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BACKGROUND: Preterm prelabor rupture of membranes is the most frequent complication of fetoscopic surgery. Strategies to seal the membrane defect created by fetoscopy have been attempted with little success. We previously developed an integrated semirigid bioadhesive patch composed of silicone and hydroxypropyl methylcellulose that achieved ex vivo sealing of membrane defects. OBJECTIVE: To evaluate the feasibility of the insertion of our integrated semirigid bioadhesive patches using a fetoscopic technique and to test the adhesion in ex vivo human membranes and in an in vivo ovine model. STUDY DESIGN: An experimental study involving 2 experiments: (1) ex vivo—human fetal membranes were mounted in a custom-designed model with saline solution simulating intraamniotic pressure. The insertion of 2 different bioadhesive patches made of silicone-hydroxypropyl methylcellulose and silicone-polyurethane-hydroxypropyl methylcellulose was performed through a 12-Fr cannula mimicking fetoscopic surgery technique. The experiment was repeated 10 times with membranes from different donors. Measures included insertion time, successful insertion, and adhesion at 5 minutes; (2) in vivo—16 patches of silicone-hydroxypropyl methylcellulose were inserted by fetoscopy in the amniotic cavity of pregnant sheep (4 bioadhesives per animal, in 4 ewes). Measures included successful insertion, adhesion at 5 minutes, and adhesion at the end of surgery. RESULTS: In the ex vivo insertion study, there was no difference in the insertion time between silicone-hydroxypropyl methylcellulose and silicone-polyurethane-hydroxypropyl methylcellulose patches (P=.49). Insertion was successful in all cases, but complete adhesion at 5 minutes was superior for silicone-hydroxypropyl methylcellulose (P=.02). In the in vivo study, insertion of silicone-hydroxypropyl methylcellulose by fetoscopy was feasible and successful in all cases, and no complications were reported. Adhesion persisted at 5 minutes and at the end of the surgery in 68.8% and 56.3% of the patches, respectively. CONCLUSION: We describe the feasibility of deploying through a fetoscopic trocar a semirigid silicone-hydroxypropyl methylcellulose patch that seals fetal membranes after an invasive fetal procedure. The results warrant further research for improving long-term adhesion and developing a clinically applicable system. This project has been funded by the Cellex Foundation and the Erasmus+ Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects only the authors’ views, and the Commission cannot be held responsible for any use that may be made of the information contained therein. T.M. was supported by a predoctoral grant from Erasmus Mundus FetalMed-PhD. E.E. has received funding from the Departament de Salut under grant number SLT008/18/00156.

Open spina bifida is the most common congenital anomaly of the central nervous system compatible with life. Prenatal repair of open spina bifida via open maternal-fetal surgery has been shown to improve postnatal neurologic outcomes, including reducing the need for ventriculoperitoneal shunting and improving lower neuromotor function. Fetoscopic repair of open spina bifida minimizes the maternal risks while providing similar neurosurgical outcomes to the fetus. The following 2 fetoscopic techniques are currently in use: (1) the laparotomy-assisted approach, and (2) the percutaneous approach. The laparotomy-assisted fetoscopic technique appears to be associated with a lesser risk of preterm birth than the percutaneous approach. However, the percutaneous approach avoids laparotomy and uterine exteriorization and is associated with lesser anesthesia risk and improved maternal postsurgical recovery. The purpose of this article was to describe our experience with a modified surgical approach, which we call percutaneous/mini-laparotomy fetoscopy, in which access to the uterus for one of the ports is done via a mini-laparotomy, whereas the other ports are inserted percutaneously. This technique draws on the benefits of both the laparotomy-assisted and the percutaneous techniques while minimizing their drawbacks. This surgical approach may prove invaluable in the prenatal repair of open spina bifida and other complex fetal surgical procedures.

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.

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. ispartof: Journal of Visualized Experiments vol:2017 issue:120 ispartof: location:United States status: published

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.

Background: The aim of this study was to compare pregnancy rates in patients undergoing IVF/ICSI with embryo transfer after 4 and 5 days of culture in a closed incubation system with integrated time-lapse imaging. Methods: Out of n = 2207 in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) cycles performed between January 2011 and April 2016 at a tertiary referral university hospital, a total of n = 599 IVF/ICSI cycles with prolonged embryo culture in an integrated time-lapse system (EmbryoScope© (Vitrolife)) until day 4 or 5 were retrospectively analyzed with regard to embryo morphology and pregnancy rates. Results: A transfer on day 5 compared to a transfer on day 4 did not result in higher implantation and clinical pregnancy rates (IR 29.4% on day 4 versus 33.0% on day 5, p = 0.310; CPR 45.2% on day 4 versus 45.7% on day 5, p = 1.0). The percentage of ideal embryos transferred on day 4 was comparable to the rate of ideal embryos transferred on day 5 (41.6% versus 44.1%, p = 0.508). However, on day 4 a significantly higher number of embryos was transferred (1.92 on day 4 versus 1.84 on day 5, p = 0.023), which did not result in higher rates of multiple pregnancies. Conclusions: Pregnancy rates in IVF/ICSI cycles with integrated time-lapse incubation and transfer on day 4 and 5 are comparable. This finding provides the clinician, IVF laboratory and patient with more flexibility. Trial registration: This study was retrospectively registered by the local ethics committee of the University of Heidelberg on December 19, 2016 (registration number S-649/2016).

Previously manual human embryology in many in vitro fertilization (IVF) centers is rapidly being replaced by closed embryo incubation systems with time-lapse imaging. Whether such systems perform comparably to manual embryology in different IVF patient populations has, however, never before been investigated. We, therefore, prospectively compared embryo quality following closed system culture with time-lapse photography (EmbryoScope™) and standard embryology. We performed a two-part prospectively randomized study in IVF (clinical trial # NCT92256309). Part A involved 31 infertile poor prognosis patients prospectively randomized to EmbryoScope™ and standard embryology. Part B involved embryos from 17 egg donor-recipient cycles resulting in large egg/embryo numbers, thus permitting prospectively alternative embryo assignments to EmbryoScope™ and standard embryology. We then compared pregnancy rates and embryo quality on day-3 after fertilization and embryologist time utilized per processed embryo. Part A revealed in poor prognosis patients no differences in day-3 embryo scores, implantation and clinical pregnancy rates between EmbryoScope™ and standard embryology. The EmbryoScope™, however, more than doubled embryology staff time (P

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.

Embryo selection in in vitro fertilization (IVF) treatment has traditionally been done manually using microscopy at intermittent time points during embryo development. Novel technique has made it possible to monitor embryos using time lapse for long periods of time and together with the reduced cost of data storage, this has opened the door to long-term time-lapse monitoring, and large amounts of image material is now routinely gathered. However, the analysis is still to a large extent performed manually, and images are mostly used as qualitative reference. To make full use of the increased amount of microscopic image material, (semi)automated computer-aided tools are needed. An additional benefit of automation is the establishment of standardization tools for embryo selection and transfer, making decisions more transparent and less subjective. Another is the possibility to gather and analyze data in a high-throughput manner, gathering data from multiple clinics and increasing our knowledge of early human embryo development. In this study, the extraction of data to automatically select and track spatio-temporal events and features from sets of embryo images has been achieved using localized variance based on the distribution of image grey scale levels. A retrospective cohort study was performed using time-lapse imaging data derived from 39 human embryos from seven couples, covering the time from fertilization up to 6.3 days. The profile of localized variance has been used to characterize syngamy, mitotic division and stages of cleavage, compaction, and blastocoel formation. Prior to analysis, focal plane and embryo location were automatically detected, limiting precomputational user interaction to a calibration step and usable for automatic detection of region of interest (ROI) regardless of the method of analysis. The results were validated against the opinion of clinical experts. © 2015 International Society for Advancement of Cytometry.

Fetoscopy has been reintroduced in fetal diagnosis and therapy, as a result of instrumental innovations. It has been suggested that fetoscopy be used to guide endoscopic operations on the fetus, but this application is still in the experimental phase. Its use for surgical interventions on the placenta, umbilical cord, and to a lesser extent the fetal membranes, could be called 'obstetrical' endoscopy. Nd:YAG laser coagulation of chorionic plate vessels for feto-fetal transfusion syndrome is the most common operation carried out today. Survival rates of 60% or more have recently been reported on both sides of the Atlantic Ocean. Neurological morbidity does not exceed 6%, which compares favorably with serial amnioreductions and may become the most important incentive for performing the operation. A randomized trial comparing both therapies as a next step is being proposed. Fetoscopy has also been used for cord ligation, but because of the complexity of the operation and the high risk for preterm prelabor rupture of the membranes, other alternatives have been investigated. Most experience has been gathered with bipolar cord occlusion, a procedure which can be performed under ultrasound guidance. The instrumental considerations and potential complications of fetoscopy are discussed.

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.

Among all the strategies available in order to improve success rates in IVF cycles, a lot of work has been done on embryo culture conditions and embryo quality evaluation. Most IVF centres use conventional incubators and select embryo according to punctual morphological evaluation, but this strategy has several limitations. Recently developed commercial devices associating more stable culture conditions and time lapse observation of embryo development provide new insights into early embryo development in IVF cycles. Among them, the Embryoscope(®) appears to be the most user-friendly, performing and suited for routine daily practice. The first Embryoscope(®) for France was installed in the University Hospital of Nantes in 2011. In our experience, it takes relatively a short time to get used to this system. Moreover, its integration in routine process yielded several advantages, such as better embryo selection according to kinetic parameters and observation of abnormal cleavage events, continuing education and training, quality control and flexibility. This leaded to an overall increase in success rates in IVF cycles.

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.

In this paper, we describe a rigid endoscope that transmits a laser beam coaxially to arbitrary points in the endoscopic view, mainly for treatment of twin-to-twin transfusion syndrome. The endoscope consists of a hotmirror for coaxial transmission of visible light and a Nd:YAG laser beam, and galvanometers for controlling the beam irradiation angle. We evaluated the transmission efficiency of the laser power, the spot size through the endoscope and accuracy in positioning the beam. The maximum laser transmission efficiency was 39% and the spot diameter was 2.2-3.2 mm at a distance of 10-20 mm. The positioning accuracy was mostly within 1.0 mm in the endoscopic view at the distance. The average laser power density on the spot was estimated to be 170-370 W/cm2, and a chicken liver was successfully coagulated by changing the laser beam irradiation angle.

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.

We describe a new technique to achieve permanent umbilical cord occlusion.A 3 mm in diameter bipolar diathermy forceps was built to house a 1.2 mm fetoscope, emerging between the blades of the forceps. The device can be inserted percutaneously through a 10 Fr Trocar into the amniotic cavity under local analgesia and ultrasound guidance. A monochorionic (MC) twin pregnancy with a twin reversed arterial perfusion sequence at 18 weeks of gestation underwent cord occlusion of the acardiac twin using this new device in 2004.The instrument allowed cord coagulation under direct visual control. The pregnancy continued until 33 weeks of gestation when a male infant of 1980 g was delivered by cesarean section following preterm labor.This new instrument might allow easier access to the cord and reduce operation time by direct visualization of the target and, therefore, improve the outcome after the procedure.

To introduce and establish a new approach in minimal invasive fetoscopic surgery in order to reduce access trauma and the iatrogenic preterm premature rupture of the membranes (PPROM) as a major complication of intrauterine treatment of congenital diaphragmatic hernia.In total, 27 pregnant sheep were operated on using fetoscopes with 1.2 and 1.0 mm optics. We used an elliptic sheath alone with a maximum diameter of 2.6/1.3 mm; in these cases the balloon was placed under ultrasound control. In comparison, we placed the balloon under fetoscopic control using the fetoscopic sheath and a 7F (2.3 mm) introducer. Therefore, the maximum access trauma was not bigger than the diameter of sheath of introducer.With this technique we successfully operated on 22 sheep. The use of real time three-dimensional ultrasound control distinctly facilitates the operation procedure.Our preliminary findings show that fetoscopic tracheal occlusion using ultrathin fetoscopes and reducing the access trauma on the level of 4.2 or even 2.65 mm(2) could be seen as a method of reducing the rate of PPROM.

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.

Oocyte and embryo selection are not highly successful, with fewer than 10% of oocytes in assisted reproduction resulting in a delivery. Techniques for oocyte and embryo selection rely on highly subjective morphology assessment, with few true quantitative techniques available. One aspect of oocyte health that could be considered is the ability to produce ATP through respiration. Using a non-invasive technology, the respiration rates of individual human oocytes were recorded in an attempt to correlate respiration and oocyte health with probable subsequent development. Oocytes used were either immature or mature, non-fertilized oocytes from a clinical assisted reproduction programme. Differences in respiration rates between oocytes within a cohort and between cohorts of oocytes were recorded. The differences between cohorts reflected many of the currently known differences in oocyte health, related to age and FSH concentrations. However, within a cohort, differences between oocytes were observed, with some having high rates and others low. Oocytes with respiration rates of between 0.48 and 0.55 nl O(2)/h were viable, with lower rates consistent with lack of continued in-vitro maturation or atresia. This technology may have a future in the clinical laboratory as a predictor of oocyte health and ability to develop into an embryo with greater potential of delivery.

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.

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