Early twin-to-twin transfusion syndrome: From early gestational physiology to diagnosis and management.

Guideline No. 440: Management of Monochorionic Twin Pregnancies

ISUOG Practice Guidelines: role of ultrasound in twin pregnancy.

It is not currently well known to what extent the sites of cord insertion influence the risk of complicated outcome in monochorionic twin pregnancy. The objectives of this study were to examine whether the sites of cord insertion, as determined on prenatal ultrasound examination, affect the risks of adverse outcome, twin-to-twin transfusion syndrome (TTTS) and discordant growth, and whether discordance in insertion sites or velamentous insertion in one or both twins best predicts risk. This was a retrospective cohort study of monochorionic diamniotic twin pregnancies followed from the first trimester. The cohort was divided into three groups of increasing discordance in cord insertion sites: concordant (normal-normal; marginal-marginal; velamentous-velamentous), intermediate (normal-marginal; marginal-velamentous) and discordant (normal-velamentous). Adverse outcome was defined as fetal or neonatal loss or birth prior to 32 weeks. The associations of adverse outcome, TTTS and discordant growth were assessed using logistic regression analysis with the following predictors: the three groups of insertion sites and velamentous insertion in one or both twins. Included in the analysis were 518 pregnancies. On univariate analysis, both discordant and velamentous insertions in one twin increased the risk of adverse outcome, TTTS and discordant growth. Intermediate insertion only increased the risk of discordant growth. Velamentous insertion in both twins increased the risk of adverse outcome and TTTS, but not of discordant growth. Multivariate logistic regression analysis showed velamentous insertion in one or both twins to independently predict adverse outcome and TTTS. For discordant growth, both intermediate/discordant and velamentous cord insertion in one twin were independent predictors. Velamentous cord insertion in one or both twins increases the risk of adverse outcome and TTTS, irrespective of discordance in the insertion sites, whereas the risk of discordant growth is determined by both discordance in insertion sites and velamentous cord insertion in one twin. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Call to action: long‐term neurodevelopment in monochorionic twins

To study the correlation of discrepancy between crown-rump length (CRL) and nuchal translucency (NT) in monochorionic twins at 11-14 weeks of gestation and subsequent development of twin-to-twin transfusion syndrome (TTTS) and selective fetal growth restriction (sFGR). Retrospective cohort study. Tertiary-care Fetal Medicine Unit, London. Monochorionic twin pregnancies with known outcome. Inter-twin discrepancy was calculated as a percentage of the larger CRL and smaller NT and compared among those developing TTTS, those with sFGR and those with normal outcome. Receiver operating characteristic (ROC) curves were constructed to evaluate the performance of inter-twin discrepancy in prediction of sFGR and TTTS. Development of TTTS and sFGR. A total of 242 monochorionic twin pregnancies were studied (102 TTTS, 36 sFGR and 104 controls). The median CRL discrepancy in the sFGR group (11.9%) was significantly higher (P < 0.001) than in the TTTS group (3.8%) and control group (3.5%). Median inter-twin NT discrepancies were not significantly different (P = 0.869) between sFGR and both TTTS and control groups (15.6%, 16.7% and 14.8%, respectively). Discrepancy in CRL performs well as a screening test for sFGR (area under ROC curve = 0.89), but not for TTTS (area under ROC curve = 0.58). First-trimester CRL discrepancy in monochorionic twins is a marker for subsequent development of sFGR rather than TTTS. Inter-twin NT discrepancy does not appear to be significantly different in these two groups from those with normal outcome.

Twin-to-twin transfusion syndrome (TTTS) is a serious complication for both fetuses occurring in 10—15% of monochorionic multiple pregnancies with various placental complications, including hypoxia, anemia, increased oxidative stress, and ischemia-reperfusion injury. Being minimally invasive surgical procedure fetoscopic laser coagulation of vascular anastomoses is the treatment of choice dramatically improves the survival rates in twin-to-twin transfusion syndrome. Objective. To study the frequency and structure of complications of fetoscopic laser coagulation of placental anastomoses in TTTS. Material and methods. A retrospective study of 258 monochorionic pregnancies complicated by TTTS which underwent laser coagulation of placental anastomoses in 2013—2021 years. Results. Fetoscopic laser coagulation of anastomoses (FLC) has complications that occur during the surgery or postoperative period. The rate of pregnancy loss after FLC is 8.5%. The overall survival rate directly correlates with the stage of FLC. The Solomon technique supports to reduce the recurrence of TTTS (9.5%), postoperative TAPS (twin anemia polycythemia sequence), the incidence of which was 2.3%. Conclusions. Laser coagulation of placental vascular anastomoses improves perinatal outcomes in monochorionic twin pregnancies. The postoperative complications does not depend of stage twin to twin transfusion syndrome, the technical comlexity of anastomosis visualization and volume of amnioreduction. Coagulation of vascular anastomoses of the placenta through the shell of the donor fetus increases the risk of dissection of the fetal membranes and premature discharge of amniotic fluid.

To assess the value of serial ultrasound examinations together with patient instructions to report the onset of symptoms in achieving timely detection of twin-to-twin transfusion syndrome (TTTS) in a cohort of monochorionic diamniotic twin pregnancies, and to evaluate sonographic TTTS predictors. Timely detection of TTTS was defined as diagnosis before severe complications of TTTS occurred, such as preterm prelabor rupture of membranes, very preterm delivery (24-32 weeks of pregnancy), fetal hydrops, or intrauterine fetal death. During a 2-year period, a prospective series of 23 monochorionic twin pregnancies was monitored from the first trimester until delivery. At least every 2 weeks we performed ultrasound and Doppler measurements (nuchal translucency thickness, presence of membrane folding, estimated fetal weight, deepest vertical pocket, bladder filling, and Doppler waveforms of the umbilical artery, ductus venosus and umbilical vein). Measurements of TTTS cases were compared with those of non-TTTS cases matched for gestational age. Furthermore, patients were informed about the symptoms caused by TTTS, and instructed to consult us immediately in case of rapidly increasing abdominal size or premature contractions. In all four TTTS cases, the diagnosis was timely. At the time of diagnosis, one case was at Quintero Stage 1, two at Quintero Stage 2, and one at Quintero Stage 3. Two of the TTTS cases became apparent after the patients' feeling of rapidly increasing girth. The identification of TTTS predictors was successful with respect to one parameter: isolated polyhydramnios in one sac, without oligohydramnios in the other, preceded the ultimate diagnosis of TTTS in two of the four TTTS cases. All other ultrasound measurements of TTTS cases, prior to the diagnosis of TTTS, were within the range of measurements of non-TTTS cases. Biweekly ultrasound examinations, with special attention to the amniotic fluid compartments of both fetuses, combined with detailed patient instructions to report the onset of symptoms resulted in timely diagnosis of all TTTS cases and appears to be a safe program for monitoring monochorionic twin pregnancies.

Doppler velocimetry for predicting fetal death in a twin pregnancy

Twin-to-twin transfusion syndrome (TTTS) is the most common serious complication of monochorionic (MC) twin pregnancies, with perinatal mortality rates of up to 90% if untreated. This study aimed to review the perinatal and perioperative outcomes of MC twin pregnancies treated for TTTS by fetoscopic laser photocoagulation (FLP) since its introduction at KK Women's and Children's Hospital (KKH), Singapore, in 2011. This was a retrospective review of five consecutive patients who underwent FLP of placental anastomoses for TTTS at KKH from June 2011 to March 2014. FLP was offered to patients who were diagnosed with TTTS of at least Quintero Stage II before 26 weeks of gestation. The main outcome measures were perioperative complications and perinatal survival rates. Five sets of MC twin pregnancies underwent FLP during the study period - three pregnancies were diagnosed with Stage III TTTS and two pregnancies with Stage II TTTS. Median gestational ages at initial presentation, laser photocoagulation and delivery were 19 (range 17-20) weeks, 20 (range 19-23) weeks and 29 (range 28-34) weeks, respectively. One patient had bleeding into the amniotic cavity intraprocedurally. Overall, the perinatal survival rate, double-infant survival rate and survival rate for at least one twin were 60% (6/10 fetuses), 40% (2/5 twins) and 80% (4/5 twins), respectively. FLP is a feasible treatment for TTTS, with minimal maternal complications. Perinatal survival rates of this patient group that was managed at our centre were comparable to those of international centres.

Twin-to-twin transfusion syndrome (TTTS) is a severe complication in monochorionic twin pregnancies, leading to high perinatal morbidity and mortality. Fetoscopic laser photocoagulation (FLP) is the gold standard treatment; however, fetal demiseremains a concern. The soluble vascular endothelial growth factor receptors, sVEGFR-1 and sVEGFR-2, play a crucial role in regulating angiogenesis and vascular function. This study evaluates changes in sVEGFR-1 and sVEGFR-2 levels before and after FLP and explores their role in predicting fetal demise post-surgery. Therefore, this study aims to evaluate pre- and post-surgical changes in sVEGFR-1 and sVEGFR-2 levels in TTTS cases treated with FLP and determine their predictive value for fetal demiseafter surgery. Methods: A prospective longitudinal study was done with 27 pregnant women with TTTS stage II-IV according to Quintero classification from 16 to 26 weeks of gestation undergoing FLS. Among them, 11 cases were carried out coagulation the placental vascular anastomoses, 16 cases were done ablation umbilical cord for the selective fetal reduction because of TTTS stage IV, selective intrauterine growth restriction (sIUGR) or proximate cord insertions. All the studies subject investigated the soluble levels of biomarkers. We quantified plasma levels of VEGF-R1, VEGF- R2 in twin pregnant with TTTS before and one week after surgery by ELISA. Many factors included maternal age, gestational age at surgery, stage of TTTS, placental location, level of polyhydramnios, FLS methods, sIUGR, amount of amniotic fluid drawn, duration of surgery, change of maternal circulating biomarker levels were analyzed to find out the association with fetal demise after FLS. Statistics showed that VEGF-R1 levels were significantly decreased after surgery and change in soluble VEGF-R1 levels after surgery had a difference between the group of fetal demise and non-fetal demise. ROC curve showed that degree of VEGF-R1 levels reduction after surgery were higher, the risk of fetal demise was bigger (AUC: 0.8472), in which, cut-off point of degree of VEGF-R1 levels reduction after surgery was 36.5% (sensitivity: 66.67%, specificity: 95.83%). Our data suggest that change in VEGF-R1 after surgery could play a prognostic role of fetal demise after fetoscopic laser surgery.

The study examines a possible association between increased nuchal translucency thickness at 10-14 weeks of gestation in monochorionic twin pregnancies and the subsequent development of severe twin-to-twin transfusion syndrome (TTS). In 132 monochorionic twin pregnancies, including 16 that developed severe TTS at 15-22 weeks of gestation and 116 that did not develop TTS, crown-rump length, nuchal translucency thickness and fetal heart rate were measured at 10-14 weeks. In those that developed severe TTS, the prevalence of nuchal translucency thickness above the 95th centile of the normal range and the intertwin difference in nuchal translucency thickness and fetal heart rate were significantly higher than in the non-TTS group; there were no significant differences between the groups in the inter-twin difference in crown-rump length. For fetal nuchal translucency above the 95th centile, the positive and negative predictive values for the development of TTS were 38% and 91%, respectively; the likelihood ratios of nuchal translucency above or below the 95th centile for the development of severe TTS were 4.4 (1.8-9.7) and 0.7 (0.4-0.9), respectively. These findings demonstrate that the underlying hemodynamic changes associated with TTS may manifest as increased fetal nuchal translucency thickness at 10-14 weeks of gestation.

Maternal serum markers of placental damage in uncomplicated dichorionic and monochorionic pregnancies in comparison with monochorionic pregnancies complicated by severe twin-to-twin transfusion syndrome and the response to fetoscopic laser ablation

Objective To investigate the efficacy and safety of radiofrequency ablation for fetal reduction in monochorionic twin pregnancies at gestational age over 26 weeks. Methods A retrospective study was performed based on the clinical data of 51 patients who underwent fetal reduction by radiofrequency ablation in the First Affiliated Hospital of Chongqing Medical University from May 2013 to July 2018. Clinical data including basic information, surgical data (such as ablation duration, power and the number of cycles), perinatal complications and pregnancy outcomes were collected. Differences in pregnancy outcomes were compared between the group with gestational age >26 weeks (n=17, group A) and that ≤26 weeks (n=34, group B) using t-test, rank-sum test and Chi-square test or Fisher's exact test. Results (1) The indications of fetal reduction were malformation in one of the twins, twin-to-twin transfusion syndrome, twin reversed arterial perfusion sequence and selective intrauterine growth restriction [45.1% (23/51), 15.7% (8/51), 19.6% (10/51) and 19.6% (10/51)]. The differences in the proportion of different indications between group A and B were statistically significant [12/17, 1/17, 0/17, 4/17 vs 32.4% (11/34), 20.6% (7/34), 29.4% (10/34), 17.7% (6/34), P=0.009]. Those in the group A required longer operation duration than the group B [M(min-max), 20(7-40) vs 15(3-29) min, Z=2.550, P=0.011]. (2) The gestational age of the 51 patients was (23.7±4.7) weeks (15+1-32+6 weeks), the overall survival rate of the remaining fetuses was 86.3% (44/51) and the preterm birth rate was 50.0% (22/44). The gestational age at operation was (28.9±2.5) weeks (26+1-32+6 week) in group A and (21.1±3.1) weeks (15+1-25+2 weeks) in group B. The survival rate of the remaining fetuses and the preterm birth rate in group A were significantly higher than those in group B [17/17 vs 79.4% (27/34), P=0.046; 12/17 vs 37.0% (10/27), χ2=4.697, P=0.030]. Conclusions Fetal reduction at gestational age >26 weeks, of which the main surgical indication is malformation in one of the twins, may increase the risk of preterm birth, but can improve the overall survival rate of the remaining fetuses without increasing the maternal and infant morbidity. Therefore, radiofrequency ablation is a safe and effective procedure for twin pregnancies >26 weeks of gestation. Key words: Pregnancy, twin; Pregnancy reduction, multifetal; Radiofrequency ablation; Pregnancy trimester, second

Twin-to-Twin Transfusion Syndrome Results From Dynamic Asymmetrical Reduction in Placental Anastomoses: A Hypothesis

Twin-to-twin transfusion syndrome (TTTS) is associated with a high risk of perinatal mortality and morbidity if not treated. However, the optimal timing and management in case of early (occurring < 18 weeks) TTTS has not been established yet. This is a systematic review and meta-analysis aiming at evaluating the outcomes of monochorionic diamniotic twin pregnancies complicated by early (ie before 18 weeks) TTTS according to different management options (expectant, laser therapy, amnioreduction or cord occlusion). The primary outcome was mortality, including single and double intrauterine, neonatal and perinatal death. Secondary outcomes were: composite morbidity, neuromorbidity, respiratory distress syndrome, admission to neonatal intensive care unit, intact survival (defined as survival free from neurological complications) and preterm birth < 32 weeks of gestation. All outcomes were reviewed according to the different management options (expectant, laser therapy, amnioreduction or cord occlusion) and reported FOR the overall population of twins, and for the donor and recipient separately. Subgroup analysis for TTTS occurring before 16 weeks of gestation was performed. Random-effect meta-analyses of proportions were used to analyse the data. Thirteen studies were included. Early TTTS occurred in 14.3% (95% confidence interval [CI] 11.9-17.0) of cases. The incidence of intrauterine death was 19.0% (95% CI 2.6-45.5) in twins managed expectantly, 32.4% (95% CI 16.5-50.7) in those who received laser treatment and 12.5% (95% CI 4.8-23.0) in those treated with amnioreduction. The incidence of neonatal death was 22.6% (95% CI 4.2-49.8) in twins managed expectantly, 24.7% (95% CI 0.5-80.3) in those who received laser and 20.2 (95% CI 5.8-43.4) in those who had amnioreduction; it was not possible to compute the incidence of these outcomes in twins undergoing cord occlusion because of insufficient sample and lack of reporting of most of the observed outcomes. Overall, the incidence of perinatal death was 43.9% (95% CI 5.9-87.7) in twins managed expectantly, 47.3% (95% CI 21.4-70.0) in those treated with laser and 28.5% in those who had amnioreduction. Twin pregnancies affected by early TTTS are at substantial risk of perinatal mortality and morbidity; however, the data come from very small studies with a high risk of selection bias.