Prevention of preterm birth in twin-to-twin transfusion syndrome: a systematic review and network meta-analysis.

OBJECTIVES: We aimed to perform a systematic review and network meta-analysis to evaluate the preventive strategies for preterm birth in twin-to-twin transfusion syndrome. METHODS: PubMed, Embase and Cochrane Central were searched from inception to December 2023 with no filters. Additionally, the reference lists of the included studies were manually examined to identify any supplementary studies. We selected randomized controlled trials and cohorts comparing interventions to prevent preterm birth in twin pregnancies complicated by twin-to-twin transfusion syndrome. A random-effects frequentist network meta-analysis was performed using RStudio version 4.3.1. Randomized controlled trials and cohorts were assessed respectively using the Risk of Bias in Non-randomized Studies of interventions tool and Cochrane Collaboration's tool for assessing risk of bias in randomized trials. RESULTS: In this systematic review and meta-analysis, we included eight studies comprising a total of 719 patients. Compared with expectant management, cerclage stood out as the only intervention associated with an increase in the survival of at least one twin (risk ratio 1.12; 95 % confidence interval 1.01-1.23). Our subgroup analysis based on different thresholds for short cervix demonstrated a significant reduction in the risk of preterm birth before 32 weeks with ultrasound-indicated cerclage using a 15 mm criterion (risk ratio 0.65; 95 % confidence interval 0.47-0.92). CONCLUSIONS: Our study suggests the potential benefit of cerclage as a preventive strategy for preterm birth in pregnancies complicated by twin-to-twin transfusion syndrome. These findings highlight the necessity for further investigation to corroborate our results and address the optimal threshold for ultrasound-indicated cerclage.

Elevated middle cerebral artery peak systolic velocity and risk of death in donor twin affected by twin-twin transfusion syndrome but not twin anemia-polycythemia sequence.

OBJECTIVES: To determine the association between elevated (> 1.5 multiples of the median (MoM)) middle cerebral artery (MCA) peak systolic velocity (PSV) and fetal demise of the donor twin in pregnancies complicated by twin-twin transfusion syndrome (TTTS) in the absence of twin anemia-polycythemia sequence (TAPS). Secondary objectives were to evaluate if donor or recipient MCA-PSV is associated with a risk for their corresponding fetal death, and to compare the proportion of donor fetuses with low MCA pulsatility index (PI) among donor twins with high MCA-PSV and those with normal MCA-PSV to evaluate the contribution of blood-flow redistribution to the fetal brain in donor twins with high MCA-PSV. METHODS: This prospective cohort study included TTTS cases that underwent laser surgery between 2011 and 2022 at a single center. TAPS cases were excluded from the study. Multivariable and Poisson regression analysis were performed to explore the association between isolated elevated donor MCA-PSV and fetal demise, adjusted for TTTS stage, selective fetal growth restriction (sFGR) and other confounders. RESULTS: Of 660 TTTS cases, donor MCA-PSV was not recorded in 48 (7.3%) cases. Of the remaining 612 patients, nine (1.5%) were lost to follow-up and 96 TAPS cases were excluded; thus, 507 cases were included in the study. High donor MCA-PSV was seen in 6.5% (33/507) of cases and was an independent risk factor for donor fetal demise (adjusted relative risk (aRR), 4.52 (95% CI, 2.72-7.50)), after adjusting for confounders. Regression analysis restricted to each Quintero TTTS stage demonstrated that high donor MCA-PSV was an independent risk factor for fetal demise of the donor in Quintero Stage II (aRR, 14.21 (95% CI, 1.09-186.2)) and Quintero Stage III (aRR, 3.41 (95% CI, 1.82-6.41)). Donor MCA-PSV in MoM was associated with fetal demise of the donor (area under the receiver-operating-characteristics curve (AUC), 0.69; P < 0.001), but recipient MCA-PSV in MoM was not associated with fetal demise of the recipient (AUC, 0.54; P = 0.44). A higher proportion of donor twins in the group with high MCA-PSV had a low MCA-PI compared to the group with normal MCA-PSV (33.3% vs 15.5%; P = 0.016). CONCLUSIONS: Elevated donor MCA-PSV without TAPS prior to laser surgery for TTTS is associated with a 4-fold increased risk for donor fetal demise, adjusted for sFGR, TTTS stage and other confounders. Doppler evaluation of donor MCA-PSV prior to laser surgery may help stratify TTTS staging to evaluate the risk of donor fetal demise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Perinatal outcomes following fetoscopic laser surgery for early twin-to-twin transfusion syndrome: Systematic review and meta-analysis.

INTRODUCTION: Our objective was to investigate outcomes in twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser surgery (FLS) at <18 weeks vs ≥18 weeks, and to conduct subgroup analysis of TTTS with FLS at <16 weeks vs 16-18 weeks. MATERIAL AND METHODS: PubMed, Scopus and Web of Science were searched systematically from inception until May 2023. Primary outcome was survival, and secondary outcomes included preterm premature rupture of membranes (PPROM), preterm birth and gestational age (GA) at delivery. RESULTS: Nine studies encompassing 1691 TTTS pregnancies were included. TTTS stage III was significantly more common in TTTS pregnancies treated with FLS at <18 weeks (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.24-6.54), and procedure duration was shorter at <18 weeks (MD -5.27 minutes, 95% CI -9.19 to -1.34). GA at delivery was significantly earlier in TTTS pregnancies treated with FLS at <18 weeks (MD -3.12 weeks, 95% CI -6.11 to -0.13). There were no significant differences in outcomes, including PPROM, PPROM at <7 days post-FLS, preterm birth at <28 and <32 weeks, delivery at <7 days post-FLS, and survival outcomes, including fetal demise, live birth and neonatal survival. Similarly, TTTS stage III was more common in TTTS with FLS at <16 weeks than at 16-18 weeks (OR 2.95, 95% CI 1.62-5.35), with no significant differences in the aforementioned outcomes. CONCLUSIONS: In early TTTS treated with FLS, outcomes were comparable between those treated at <18 weeks compared with ≥18 weeks except for GA at delivery, which was 3 weeks earlier. In the subset treated at <16 weeks vs 16-18 weeks, the procedure was feasible without an increased risk of very early preterm birth or perinatal mortality.

Stage-based recipient and donor outcome in twin-to-twin transfusion syndrome treated by fetoscopic laser surgery using Solomon technique.

OBJECTIVE: To evaluate twin survival stratified by Quintero stage in patients with twin-to-twin transfusion syndrome (TTTS) after Solomon laser treatment. METHODS: This was a single-center study at Johns Hopkins Center for Fetal Therapy, investigating a cohort of consecutive twin pregnancies treated with the Solomon laser technique for TTTS. Preoperative Quintero stage, perioperative characteristics and obstetric factors were investigated in relation to neonatal survival of the recipient and donor twins at discharge. Determinants of twin survival were evaluated using univariate logistic regression and cumulative survival probability analyses. RESULTS: Of 402 pregnancies with TTTS that underwent Solomon laser treatment, 80 (19.9%) were diagnosed with Quintero Stage-I TTTS, 126 (31.3%) with Stage II, 169 (42.0%) with Stage III and 27 (6.7%) with Stage IV. Post-laser twin anemia polycythemia sequence or recurrent TTTS occurred in 19 (4.7%) patients and 11 (2.7%) required repeat laser surgery. Preterm prelabor rupture of membranes occurred in 150 (37.3%) patients and median gestational age at delivery was 32 + 1 weeks. In 303 (75.4%) patients, both twins were alive at discharge; 67/80 (83.8%) were Stage I, 101/126 (80.2%) were Stage II, 113/169 (66.9%) were Stage III and 22/27 (81.5%) were Stage IV (P = 0.062). Donor twin survival was lower than that of recipients in cases with Stage-III TTTS (118/169 (69.8%) vs 145/169 (85.8%) (χ2 = 26.076, P < 0.0001)). Higher intertwin size discordance and absent or reversed umbilical artery (UA) end-diastolic velocity (EDV) were associated with donor demise (Nagelkerke R2, 0.38; P < 0.001). Overall, spontaneous post-laser donor demise occurred in 53 (39.6%) patients, accounting for the majority of all losses. Cumulative donor survival decreased from 92% to 65% when intertwin size discordance was >30% and to 48% when UA-EDV was absent or reversed (P < 0.001). CONCLUSIONS: The Solomon laser technique achieves TTTS resolution and double twin survival in a high proportion of cases. Recipient and donor survival is comparable unless there is significant intertwin size discordance and placental dysfunction. This degree of unequal placental sharing, typically found in Stage-III TTTS, is the primary factor preventing double survival due to a higher rate of donor demise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Outcomes of laser surgery for stage I twin-twin transfusion syndrome.

OBJECTIVE: A recent randomized controlled trial (RCT) demonstrated no difference in 6 month survival in expectantly managed stage I twin-twin transfusion syndrome (TTTS) patients and those undergoing immediate laser surgery. We aimed to describe outcomes following immediate laser surgery at a single fetal surgery center. METHODS: A retrospective study of monochorionic diamniotic twins diagnosed with stage I TTTS who underwent laser surgery between 16 and 26 gestational weeks from 2006 to 2019. The primary outcome was 6 month survivorship. Intact survival was also assessed. Secondarily, outcomes were compared to the RCT expectant management group. RESULTS: Of 126 consecutive stage I TTTS patients, 114 (90.5%) met inclusion criteria. Median (range) gestational age at delivery was 34.1 (20.6-39.4) weeks. At 6 months, the proportion of patients with at-least-one survivor in the single-center-laser cohort was 97.4%, with 88.6% dual survivorship. Neurological morbidity outcomes were available in 110 pregnancies (220 fetuses). Severe neurological morbidity occurred in 2.7% (6/220), and 6 month survival without severe neurological morbidity was 90.0%. Outcomes compared favorably with the RCT expectant management group. CONCLUSIONS: Given favorable survival and neurological outcomes, laser surgery is a reasonable treatment option for stage I TTTS at experienced fetal surgery centers. Further study is warranted to optimize treatment strategies.

Fetoscopic laser ablation therapy in monochorionic diamniotic twin pregnancies with twin-to-twin transfusion syndrome treated at a single centre over 10 years: a retrospective study.

OBJECTIVES: To review experience with fetoscopic laser ablation of placental anastomoses to treat monochorionic diamniotic (MCDA) twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) in a single centre over a ten-year period. METHODS: A retrospective study on 142 MCDA twin pregnancies complicates by TTTS treated with equatorial laser ablation of placental anastomoses (2008-2018). Solomon technique was also applied after 2013. Survival rates, neonatal outcome, intraoperative and post-laser complications were recorded, and prognostic factors analysed. RESULTS: A total of 133 cases were included in the final analysis; 41 patients were at stage II (30.8%), 73 were at stage III (62.9%), while only 12 (9%) at stage I and two patients (1.7%) at stage IV. Solomon technique was applied in 39 cases (29.3%). Survival of both twins was 51.1% (68/133), of a single twin 20.3% (27/133), and of at least one 71.5% (95/133), with an overall survival of 61.3% (163/266). TAPS and recurrent TTTS occurred in 8 (6%) and 15 (11.3%) patients. Survival of both fetuses increased over time (44.6 vs. 57.3%). A posterior placenta (p<0.003) and the use of the Solomon technique (p<0.02) were more frequent in cases with survival of both fetuses, while TTTS recurrence was significantly associated to the loss of one or two fetuses (p<0.01). Such associations were confirmed at logistic regression analysis. CONCLUSIONS: Survival of both twins can improve over time and seems to be favourably associated with a placenta in the posterior location and the use of the Solomon technique.

Outcomes of laparoscopy-assisted fetoscopic laser photocoagulation for twin-twin transfusion syndrome: An established alternative for inaccessible anterior placenta.

OBJECTIVE: To evaluate laparoscopy-assisted fetoscopic laser photocoagulation (FLPC) of placental anastomoses in the treatment of twin-to-twin-transfusion syndrome (TTTS). STUDY DESIGN: We performed a retrospective cohort study analyzing pregnancies complicated by TTTS who underwent FLPC in a single university-affiliated tertiary medical-center. Outcomes were compared between patients who received laparoscopy-assisted FLPC (study group) and patients who underwent the conventional FLPC technique (control group). Baseline characteristics, sonographic findings, procedure details, and neonatal outcomes were compared between groups. RESULTS: The cohort included 278 women with 31 in the study group and 247 in the control group. Sonographic parameters, including fetal biometry and TTTS stage, were comparable between study groups. Gestational age at delivery did not differ between the groups (29.22 ± 4.55 weeks in the study group vs. 30.62 ± 4.3 weeks in the control group, p = 0.09). There were no differences in neonatal survival rates at birth and at 30 days between both groups. A subanalysis comparing the laparoscopy-assisted group to only those patients with anterior placenta in the control group, showed a lower rate of incomplete Solomonization in the laparoscopy-assisted study group (3.4% vs. 33%, p = 0.01). CONCLUSION: Laparoscopy-assisted FLPC is a reasonable and safe option that may be offered in cases of FLPC where an anterior placenta restricts adequate surgical access.

Dual demise following laser surgery for twin-twin transfusion syndrome: Analysis of 52 cases at a single fetal surgery center.

OBJECTIVE: To evaluate all individual cases of dual twin demise following laser surgery for twin-twin transfusion syndrome (TTTS). METHOD: This is an analysis of all monochorionic diamniotic twin gestations with TTTS complicated by dual demise following laser surgery from 2006 to 2019. Cases were reviewed by (1) a fetal surgeon researcher and (2) a panel of independent experienced maternal-fetal medicine specialists to code an etiology of demise for the donor and recipient, and to assess for possible preventability. RESULTS: Of 753 twins that underwent laser surgery for TTTS, 52 (6.9%) had postoperative dual demise. In this subgroup, gestational age at surgery was 19.5 (16.1-24.9) weeks, and 36 (69.2%) patients were Quintero stage III and IV. The most common etiology was the spectrum of disorders leading to preterm delivery, which included cervical insufficiency, preterm premature rupture of membranes, and preterm labor (44.2% and 48.1%, donor and recipient, respectively). Some degree of preventability was estimated for 23.1% of dual demises. CONCLUSIONS: The most common cause of dual demise post laser surgery for TTTS was preterm birth, reinforcing the need for studies regarding the etiology and prevention of post-fetoscopy prematurity. Nearly one-quarter of dual demise cases were deemed potentially preventable.

Re-evaluation of the predictive value of Quintero staging of twin-twin transfusion syndrome for fetal death after fetoscopic laser photocoagulation.

OBJECTIVE: To elucidate the significance of sonographic indices, including Doppler waveforms, that constitute the Quintero classification for predicting death of the recipient or donor after fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS). METHODS: Prospectively collected data of twins who underwent FLP for TTTS were reviewed. Among the abnormal indices of ultrasound performed just before FLP, factors that were significantly associated with fetal and neonatal deaths in the log-rank test, including fetal demise of co-twins and preterm birth before 28 weeks of gestation, were introduced into the Cox proportional-hazards model to calculate risk ratio (RR). RESULTS: We included 235 cases with a prevalence of recipient and donor deaths of 7% and 14%, respectively. In the proportional-hazards model, absent or reversed umbilical artery end-diastolic velocity (UA AREDV) of recipients (n = 7) was independently associated with recipient death (RR = 6.97). In recipients without UA AREDV, reversed ductus venosus (DV) a-wave of recipients (RR = 3.55) was independently associated with recipient death. In donors, UA AREDV with a visible bladder (stage III atypical donor) was independently associated with donor death (RR = 4.24). CONCLUSION: Some individual components of the Quintero stage are associated with death of either recipient or donor twins following FLP.

Twin-twin transfusion syndrome and the definition of recipient polyhydramnios.

BACKGROUND: Controversy exists regarding the threshold of recipient twin polyhydramnios required to diagnose twin-twin transfusion syndrome at a gestational age of ≥20 weeks. One criterion set (Quintero staging) requires the amniotic fluid maximum vertical pocket for the recipient twin to measure ≥8 cm, whereas another (European) system uses a maximum vertical pocket for the recipient twin of ≥10 cm. OBJECTIVE: This study aimed to characterize the patients with twin-twin transfusion syndrome who were treated with laser surgery and would be excluded from laser surgery according to the European criteria. STUDY DESIGN: A total of 366 monochorionic diamniotic twins diagnosed with twin-twin transfusion syndrome from 20 to 26 weeks' gestation who underwent laser surgery at our center were studied. A maximum vertical pocket for the recipient twin of ≥8 cm was used to diagnose twin-twin transfusion syndrome. Patients were retrospectively divided into the following 2 groups: group A with a maximum vertical pocket for the recipient twin of ≥8 cm and <10 cm and group B with a maximum vertical pocket for the recipient twin of ≥10 cm. The association of each of the groups with the survivorship outcomes was tested. Bivariate associations between the patient characteristics and the 30-day donor twin and dual survivorship outcomes were evaluated. Tests used in the analysis were chi-square or Fisher exact tests as appropriate for categorical variables and Kruskal-Wallis tests for continuous variables. Multiple logistic regression models for each of the survivorship outcomes were then assessed. The results are reported as mean±standard deviation. RESULTS: Of the 366 studied patients, 53 (14.5%) had a maximum vertical pocket for the recipient twin of ≥8 and <10 cm (group A) and 313 (85.5%) had a maximum vertical pocket for the recipient twin of ≥10 cm (group B). Groups A and B did not differ in the Quintero stage. Notably, 60.4% (32 of 53) of group A patients were stage III or IV. When compared with group B, group A was diagnosed with twin-twin transfusion syndrome at an earlier gestational age (21.7±1.6 vs 22.3±1.6 weeks; P=.0037) and had a higher prevalence of donor growth restriction (81.1% [43 of 53] vs 65.5% [205 of 313]; P=.0260). Rates of at least 1 twin and dual twin survival between group A and B were similar (98.1% [52 of 53] vs 95.8% [300 of 313]; P=.7023, and 79.2% [42 of 53] vs 83.4% [261 of 313]; P=.4369, respectively). Logistic regression models adjusted for perioperative characteristics showed no difference in the outcomes between the groups (group B as reference) (donor twin survival odds ratio, 0.64; 95% confidence interval, 0.29-1.42; P=.2753; and dual survivor odds ratio, 0.90; 95% confidence interval, 0.42-1.91; P=.7757). CONCLUSION: Restriction of the definition of twin-twin transfusion syndrome to a maximum vertical pocket for the recipient of ≥10 cm beyond 20 weeks gestational age would potentially exclude 14.5% of patients from laser surgery, the majority of whom had advanced stage twin-twin transfusion syndrome. A unifying criterion of a maximum vertical pocket for the recipient of ≥8 cm regardless of gestational age would allow inclusion of these patients and access to surgical management.

Intertwin differences in umbilical artery pulsatility index are associated with infant survival in twin-to-twin transfusion syndrome.

OBJECTIVES: To evaluate the association of intertwin differences in umbilical artery pulsatility index (DUAPI) and infant survival in twin-to-twin transfusion syndrome (TTTS). METHODS: Absolute DUAPI was calculated prior to laser surgery. Receiver-operating characteristics (ROC) curve analysis provided an intertwin DUAPI cutoff of 0.4 for the prediction of double twin survival to 30 days of life. Infant survival was compared between women with an intertwin DUAPI <0.4 and ≥0.4 in the whole cohort, in TTTS cases with Quintero stages I/II and in those with Quintero stages III/IV. Regression analyses were performed to evaluate the association of intertwin DUAPI <0.4 and infant survival adjusted for confounders. RESULTS: In total, 349 TTTS cases were included. Double twin survival to 30 days was observed in 67% (234/349) of cases. Significant differences in double twin survival was seen between intertwin DUAPI groups in the whole cohort (76.8 vs. 52.2%; p<0.001), in women with TTTS Quintero stage I or II (77.8 vs. 58.5%; p=0.015) as well as in women with TTTS Quintero stage III or IV (75 vs. 49.5%; p=0.001). Intertwin DUAPI <0.4 conferred a threefold increased chance for double twin survival. CONCLUSIONS: Small intertwin DUAPI is associated with increased double infant survival in early and advanced TTTS stages.

Predicting fetal and neonatal demise after fetoscopy for twin-twin transfusion syndrome using recursive partitioning.

OBJECTIVE: Donor demise after laser surgery for twin-twin transfusion syndrome (TTTS) is well-characterized, but recipient demise is not, nor is neonatal death. This study aims to characterize factors associated with recipient death, donor death, and dual twin death after laser, both before and after birth. METHODS: This is a prospective cohort study of monochorionic twin pairs who underwent laser ablation for TTTS. Risk factors for fetal and neonatal death of both twins were identified using univariable analysis and recursive partitioning, a novel statistical method to quantify contributions of each factor to outcomes. RESULTS: In 413 twin pairs, death of both twins occurred in 9.2% (38/413), donor death in 12.1% (50/413), and recipient death in 2.4% (10/413). Recursive partitioning showed that gestational age at delivery predicts dual twin death (below 23.7 weeks, likely [p < 0.001], above 28.3 weeks, unlikely [p = 0.004]). Abnormal umbilical artery Doppler and weight discordance predict donor demise (p < 0.001 and p = 0.033, respectively). Cervical length under 16 mm predicts neonatal death of both twins (p < 0.001). CONCLUSIONS: Parents can gain individualized information about the survival of each fetus based on variables available from preoperative and delivery variables. Short cervix and premature delivery cause significant mortality in TTTS.

Perinatal outcome of twin-to-twin transfusion syndrome complicated with incidental septostomy after laser photocoagulation: A systematic review and meta-analysis.

AIM: To evaluate perinatal outcomes of incidental septostomy (IS) after laser photocoagulation for twin-to-twin transfusion syndrome (TTTS), and to compare the outcomes with those who had intact intertwin membrane. METHODS: Databases such as PubMed, Web of Science, Scopus, and Embase were systematically searched from inception up to August 2020. The random-effects model was used to pool the mean difference (MD) or odds-ratio (OR) with the corresponding 95% confidence intervals (CIs). Primary outcome was incidence of preterm delivery, and preterm premature rupture of membranes (PPROM), while secondary outcomes included gestational age (GA) at intervention, GA at delivery, neonatal survival, and incidence of pseudoamniotic band syndrome (PABS). RESULTS: Four studies (1442 patients) met our inclusion criteria. Postoperative identification of IS was associated with earlier GA at delivery (MD = -2.52; 95% CI: -3.22, -1.82; p < 0.00), higher risk of PPROM < 32 weeks (OR = 2.82; 95% CI: 1.80, 4.40; p < 0.001), and preterm delivery < 32 weeks (OR = 4.01; 95% CI: 1.27, 12.63; p = 0.02). No differences were noted in pseudoamniotic band syndrome, at least one or dual neonatal survival rate between IS and non-IS groups. CONCLUSIONS: Occurrence of IS after laser photocoagulation for TTTS is associated with earlier GA at delivery, increased risk for PPROM and preterm delivery <32 weeks' gestation. However, neonatal survival does not appear to be affected by this complication.

Influence of indications on perinatal outcomes after radio frequency ablation in complicated monochorionic pregnancies: a retrospective cohort study.

BACKGROUND: Radiofrequency ablation (RFA) is recommended to prevent potential neurological injury or intrauterine foetal death (IUFD) of the co-twin(s) in complicated monochorionic (MC) pregnancies. However, the impacts of various indications on the pregnancy outcome following RFA remain unclear. This study aimed to determine how the indications influence the perinatal outcomes in complicated MC pregnancies undergoing radiofrequency ablation. METHODS: This was a retrospective cohort study performed in a single centre. All consecutive MC pregnancies treated with RFA between July 2011 and July 2019 were included. The adverse perinatal outcomes and the survival rate were analysed based on various indications. The continuous variables with and without normal distribution were compared between the groups using Student's t-test and Mann-Whitney U test, respectively, and for categorical variables, Chi-square and Fisher's exact tests were used. P < 0.05 indicated a significant difference. RESULTS: We performed 272 RFA procedures in 268 complicated MC pregnancies, including 60 selective intrauterine growth restriction (sIUGR), 64 twin-twin transfusion syndrome (TTTS), 12 twin reversed arterial perfusion sequence (TRAPs), 66 foetal anomaly and 66 elective foetal reduction (EFR) cases. The overall survival rate of the co-twin was 201/272 (73.9%). The overall technical successful rate was determined at 201/263 (76.7%). The IUFD rate in the co-twin was 20/272 (7.4%). The TTTS group had recorded the lowest survival rate (37/64, 57. 8%), and the survival rate was significantly correlated with Quintero stages (P = 0.029). Moreover, the sIUGR III subgroup had a lower survival rate compared with sIUGR II (55.6%, versus 84.3%). The subgroup of foetal anomaly of gastroschisis or exomphalos had the highest IUFD rate (4/10, 40%), followed by sIUGR III (2/9, 22.2%) and dichorionic triamniotic (DCTA) subgroup (8/46, 17.9%). In EFR group, eight IUFD cases were all coming from the DCTA subgroup and received RFA before 17 weeks. CONCLUSIONS: The perinatal outcome of RFA was correlated with the indications, with the lowest survival rate in TTTS IV and the highest IUFD incidence in abdominal wall defect followed by sIUGR III. Elective RFA after 17 weeks may prevent IUFD in DCTA pregnancies.

Twin-twin transfusion syndrome - a University Hospital experience with intrauterine treatment.

INTRODUCTION: twin-to-twin transfusion syndrome (TTTS), defined by combination of polyhydramnios-oligohydramnios, is the most prevalent (5%-35%) of the abnormalities due to placental vascular anastomoses and the most lethal (80%-100% mortality) if untreated. Fetoscopic laser ablation of abnormal vasculature using the Solomon technique is the gold standard approach. It consists of interrupting the intertwin blood flow. OBJECTIVES: to present our initial experience at the Fetal Surgery Service of the Hospital de Clinicas of the Federal University of Parana (HC-UFPR) and to compare our results with those reported in the literature. METHODS: we conducted a retrospective analysis of pregnancies who had undergone laser ablation, assessing data on Quintero's staging, gestational age at diagnosis and at the time of the procedure, placental position, immediate post-procedure survival, and survival after the neonatal period. We then compared these data with the most recent data available in the literature. RESULTS: we analyzed ten TTTS cases. The diagnosis was performed before the 26th week of pregnancy (median 20.8 weeks) and treatment occurred in a median of 9.5 days later. The distribution by the Quintero's staging was of three cases in stage II, five in stage III, and two in stage IV. In 50% of the gestations, at least one of the fetuses survived through the neonatal period. CONCLUSION: the treatment of TTTS in the HC-UFPR had a positive impact in the survival of the affected fetuses, although the results were worse than the ones reported in the literature, probably due to the delay in referencing the patients to our service, leading to a prolonged interval between diagnosis and treatment.

Prediction of post-laser fetal death in selective growth restriction complicating twin-twin transfusion syndrome using standardized definitions.

OBJECTIVE: Selective fetal growth restriction (sFGR) complicating twin-twin transfusion syndrome (TTTS) is associated with a 3-6-fold increased risk of fetal demise after fetoscopic laser surgery (FLS). Identifying these patients is challenging due to varying definitions of sFGR used in the literature. The objective of this study was to determine the association of three currently used definitions for sFGR with demise of the smaller twin, typically the donor, following FLS for TTTS. METHODS: This was a retrospective cohort study of monochorionic diamniotic twin pregnancies undergoing FLS for TTTS between January 2015 and December 2018. Classification of the cohort as sFGR or non-sFGR was performed using three different definitions: (1) estimated fetal weight (EFW) of one twin < 10th centile and intertwin EFW discordance > 25%, according to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) (Definition A); (2) EFW of one twin < 3rd centile, according to the solitary criterion for sFGR reported in a Delphi consensus (Definition B); and (3) presence of at least two of four of the following criteria: EFW of one twin < 10th centile, abdominal circumference of one twin < 10th centile, intertwin EFW discordance of ≥ 25% and umbilical artery pulsatility index of the smaller twin > 95th centile, according to the contributory criteria for sFGR in monochorionic diamniotic twin pregnancies reported in the Delphi consensus (Definition C). Pearson's χ2 and univariate and multivariate logistic regression analyses were performed to assess the association of classification as sFGR according to the different definitions with fetal demise within 48 h after FLS. RESULTS: A total of 124 pregnancies underwent FLS for TTTS during the study period. Of these, 46/124 (37.1%) were identified as having sFGR according to the ISUOG criteria (Definition A), 57/124 (46.0%) based on EFW < 3rd centile (Definition B) and 70/124 (56.5%) according to the Delphi contributory criteria (Definition C). There were no differences in maternal body mass index, recipient twin amniotic fluid volume, gestational age (GA) at intervention or GA at delivery between sFGR and non-sFGR cases for any of the three definitions. There were also no differences in the rates of postprocedure recipient demise or Doppler abnormalities in the recipient. Regardless of the definition used, sFGR cases showed a significantly higher rate of postprocedure donor twin demise compared with that in non-sFGR cases (Definition A: 28.3% vs 3.8%, P < 0.01; Definition B: 22.8% vs 4.5%, P = 0.02; Definition C: 22.9% vs 0%, P < 0.01). For all of the sFGR definitions, the rate of Stage-III TTTS was increased in sFGR compared to non-sFGR cases (Definition A: 65.2% vs 35.9%, P ≤ 0.01; Definition B: 59.6% vs 35.8%, P = 0.04; Definition C: 62.9% vs 25.9%, P < 0.01). All cases of donor demise met the criteria for sFGR according to Definition C. Classification as sFGR according to Definition C was associated with a significantly higher rate of post-FLS donor demise compared to Definitions A and B (χ2 , 15.32; P < 0.01). Logistic regression analysis demonstrated that sFGR cases had an increased risk of donor demise (Definition A: odds ratio (OR), 4.97 (95% CI, 1.77-13.94), P < 0.01; Definition B: OR, 4.39 (95% CI, 1.36-14.15), P = 0.01) and that staging of TTTS was also predictive of demise (OR, 2.26 (95% CI, 1.14-4.47), P = 0.02). After adjusting for GA at intervention and stage of TTTS, the results were similar (Definition A: OR, 6.48 (95% CI, 2.11-24.56), P = 0.002; Definition B: OR, 4.16 (95% CI, 1.35-15.74), P = 0.02). CONCLUSIONS: The rate of fetal demise following FLS for TTTS is increased in the presence of sFGR. Improving diagnosis of sFGR should improve counseling and may affect management. The Delphi method of defining sFGR based on the presence of at least two of four contributory criteria had the highest predictive value for donor demise following FLS for TTTS. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Early laser surgery is not associated with very preterm delivery or reduced neonatal survival in TTTS.

OBJECTIVE: To evaluate the association of laser photocoagulation of placental anastomoses (LPA) prior to 18 weeks' gestation (early LPA) with very preterm delivery and neonatal survival in pregnancies with twin-twin transfusion syndrome (TTTS). METHODS: This was a retrospective cohort study of monochorionic diamniotic twin pregnancies with TTTS undergoing LPA between 2002 and 2018 at two institutions. The rates of delivery < 28, < 30 and < 32 weeks' gestation, preterm prelabor rupture of membranes (PPROM) and 30-day survival of one or both infants were compared between pregnancies undergoing early LPA and those undergoing LPA ≥ 18 weeks' gestation. Regression analysis was performed to determine the association of early LPA with very preterm delivery and 30-day survival, adjusted for Quintero stage, study phase, selective fetal growth restriction, gestational age at delivery, maternal age ≥ 35 years, body mass index > 35 kg/m2 , placental location, use of Seldinger method to place the operative trocar, size of the trocar, participating center, use of Solomon technique, cerclage and PPROM. Survival analysis using the Cox proportional hazard model was applied to examine the LPA-to-delivery interval according to the timing of surgery, adjusted for confounding variables. RESULTS: A total of 414 TTTS pregnancies were included in the study, of which 68 (16.4%) underwent early LPA. In the total cohort, the incidence of delivery at < 28, < 30 and < 32 weeks' gestation was 22.7%, 39.6% and 53.4%, respectively. Survival of both twins and survival of at least one twin at 30 days were 67.5% and 90.8%, respectively. No significant difference was noted between pregnancies that underwent early LPA and those that had LPA ≥ 18 weeks in the rate of delivery < 28 weeks (19.1% vs 23.4%; P = 0.4), < 30 weeks (38.2% vs 39.9%; P = 0.8) and < 32 weeks (44.1% vs 55.2%; P = 0.1) and PPROM (29.0% vs 24.1%; P = 0.4), or in the incidence of double-twin survival (63.9% vs 68.1%; P = 0.5) and survival of at least one infant (91.8% vs 90.6%; P = 0.7) at 30 days. Early LPA was not associated with very preterm delivery or neonatal survival in the regression analyses. Early LPA was associated with a longer LPA-to-delivery interval compared with LPA performed ≥ 18 weeks (median, 106.9 days (range, 2-164 days) vs median, 69.3 days (range, 0-146 days); P < 0.001) when adjusted for confounding variables (hazard ratio, 2.56 (95% CI, 1.76-3.73); P < 0.001). CONCLUSION: Laser surgery before 18 weeks is not associated with an increased rate of very preterm delivery and PPROM or with reduced neonatal survival when compared with LPA after 18 weeks. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Differentiation between TTTS Stages I vs II and III vs IV does not affect probability of double survival after laser therapy.

OBJECTIVE: To compare the perinatal outcome of monochorionic twin pregnancies with twin-twin transfusion syndrome (TTTS), according to the disease severity, defined using Quintero staging, after treatment with fetoscopic laser surgery. METHODS: This was a single-center study of 1020 consecutive cases with severe TTTS, which were treated with fetoscopic laser surgery. During the study period from January 1995 to March 2013, the participants were included at a mean ± SD gestational age of 20.8 ± 2.2 weeks. Perinatal survival analysis, including the rates of double survival and survival of at least one fetus, was undertaken according to the Quintero staging system. For blockwise comparisons of data, the whole population was divided into five chronologically consecutive study subgroups of 200 patients in each of the first four subgroups and 220 in the last one. RESULTS: For the entire study population with known outcome (n = 1019), the rate of pregnancy with double fetal survival was 69.0% (127/184) in Stage-I, 71.4% (257/360) in Stage-II, 55.4% (236/426) in Stage-III and 51.0% (25/49) in Stage-IV TTTS cases. At least one twin survived in 91.3% (168/184) of pregnancies with Stage-I, 89.7% (323/360) of those with Stage-II, 83.1% (354/426) of those with Stage-III and 77.6% (38/49) of those with Stage-IV TTTS. The rates of double survival and survival of at least one fetus were both significantly higher in Stage-II TTTS compared with those in Stage-III TTTS cases (P < 0.001 and P = 0.011, respectively). Survival rates between pregnancies with Stage-I vs Stage-II TTTS and between those with Stage-III vs Stage-IV TTTS were not significantly different. Therefore, we combined pregnancies with Stage-I or Stage-II TTTS, and those with Stage-III or Stage-IV TTTS. The double survival rate was 70.6% (384/544) in combined Stage-I and Stage-II vs 54.9% (261/475) in combined Stage-III and Stage-IV TTTS cases (P < 0.001). At least one twin survived in 90.3% (491/544) of pregnancies with Stage-I or Stage-II TTTS vs 82.5% (392/475) in those with Stage-III or Stage-IV TTTS (P < 0.001). The double survival rate increased between the first and the last consecutive study subgroups from 59.8% (55/92) to 75.0% (96/128) (adjusted odds ratio (aOR)linear trend , 1.26 (95% CI, 1.01-1.56); P = 0.037) in pregnancies with Stage-I or Stage-II TTTS and from 41.7% (45/108) to 62.0% (57/92) (aORlinear trend , 1.21 (95% CI, 0.98-1.50); P = 0.082) in those with Stage-III or Stage-IV TTTS. Double survival rate was the lowest for Stage-III cases in which the donor twin was affected by severely abnormal Doppler findings (45.4% (64/141)). CONCLUSIONS: Double survival and survival of at least one fetus in monochorionic twin pregnancies with TTTS were related significantly to Quintero stage. However, our data show that the differentiation between Stages I vs II and Stages III vs IV does not have any significant prognostic implication for perinatal survival. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Twin-twin transfusion syndrome - a University Hospital experience with intrauterine treatment / Síndrome da transfusão feto-fetal - experiência de um hospital universitário com tratamento intrauterino

ABSTRACT Introduction: twin-to-twin transfusion syndrome (TTTS), defined by combination of polyhydramnios-oligohydramnios, is the most prevalent (5%-35%) of the abnormalities due to placental vascular anastomoses and the most lethal (80%-100% mortality) if untreated. Fetoscopic laser ablation of abnormal vasculature using the Solomon technique is the gold standard approach. It consists of interrupting the intertwin blood flow. Objectives: to present our initial experience at the Fetal Surgery Service of the Hospital de Clinicas of the Federal University of Parana (HC-UFPR) and to compare our results with those reported in the literature. Methods: we conducted a retrospective analysis of pregnancies who had undergone laser ablation, assessing data on Quintero's staging, gestational age at diagnosis and at the time of the procedure, placental position, immediate post-procedure survival, and survival after the neonatal period. We then compared these data with the most recent data available in the literature. Results: we analyzed ten TTTS cases. The diagnosis was performed before the 26th week of pregnancy (median 20.8 weeks) and treatment occurred in a median of 9.5 days later. The distribution by the Quintero's staging was of three cases in stage II, five in stage III, and two in stage IV. In 50% of the gestations, at least one of the fetuses survived through the neonatal period. Conclusion: the treatment of TTTS in the HC-UFPR had a positive impact in the survival of the affected fetuses, although the results were worse than the ones reported in the literature, probably due to the delay in referencing the patients to our service, leading to a prolonged interval between diagnosis and treatment.

RESUMO Introdução: a síndrome de transfusão feto-fetal (STFF), definida pela combinação polidrâmnio-oligohidrâmnio, é a mais prevalente (5 a 35%) das anormalidades associadas às anastomoses vasculares placentárias e tem a maior letalidade (80 a 100%) se não tratada. A ablação a laser destes vasos por via fetoscópica com a técnica de Solomon é o tratamento de escolha atual para a interrupção das anastomoses vasculares. Objetivo: apresentar a experiência inicial do Serviço de Cirurgia Fetal do Hospital de Clínicas da Universidade Federal do Paraná (HC-UFPR) e comparar nossos resultados com os da literatura. Métodos: foram revisados os prontuários de todas as pacientes submetidas ao procedimento de ablação a laser, sendo analisados os dados referentes ao estadiamento de Quintero, à idade gestacional ao diagnóstico e ao procedimento, à posição placentária, à sobrevida imediata pós-procedimento e sobrevida após o período neonatal. Os dados foram então comparados com os mais recentes disponíveis na literatura. Resultados: dez casos de STFF foram analisados. Todos diagnosticados antes da 26a semana (mediana 20,79) e o intervalo diagnóstico-tratamento teve mediana de 9,5 dias. A distribuição pelo estadiamento de Quintero foi: três casos no estádio II, cinco casos no III e dois casos no IV. Em 50% das gestações pelo menos um dos fetos sobreviveu ao período neonatal. Conclusão: o tratamento da STFF no HC-UFPR impactou positivamente a sobrevida dos fetos acometidos. Entretanto, nossos resultados estão aquém dos reportados na literatura, possivelmente pelo demora no referenciamento das pacientes, com intervalo aumentado entre diagnóstico e tratamento.

The incidence, maternal, fetal and neonatal consequences of single intrauterine fetal death in monochorionic twins: A prospective observational UKOSS study.

OBJECTIVE: Report maternal, fetal and neonatal complications associated with single intrauterine fetal death (sIUFD) in monochorionic twin pregnancies. DESIGN: Prospective observational study. SETTING: UK. POPULATION: 81 monochorionic twin pregnancies with sIUFD after 14 weeks gestation, irrespective of cause. METHODS: UKOSS reporters submitted data collection forms using data from hospital records. MAIN OUTCOME MEASURES: Aetiology of sIUFD; surviving co-twin outcomes: perinatal mortality, central nervous system (CNS) imaging, gestation and mode of delivery, neonatal outcomes; post-mortem findings; maternal outcomes. RESULTS: The commonest aetiology was twin-twin transfusion syndrome (38/81, 47%), "spontaneous" sIUFD (22/81, 27%) was second commonest. Death of the co-twin was common (10/70, 14%). Preterm birth (<37 weeks gestation) was the commonest adverse outcome (77%): half were spontaneous and half iatrogenic. Only 46/75 (61%) cases had antenatal CNS imaging, of which 33 cases had known results of which 7/33 (21%) had radiological findings suggestive of neurological damage. Postnatal CNS imaging revealed an additional 7 babies with CNS abnormalities, all born at <36 weeks, including all 4 babies exhibiting abnormal CNS signs. Major maternal morbidity was relatively common, with 6% requiring ITU admission, all related to infection. CONCLUSIONS: Monochorionic twin pregnancies with single IUD are complex and require specialist care. Further research is required regarding optimal gestation at delivery of the surviving co-twin, preterm birth prevention, and classifying the cause of death in twin pregnancies. Awareness of the importance of CNS imaging, and follow-up, needs improvement.