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PubMed2003

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↗
PubMed2001

Transcervical embryoscopy in missed abortion.

PURPOSE: The present study was conducted to determine the usefulness of transcervical embryoscopy in diagnosing localized and systemic defects in embryonic morphogenesis of missed abortions. METHODS: The study population consisted of 24 women with the final diagnosis of missed abortion. Prior to the instrumental evacuation of the uterus a rigid hysteroscope was passed transcervically into the amniotic cavity to obtain a detailed view of the embryo. Karyotyping was attempted in all cases included in this study. RESULTS: An embryo could be visualized in 19 cases. Ten embryos showed multiple developmental defects. CONCLUSIONS: In cases of early failure of pregnancy, embryoscopy permits visualization of the embryo in utero, unaffected by the damage usually caused by its instrumental evacuation or spontaneous passage. This technique can be a helpful tool for pathologists and geneticists in enhancing their understanding of human embryonic malformations, but more importantly, it improves clinical care and follow-up, especially in cases of repeated abortions.

Abnormalities, Multiple↗
PubMed2004

Widespread and efficient marker gene expression in the airway epithelia of fetal sheep after minimally invasive tracheal application of recombinant adenovirus in utero.

Cystic fibrosis is a common lethal genetic disease caused by functional absence of the cystic fibrosis transmembrane conductance regulator (CFTR). Although a candidate disease for in utero gene therapy, demonstration of potentially therapeutic levels of transgene expression in the fetal airways after minimally invasive gene delivery is a mandatory prerequisite before application of this approach in humans can be considered. We report here on the delivery of a beta-galactosidase expressing adenovirus directly to the airways of fetal sheep in utero using ultrasound-guided percutaneous injection of the trachea in the fetal chest. Injection of adenoviral particles to the fetal airways was not associated with mortality and resulted in low-level expression in the peripheral airways. However, complexation of the virus with DEAE dextran, which confers a positive charge to the virus, and pretreatment of the airways with Na-caprate, which opens tight junctions, increased transgene expression, and a combination of these two enhancers resulted in widespread and efficient gene transfer of the fetal trachea and bronchial tree. Using a percutaneous ultrasound-guided injection technique, we have clearly demonstrated proof of principle for substantial transgene delivery to the fetal airways providing levels of gene expression that could be relevant for a therapeutic application of CFTR expressing vectors.

Adenoviridae↗
PubMed1995

Toward fetal therapy using needle embryofetoscopy.

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.

Abortion, Induced↗
PubMed1997

Umbilical cord coagulation by operative microendoscopy at 16 weeks' gestation in an acardiac twin.

Twin reversed arterial perfusion (TRAP) sequence carries high mortality and morbidity in the normal twin due to a hemodynamic imbalance through the feto-fetal vascular anastomosis. This report describes the ultrasound features of TRAP in the first trimester and a new technique for selective fetocide in the early second trimester in monochorionic twin pregnancies complicated by the TRAP sequence. Laser coagulation of the umbilical cord of the acardiac twin was performed under sonoendoscopic control. The blood flow in the umbilical cord of the acardiac twin was successfully arrested and the survivor developed normally. TRAP sequence can be recognized in the first trimester and successfully arrested by microendoscopic surgery.

Adult↗
PubMed1998

Alternative technique for Nd: YAG laser coagulation in twin-to-twin transfusion syndrome with anterior placenta.

Nd: YAG laser coagulation is used to treat severe twin-to-twin transfusion syndrome (TTS). Success of the technique depends on visualization of the placenta, the fetal membranes and the targeted vessels, as well as obtaining an optimal inclination angle for laser coagulation. In the rare case of an extensive anterior placenta, it may be difficult to achieve these conditions using the percutaneous approach. Here, we propose an alternative to the percutaneous procedure. Modifications involve an open access and the use of a flexible cannula and bent scope. An extraplacental area, usually at the fundus, is identified by B-mode and color Doppler imaging. A mini-laparotomy is made under general anesthesia. The viscera are retracted and the cannula is inserted under direct view and ultrasound control by the Seldinger technique. The curved fiberscope is passed through the flexible cannula, allowing adequate inspection of the placenta, and target vessels can be coagulated at an angle close to 90 degrees. After the procedure, the uterus is closed primarily to prevent postoperative leakage of amniotic fluid or hemorrhage. This technique has been successfully used in six patients with TTS and a completely anterior placenta, with a gestational age between 18.5 and 22.0 weeks. In all patients, the amniotic cavity was accessed without hemorrhage. The outcomes are similar to those published previously for laser coagulation. The mean interval from intervention until delivery was 10.5 weeks. All 12 fetuses were live born but four died from complications of extreme prematurity. No maternal complications occurred.

Female↗
PubMed1999

Prognostic factors in severe twin-twin transfusion syndrome treated by endoscopic laser surgery.

OBJECTIVE: The aim of this study was to investigate clinical and sonographic parameters, in particular Doppler blood flow measurements, in severe second-trimester twin-twin transfusion syndrome before and after endoscopic laser coagulation of the placental vascular anastomoses, to correlate these data with fetal outcome and to determine whether fetal blood flow measurements could help to estimate the probability of fetal survival. METHODS: In 121 cases of severe twin-twin transfusion syndrome examined between 17 and 26 weeks of gestation, the following investigations were performed: fetal biometry, placental location, deepest pool of amniotic fluid, echocardiography and Doppler sonography of the umbilical arteries and the ductus venosus of both twins before and after fetoscopic laser ablation of the placental anastomoses. RESULTS: The overall survival rate was 64% (156/242). Both fetuses survived in 48% (58/121) and one fetus survived in 33% (40/121), resulting in 81% (98/121) of pregnancies with at least one survivor. Gestational age at the time of the procedure and placental location had no significant influence on fetal survival. The amniotic fluid volume drained after laser coagulation correlated significantly (p = 0.038) with the risk of miscarriage or extremely premature delivery within 4 weeks of the procedure. Intertwin discrepancy in abdominal circumference showed a significant negative correlation (p = 0.004) with the probability for survival of donor fetuses. Before the procedure, 19% (23/121) of donor twins and 5% (6/121) of recipient twins showed absent or reversed end-diastolic flow in the umbilical artery (p = 0.001). This finding had no significant influence on the survival rate of donors. An increase of waveform indices in the umbilical artery 1 day after the procedure compared to immediately after the procedure correlated significantly with a lower probability for survival of donors (p = 0.042) and recipients (p = 0.018). Before the procedure, 37% (45/121) of recipient twins and 9% (10/113) of donor twins showed absent or reversed flow during atrial contraction in the ductus venosus (p < 0.0001). This finding had a significant negative influence on the survival rate of recipient fetuses (p = 0.02). Furthermore, an increase of waveform indices in the ductus venosus 1 day after the procedure compared to immediately after the procedure correlated significantly with a lower probability of survival in recipients (p = 0.005). CONCLUSIONS: Fetoscopic laser coagulation of the placental vascular anastomoses in severe mid-trimester twin-twin transfusion is a potentially corrective and effective, minimally invasive procedure. Doppler investigation of the umbilical and fetal circulations provides important information on the fetal condition, prognosis and therapeutic effects of the intervention. Signs of congestive heart failure in the recipient may reduce the probability of survival, whereas increased placental resistance in the donor before the procedure is not necessarily associated with a reduction in the probability of survival after laser coagulation.

Arteriovenous Anastomosis↗
PubMed1999

Intrauterine sling: a complication of the stuck twin syndrome.

Stuck twin syndrome usually presents with polyhydramnios in the recipient sac and severe oligohydramnios in the donor sac. The donor is displaced against the uterine wall and remains adherent in that position. We present a case in which the diagnosis was more complicated, owing to the suspension of the stuck twin by a sling within the sac of the recipient. A monochorionic diamnionic twin gestation was complicated by twin-twin transfusion syndrome at 18 weeks of gestation. In our example, the stuck twin was suspended by a sling from the placenta. The sling band represented the intertwin membrane that was folded upon itself. Amniotic fluid from the recipient twin was present in three dimensions around the stuck twin, except for the sling band. The suspension of the stuck twin by a sling within the amniotic fluid of the recipient is an unusual manifestation of the stuck twin syndrome.

Adult↗
PubMed2000

Transabdominal first trimester embryofetoscopy as a potential approach to early in utero stem cell transplantation and gene therapy.

OBJECTIVE: To explore the potential of embryofetoscopy for early diagnosis and for access to the fetal circulation in the first trimester of gestation. DESIGN: Transabdominal embryofetoscopy was performed in 14 patients scheduled for termination of pregnancy using a 1-mm semirigid fibreoptic telescope with a 18 gauge examination sheath and a single-chip digital camera. A 25 gauge needle was inserted through an additional 21 gauge side port to access the fetal circulation. RESULTS: Fetal head, face, abdomen, complete upper and lower limbs could be visualized in over 80% of cases. On the contrary, the fetal back and external genitalia could be examined in detail only in some cases (35.7% and 64.3%, respectively). Injection of 10-20 ml saline improved visibility in 43% of cases. Funipuncture was successful in two of three attempts. CONCLUSIONS: Our experience suggests that embryofetoscopy is a useful tool for early diagnosis in the first trimester of pregnancy. Funipuncture is possible thus providing the means for an early intravascular stem cell application.

Adult↗
PubMed2000

Selective versus non-selective laser photocoagulation of placental vessels in twin-to-twin transfusion syndrome.

OBJECTIVE: We have recently described a surgical technique for the treatment of twin-to-twin transfusion syndrome (TTTS) that allows precise identification of vascular anastomoses (selective laser photocoagulation of communicating vessels, or S-LPCV). The purpose of this study was to compare S-LPCV with the previous non-selective technique (NS-LPCV) that targeted all vessels crossing the dividing membrane. MATERIALS AND METHODS: Patients with TTTS were treated with NS-LPCV from May 1994 to June 1997 and with S-LPCV from July 1997 to December 1999. TTTS was defined as polyhydramnios of > or = 8 cm maximum vertical pocket (MVP) in the recipient twin and oligohydramnios of < or = 2 cm MVP in the donor twin. Outcome was measured as survival per number of pregnancies and per number of fetuses together with limited morbidity data. RESULTS: NS-LPCV was used in 18 patients and 74 were treated with S-LPCV. Three patients interrupted their pregnancies electively after surgery (S-LPCV) and were removed from further analysis. Survival of at least one fetus was higher in S-LPCV (83.1%) than in NS-LPCV (61.1%) (P = 0.04), mostly due to a lower rate of dual intra-uterine fetal demise in S-LPCV (5.6%) than in NS-LPCV (22%) (P = 0.05). There were more hydropic fetuses in the NS-LPCV group (27%) than in the S-LPCV group (5.4%), but this difference did not account for the results. There was no difference in the survival per number of fetuses between the two groups. CONCLUSIONS: S-LPCV represents an important evolution in the surgical treatment of TTTS. The use of this technique by all centers should allow better comparison of fetal survival and morbidity rates. S-LPCV should be the standard technique in trials comparing amniocentesis versus laser for the treatment of severe TTTS.

Arteriovenous Anastomosis↗
PubMed2002

Transient hydropic signs in the donor fetus after fetoscopic laser coagulation in severe twin-twin transfusion syndrome: incidence and clinical relevance.

OBJECTIVE: To evaluate the incidence, characteristics, and impact on perinatal outcome of the development of hydropic signs in the donor fetus after laser coagulation for severe twin-twin transfusion syndrome in the second trimester. METHODS: Forty cases of second-trimester severe twin-twin transfusion underwent fetoscopic laser coagulation of placental anastomoses and were followed up with serial ultrasound up to 14 days after therapy. Ultrasound scans were performed just before, and on days 1, 3, 5 and 14 after therapy, and fetuses were monitored for the presence of hydropic signs (skin edema, pleural effusion, ascites and pericardial effusion). Response to therapy and perinatal outcome in terms of neonatal survival were recorded for all cases. RESULTS: Four recipients (10%) and three donors (7.5%) died over the first 72 h after therapy. During the study period, two recipients (5.5%) developed frank hydrops fetalis, and eventually died in utero. Ten donors (27.0%) developed one or more hydropic signs. In nine (90%), signs were mild or moderate and transient (mean, 3.2 days), while in one case hydrops worsened and the fetus eventually died. No donors with transient hydrops died in utero, and two died postnatally due to extreme prematurity. Gestational age at procedure and deepest amniotic fluid vertical pocket were similar between hydropic and non-hydropic donors. Discrepancy in estimated fetal weight at procedure was significantly lower in donors developing hydrops (9.6 (SD, 6.4) vs. 17.8 (14.4)%,P = 0.018). In pregnancies with hydropic donors, gestational age at delivery (33.1 (3.4) vs. 29.7 (3.5) weeks,P = 0.015) and birth weight for recipient (2392 (423) vs. 1631 (576) g, P < 0.001) and donor (1908 (774) vs. 1281 (583) g,P = 0.021) were significantly higher. The development of transient hydrops had no influence on neonatal survival at 28 days nor on the rate of clinical resolution of intertwin transfusion. CONCLUSIONS: Transient hydropic signs may develop in a proportion of donor fetuses after laser coagulation for severe twin-twin transfusion syndrome. This phenomenon is normally not associated with a poor prognosis, and possibly indicates an hemodynamic adaptation response following interruption of the transfusion process.

Female↗
PubMed2002

Impact of laser coagulation in severe twin-twin transfusion syndrome on fetal Doppler indices and venous blood flow volume.

OBJECTIVE: To evaluate the impact of fetoscopic laser coagulation of placental anastomoses in severe twin-twin transfusion syndrome on fetal Doppler indices and umbilical vein blood flow volume as calculated with Doppler and two-dimensional ultrasound. METHODS: Thirty-two cases of second-trimester severe twin-twin transfusion undergoing laser therapy were examined with serial ultrasound before and 1, 3 and 5 days after therapy. Pulsatility indices in the umbilical artery and ductus venosus were measured. Blood volume flow at the level of the intra-abdominal umbilical vein was calculated by means of Doppler and two-dimensional ultrasound. The development of hydropic signs in donors was recorded. Perinatal outcome in terms of neonatal survival was recorded for all cases. RESULTS: In recipients, ductus venosus pulsatility index decreased progressively after therapy and, by day 5, median pulsatility index was significantly lower than that before therapy (0.97 vs. 0.82, P < 0.0001). Umbilical vein blood flow volume in recipient twins showed no significant variations before and after laser. In donors, umbilical artery pulsatility index decreased significantly by the first day following therapy (2.1 vs. 1.6, P < 0.0001). Previously absent or reverse umbilical end-diastolic flow reappeared after therapy in 46% (7/15) of donors. Ductus venosus pulsatility index in donors increased significantly by day 1 after therapy (0.99 vs. 1.35, P < 0.0001) but, over days 3 and 5, it returned towards preoperative values. Umbilical vein flow volume measurements (mL/min/kg) in the donor increased by approximately 50% the day after treatment (151 vs. 232, P < 0.0001) and remained elevated. Umbilical vein flow volume before laser therapy was significantly lower in donors compared to recipients (151 vs. 260, P < 0.0001), but the difference was non-significant after treatment (240 vs. 267). One or more hydropic signs developed in eight (25%) donors during the 5 days' observation after therapy. CONCLUSIONS: Laser therapy induced important changes in fetal hemodynamic parameters, resulting in a reversion of the disturbances associated with severe twin-twin transfusion syndrome. The recipient twin showed a progressive improvement of previous signs of right cardiac overload. The donor experienced a substantial increase in umbilical vein blood volume flow accompanied by a transitory state of relative right overload, which may explain the development of transient hydropic signs in a proportion of donors.

Female↗