Endoscopic Fetal Surgery Research Articles

Training model for the fetal myelomeningocele correction with multiportal endoscopic technique.

The recent history of myelomeningocele has shown that treatment during the fetal life may reduce the risk of developing hydrocephalus in individuals by approximately 50%. Thus, a significant advancement involves fetal surgery performed through an endoscopic technique in which portals are placed to introduce the forceps and laparoscopic instruments. However, the development of this technique requires training; therefore, this study aimed to develop a training model for fetal myelomeningocele repair technique with multi-portal endoscopy. Two stages of endoscopic technique development were performed. The first stage consisted of exercises in order to familiarize the surgeon with 2D-vision endoscopic surgery, associated with the application of exercises focused on surgical skills, such as the development of laparoscopic knots in a synthetic model. The second stage involved the creation and application of the stages of myelomeningocele closure with a non-living animal model consisting of a chicken breast to simulate the myelomeningocele and a basketball to simulate the gravid uterus, in which perforations were made to introduce vascular introducers (portals) that, as in vivo, are used as portals (trocars) for the introduction of laparoscopic instruments. Overall, two different scenarios with three portals and two portals were tested. In three-portal simulator, the triangular apex trocar was used for the introduction of 4-mm 0° or 30° optics or even Minop type neurodoscope (Aesculap®, Germany) that was operated by the assistant surgeon; the other two portals are used for the introduction of laparoscopic instruments. Thus, the surgeon is able to perform maneuvers bimanually since dissection to laparoscopic sutures. In two-portal simulator, the surgeon and assistant stay side by side and one of the portals is used for the optic and the other for the laparoscopic instruments. There is no possibility of bimanual dissection in this method. Realistic simulation models for endoscopic fetal surgery for myelomeningocele correction are easily performed and help develop the necessary skills for fetal surgery teams.

Virtual navigation for the improvement of parents counseling and the planning of fetal endoscopic myelomeningocele repair

Myelomeningocele (MMC) is the most severe form of spina bifida with intrauterine repairs becoming more prevalent. The development of three-dimensional ultrasound (3DUS) and magnetic resonance imaging (MRI) has drastically improved the visualization of fetal anatomy. Virtual Navigation (VN) results from a technology that uses software generated realistic images to replicate the immersive feeling of a real environment. This report aims to demonstrate VN in a Chiari II malformation case, obtained from 3DUS and MRI files, comparing this with the fetal endoscopic surgery for MMC.

Minimizing Individual Learning Curves in a Mature Endoscopic Fetal Surgery Program

Introduction: Twin-to-twin transfusion syndrome affects monochorionic twin pregnancies and can result in fetal death. Endoscopic laser treatment remains a relatively infrequent procedure for this condition. This presents difficulties for maintaining proficiency and for training new personnel. Objective: The dual mentoring program at our institution allows for continuous mentoring of new providers. We hypothesize that this approach stabilizes program proficiency despite the addition of new practitioners. Methods: Query of the fetal treatment program database returned 146 cases of laser ablation between 2000 and 2019. Patient and pregnancy characteristics as well as operative time and outcomes were recorded. The learning curve-cumulative summation method and rolling averages were used to analyze outcomes. Results: Overall survival was 69%, and survival of at least 1 twin was 89%. Mean operative time was 53.6 ± 20.9 min. Overall twin survival stabilized after the first 40 cases. Rolling averages for operative time decreased from 71 to 49 min for the most recent cases. These results were not affected by the introduction of new surgeons. Conclusions: Creative mentoring can maintain stable overall program outcomes despite changes in team composition. This training approach may be applicable to other rare procedures in fetal surgery.

Fetal surgery and stem cell therapy for meningomyelocele.

To review the advance of maternal--fetal surgery, the research of stem cell transplantation and tissue engineering in prenatal management of fetal meningomyelocele (fMMC). Advance in the imaging study provides more accurate assessment of fMMC in utero. Prenatal maternal--fetal surgery in fMMC demonstrates favourable postnatal outcome. Minimally invasive fetal surgery minimizes uterine wall disruption. Endoscopic fetal surgery is performed via laparotomy-assisted or entirely percutaneous approach. The postnatal outcome for open and endoscopic fetal surgery shares no difference. Single layer closure during repair of fMMC is preferred to reduce postnatal surgical intervention. All maternal--fetal surgeries impose anesthetic and obstetric risk to pregnant woman. Ruptured of membrane and preterm delivery are common complications. Trans-amniotic stem cell therapy (TRASCET) showed potential tissue regeneration in animal models. Fetal tissue engineering with growth factors and dura substitutes with biosynthetic materials promote spinal cord regeneration. This will overcome the challenge of closure in large fMMC. Planning of the maternal--fetal surgery should adhere to ethical framework to minimize morbidity to both fetus and mother. Combination of endoscopic fetal surgery with TRASCET or tissue engineering will be a new vision to achieve to improve the outcome of prenatal intervention in fMMC.

Minimally Invasive Surgical Device for Precise Application of Bioadhesives to Prevent iPPROM

Introduction: The benefits of endoscopic fetal surgery are deteriorated by the high risk of iatrogenic preterm prelabor rupture of fetal membranes (iPPROM). While previous studies have reported good sealing candidates to prevent membrane rupture, the delivery of these materials to the location of membrane puncture remains unsolved. Materials and Methods: We describe an approach to apply sealing materials onto the amnion through the fetoscopy port. We developed a device composed of an umbrella-shaped polyester coated nitinol mesh and an applicator. The spontaneously unfolding umbrella is pushed through the port, pulled against the amnion, and glued onto the amnion defect site. We tested the adhesion strength of multiple glues and tested the feasibility and reproducibility of this fetal membrane sealing approach in an ex vivo model. Results: The umbrella unfolded and was well positioned in all tests (n = 18). When applied via the fetoscopy port, umbrellas were successfully glued onto the fetal membrane, and all of them completely covered the defect (n = 5). The mean time needed for the whole procedure was 3 min. Discussion: This study is a proof of concept presenting a potential future solution for the precise local application of bioadhesives for the prevention of iPPROM.

Low-Fidelity Simulator for the Standardized Training of Fetoscopic Meningomyelocele Repair.

Fetoscopic meningomyelocele repair in a gas-filled uterus is a new technique performed in very few centers. There are few opportunities as well as ethical prohibitions on the initial development and subsequent refinement of innovative fetal surgery techniques in humans, and using an animal model is both very expensive and logistically difficult. We developed a low-fidelity endoscopic fetal surgery simulation using a plastic doll and pieces of chicken breast to simulate a fetal meningomyelocele, and a polyurethane ball to simulate a gas-filled uterus, along with a standard endoscopy system and instruments. A unique two-port technique with significant differences from the standard laparoscopic surgery procedure was developed and refined through an iterative phase into a standardized methodology, and the simulator was then used to train three other teams to perform standardized fetoscopic meningomyelocele repair. A low-fidelity fetoscopic surgery simulator is a useful tool for developing new fetoscopic operations and for training multidisciplinary fetal surgery teams without the need for extensive use of an animal model. This simulator may be used to further explore the human uterus as a new surgical space for additional fetal surgeries.

Current controversies in prenatal diagnosis 1: in utero therapy for spina bifida is ready for endoscopic repair.

What's already known about this topic? There is level 1 (RCT) evidence for improved neurological outcomes after open fetal surgery for spina bifida versus postnatal surgery. There is a lack of standardization of techniques and comparative outcome data in clinical trials for endoscopic fetal surgery for spina bifida. What does this study add? Different techniques, their strengths, limitations and clinical implications of endoscopic versus open fetal surgery for spina bifida are discussed. Open fetal surgery anticipates postnatal surgery, whereas novel and less invasive endoscopic approaches aim to simplify the technique. More data on long‐term follow‐up of intrauterine closure of spina bifida are needed, and open surgery is one step ahead of fetoscopic approaches.

Outcomes of infants followed-up at least 12 months after fetal open and endoscopic surgery for meningomyelocele: a systematic review and meta-analysis.

To assess the outcomes of infants followed-up at least 12 months after open and endoscopic fetal surgery for the treatment of spina bifida. A searching in The Cochrane Library, LILACS, PubMed and SCOPUS databases for fetal meningomyelocele (MMC) open or endoscopic surgery in humans from 2003 on-wards with follow-up at least 12 months. The rate of the estimated proportions was evaluated by the 95% confidence interval (CI). A total of 19 studies were finally included (17 open and 2 endoscopic surgery). The results suggested that the rate for ventriculoperitoneal shunt placement were 40% (29%, 51%) versus 45% (34%, 56%) for open surgery group and endoscopic surgery group. The rate of hindbrain herniation reversal was 34% (28%, 52%) versus 86% (49%, 97%), the lower extremity function rates for both groups were 47% (30%, 64%) versus 86% (49%, 97%), and bladder dysfunction rates for both groups were 72% (53%, 88%) versus 29% (8%, 64%), respectively. Open and endoscopic fetal surgery for MMC presented similar ventriculoperitoneal shunt rates. Open and endoscopic fetal surgery for MMC presented similar ventriculoperitoneal shunt rates in infants followed at least 12 months.

Advances in fetal surgery.

ABSTRACTThis paper discusses the main advances in fetal surgical therapy aiming to inform health care professionals about the state-of-the-art techniques and future challenges in this field. We discuss the necessary steps of technical evolution from the initial open fetal surgery approach until the development of minimally invasive techniques of fetal endoscopic surgery (fetoscopy).

PROCEDIMIENTOS INVASIVOS EN LA TERAPÉUTICA FETAL

El tratamiento intrauterino o terapia fetal se ha desarrollado solo en los últimos 30 años. En 1963, el Dr. A.W. Liley realizó la primera transfusión intrauterina en un caso de enfermedad hemolítica, constituyendo la primera terapia fetal realizada en la historia. Posteriormente, en la década de los 80 surgen nuevas posibilidades de terapia fetal percutánea y de cirugía fetal abierta para llegar a la década de los 90 con la cirugía fetal endoscópica. En este capítulo revisaremos los diferentes tipos de procedimientos invasivos que incluyen, terapia percutánea y cirugía fetal.

Maternal and fetal safety of fluid-restrictive general anesthesia for endoscopic fetal surgery in monochorionic twin gestations

Study ObjectiveTo review our experience with general anesthesia in endoscopic fetal surgery for twin-to-twin transfusion syndrome (TTTS), and to compare fetomaternal outcome before and after protocol implementation. DesignRetrospective impact study. SettingUniversity-affiliated medical center. MeasurementsData from 85 consecutive patients who underwent endoscopic laser ablation of placenta vessels for severe TTTS were studied. Outcomes were compared in patients before (2000–2007) and after (2008–2012) a change to strict intraoperative intravenous (IV) fluid and liberal vasopressor management. Perioperative parameters (IV fluid administration, vasopressor use, maternal hemoglobin [Hb] concentration); maternal complication rate (respiratory, hemorrhagic); pregnancy outcome; and fetal and neonatal survival were recorded. Main ResultsPatients in the early group (2000–2007; n = 55) received 1634 ± 949 mL of crystalloid fluid intraoperatively, compared with 485 ± 238 mL (P < 0.001; Student’s t test) given to the late group (2008–2012; n = 30). Maternal pulmonary edema and any respiratory distress were seen in 5.5% and 12.7% of patients in the early group, respectively, and in none of the late group patients (P < 0.05; Chi-square analysis). ConclusionsA significant risk of maternal respiratory complications exists after general anesthesia for endoscopic fetal surgery. Judicious fluid management significantly decreases this risk.

Long-term morbidity after fetal endoscopic surgery for severe twin-to-twin transfusion syndrome

Background/Purpose Severe twin-to-twin transfusion syndrome (TTTS) leads to 80% to 100% dual mortality. Endoscopic laser coagulation of connecting vessels improves outcome to 80% survival of at least 1 twin. There is limited long-term follow-up of surviving TTTS patients. The aim of this study was to analyze gestational age-stratified, long-term morbidity in these patients. Methods A retrospective case-control study of TTTS surviving patients (38 patients, 72% follow-up rate) from one center. Perinatal and pediatric records were reviewed, and outcomes were compared with published reports and gestational age-matched controls. Results Forty percent (15/38) had at least 1 major sequela, all but 6 of which were fully resolved at a median follow-up of 4.4 years. There were no permanent cardiac, genitourinary, renal, or respiratory sequelae. All major complications were in patients born <29 weeks. There were no significant differences in complications between this cohort of patients and gestational age (GA)-matched control patients. Conclusions The long-term morbidity of monochorionic twins after fetal laser surgery for severe TTTS is 13%. At a median follow-up of more than 4 years, these children fare no worse than gestational age-matched, non-operated twins and singletons. The degree of prematurity at birth is the best predictor of temporary or permanent sequela in this group of patients.

Fetal endoscopic myelomeningocele closure preserves segmental neurological function

Our aim was to compare the effect of prenatal endoscopic with postnatal myelomeningocele closure (fetally operated spina bifida aperta [fSBA]) versus neonatally operated spina bifida aperta [nSBA]) on segmental neurological leg condition. Between 2003 and 2009, the fetal surgical team (Department of Obstetrics, University of Bonn, Germany) performed 19 fetal endoscopic procedures. Three procedures resulted in fetal death, three procedures were interrupted by iatrogenic hemorrhages and 13 procedures were successful. We matched each successfully treated fSBA infant with another nSBA infant of the same age and level of lesion, resulting in 13 matched pairs (mean age 14 mo; SD 16 mo; f/m=1.6; female-16, male-10). Matched fSBA and nSBA pairs were compared in terms of segmental neurological function and leg muscle ultrasound density (MUD). We also determined intraindividual difference in MUD (dMUD) between myotomes caudal and cranial to the myelomeningocele (reflecting neuromuscular damage by the myelomeningocele) and compared dMUD between fSBA and nSBA infants. Finally, we correlated dMUD with segmental neurological function. We found that, on average, the fSBA group were born at a lower gestational age than the nSBA group (median 32 wks [range 25-34 wks] vs 39 wks [34-41 wks]; p=0.001) and experienced more complications (chorioamnionitis, premature rupture of the amniotic membranes, oligohydramnios, and infant respiratory distress syndrome necessitating intermittent positive-pressure ventilation). Neurological function was better preserved after fSBA than after nSBA (median motor and sensory gain of two segments; better preserved knee-jerk [p=0.006] and anal [p=0.032] reflexes). The dMUD was smaller in fSBA than in nSBA infants (mean difference 24, 95% confidence interval [CI] 15-33; p<0.05), which was associated with better preserved segmental muscle function. Fetal endoscopic surgery is associated with spinal segmental neuroprotection, but it results in more complications. Before considering clinical implementation of fetal endoscopic myelomeningocele closure as standard care, the frequency of complications should be appropriately reduced and results assessed in larger groups over a longer period of time.

Laser Ablation of Placental Vessels in Twin-to-Twin Transfusion Syndrome: A Paradigm for Endoscopic Fetal Surgery

Endoscopic fetal surgery is most commonly used for the treatment of twin-to-twin transfusion syndrome (TTTS), but the surgical techniques can be applied to other forms of fetal surgery. We present our experience with endoscopic fetal surgery over the past 10 years. From 2000 to 2010, 70 endoscopic laser ablations of placental vessels for TTTS were performed. Median number of placental vessels ablated was four. The incidence of preterm rupture of membranes (PROM) was 6%. Overall survival was 70%, with at least one twin surviving in 82%. Tocolysis was used in 73% of patients for a median of 12 hours. The combination of an open surgical approach, Seldinger technique, and uterine plugging led to outcomes similar to other reports, with a significantly lower PROM rate. Although TTTS is the most common application of endoscopic fetal surgery, this approach is applicable for other indications. Insertion and removal of tracheal occlusion balloons for severe congenital diaphragmatic hernia are currently being performed at our institution.

Reflectance spectrometry for real-time hemoglobin determination of placental vessels during endoscopic laser surgery for twin-to-twin transfusion syndrome

Objective The objective of the study was to develop a noninvasive technique to determine hemoglobin (Hb) content through spectral analysis of diffusely reflected broadband visible illumination from individual blood vessels during endoscopic fetal surgery for twin-to-twin transfusion syndrome (TTTS). Methods The reflection of an incoming xenon endoscopic light source was captured through a 630- μm–diameter optic fiber coupled to a fixed grating spectrometer (2-nm resolution). A 450- to 700-nm wavelength range was used for analysis. Three data-capturing methods were studied: (1) fixed-image spectrum capture with fiber aimed at (but not touching) center of a vessel, (2) no-touch scanning perpendicular to the vessel and dynamic spectral capture, and (3) dynamic spectral capture and analysis of the reflectance spectra during brief vessel touch. Results Eight controls (elective laparoscopic and thoracoscopic operations in children aged 1-17 years) were enrolled. Four vessels were analyzed in each case. The brief-touch technique with intensity peak analysis yielded the most reproducible results between multiple vessels in the same patient. Spectrometry was also applied to 2 TTTS patients. The (anemic) donor and (polycythemic) recipient twin fetuses could be differentiated with good correlation between vessels (arteries and vein) of the same fetus. Conclusions It is possible to differentiate donor from recipient placental vessels by spectral analysis of the reflected light through the endoscope using a noninvasive and real-time method. This may improve the accuracy of endoscopic laser ablation of placental vessels in TTTS and may allow instant endoscopic Hb determination for laparoscopic procedures as well.

Fetus‐supporting flexible manipulator with balloon‐type stabilizer for endoscopic intrauterine surgery

Minimally invasive endoscopic fetal surgery enables intrauterine intervention with reduced risk to the mother and fetus. A novel surgical manipulator is described for stabilizing the fetus and restraining it from floating free during endoscopic intrauterine surgery. We designed and fabricated a prototype fetus-supporting manipulator equipped with flexible joint and bending mechanisms and a soft balloon stabilizer. The flexible joint and bending mechanisms enable the stabilizer to reach the target sites within the confined space of the uterus under the guidance of an ultrasound device. The balloon stabilizer could be inserted into the uterus through a small incision. The accuracy evaluation showed that the maximum error of the bending mechanism was as small as 7 mm and the standard deviation of the joint mechanism was just 1.6 degrees. In the experiments using a fetus model, the manipulator could be well controlled with guidance from ultrasound images and its bending mechanism with the balloon stabilizer could be clearly visualized while stabilizing the fetus model. The manipulator has the potential to be used in minimally invasive intrauterine surgery, although further improvements and experiments remain to be carried out.

Gasless Fetoscopy: A New Approach to Endoscopic Closure of a Lumbar Skin Defect in Fetal Sheep

Objective: To develop a new endoscopic approach to the correction of a myelomeningocele-like defect in fetal sheep. Methods: The fetuses of 9 pregnant ewes, with an average gestational age of 115 days, were subjected to a 3.0 × 2.0 cm removal of the skin over the lumbar spine, performed through hysterotomy. The uterus was closed, and three 5-mm endoscopic cannulas, without valve mechanisms, were inserted. In the pilot phase (2 animals), we initially worked exclusively in the amniotic fluid space. In the study phase, we partially withdrew the fetus from the amniotic fluid to completely expose its back. By simply allowing air to enter the amniotic cavity (without gas injection), a working space was created using a uterine lift device. The skin around the defect was dissected, and a biosynthetic cellulose material was applied to cover the area. A continuous suture of the skin was performed to completely hide the material. Results: The combined air/fluid space allowed the skin to be successfully closed in 6 out of 7 cases in the study phase. All fetuses were alive at the end of the procedures. Time to complete the endoscopic part of the procedure fell from 3 to 1 h by the end of this series. Premature birth occurred in 2 of the 4 cases allowed to continue with the pregnancy. Conclusion: A new gasless fetoscopic surgery technique was developed as an alternative to current techniques used for fetal endoscopic surgery.

Endoscopic fetal surgery: in vitro thermic effect of electrosurgical units

The study focused on the safety of electrosurgical devices in endoscopic fetal surgery. The thermic effects of monopolar electric waves were studied in vitro in order to obtain safety indications in terms of mode of intramniotic application of electrical devices (time and number of shots; volts; and distance from tissues to be preserved). A glass model filled with saline solution, and an electrical device with resistor and voltage supply, were constructed to reproduce the physical effects of thermic conductivity in vitro; a Swan-Ganz thermic sensor was used to measure the temperature inside the beuta. Different series of tests were carried out. The maximal increase (8.60 +/- 0.04 degrees C) takes place at the external surface of the resistor (distance: 0 cm), while at 2 cm, the temperature of the saline solution does not change. Our tests demonstrate that in order to avoid any kind of risk during electrosurgical procedures on fetuses, the electrode must be placed at least 0.5 cm from delicate tissues.

Micro Manipulator and Forceps Navigation for Endoscopic Fetal Surgery

In this report, we propose newly devised surgical assistance for endoscopic fetal surgery using a micro manipulator and a new forceps navigation system. For this purpose, we fabricated a prototype of a micro manipulator 2.4mm in diameter. The manipulator on which a laser fiber is mounted bends in any direction using ball joints driven by four wires. We also developed a forceps navigation system in which computer graphics can indicate forceps positions even when they stay outside the endoscopic view. This navigation is expected to make endoscopic surgery much more feasible.

Port insertion and removal techniques to minimize premature rupture of the membranes in endoscopic fetal surgery

Background Premature rupture of membranes (PROM) remains a significant complication of fetal surgery. Rates of 40% to 100% have been reported after both open and endoscopic fetal surgery. We describe a technique of endoscopic port insertion and removal that minimizes trauma to the membranes. Methods Twenty-seven consecutive patients undergoing endoscopic laser ablation for twin-to-twin transfusion syndrome were reviewed. In each case, a minilaparotomy was performed, and the amniotic cavity was entered under direct vision of the uterus using a Seldinger technique. The entry site was carefully dilated to accommodate a 4.0-mm-diameter cannula. A gelatin sponge plug was placed at port removal. Postoperative management and outcome were evaluated. Results Median gestational age at operation was 21.3 weeks. Median operating time was 60 minutes. One patient delivered intraoperatively because of fetal distress. Seventeen (65.4%) patients required postoperative tocolysis (median duration, 12 hours). Median postoperative gestation was 6.5 weeks (range, 1-20 weeks). Only 1 (4.2%) of 24 patients with successful gelatin sponge placement developed PROM. Conclusions Meticulous technique and atraumatic insertion and removal of ports help minimize the risk of postoperative amniotic leak after endoscopic fetal surgery. Our PROM rate of 4.2% contrasts sharply with previously reported rates after similar operations.