonged exposure of the spinal cord and nerves to the intrauterine environment and a suction gradient due to cerebrospinal fluid leakage, leading to progressive downward displacement of the hindbrain. This natural history can be reversed by prenatal repair. A randomised controlled trial demonstrated that mid-gestational maternal-fetal surgery for SBA decreases the need for ventriculoperitoneal shunting and hindbrain herniation at 12 months and improves neurological motor function at 30 months of age. This came at the price of maternal and fetal risks, the most relevant ones being increased prematurity and a persistent uterine corporeal scar. Recently minimally invasive fetal approaches have been introduced clinically yet they lack extensive experimental or clinical trials. We aim to provide clinicians with the essential information necessary to counsel SBA parents as the basis for considering referral of selected patients to expert fetal surgery centres. We review the reported clinical outcomes and discuss recent developments of potentially less invasive fetal SBA approaches., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Intrauterine foetal surgery is the treatment option for several congenital malformations. For twin-to-twin transfusion syndrome (TTTS), interventions involve the use of laser fibre to ablate vessels in a shared placenta. The procedure presents a number of challenges for the surgeon, and computer-assisted technologies can potentially be a significant support. Vision-based sensing is the primary source of information from the intrauterine environment, and hence, vision approaches present an appealing approach for extracting higher level information from the surgical site., Methods: In this paper, we propose a framework to detect one of the key steps during TTTS interventions-ablation. We adopt a deep learning approach, specifically the ResNet101 architecture, for classification of different surgical actions performed during laser ablation therapy., Results: We perform a two-fold cross-validation using almost 50 k frames from five different TTTS ablation procedures. Our results show that deep learning methods are a promising approach for ablation detection., Conclusion: To our knowledge, this is the first attempt at automating photocoagulation detection using video and our technique can be an important component of a larger assistive framework for enhanced foetal therapies. The current implementation does not include semantic segmentation or localisation of the ablation site, and this would be a natural extension in future work.

Congenital diaphragmatic hernia is rare birth defect, which can be easily corrected after birth. The main problem is that herniation of viscera during fetal life impairs lung development, leading to a 30% mortality and significant morbidity. In isolated cases the outcome can be accurately predicted prenatally by medical imaging. Cases with a poor prognosis can be treated before birth; clinically this is by fetoscopic endoluminal tracheal occlusion. Obstruction of the airways triggers lung growth. This procedure is currently being evaluated in a global clinical trial for left sided cases; right sided cases with poor prognosis are offered the procedure clinically. The search for more potent and less invasive therapies continues. Prenatal transplacental sildenafil administration will in due course be tried clinically, with the aim to reduce the occurrence of persistent pulmonary hypertension, either alone or in combination with fetal surgery. Other medical approaches are in an earlier translational phase.

Purpose: The standard clinical treatment of Twin-to-Twin transfusion syndrome consists in the photo-coagulation of undesired anastomoses located on the placenta which are responsible to a blood transfer between the two twins. While being the standard of care procedure, fetoscopy suffers from a limited field-of-view of the placenta resulting in missed anastomoses. To facilitate the task of the clinician, building a global map of the placenta providing a larger overview of the vascular network is highly desired., Methods: To overcome the challenging visual conditions inherent to in vivo sequences (low contrast, obstructions or presence of artifacts, among others), we propose the following contributions: (1) robust pairwise registration is achieved by aligning the orientation of the image gradients, and (2) difficulties regarding long-range consistency (e.g. due to the presence of outliers) is tackled via a bag-of-word strategy, which identifies overlapping frames of the sequence to be registered regardless of their respective location in time., Results: In addition to visual difficulties, in vivo sequences are characterised by the intrinsic absence of gold standard. We present mosaics motivating qualitatively our methodological choices and demonstrating their promising aspect. We also demonstrate semi-quantitatively, via visual inspection of registration results, the efficacy of our registration approach in comparison with two standard baselines., Conclusion: This paper proposes the first approach for the construction of mosaics of placenta in in vivo fetoscopy sequences. Robustness to visual challenges during registration and long-range temporal consistency are proposed, offering first positive results on in vivo data for which standard mosaicking techniques are not applicable.

Background: An improved survival and quality of life for neonatal survivors after fetoscopic laser therapy for twin-twin transfusion syndrome has been reported. However, little is known about the medium-term maternal effects after fetoscopic laser therapy with respect to reproductive and gynecologic outcomes., Objective: The objective of this study was to document reproductive, obstetric, gynecological, and psychological outcomes in women who underwent fetoscopic laser therapy for twin-twin transfusion syndrome., Study Design: This was a monocentric controlled study on consecutive women who underwent fetoscopic laser therapy for twin-twin transfusion syndrome between 2007 and 2013 at the University Hospitals Leuven (cases; n = 198). Controls were women followed up during the same time period for an uncomplicated monochorionic diamniotic twin pregnancy and with an uneventful course (controls; n = 211). All patients received a questionnaire inquiring on their fertility, later pregnancies, and gynecological outcomes., Results: The response rate was 50.4% (cases: n = 95; controls: n = 109). Most baseline characteristics were similar across both groups. Women in the fetoscopic laser therapy group attempted a new pregnancy more frequently (34% [31 of 92] vs 21% [22 of 107] in controls; P < .05) and became pregnant more often (100% [31 of 31] vs 82% [18 of 22]; P < .05).We observed a shorter interpregnancy interval in cases than controls (median interval, 12 [interquartile range, 5-27] vs 24 [interquartile range, 15-30] months) (P < .05). This was also observed in cases who lost one or both fetuses or babies in the index pregnancy (median interval, 9 [interquartile range, 3.5-25.5] months; P < .05). The complication rate during subsequent pregnancies (26% [8 of 31] vs 11% [2 of 19]; P = .194) and at delivery (17% [5 of 30] vs 11% [2 of 19]; P = .554) were comparable. More women who underwent fetoscopic laser coagulation reported relevant psychological symptoms (44% [40 of 92] vs 21% [23 of 107]; P < .05). When only women in whom there was a double-surviving twin pair were considered, there were no differences in psychological symptoms compared with controls (16% [15 of 55] vs 21% [23 of 107]; P = .411). Gynecological problems were equally frequent in both groups (20% [18 of 92] vs 31% [33 of 107]; P = .069)., Conclusion: No adverse medium-term maternal effects with respect to fertility, obstetric, and gynecological outcomes were observed after fetoscopic laser therapy. However, these women reported more psychological or emotional problems than women with monochorionic diamniotic who did not have laser therapy, in particular when this was complicated by a fetal loss., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Congenital diaphragmatic hernia is surgically correctable, yet the poor lung development determines mortality and morbidity. In isolated cases the outcome may be predicted prenatally by medical imaging. Cases with a poor prognosis could be treated before birth. However, prenatal modulation of lung development remains experimental. Fetoscopic endoluminal tracheal occlusion triggers lung growth and is currently being evaluated in a global clinical trial. Prenatal transplacental sildenafil administration may in due course be a therapeutic approach, reducing the occurrence of persistent pulmonary hypertension, either alone or in combination with fetal surgery., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Isolated congenital diaphragmatic hernia defect allows viscera to herniate into the chest, competing for space with the developing lungs. At birth, pulmonary hypoplasia leads to respiratory insufficiency and persistent pulmonary hypertension that is lethal in up to 30% of patients. Antenatal measurement of lung size and liver herniation can predict survival after birth. Prenatal intervention aims at stimulating lung development, clinically achieved by percutaneous fetal endoscopic tracheal occlusion under local anesthesia. This in utero treatment requires a second intervention to reestablish the airway, either before birth or at delivery., Objective: To describe our experience with in utero endotracheal balloon removal., Materials and Methods: This is a retrospective analysis of prospectively collected data on consecutive patients with congenital diaphragmatic hernia treated in utero by fetal endoscopic tracheal occlusion from 3 centers. Maternal and pregnancy-associated variables were retrieved. Balloon removal attempts were categorized as elective or emergency and by technique (in utero: ultrasound-guided puncture; fetoscopy; ex utero: on placental circulation or postnatal tracheoscopy)., Results: We performed 351 balloon insertions during a 144-month period. In 9 cases removal was attempted outside fetal endoscopic tracheal occlusion centers, 3 of which were deemed impossible and led to neonatal death. We attempted 302 in-house balloon removals in 292 fetuses (217 elective [71.8%], 85 emergency [28.2%]) at 33.4 ± 0.1 weeks (range: 28.9-37.1), with a mean interval to delivery of 16.6 ± 0.8 days (0-85). Primary attempt was by fetoscopy in 196 (67.1%), by ultrasound-guided puncture in 62 (21.2%), by tracheoscopy on placental circulation in 30 (10.3%), and postnatal tracheoscopy in 4 cases (1.4%); a second attempt was required in 10 (3.4%) cases. Each center had different preferences for primary technique selection. In elective removals, we found no differences in the interval to delivery between fetoscopic and ultrasound-guided puncture removals. Difficulties during fetoscopic removal led to the development of a stylet to puncture the balloon, leading to shorter operating time and easier reestablishment of airways., Conclusion: In these fetal treatment centers, the balloon could always be removed successfully. In 90% this was in utero, with the use of fetoscopy preferred over ultrasound-guided puncture. Ex utero removal was a fall-back procedure. In utero removal does not seem to precipitate immediate membrane rupture, labor, or delivery, although the design of the study did not allow for a formal conclusion. For fetoscopic removals, the introduction of a stylet facilitated retrieval. Successful removal may rely on a permanently prepared team with expertise in all possible techniques., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We have developed a calibration target for use with fluid-immersed endoscopes within the context of the GIFT-Surg (Guided Instrumentation for Fetal Therapy and Surgery) project. One of the aims of this project is to engineer novel, real-time image processing methods for intra-operative use in the treatment of congenital birth defects, such as spina bifida and the twin-to-twin transfusion syndrome. The developed target allows for the sterility-preserving optical distortion calibration of endoscopes within a few minutes. Good optical distortion calibration and compensation are important for mitigating undesirable effects like radial distortions, which not only hamper accurate imaging using existing endoscopic technology during fetal surgery, but also make acquired images less suitable for potentially very useful image computing applications, like real-time mosaicing. In this paper proposes a novel fabrication method to create an affordable, sterilizable calibration target suitable for use in a clinical setup. This method involves etching a calibration pattern by laser cutting a sandblasted stainless steel sheet. This target was validated using the camera calibration module provided by OpenCV, a state-of-the-art software library popular in the computer vision community.

Background: Congenital diaphragmatic hernia (CDH) is an abnormal development of the diaphragm leading to high neonatal mortality and morbidity. Beyond the neonatal period, prospective data on overall long-term outcome in CDH survivors is scarce. In particular, for those treated with fetoscopic endoluminal tracheal occlusion (FETO), a promising new technique to increase survival chances for severe cases, the outcomes are even less documented., Aim: To prospectively document the clinical outcome of CDH at 1 year including FETO-treated infants in relation to ante- and postnatal variables., Methods: A single-centre prospective clinical follow-up at 1 year of age included a standardised respiratory questionnaire., Results: Thirty-four CDH survivors were included, 10 of which were FETO-treated infants. At 1 year, the median weight z score was -1.50 (interquartile range [IQR]: -2.45 to -0.88) and 10/34 were "failure to thrive" (FTT) cases. Gastro-intestinal (GI) problems at 1 year were mainly related to gastro-oesophageal reflux (16/34) with a high need for tube feeding in the first year (9/34). Tachypnoea was present in 10/29 (34%) and 8/34 (24%) were on chronic inhaled medication. The median total respiratory symptom score was 20 (IQR: 13-32) and correlated with the number of neonatal ventilation days (p = 0.048). Hospital re-admission occurred in 19/34 infants (56%), and was for respiratory problems in almost half of them (8/19)., Conclusion: In this CDH cohort, morbidity at 1 year was determined more by GI problems and FTT than respiratory morbidity. The respiratory questionnaire may, however, have underestimated the respiratory morbidity since respondents had a 1-in-4 chance to have persistent tachypnoea and be on chronic inhalation therapy., (© 2017 S. Karger AG, Basel.)

Study Question: What is the impact of fetoscopic surgery for isolated Congenital Diaphragmatic Hernia (CDH) on future reproductive and gynecological outcomes?, Summary Answer: We did not observe an increase of obstetric or gynecological problems after fetoscopic surgery nor was there an increased risk for subsequent infertility., What Is Known Already: The reproductive and gynecological outcomes of patients undergoing open maternal-fetal surgery are known. The most relevant counseling items are the elevated risk for uterine dehiscence and rupture (up to 14%)., Study Design, Size, Duration: Bi-centric study over a 10-year period including 371 women carrying a fetus with isolated CDH either managed expectantly (n = 167) or operated in utero (n = 204)., Participants/materials, Setting, Methods: Consenting patients filled out a survey with 23 questions (2 open and 21 multiple choice). Questionnaires were custom designed to obtain information on subsequent reproductive or gynecological problems as well as psychological impact., Main Results and the Role of Chance: The response rate was 40% (147/371). More women in the FETO group attempted a subsequent pregnancy: 70% (62/89) when compared with 47% (27/58) in controls (P = 0.009). This coincided with a longer follow-up in the FETO group (76 versus 59 months; P < 0.001) and a lower survival rate in the index pregnancy (53 versus 72%; P = 0.028). There was no difference in the number of nulliparous or parous women, neither in the conception rate. In total, there were 129 subsequent pregnancies. Nobody reported secondary fertility problems. Four women in the FETO group and one in the control reported a congenital anomaly in a subsequent pregnancy. Twenty-one pregnancies were reported with at least one complication (FETO: 23% (14/60), controls 27% (7/26)). During delivery or in the post-partum period 11 patients reported at least 1 complication (FETO 17% (10/59), controls 4% (1/24)). New onset gynecological problems occurred in 14 participants (10%). None of these events were more likely in one or the other group. Psychological and emotional impacts were frequent in both the FETO (41%) and the control groups (46%) (P = 0.691)., Limitations, Reasons for Caution: The response rate was 40% (147/371), less than desired. The use of unvalidated self-reported outcomes may skew exact determination of the nature and severity of medical complications. The number of observations for uncommon events was low. The mean follow-up period to detect gynecological complications may be too short., Wider Implications of the Findings: This is the first evidence that fetoscopic surgery for CDH does not compromise future reproductive potential or obstetrical outcome when compared with expectant management. A pregnancy complicated by a serious congenital birth defect, such as CDH, frequently has a measurable psychological impact., Study Funding/competing Interest: The authors have no conflicts to declare. J.D. receives a fundamental clinical research grant of the Fonds Wetenschappelijk Onderzoek - Vlaanderen (FWO; 18.01207). A.C.E. is supported by the Erasmus+Program of the European Union (Framework agreement number 2013-0040; contract 1011990). This was presented at the 61st meeting of the Society of Gynaecologic Investigation, in Florence, March 2014 (F-111)., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Fetoscopic laser surgery for twin-twin transfusion syndrome is a procedure for which no objective tools exist to assess technical skills. To ensure that future fetal surgeons reach competence prior to performing the procedure unsupervised, we developed a performance assessment tool. The aim of this study was to validate this assessment tool for reliability and construct validity., Methods: We made use of a procedure-specific evaluation instrument containing all essential steps of the fetoscopic laser procedure, which was previously created using Delphi methodology. Eleven experts and 13 novices from three fetal medicine centers performed the procedure on the same simulator. Two independent observers assessed each surgery using the instrument (maximum score: 52). Interobserver reliability was assessed using Spearman correlation. We compared the performance of novices and experts to assess construct validity., Results: The interobserver reliability was high (Rs  = 0.974, P < 0.001). Checklist scores for experts and novices were significantly different; the median score for novices was 28/52 (54%), whereas that for experts was 47.5/52 (91%) (P < 0.001). The procedure time and fetoscopy time were significantly shorter (P < 0.001) for experts. Residual anastomoses were found in 1/11 (9%) procedures performed by experts and in 9/13 (69%) procedures performed by novices (P = 0.005). Multivariable analysis showed that the checklist score, independent of age and gender, predicted competence., Conclusions: The procedure-specific assessment tool for fetoscopic laser surgery shows good interobserver reliability and discriminates experts from novices. This instrument may therefore be a useful tool in the training curriculum for fetal surgeons. Further intervention studies with reassessment before and after training may increase the construct validity of the tool. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To compare outcomes of fetoscopic spina bifida aperta repair (FSBAR) with the results of the open approach (OSBAR) as in the Management Of Myelomeningocele Study (MOMS)., Methods: This was a systematic comparison of reports on FSBAR with data from the MOMS (n = 78). Inclusion criteria were studies of spina bifida aperta patients who underwent FSBAR and were followed for ≥12 months. Primary outcome was perinatal mortality. Secondary outcomes included operative, maternal, fetal, neonatal and infant outcomes., Results: Out of 16 reports, we included 5 from 2 centers. Due to bias and heterogeneity, analysis was restricted to two overlapping case series (n = 51 and 71). In those, FSBAR was technically different from OSBAR, had comparable perinatal mortality (7.8 vs. 2.6%, p = 0.212) and shunt rate at 12 months (45 vs. 40%, p = 0.619), longer operation time (223 vs. 105 min, p < 0.001), higher preterm prelabor membrane rupture rate (84 vs. 46%, p < 0.001), earlier gestational age at birth (32.9 vs. 34.1 weeks, p = 0.03), higher postnatal reoperation rate (28 vs. 2.56%, p < 0.001) and absence of uterine thinning or dehiscence (0 vs. 36%, p < 0.001). Functional outcomes were not available., Conclusion: FSBAR utilizes a different neurosurgical technique, takes longer to complete, induces more prematurity, requires additional postnatal procedures, yet has a comparable shunt rate and is not associated with uterine thinning or dehiscence. Long-term functional data are awaited., (© 2016 S. Karger AG, Basel.)

Image guidance plays a central role in minimally invasive fetal surgery such as photocoagulation of inter-twin placental anastomosing vessels to treat twin-to-twin transfusion syndrome (TTTS). Fetoscopic guidance provides insufficient sensitivity for imaging the vasculature that lies beneath the fetal placental surface due to strong light scattering in biological tissues. Incomplete photocoagulation of anastamoses is associated with postoperative complications and higher perinatal mortality. In this study, we investigated the use of multi-spectral photoacoustic (PA) imaging for better visualization of the placental vasculature. Excitation light was delivered with an optical fiber with dimensions that are compatible with the working channel of a fetoscope. Imaging was performed on an ex vivo normal term human placenta collected at Caesarean section birth. The photoacoustically-generated ultrasound signals were received by an external clinical linear array ultrasound imaging probe. A vein under illumination on the fetal placenta surface was visualized with PA imaging, and good correspondence was obtained between the measured PA spectrum and the optical absorption spectrum of deoxygenated blood. The delivery fiber had an attached fiber optic ultrasound sensor positioned directly adjacent to it, so that its spatial position could be tracked by receiving transmissions from the ultrasound imaging probe. This study provides strong indications that PA imaging in combination with ultrasonic tracking could be useful for detecting the human placental vasculature during minimally invasive fetal surgery.

Objective: To evaluate the effect of a newly developed training curriculum on the performance of fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS) using an advanced high-fidelity simulator model., Methods: Ten novices were randomized to receive verbal instructions and either skills training using the simulator (study group; n = 5) or no training (control group; n = 5). Both groups were evaluated with a pre-training and post-training test on the simulator. Performance was assessed by two independent observers and comprised a 52-item checklist for surgical performance (SP) score, measurement of procedure time and number of anastomoses missed. Eleven experts set the benchmark level of performance. Face validity and educational value of the simulator were assessed using a questionnaire., Results: Both groups showed an improvement in SP score at the post-training test compared with the pre-training test. The simulator-trained group significantly outperformed the control group, with a median SP score of 28 (54%) in the pre-test and 46 (88%) in the post-test vs 25 (48%) and 36 (69%), respectively (P = 0.008). Procedure time decreased by 11 min (from 44 to 33 min) in the study group vs 1 min (from 39 to 38 min) in the control group (P = 0.69). There was no significant difference in the number of missed anastomoses at the post-training test between the two groups (1 vs 0). Subsequent feedback provided by the participants indicated that training on the simulator was perceived as a useful educational activity., Conclusions: Proficiency-based simulator training improves performance, indicated by SP score, for fetoscopic laser therapy. Despite the small sample size of this study, practice on a simulator is recommended before trainees carry out laser therapy for TTTS in pregnant women., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To determine, by expert consensus, the essential substeps of fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) that could be used to create an authority-based curriculum for training in this procedure among fetal medicine specialists., Methods: A Delphi survey was conducted among an international panel of experts (n = 98) in FLS. Experts rated the substeps of FLS on a five-point Likert-type scale to indicate whether they considered them to be essential, and were able to comment on each substep, using a dedicated online platform accessed by the invited tertiary care facilities that specialize in fetal therapy. Responses were returned to the panel until consensus was reached (Cronbach's α ≥ 0.80). All substeps that were rated  ≥ 4 by 80% of the experts were included in the evaluation instrument., Results: After the first iteration of the Delphi procedure, a response rate of 74% (73/98) was reached, and in the second and third iterations response rates of 90% (66/73) and 81% (59/73) were reached, respectively. Among a total of 81 substeps rated in the first round, 21 substeps had to be re-rated in the second round. Finally, from the initial list of substeps, 55 were agreed by experts to be essential. In the third round, the 18 categorized substeps were ranked in order of importance, with 'coagulation of all anastomoses that cross the equator' and 'determination of fetoscope insertion site' as the most important., Conclusions: A total of 55 substeps of FLS for TTTS were defined by a panel of experts to be essential in the procedure. This list is the first authority-based evidence to be used in the development of a final training model for future fetal surgeons., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Congenital diaphragmatic hernia (CDH) may be isolated or associated with other structural anomalies, the latter with poor prognosis. The defect allows viscera to herniate through the defect into the chest, competing for space with the developing lungs. At birth, pulmonary hypoplasia leads to respiratory insufficiency and persistent pulmonary hypertension that is lethal in up to 30% of patients. When isolated, survival chances can be predicted by antenatal measurement of lung size and liver herniation. Chromosomal microarrays and exome sequencing contribute to understanding genetic factors underlying isolated CDH. Prenatal intervention aims at stimulating lung development, clinically achieved by percutaneous fetal endoscopic tracheal occlusion (FETO) under local anesthesia. The Tracheal Occlusion To Accelerate Lung growth trial (www.totaltrial.eu) is an international randomized trial investigating the role of fetal therapy for severe and moderate pulmonary hypoplasia. Despite an apparent increase in survival following FETO, the search for lesser invasive and more potent prenatal interventions must continue., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome are typically treated with fetoscopic laser coagulation. Postoperative complications can occur due to residual vascular anastomoses on the placenta. We aimed to assess the efficacy and safety of a novel surgery technique that uses laser coagulation of the entire vascular equator (Solomon technique)., Methods: We undertook an open-label, international, multicentre, randomised controlled trial at five European tertiary referral centres. Women with twin-to-twin transfusion syndrome were randomly assigned by online randomisation (1:1) with permuted blocks to the Solomon technique or standard laser coagulation. The primary outcome was a composite of incidence of twin anaemia polycythaemia sequence, recurrence of twin-to-twin transfusion syndrome, perinatal mortality, or severe neonatal morbidity. Analyses were by intention to treat, with results expressed as odds ratios (ORs) and 95% CIs. This trial is registered with the Dutch Trial Registry, number NTR1245., Findings: Between March 11, 2008, and July 12, 2012, 274 women were randomly assigned to either the Solomon group (n=139) or the standard treatment group (n=135). The primary outcome occurred in 94 (34%) of 274 fetuses in the Solomon group versus 133 (49%) of 270 in the standard treatment group (OR 0·54; 95% CI 0·35-0·82). The Solomon technique was associated with a reduction in twin anaemia polycythaemia sequence (3% vs 16% for the standard treatment; OR 0·16, 95% CI 0·05-0·49) and recurrence of twin-to-twin transfusion syndrome (1% vs 7%; 0·21, 0·04-0·98). Perinatal mortality and severe neonatal morbidity did not differ significantly between the two groups. Outside of the common and well-known complications of twin-to-twin transfusion syndrome and its treatment, no serious adverse events occurred., Interpretation: Fetoscopic laser coagulation of the entire vascular equator reduces postoperative fetal morbidity in severe twin-to-twin transfusion syndrome. We recommend that fetoscopic surgeons consider adopting this strategy for treatment of women with twin-to-twin transfusion syndrome., Funding: Netherlands Organization for the Health Research and Development (ZonMw 92003545)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: Large solid sacrococcygeal teratomas (SCT) can cause high-output cardiac failure and fetal or neonatal death. The aim of this study was to describe the outcomes of minimally invasive antenatal procedures for the treatment of fetal SCT., Methods: A case review was performed of five fetuses with a large SCT treated antenatally using minimally invasive techniques, and a systematic literature review on fetal therapy for solid SCTs was carried out., Results: Five women were referred between 17 + 5 and 26 + 4 weeks' gestation for a large fetal SCT with evidence of fetal cardiac failure. Vascular flow to the tumors was interrupted by fetoscopic laser ablation (n = 1), radiofrequency ablation (RFA; n = 2) or interstitial laser ablation  ±  vascular coiling (n = 2). There were two intrauterine fetal deaths. The other three cases resulted in preterm labor within 10 days of surgery. One neonate died. Two survived without procedure-related complications but had long-term morbidity related to prematurity. The systematic literature review revealed 16 SCTs treated minimally invasively for (early) hydrops. Including our cases, six of 20 hydropic fetuses survived after minimally invasive therapy (30%). Survival after RFA or interstitial laser ablation was 45% (5/11). Of 12 fetuses treated for SCT without obvious hydrops and for which perinatal survival data were available, eight (67%) survived. Mean gestational age at delivery after minimally invasive therapy was 29.7 ± 4.0 weeks. Survival after open fetal surgery in hydropic fetuses was 6/11 (55%), with a mean gestational age at delivery of 29.8 ± 2.9 weeks., Conclusions: Fetal therapy can potentially improve perinatal outcomes for hydropic fetuses with a solid SCT, but is often complicated by intrauterine death and preterm birth., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: This study aimed to analyze perinatal outcome in monoamniotic (MA) pregnancies that underwent antenatal surgical interventions for fetal complications., Methods: Review of all MA pregnancies treated with antenatal surgical interventions in three fetal treatment centers between 2000 and 2013. Indications were twin-twin transfusion syndrome, twin reversed arterial perfusion sequence, discordant anomalies, or elective reduction. We analyzed associations between indication, type of intervention, perinatal survival, and gestational age (GA) at birth and compared our results with a systematic review of the literature., Results: Fifty-eight MA pregnancies were included. Median GA at treatment was 18.0 weeks (range: 13.1-33.0). Procedures included cord coagulation plus transection (n = 42), cord coagulation without transection (n = 7), laser coagulation of placental anastomoses (n = 7), and one case each with interstitial laser and radiofrequency ablation. Median GA at birth was 34 weeks (range 16.0-41.0), and 75% (53/71) of fetuses intended to survive indeed survived. Literature review included 20 articles, reporting on a total of 45 cases of surgically treated MA pregnancies, showing similar outcome results., Conclusion: We present the largest series concerning surgical interventions in complicated MA pregnancies. Despite being rare in experienced hands, a 75% survival is achieved. Collaboration between centers, data sharing, and benchmarking may further improve outcome., (© 2014 John Wiley & Sons, Ltd.)

Objectives The objective of this article is to describe the development of an anatomically accurate simulator in order to aid the training of a perinatal team in the insertion and removal of a fetal endoscopic tracheal occlusion (FETO) balloon in the management of prenatally diagnosed congenital diaphragmatic hernia. Methods An experienced perinatal team collaborated with a medical sculptor to design a fetal model for the FETO procedure. Measurements derived from 28-week fetal magnetic resonance imaging were used in the development of an anatomically precise simulated airway within a silicone rubber preterm fetal model. Clinician feedback was then used to guide multiple iterations of the model with serial improvements in the anatomic accuracy of the simulator airway. Results An appropriately sized preterm fetal mannequin with a high-fidelity airway was developed. The team used this model to develop surgical skills with balloon insertion, and removal, and to prepare the team for an integrated response to unanticipated delivery with the FETO balloon still in situ. Conclusions This fetal mannequin aided in the ability of a fetal therapy unit to offer the FETO procedure at their center for the first time. This model may be of benefit to other perinatal centers planning to offer this procedure., (© 2013 John Wiley & Sons, Ltd.)

Introduction: Percutaneous fetoscopic endoluminal reversible tracheal occlusion (FETO) was developed to prevent the pulmonary complications of fetal congenital diaphragmatic herniation. There is an urgent need to establish the closest to human translational model of FETO in order to improve fetal outcomes and to determine new clinical approaches and applications., Material and Methods: Seven non-human primates underwent two subsequent surgeries: the first, the FETO in the experimental group (n = 3) or sham operation in the control animals (S-FETO, n = 4) at 132-142 days of gestation (dGA); the second, the reversal of occlusion or sham operation at 162 ± 5 dGA. Maternal stress axis, complete blood count, and biochemical parameters were evaluated and newborn tracheal radiography was performed., Results: The average pregnancy duration and neonatal weights in the FETO group did not differ from the animals in the S-FETO group. There was no bleeding or premature fetal membrane rupture during the procedures in any of the baboons. The maximal tracheal width was 7.02 ± 0.6 mm in the FETO versus 5.46 ± 0.6 mm in S-FETO group., Discussion: This is the very first report of a successful FETO model in non-human primates. Similarities to human tracheomegaly were for the first time documented in any model studied., (© 2014 S. Karger AG, Basel.)

Objectives: To investigate the efficacy of collagen plugs at reducing the risk of preterm premature rupture of membranes (PPROM) after fetoscopic surgery for congenital diaphragmatic hernia (CDH)., Methods: This was a single-center cohort study on all consecutive cases undergoing fetoscopic endoluminal tracheal occlusion (FETO) for severe or moderate CDH, between April 2002 and May 2011 (n = 141). Cases either received a collagen plug for sealing the fetal membrane defect after FETO or did not, depending on the operating surgeon. The principal outcome measure was the time from fetal surgery to PPROM, further referred to as 'latency'. A multivariable Cox regression model was used to investigate the association between collagen plug and latency while adjusting for risk factors for PPROM., Results: Of the 141 cases, 54 (38%) received a collagen plug and 87 (62%) did not. Sixty cases experienced PPROM, 26 among cases with and 34 among cases without a plug (48 vs 39%). The hazard ratio of plug use was 1.29 (95% CI, 0.76-2.19), which does not exclude a potentially increased risk for PPROM when a collagen plug is used. For cases with a plug, 24% had PPROM before balloon removal and 24% had PPROM after elective balloon removal. For cases without a plug, these rates were 30 and 9%, respectively. Perinatal outcomes were similar in both groups., Conclusions: No evidence was found that collagen plugs reduce the risk of PPROM after FETO for CDH., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: The aim of this study is to evaluate the independent and combined value of gestational age, fetal weight, fetoplacental Doppler, and myocardial performance index for the prediction of individual risk of early (≤7 days) intrauterine fetal death (IUFD) after laser therapy in twin-to-twin transfusion syndrome (TTTS)., Material and Methods: A consecutive series of 215 cases of TTTS treated with laser therapy in three centers was prospectively studied. Ultrasound evaluation within 24 h of surgery included estimated fetal weight discordance, umbilical artery, pulsatility index (PI) and diastolic flow evaluation, middle cerebral artery PI and middle cerebral artery peak systolic velocity, ductus venosus PI and atrial flow assessment, and modified myocardial performance index. Logistic regression analysis was used to explore the association of preoperative parameters with IUFD., Results: Intrauterine fetal death occurred in 17 (7.9%) of the recipients and 33 (15.3%) donors (p = 0.016). The only independent predictors of IUFD in recipients was the middle cerebral artery peak systolic velocity >1.5 MoM (OR = 22, p = 0.015), but this event was present in only 3% of recipients. In donors, reverse end diastolic flow in the umbilical artery (OR = 14.748, p = 0.033), estimated fetal weight discordance (OR = 1.054, p = 0.036), and gestational age (OR = 0.757, p = 0.046) were independent predictors., Conclusion: In TTTS, preoperative fetal assessment can identify independent risk factors for early post-operative IUFD, particularly in donors., (© 2013 John Wiley & Sons, Ltd.)

Objectives: To investigate neonatal morbidity in fetuses with severe congenital diaphragmatic hernia (CDH) treated with fetoscopic endoluminal tracheal occlusion (FETO) and compare it with historical controls with less severe forms of CDH that were managed expectantly., Methods: This was a prospective, multicenter study on neonatal outcomes and prenatal predictors in 90 FETO survivors (78 left-sided, 12 right) and 41 controls from the antenatal CDH registry with either severe or moderate hypoplasia who were managed expectantly. We also investigated early neonatal morbidity indicators, including the need for patch repair, duration of mechanical ventilation and supplemental oxygen, age at full enteral feeding and incidence of pulmonary hypertension., Results: Gestational age at delivery was predictive of duration of assisted ventilation (P = 0.046), days on supplemental oxygen (P = 0.019) and age at full enteral feeding (P = 0.020). When delivery took place after 34 weeks' gestation, neonatal morbidity of FETO cases was comparable with that of expectantly managed cases with moderate hypoplasia., Conclusions: Fetal intervention for severe CDH is associated with neonatal morbidity that is comparable with that of an expectantly managed group with less severe disease., (Copyright © 2013 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: Our knowledge about miscarriages mainly concerns pregnancies of at least 8 weeks' gestation. Information about the morphology and the genetic determinants of early aborted embryos remains limited. In addition, it is known that aneuploidies account for less than half of recurrent spontaneous abortions. We hypothesized that (recurrent) early pregnancy losses might have other genetic causes., Method: Products of conception from 51 couples with at least one previous miscarriage were collected by hystero-embryoscopy. The extracted DNA was analyzed by low resolution array comparative genomic hybridization and high resolution single nucleotide polymorphism arrays to detect aneuploidies, polyploidies, submicroscopic copy number variants or copy neutral loss of heterozygosity., Results: Chromosomal aberrations were identified in 65.6% (21/32) of miscarriages and in 89% (8/9) of anembryonic cases. Interestingly, 4/11 chromosomally euploid embryos contained regions of loss of heterozygosity >5 Mb, suggesting the miscarriages might be due to an underlying lethal recessive disease., Conclusion: Hystero-embryoscopic biopsy followed by array comparative genomic hybridization is a valuable diagnostic tool for early and recurrent miscarriages. Genome-wide high resolution single nucleotide polymorphism microarray analysis of a larger group of miscarriages could provide more insight into the genetic causes of recurrent spontaneous abortion., (© 2012 John Wiley & Sons, Ltd.)

Background: The past decade has seen much progress in intrauterine surgery. Randomized trials have documented the benefit of some procedures of this type for the unborn child., Method: Selective literature review, Results: Randomized trials have demonstrated the benefit of fetoscopic laser coagulation of placental anastomoses in twin-to-twin transfusion syndrome (TTTS) and of intrauterine surgery via hysterotomy for the repair of spina bifida. Other fetoscopic procedures have yielded promising initial results but are not yet supported by findings from randomized trials. Some intrauterine surgical procedures must still be considered experimental in view of the lack of randomized trials and the rarity of the conditions they are designed to treat. Fetoscopic laser coagulation for TTTS is by far the most common procedure in fetal surgery; TTTS arises in roughly 1 in 2500 pregnancies. The other procedures discussed in this article are performed much less often and for rarer indications. In general, intrauterine surgery is indicated only to treat conditions that would otherwise lead to intrauterine death or irreversible prenatal damage., Conclusion: Intrauterine surgery is a rapidly developing field. Prenatal intervention by laser coagulation is indicated to treat severe TTTS, as its benefit has been shown in a randomized trial. Not enough evidence is yet available for the possible benefit of intrauterine surgery to treat myelomeningocele and congenital diaphragmatic hernia. Other indications are experimental. When an indication for intrauterine surgery exists, the parents should be informed and, depending on their wishes, referred to a center where it can be performed.

Objective: To compare the outcomes of twin-to-twin transfusion syndrome (TTTS) cases treated with fetoscopic laser coagulation of vascular anastomoses before 25 + 6 weeks of gestation and between 26 and 28 weeks of gestation., Material and Methods: 28 consecutive cases of TTTS at Quintero stages II-IV treated with laser therapy between 26 + 0 and 28 + 6 weeks of gestation were compared with 324 cases treated between 15 + 0 and 25 + 6 weeks during a 3-year period in two centers. The following data were recorded and compared: duration of the fetoscopy, rate of complications (preterm labor before 28 weeks and before 32 weeks, chorioamnionitis, twin anemia-polycythemia syndrome and recurrent TTTS), gestational age at delivery and neonatal survival rate., Results: The study groups were similar as regards Quintero staging and the frequency of anterior placental location (50.0 vs. 47.8%, p = 0.85 in late and conventional laser, respectively). There were no significant differences in the duration of surgery (29 vs. 30, p = 0.27, respectively) and in the rates of any of the complications evaluated. Gestational age at delivery (33 vs. 33.3 weeks, p = 0.69) and neonatal survival of at least one fetus (92.3 vs. 88.6%, p = 0.24) were also similar., Conclusion: Fetoscopic laser coagulation for TTTS performed between 26 + 0 and 28 + 6 weeks of gestation was associated with similar outcomes as those observed in cases treated before 26 weeks., (Copyright © 2011 S. Karger AG, Basel.)

Objective: Fetuses with congenital diaphragmatic hernia (CDH) and for whom additional ultrasound findings are abnormal typically are considered to have a dismal prognosis. Our aim was to assess the outcome of fetuses with CDH and associated intrafetal fluid effusions., Methods: This was a retrospective bicentric cohort study on the perinatal management of fetuses with CDH and intrafetal fluid effusions., Results: The incidence of effusions was 5.2% (n = 14) in 269 consecutive cases of left-sided CDH and 29.2% (n = 14) in 48 cases of right-sided CDH. Hydrothorax (n = 19 (68%)) and ascites (n = 16 (57%)) were the most common effusions. A combination of both was present in 11 (39%) fetuses. Of 20 ongoing pregnancies with CDH and fluid effusions, without other anomalies, five with moderate or mild pulmonary hypoplasia were managed without fetoscopic endoluminal tracheal occlusion (FETO). The 15 other cases underwent FETO because of severe pulmonary hypoplasia. Neonatal survival rate was similar in both groups (n = 2/5 and n = 6/15, respectively (P = 1.0)). Survival among those who underwent FETO was similar to previously published results concerning isolated cases undergoing FETO., Conclusions: Our observations do not support the view that intrafetal effusions are an adverse prognostic factor in fetuses with CDH. In CDH fetuses with effusions and severe pulmonary hypoplasia treated with FETO, neonatal survival is similar to that in isolated cases undergoing the intervention. Whether pleural effusions should be addressed by thoracic drainage procedures remains unproven., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)

In isolated congenital diaphragmatic hernia, lung size and/or the position of the liver are predictive of neonatal outcome. Percutaneous Fetal Endoscopic Tracheal Occlusion (FETO) by a balloon can be undertaken to prompt lung growth in the worst cases. The feasibility and safety of FETO is no longer at stake, and it is associated with an apparent increase in neonatal survival. The gestational age at birth, the pre-existing lung size, the ability to remove the balloon prior to birth, and the lung response are predicting outcome. The most frequent complication is preterm premature rupture of the membranes, and as a consequence preterm delivery, which also complicates balloon removal. We have set up a randomized trial for the formal evaluation of FETO in Europe, including criteria for fetoscopy centers. Training of European as well as North American centers is taking place, so that the procedure could be safely and more widely offered., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)