Objective
The objective of the study was to compare the outcome in women with twin-twin transfusion syndrome (TTTS) who were managed by selective laser ablation of placental anastomoses (S-LASER) vs equatorial dichorionization of the anastomoses and chorionic plate (ED-LASER).
Study Design
We conducted an analysis of 2 consecutive cohorts with TTTS treated with S-LASER and ED-LASER. Preoperative, procedural, delivery, and outcome details were compared between treatment groups.
Results
A total of 147 twin pregnancies had laser (S-LASER, n = 71; ED-LASER, n = 76). Obstetric history, Quintero stage, placental location, individual arterial and venous Doppler parameters, and gestational age at laser and delivery did not differ. Use of lens fetoscope (96.1% vs 50.7%), coagulated anastomosis count (11 vs 15, P < .001), complete equatorial plate visualization (77.5% vs 92.1%, P = .019), and amniotic fluid transparency (80.3% vs 94.7%, P = .011) was greater during ED-LASER. Procedure-related complications, gestational age at delivery, and perinatal details were comparable between groups. ED-LASER was associated with significantly lower recurrence of TTTS (3.9% vs 8.5%), twin anemia polycythemia sequence (2.6% vs 4.2%), and amniotic fluid abnormalities (0% vs 5.6%, P < .05 for all comparisons). Logistic regression identified complete visualization of the equator as the primary determinant for successful TTTS treatment and coagulation of the chorionic plate as an independent cofactor. Double survival at age 6 months was significantly higher after ED-LASER (68.4% vs 50.7%, P < .05), attributable to a lower postlaser and neonatal mortality rates.
Conclusion
In patients with TTTS, photocoagulation of causative anastomoses and the chorionic plate along the vascular equator decreases recurrence without increasing adverse outcome and improves survival compared with the selective technique.
The vascular source of imbalance causing twin-to-twin transfusion syndrome (TTTS) in monochorionic placentation is at the vascular equator, the watershed of the vascular territories of each twin. Fetoscopic visualization and laser ablation of causative placental anastomoses (LASER) is the established first-line curative therapy. When this is done by identifying each individual anastomosis along the equator (selective LASER [S-LASER]), closure of the causative connections and preservation of the placental territory offers the greatest survival benefit compared with amnioreduction and nonselective techniques. Unsuccessful LASER can result in treatment failure, recurrence of amniotic fluid discordance, twin anemia polycythemia sequence (TAPS), or decreased twin survival.
Evidence of incomplete treatment has been reported in up to 19% of patients and in those undergoing placental studies can be related to the presence of residual anastomses. Residual anastomoses have been attributed to several causes including secondary enlargement of small or collapsed vessels that were missed by S-LASER.
A laser technique that coagulates the surface of the chorionic plate between the main anastomotomotic channels along the vascular equator has been described ( Figure and personal communication, Professor K. H. Nicolaides). This equatorial dichorionization, or Solomon technique, has been suggested to decrease recurrence rate by targeting the placental territories left untreated by S-LASER ( www.trialregister.nl ; NTR1245). The aim of this study was to test the hypothesis that equatorial dichorionization and LASER photocoagulation of vessels (ED-LASER) decreases TTTS recurrence compared with S-LASER, without adverse effect on perinatal outcome.
Materials and Methods
This was a retrospective analysis of patients referred for treatment of TTTS between 2005 and 2011. Patients who met the following criteria were eligible for inclusion: (1) monochorionic twin gestation; (2) diagnosis of TTTS established before 26 weeks’ gestation; and (3) polyhydramnios in the recipient twin’s amniotic sac (maximum vertical pool greater than 8 cm at less than 20 weeks’ gestation and greater than 10 cm at 21-25 weeks’ gestation) and oligohydramnios in the donor (stuck) twin’s amniotic sac less than 2 cm. Exclusion criteria were fetal death, ruptured membranes, and preterm labor.
Following a detailed ultrasound evaluation of fetal anatomy, amniotic fluid volume, bladder filling, and cardiovascular parameters, the severity of TTTS was assigned according to the Quintero staging system. We analyzed cases that were referred after the primary surgeon (A.A.B.) completed 1 year of training at a center with an average case load of 2 fetoscopic LASER procedures per week and personally performed 30 of these procedures. The choice of analgesia, intraoperative recording of procedure details, postdelivery follow-up, and acquisition of source documentation by the fetal therapy team was identical throughout the entire study period. The following approach was utilized for the LASER treatment.
After local or regional anesthesia, the trocar was inserted percutaneously under ultrasound guidance into the recipient sac. For a posterior placenta, a 2 mm 0° fetoscope and an insertion sheath with a working channel (outer diameter 3.2 mm, 11603AA or 26008AA, and 26161 U; Karl Storz GmbH, Tuttlingen, Germany) were used. For anterior placenta, a 2 mm 30° fetoscope and double sheath with Albaran mechanism (outer diameter of 3.8 mm, 26008 BUA, 26161 UH and 26161 UF; Karl Storz GmbH) were used.
Photocoagulation was carried out using KTP laser energy, adjusting the delivery watts as required to achieve vessel coagulation (600 μm bare fiber; Endostat, Laserscope, San Jose, CA). This is a neodymium:YAG laser that is directed through a potassium titanyl phosphate crystal reducing the output wavelength to 532 nm. During S-LASER all visible intertwin anastomoses and vessels with uncertain course were coagulated if they crossed the equator. During ED-LASER the same approach was chosen for the coagulation of the anastomoses. However, in addition, the chorionic plate was coagulated along the line that connected the anastomoses until visual blanching was observed ( Figure ). For bidirectional vessels the nearest arteriovenous anastomoses were chosen as reference points for the equator.
Intraoperatively, anastomosis type and size, location of intertwin membrane, equator visualization, and amniotic fluid transparency (categorized as clear or cloudy) were recorded. Complete anastomosis visualization indicated that vessel origins and connection could be verified. Complete visualization of the vascular equator indicates that the line connecting all anastomoses could be visually inspected from 1 placental edge to the other. Coagulation was noted as being satisfactory if complete blanching of the vessel or chorionic plate was achieved. At the end of the procedure, amniodrainage was performed to reduce the fluid in the recipient sac to a maximum vertical pocket of 6 cm or less. The procedure time, maximum watts, minutes and joules of laser energy, and intraoperative complications were recorded. Ultrasound follow-up was performed for 2 days postoperatively and then was tailored in frequency as clinically indicated.
For patients returning to their referring providers, contact was maintained through our program coordinator to ascertain follow-up. Following delivery, copies of medical records were obtained for all patients to verify prenatal course, delivery circumstances, and outcome.
Treatment success was defined as complete resolution of TTTS. Recurrent TTTS was defined as disease persistence after 1 week. The definition of TAPS included an increase in the middle cerebral artery (MCA) peak systolic velocity following single twin demise. Persistence of abnormal amniotic fluid pocket in either twin was recorded. For the purpose of this study any of these findings were considered as disease recurrence.
To account for mortality that relates to the procedure, peripartum, and neonatal variables, we defined survival as a live infant at age 6 months. Between January 2005 and June 2008, all procedures were performed with the intention to carry out S-LASER. Following this, ED-LASER was the intended treatment choice for all cases. Procedure details, recurrence rates and details, delivery cicumstances, and survival until age 6 months were compared between these 2 cohorts.
Statistical analysis was performed using SSPS 19 (SSPS Inc, Chicago, IL). For all values, a value of P < .05 was considered statistically significant. The study protocol was approved by the institutional review board, and all patients signed informed written consent.
Results
Among 147 patients meeting inclusion criteria 71 (48.3%) had S-LASER and 76 (51.7%) had ED-LASER. Patients undergoing equatorial dichorionization had a higher body mass index, were more likely of African American ethnicity, and were more frequently conceived through assisted reproductive treatment ( Table 1 ). Other maternal characteristics, gestational age at referral, fetal growth, amniotic fluid pockets, placental location, and Doppler parameters were identical in both treatment groups. Hydrops at presentation was twice as frequent in patients undergoing S-LASER (7 vs 3 patients, χ 2 P = .03, Table 2 ).
| Characteristic | Selective LASER (n = 71) | Equatorial dichorionization (n = 76) | P value |
|---|---|---|---|
| Maternal age | 30 (18–49) | 30 (18–50) | .741 |
| Body mass index | 21.6 (11.5–46.1) | 24.8 (17.2–39.1) | .010 |
| Ethnicity | |||
| Caucasian | 59 (83.1%) | 55 (72.4%) | |
| African American | 9 (12.7%) | 17 (22.4%) | .018 |
| Hispanic | 3 (4.2%) | — | |
| Asian-Indian | — | 4 (5.3%) | |
| Parity | |||
| 0 | 43 (60.6) | 41 (53.9) | |
| 1 | 22 (31.0) | 22 (29.0) | .414 |
| 2 | 5 (7.0) | 11 (14.5) | |
| ≥3 | 1 (1.4) | 2 (2.6) | |
| Conception through ART | 2 (2.8) | 12 (15.8) | .010 |
| Prior preterm birth | 3 (4.2) | 5 (6.6) | .720 |
| Cervical length | 35 (10–52) | 35 (5–62) | .512 |
| Prelaser cerclage | 1 (1.4) | — | |
| Postlaser cerclage | 2 (2.8) | 6 (7.9) | .278 |
| Variable | Selective LASER (n = 71) | Equatorial dichorionization (n = 76) | P value |
|---|---|---|---|
| Gestational age at presentation | 19.2 (16–25.5) | 19.5 (15.3–25.2) | .120 |
| Estimated fetal weight | |||
| Recipient | 350 (178–800) | 364 (145–920) | .462 |
| Donor | 244 (132–551) | 276 (119–672) | .375 |
| Weight discordance | 24% (–4 to 51) | 26% (–5 to 51) | .575 |
| Maximum amniotic fluid pocket | |||
| Recipient | 10.4 (8–18) | 10.9 (8–18) | .468 |
| Donor | 0.8 (0–2) | 0.9 (0–1.5) | .436 |
| Placental location | |||
| Anterior | 31 (43.7) | 32 (42.1) | |
| Posterior | 39 (54.9) | 43 (56.6) | .563 |
| Lateral | 1 (1.4) | — | |
| Fundal | — | 1 (1.3) | |
| Umbilical artery AEDV | |||
| Recipient | 3 (4.2) | 5 (6.6) | .721 |
| Donor | 10 (14.1) | 13 (17.1) | .651 |
| DV absent/reversed a-wave | |||
| Recipient | 14 (19.7) | 13 (17.1) | .667 |
| Donor | 2 (2.8) | 4 (5.3) | .682 |
| Umbilical vein pulsations | |||
| Recipient | 23 (32.4) | 25 (32.9) | .450 |
| Donor | 7 (9.9) | 14 (18.4) | .462 |
| Hydrops | |||
| Recipient | 7 (9.9) | 3 (3.9) | .035 |
| Donor | — | — | — |
| Quintero stages | |||
| I | 8 (11.3) | 10 (13.2) | |
| II | 27 (40.8) | 30 (36.8) | |
| III | 24 (38.0) | 38 (46.1) | .432 |
| IV | 7 (9.9) | 3 (3.9) |
The median gestational age at fetoscopy was 20 weeks 4 days. The number of observed anastomoses and procedures with completely visualized vascular equator and clear amniotic fluid was greater in ED-LASER ( Table 3 ). There were no differences in operative time, amount of laser energy used, visual appreciation of anastomoses, and coagulation between the procedure types. The higher rate of unintentional septostomy after S-LASER did not translate into significant differences in postprocedure complication rates. Following fetoscopy, 76.1% of patients with S-LASER and 84.2% with ED-LASER were discharged with 2 survivors after 48 hours. Preterm birth complicated 8.5 of selective and 5.2% of ED-LASER procedures ( Table 3 ).
| Variable | Selective LASER (n = 71) | Equatorial dichorionization (n = 76) | P value |
|---|---|---|---|
| Gestational age at fetoscopy, wks | 20.4 (16.2–25.6) | 20.5 (16–26) | .555 |
| Fetoscope | |||
| Fiberscope | 35 (49.3) | 3 (3.9) | < .001 |
| Rod lens | 36 (50.7) | 73 (96.1) | |
| Laser energy used | |||
| Maximum watts | 15 (5–50) | 15 (10–30) | .980 |
| Minutes of laser coagulation | 2.41 (0.10–12.4) | 2.36 (0.10–8.2) | .658 |
| Total joules used | 1890 (190–17437) | 2388 (158–9214) | .243 |
| Procedure length | |||
| Fetoscopy time, min | 39.5 (9–76) | 38 (10–71) | .912 |
| Amnioreduction time, min | 5 (0.5–12) | 5 (0.5–13) | .184 |
| Amnioreduction, mL | 1600 (0–3500) | 1500 (0–3500) | .232 |
| Number of coagulated anastomoses | 11 (3–35) | 15 (2–39) | < .001 |
| Visualization | |||
| All anastomoses visualized | 51 (71.8) | 64 (84.2) | .076 |
| Coagulation visually complete | 64 (90.1) | 71 (93.4) | .554 |
| Vascular equator visualized | 55 (77.5) | 70 (92.1) | .019 |
| Good visibility | 57 (80.3) | 72 (94.7) | .011 |
| Intraoperative complications | |||
| Septostomy | |||
| Intentional | 1 (1.4) | — | |
| Unintentional | 6 (8.5) | 1 (1.3) | .049 |
| Chorioamniotic separation | 3 (4.2) | 3 (3.9) | .559 |
| Maternal bleeding | 2 (2.8) | 1 (1.3) | .610 |
There were no differences in preoperative Doppler and growth parameters between stillbirths and surviving recipients. In contrast, donors with postlaser demise had significantly higher preoperative umbilical artery Doppler resistance (umbilical artery-pulsatility indes [PI], 1.67; range, 0.77–4.27 vs 1.48; range, 0.73–4.34; Mann-Whitney U P = .041) and lower MCA Doppler index (MCA-PI, 1.60; range, 0.99–2.2 vs 1.81; range, 1.2–2.4; Mann-Whitney U P = .027).
Treatment with S-LASER resulted in 21.1% of patients and 6.6% with ED-LASER having incomplete resolution (Fisher exact P = .009, Table 4 ). Patients with TAPS and amniotic fluid abnormalities were all managed conservatively. Of the 5/6 cases with recurrent TTTS following S-LASER did not qualify for repeat laser because of PPROM, preterm labor, or patient preference. The reduction of recurrent TTTS from 8.5% to 3.9% with ED-LASER did not reach statistical significance. However, although recurrences following S-LASER included TTTS, TAPS, and amniotic fluid abnormalities, recurrence after ED-LASER was confined to TTTS or TAPS ( P = .048). This was anticipated intraoperatively in 4 of 5 cases because of incomplete visualization of anastomoses or the equator.
| Outcome | Selective LASER (n = 71) | Equatorial dichorionization (n = 76) | P value |
|---|---|---|---|
| Obstetric complications within 14 days | |||
| Chorioamnionitis | 1 (1.4) | — | .483 |
| Preterm rupture of membranes | 2 (2.8) | 1 (1.3) | .610 |
| Preterm birth | 6 (8.5) | 4 (5.2) | .523 |
| Any recurrence | 15 (21.1) | 5 (6.6) | .009 a |
| Primary presentation of recurrence | |||
| TTTS | 6 (8.5) | 3 (3.9) | .048 |
| TAPS | 3 (4.2) | 2 (2.6) | |
| Discordant amniotic fluid | 4 (5.6) | — | |
| Repeat laser | 1 (1.4) | 3 (3.9) | .336 a |
| Gestational age at delivery, wks | 32.3 (19.3–39.0) | 33.0 (19.3–41.1) | .716 |
| Laser delivery interval, d | 82 (1–139) | 84 (1–221) | .808 |
| Elective delivery | 14 (19.7) | 29 (38.2) | .012 |
| Indications for nonelective delivery | |||
| Preterm labor/labor | 20 (28.2)/5 (7) | 17 (22.4)/5 (6.6) | |
| PPROM/chorioamnionitis | 10 (14.2)/2 (2.8) | 2 (2.6)/5 (6.6) | |
| Nonreassuring fetal testing | 10 (14.2) | 8 (10.5) | .171 |
| Twin demise | 4 (5.6) | 2 (2.6) | |
| Placental abruption | 1 (1.4) | 6 (7.9) | |
| Maternal/obstetric indications | 3 (4.2) | 2 (2.6) | |
| Route of delivery | |||
| Cesarean delivery | 49 (69.0) | 55 (72.4) | .396 |
| Vaginal delivery | 22 (31.0) | 21 (27.6) | |
| Gestational age at PPROM | 28 (19.2–32) | 30.4 (19.4–36) | .039 |
| Days between laser and PPROM | 3 (0–84) | 6 (0–95) | .015 |
| Birthweight of live births | |||
| Recipient | 1820 (180–3200) | 2006 (260–3885) | .542 |
| Donor | 1530 (110–3165) | 1701 (125–3010) | .291 |
| Birthweight percentile | |||
| Recipient | 36.8 (1–94) | 41.8 (1–99) | .057 |
| Donor | 26.5 (0–92) | 28.9 (0–68) | .109 |
| Birthweight less than 10th percentile | |||
| Recipient | 13 (20.3) | 8 (11.6) | .236 |
| Donor | 21 (38.2) | 21 (32.8) | .338 |
| Percent birthweight discordance | 16.8 (–42 to 66.7) | 12.6 (–30.1 to 68.3) | .144 |
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