Feasibility of fetoscopic laser coagulation in triplet pregnancy

1. Diagnosis of TTTS

The diagnostic criteria for TTTS in triplet pregnancies were the same as those for twins, with the diagnosis based on sonographic findings of: 1) a maximum vertical pocket (MVP) of >8 cm in one sac (polyhydramnios) and 2) an MVP of <2 cm in the other sac (oligohydramnios) at any gestational age [3]. Once TTTS was diagnosed, the umbilical artery (UA), middle cerebral artery, and ductus venosus (DV) were evaluated in all fetuses using color and pulsed-wave Doppler to detect abnormal findings such as absent or reversed end-diastolic flow in the UA and reversed flow in the DV. Additionally, the left ventricular modified myocardial performance index (mod-MPI) was measured in all patients by positioning the Doppler sample volume in the internal leaflet of the mitral valve in an apical four-chamber view. The isovolumetric contraction time (ICT), relaxation time (IRT), and ejection times (ET) were measured using the valve click method. The mod-MPI was calculated as follows: (ICT+IRT)/ET [4].

2. Diagnosis of selective fetal growth restriction (sFGR)

The World Health Organization fetal growth charts (https://srhr.org/fetalgrowthcalculator/#/) were used to determine the weight percentile [5]. Discordance in the estimated fetal weight (EFW) was calculated by subtracting the EFW of the smaller twin from that of the larger twin, dividing by the EFW of the larger twin, and multiplying by 100. We defined sFGR as an EFW in the <10th percentile in one fetus with an intertwin EFW discordance of >25% [6].

3. Fetoscopic laser coagulation

FLC was performed in patients with TTTS at stage II or higher, symptomatic polyhydramnios, or cardiac dysfunction. Once the diagnosis of TTTS was confirmed, parents were provided counseling on the outcome, and offered various treatment options, including expectant treatment, serial amnioreduction, selective fetal termination, or FLC of the communicating placental vessels. After obtaining written informed consent from the parents, the procedure was performed by the same fetal therapy team, comprising two maternal-fetal medicine specialists (H.S.W. and M.Y.L.), three experienced nurses, and expert-trained assistants specializing in maternal-fetal medicine.

The operators used spinal anesthesia combined with a local lidocaine injection to perform FLC without intravenous sedation, enabling communication with the patient. The procedure was performed using a single 10-French flexible introducer inserted percutaneously into the recipient sac using the Seldinger technique. Depending on the placental location, a 2 mm fetoscope or 1.3 mm semi-rigid scope (Karl Storz GmbH, Tuttlingen, Germany) was passed through the cannula. Selective coagulation of all communicating vessels, including arteriovenous, arterio-arterial, and veno-venous anastomoses between the twins on the chorionic plate of the placenta, was performed using the diode laser at a power setting of 30 W with a 600 μm diameter laser fiber (WON TECH Co., Ltd, Seoul, Korea; or DiNonA Inc., Seoul, Korea). Amnioinfusion was performed with 0.9% normal saline to improve visualization during FLC, as necessary. Routine solomonization was performed, and the amniotic fluid was removed from the sac of the recipient at the end of the procedure. Transvaginal cervical cerclage was performed after FLC when the cervical length was less than 20 mm or the cervix was open.

4. Peri- and post-operative management

Perioperative management of patients who underwent FLC included prophylactic tocolytic agents and intravenous antibiotics (cephalosporins). Ultrasound examination was performed within 24 hours postoperatively, followed by daily ultrasound until the patient was discharged from the hospital. Weekly or biweekly follow-up ultrasonography was performed at our center. Complications such as intra-operative intrauterine bleeding, prelabor premature rupture of membranes (PPROM), chorioamnionitis, chorioamniotic membrane separation, recurrent TTTS, and post-operative twin anemia-polycythemia sequence (TAPS) were recorded. The decision to deliver was based on obstetric indications. Obstetric and neonatal outcome data were collected from the medical charts.

1. FLC cases selection in triple pregnancies

During the study period of 2017–2022, seven of 98 triplet pregnancies (7.1%) were complicated by TTTS, and all were dichorionic-triamnotic triplets. Of these, four patients underwent FLC, while the remaining three patients received amnioreduction, radiofrequency ablation (RFA), and expectant treatment (Fig. 1). Although all seven cases met the indications for FLC as they were stage II or higher, in three of these cases, FLC was not performed for the following reasons: in case no. 5, it was difficult to attempt FLC due to difficulties in surgical access because of the placental location, and only the recipient’s amnioreduction was performed. In case no. 6, due on the presence of 41% intertwin weight discordance with deterioration of Doppler findings in donor, RFA was performed on the donor. Case 7 was transferred to the recipient with fetal hydrops at a gestational age of 25 weeks, making it impossible to perform FLC. Details on the gestational age at the time of treatment and preoperative ultrasonographic findings in the seven TTTS-complicated cases are presented in Tables 1 and 2, respectively.

Fig. 1

Flowchart illustrating the survival and management of chorionicity and amnionicity in triplet pregnancy. In our center, 7 of 98 triplet pregnancies (7.1%) were complicated by TTTS, and all were DCTA triplets. During the study period, four dichorionic triamniotic triplets underwent FLC at our center. MCTA, monochorionic-triamniotic; DCTA, dichorionic-triamniotic; TCTA, trichorionic-triamniotic; SFR, selective fetal reduction; FDIU, fetal death in utero; TTTS, twin to twin transfusion syndrome; FCL, fetoscopic laser coagulation; RFA, radiofrequency ablation.

Table 1

Baseline characteristics of the study population

Table 2

Preoperative ultrasonographic findings in both fetuses

2. Prenatal and procedure related characteristics of FLC cases

During the study period, four patients with DC triamniotic triplets underwent FLC at our center. Diagnosis was made at a median gestational age of 19 weeks, with one case classified as Quintero stage II and three cases as Quintero stage III; there were no stage IV cases. In case no. 2, although the recipient’s MVP was 69 mm, the quantitative measurement of amniotic fluid can be influenced by maternal position, fetal positioning, and other factors. Furthermore, typical features of TTTS, including the recipient’s enlarged bladder with cardiomyopathy and the donor’s invisible bladder with selective fetal growth restriction, were observed. Karyotyping was performed in one case, which revealed normal findings, and no sonographic structural anomalies were identified in any of the cases.

The mean interval between diagnosis and FLC was 1.2 days, and the mean procedure time was 41.7 minutes. No procedure-related complications such as recurrent TTTS or post-operative TAPS occurred, and no maternal complications such as hemoperitoneum or placental abruption were observed.

3. Perinatal outcomes of FLC cases

The survival rate and median gestational age at delivery were higher in FLC cases than in other management cases. In FLC cases, four donor and four recipient triplets survived, with a median gestational age at delivery of 33 weeks and a median birth weight of 1,753 g. In other management cases, two donor and two recipient triplets survived, with a median gestational age at delivery of 29.3 weeks and a median birth weight of 1,285 g.

PPROM occurred 72 days after FLC in only one patient (case no. 1). Otherwsie, all patients with FLC had an uncomplicated postpartum course, and pathological examination of the placenta after delivery revealed a DC triamniotic placenta with no vascular anastomoses between the donor and recipient (Fig. 2). In case no. 7, in which expectant treatment was administered, the recipient died within 2 days after birth. The median stay of neonates in the intensive care unit was lower in FLC cases (21.8 days vs. 47.5 days).

Fig. 2

Photographs of the delivered placenta. There were no residual anastomoses between the recipient (fetus B) and donor (fetus C) in case no. 3. The territory of monochorionic placenta was successfully complete dichorionized by fetoscopic laser coagulation.

Three FLC cases were complicated by respiratory distress syndrome, and two had symptomatic patent ductus arteriosus requiring medical treatment. In one case, the recipient of case no. 1 was diagnosed with white matter injury, which was suspected as being hypoxic-ischemic encephalopathy (HIE) by brain ultrasonography (Fig. 3B). However, neurological symptoms were not observed until 20 months of age. None of the cases had poor neonatal outcomes, such as intraventricular hemorrhage (stage ≥III), necrotizing enterocolitis (stage ≥II), or moderate-to-severe bronchopulmonary dysplasia. The median follow-up duration was 21 months; seven patients showed normal growth and neurodevelopment, the recipient of case no. 4 exhibited delayed language development (Table 3).

Fig. 3

Brain images the recipient of case no. 1 with a complicated cerebral injury. (A) Antenatal sonographic image at gestational age 28 weeks showing normal structures. (B) Postnatal sonographic image at 4 days of age showing multifocal echogenic foci (arrow) at the bilateral periventricular white matter, indicating white matter injury such as hypoxic-ischemic encephalopathy. (C) Postnatal brain magnetic resonance imaging at 1 month of age showing punctate white matter frontoparietal lesions (arrow) with hemorrhage showing as dark signal intensity on susceptibility weighted imaging.

Table 3

Postnatal characteristics of all surviving patients