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Invasive antenatal interventions in complicated multiple pregnancies.

Multiple pregnancies still pose challenging problems for modern medicine. Complications in monochorionic multiple pregnancies have sparked a revival of fetoscopy as a means surgery on the placenta and umbilical cord. As such, fetoscopic laser coagulation is currently the best first-line treatment for severe twin-to-twin transfusion syndrome. Also, fetoscopic or ultrasound-guided cord coagulation seems to be an effective technique for selective feticide in monochorionic twins, albeit with still considerably higher fetal loss rates compared with selective feticide by potassium chloride injection in dichorionic twins.

Chorion↗

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↗

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↗

Transabdominal intra-amniotic endoscopic assessment of previable premature rupture of membranes.

OBJECTIVE: Our purpose was to describe the endoscopic characteristics of the site of rupture in vivo in patients with spontaneous premature rupture of membranes. STUDY DESIGN: Patients with preterm premature rupture of membranes between 16 and 26 weeks of gestation, without evidence of intra-amniotic infection, and with a normal karyotype underwent transabdominal endoscopic examination of the amniotic cavity. Subsequently, an amniopatch of a combination of platelets and cryoprecipitate to seal the membrane defect was administered. The study was approved by the Institutional Review Board of St. Joseph's Hospital in Tampa, Florida, and all patients gave written informed consent. RESULTS: Four patients underwent endoscopic examination and amniopatch administration; three had spontaneous preterm premature rupture of membranes, and in the other the membranes ruptured after an early amniocentesis. The location of the site of rupture was over the internal os in the 3 cases with spontaneous preterm premature rupture of membranes. This area was normal in the patient with iatrogenic preterm premature rupture of membranes. The longer the time between preterm premature rupture of membranes and fetoscopy, the larger and less defined was the site of rupture. The amniopatch restored amniotic integrity for a maximum of 72 hours. CONCLUSIONS: This is the first in vivo endoscopic visualization of the site of spontaneous rupture of membranes from within the uterine cavity. The defect is located over the internal cervical os in patients with spontaneous preterm premature rupture of membranes. There appear to be time-related changes in the morphologic characteristics of the site of rupture. Endoscopic visualization of the site of rupture has the potential for improving our understanding of spontaneous preterm premature rupture of membranes and in the development of possible therapeutic alternatives.

Abdomen↗

Fetoscopic gene therapy for congenital lung disease.

Fetal gene therapy offers the promise of cure for certain genetic diseases, like cystic fibrosis and surfactant protein B deficiency. The authors hypothesized that a fetoscopic approach could attain a high level of organ-specific gene transfer to the fetal lung late in gestation. To test this hypothesis the authors examined the efficacy, specificity, and toxicity of recombinant adenovirus-mediated transfer of the beta-galactosidase marker gene to the lung of late gestation fetal sheep using a fetoscopic technique. Twelve fetal sheep of 125 to 135 days' gestation (term, 145 days) underwent fetoscopic bronchoscopy and intratracheal administration of a replication-deficient adenoviral vector that transduces the beta-galactosidase marker gene. Escape of administered virus was prevented by the fetoscopic deployment of a detachable silicone balloon in the fetal trachea. All fetuses survived until being killed at 2 days after vector delivery for the histopathologic assessment of vector efficacy and specificity. Optimal beta-galactosidase transgene expression was observed at a viral titer of 2 x 10(12) particles per milliliter of administered volume. Expression was greatest in the distal pulmonary parenchyma, particularly in type II pneumocytes, and extended out to the pleura. There was no evidence of gene transfer in either the large conducting airways or in any other fetal organ. The authors have developed a minimally invasive technique for the specific pulmonary delivery of gene therapy vectors to the fetus with no associated acute toxicity. Gene transfer to the late gestation fetus for the treatment of congenital pulmonary disease may be feasible through fetoscopy.

Adenoviruses, Human↗

Fetendo-clip: a fetal endoscopic tracheal clip procedure in a human fetus.

Fetal tracheal occlusion accelerates lung growth and corrects the often fatal pulmonary hypoplasia seen in fetuses with congenital diaphragmatic hernia. Fetoscopy presents a unique opportunity to glimpse into the world of the fetus, but its use, until recently, has been limited to diagnostic and simple procedures. Using fetoscopic techniques ("Fetendo"), we now report successful tracheal occlusion in a 30-week-old fetus for the treatment of congenital diaphragmatic hernia.

Adult↗

Prenatal diagnosis of epidermolysis bullosa letalis.

The prenatal diagnosis of epidermolysis bullosa letalis was made by electron microscopy of a biopsy specimen of fetal skin taken under direct vision by fetoscopy at 18 weeks' gestation. The diagnosis was confirmed after termination of pregnancy. Abnormalities were found in the number, size, and scanning-electron-microscope appearance of amniotic-fluid cells. These techniques have considerable potential for rapid diagnostic studies in a number of other conditions.

Adult↗

Troubles with twins: fetoscopic therapy.

Monochorionic twin gestations present challenges in perinatal management not seen in dichorionic twins or singleton pregnancies. Monochorionic twin gestations may be complicated by (1) a monoamniotic presentation, (2) a structurally anomalous cotwin, (3) twin reversed arterial perfusion sequence, (4) and the twin-twin transfusion syndrome. Each of these conditions is associated with increased morbidity and mortality rates. Although a variety of therapeutic interventions are available, fetoscopic surgery is a promising new approach to these conditions. Advances in microinstrumentation have allowed for the wider application of fetoscopy for a variety of prenatally diagnosed conditions, including "troubles with twins." This article examines the natural history, pathophysiology, diagnosis, and indications for fetoscopic surgery in complicated monochorionic twin gestations.

Chorion↗

Antenatal diagnosis of genodermatoses.

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

Biopsy, Needle↗

In utero endoscopic devascularization of a large chorioangioma.

Clinically significant chorioangiomas, i.e. those greater than 4 cm in diameter, are associated with an overall fetal loss rate of approximately 40%. Maternal complications may also be present. Most patients diagnosed with chorioangiomas have been managed expectantly. A patient with a large chorioangioma was referred to our institution, with a fetus that was hydropic and showed sonographic signs of over heart failure. Fetal anemia, marked erythropoiesis and hypoalbuminemia were documented on cordocentesis. The blood supply to the mass consisted of an artery and a vein of 9 mm in diameter. The vascular supply to the tumor was ablated via operative fetoscopy by suture ligation of the arterial supply, after subchorionic dissection of the vessel. The remaining blood supply was electrocoagulated with bipolar cautery. Although the procedure was technically successful, the fetus died on the 3rd postoperative day. This case illustrates ablation of the blood supply of placental chorioangiomas as a potential management alternative for those patients with large chorioangiomas. Early identification and treatment may result in a successful outcome.

Endoscopy↗

Harlequin fetus: three-dimensional sonographic findings and new diagnostic approach.

Congenital ichthyosis, otherwise known as harlequin fetus, is a severe, generally lethal, anomaly. Prenatal diagnosis is usually possible in families at risk but requires invasive fetoscopy for skin biopsy. The application of three-dimensional ultrasound enables a greatly improved analysis of the facial morphology and thus provides an important contribution to prenatal diagnosis. Although such three-dimensional diagnostic procedures are performed in specialized centers, sonographers should be aware of the signs observed at routine two-dimensional ultrasound examination in order to ensure appropriate referral for diagnosis. We describe two consecutive pregnancies of the same parents in which two- and three-dimensional ultrasound were used in the prenatal diagnosis of harlequin fetus.

Adult↗

Ex vivo testing of a temperature- and pressure-controlled amnio-irrigator for fetoscopic surgery.

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

Equipment Design↗

Placental vascular anastomoses visualized during fetoscopic laser surgery in severe mid-trimester twin-twin transfusion syndrome.

The aim of this study was to describe the type and number of placental vascular anastomoses identified during fetoscopic laser coagulation in severe mid-trimester twin-twin transfusion syndrome (TTS). In 126 patients with severe TTS, undergoing fetoscopic laser coagulation between 16 and 25 weeks of gestation, the different types of placental anastomoses [arterio-venous (AV), arterio-arterial (AA) and veno-venous (VV)] were counted. In cases of AV anastomoses their direction was identified and four groups were defined: in group 1 there were only anastomoses shunting from donor to recipient. Group 2 consisted of placentae with more anastomoses shunting from donor to recipient than in the opposite direction, group 3 showed an equal number in both directions and in group 4 there were more anastomoses shunting from recipient to donor than in the opposite direction. In 9 cases (7 per cent) the anastomoses could not be clearly identified due to impaired visualization, leaving 117 cases for analysis. The median number of anastomoses found was 5 with a range from 1-14. In all cases AV anastomoses from donor to recipient were present, 36 cases (31 per cent) had also AA anastomoses and 14 cases (12 per cent) showed VV anastomoses. Regarding the direction of AV anastomoses, the results were as follows: there were 35 cases (30 per cent) in group 1, 52 cases (44 per cent) in group 2, 14 cases (12 per cent) in group 3 and 16 cases (14 per cent) in group 4. In 54 (46 per cent) placentae there was at least one thin anastomosis whose type was unclassifiable. There were no placentae showing AV anastomoses only from the recipient to the donor fetus. This study demonstrates that AV anastomoses are the prerequisite for the development of TTS in monochorionic placentae. The majority (74 per cent) of cases showed a higher number of AV anastomoses from donor to recipient than in the opposite direction. In approximately one third of placentae there are also AA anastomoses and the overall number of anastomoses seen and coagulated during fetoscopy is higher than reported in postnatal studies.

Arterio-Arterial Fistula↗

A preliminary report about transcervical embryoscopy.

Transabdominal amniocentesis and occasionally fetoscopy are used as a means of early diagnosis of fetal damage or abnormality after the 14th week of pregnancy. For medical reasons a still earlier method of diagnosis is desirable. We report about the transcervical approach- using CO2-gas-hysteroscopy to visualize the amnion sac and its contents.

Amniocentesis↗

Prenatal diagnosis of hemoglobinopathies. A review of 15 cases.

We attempted prenatal diagnosis of hemoglobinopathies in 15 cases--11 for beta-thalassemia and four for sickle-cell disease. Fetoscopy was used in seven cases, and placental aspiration in eight. One premature labor, with fetal loss, followed placental aspiration. Globin synthesis was assessed by incubation of samples with 3H-leucine and chain separation on carboxymethylcellulose columns. Homozygous disease was predicted in two pregnancies, which were interrupted, and the diagnosis confirmed. In one case homozygosity was suspected. A repeat test was advised but not accepted. The fetus had thalassemia trait. One pregnancy was interrupted despite our prediction of thalassemia trait. Eight pregnancies went to term. Seven predictions that the infants would not have homozygous disease were confirmed. One prediction of sickle trait proved to be sickle-cell disease. Although prenatal diagnosis of hemoglobinopathies is feasible, the present frequency of fetal loss and diagnostic error indicates need for improvement.

Anemia, Sickle Cell↗

Monoamniotic twins: an update on antenatal diagnosis and treatment.

OBJECTIVE: Monoamniotic twins are very uncommon and are characterized by a high perinatal mortality rate. Cord entanglement, prematurity, congenital anomalies and twin to twin transfusion are reportedly the main causes of death, which usually occurs before 24 weeks' gestation. The aim of this study was to review the newly developed methods for diagnosis and treatment and suggest a reasonable approach to the management of these rare cases. METHOD: We reviewed the English-language literature in the past 15 years through Medline search and subsequent examination of individual publications. RESULTS: In the past two decades, newer technologies such as advanced ultrasonography and color flow Doppler studies have enabled early diagnosis of this condition and its complications. Furthermore, new treatment modalities such as fetoscopy with laser coagulation of vascular anastomoses and treatment with non-steroidal anti-inflammatory drugs such as sulindac, to reduce amniotic fluid volume, may have contributed to a better outcome. Also, occlusion of one umbilical cord (fetal reduction) at an early stage has been suggested to prevent late complications. CONCLUSION: Cumulative experience suggests that the majority of cases can be diagnosed reliably at an early gestational age. Treatment with medical amnioreduction, surgical amnioreduction or fetal reduction in selected cases may be offered before 24 weeks' gestation. Later, intensive antepartum fetal surveillance should probably be offered until 32 weeks, at which point elective preterm delivery may be considered to prevent possible fetal death.

Amnion↗

Fetoscopic placement of a transurethral stent for intrauterine obstructive uropathy.

PURPOSE: Fetal urinary obstructive uropathy and consecutive oligohydramnios result in a poor outcome. Usually renal insufficiency and life threatening lung hypoplasia have developed at term. We report a case of in utero fetal cystoscopy and successful placement of a transurethral vesico-amniotic Double-J (Medical Engineering Corp., New York, New York) stent. Indications, results and the potential benefits of different techniques are discussed. MATERIAL AND METHODS: A 36-year-old woman (primipara) was evaluated at week 26 due to a male fetus with bilateral hydronephrosis, massive distended bladder and an open posterior urethra. Using local anesthesia the fetal bladder was punctured, a 2.6 mm endoscope was inserted and a wire was advanced antegrade through the penis. A 2.8Fr Double-J stent was then placed between the bladder and amniotic cavity. RESULTS: The bladder drained into the amnion, hydronephrosis disappeared and the lung developed normally. At week 37 a healthy infant was delivered who voided spontaneously. CONCLUSIONS: After careful selection of candidates for fetal intervention in obstructive uropathy direct vision fetoscopy and transurethral stent placement can be performed in patients with oligohydramnios, favorable urinary electrolytes and normal appearing kidneys.

Adult↗

Antenatal diagnosis of recessive dystrophic epidermolysis bullosa: collagenase expression in cultured fibroblasts as a biochemical marker.

We performed fetoscopy and skin biopsy on a 19-week fetus at risk for recessive dystrophic epidermolysis bullosa (RDEB). Ultrastructural analysis of the tissue revealed dermolytic blister formation in the skin characteristic of the disease. To develop a biochemical test for use in antenatal diagnosis of RDEB, we established skin fibroblast cultures from the 20-week aborted fetus. The collagenase production by fetal RDEB fibroblast cultures was greater than seen in normal fetal fibroblast cultures. The concentration in culture medium from fetal RDEB cultures was 5.42 +/- 0.74 micrograms/ml (mean +/- SE) compared with 2.24 +/- 1.11 micrograms/ml in normal adult control cultures and 2.05 +/- 0.61 micrograms/ml in cultures from patients with other genetic forms of epidermolysis bullosa (p less than 0.025). In contrast, the concentration of collagenase in the fetal RDEB culture medium was not different from that seen in cell cultures from known patients with RDEB (5.34 +/- 1.12 micrograms/ml). Collagenase activity of the fetal RDEB medium was also increased approximately 3.5-fold. These data indicate that enhanced expression of collagenase by fetal RDEB skin fibroblasts can serve as a biochemical adjunct, and possibly an alternative, to morphologic examination of tissue for antenatal diagnosis.

Biopsy↗