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PubMed2000

Operative techniques and strategies for minimally invasive fetoscopic fetal cardiac interventions in sheep.

BACKGROUND: Recent efforts to develop procedures for fetoscopic fetal cardiac interventions have been prompted by the development of severe secondary damage to the fetal heart due to semilunar valvar obstructions and the poor outcome of therapy-refractory fetal arrhythmias. The purpose of our manuscript is to analyze and share our experience with the creation of an operative setup for these procedures in sheep. METHODS: We studied a total of 48 fetal sheep between 81 and 106 days of gestation (term, 145 days). After entering the amniotic cavity by a percutaneous approach, we performed various fetoscopic fetal cardiac procedures. We analyzed the success of percutaneous fetal access, methods of trocar support, the incidence and management of trocar dislodgement or accidental insertion into the chorioamniotic space, problems related to amniotic insufflation and trocar placement, as well as techniques for fetal posturing and uterine closure. RESULTS: Percutaneous fetal access was achieved in all sheep. The use of resterilizable trocars substantially decreased the costs of our procedures. Utilizing a percutaneous transuterine purse-string suture for trocar support helped to minimize the number of nonabsorbable T-fasteners remaining inside the uterus postoperatively. As complications such as trocar dislodgement, insertion of the trocar into the chorioamniotic space, and problems with intraamniotic insufflation and gas loss were mastered, conversion to an open operative approach was never required. A novel strategy that we devised for percutaneous fetal posturing permitted adequate fetal posturing with ease and minimal trauma to the fetal skin. CONCLUSION: As operative techniques have become more refined, the feasibility of performing fetoscopic fetal cardiac interventions in human fetuses now depends mainly on technical improvements in imaging and interventional catheters, as well as advances in pacemaker equipment.

Animals↗
PubMed1996

Transesophageal echocardiography in fetal sheep. A monitoring tool for open and fetoscopic cardiac procedures.

BACKGROUND: Cardiac procedures in exteriorized fetuses or assisted by fetoscopy require monitoring capabilities not attended by conventional maternal transabdominal echocardiography. METHODS: We, therefore, assessed the potential of fetal transesophageal echocardiography (TEE) utilizing an intravascular ultrasound catheter (IVUC) for fetal cardiac monitoring. We inserted a 10-F-10-MHz IVUC into the esophagus in 12 exteriorized fetal sheep and by a fetoscopic approach in 4 fetal sheep. Cardiac events were observed. Heart rate, cardiac rhythm, patency of the foramen ovale and ductus arteriosus, and the width of the branch pulmonary arteries could be assessed in all fetuses. Ventricular contractility could be assessed only in fetuses weighing less than 2.5 kg. Larger fetuses did not allow adequate imaging of the apical portion of the ventricles because of limited tissue penetration of the IVUC. Fetal TEE permitted placing small guide wires in the cardiac atria and left ventricle. Short-lived premature beats following intracardiac manipulations of these wires could be observed by fetal TEE in all cases. RESULTS: At autopsy, no complications from IVUC insertion were observed in the exteriorized fetuses. Fetoscopic placement of the IVUC resulted in minor perioral skin erosion in two nonexteriorized fetuses. CONCLUSIONS: In conclusion, fetal TEE can be achieved with minor fetal injury and may provide useful information during open and fetoscopic cardiac procedures. Further improvements in IVUC design will permit the application of this technique to monitor human fetal cardiac procedures.

Animals↗
PubMed1995

Fetoscopic laser ablation of placental vessels in severe previable twin-twin transfusion syndrome.

OBJECTIVE: We undertook a pilot study to determine the feasibility and efficacy of fetoscopic laser occlusion of chorioangiopagous vessels in severe previable twin-twin transfusion syndrome. STUDY DESIGN: A total of 35 patients were referred to the investigators with ultrasonographic findings consistent with twin-twin transfusion syndrome, posterior placental implantation, gestational age < 25 weeks, and clinical hydramnios. Placental vessel occlusion was performed with a rigid 2.9 x 3.85 mm dual-channel fetoscope and neodymium:yttrium-aluminum-garnet laser light. RESULTS: Of the original 35 patients, 5 were eliminated preoperatively and 4 intraoperatively for various factors. The 26 treated patients had a mean gestational age of 20.8 weeks (range 18 to 24) and a mean fundal height of 36.1 cm (range 29 to 44). One patient has surviving triplets, 8 have surviving twins, 9 have a single survivor (2 neonatal and 7 fetal deaths occurred in this group), and 8 have no survivors (all had pregnancy loss within 3 weeks of treatment). The cases with survivors were delivered for obstetric indications at a mean of 32.2 weeks (range 26 to 37), having gained a mean of 11.7 weeks (range 6 to 17) in utero. Fifty-three percent (28/53) of the fetuses survived with 96% (27/28) developing normally at a mean age of 35.8 months (range 1 to 68). Thirty-three of 35 placentas were monochorionic with chorioangiopagous vessels on gross and microscopic evaluation. CONCLUSIONS: Fetoscopic laser occlusion of chorioangiopagous vessels is technically feasible and improves the course and outcome of severe twin-twin transfusion syndrome in previable fetuses.

Feasibility Studies↗
PubMed2004

Fetoscopic surgery in triplet pregnancies: a multicenter case series.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of fetoscopic surgery in complicated monochorionic and dichorionic triplet pregnancies. STUDY DESIGN: This was a case series of fetoscopic surgery in 12 cases of monochorionic (n = 5) or dichorionic (n = 7) triamniotic triplets complicated by severe feto-fetal transfusion (n = 8), twin reversed arterial perfusion sequence (n = 3), or discordant for an anomaly (n = 1). Six underwent cord occlusion, and 6 had laser coagulation of the vascular anastomoses. RESULTS: All procedures were successfully completed, and the outcome was comparable to that reported for similar procedures in twins. Eighty-three percent of fetuses survived, and 13% had long-term problems. CONCLUSION: Fetoscopic surgery may be considered as a therapeutic option in complicated triplet pregnancies, with results similar to those found in twins.

Adult↗
PubMed2006

Incidence, origin, and character of cerebral injury in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery.

OBJECTIVE: The objective of the study was to determine the incidence, origin, and character of cerebral lesions in monochorionic twins with twin-to-twin transfusion syndrome treated with fetoscopic laser surgery. STUDY DESIGN: This was a prospective study of monochorionic twins with twin-to-twin transfusion syndrome treated with fetoscopic laser surgery and monochorionic twins without twin-to-twin transfusion syndrome delivered at our center between June 2002 and September 2005, using cranial ultrasonography. RESULTS: Incidence of antenatally acquired severe cerebral lesions in the twin-to-twin transfusion syndrome group was 10% (8/84) and 2% (2/108) in the non-twin-to-twin transfusion syndrome group (P = .02). Incidence of severe cerebral lesions at discharge was 14% (12/84) in the twin-to-twin transfusion syndrome group and 6% (6/108) in the non-twin-to-twin transfusion syndrome group (P = .04). Antenatal injury was responsible for severe cerebral lesions in 67% (8/12) of the twin-to-twin transfusion syndrome group. CONCLUSION: Incidence of severe cerebral lesions in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery is high and results mainly from antenatal injury.

Brain Injuries↗
PubMed2005

A histological study of fetoscopic membrane defects to document membrane healing.

OBJECTIVE: To evaluate the rate of spontaneous healing in human fetal membranes after fetoscopy. STUDY DESIGN: Membranes from patients that had undergone fetoscopic interventions and delivered in one of the two treatment centers were included in the study. The membranes were examined macroscopically for any remaining defects and if present, the size of the defect in chorion and amnion was measured. Subsequently, the defect was excised and stained with HE for histological evaluation. Additional immunohistochemical staining was performed with Ki-67, cytokeratin and vimentin. The proliferation index (percentage of proliferating cells) was calculated in amnion and chorion. RESULTS: Nineteen membrane defects were included in the study. The median time interval between invasive procedures and delivery was 60 days (range 3-112). All fetoscopic defects (n=19) could be identified in the gestational sac and in none spontaneous closure had occurred. Proliferation indices as measured by inmunohistochemistry were very low (median 2.8%, range 0-7%) in the chorion and 0% in the amnion. CONCLUSION: No evidence of spontaneous membrane healing was found after fetoscopic procedures, suggesting that the membrane defect normally persists until delivery. Absence of amniotic fluid leakage after invasive procedures may be based on mechanisms other than histologic membrane repair.

Amnion↗
PubMed2006

Fetoscopic surgery: encouraged by clinical experience and boosted by instrument innovation.

Today, modern ultrasound equipment and the wide implementation of screening programmes allow the timely diagnosis of many congenital anomalies. For some of these, fetal surgery may be a life-saving option. In Europe, open fetal surgery became poorly accepted because of its invasiveness and the high incidence of postoperative premature labour and rupture of the fetal membranes. In the 1990s, the merger of fetoscopy and advanced video-endoscopic surgery formed the basis for endoscopic fetal surgery. We review the current applications of fetal surgery via both methods of access. The first clinical fetoscopic surgeries were interventions on the umbilical cord and the placenta, often referred to as obstetrical endoscopy. The outcome of a randomized clinical trial demonstrating that fetoscopic laser coagulation of chorionic plate vessels is the most effective treatment for twin-twin transfusion syndrome (TTTS) has revived interest in endoscopic fetal therapy. Operating on the fetus is another more challenging enterprise. Clinical fetal surgery programmes were virtually non-existent in Europe until minimally invasive fetoscopic surgery made such operations clinically possible as well as maternally acceptable. At present, most experience has been gathered with fetal tracheal occlusion as a therapy for severe congenital diaphragmatic hernia. As in other fields, minimally invasive surgery has pushed back boundaries and now allows safe operations to be performed on the fetal patient. Whereas minimal access seems to solve the problem of preterm labour, all procedures remain invasive, and carry a risk to the mother and a substantial risk of preterm prelabour rupture of the membranes (PPROM). The latter problem may prove to be a bottleneck for further developments, although treatment modalities are currently being evaluated.

Cystic Adenomatoid Malformation of Lung, Congenita↗
PubMed1998

Correction of congenital diaphragmatic hernia in utero IX: fetuses with poor prognosis (liver herniation and low lung-to-head ratio) can be saved by fetoscopic temporary tracheal occlusion.

BACKGROUND/PURPOSE: Fetuses with congenital diaphragmatic hernia (CDH) who have a "poor prognosis" with postnatal treatment now can be identified on the basis of liver herniation, early diagnosis (before 25 weeks' gestation) and a low lung-to-head ratio (LHR). Because complete in utero repair proved unsuccessful for this group, the strategy of temporary tracheal occlusion was developed to gradually enlarge the hypoplastic fetal lung. The purpose of this study is to compare the outcome of patients in the poor-prognosis group treated by one of three methods: (1) standard postnatal care, (2) fetal tracheal occlusion via open hysterotomy, and (3) the recently developed video-fetoscopic (Fetendo) technique of tracheal occlusion without hysterotomy. METHODS: In the past 3 years, 34 of 86 fetuses with an isolated left CDH met criteria for the poor-prognosis group. Thirteen families chose postnatal treatment at an extracorporeal membrane oxygenation (ECMO) center, 13 underwent open fetal tracheal occlusion, and eight underwent fetoscopic tracheal occlusion. RESULTS: The survival rate was 38% in the group treated by standard postnatal therapy, 15% in the open tracheal occlusion group, and 75% in the Fetendo group. There were less postoperative pulmonary complications noted in mothers who underwent the Fetendo procedure versus the open tracheal occlusion. All but one Fetendo clip patient had a striking physiological response demonstrated by sonographic enlargement of the small left lung that was documented postnatally by plain radiographs and its subjective appearance during repair of the CDH. In contrast, only 5 of the 13 open tracheal occlusion patients demonstrated lung growth. CONCLUSION: Fetuses with a left CDH who have liver herniation and a low LHR are at high risk of neonatal demise and appear to benefit from temporary tracheal occlusion when performed fetoscopically, but not when performed by open fetal surgery.

Adult↗
PubMed1998

Experience with fetoscopic cord ligation.

OBJECTIVE: In the case of a monochorionic multiple pregnancy with one non-viable fetus who compromises its co-twin, fetoscopic cord ligation may be performed. We describe our fetoscopic cord ligation technique and discuss the efficacy of cord ligation for salvaging the co-twin, based on available data. STUDY DESIGN: Descriptive case series of four cases and review of the cases published up to 1996. RESULTS: We performed four successful ligations. Of the 23 reported cases, which include the present series, two ligations failed. Four fetuses died in utero, and 17 were born alive at a mean of 8 weeks following the procedure. Two babies died in the perinatal period, a third after 60 days. Preterm uterine contractions do not seem to be a clinical problem. Preterm prelabour rupture of the membranes (PPROM) complicates about 40% of cases, the majority occurring prior to 32 weeks. CONCLUSION: Fetoscopic cord ligation is a feasible procedure with a 71% survival rate and a high risk for PPROM.

Adult↗
PubMed2002

Intra-amniotic multimodal fetal echocardiography in sheep: a novel imaging approach during fetoscopic interventions and for assessment of high-risk pregnancies in which conventional imaging methods fail.

During fetoscopic interventions, intraesophageal placement of intravascular ultrasound (US) catheters for fetal hemodynamic monitoring may result in esophageal injury in very small fetuses. Moreover, conventional fetal imaging by the transvaginal or transabdominal routes may be impossible in some high-risk pregnancies. The purpose of our study in sheep was to assess the potential of a phased-array intravascular US catheter for intra-amniotic fetal echocardiography. The catheter was percutaneously inserted into the amniotic cavity in seven pregnant ewes at between 78 to 98 days of gestation and permitted high-quality 2-D imaging of the fetal heart and multimodal Doppler assessment of fetal cardiovascular flows. Fetoscopic examination of intra-amniotic contents after intra-amniotic imaging was finished did not display any injury to intra-amniotic contents. The intra-amniotic imaging approach may provide an effective alternative in humans for monitoring during fetoscopic interventions, and to assess fetal anatomy and hemodynamics in high-risk pregnancies when sufficient images cannot be obtained by conventional routes.

Amniotic Fluid↗
PubMed2006

Encouraging early clinical experience with deliberately delayed temporary fetoscopic tracheal occlusion for the prenatal treatment of life-threatening right and left congenital diaphragmatic hernias.

OBJECTIVE: In order to assess the effect of deliberately delayed percutaneous fetoscopic tracheal occlusion on survival of fetuses with life-threatening congenital diaphragmatic hernia. METHODS: Eight fetuses with life-threatening congenital diaphragmatic hernia underwent fetoscopic tracheal balloon occlusion between 29 + 0 and 32 + 4 weeks of gestation. Delayed occlusion was chosen in order to minimize potentially negative pulmonary effects from premature delivery as a result of fetal surgery. In addition, we wanted to become able to provide all available postnatal intensive care treatment means in these patients. RESULTS: Six of the 8 fetuses survived to discharge from hospital. CONCLUSION: Delayed fetoscopic tracheal balloon occlusion may be rewarded with lung growth sufficient to allow survival of fetuses with life-threatening congenital diaphragmatic hernia.

Balloon Occlusion↗
PubMed2007

Fetoscopic laser surgery in 100 pregnancies with severe twin-to-twin transfusion syndrome in the Netherlands.

OBJECTIVE: In this prospective cohort study, we evaluated the initial results of fetoscopic laser surgery for severe second trimester twin-to-twin transfusion syndrome (TTTS) treated at our centre. METHOD: A total of 100 consecutive pregnancies with severe second trimester TTTS treated at our centre with selective fetoscopic laser coagulation of vascular anastomoses on the placental surface between August 2000 and November 2004 were included in the study. Perinatal survival was analysed in relation to Quintero stage. RESULTS: Median gestational age was 20 weeks at fetoscopy (range: 16-26) and 33 weeks at delivery (range: 18-40). Perinatal survival rate was 70% (139/200). The treatment resulted in at least one survivor at the age of 4 weeks in 81% of pregnancies. Perinatal survival was significantly higher when treatment was performed in the early Quintero stages (95% in stage 1, 76% in stage 2, 70% in stage 3, 50% in stage 4) (p = 0.02). CONCLUSION: Results of fetoscopic laser surgery for TTTS in our centre are similar to those in specialised centres in other countries. Diagnosis and treatment in the early Quintero stages resulted in significantly higher perinatal survival.

Female↗
PubMed2000

Fetoscopic direct fetal cardiac access in sheep : An important experimental milestone along the route to human fetal cardiac intervention.

BACKGROUND: Fetal cardiac interventions by direct ultrasound-guided approaches or open fetal cardiac surgery have been fraught with technical difficulties, as well as with significant maternal and fetal morbidity in humans. Therefore, the purpose of our study in sheep was to assess the feasibility and potential of fetoscopic direct fetal cardiac access. METHODS AND RESULTS: In 15 anesthetized pregnant ewes (88 to 109 days of gestation; term, 145 days), 3 to 4 trocars were percutaneously placed in the uterus. Using videofetoscopic equipment, we assessed the feasibility of achieving direct fetal cardiac access. Minimally invasive direct fetal cardiac access by operative fetoscopy was achieved in 10 of the 15 fetal sheep. In 7 fetuses, the approach was successfully tested for fetal cardiac pacing (n=5) or antegrade fetal cardiac catheterization (n=2). Access was not achieved in 5 fetuses because of bleeding complications (n=2) or because the fetoscopic setup could not be established (n=3). All but 2 fetal sheep were alive at the end of the procedure. Acute fetal demise resulted from maternal hypotension or kinking of the fetal inferior caval vein by sternal suspension. Six ewes continued gestation; 3 of these went to term, with a normal fetal outcome. Two ewes died from septicemia 3 and 7 days after the procedure, and 1 ewe aborted 1 month after the procedure. CONCLUSIONS: Minimally invasive direct fetal cardiac access by operative fetoscopy is feasible in fetal sheep. The fetoscopic approach carries important potential for fetal cardiac pacing, antegrade fetal valvuloplasties, and resection of fetal intrapericardial teratomas in human fetuses.

Animals↗
PubMed2004

[The initial results of fetoscopic laser treatment for severe second trimester twin-to-twin transfusion syndrome in the Netherlands are comparable to international results].

OBJECTIVE: Evaluation of the initial results of selective fetoscopic laser coagulation of placental blood vessels for severe second-trimester twin-to-twin transfusion syndrome in the Netherlands. DESIGN: Prospective cohort study. METHOD: Between August 2000 and December 31, 2002, 49 patients were included with severe second-trimester twin-to-twin transfusion syndrome. Treatment took place in the Leiden University Medical Centre and consisted of selective fetoscopic laser coagulation of anastomoses along the vascular equator on the placental surface. Follow-up was complete until six weeks after delivery. RESULTS: Median gestational age was 20 weeks at fetoscopy and 34 weeks at birth. Perinatal survival rate was 65% (64/98). The treatment resulted in at least one surviving child in 80% of pregnancies. CONCLUSION: The results of fetoscopic laser treatment for severe second-trimester twin-to-twin transfusion syndrome in the Netherlands are similar to the recent results in specialised foreign centres.

Cohort Studies↗
PubMed1992

Fetoscopic surgery for the treatment of congenital anomalies.

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.

Animals↗
PubMed1997

Reducing the deleterious effects of intrauterine CO2 during fetoscopic surgery.

The fetoscopic approach to fetal intervention is a promising minimally invasive technique for correcting congenital anomalies in utero. However, expansion of the amniotic cavity with CO2 to visualize the fetus causes fetal hypercarbia and acidosis. We assessed whether maternal hyperventilation during intrauterine CO2 insufflation could attenuate the fetal hypercarbic acidosis. Seven fetal lambs of 105 +/- 2 days (mean +/- SEM) gestation (term = 145 days) were instrumented with a carotid arterial catheter in utero. After 7 +/- 1 days of recovery, fetoscopic exposure was obtained with intrauterine insufflation of CO2 at 10 mmHg of intraamniotic pressure. After 30 min, the ewe was hyperventilated at a mean respiratory rate of 23/min for 30 min under continuous insufflation. The uterus was then deflated and following 1 hr of stabilization, and the same protocol of CO2 pneumometrium was repeated. Fetal and maternal arterial blood was sampled at baseline and at 15 min intervals. Fetal PaCO2 increased during 30 min of CO2 insufflation (50.8 +/- 2.8 vs. 72.3 +/- 5.0 mmHg, P < 0.01); however, this change was reversed (to 51.5 +/- 3.0 mmHg, P < 0.01) by 30 min of maternal hyperventilation. The fetus developed acidosis after 30 min of CO2 pneumometrium (pH 7.350 +/- 0.012 vs. 7.236 +/- 0.026, P < 0.01); this was also reversed (to 7.366 +/- 0.019, P < 0.01) by maternal hyperventilation. These results were reproducible during the second CO2 insufflation challenge. Fetal hypercarbic acidosis during fetoscopy with CO2 insufflation is reduced by maternal hyperventilation.

Acidosis↗
PubMed1997

Percutaneous fetal access and uterine closure for fetoscopic surgery. Lessons learned from 16 consecutive procedures in pregnant sheep.

BACKGROUND: Maternal morbidity and preterm labor from fetal surgery might be minimized by a percutaneous technique for fetal access and uterine closure. METHODS: In each of 16 ewes, we inserted three trocars percutaneously into the amniotic cavity using ultrasound and fetoscopic guidance. In six ewes, percutaneous uterine closure after the procedure was attempted. We assessed feasibility and acute complications of our technique during surgery and at autopsy. RESULTS: We achieved percutaneous fetal access in 14 ewes and closed the uterus percutaneously in all six ewes attempted. Fetal injury was related to amnioinfusion or fixation of chorioamniotic membranes. Other complications were trocar dislodgment and damage to uterine wall and chorioamniotic membranes. The latter complication was prevented using balloon-tipped trocars. CONCLUSIONS: Percutaneous intraamniotic access and uterine closure for fetoscopic surgery can be achieved reliably with little maternal and fetal morbidity in sheep. Minor modifications are desired to apply this approach in humans.

Amnion↗
PubMed1983

Fetoscopic visualization in second-trimester pregnancies.

Fetoscopic visualization may be required for the prenatal diagnosis of external fetal malformations which cannot be clearly defined by ultrasound. The synchronous use of real-time ultrasound guidance during the fetoscopic procedure has permitted successful visualization to be achieved in pregnancies of greater than 18 weeks' gestation. The chances of successful visualization and the influence of advancing gestational age have been critically evaluated. Between 18 and 23 weeks', when these techniques were used, advancing gestational age did not appear to exert a significant effect on the chances of successful visualization. Analysis of placental position indicated that an anterior placenta did not significantly affect bloodstaining of the fluid or preclude access to placental vessels for blood sampling.

Adolescent↗