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[Results of fetoscopic examinations at our hospital].

From 1983 to 1985, antenatal diagnosis by fetoscopy under ultrasound guidance has been performed at our institute for 17 pregnant women between 15 and 34 weeks of gestation. Indications for fetoscopy were visualization of the fetus, placenta, and amniotic membrane for morphological anomaly and fetal blood sampling for coagulation disorder. The diagnosis, made by visual observation of the fetus, blood coagulation tests, and karyotyping revealed 12 normal fetuses and 5 abnormal fetuses (one having chromosome abnormality, one amniotic band syndrome, one cephalothracopagus, one Beckwith-Wiedemann syndrome, and one sacral tumor). Courses of pregnancy following fetoscopy resulted in four normal full-term deliveries, six premature deliveries due to four hydramnions and two spontaneous ruptures of the membrane more than 14 weeks after fetoscopy. Three other pregnancies were interrupted due to intrauterine fetal death 11 weeks after fetoscopy in one case and to therapeutic abortion for maternal complications such as toxemia of pregnancy in two cases. The outcome of one case was unknown because the mother had moved away. The other pregnancy is still under observation at the third trimester. Although no complications in the fetuses were seen following fetoscopy, complications in the mothers included two cases of genital bleeding, one case of amniotic fluid leakage, and one cases of abruption of the fetal membrane. Symptoms in all four cases disappeared during several days of bed rest. These results demonstrate the importance of fetoscopy in prenatal diagnosis.

Amniotic Band Syndrome↗

In utero repair of myelomeningocele: experimental pathophysiology, initial clinical experience, and outcomes.

HYPOTHESIS: Experimental work raises the possibility that in utero repair of myelomeningocele (MMC) may improve lower extremity, bladder, and bowel function, ameliorate the Arnold-Chiari malformation, and decrease the need for postnatal shunting. DESIGN: We previously developed fetal lamb models to create and reverse lower extremity damage and the Arnold-Chiari malformation in utero. We then applied our extensive experience with fetal surgery, including fetal endoscopic (fetoscopic) surgical manipulation, to develop techniques for MMC repair. SETTING: A tertiary referral center. PATIENTS: All patients treated between 1998 and 2002 for a prenatally diagnosed MMC. INTERVENTIONS: Either fetoscopic MMC repair, fetoscopic patch repair, or limited maternal hysterotomy and microsurgical 3-layered fetal MMC repair was performed. MAIN OUTCOME MEASURES: Gestational age at delivery, survival, neurologic outcome, and need for ventricular shunting at 1 year. RESULTS: Complete fetoscopic repair was accomplished in 1 fetus. Two other fetuses underwent partial fetoscopic procedures. The remaining 10 patients underwent limited maternal hysterotomy and microsurgical 3-layered fetal MMC repair. Four of 13 patients died, and the mean gestational age at delivery of 11 fetuses born alive was 31 weeks. Five of 9 required ventricular shunting by age 1 year. In 2 patients, lower extremity function improved by more than 2 vertebral levels compared with prenatal ultrasonography. Five of 10 patients who lived longer than 3 weeks required postnatal wound revision within 7 days after birth. CONCLUSIONS: Fetoscopic repair, although feasible, does not yet yield optimal surgical results. Open surgical repair before 22 weeks' gestation is physiologically sound and technically feasible. One third of patients appear to be spared the need for a shunt at age 1 year, but improvement in distal neurologic function is less clear. Additionally, fetal mortality is associated with this procedure. Our results complement the data published by groups at Children's Hospital of Philadelphia, in Pennsylvania, and Vanderbilt University, Nashville, Tenn. A National Institutes of Health-sponsored prospective randomized trial is now underway at these 3 centers to compare fetal repair with postnatal repair.

Adult↗

Prenatal diagnosis of hemoglobinopathies in twin pregnancies by double simultaneous 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 beta-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.

Diseases in Twins↗

Fetal lung-to-head ratio in the prediction of survival in severe left-sided diaphragmatic hernia treated by fetal endoscopic tracheal occlusion (FETO).

OBJECTIVE: The objective of the study was to investigate the value of fetal lung area to head circumference ratio in the prediction of the postnatal outcome in left-sided congenital diaphragmatic hernia treated by fetoscopic endoluminal tracheal occlusion. STUDY DESIGN: The lung area to head circumference ratio was measured before fetoscopic endoluminal tracheal occlusion in 28 fetuses with congenital diaphragmatic hernia at 25 to 29 weeks. Regression analysis was used to investigate the effect on survival of lung area to head circumference ratio, gestation at fetoscopic endoluminal tracheal occlusion, gestation at delivery, preterm amniorrhexis following fetoscopic endoluminal tracheal occlusion, and prenatal removal of the balloon. RESULTS: The median lung area to head circumference ratio prior to fetoscopic endoluminal tracheal occlusion was 0.7 (range 0.5 to 0.9). The median gestation at delivery was 34 (range 27 to 39) weeks, and there were 16 survivors (57%). Only lung area to head circumference ratio provided significant prediction of survival, which increased from 17% for lung area to head circumference ratio of 0.4 to 0.5 to 62% for lung area to head circumference ratio of 0.6 to 0.7 and 78% for lung area to head circumference ratio of 0.8 to 0.9. CONCLUSION: In congenital diaphragmatic hernia treated by fetoscopic endoluminal tracheal occlusion, postnatal survival can be predicted by the lung area to head circumference ratio measured prior to the procedure.

Balloon Occlusion↗

[Clinical experience with fetoscopy (author's transl)].

A fetoscope with a trocar of an external diameter of 3.9 and internal diameter of 2.9 mm was used. The optical equipment of the fetoscope had lenses with external diameters of 2.2 and 2.7 mm. The fetoscope can be inserted into the uterine cavity through the abdominal wall with local anaesthesia and insertion controlled by ultrasound. This type of insertion is uncomplicated and relatively free of risks. Thus an essential prerequisite for a successful fetoscopy is fulfilled. For the success of the fetoscopy, it is important to know what the diagnostic value of the procedure is and what can be seen through the fetoscope. The direct intrauterine visualization of the fetus or parts of the fetus is with the fetoscope under evaluation possible and was successful in 23 of 26 fetuses. The field of visualization is limited to 50 degrees by the optical system and only small parts of the fetus can be seen at a time. The extent of visualization of the fetus depends besides the optical system, on the quality of the amniotic fluid and the optimal timing of the fetoscopy in the second trimester between 15 and 18 weeks. Success is also dependant on the endoscopic experience and the technical training of the observer. After 13 of 26 fetoscopies the improvement was approximately 70%. Inspection of some parts of the fetus, for intance, the face is successful in every detail but still more or less fortuitous. Fetoscopy can only be deemed to be successful when a more or less total visualization of the fetus has heen accomplished. This was the case in 39% of the cases. Fetoscopy was used for diagnostic purpose in one case with the term delivery of a healthy infant. Fetal blood sampling by puncture of placental vessels under visualization is in its infancy. Fetoscopy is a justified procedure at this time in cases with a high genetic risk and for the avoidance of an abruptio.

Amniotic Fluid↗

Fetoscopy.

Fetoscopy involves the application of microlaparoscopic technology to fetal diagnosis and therapeutic intervention. Though fetoscopy presents many potential advantages over open fetal surgery, the primary one is that of decreased procedure-induced preterm labor and fetal loss from preterm delivery. The small uterine puncture sites required for fetoscopic surgery should, in theory, obviate the morbidity of a large hysterotomy. Fetoscopic instrumentation is small by design, but this has not limited the breadth of the interventional spectrum, because creative applications have been used for the treatment of twin-twin transfusion syndrome, twin reversed arterial perfusion sequence, hydronephrosis, congenital diaphragmatic hernia, fetal tumors, and myelomeningocele. This article examines the fetoscopic experience for these applications, involving over 150 cases. The results for many procedures are auspicious and will improve as further operative experience and newer fetoscopic technologies become available. However, as with any novel technology, responsible application must involve careful experimentation and an analysis of potential maternal and fetal benefits.

Animals↗

Sampling pure fetal blood in twin pregnancies by fetoscopy using a single uterine puncture.

A technique for sampling pure fetal blood in twin pregnancies using a single uterine entry with a fetoscope is described. The fetoscope was inserted into one sac and after blood had been obtained from that twin, the fetus in the other sac was sampled by trans-septal passage of the blood-sampling needle. This was done in six out of seven patients, the first in the series having two separate insertions of the fetoscope, one into each sac. Pure fetal blood was taken from all 14 fetuses, either from the placental insertion of the umbilical cord or the umbilicus, and the volume of the samples ranged from 200 mul to 1200 mul. In six patients the fetuses were at risk of beta-thalassaemia and in one of haemophilia A. Some observations are made relating zygosity to the ultrasonic and fetoscopic appearance of the septum between the sacs.

Abortion, Induced↗

Minimal access techniques for fetal surgery.

The impetus for the development of minimal access techniques for fetal surgery was the unusual occurrence with open hysterotomy of preterm labor, premature rupture of membranes, and the maternal complications resulting from tocolytic therapy. This strategy involves a constellation of techniques that allow surgical procedures to be performed inside the uterus without a hysterotomy. The unique requirements of this approach necessitated modifications of existing endoscopic techniques, development of novel fetoscopic instruments, and utilization of the expertise of a wide variety of specialists. Technical expertise in the field and a natural evolution of techniques have given rise to innovative repairs previously not envisioned. Severe congenital diaphragmatic hernia, diseases of monochorionic twins, and obstructive uropathy have already been successfully treated using fetoscopic surgical techniques. Fetoscopic correction of many other non-life-threatening anomalies continues to evolve. The future of fetoscopic surgical intervention depends on the continual evolution of novel techniques, the elucidation of the pathophysiology and treatment of other fetal disorders, and a better understanding of treatment of complications of intervention.

Amniotic Band Syndrome↗

Fetal endoscopic tracheal occlusion ('Fetendo-PLUG') for congenital diaphragmatic hernia.

Despite recent advances in surgical technique, posthysterotomy preterm labor remains a major determinant of postoperative fetal morbidity and mortality after in utero repair of congenital diaphragmatic hernia (CDH). Temporary fetal tracheal occlusion, or "PLUG" (Plug the Lung Until it Grows), reverses the pulmonary hypoplasia seen in experimental models of CDH and provides an alternative treatment strategy for some fetuses with CDH. Adaptation of current, minimally invasive surgical technology to the PLUG technique allows treatment of CDH without opening the uterus. In this report the authors describe a video-fetoscopic, intrauterine technique of tracheal occlusion (called Fetendo-PLUG) that could be used in human fetuses with CDH. The technique was developed in four fetal lambs that underwent video-fetoscopic intervention at 110 days' gestation (full term, 145 days), having undergone open creation of diaphragmatic hernias at 75 days. After maternal laparotomy and uterine exposure, the fetal head was located and a 5-mm curved, balloon-cuffed trocar was introduced through a uterine puncture directly into the fetal oral cavity. A steerable "bronchoscope" (with an instrument channel) was used to endoscopically intubate the trachea through the trocar, and the trocar was advanced over the bronchoscope and its balloon inflated to provide secure tracheal access below the vocal cords. Next, a 10-mm trocar was placed directly over the fetal neck, and the amniotic space was expanded with warm saline. A 5-mm laparoscope was introduced, and under simultaneous, dual video-fetoscopic (endotracheal and endoamniotic) visualization, a 1-mm nephrostomy puncture wire was advanced along the instrument channel of the bronchoscope, through the anterior wall of the trachea and fetal neck, into the amniotic space, then through the uterine wall to the outside. Withdrawal of the bronchoscope over the wire left a 5-mm endotracheal "trocar channel" along which a compressed, gelatin-encapsulated, polymeric foam insert (outer diameter, 4.8 mm) could be delivered by suture attachment to the guide wire. Once the foam was in its final endotracheal position, dissolution of the gelatin membrane allowed expansion of the foam to produce a water impervious tracheal occlusion. This two-trocar video-fetoscopic PLUG technique was performed successfully in all four fetuses, with a sequential decrease in operating time (median, 3.5 hours). Although two fetuses aborted postoperatively, the other two were carried successfully to term and demonstrated the anticipated physiological effects of adequate tracheal occlusion at the time of delivery.

Animals↗

BAPS Prize--1997. Fetal gene therapy: efficacy, toxicity, and immunologic effects of early gestation recombinant adenovirus. British Association of Paediatric Surgeons.

BACKGROUND/PURPOSE: Advancements in gene transfer technology and prenatal diagnosis have allowed investigators to consider an in utero gene therapy approach for fatal genetic diseases. The authors sought to develop fetoscopic techniques for gene delivery and investigate the efficacy and safety of recombinant adenoviral vectors in the fetus. METHODS: Fetal sheep between 60 and 130 days' gestation (dGA) underwent either fetoscopic intratracheal injection or umbilical vein (UV) injection of recombinant adenovirus, AdCMVlacZ. At death, fetal organs were examined for beta-galactosidase expression, histopathology, and CD45 immunostaining. Fetal serum was compared with preimmune serum for transaminase levels and the presence of antiadenoviral neutralizing antibodies. RESULTS: Fetoscopic intratracheal delivery of AdCMVlacZ in late-gestation sheep fetuses resulted in efficient alveolar gene transfer, but, antiadenoviral immunologic reactions limited the longevity of transgene expression to 14 days. This prompted an examination of whether early gestational exposure could induce tolerance in the fetus to adenoviral and transgene antigens. AdCMVlacZ (1 x 10(11) particles) was injected via UV into fetuses at 60 dGA. Within 3 days, beta-galactosidase expression was localized to the fetal liver, adrenal glands, kidneys, and endocardium. Although adrenal expression was nearly constant over 28 days, expression in fetal liver disappeared within 14 to 28 days. Loss of hepatic expression did not appear to be immune mediated because there was no evidence of hepatic inflammation or appearance of antiadenoviral neutralizing antibodies. Fetuses injected with AdCMVlacZ at 60 dGA were reinjected with 1 x 10(13) particles at 125 dGA and antiadenoviral humoral immune responses were recorded. Despite early-gestation adenovirus injection, fetuses still responded to the late-gestation adenoviral exposure, developing antiadenoviral neutralizing antibodies similar to control fetuses. CONCLUSIONS: The authors developed fetoscopic access for pulmonary adenovirus delivery in late-gestation sheep. Although initial alveolar transduction was highly efficient, antiadenoviral immune responses limited the duration of transgene expression. In contrast, early-gestation adenoviral delivery did not elicit antiadenoviral immune responses despite achieving efficient transduction of many fetal tissues. Furthermore, early-gestation adenovirus delivery did not affect late-gestation antiadenoviral immune responses. These findings suggest that the early-gestation sheep fetus is not amenable to adenoviral tolerance induction by UV injection and that it is incompetent of immunologic response to adenovirus. For the purposes of in utero gene therapy, recombinant adenovirus may be applied optimally to genetic diseases requiring transient in utero expression.

Adenoviridae↗

Endoscopic techniques in fetal surgery.

Fetal endoscopic surgery (FETENDO) involves many techniques that allow surgical procedures to be performed inside the uterus without an hysterotomy. The impetus for developing these minimal access techniques for fetal surgery is the unusual occurrence with an open hysterotomy of preterm labor, premature rupture of membranes, and maternal complications resulting from tocolytic therapy. The unique requirements of this approach necessitated a modification of existing endoscopic techniques, the development of novel fetoscopic instruments, and the inclusion of a wide variety of specialists. Technical expertise in the field and a natural evolution of techniques have given rise to innovative repairs previously not envisioned. Severe congenital diaphragmatic hernia, diseases of monochorionic twins, and obstructive uropathy have already been successfully treated using fetoscopic surgical techniques. Fetoscopic correction of many other non-life threatening anomalies continues to evolve. The future of fetoscopic surgical intervention depends on the continual evolution of novel approaches to disease, the elucidation of the pathophysiology and treatment of other fetal disorders, and a better understanding of treatment of complications of such intervention.

Anesthesia↗

Fetoscopy--a new endoscopic approach.

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.

Abortion, Therapeutic↗

The treatment of twin-twin transfusion syndrome.

The twin-twin transfusion syndrome (TTTS) is the most common serious complication of monochorionic twin gestations, affecting between 4% and 35% of monochorionic twin pregnancies each year in the United States. The TTTS accounts for 17% of all perinatal mortality associated with twin gestations. Standard therapy in the United States has most commonly been serial amnioreduction, which appears to improve the overall outcome. Intertwin microseptostomy similarly improves outcome but has no survival advantage over serial amnioreduction. Survivors of TTTS treated by serial amnioreduction have an 18% to 26% incidence of sonographically detectable brain abnormalities. Selective fetoscopic laser photocoagulation of chorioangiopagus has emerged as an alternative treatment strategy in TTTS with at least comparable if not superior survival to serial amnioreduction. The superiority of fetoscopic laser treatment of TTTS remains unproven and is the subject of a National Institutes of Health (NIH)-sponsored prospective randomized clinical trial comparing aggressive serial amnioreduction with selective fetoscopic laser photocoagulation for severe TTTS.

Amnion↗

Fetal endoscopic telesurgery using an Internet Protocol connection: clinical and technical challenges.

Until recently, fetoscopic laser surgery to seal the placental anastomoses that cause severe twin-to-twin transfusion syndrome has been available in only a few centres worldwide. The technique typically takes a long time to learn. We have used a dedicated Internet Protocol (IP) connection for tele-education to assist the introduction of fetoscopic laser surgery to Australia. During the implementation of the international telemedicine link, there were multiple clinical and technical problems, which were eventually overcome. The quality of images and of video-sequences was comparable to that supported by an ISDN connection. Pictures of live surgery performed by an expert in Florida, USA, were transmitted and viewed by a novice team in Brisbane, Australia. The Australian team has performed 19 fetoscopic laser operations to date. Preliminary results are comparable to those from centres that have performed over 100 procedures.

Australia↗