Randomized controlled trial of twin-twin transfusion syndrome laser surgery: the sequential trial.

BACKGROUND: Intraoperative blood transfer between twins during laser surgery for twin-twin transfusion syndrome can vary by surgical technique and has been proposed to explain differences in donor twin survival. OBJECTIVE: This trial compared donor twin survival with 2 laser techniques: the sequential technique, in which the arteriovenous communications from the volume-depleted donor to the volume-overloaded recipient are laser-occluded before those from recipient to donor, and the selective technique, in which the occlusion of the vascular communications is performed in no particular order. STUDY DESIGN: A single-center, open-label, randomized controlled trial was conducted in which twin-twin transfusion syndrome patients were randomized to sequential vs selective laser surgery. Nested within the trial, a second trial randomized patients with superficial anastomoses (arterioarterial and venovenous) to ablation of these connections first (before ablating the arteriovenous anastomoses) vs last. The primary outcome measure was donor twin survival at birth. RESULTS: A total of 642 patients were randomized. Overall donor twin survival was similar between the 2 groups (274 of 320 [85.6%] vs 271 of 322 [84.2%]; odds ratio, 1.12 [95% confidence interval, 0.73-1.73]; P=.605). Superficial anastomoses occurred in 177 of 642 cases (27.6%). Donor survival was lower in the superficial anastomosis group vs those with only arteriovenous communications (125 of 177 [70.6%] vs 420 of 465 [90.3%]; adjusted odds ratio, 0.33 [95% confidence interval, 0.20-0.54]; P<.001). In cases with superficial anastomoses, donor survival was independent of the timing of ablation or surgical technique. The postoperative mean middle cerebral artery peak systolic velocity was lower in the sequential vs selective group (1.00±0.30 vs 1.06±0.30 multiples of the median; P=.003). Post hoc analyses showed 2 factors that were associated with poor overall donor twin survival: the presence or absence of donor twin preoperative critical abnormal Doppler parameters and the presence or absence of arterioarterial anastomoses. Depending on these factors, 4 categories of patients resulted: (1) Category 1 (347 of 642 [54%]), no donor twin critical abnormal Doppler + no arterioarterial anastomoses: donor twin survival was 91.2% in the sequential and 93.8% in the selective groups; (2) Category 2 (143 of 642 [22%]), critical abnormal Doppler present + no arterioarterial anastomoses: donor survival was 89.9% vs 75.7%; (3) Category 3 (73 of 642 [11%]), no critical abnormal Doppler + arterioarterial anastomoses present: donor survival was 94.7% vs 74.3%; and (4) Category 4 (79 of 642 [12%]), critical abnormal Doppler present + arterioarterial anastomoses present: donor survival was 47.6% vs 64.9%. CONCLUSION: Donor twin survival did not differ between the sequential vs selective laser techniques and did not differ if superficial anastomoses were ablated first vs last. The donor twin's postoperative middle cerebral artery peak systolic velocity was improved with the sequential vs the selective approach. Post hoc analyses suggest that donor twin survival may be associated with the choice of laser technique according to high-risk factors. Further study is needed to determine whether using these categories to guide the choice of surgical technique will improve outcomes.

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.

Consensus protocol for management of early and late twin-twin transfusion syndrome: Delphi study.

OBJECTIVE: Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 and 26 weeks' gestation. High-quality evidence and guidelines regarding the optimal clinical management of very early (prior to 16 weeks), early (between 16 and 18 weeks) and late (after 26 weeks) TTTS are lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS. METHODS: A Delphi procedure was conducted among an international panel of experts. Participants were chosen based on their clinical expertise, affiliation and relevant publications. A four-round Delphi survey was conducted using an online platform and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the second and third rounds, participants were asked to grade each statement on a Likert scale (1, completely disagree; 5, completely agree) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of 5 without suggestions for change were accepted as the consensus. Statements with a median grade of 3 or less were excluded from the Delphi process. Statements with a median grade of 4 were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree with the statements, and those with more than 70% agreement without suggestions for change were considered the consensus. RESULTS: A total of 122 experts met the inclusion criteria and were invited to participate, of whom 53 (43.4%) agreed to take part in the study. Of those, 75.5% completed all four rounds. A consensus on the optimal management of early and late TTTS was obtained. FLP can be offered as early as 15 weeks' gestation for selected cases, and can be considered up to 28 weeks. Between 16 and 18 weeks, management should be tailored according to Doppler findings. CONCLUSIONS: A consensus-based treatment protocol for early and late TTTS was agreed upon by a panel of experts. This protocol should be modified at the discretion of the operator, according to their experience and the specific demands of each case. This should advance the quality of future studies, guide clinical practice and improve patient care. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Placental architectural characteristics following laser ablation within monochorionic twins complicated by twin-twin transfusion syndrome: A systematic review and meta-analysis of outcomes.

INTRODUCTION: Twin-twin transfusion syndrome (TTTS) complicates approximately 10%-15% of all monochorionic twin pregnancies. The aim of this review was to evaluate the placental architectural characteristics within TTTS twins following laser and elucidate their impact on fetal outcomes and operative success. MATERIAL AND METHODS: Five databases were searched from inception to August 2023. Studies detailing post-delivery placental analysis within TTTS twins post-laser were included. Studies were categorized into two main groups: (1) residual anastomoses following laser and (2) abnormal cord insertion: either velamentous and/or marginal or proximate. The primary outcome was to determine the proportion of TTTS placentas with residual anastomoses and abnormal cord insertions post-laser. Secondary outcomes included assessing residual anastomoses on post-laser fetal outcomes and assessing the relationship between abnormal cord insertion and TTTS development. Study bias was critiqued using the Joanna Briggs Institute checklists and Cochrane risk of bias tool. Random-effects meta-analysis was used, and results were reported as pooled proportions or odds ratio (OR) with 95% confidence interval (CI). PROSPERO registration: CRD42023476875. RESULTS: Twenty-six studies, comprising 4013 monochorionic twins, were included for analysis. The proportion of TTTS placentas with residual anastomoses following laser was 24% (95% CI, 0.12-0.41), with a mean and standard deviation of 4.03 ± 2.95 anastomoses per placenta. Post-laser residual anastomoses were significantly associated with intrauterine fetal death (OR, 2.38 [95% CI, 1.33-4.26]), neonatal death (OR, 3.37 [95% CI, 1.65-6.88]), recurrent TTTS (OR, 24.33 [95% CI, 6.64-89.12]), and twin anemia polycythemia sequence (OR, 13.54 [95% CI, 6.36-28.85]). Combined abnormal cord (velamentous and marginal), velamentous cord, and marginal cord insertions within one or both twins following laser were reported at rates of 49% (95% CI, 0.39-0.59), 27% (95% CI, 0.18-0.38), and 28% (95% CI, 0.21-0.36), respectively. Combined, velamentous and marginal cord insertions were not significantly associated with TTTS twins requiring laser (p = 0.72, p = 0.38, and p = 0.71, respectively) vs non-TTTS monochorionic twins. CONCLUSIONS: To the best of our knowledge, this is the first review to conjointly explore outcomes of residual anastomoses and abnormal cord insertions within TTTS twins following laser. A large prospective study is necessitated to assess the relationship between abnormal cord insertion and residual anastomoses development post-laser.

Fetoscopic laser coagulation for twin-to-twin transfusion syndrome: a comparison of flexible 1.0/1.2 mm fetoscopes with curved sheaths of 2.7/3.3 mm2 vs. 2 mm fetoscopic lens technique with sheaths of 6.6/11.3 mm2.

OBJECTIVES: Fetoscopic laser coagulation of placental anastomoses is usually performed for a treatment of twin-to-twin transfusion syndrome (TTTS). A common complication of fetoscopic laser coagulation for TTTS is preterm preliminary rupture of fetal membranes (PPROM) aggravating the neonatal outcome significantly. However, use of an flexible 1 mm fetoscope with an curved sheath could reduce iatrogenic damage of the amniotic membrane and improve neonatal outcomes after laser treatment. The aim of this study was to compare neonatal outcomes using this flexible fetoscope with curved sheath vs. use of a standard lens technique. METHODS: Outcomes were retrospective analyzed after use of a standard lens fetoscope of 2 mm (sheath 6.63 mm2 or 11.27 mm2 for anterior placenta) and a flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2) in two German centers of fetal surgery, performed during 2006-2019. RESULTS: Neonatal outcome of 247 TTTS patients were analyzed including the rates of double and single fetal survival. The survival of at least one fetus was 97.2 % in the group with the ultrathin technique (n=154) compared to 88.3 % (n=93) in the group with the standard lens fetoscope (p=0.008). Survival of both fetuses was not different between groups (81.0 vs. 75.3 %). The procedure to delivery interval was significantly increased using the ultrathin fetoscope (89.1±35.0 d vs. 71.4±35.4 d, p=0.001) resulting in an increased gestational age at delivery by 11 days on average (231.9±28.1 d vs. 221.1±32.7 d, p=0.012). CONCLUSIONS: Fetal survival can be significantly increased following TTTS using flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2).

Perinatal outcome of monochorionic triamniotic triplet pregnancy: multicenter cohort study.

OBJECTIVE: Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcome and the timing and methods of fetal intervention in these pregnancies. METHODS: This was a multicenter retrospective cohort study of MC triamniotic (TA) triplet pregnancies managed in 21 participating centers around the world from 2007 onwards. Data on maternal age, mode of conception, diagnosis of major fetal structural anomalies or aneuploidy, gestational age (GA) at diagnosis of anomalies, twin-to-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence and or selective fetal growth restriction (sFGR) were retrieved from patient records. Data on antenatal interventions were collected, including data on selective fetal reduction (three to two or three to one), laser surgery and any other active fetal intervention (including amniodrainage). Data on perinatal outcome were collected, including numbers of live birth, intrauterine demise, neonatal death, perinatal death and termination of fetus or pregnancy (TOP). Neonatal data such as GA at birth, birth weight, admission to neonatal intensive care unit and neonatal morbidity were also collected. Perinatal outcomes were assessed according to whether the pregnancy was managed expectantly or underwent fetal intervention. RESULTS: Of an initial cohort of 174 MCTA triplet pregnancies, 11 underwent early TOP, three had an early miscarriage, six were lost to follow-up and one was ongoing at the time of writing. Thus, the study cohort included 153 pregnancies, of which the majority (92.8%) were managed expectantly. The incidence of pregnancy affected by one or more fetal structural abnormality was 13.7% (21/153) and that of TRAP sequence was 5.2% (8/153). The most common antenatal complication related to chorionicity was TTTS, which affected just over one quarter (27.6%; 42/152, after removing a pregnancy with TOP < 24 weeks for fetal anomalies) of the pregnancies, followed by sFGR (16.4%; 25/152), while TAPS (spontaneous or post TTTS with or without laser treatment) occurred in only 4.6% (7/152) of pregnancies. No monochorionicity-related antenatal complication was recorded in 49.3% (75/152) of pregnancies. Survival was apparently associated largely with the development of these complications: there was at least one survivor beyond the neonatal period in 85.1% (57/67) of pregnancies without antenatal complications, in 100% (25/25) of those complicated by sFGR and in 47.6% (20/42) of those complicated by TTTS. The overall rate of preterm birth prior to 28 weeks was 14.5% (18/124) and that prior to 32 weeks' gestation was 49.2% (61/124). CONCLUSION: Monochorionicity-related complications, which can impact adversely perinatal outcome, occur in almost half of MCTA triplet pregnancies, creating a challenge with regard to counseling, surveillance and management. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of preterm birth by measurement of cervical length on transvaginal ultrasound and magnetic resonance imaging in pregnancies complicated by twin-twin transfusion syndrome and treated with laser surgery.

OBJECTIVES: Twin pregnancies complicated by twin-twin transfusion syndrome (TTTS) are at particularly high risk of preterm birth. Cervical length (CL) measurement on transvaginal ultrasound (TVS) is a powerful predictor of preterm birth, but the predictive accuracy of CL measurement on magnetic resonance imaging (MRI) has not yet been established. We sought to investigate the correlation between CL measurements obtained on preoperative TVS and on MRI and to quantify their predictive accuracy for preterm birth among pregnancies complicated by TTTS that underwent selective fetoscopic laser photocoagulation (SFLP), to identify whether MRI is a useful adjunct to TVS. METHODS: This was a retrospective cohort study of pregnancies that were treated for TTTS with SFLP at a single center between April 2010 and June 2019 and that underwent TVS and MRI evaluation. Correlation was estimated using Pearson's coefficient, mean CL measurements were compared using the two-tailed paired t-test and the frequency at which a short cervix was detected by the two imaging modalities was compared using the χ-square test. Generalized linear models were used to estimate relative risk and receiver-operating-characteristics (ROC)-curve analysis was used to estimate the predictive accuracy of CL for preterm birth. RESULTS: Among 626 pregnancies complicated by TTTS that underwent SFLP, CL measurements were obtained on preoperative TVS in 579 cases and on preoperative MRI in 434. CL ≤ 2.5 cm was recorded in 39 (6.7%) patients on TVS and 47 (10.8%) patients on MRI (P = 0.0001). Measurements of CL made on MRI correlated well with those obtained on TVS overall (r = 0.63), but correlation was weak at the shortest CLs (r < 0.20). MRI failed to detect two (40.0%), three (18.8%), nine (32.1%) and 13 (28.9%) cases diagnosed as having a short cervix on TVS at cut-offs of ≤ 1.5 cm, ≤ 2.0 cm, ≤ 2.5 cm and ≤ 2.8 cm, respectively. Over half of the pregnancies with a preoperative CL of ≤ 2.5 cm delivered by 28 weeks' gestation, regardless of imaging modality. CL measurement on TVS was superior to that on MRI to predict preterm birth, the latter performing poorly at all CL cut-offs. A CL measurement of ≤ 2.0 cm on preoperative TVS had the highest predictive ability for preterm birth, with an area under the ROC curve for delivery before 32 weeks of 0.82. CONCLUSIONS: Although measurement of CL on MRI correlates well with that on TVS overall, it performs poorly at accurately detecting a short cervix. TVS outperforms MRI in evaluation of the cervix and remains the optimal modality for CL measurement in pregnancies at high risk for preterm birth, such as those undergoing SFLP for TTTS. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Outcome following laser surgery of twin-twin transfusion syndrome complicated by selective fetal growth restriction: systematic review and meta-analysis.

OBJECTIVE: The published literature reports mostly on the outcome of twin pregnancies complicated by twin-twin transfusion syndrome (TTTS) without considering whether the pregnancy is also complicated by another pathology, such as selective fetal growth restriction (sFGR). The aim of this systematic review was to report on the outcome of monochorionic diamniotic (MCDA) twin pregnancies undergoing laser surgery for TTTS that were complicated by sFGR and those not complicated by sFGR. METHODS: MEDLINE, EMBASE and Cochrane databases were searched. The inclusion criteria were studies reporting on MCDA twin pregnancies with TTTS undergoing laser therapy that were complicated by sFGR and those not complicated by sFGR. The primary outcome was the overall fetal loss following laser surgery, defined as miscarriage and intrauterine death. The secondary outcomes included fetal loss within 24 h after laser surgery, survival at birth, preterm birth (PTB) prior to 32 weeks of gestation, PTB prior to 28 weeks, composite neonatal morbidity, neurological and respiratory morbidity, and survival free from neurological impairment. All outcomes were explored in the overall population of twin pregnancies complicated by sFGR vs those not complicated by sFGR in the setting of TTTS and in the donor and recipient twins separately. Random-effects meta-analysis was used to combine data and the results are reported as pooled odds ratios (OR) with 95% CI. RESULTS: Five studies (1710 MCDA twin pregnancies) were included in the qualitative synthesis and four in the meta-analysis. The overall risk of fetal loss after laser surgery was significantly higher in MCDA twin pregnancies with TTTS complicated by sFGR (20.90% vs 14.42%), with a pooled OR of 1.6 (95% CI, 1.3-1.9) (P < 0.001). The risk of fetal loss was significantly higher in MCDA twin pregnancies with TTTS and sFGR for the donor but not for the recipient twin. The rate of live twins was 79.1% (95% CI, 72.6-84.9%) in TTTS pregnancies with sFGR and 85.6% (95% CI, 81.0-89.6%) in those without sFGR (pooled OR, 0.6 (95% CI, 0.5-0.8)) (P < 0.001). There was no significant difference in the risk of PTB prior to 32 weeks of gestation (P = 0.308) or prior to 28 weeks (P = 0.310). Assessment of short- and long-term morbidity was affected by the small number of cases. There was no significant difference in the risk of composite (P = 0.506) or respiratory (P = 0.531) morbidity between twins complicated by TTTS with vs those without sFGR, while the risk of neurological morbidity was significantly higher in those with TTTS and sFGR (pooled OR, 1.8 (95% CI, 1.1-2.9)) (P = 0.034). The risk of neurological morbidity was significantly higher for the donor twin (pooled OR, 2.4 (95% CI, 1.1-5.2)) (P = 0.029) but not for the recipient twin (P = 0.361). Survival free from neurological impairment was observed in 70.8% (95% CI, 45.0-91.0%) of twin pregnancies with TTTS complicated by sFGR and in 75.8% (95% CI, 51.9-93.3%) of those not complicated by sFGR, with no difference between the two groups. CONCLUSIONS: sFGR in MCDA pregnancies with TTTS represents an additional risk factor for fetal loss following laser surgery. The findings of this meta-analysis may be useful for individualized risk assessment of twin pregnancy complicated by TTTS and tailored counseling of the parents prior to laser surgery. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Perinatal outcomes of fetoscopic laser surgery for twin-twin transfusion syndrome in triplet pregnancy: cohort study, systematic review and meta-analysis.

OBJECTIVES: The aims of this study were to investigate the perinatal outcome of dichorionic triamniotic (DCTA) and monochorionic triamniotic (MCTA) triplet pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP) in two academic fetal centers, and to conduct a systematic review of previously published data to investigate perinatal survival in this targeted population. METHODS: The first part of the study was a retrospective cohort study of prospectively collected data of consecutive triplet pregnancies with TTTS that underwent FLP at two fetal treatment centers between 2012 and 2020. Demographic, preoperative and operative variables and postoperative outcome were collected. Perinatal outcomes were investigated. The second part of the study was a systematic review and meta-analysis of studies evaluating the outcome of DCTA and/or MCTA triplet pregnancies, including our cohort study. PubMed, Web of Science and Scopus were searched from inception to September 2020. Primary outcomes were fetal survival (survival to birth), neonatal survival (survival to 28 days of age) and gestational age (GA) at birth. RESULTS: A total of 31 sets of triplets with TTTS managed with FLP were included in the cohort study. Of these, 24 were DCTA and seven were MCTA. There were no significant differences in preoperative and operative variables between the two groups. There were also no significant differences between groups in GA at delivery or perinatal survival rate, including fetal and neonatal survival of at least one triplet, at least two triplets and all three triplets. Nine studies, including our cohort study, were included in the systematic review (156 DCTA and 37 MCTA triplet pregnancies treated with FLP). The overall fetal and neonatal survival was 79% (95% CI, 75-83%) and 75% (95% CI, 71-79%), respectively, in DCTA cases and 74% (95% CI, 52-92%) and 71% (95% CI, 49-89%), respectively, in MCTA cases. The rate of preterm birth before 28 weeks and before 32 weeks' gestation was 14% (95% CI, 4-29%) and 61% (95% CI, 50-72%), respectively, in DCTA triplets and 21% (95% CI, 3-45%) and 82% (95% CI, 62-96%), respectively, in MCTA triplets. CONCLUSIONS: Triplet pregnancies with TTTS are at high risk of adverse perinatal outcome and preterm birth, regardless of chorionicity. The rate of survival after FLP in MCTA triplets was higher in our study than that reported in previous studies and is currently comparable with survival in DCTA triplets, which could be due to improved surgical skills. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Correction of fetal umbilical vein flow imbalance following laser surgery for twin-twin transfusion syndrome.

OBJECTIVES: Twin-twin transfusion syndrome (TTTS) is characterized by unequal hemodynamics between the twins. We aimed to assess preoperatively the difference in umbilical vein flow (UVF) between the recipient and donor monochorionic diamniotic twins and evaluate the change in UVF following laser surgery in both twins. METHODS: This was a retrospective cohort study of differences in UVF that occurred following laser surgical treatment of TTTS. Sonographic assessment of the umbilical vein before and 24 h after fetoscopic laser surgery for TTTS was performed. Umbilical vein diameter and time-averaged maximum velocity were measured, and UVF per kg (UVF/kg) was converted into a Z-score by a calculator created using gestational age as an independent variable. Z-score values were converted into centiles, which were evaluated statistically. Median differences in UVF/kg centile values were adjusted for TTTS stage and presence of arterioarterial anastomoses. RESULTS: The study population consisted of 363 TTTS patients. The adjusted preoperative median difference in UVF/kg centile between the recipient vs donor twin was 17.9% (-17.1% to 57.6%), P < 0.0001. The adjusted median difference in UVF/kg centile between the postoperative vs preoperative period among recipients was 2.2% (-10.8% to 13.8%), P < 0.0001, while the adjusted median difference among donors was 27.3% (8.2%-34.6%), P < 0.0001. CONCLUSION: The preoperative difference in UVF between the recipient and donor twins confirms the pathophysiology of TTTS. Postoperatively, the substantial increase in UVF of the donor twin and the relatively small increase in UVF of the recipient twin confirm that ablation of the vascular communications resulted in rapid improvement in perfusion of the donor twin. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Solomon technique vs selective fetoscopic laser photocoagulation for twin-twin transfusion syndrome: systematic review and meta-analysis of maternal and perinatal outcomes.

OBJECTIVE: To ascertain maternal and perinatal outcomes of monochorionic twin pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated with the Solomon technique compared with selective fetoscopic laser photocoagulation (SFLP) of placental anastomoses. METHODS: MEDLINE, EMBASE and The Cochrane Library were searched to identify relevant studies. The outcomes observed were perinatal loss and survival, preterm prelabor rupture of membranes (PPROM), preterm birth (PTB), gestational age (GA) at delivery, interval between laser treatment and delivery, maternal bleeding, septostomy or chorioamniotic separation, placental abruption, twin anemia-polycythemia sequence (TAPS), recurrence of TTTS, neonatal morbidity and neurological morbidity. Random-effects head-to-head meta-analyses were used to analyze the data. Pooled odds ratios (OR) and mean differences (MD) and their 95% CIs were calculated. RESULTS: Nine studies were included in the systematic review. There was generally no difference in the main maternal and pregnancy characteristics between pregnancies treated using the Solomon technique and those treated using SFLP of placental anastomoses. The risks of fetal loss (pooled OR, 0.69 (95% CI, 0.50-0.95); P = 0.023), neonatal death (pooled OR, 0.37 (95% CI, 0.16-0.84); P = 0.018) and perinatal loss (pooled OR, 0.56 (95% CI, 0.38-0.83); P = 0.004) were significantly lower in pregnancies treated using the Solomon technique than in those treated with SFLP. Likewise, pregnancies treated using the Solomon technique had a significantly higher chance of survival of at least one twin (pooled OR, 2.31 (95% CI, 1.03-5.19); P = 0.004) and double survival (pooled OR, 2.18 (95% CI, 1.29-3.70); P = 0.001). There was no difference in the risk of PPROM (P = 0.603), PPROM within 10 days from laser surgery (P = 0.982), PTB (P = 0.207), maternal bleeding (P = 0.219), septostomy or chorioamniotic separation (P = 0.224) or chorioamnionitis (P = 0.135) between the two groups, while the risk of placental abruption was higher in pregnancies treated using the Solomon technique (pooled OR, 2.90 (95% CI, 1.55-5.44); P = 0.001). In the Solomon technique group, pregnancies delivered at a significantly earlier GA than did those treated with SFLP (pooled MD, -0.625 weeks (95% CI, -0.90 to -0.35 weeks); P < 0.001), while there was no difference in the interval between laser treatment and delivery (P = 0.589). The rate of recurrence of TTTS was significantly lower in pregnancies undergoing the Solomon technique (pooled OR, 0.43 (95% CI, 0.22-0.81); P < 0.001), while there was no difference in the risk of TAPS between the two groups (P = 0.792). Finally, there was no difference in the overall risk of neonatal morbidity (P = 0.382) or neurological morbidity (P = 0.247) between the two groups. CONCLUSIONS: Monochorionic twin pregnancies complicated by TTTS undergoing laser treatment using the Solomon technique had a significantly higher survival rate and lower recurrence rate of TTTS but were associated with an increased risk of placental abruption and earlier GA at delivery compared to those treated with SFLP. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Incidence and outcome of prenatal brain abnormality in twin-to-twin transfusion syndrome: systematic review and meta-analysis.

OBJECTIVES: To evaluate the incidence of antenatally diagnosed brain injury in twin pregnancy complicated by twin-to-twin transfusion syndrome (TTTS) and to quantify the perinatal mortality, morbidity and long-term neurodevelopmental outcome of these fetuses. METHODS: MEDLINE, EMBASE, ClinicalTrials.gov and The Cochrane Library databases were searched. Inclusion criteria were studies reporting on brain abnormality diagnosed antenatally in twin pregnancies complicated by TTTS. The primary outcome was the incidence of prenatal brain abnormality. The secondary outcomes were intrauterine demise (IUD), neonatal death, termination of pregnancy (TOP) and long-term morbidity. Outcomes were explored in the population of fetuses with antenatal diagnosis of brain abnormality. Subgroup analysis according to the type of treatment, gestational age, Quintero stage at diagnosis and/or treatment, and cotwin death was planned. Meta-analysis of proportions was used to combine data and pooled proportions and their 95% CI were reported. RESULTS: Thirteen studies including 1573 cases of TTTS and 88 fetuses with an antenatal diagnosis of brain abnormality were included in the systematic review. The meta-analysis included only studies reporting on brain abnormality in twin pregnancy complicated by TTTS cases and treated with laser surgery. Overall, brain injury occurred in 2.2% (52/2410) of fetuses (eight studies). Brain abnormality was reported in 1.03% and 0.82% of recipients and donors, respectively. The most common type of abnormality was ischemic lesions (30.4% (95% CI, 19.1-43.0%)), followed by destructive lesions (23.9% (95% CI, 13.7-35.9%)), ventriculomegaly (19.9% (95% CI, 10.6-31.3%)) and hemorrhagic lesions (15.3% (95% CI, 7.1-25.8%)). Spontaneous IUD occurred in 13.4% (95% CI, 5.1-24.8%) of fetuses, while TOP was chosen by parents in 53.5% (95% CI, 38.9-67.8%) cases. Neonatal death was reported by only three studies, with an incidence of 15.4% (95% CI, 2.8-35.4%). Finally, only two studies reported on composite morbidity, with an overall rate of the outcome of 20.4% (95% CI, 2.5-49.4%) and rates of 29.7% and 20.4% in the recipient and donor fetuses, respectively. Due to the small numbers, only composite morbidity was analyzed and no information on neonatal intensive care unit admission, respiratory distress syndrome or other long-term outcomes, such as neurodevelopmental delay and cerebral palsy, could be retrieved reliably. CONCLUSIONS: The overall incidence of antenatally diagnosed fetal brain abnormality in twin pregnancy complicated by TTTS treated with laser surgery is around 2% and is mainly ischemic in nature (30.4%). TOP was chosen by parents in more than half of cases (53.5%). No information could be retrieved on morbidity outcomes, highlighting the urgent need for long-term follow-up studies of these children. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

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.

Perinatal outcomes of iatrogenic chorioamniotic separation following fetoscopic surgery: systematic review and meta-analysis.

OBJECTIVE: To compare the perinatal outcomes between pregnancies with and those without iatrogenic chorioamniotic separation (iCAS) following fetoscopic intervention. METHODS: We performed a search in PubMed, EMBASE, Scopus, Web of Science and Google Scholar from inception up to December 2020 for studies comparing perinatal outcomes between pregnancies that developed and those that did not develop iCAS after fetoscopic intervention for twin-to-twin transfusion syndrome (TTTS), open neural tube defect (ONTD) or congenital diaphragmatic hernia. A random-effects model was used to pool the mean differences (MD) or odds ratios (OR) and the corresponding 95% CI. The primary outcome was neonatal survival. Secondary outcomes included gestational age (GA) at intervention and at delivery, interval from intervention to delivery and incidence of preterm prelabor rupture of membranes (PPROM) and preterm delivery. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa scale. RESULTS: The search identified 348 records, of which seven studies (six on fetoscopic laser photocoagulation (FLP) for TTTS and one on fetoscopic repair for ONTD) assessed the perinatal outcomes of pregnancies that developed iCAS after fetoscopic intervention. Given that only one study reported on fetoscopic ONTD repair, the meta-analysis was limited to TTTS pregnancies and included six studies (total of 1881 pregnancies). Pregnancies that developed iCAS after FLP for TTTS, compared with those that did not, had significantly lower GA at the time of intervention (weeks) (MD, -1.07 (95% CI, -1.89 to -0.24); P = 0.01) and at delivery (weeks) (MD, -1.74 (95% CI, -3.13 to -0.34); P = 0.01) and significantly lower neonatal survival (OR, 0.41 (95% CI, 0.24-0.70); P = 0.001). In addition, development of iCAS after FLP for TTTS increased significantly the risk for PPROM < 34 weeks' gestation (OR, 3.98 (95% CI, 1.76-9.03); P < 0.001) and preterm delivery < 32 weeks (OR, 1.80 (95% CI, 1.16-2.80); P = 0.008). CONCLUSIONS: iCAS is a common complication after FLP for TTTS. In patients undergoing FLP for TTTS, iCAS develops more often with earlier GA at intervention and is associated with earlier GA at delivery, higher risk of PPROM < 34 weeks' gestation and preterm delivery < 32 weeks and lower neonatal survival. Given the limitations of this meta-analysis and lack of literature reporting on other types of fetoscopic intervention, the presented findings should be interpreted with caution and should not be generalized to fetoscopic procedures used to treat other fetal conditions. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal cardiac filling and ejection time fractions by pulsed-wave Doppler: reference ranges and potential clinical application.

OBJECTIVES: Fetal cardiac function can be evaluated using a variety of parameters. Among these, cardiac cycle time-related parameters, such as filling time fraction (FTF) and ejection time fraction (ETF), are promising but rarely studied. We aimed to report the feasibility and reproducibility of fetal FTF and ETF measurements using pulsed-wave Doppler, to provide reference ranges for fetal FTF and ETF, after evaluating their relationship with heart rate (HR), gestational age (GA) and estimated fetal weight (EFW), and to evaluate their potential clinical utility in selected fetal conditions. METHODS: This study included a low-risk prospective cohort of singleton pregnancies and a high-risk population of fetuses with severe twin-twin transfusion syndrome (TTTS), aortic stenosis (AoS) or aortic coarctation (CoA), from 18 to 41 weeks' gestation. Left ventricular (LV) and right ventricular inflow and outflow pulsed-wave Doppler signals were analyzed, using valve clicks as landmarks. FTF was calculated as: (filling time/cycle time) × 100. ETF was calculated as: (ejection time/cycle time) × 100. Intraclass correlation coefficients (ICC) were used to evaluate the intra- and interobserver reproducibility of FTF and ETF measurements in low-risk fetuses. The relationships of FTF and ETF with HR, GA and EFW were evaluated using multivariate regression analysis. Reference ranges for FTF and ETF were then constructed using the low-risk population. Z-scores of FTF and ETF in the high-risk fetuses were calculated and analyzed. RESULTS: In total, 602 low-risk singleton pregnancies and 54 high-risk fetuses (nine pairs of monochorionic twins with severe TTTS, 16 fetuses with AoS and 20 fetuses with CoA) were included. Adequate Doppler traces for FTF and ETF could be obtained in 95% of low-risk cases. Intraobserver reproducibility was good to excellent (ICC, 0.831-0.905) and interobserver reproducibility was good (ICC, 0.801-0.837) for measurements of all timing parameters analyzed. Multivariate analysis of FTF and ETF in relation to HR, GA and EFW in low-risk fetuses identified HR as the only variable predictive of FTF, while ETF was dependent on both HR and GA. FTF increased with decreasing HR in low-risk fetuses, while ETF showed the opposite behavior, decreasing with decreasing HR. Most recipient twins with severe TTTS showed reduced FTF and preserved ETF. AoS was associated with decreased FTF and increased ETF in the LV, with seemingly different patterns associated with univentricular vs biventricular postnatal outcome. The majority of fetuses with CoA had FTF and ETF within the normal range in both ventricles. CONCLUSIONS: Measurement of FTF and ETF using pulsed-wave Doppler is feasible and reproducible in the fetus. The presented reference ranges account for associations of FTF with HR and of ETF with HR and GA. These time fractions are potentially useful for clinical monitoring of cardiac function in severe TTTS, AoS and other fetal conditions overloading the heart. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Outcome of radiofrequency ablation for selective fetal reduction before vs at or after 16 gestational weeks in complicated monochorionic pregnancy.

OBJECTIVE: To investigate whether gestational age at intervention (< or ≥ 16 weeks) and other factors affect the risk of loss of the cotwin after selective fetal reduction using radiofrequency ablation (RFA) in monochorionic (MC) pregnancy. METHODS: This was a single-center retrospective analysis of 63 consecutive RFA procedures performed at our institution from January 2011 to October 2019 for selective fetal reduction in complicated MC pregnancies. Indications for RFA were twin reversed arterial perfusion sequence (13 cases), twin-to-twin transfusion syndrome (12 cases), twin anemia-polycythemia sequence (two cases), selective fetal growth restriction (10 cases), discordant anomalies (17 cases) and multifetal pregnancy reduction in triplets or quadruplets with a MC pair (nine cases). Twenty-six (41.3%) of these procedures were performed before and 37 (58.7%) after 16 weeks. Potential factors that could affect the risk of loss of the cotwin, including gestational age at RFA, order of multiple pregnancy, amnionicity, indication for RFA and number of ablation cycles, were assessed first by univariate analysis and then by multivariate analysis. RESULTS: There were 17 (27.0%) cotwin losses. Ablation cycles numbering four or more was the only factor among those investigated to be associated with loss of the cotwin after RFA (P = 0.035; odds ratio, 5.21), while the indication for RFA, order of multiple pregnancy, amnionicity and gestational age at RFA had no effect. Comparing RFA performed at < 16 vs ≥ 16 weeks, there was no difference in the rate of cotwin loss (23.1% vs 29.7%; P = 0.558) or preterm prelabor rupture of the membranes before 34 weeks (7.7% vs 5.4%; P = 0.853), or in the median gestational age at delivery (36.2 vs 37.3 weeks; P = 0.706). CONCLUSIONS: RFA is a promising tool for early selective fetal reduction in MC pregnancy before 16 weeks. Four or more ablation cycles is a major risk factor for cotwin loss. Careful assessment pre- and post-RFA, together with proficient operative skills to minimize the number of ablation cycles, are the mainstay to ensure that this procedure is effective and safe. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Outcomes of fetoscopic laser surgery for twin-to-twin transfusion syndrome between 26 and 27 weeks of gestation in Japan.

AIM: The purpose of this study was to investigate the outcomes of fetoscopic laser photocoagulation (FLP) for twin-to-twin transfusion syndrome (TTTS) in Japan. METHODS: The retrospective cohort study (2012-2018) was conducted in monochorionic twin pregnancies that underwent FLP for TTTS between 26 and 27 weeks from 2012 to 2018. The perioperative data, maternal complications, gestational age (GA) at delivery, neonatal complications, and survival of infants at 28 days of age were analyzed. At term-equivalent age, severe neurological complications were identified by imaging study. RESULTS: Of 644 patients, 28 (4.3%) underwent FLP between 26 and 27 weeks, and 26 were analyzed. FLP procedures were technically successful in all cases. There were no cases of major maternal complications after surgery. Preterm rupture of membranes occurred in 34.6% of cases, and the mean GA at delivery was 33.2 ± 3.1 weeks. The survival of both twins was found in 23 (88.4%) cases, and the perinatal survival rate of at least one twin at 28 days of age was 100%. Severe neurological complications were found in six (12.2%) cases out of 49. CONCLUSIONS: FLP for TTTS between 26 and 27 weeks provided a good prognosis and caused no major maternal complications. However, severe neurological findings were found in 12% of infants.

Outcome of twin-to-twin transfusion syndrome in monochorionic monoamniotic twin pregnancy: systematic review and meta-analysis.

OBJECTIVES: To explore the outcome of monochorionic monoamniotic (MCMA) twin pregnancies affected by twin-to-twin transfusion syndrome (TTTS). METHODS: MEDLINE and EMBASE databases were searched for studies reporting the outcome of MCMA twin pregnancies complicated by TTTS. The primary outcome was intrauterine death (IUD); secondary outcomes were miscarriage, single IUD, double IUD, neonatal death (NND), perinatal death (PND), survival of at least one twin, survival of both twins and preterm birth (PTB) before 32 weeks' gestation. Outcomes were assessed in MCMA twins affected by TTTS not undergoing intervention and in those treated with amniodrainage, laser therapy or cord occlusion. Subgroup analysis was performed including cases diagnosed before 24 weeks. Random-effects meta-analysis of proportions was used to analyze the data. RESULTS: Fifteen cohort studies, including 888 MCMA twin pregnancies, of which 44 were affected by TTTS, were included in the review. There was no randomized trial comparing the different management options in MCMA twin pregnancies complicated by TTTS. In cases not undergoing intervention, miscarriage occurred in 11.0% of fetuses, while the incidence of IUD, NND and PND was 25.2%, 12.2% and 31.2%, respectively. PTB complicated 50.5% of these pregnancies. In cases treated by laser surgery, the incidence of miscarriage, IUD, NND and PND was 19.6%, 27.4%, 7.4% and 35.9%, respectively, and the incidence of PTB before 32 weeks' gestation was 64.9%. In cases treated with amniodrainage, the incidence of IUD, NND and PND was 31.3%, 13.5% and 45.7% respectively, and PTB complicated 76.2% of these pregnancies. Analysis of cases undergoing cord occlusion was affected by the very small number of included cases. Miscarriage occurred in 19.2%, while there was no case of IUD or NND of the surviving twin. PTB before 32 weeks occurred in 50.0% of these cases. CONCLUSIONS: MCMA twin pregnancies complicated by TTTS are at high risk of perinatal mortality and PTB. Further studies are needed in order to elucidate the optimal type of prenatal treatment in these pregnancies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Early- and late-onset selective fetal growth restriction in monochorionic diamniotic twin pregnancy: natural history and diagnostic criteria.

OBJECTIVES: To evaluate the natural history and outcome of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancy, according to gestational age at onset and various reported diagnostic criteria, and to quantify the risk of superimposed twin-to-twin transfusion syndrome (TTTS). METHODS: This was a cohort study of MCDA twin pregnancies that had their routine antenatal care from the first trimester at St George's Hospital, London, UK. Pregnancies had ultrasound examinations every 2 weeks at 16-24 weeks and then every 2-3 weeks until delivery. The diagnostic criteria for sFGR were estimated fetal weight (EFW) of one twin < 10th centile and intertwin EFW discordance ≥ 25%. We also applied other diagnostic criteria reported in a recent Delphi consensus. Pregnancies in which the diagnosis of TTTS was made before that of sFGR were not included in the analysis. Pregnancies that underwent fetal intervention for sFGR were excluded. The incidence of sFGR was compared between the different diagnostic criteria, overall and according to gestational age at onset. In all subsequent analyses, cases of sFGR included those diagnosed according to any of the criteria. The Gratacós classification of sFGR was applied (Type I, II or III). Pregnancy outcomes included miscarriage, intrauterine death, neonatal death and admission to the neonatal unit. Comparisons between groups were carried out using the Mann-Whitney U-test for continuous variables and the chi-square or Fisher's exact test for categorical variables. RESULTS: The analysis included 287 MCDA twin pregnancies. According to the International Society of Ultrasound in Obstetrics and Gynecology diagnostic criteria, the incidence of early (< 24 weeks) sFGR was 4.9%, while that of late sFGR was 3.8%. When applying the various diagnostic criteria, the incidence of early sFGR varied from 1.7% to 9.1% and that of late sFGR varied from 1.1% to 5.9%. In early-onset cases, the incidence of Type I sFGR was 80.8%, that of Type II was 15.4% and that of Type III was 3.8%. The corresponding figures in late-onset cases were 94.4%, 5.6% and 0%. The incidence of superimposed TTTS was 26.9% in cases affected by early-onset sFGR and 5.6% in those affected by late-onset sFGR. The incidence of perinatal death was 8.0% in early-onset sFGR and 5.6% in late-onset sFGR (P = 0.661). Admission to the neonatal unit occurred in 61.0% and 52.9% of cases, respectively (P = 0.484). CONCLUSIONS: In MCDA twin pregnancies, early-onset sFGR is slightly more common than is late-onset sFGR, although this difference was not significant, and is associated with worse perinatal outcome. The incidence of Types II and III sFGR is higher in early-onset sFGR. The incidence also varies according to the diagnostic criteria used, which supports the use of standardized international diagnostic criteria. Superimposed TTTS is more common in early- than in late-onset sFGR. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Outcome of twin-twin transfusion syndrome according to Quintero stage of disease: systematic review and meta-analysis.

OBJECTIVES: To report the outcome of pregnancies complicated by twin-twin transfusion syndrome (TTTS) according to Quintero stage. METHODS: MEDLINE, EMBASE and CINAHL databases were searched for studies reporting the outcome of pregnancies complicated by TTTS stratified according to Quintero stage (I-V). The primary outcome was fetal survival rate according to Quintero stage. Secondary outcomes were gestational age at birth, preterm birth (PTB) before 34, 32 and 28 weeks' gestation and neonatal morbidity. Outcomes are reported according to the different management options (expectant management, laser therapy or amnioreduction) for pregnancies with Stage-I TTTS. Only cases treated with laser therapy were considered for those with Stages-II-IV TTTS and only cases managed expectantly were considered for those with Stage-V TTTS. Random-effects head-to-head meta-analysis was used to analyze the extracted data. RESULTS: Twenty-six studies (2699 twin pregnancies) were included. Overall, 610 (22.6%) pregnancies were diagnosed with Quintero stage-I TTTS, 692 (25.6%) were Stage II, 1146 (42.5%) were Stage III, 247 (9.2%) were Stage IV and four (0.1%) were Stage V. Survival of at least one twin occurred in 86.9% (95% CI, 84.0-89.7%) (456/552) of pregnancies with Stage-I, in 85% (95% CI, 79.1-90.1%) (514/590) of those with Stage-II, in 81.5% (95% CI, 76.6-86.0%) (875/1040) of those with Stage-III, in 82.8% (95% CI, 73.6-90.4%) (172/205) of those with Stage-IV and in 54.6% (95% CI, 24.8-82.6%) (5/9) of those with Stage-V TTTS. The rate of a pregnancy with no survivor was 11.8% (95% CI, 8.4-15.8%) (69/564) in those with Stage-I, 15.0% (95% CI, 9.9-20.9%) (76/590) in those with Stage-II, 18.6% (95% CI, 14.2-23.4%) (165/1040) in those with Stage-III, 17.2% (95% CI, 9.6-26.4%) (33/205) in those with Stage-IV and in 45.4% (95% CI, 17.4-75.2%) (4/9) in those with Stage-V TTTS. Gestational age at birth was similar in pregnancies with Stages-I-III TTTS, and gradually decreased in those with Stages-IV and -V TTTS. Overall, the incidence of PTB and neonatal morbidity increased as the severity of TTTS increased, but data on these two outcomes were limited by the small sample size of the included studies. When stratifying the analysis of pregnancies with Stage-I TTTS according to the type of intervention, the rate of fetal survival of at least one twin was 84.9% (95% CI, 70.4-95.1%) (94/112) in cases managed expectantly, 86.7% (95% CI, 82.6-90.4%) (249/285) in those undergoing laser therapy and 92.2% (95% CI, 84.2-97.6%) (56/60) in those after amnioreduction, while the rate of double survival was 67.9% (95% CI, 57.0-77.9%) (73/108), 69.7% (95% CI, 61.6-77.1%) (203/285) and 80.8% (95% CI, 62.0-94.2%) (49/60), respectively. CONCLUSIONS: Overall survival in monochorionic diamniotic pregnancies affected by TTTS is higher for earlier Quintero stages (I and II), but fetal survival rates are moderately high even in those with Stage-III or -IV TTTS when treated with laser therapy. Gestational age at birth was similar in pregnancies with Stages-I-III TTTS, and gradually decreased in those with Stages-IV and -V TTTS treated with laser and expectant management, respectively. In pregnancies affected by Stage-I TTTS, amnioreduction was associated with slightly higher survival compared with laser therapy and expectant management, although these findings may be confirmed only by future head-to-head randomized trials. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Resultado del síndrome de transfusión feto-fetal según el estadio de Quintero de la enfermedad: revisión sistemática y metaanálisis OBJETIVOS: Informar sobre el resultado de los embarazos complicados por el síndrome de transfusión feto-fetal (TTTS, por sus siglas en inglés) según el estadio de Quintero. MÉTODOS: Se hicieron búsquedas en las bases de datos de MEDLINE, EMBASE y CINAHL de estudios que hubieran informado sobre el resultado de embarazos complicados por TTTS, estratificados según el estadio de Quintero (I-V). El resultado primario fue la tasa de supervivencia fetal según el estadio de Quintero. Los resultados secundarios fueron la edad gestacional al nacer, el parto pretérmino (PPT) antes de las 34, 32 y 28 semanas de gestación y la morbilidad neonatal. Los resultados se reportan de acuerdo con las diferentes opciones de tratamiento (expectante, terapia de láser o amniorreducción) para los embarazos con TTTS en Estadio I. Sólo se consideraron los casos tratados con terapia de láser para aquellos con TTTS de las Etapas II-IV y sólo se consideraron los casos tratados de manera expectante para aquellos con TTTS de la Etapa V. Para analizar los datos extraídos se utilizó un metaanálisis directo de efectos aleatorios. RESULTADOS: Se incluyeron veintiséis estudios (2699 embarazos de gemelos). En total, 610 (22,6%) embarazos fueron diagnosticados con TTTS de Estadio I de Quintero, 692 (25,6%) de Estadio II, 1146 (42,5%) de Estadio III, 247 (9,2%) de Estadio IV y cuatro (0,1%) de Estadio V. La supervivencia de al menos un gemelo se produjo en el 86,9% (IC 95%, 84,0-89,7%) (456/552) de los embarazos en Estadio I, en el 85% (IC 95%, 79,1-90,1%) (514/590) de aquellos en Estadio II, en el 81,5% (IC 95%, 76,6-86,0%) (875/1040) de aquellos en Estadio-III, en el 82,8% (IC 95%, 73,6-90,4%) (172/205) de aquellos en Estadio-IV y en el 54,6% (IC 95%, 24,8-82,6%) (5/9) de aquellos en Estadio-V de TTTS. La tasa de embarazos sin supervivientes fue del 11,8% (IC 95%, 8,4-15,8%) (69/564) de aquellos en Estadio-I, 15,0% (IC 95%, 9,9-20,9%) (76/590) de aquellos en Estadio-II, 18,6% (IC 95%, 14,2-23,4%) (165/1040) de aquellos en Estadio-III, 17,2% (IC 95%, 9,6-26,4%) (33/205) de aquellos en Estadio-IV y en el 45,4% (IC 95%, 17,4-75,2%) (4/9) de aquellos en Estadio-V de TTTS. La edad gestacional al nacer fue similar en los embarazos con TTTS en los Estadios I-III, y disminuyó gradualmente en aquellos con TTTS en los Estadios IV y V. En general, la incidencia de PPT y la morbilidad neonatal aumentaron a medida que se incrementó la gravedad del TTTS, pero los datos sobre estos dos resultados se vieron limitados por el pequeño tamaño de la muestra de los estudios incluidos. Al estratificar el análisis de los embarazos con TTTS en Estadio I según el tipo de tratamiento, la tasa de supervivencia fetal de al menos un gemelo fue del 84,9% (IC 95%, 70,4-95,1%) (94/112) en los casos tratados de forma expectante, del 86,7% (IC 95%, 82,6-90.4%) (249/285) en los sometidos a terapia láser y del 92,2% (IC 95%, 84,2-97,6%) (56/60) en los sometidos a amniorreducción, mientras que la tasa de supervivencia doble fue del 67,9% (IC 95%, 57,0-77,9%) (73/108), del 69,7% (IC 95%, 61,6-77,1%) (203/285) y del 80,8% (IC 95%, 62,0-94,2%) (49/60), respectivamente. CONCLUSIONES: La supervivencia en general en los embarazos biamnióticos monocoriónicos afectados por TTTS es mayor en los estadios tempranos de Quintero (I y II), pero las tasas de supervivencia fetal son moderadamente altas incluso en aquellos con TTTS en estadios III o IV cuando se tratan con terapia láser. La edad gestacional al nacer fue similar en los embarazos con TTTS en los Estadios I-III, y disminuyó gradualmente en aquellos con TTTS en los Estadios IV y V tratados con láser y tratamiento expectante, respectivamente. En los embarazos afectados por TTTS en Estadio I, la amniorreducción estuvo asociada con una supervivencia ligeramente mayor en comparación con la terapia de láser y el tratamiento expectante, aunque estos hallazgos solo pueden confirmarse mediante futuros estudios aleatorizados directos. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.