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Objective To assess the safety and efficacy of a modified fetoscopic laser ablation technique for the management of severe twin–twin transfusion syndrome (TTTS) in a large series of pregnancies.
Design Prospective cohort study.
Setting Tertiary referral fetal medicine unit.
Population Women with pregnancies complicated by severe TTTS (Quintero stage III or IV), before 26 weeks of gestation.
Methods Fetoscopic laser ablation of placental anastomoses was performed. The sonoendoscopic approach was used to identify the placental vascular equator and to photocoagulate crossing vessels.
Main outcome measures Overall survival, fetal and perinatal mortalities, gestational age at delivery, birthweight, operating time and recurrence of TTTS.
Results A total of 77 women underwent the procedure. The mean gestational age at treatment was 20 (range 16–26) weeks. On average, four vessels were ablated during each procedure, with a mean operative time of 15 (range 5–25) minutes. None of the women required a repeat fetoscopic laser treatment for recurrence of the TTTS. There was at least one survivor in 74% (57/77) of pregnancies, and the overall survival rate was 57% (88/154).
Conclusions Fetoscopic laser ablation is a safe and effective form of treatment in the management of severe TTTS. The technique of identifying the common villous district of the placenta by ultrasound and photocoagulating any vessels crossing the vascular equator appears to be an acceptable alternative to both the nonselective and highly selective methods described so far. This approach is associated with a short operating time, low likelihood of TTTS recurrence or fetal anaemia and with survival results that are equivalent to previously reported techniques.
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Twin-to-twin transfusion syndrome (TTTS) is a recognised midtrimester complication occurring in up to 15% of monochorionic gestations.1 If left untreated, the mortality of this condition exceeds 90%, with significant neurological morbidity in 30–50% of surviving twins.2,3 The most well established treatment options for TTTS include serial amnioreduction and fetoscopic laser ablation of the placental vascular anastomoses. The reported survival rates for amnioreduction are 39–64% compared with 56–62% for fetoscopic laser ablation.4–7 Long-term neurodevelopmental morbidity rates for amnioreduction are 7–26%3,8–12 compared with 6–11% for laser ablation.13–15 In 2005, a systematic review confirmed the significant increase in survival rates and reduction in neurological morbidity with the use of laser ablation compared with amnioreduction in severe TTTS.16 However, laser ablation is a more complex technique and less readily available than amnioreduction.
In the nonselective fetoscopic laser technique, all vessels crossing the intertwin membrane are photocoagulated.4 This approach is thought to be associated with higher fetal loss rates than the highly selective technique, where all vessels are followed systematically from the point they cross the intertwin membrane until it can be verified whether they are normal or resulting in an anastomoses with the co-twin.17 Although the highly selective technique may have a higher survival rate, it is a time-consuming operation, with an average operating time of 73 minutes (range 20–178 minutes).17 We previously described an alternative, simpler, faster technique for undertaking selective laser ablation using preoperative ultrasound identification of the placental common villous district and vascular equator of the placenta by determining the umbilical cord placental insertion sites.18 The aim of this study was to evaluate the use of the placental vascular equator technique for fetoscopic laser ablation in severe TTTS.
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Between January 2002 and March 2006, fetoscopic laser coagulation was carried out in 77 pregnancies complicated by severe TTTS (Quintero stage III or IV).19 In all cases, first-trimester ultrasound established monochorionicity by showing a single placental mass and the absence of the lambda sign of the intertwin membrane.20 All pregnancies showed characteristic ultrasound features of TTTS: polyhydramnios (deepest vertical pool of ≥8 cm) and a distended bladder in the recipient, and oligohydramnios (deepest vertical pool of ≤1 cm) and a collapsed bladder in the donor. The Quintero staging system was used to describe the severity of the TTTS.19
Women were counselled regarding the possible outcomes of the available options, including expectant management, amnioreduction and fetoscopic laser coagulation.
Preoperative ultrasound assessment
Prior to the procedure, ultrasound was used to visualise the placental site, the donor and recipient umbilical cord placental insertions and to identify the common villous district of the placenta, as previously described.18 In short, the common villous district was estimated to run midway and perpendicular to an imaginary line running between the donor and recipient cord placental insertion sites.18 The anatomical relationship of the cord insertions and common villous district described above are well established.21 In 2005, this anatomical relationship was used to accurately describe placental territories in a placental morphology study after fetoscopic laser ablation.22 The marginal cord insertions seen in the majority of TTTS pregnancies mean that the common villous district is usually eccentrically positioned, with a smaller placental territory for the donor. The placental disc, cord insertions and vascular equator were then marked on the maternal abdomen to help determine the site of fetoscope entry and to shorten operating times.
The fetoscope entry site was chosen in order to enter the recipient sac on the opposite side of the uterus to the placenta without injury to the mother or the fetuses. Local anaesthesia (1% lignocaine) was injected from skin to myometrium, and intravenous antibiotic prophylaxis (cefuroxime 750 mg) and intravenous maternal sedation (5–10 mg diazepam as required) were given perioperatively. A rigid 2-mm-diameter 0° fetoscope in a 2.8-mm operating sheath (Olympus Keymed, Southend-on-Sea, UK) was introduced into the recipient sac under continuous ultrasound guidance. A 400-μm-diameter laser fibre (KTP/Nd:YAG Laserscope; Gwent, UK) was passed down the operating channel until the tip was just visible through the fetoscope. When the placenta was positioned anteriorly, a lateral fetoscope insertion in the maternal flank was used, and the maternal abdomen was depressed manually to bring the equatorial region into view.
Ultrasound guidance was used to bring the fetoscope tip close to the common villous district previously marked on the maternal abdomen. Once the placenta was visible fetoscopically, the rest of the procedure was conducted under direct vision. Transabdominal ultrasound was used to guide the tip of the fetoscope along the predrawn line on the abdomen, and fetoscopy was used to visualise the vessels directly. The fetoscope was always orientated using a ‘cardinal’ point system: north (donor cord insertion) and south (recipient cord insertion). The fetoscope was then moved along the ultrasonographically determined common villous district (traversing the placenta in an east–west orientation) to visualise any vessels crossing the placental equator. All vessels judged to cross the vascular equator were coagulated using a pulsed laser with an output of 30–60 watts in 3-second bursts. In the vast majority of cases, the vessels seen in the common villous district were not paired by another vessel from the same fetus. Such single, unpaired vessels were always photocoagulated. On rare occasions, paired vessels from the same twin were seen in the common villous district. These were ablated whenever vessels from the co-twin were visible in close proximity in order to ensure that there were no persistent postoperative intertwin vascular connections.
At the end of the procedure, amniotic fluid was drained until the amniotic fluid index in the recipient normalised. A 40-ml recipient amniotic fluid sample was always sent for fetal karyotyping. In order to reduce the risks for preterm delivery, tocolytic therapy (glyceryl trinitrate patch 5 mg) was administered for 24 hours. The women were discharged from the hospital from 8 hours postoperatively, and serial follow-up appointments to check the effects of therapy were scheduled for 2 and 8 weeks later.
The outcomes measured included the severity of the TTTS at presentation, operative details (gestation, operative time from fetoscope insertion to removal, laser power used and amount of fluid drained), delivery details (gestation and birthweight) and perinatal outcome (spontaneous miscarriage, medical termination, intrauterine death, neonatal death and infant survival). Outcome measures were evaluated on the basis of the number of pregnancies or the number of fetuses or infants, as appropriate.
Continuous variables were reported as medians (±range). In the analysis of the time to delivery, data were censored at the time of the termination of pregnancy.
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Seventy-seven monochorionic twin pregnancies were diagnosed with severe TTTS and underwent fetoscopic laser ablation during the study period. All cases were diagnosed as either Quintero stage III (n= 68) or stage IV (n= 9). The cord insertion was noted to be marginal in 67 (87%) donors and central in 61 (79%) recipients. The operative details are shown in Table 1. An average of four (range 1–11) vessels were photocoagulated intraoperatively. The delivery details and perinatal outcomes are shown in Tables 2 and 3. The median interval between treatment and delivery in all pregnancies, including miscarriages, was 9 weeks (interquartile range 3–13 weeks). There was at least one surviving infant in 74% (95% CI: 63–83%) of the pregnancies treated. The overall fetal survival rate was 57% (88/154, 42 donors and 46 recipients).
Table 1. Operative outcomes with details of gestational age at treatment, operating time from fetoscope entry to exit, amount of laser energy used for the ablation and quantity of amniotic fluid drained at the end of the procedure
| ||Median (range)|
|Gestational age (weeks)||20 (16–26)|
|Operating time (minutes)||15 (5–25)|
|Laser power (joules)||2526 (469–9254)|
|Amniotic fluid drained (ml)||1000 (200–7000)|
Table 2. Obstetric outcomes with details of survival (%), gestational age range at delivery (%) and birthweight (median and range)
| ||No. of pregnancies (%)|
|0 survivors||20 (26)|
|At least one survivor||57 (74)|
|One survivor||26 (34)|
|Two survivors||31 (40)|
|Gestational age at delivery (weeks)|
|24 to <28||14 (18)|
|28 to <32||7 (9)|
|Birthweight (g)||Median (range)|
Table 3. Fetal and perinatal mortalities, expressed as number of fetuses and percentage of 154 fetuses overall
| ||n (%)|
|Intrauterine death||39 (25)|
|Neonatal death||10 (6)|
There were five spontaneous miscarriages within 7 days of the procedure (Table 3, ten fetal losses). In a further six pregnancies (seven fetuses), the parents requested medical termination of pregnancy because of the death of one twin (n= 3) or the diagnosis of cerebral haemorrhage (n= 4). In the latter four cases, the diagnosis was made immediately after the procedure because amniodrainage significantly improved ultrasound visualisation.
There was no evidence of a recurrence/persistence of TTTS or fetal anaemia evident on ultrasound monitoring in the continuing pregnancies. Repeat fetoscopic laser ablation, amniodrainage or fetal intravascular transfusion was not required prior to delivery in any of the cases.