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BACKGROUND Twin-to-twin transfusion syndrome (TTTS) could be treated with fetoscopic laser photocoagulation. For patients with placenta located on the anterior wall of uterus, surgical procedures are difficult. To solve this problem, a flexible fetoscope was designed in our department. METHODS The flexible fetoscope was made up of polyurethane, fiberglass and stainless steel coils. The specular body was soft and could bend encountering obstacles, which reduced the possibility of injury to the fetus and placenta. The distal tip of the body could curve from -180° to +270° with the control of the handweel. Three pregnant women of TTTS with anterior placenta was operated with this instrument. RESULT All pregnant women were treated smoothly and gave live twins birth at term. Through angiography, it was demonstrated that the vascular connections on the surface had been coagulated. CONCLUSION The flexible fetoscope was a novel instrument in treating TTTS, especially for the anterior placenta.

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.

Endoscopic surgery has become an accepted major type of minimally invasive surgery. However, complications arising from heat generated by sources of endoscopic illumination can include surgical fire or burns, and intense illumination during ob-gyn/fetoscopic surgery might damage fetal ocular development. Fiber-optic bundles for illumination within the endoscope essentially double the outer diameter of the endoscope, which is a major obstacle to miniaturization and decreasing costs. Light cables also decrease the maneuverability of the endoscope We developed a novel endoscope with ultralow illumination to visualize dark body cavities and investigated its feasibility in vivo. An adaptor was created to connect a conventional endoscope to an ultrahigh-sensitivity camera developed by the Japan Broadcasting Corporation (NHK) for broadcasting. The ability to visualize rabbit visceral blood vessels in vivo by the new prototype and by a current endoscope under ultralow illumination provided by a standard light source was compared. In addition, the performance of the two endoscopes was compared using only an extracorporeal flashlight without any specific light source placed within body cavities. The new endoscope could visualize the target under ultralow illumination of approximately 100 lx. Very little could be visualized using the current endoscope, whereas the prototype generated clear images of the rabbit blood vessels under both ultralow illumination and extracorporeal illumination provided by a flashlight. The potential for damage caused by a light source can be minimized using our new endoscope, which results in safer and less invasive procedures. Further studies are under way to develop a nonilluminated endoscope without a light cable or source and to miniaturize the camera to decrease costs and improve the maneuverability of the entire endoscope system.

Background 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. Methods 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. Results 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 ◦ . 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. Conclusions The manipulator has the potential to be used in minimally invasive intrauterine surgery, although further improvements and experiments remain to be carried out. Copyright  2008 John Wiley & Sons, Ltd.

Fetal urinary tract obstruction with oligohydramnios produces pulmonary hypoplasia and renal dysplasia. Decompression of the obstructed urinary tract may restore amniotic fluid and allow lung growth, but transabdominal catheter shunt decompression is often inadequate and does not allow for cycling of the bladder, while open procedures cause significant maternal morbidity. Disruption of the anatomic obstruction, usually posterior urethral valves in a male fetus, would be ideal but has proven technically difficult. Here we describe a new technique of percutaneous fetal cystoscopy and disruption of posterior urethral valves, and the case report of our first application of this technique. We pre-sent a case of a 17-week male fetus with posterior urethral valves which underwent fetal cystoscopy for mechanical disruption of posterior urethral valves. This minimally invasive approach to disruption of posterior urethral valves in a fetus is a novel method for decompressing the urinary tract. The technique offers a minimal degree of maternal morbidity and, if instituted early enough, can restore amniotic fluid volume, avert fatal pulmonary hypoplasia and may preserve renal function.

Intermittent fetal tracheal occlusion is considered one actual therapeutic option for a severe isolated congenital diaphragmatic hernia (CDH). 1 To reduce maternal risks such as maternal hemorrhage, premature rupture of membranes, and preterm labor, minimally invasive procedures with extremely thin endoscopes have been introduced. 1,2 The thinnest cannula used up to now was 3.3 mm with an endoscope of 1.2 mm.' This procedure is usually guided by conventional 2-dimensional ultrasonography (2DUS). Recently, 4-dimensional ultrasonography (4DUS) was used to guide invasive obstetric procedures such as amniocentesis, chorionic villus sampling, and cordocentesis, 3,4 as well as cauterization of an umbilical cord in twin-twin transfusion syndrome.5 The advantage of 4DUS may be related to the reduction of procedure time and the ability to use thinner endoscopes. We report another possible contribution of 4DUS in the guidance of introduction of a thinner fetoscope (1.0 mm) into the fetal oral cavity.

The development of fetal surgery has led to promising therapeutic options for a number of congenital malformations. However, preterm labor (PTL) and premature rupture of membranes continue to be ubiquitous risks for both mother and fetus. To reduce maternal morbidity and the risk of prematurity, minimal access surgical techniques were developed and are increasingly employed. Congenital diaphragmatic hernia (CDH), obstructive uropathy, twin-to-twin transfusion syndrome (TTTS), and sacrococcygeal teratoma have already been successfully treated using minimal access fetal surgical procedures. Other life-threatening diseases as well as severely disabling but not life-threatening conditions are potentially amenable to treatment. The wider application of minimal access fetal surgery depends on a continued improvement in technology and a better understanding of complications associated with fetal intervention.

Current protocols for fetal surgery require cesarean section and partial fetal extraction, both of which impart significant risks to the mother and fetus. Endoscopic fetal surgery is less invasive and will likely reduce some of these risks, but the technical difficulties and feasibility in a primate model have yet to be explored fully. Four pregnant baboons (95 days gestation) were anesthetized, their uteruses exposed via an abdominal incision, and blunt-tipped flanged endoscopic ports inserted. Amniotic fluid was removed, and warmed saline was infused to dilate the uterus. To evaluate instrumentation and wound closure, the tip of the snout was externalized and bilateral cleft lip-like defects made. The lips were then endoscopically repaired by suture (Endostitch, U.S. Surgical) or unique nonpenetrating clips (VCS, U.S. Surgical). The saline was then removed, amniotic fluid returned, and the ports carefully removed. After 4 weeks, the fetuses were delivered and evaluated. Eight cleft lip-like defects were successfully repaired in all four cases. Operative time averaged 83 min. No infections, amniotic leaks, or adhesions developed. Survival was 50% with two fetuses delivering within 48 hours postoperatively: one from preterm labor, the other with fetal demise from retroperitoneal hemorrhage after operative blunt abdominal trauma. We demonstrate the feasibility of endoscopic fetal surgery in primates. The use of blunt-tipped flanged ports provides a fluid tight seal and allows appropriate closure of the fetal membranes, but requires laparotomy and uterine exposure. Distension of the uterus with warmed saline affords a larger operating field, enhancing visualization and instrumentation of the fetus. Grasping the fetus through the exposed uterus gives excellent control for repair. However, such control is also needed in a percutaneous approach. Further instrumentation development is needed to accomplish similar control for the percutaneous approach.

Endoscopic fetal surgery may reduce preterm labor associated with open hysterotomy but is partially limited by current visualization technology. We investigated a three-dimensional (3D) imaging system coupled to a head-mounted display (3D-HMD) and also employed a computer-controlled zoom endoscope for noninsufflated amnioscopy. Pregnant sheep were prepared in aseptic fashion for general anesthesia. Uterine access was obtained following maternal laparoscopy. A 10-mm zoom endoscope (Vista Medical Technologies, Carlsbad, CA) was used to examine the fetus and uterine contents. Fetal limbs were exteriorized for microsurgery. A new system (Vista Medical Technologies) was attached to an operative microscope, permitting projection of a 3D image via an HMD. The fetus and umbilical cord were inspected using the zoom endoscope, which changes the depth of focus under computer control. Basic manipulations of the fetus and cord were easily completed. Real-time 3D fetal imaging was accomplished. The added depth perception enabled detailed fetal and placental examination, fostering manipulation of the fetus and cord. The HMD was adjusted to fit several surgeons, permitting a natural operative posture. This unit has the capacity to display any video, CT, MR, or ultrasound image as a picture-in-picture. The success of minimally invasive fetal surgery is in part dependent on the development of video technologies capable of providing both magnification and optimal resolution. The zoom endoscope affords excellent visibility of multiple surgical targets without instrument repositioning. A 3D HMD system such as this provides greater anatomic detail and an appreciation of fetal movements that may make intrauterine procedures more feasible.

Objective To determine whether incubation in the integrated EmbryoScope time-lapse monitoring system (TMS) and selection supported by the use of a multivariable morphokinetic model improve reproductive outcomes in comparison with incubation in a standard incubator (SI) embryo culture and selection based exclusively on morphology. Design Prospective, randomized, double-blinded, controlled study. Setting University-affiliated private in vitro fertilization (IVF) clinic. Patient(s) Eight hundred forty-three infertile couples undergoing intracytoplasmic sperm injection (ICSI). Intervention(s) No patient intervention; embryos cultured in SI with development evaluated only by morphology (control group) and embryos cultured in TMS with embryo selection was based on a multivariable model (study group). Main Outcome Measure(s) Rates of embryo implantation, pregnancy, ongoing pregnancy (OPR), and early pregnancy loss. Result(s) Analyzing per treated cycle, the ongoing pregnancy rate was statistically significantly increased 51.4% (95% CI, 46.7–56.0) for the TMS group compared with 41.7% (95% CI, 36.9–46.5) for the SI group. For pregnancy rate, differences were not statistically significant at 61.6% (95% CI, 56.9–66.0) versus 56.3% (95% CI, 51.4–61.0). The results per transfer were similar: statistically significant differences in ongoing pregnancy rate of 54.5% (95% CI, 49.6–59.2) versus 45.3% (95% CI, 40.3–50.4) and not statistically significant for pregnancy rate at 65.2% (95% CI, 60.6–69.8) versus 61.1% (95% CI, 56.2–66.1). Early pregnancy loss was statistically significantly decreased for the TMS group with 16.6% (95% CI, 12.6–21.4) versus 25.8% (95% CI, 20.6–31.9). The implantation rate was statistically significantly increased at 44.9% (95% CI, 41.4–48.4) versus 37.1% (95% CI, 33.6–40.7). Conclusion(s) The strategy of culturing and selecting embryos in the integrated EmbryoScope time-lapse monitoring system improves reproductive outcomes. Clinical Trial Registration Number NCT01549262.

Embryoscopy is a new technique that allows direct visualization of the embryo/fetus as early as the first trimester of pregnancy. A rigid fiberoptic endoscope is passed transcervically into the extracoelomic cavity and is used to identify developmental milestones and diagnose structural anomalies. Fetal blood sampling has also been performed, and using this technology, has established the feasibility of access to the human embryonic circulation. Future applications for embryoscopy include direct targeted embryonic or fetal interventions, such as gene or stem cell therapy.

To demonstrate the efficacy of first-trimester needle embryofetoscopy (or embryoscopy) for prenatal diagnosis in a continuing pregnancy.A patient at risk for giving birth to an infant with Robert's syndrome was referred for prenatal diagnosis at 12 weeks of gestation.Transabdominal embryoscopy and amniocentesis were performed. Direct visualization of the embryo was achieved and no gross limb or facial abnormalities were seen. Chromosome studies of the amniotic fluid revealed a normal male 46, XY. Special studies with C-banding and DAPI techniques revealed no evidence of premature separation of centromeres. Two- and three-dimensional ultrasound also demonstrated no gross limb or facial abnormalities.This case confirms the efficacy of embryoscopy as a simple and relatively low-risk approach to first-trimester diagnosis for continuing pregnancies.

Objective: The aim of the study was to investigate the efficacy of flexible embryofetoscopy for visualization of the first trimester human embryo and fetus. Method: Twelve pregnant women scheduled for legal termination of pregnancy at 6–12 weeks' gestation were included in the study. A flexible fiber optic endoscope with an eyepiece connected to a monitor was used. The sterile endoscope was passed transcervically under ultrasound guidance through the chorion into the chorionic cavity. Embryos/fetuses were observed directly through the intact amniotic membrane. Result: Successful embryofetoscopies with clear visualization of the embryo or fetus were accomplished in 50% of cases. There were no procedure-related complications. Conclusion: Preliminary experience employing transcervical flexible embryofetoscopy for direct visualization of the first trimester human embryo and fetus suggest that this technique may be used for the early identification of congenital anomalies suspected by ultrasound and is expected to offer opportunities for embryo/fetal tissue sampling as well as for gene and cell therapies.

Our objective was to explore the feasibility of using both transvaginal endoscopy and transabdominal needle embryofetoscopy for early prenatal diagnosis. Our experience with both terminating and continuing pregnancies is presented in this report. Following the granting of informed consent, patients undergoing first-trimester terminations were invited to participate in this program. Initially, a transvaginal endoscope was used in these studies: a rigid fiberoptic endoscope 30 cm in length with a diameter of 1.5 mm. Subsequently, a specially designed 16-gauge, double-barrel needle sheath, equipped with a 0.8-mm fiberoptic endoscope and a customized 27-gauge heparinized needle were used. In either case, the endoscope was passed under ultrasound guidance into the exocelomic space, from which the anatomy of the embryo/fetus was scrutinized. For continuing pregnancies, patients were selected when at high risk for various dysmorphology syndromes. To date, we have successfully performed more than 300 transvaginal procedures, successfully visualized the fetus in 95% of cases, and verified sonographically suspected anomalies in all of the five cases studied. We have also performed 20 transabdominal procedures, 15 in terminating pregnancies and five in continuing pregnancies, without adverse effects. Our experience establishes the feasibility of first-trimester diagnostic endoscopy. This new development is expected to serve as a prelude for further studies that attempt to diagnose and treat congenital diseases in early pregnancy. Potential applications include gene and stem-cell therapy at a time when the embryo is immunologically naive.

To study the feasibility, learning curve, and safety of fetoscopy, so that fetal surgery can be confidently performed in ongoing pregnancies. Fetoscopy was performed at 12–20 weeks of gestation, in 12 women with fetal congenital malformations and/or for termination of pregnancy, under local anesthesia using fine fetoscopes ranging from 1 to 2-mm diameter. The fetal parts and placenta were examined for clarity of vision, identification, and anomalies. Fetoscopy required great skill, patience, and extensive use of ultrasound for correct orientation. Visualization was better with endoscope of 2-mm diameter. Laser coagulation of placental vessels using diode laser system was possible in the last two cases. There were no major complications. Fetal endoscopy is a feasible procedure, safe in experienced hands but has an appreciable learning curve.

Objective To improve neonatal outcome using ultrathin fetoscope for laser treatment of twin-to-twin transfusion syndrome. Methods Retrospective cohort study of a series of 80 cases of twin-to-twin-transfusion syndrome prior to 26-weeks' gestation subjected to laser coagulation by means of a 1.0/1.2 mm fiber fetoscope with a sheath sectional area 2.65 mm(2)/3.34 mm(2) (n=27) and a 2.0 mm classic lens fetoscope with a sheath sectional area: 6.63 mm(2)/11.27 mm(2) (n=53). Results The survival rates of at least one twin in the compared groups were 94.4% (classic optic) and 100% (ultrathin optic), for both twins: 75.5% and 83.3%, respectively. By decreasing sheath diameter a pregnancy was prolonged by an average of 21.3 days (P=0.0045), with a resulting increase in the recipient's weight of 389 g (P=0.0049) and an increase in the donor's Apgar score. However, the intervention with ultrathin optic took 11 min longer (P=0.031). Conclusion The reduction of the iatrogenic damage of the amniotic membrane using ultrathin fetoscope with a small sheath, significantly improves the neonatal outcome after laser treatment of twin-to-twin-transfusion syndrome. The operator should only commence working with the 1 mm fetoscope after the learning curve has been accomplished.

OBJECTIVE: Our aim was to develop and evaluate a transabdominal endoscopic technique to visualize the embryo or fetus with thin-gauge needles and submillimetric fiberoptic endoscopes. METHODS: Under ultrasonographic guidance, an 18- or 19-gauge thin-wall needle was introduced into the uterus of 28 patients undergoing first-trimester or early second-trimester termination of pregnancy. A 0.7 mm endoscope was threaded through the lumen of the needle after removal of the stylet. Visualization of the embryo-fetus was attempted before 14 weeks' gestation ( n = 20). From 16 to 20 weeks ( n = 8), the needle and endoscope were directed to the placental insertion of the umbilical cord, and a cordocentesis was performed. RESULTS: Excellent visualization of the surface anatomy of fetuses from 7 to 13 weeks was obtained in 85% of cases (17/20). A diagnosis of Meckel-Gruber syndrome was made at 11 weeks' menstrual age by visualizing postaxial polydactyly and an occipital encephalocele. Endoscopically assisted cordocentesis allowed visualization of the lumen of the umbilical vein and of the blood flow within it. CONCLUSION: Endoscopic visualization of the embryo or fetus can be performed transabdominally in the first trimester with small needle-delivered endoscopes. This represents a clear advantage over previous endoscopic approaches to the human pregnancy. Potential applications of this technique include a precise description of fetal anatomy and physiologic features, diagnosis of anomalies, and therapeutic fetal interventions.

Fetoscopic techniques may broaden the indications for prenatal surgical intervention by obviating the risks of hysterotomy. For example, congenital obstructive uropathy has been treated by open vesicostomy and percutaneous catheter placement. The open approach is appropriate only for highly selected fetuses because of the inherent risks, whereas catheter drainage, though a safer procedure, is only useful for short-term therapy late in gestation due to frequent catheter obstruction and migration. The natural history of congenital obstructive uropathy mandates the need for improved therapy earlier in gestation, in order to salvage fetuses who would otherwise die of renal failure and pulmonary hypoplasia. We have developed a potential solution to this problem in which surgery is performed on the fetus without the risks of hysterotomy. Endoscopic fetal surgery uses a telescopic lens and operating instruments that are passed through small "ports" in the uterus. A bubble of CO2 is used to displace amniotic fluid and provides excellent visualization in a magnified field. This approach is considerably less invasive than open fetal surgery and, therefore, is less likely to provoke preterm labor. In this study we corrected obstructive uropathy in midgestation fetal lambs using a new, expandable wire mesh stent that is placed endoscopically and should provide more reliable bladder drainage than existing catheters. The fetoscopic surgical approach can potentially expand the indications for in utero surgery by decreasing fetal risks, facilitating intervention earlier in gestation, and reducing preterm labor. As a consequence, the potential now exists to correct non-life-threatening malformations in utero.

This paper describes a fast image mapping system that integrates endoscopic image mosaics with three-dimensional (3-D) ultrasound images for assisting intrauterine laser photocoagulation treatment. Endoscopic laser photocoagulation treatment has a good survival rate and a low complication rate for twins. However, the small field of view and lack of surrounding information makes the identification of vessel anastomosis difficult. We have developed an extended visualization system with the fusion of endoscopic image mosaics with a 3-D ultrasound-image model. Fully automatic and fast calibration is used for endoscope calibration in fluid. The 3-D spatial position of the endoscopic images and the ultrasound image are tracked by a 3-D position tracking device. The mosaiced endoscope images are registered to the surface of the 3-D ultrasound placenta model by using a fast GPU-based image rendering method and a seamless multi-images processing. Experimental results show that the system may provide an improved and efficient way of planning and guidance in laser photocoagulation treatment.

Minimal invasive intrauterine interventions have gained their place in fetal medicine. Interventions on the placenta, umbilical cord, fetal membranes or on the fetus require special endoscopes with their respective sheaths, cannulas and additional instruments. Instruments for fetal therapy are purpose designed for the procedure of interest and most gynaecologists are therefore not familiar with them. We review the currently available instrumentation used during operations for complicated monochorionic multiple pregnancies, congenital diaphragmatic hernia, amniotic band syndrome, urinary tract obstruction and hydrothorax.

Objective: The most common complication of intrauterine tracheal balloon occlusion is the preterm premature rupture of membranes (PPROM) which increases the rate of neonatal morbidity and mortality. Ultrathin fetoscopy may be a method of reducing the risk of PPROM. Materials and Methods: The operation was performed at the 27th week of gestation after sedation and relaxation of a fetus with bilateral congenital diaphragmatic hernia and with the liver lifted upwards into the thorax. An ultrathin sheath with a 1.2-mm fetoscope was used under real-time 3-D ultrasound guidance. The patient delivered in the 38th week of gestation and did not display PPROM after surgery until delivery. Conclusion: Fetal tracheal occlusion using ultrathin fetoscopic equipment in combination with real-time 3-D ultrasound may reduce the risk of PPROM.

Fetal surgery is receiving considerable attention. However, surgeons must have great skill to perform this surgery. For assisting with the operation, the three-dimensional (3D) endoscope is very useful because it allows the surgeon depth perception. However, the diameter of existing 3D endoscopes is approximately 10 mm. Therefore, the authors have developed a high-resolution, thin, 3D endoscope for use in fetal surgery.The authors' system uses two 1/10-in. micro charge-coupled device (CCD) cameras at the tip of the endoscope and achieves a diameter of 5.4 mm. The endoscope's angle of convergence is 2.6 masculine, which very closely approximates the angle of convergence for humans. Thus, the surgeon experiences little visual fatigue. The view angle is 87 masculine.The authors compared image quality and depth perception between their system and conventional 3D and 2D endoscopes. Theoretical investigation of image quality allowed the surgeon to distinguish a line 0.2 to 0.25 mm wide. Furthermore, the depth perception with the thin 3D endoscope was almost the same as with an 11-mm normal 3D endoscope. In addition, with the 3D endoscope, a higher percentage of questions were answered correctly in the depth perception evaluation experiment in a water environment than with the 2D instrument.According to these experiments, the thin 3D endoscope has a sufficiently high image quality and depth perception even in a water environment.

Objective To assess outcome after fetoscopic laser coagulation (FLC) of placental vascular anastomoses with the 30° fetoscope in mid-trimester severe twin-to-twin transfusion syndrome (TTTS) with completely anterior placenta compared with the regular 0° fetoscope in TTTS with other placental locations. Methods This was a prospective study of 176 consecutive monochorionic twin pregnancies undergoing FLC for severe TTTS. Of these, 51 patients required use of the 30° fetoscope (study group) and 125 placental locations permitted use of the 0° fetoscope (controls). Results The two groups had very similar outcomes. The median gestational age at FLC in the study group vs. control group was 21.0 (range, 17.4–24.6) weeks vs. 20.6 (range, 15.9–24.6) weeks. Both fetuses survived in 58.8% (30/51) of study patients vs. 66.4% (83/125) of controls. At least one fetus survived in 84.3% (43/51) of study patients and 88.8% (111/125) of controls (P = 0.45). Study patients delivered at a median of 34.1 (range, 25.0–38.4) weeks and controls at 34.0 (range, 25.0–40.3) weeks' gestation. Conclusions Use of a 30° fetoscope for FLC in cases of technically challenging extensive anterior placentation is associated with an outcome that is very similar to that achieved when a 0° fetoscope is used in cases of more favorable placental location. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.

Recent typical therapy for twin-to-twin transfusion syndrome (TTTS) is selective laser photocoagulation of anastomotic communicating vessels on the placenta using the fetoscopic approach. The difficulty of a conventional laser device approach for this procedure depends significantly on the placental location, so a new robotized device is required to bend the direction of laser irradiation flexibly within the narrow uterus.The authors designed a miniature bending mechanism impelled by a wire-guided linkage driving method that provides a stable procedure for bending laser irradiation from -90 degrees to 90 degrees . Using this bending mechanism, the authors developed a bending manipulator with a diameter of 3.5 mm and a hollow central channel with a diameter of 0.8 mm for passing a glass fiber for neodymium:yttrium-aluminum-garnet (Nd:YAG) laser photocoagulation. The bending mechanism is motorized by an electrical actuator and controlled by a grip-type interface with a small joystick. The robotized tip's part and the actuator's part are easily separable for cleaning and sterilization.In performance evaluations of the manipulator, the bending characteristics with a glass fiber were examined. The bending range was -52.6 degrees to 80 degrees, with a very small hysteresis error, and the bending repeatability error was 0.5 degrees +/- 0.2 degrees, which corresponds with the high accuracy of 0.2 +/- 0.1-mm positioning error at the glass fiber's tip. In the evaluation of Nd:YAG laser photocoagulation, the study confirmed that the manipulator performed effective laser photocoagulation of the placental phantom surface (underwater chicken liver). The large bending range, reaching 80 degrees, enabled a flexible approach from various directions with a high irradiation efficiency of no less than 96.6%.The authors' original miniature bending manipulator can change the laser irradiating direction with highly repeatable positioning accuracy for speedy, safe, and effective vessel occlusion in clinical practice.

Background/Purpose: Prenatal tracheal occlusion currently is being assessed as a treatment modality for congenital diaphragmatic hernia (CDH). The development of a totally percutaneous fetoscopic access system would help avoid the need for maternal laparotomy and reduce the morbidity rate of fetal surgical procedures for the mother. Laparoscopic radial expansion sheaths and Seldinger technique– based vascular catheters both have been advocated as means of achieving amniotic cavity access. The authors have investigated these 2 systems in an attempt to develop a reliable method for achieving safe percutaneous fetoscopic access and present the first successful attempt to deploy an intratracheal balloon using an entirely percutaneous approach through a single port in an ovine model. Methods: A number of prototype systems were evaluated sequentially over a 3-year period in an ovine model: (1) the radially expanding InnerDyne step port system, (2) a new rigid cannula with a bulbous/sharp end preloaded onto the radially expanding InnerDyne port, (3) a conical removable addition to the rigid cannula in 2, (4) a modified bulbous/ sharp ended cannula incorporating a circumferential protective insert, (5) a rigid split sheath with the radially expanding port placed through the lumen of the split sheath, (6) a flexible introducer and dilator with the split sheath (used in the Seldinger placement of central lines), and (7) a 2-needle approach using a superelastic shape-memory alloy NickelTitanium wire with the flexible dilator and sheath, incorporating a side perfusion port. For balloon tracheal occlusion, live anaesthetized time-mated pregnant ewes were used at 110 days’ gestation. Tracheobronchoscopy was achieved using a 3-mm 0° telescope, and the cutaneotracheal tract was secured by a 3.3-mm sheath incorporating a side-perfusion port. The rigid telescope was replaced by a flexible choledochoscope preloaded with a silicone balloon. The balloon was deployed 2 cm above the carina proximal to the right upper lobe bronchus. Results: The many problems encountered in the evolution of the preferred system related mainly to separation and tenting of the chorioamniotic membranes in the ovine uterus and inconsistent access to the fetal parts of interest. Each resulted in significant modifications to our approach. Furthermore, the use of rigid access devices commonly caused fetal injury. Successful access to the intrauterine cavity and cannulation of the trachea was achieved consistently with minimal trauma, irrespective of fetal position by method 7. Multiple port placement allowed visualization of the entry of all components of the system confirming minimal chorioamniotic membrane separation and tenting. Single port tracheal occlusion was undertaken first on 6 cadavers before being performed successfully on 3 live anaesthetized ewes. Fetoscopic access and cannulation of the trachea was achieved consistently in all live animals irrespective of fetal position. Conclusions: This modified Seldinger technique using the unique properties of the memory-shaped alloy wire for initial uterine access offers a safe method for the percutaneous placement of fetoscopic ports in the ovine model for prenatal intervention. Successful placement of a tracheal balloon entirely through a single percutaneously placed port represents a further advance in prenatal therapy for CDH.

Currently, amnioinfusion fluids used in operative fetoscopy usually are preheated to body temperature. As the complexity of procedures increases, purposed designed devices should be designed that allow control of pressure and temperature during amnioinfusion or amnioexchange. In the current study, a prototype amnio-irrigator and fluid heater were evaluated.The medical fluid heater heats fluid by conduction up to 37 degrees C. The maximum irrigation pressure and flow rates can be preset. Actual irrigation pressure (0 to 30 mm Hg) and flow rate (0 to 300 mL/min) can be read on the front panel. A series of ex vivo experiments were set up to determine the relationship between the flow rate (FR) and lumen of the instruments as well as the maximum flow rate (MFR) with and without the pressure control. Further, the relationship between FR and the irrigation pressure (IP) was determined. In an artificial pseudoamniotic sac the relationship between FR and change in temperature was measured, with and without the use of the medical fluid heater.When the IP was limited to 24 mm Hg, FR and pressure were correlated (r = 0.34; P.001). The larger the functional lumen of the fetoscopic instrumentation, the higher the flow (r = 0.43; P.001) and the lower the increase in IP (r = -0.47; P.001). A quadratic relation between flow and temperature was observed both for preheated fluid as when using the fluid heater (r(2) = 0.71 and r(2) = 0.88; P.001). However, at low flow rates, a thermal decrease of over 3 degrees C was observed when the fluid heater was not used.The current study quantifies an expected relationship between the diameter of the irrigation channel and achievable flow rates. It also shows that a medical fluid heater is needed when strict control of temperature would be desired.

Objective: To describe a minimally invasive micro-endoscopic technique for fetal skin biopsy and direct examination for a lethal skin condition. Materials and Methods: Direct fetoscopic examination of a fetus was undertaken along with full thickness skin biopsies at 19 weeks’ gestation. Results: No phenotypic expressions of the lethal condition were visualized and six full thickness skin biopsies were collected. Pathological examination revealed normal skin structures not consistent with junctional epidermolysis bullosa (JEB). Conclusion: Minimally invasive examination with the 1 mm endoscope allows direct fetal phenotypic evaluation, full thickness skin biopsies, with risks similar to amniocentesis.

Background Shortening the prenatal disease course of severe aortic and pulmonary stenoses by balloon valvuloplasty may diminish their postnatal expression. The purpose of this study in fetal sheep was to assess the feasibility of fetoscopic and open transumbilical fetal cardiac catheterization guided by fetal transesophageal echocardiography to provide alternative approaches for human fetal cardiac intervention. Methods and Results We studied a total of nine fetal sheep (95 to 103 days of gestation; term=145 to 150 days) and performed transumbilical fetal cardiac catheterization by a minimally invasive fetoscopic (n=6) or an open fetal surgical approach (n=3). Monitored by fetal transesophageal echocardiography, with an 8F or 10F, 10-MHz intravascular ultrasound catheter we placed guidewires and interventional catheters via the umbilical arterial route into the fetal heart. In three of the fetuses, we created supravalvar pulmonary artery stenosis by open fetal cardiac surgery. After fetal and maternal recovery, we exteriorized these fetuses and performed open transumbilical fetal cardiac catheterization with successful pulmonary arterial angioplasty in two. Three fetuses survived fetoscopic transumbilical catheterization for 1 or 2 days and died most likely of blood loss after sheath dislodgment (n=1) or removal (n=2). By securing the sheath insertion site with a suture, we prevented sheath dislodgment and minimized bleeding during sheath removal in three fetuses. These fetuses then survived fetoscopic transumbilical fetal cardiac catheterization for 1 to 2 weeks before being killed. Conclusions This study in fetal sheep demonstrates that fetoscopic and open transumbilical fetal cardiac catheterization are feasible and, guided by fetal transesophageal echocardiography, provide potential alternative approaches for human fetal cardiac intervention.

In utero open surgery can salvage many fetuses with life-threatening anomalies. This approach carries risks, especially from preterm labor induced by the hysterotomy incision. In an effort to decrease uterine injury during hysterotomy, we developed techniques for endoscopic manipulation of the fetus. We developed these methods in fetal lambs. The uterus was exposed and insufflated with CO2. As a model for in utero surgery, a simulated cleft lip was created and immediately repaired using intracorporeal suturing and knot-tying procedures. The techniques for endoscopic suture placement and knot-tying were based on microsurgical principles. We also designed and created several specialized instruments to facilitate precise work in this highly magnified surgical field. The novel techniques of endoscopic fetal surgery described here offer an alternate approach to fetal intervention. Our future goals include the application of these techniques to a nonhuman primate model and the development of percutaneous access methods.

The technics of fetoscopy and fetal skin biopsy have expanded our capabilities for antenatal diagnosis of certain hereditary skin disorders (genodermatoses). The fetus and placenta can be visualized directly and skin biopsy specimens can be obtained for light and electron microscopic studies, tissue culture, and biochemical analysis. These technics have been utilized successfully in the prenatal diagnosis or exclusion of epidermolysis bullosa, epidermolytic hyperkeratosis, and harlequin ichthyosis in fetuses known to be at risk for these disorders, and they offer tremendous potential for prenatal diagnosis in a variety of other genodermatoses. Studies of tissue obtained by this procedure will undoubtedly expand our knowledge of the morphogenesis and biochemistry of fetal skin and will provide needed baseline data for the further development of these technics.

Attempts were made upon a small series of human patients to introduce an endoscope through the anterior abdominal wall and uterus at 16 to 18 weeks of intrauterine pregnancy for fetal observation and biopsy. The results of that procedure were technically successful but the fetus died in each case. Research and development are needed to improve this potentially valuable diagnostic technique.

Two male fetuses at risk for ornithine carbamyl transferase deficiency (OCTD) were investigated by a fetoscopic technique for fetal liver biopsy. In one OCT activity was absent in the liver and the pregnancy was terminated. Necropsy confirmed the presence of OCTD. In the other fetus, liver OCT activity was normal and a healthy baby was delivered at term.

Chorionic villus sampling (CVS) is a new prenatal diagnostic technique which is performed in the first trimester of pregnancy. Traditional methods of prenatal diagnosis, including amniocentesis and fetoscopy, must be performed in the midtrimester. In concert with the development of DNA methods of fetal cell analysis, first trimester fetal diagnosis utilizing CVS offers many advantages over traditional mid-trimester techniques. In addition, CVS may potentially allow therapeutic intervention to prevent or ameliorate some congenital defects.

A total of 105 fetoscopies were performed either prior to therapeutic abortions or, in 29 cases, for diagnostic purposes. In these latter cases the fetuses were at increased risk for congenital syndromes, limb deformities, cleft lip and palate or neural-tube defects. The procedure is performed transabdominally under local anaesthesia. The studies confirmed the practicability of the fetoscopic technique as described. Done under direct vision, using simultaneous real-time ultrasound-scanning, the fetoscope can be introduced without damage to fetus and placenta. In diagnostic cases, a total visualization of the entire fetus is not always necessary, as recognition and examination of specific fetal parts is often sufficient for prenatal diagnosis. Viewed in this way, the rate of diagnostic fetoscopies reached 78%. In these cases, the targets chosen for inspection could, in fact, be reached by the fetoscope. A total inspection of the fetus was aimed at in those fetoscopies performed prior to planned abortions in order to gain practice, and this was achieved in 42% of cases. In 5 of the 29 patients already mentioned, the pregnancy was terminated immediately after fetoscopy, and in 24 cases pregnancy was continued. Abortions have so far been recorded in 4 cases, not all of which were necessarily due to the fetoscopy, however. In general, fetoscopy appears to hold less danger for mother and child than had previously been anticipated.

A new instrument and method for amnioscopy is described. Amnioscopy increases the precision and safety of prenatal transfusion and opens new avenues for fetal research and the photographic recording of prenatal events.

A procedure enabling the direct endoscopic examination of rat fetuses in utero without the need for surgical externalization of the uterus is described.

Fetal blood unmixed with maternal blood or amniotic fluid was obtained by direct-vision fetoscopy in 22 consecutive cases at 15--22 weeks' gestation; the investigation was done either for prenatal diagnosis or before therapeutic abortion. Fetal plasma factors VIIIC and IX averaged 50 I.U./dl (S.D. 12.8) and 12.5 I.U./dl (S.D. 2.4), respectively. Two male fetuses at risk of haemophilia had normal factor VIIIC levels by these criteria, and both pregnancies ended in the birth of a normal boy. Five others gave 3 normal and 2 haemophilic results, which were confirmed in two of the three terminated pregnancies.

Throughout pregnancy, fetal medical care is compromised by the inaccessibility of the fetus. In the second trimester, the diagnosis of fetal disease could be significantly improved by direct visualization of the fetus (fetoscopy) and by direct access to fetal tissue or blood. This report documents our initial experiences with second-trimester fetoscopy and fetal blood sampling in the pregnant ewe and in the pregnant woman. The potential diagnostic and therapeutic applications of fetoscopy and the current limitations and problems identified in our studies are presented. In light of our experience, and because of the many unanswered questions which remain concerning the safety and methodology of fetoscopy, we conclude that further instrument modification and research are required before second-trimester fetoscopy and fetal tissue sampling can be accepted as a simple, safe, and practical clinical approach.

One of the major goals in modern obstetrics is to provide more detailed information on prenatal fetal physiology. Since 1972, more than 200 amniocenteses were performed in our department of Obstetrics and Gynecology. The importance of prenatal genetic diagnosis has been well recognized, indicating the necessity of the development of other methods to obtain further direct data on the fetus within the uterine cavity. Among gynecological endoscopies, fetoscopy which is the direct visualization of the fetus by introduction of an endoscope into the amniotic cavity can be expected to obtain direct information from the uterine environment in pregnant women. With our newly developed fetoscope, we investigated the clinical indications and contraindications of fetoscopy as well as future possibilities of this endoscope. Our present study indicates that further development and future benefits of fetoscopy entirely depend on the progress of laboratory techniques which can provide more accurate data through specimens obtained by fetoscopy.

The amount of fetal-maternal transfusion during invasive intrauterine diagnostic instrumentation was determined by measuring the increase in maternal serum alpha-fetoprotein (delta AFP) caused by the procedure. Fetal liver biopsy or fetoscopy for purposes other than blood sampling caused a mean delta AFP of 11.4 ng/ml and 34.2 ng/ml, respectively. Fetoscopy with fetal blood sampling produced a mean delta AFP of 211.8 ng/ml, while fetoscopy followed by placentesis caused a mean delta AFP of 462.8 ng/ml (representing a 1.07 ml fetal-maternal transfusion). Although this magnitude of fetal-maternal transfusion is an acceptable risk for the fetus, it is a sufficient transfusion to cause blood cell antigen sensitization.

This article details the developing consensus concerning the techniques, indications, and safety of fetoscopy.

A new technique for sampling fetal blood in twin pregnancies using two fetoscopes simultaneously is described. Two fetoscopes were inserted, one after the other, into both amniotic cavities and fetal blood samples were obtained from either the chorionic plate vessels or the umbilical cord insertion area. The observation of the bright tip of the second fetoscope behind the septum using the first fetoscope assured the successful entry of the two fetoscopes into the two different amniotic sacs. This technique was performed on 15 out of 17 patients. In all patients the fetuses were at risk of β-thalassemia major. Sampling was successful in all cases. Double simultaneous fetoscopy seems to be a safe and accurate technique without technical problems or complications. The simultaneous use of two fetoscopes opens new possibilities in intrauterine fetal surgery and research.