Society for Maternal-Fetal Medicine Consult Series #72: Twin-twin transfusion syndrome and twin anemia-polycythemia sequence.

Thirty percent of spontaneously occurring twins are monozygotic, of which two-thirds are monochorionic, possessing a single placenta. A common placental mass with shared intertwin placental circulation is key to the development and management of complications unique to monochorionic gestations. In this Consult, we review general considerations and a contemporary approach to twin-twin transfusion syndrome and twin anemia-polycythemia sequence, providing management recommendations based on the available evidence. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend routine first-trimester sonographic determination of chorionicity and amnionicity (GRADE 1B); (2) we recommend that ultrasound surveillance for twin-twin transfusion syndrome begin at 16 weeks of gestation for all monochorionic-diamniotic twin pregnancies and continue at least every 2 weeks until delivery, with more frequent monitoring indicated with clinical concern (GRADE 1C); (3) we recommend that routine sonographic surveillance for twin-twin transfusion syndrome minimally include assessment of amniotic fluid volumes on both sides of the intertwin membrane and evaluation for the presence or absence of urine-filled fetal bladders, and ideally incorporate Doppler study of the umbilical arteries (GRADE 1C); (4) we recommend fetoscopic laser surgery as the standard treatment for stage II through stage IV twin-twin transfusion syndrome presenting between 16 and 26 weeks of gestation (GRADE 1A); (5) we recommend expectant management with at least weekly fetal surveillance for asymptomatic patients continuing pregnancies complicated by stage I twin-twin transfusion syndrome, and consideration for fetoscopic laser surgery for stage I twin-twin transfusion syndrome presentations between 16 and 26 weeks of gestation complicated by additional factors such as maternal polyhydramnios-associated symptomatology (GRADE 1B); (6) we recommend an individualized approach to laser surgery for early- and late-presenting twin-twin transfusion syndrome (GRADE 1C); (7) we recommend that all patients with twin-twin transfusion syndrome qualifying for laser therapy be referred to a fetal intervention center for further evaluation, consultation, and care (Best Practice); (8) after laser therapy, we suggest weekly surveillance for 6 weeks followed by resumption of every-other-week surveillance thereafter, unless concern exists for post-laser twin-twin transfusion syndrome, post-laser twin anemia-polycythemia sequence, or fetal growth restriction (GRADE 2C); (9) following the resolution of twin-twin transfusion syndrome after fetoscopic laser surgery, and without other indications for earlier delivery, we recommend delivery of dual-surviving monochorionic-diamniotic twins at 34 to 36 weeks of gestation (GRADE 1C); (10) in twin-twin transfusion syndrome pregnancies complicated by posttreatment single fetal demise, we recommend full-term delivery (39 weeks) of the surviving co-twin to avoid complications of prematurity unless indications for earlier delivery exist (GRADE 1C); (11) we recommend that fetoscopic laser surgery not influence the mode of delivery (Best Practice); (12) we recommend that prenatal diagnosis of twin anemia-polycythemia sequence minimally require either middle cerebral artery Doppler peak systolic velocity values >1.5 and <1.0 multiples of the median in donor and recipient twins, respectively, or an intertwin Δ middle cerebral artery peak systolic velocity >0.5 multiples of the median (GRADE 1C); (13) we recommend that providers consider incorporating middle cerebral artery Doppler peak systolic velocity determinations into all monochorionic twin ultrasound surveillance beginning at 16 weeks of gestation (GRADE 1C); and (14) consultation with a specialized fetal care center is recommended when twin anemia-polycythemia sequence progresses to a more advanced disease stage (stage ≥II) before 32 weeks of gestation or when concern arises for coexisting complications such as twin-twin transfusion syndrome (Best Practice).

Role of gestational age at time of placental laser surgery in outcomes of twin-to-twin transfusion syndrome.

OBJECTIVE: There are conflicting data on whether fetoscopic laser photocoagulation of placental anastomoses (FLP) for treating twin-to-twin transfusion syndrome (TTTS) is associated with lower rates of overall survival. The objective of this study is to characterize survival and other associated morbidity after FLP across gestational ages of FLP. METHODS: This is a secondary analysis of prospectively collected data on patients with monochorionic-diamniotic twins that had FLP for TTTS at two centers between 2011 and 2022. Patients were divided into gestational age epochs for FLP before 18 wks, 18 0/7 - 19 6/7 wks, 20 0/7 - 21 6/7 wks, 22 0/7 - 23 6/7 wks, 24 0/7 - 25 6/7 wks and after 26 wks. Demographic characteristics, sonographic characteristics of TTTS and operative characteristics were compared across the gestational age epochs. Outcomes including overall survival, preterm delivery, preterm prelabor rupture of membranes (PPROM), intrauterine fetal demise (IUFD) and neonatal demise (NND) were also compared across gestational age epochs. Multivariate analysis was performed by fitting logistic regression models for these outcomes. Kaplan-Mejer curves were constructed to compare the interval from PPROM to delivery for each gestational age epoch. RESULTS: There were 768 patients that met inclusion criteria. The dual survival rate was 61.3% for FLP performed prior to 18 weeks compared to 78.0% - 86.7% across later gestational age epochs. This appears to be related to increased rates of donor IUFD following FLP performed before, versus after 18 weeks (28.0% vs. 9.3% - 14.1%). Rates of recipient IUFD/NND and donor NND were similar regardless of gestational age of FLP. Rates of PPROM were higher for earlier FLP, ranging from 45.6% for FLP before 18 weeks to 11.9% for FLP at 24 - 26 weeks gestational age. However, the gestational age of delivery was similar across gestational age epochs with a median of 31.7 weeks. In multivariate analysis, donor loss was independently associated with FLP before 18 weeks after adjusting for selective fetal growth restriction, Quintero stage and other covariates. PPROM and PTD were also associated with FLP before 18 weeks after adjusting for cervical length, placental location, trocar size, laser energy and amnioinfusion. CONCLUSION: FLP performed at earlier gestational ages is associated with lower overall survival, which is driven by higher risk of donor IUFD, as opposed to differences in PPROM or PTD. Counseling regarding survival should account for gestational age of presentation. This article is protected by copyright. All rights reserved.

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.

Fetal and neonatal neuroimaging in twin-twin transfusion syndrome.

OBJECTIVES: To describe the types of brain injury and subsequent neurodevelopmental outcome in fetuses and neonates from pregnancies with twin-twin transfusion syndrome (TTTS). Additionally, to determine risk factors for brain injury and to review the use of neuroimaging modalities in these cases. METHODS: This was a retrospective cohort study of consecutive TTTS pregnancies treated with laser surgery in a single fetal therapy center between January 2010 and January 2020. The primary outcome was the incidence of brain injury, classified into predefined groups. Secondary outcomes included adverse outcome (perinatal mortality or neurodevelopmental impairment), risk factors for brain injury and the number of magnetic resonance imaging (MRI) scans. RESULTS: Cranial ultrasound was performed in all 466 TTTS pregnancies and in 685/749 (91%) liveborn neonates. MRI was performed in 3% of pregnancies and 4% of neonates. Brain injury was diagnosed in 16/935 (2%) fetuses and 37/685 (5%) neonates and all predefined injury groups were represented. Four fetal and four neonatal cases of cerebellar hemorrhage were detected. Among those with brain injury, perinatal mortality occurred in 11/16 (69%) fetuses and 8/37 (22%) neonates. Follow-up was available for 29/34 (85%) long-term survivors with brain injury and the mean age at follow-up was 46 months. Neurodevelopmental impairment was present in 9/29 (31%) survivors with brain injury. Adverse outcome occurred in 28/53 (53%) TTTS individuals with brain injury. The risk of brain injury was increased after recurrent TTTS/post-laser twin anemia-polycythemia sequence (TAPS) (odds ratio (OR), 3.095 (95% CI, 1.581-6.059); P = 0.001) and lower gestational age at birth (OR per 1-week decrease in gestational age, 1.381 (95% CI, 1.238-1.541); P < 0.001). CONCLUSIONS: Based on dedicated neurosonography and limited use of MRI, brain injury was diagnosed in 2% of fetuses and 5% of neonates with TTTS. Adverse outcome was seen in over half of cases with brain injury. Brain injury was related to recurrent TTTS/post-laser TAPS and a lower gestational age at birth. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

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.

Neurodevelopmental outcome in complicated twin pregnancy: prospective observational study.

OBJECTIVE: Twin pregnancy is associated with increased perinatal mortality and morbidity, but long-term neurodevelopmental outcome remains underinvestigated. The primary objective of this study was to investigate the incidence of adverse neurodevelopment after 1 year of age in complicated monochorionic diamniotic (MCDA) twin pregnancies compared with uncomplicated twin pregnancies. METHODS: This was a prospective cohort study conducted at St George's University Hospital NHS Foundation Trust, London, UK. Women with a twin pregnancy culminating in at least one surviving child, aged between 12 and 60 months (corrected for prematurity) at the time of assessment, were invited to complete the relevant Ages and Stages Questionnaire® version 3 (ASQ-3) test. The two study groups were: (1) complicated MCDA twin pregnancies, including those with twin-twin transfusion syndrome, twin anemia-polycythemia sequence, selective fetal growth restriction, twin reversed arterial perfusion sequence and/or single intrauterine demise; and (2) uncomplicated MCDA and dichorionic diamniotic twin pregnancies. The primary outcome measure was an abnormal ASQ-3 score, defined as a score of more than 2 SD below the mean in any one of the five domains. Mixed-effects multivariable logistic regression analysis was performed to determine whether a complicated MCDA twin pregnancy was associated independently with an abnormal ASQ-3 score. RESULTS: The study included 174 parents who completed the questionnaire for one or both twins; therefore, 327 ASQ-3 questionnaires were available for analysis. Of those, 117 (35.8%) were complicated MCDA twin pregnancies and 210 (64.2%) were controls. The overall rate of an abnormal ASQ-3 score in children born of a complicated MCDA twin pregnancy was nearly double that of those from uncomplicated twin pregnancies (14.5% vs 7.6%; P = 0.056). Children born of a complicated MCDA twin pregnancy had a significantly higher rate of impairment in the gross-motor domain compared with the control group (8.5% vs 2.9%; P = 0.031). Complicated MCDA twin pregnancies that underwent prenatal intervention had a significantly higher rate of abnormal ASQ-3 score compared with those that did not undergo prenatal intervention (28.1% vs 1.7%; P < 0.001). On multilevel logistic regression analysis, complicated MCDA twin pregnancy was an independent predictor of abnormal ASQ-3 score (adjusted odds ratio, 3.28 (95% CI, 3.27-3.29); P < 0.001). CONCLUSIONS: This study demonstrates that survivors of complicated MCDA twin pregnancies have a higher rate of adverse neurodevelopmental outcome, independently of prematurity. Long-term neurodevelopmental follow-up in these pregnancies can ensure timely and optimal management of those affected. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of 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.

Fetoscopic laser versus amnioreduction, septostomy, and expected management for the treatment of twin-twin transfusion syndrome (TTTS): an economic evaluation analysis in Iran.

BACKGROUND: Twin-twin transfusion syndrome (TTTS) affects 10-15% of monochorionic twin pregnancies. Without treatment, their mortality rates would be considerable. There are differences in survival rate between different therapeutic modalities. This study aims to compare the cost-effectiveness of Fetoscopic laser versus amnioreduction, septostomy, and expected management in the treatment of twin-to-twin transfusion syndrome (TTTS). METHODS: This is a cost-effectiveness analysis of the treatment strategies in patients with TTTS. A decision tree model was used to estimate the clinical and economic outcomes with a pregnancy period time horizon. Medical direct costs were extracted in a quantitative study, and survival rates were determined as effectiveness measures based on a review. A probabilistic sensitivity analysis was used to measure the effects of uncertainty in the model parameters. The TreeAge, Excel and R software were used for analyzing data. RESULTS: In the first phase, 75 studies were included in the review. Based on the meta-analysis, a total of 7183 women treated with Fetoscopic laser, the perinatal survival of at least one twin-based pregnancy was 69%. In the second phase, the results showed that expected management and amnioreduction have the lowest (791.6$) and highest cost (2020.8$), respectively. Based on the decision model analysis, expected management had the lowest cost ($791.67) and the highest rate in at least one survival (89%), it was used only in early stages of TTTS. Fetoscopic laser surgery, with the mean cost 871.46$ and an overall survival rate of 0.69 considered the most cost-effectiveness strategy in other stages of TTTS. CONCLUSION: Our model found Fetoscopic laser surgery in all stages of TTTS to be the most cost-effective therapy for patients with TTTS. Fetoscopic laser surgery thus should be considered a reasonable treatment option for TTTS.

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) versus 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).

Should We Stitch-Close the Fetoscopic Percutaneous Access? A Case-Series of Laparotomy to Trans-Amniotic Membrane Suturing for Intrauterine Port Placement in Fetoscopic Surgery for Twins.

INTRODUCTION: Maternal laparotomy-assisted fetoscopic surgery for in-utero myelomeningocele repair has shown that a trans-amniotic membrane suture during fetoscopic port placement can reduce postsurgical complications. Fetoscopic laser photocoagulation (FLP) for complex twins is typically performed percutaneously without a transmembrane stitch. However, in scenarios without a placental-free window, maternal laparotomy may be used for recipient sac access. Here, we present the outcomes of our series of laparotomy-assisted FLP cases, including a trans-amniotic membrane suturing of the fetoscopic port. METHODS: Retrospective series of twin-twin transfusion syndrome or twin anemia-polycythemia sequence (TAPS) cases treated at 2 fetal centers that underwent maternal laparotomy to FLP from September 2017 to January 2023. We recorded preoperative and operative characteristics, as well as pregnancy and neonatal outcomes. RESULTS: During the study period, 9 maternal laparotomy to FLP cases were performed. Two were excluded for prior percutaneous FLP in the pregnancy. The remaining seven utilized a maternal laparotomy to trans-amniotic membrane stitch with confirmation of proper suture placement under ultrasound guidance, and all surgeries were performed with a single 10 F Check-Flo® cannula. Mean gestational age (GA) at surgery was 19.1 weeks (range 16 weeks 4 days-23 weeks 3 days), with delivery occurring at a mean GA of 35.0 weeks (range 32 weeks 0 days-37 weeks 1 day), resulting in a mean latency of 15.8 weeks, significantly longer than what is reported in the literature and our own data (mean latency for percutaneous FLP 10.2, 95% CI 9.9-10.5). Furthermore, all cases underwent iatrogenic delivery before labor onset, with the lone delivery prior to 34 weeks due to concern for post-laser TAPS. CONCLUSION: This case series of laparotomy to FLP with trans-amniotic stitch, demonstrated no cases of spontaneous preterm birth and a longer-than-expected latency from surgery to delivery. Larger studies are warranted to investigate this approach.

IFMSS at Forty: You Heard It Here First.

BACKGROUND: The International Fetal Medicine and Surgery Society (IFMSS) was founded a little over 40 years ago, to offer a collegial, interdisciplinary forum for fetal specialists worldwide. Its inclusive culture has allowed innovations, successes, and failures to be reported freely. The present report examines progress in the field of fetal medicine, as reflected by the diversity and frequency of IFMSS presentations. We also test the hypothesis that throughout the decades, IFMSS has remained at the forefront of new developments in fetal diagnosis and therapy. SUMMARY: The scientific programs of annual conferences were reviewed for title and subject and assigned one or more keywords, and a single category (resulting in absolute, rather than relative incidences of topics). Select procedures covered at IFMSS meetings were plotted over time against comparable queries in PubMed. 5,467 presentations were reviewed and categorized. Keywords were plotted as a heatmap, showing a gradual shift from mostly observational to increasingly invasive studies. The relative interest of particular topics varied widely over the years, from bladder obstruction and renal pathology in early meetings, to complicated twin gestations, to fetal surgery for diaphragmatic hernia and myelomeningocele. Reports on the treatment of twin-to-twin transfusion syndrome, fetal surgery for myelomeningocele and stem cell therapy preceded similar publications in the world literature by several years. KEY MESSAGES: In its 40-year history, IFMSS has continued to offer an interdisciplinary forum for fetal medicine specialists, even as the topics of interests have evolved with the pace of technology, long-term follow-up, and new scientific discoveries.

Pre- and Periviable PPROM after Fetoscopic Laser Surgery: Are Survival Outcomes Better than We Think?

INTRODUCTION: Limited data exist regarding outcomes when pre- and periviable PPROM (PPROM ≤26 weeks of gestation) occurs as a complication of fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS). METHODS: This is a retrospective cohort study of FLS cases performed at a single institution between January 2015 and May 2021. Study inclusion was limited to patients with monochorionic-diamniotic twin pregnancies complicated by TTTS who underwent FLS. Patients were grouped by pPPROM status, and further stratified to those continuing with expectant management, and outcomes were compared between groups. The primary outcome was survival to live birth of at least one twin. RESULTS: During the study period, 171 patients underwent FLS and a total of 96 (56.1%) subjects satisfied inclusion criteria. Among included subjects, 18 (18.8%) experienced pPPROM after FLS and 78 (81.2%) did not. Baseline characteristics were similar between groups. Among patients with pPPROM, 11 (61.1%) pursued expectant management and 7 (38.9%) opted for pregnancy termination. Among expectantly managed subjects, median pPPROM-to-delivery interval was 47.0 days (6.0-66.0 IQR) with a median gestational age at delivery of 29+1 weeks (24 + 4-33 + 6 IQR). Rates of survival to live birth of at least one twin (90.9% vs. 96.2% p = 0.42) were similar between those with pPPROM undergoing expectant management and those without pPPROM. Dual survivorship (45.5% vs. 78.2%, p = 0.03), perinatal survival to live birth (68.2% vs. 87.2%, p = 0.05), and perinatal survival to newborn hospital discharge (59.1% vs. 85.9%, p = <0.01) were all significantly lower among those with pPPROM. Gestational age at delivery was lower among those continuing with pregnancies complicated by pPPROM (29 + 1 vs. 32+5 weeks, p = <0.01). CONCLUSION: Survival of at least one twin to live birth remained high among those pursing expectant management after experiencing post-FLS pPPROM, suggesting that the outlook after this complication is not necessarily poor. However, this complication was associated with lower chances of dual survival and greater prematurity.

Temporal ultrasound findings in the first trimester of a dual fetal demise occurring in a monochorionic diamniotic twin gestation.

Single fetal demise in monochorionic gestations in the 2nd and 3rd trimester is associated with adverse outcomes for the co-twin. We present a case of single demise in a monochorionic gestation in the 1st trimester with evidence of subsequent hemodynamic aberrations in the co-twin, supportive of feto-fetal hemorrhage occurring early in gestation.

Prediction of dual survival following fetoscopic laser photocoagulation for twin-twin transfusion syndrome.

OBJECTIVE: To develop a model based on factors available at the time of diagnosis of twin-twin transfusion syndrome (TTTS) for predicting the probability of dual twin survival following fetoscopic laser photocoagulation (FLP) using a machine-learning algorithm. METHODS: This was a retrospective study of data collected at two university-affiliated tertiary fetal centers between 2012 and 2021. The cohort included monochorionic diamniotic twin pregnancies complicated by TTTS that underwent FLP. Data were stratified based on survival 30 days after delivery, and cases with dual survival were compared to those without dual survival. A random forest machine-learning algorithm was used to construct a prediction model, and the relative importance value was calculated for each parameter that presented a statistically significant difference between the two study groups and was included in the model. The holdout method was applied to check overfitting of the random forest algorithm. A prediction model for dual twin survival 30 days after delivery was presented based on the test set. RESULTS: The study included 537 women with monochorionic diamniotic twin pregnancy, of whom 346 (64.4%) had dual twin survival at 30 days after delivery and were compared with 191 (35.6%) cases that had one or no survivors. Univariate analysis demonstrated no differences in demographic parameters between the groups. At the time of diagnosis, the dual-survival group had lower rates of estimated fetal weight (EFW) < 10th centile for gestational age in the donor twin (56.4% vs 69.4%; P = 0.004), intertwin EFW discordance > 25% (40.8% vs 56.5%; P = 0.001) and anterior placenta (40.5% vs 50.0%; P = 0.034). Comparison of Doppler findings between the two groups demonstrated significant differences in the donor twin, with a lower rate of pulsatility index (PI) > 95th centile in the umbilical artery and ductus venosus and a lower rate of PI < 5th centile in the fetal middle cerebral artery in the dual-survival group. Relative importance values for each of these six parameters were calculated, allowing the construction of a prediction model with an area under the receiver-operating-characteristics curve of 0.916 (95% CI, 0.887-0.946). CONCLUSIONS: We developed a predictive model for dual survival in monochorionic twin pregnancies following FLP for TTTS, which incorporates six variables obtained at the time of diagnosis of TTTS, including donor EFW < 10th centile, intertwin EFW discordance > 25%, anterior placenta and abnormal PI in the umbilical artery, ductus venosus and middle cerebral artery of the donor twin. This clinically applicable tool may improve treatment planning and patient counseling. © 2022 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.

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.

Impact of Selective Fetal Growth Restriction on Laser Therapy Outcomes in Twin-Twin Transfusion Syndrome.

INTRODUCTION: The aim of this study was to determine if outcomes of fetoscopic laser photocoagulation in isolated twin-twin transfusion syndrome (TTTS) differ from TTTS with concomitant selective fetal growth restriction (sFGR). METHODS: This is a retrospective cohort study of all cases of TTTS treated at the CHU Sainte-Justine between February 2006 and January 2020. Data were collected from maternal, obstetrical, and neonatal chart review. RESULTS: A total of 149 patients were included in our study. Forty-seven patients (31.5%) had a pregnancy complicated by TTTS and sFGR. Mean gestational age at diagnosis and at treatment was 20+4 weeks and 20+6 weeks for TTTS alone, and 20+5 weeks and 21+2 weeks with concomitant sFGR. The presence of concomitant sFGR negatively impacted survival. Double survival in the TTTS + sFGR was 48.9% (23/47) versus 68.6% (70/102) in the TTTS-only group (p = 0.021). Fetal donor survival was 59.6% (28/47) in the TTTS + sFGR group and 84.3% (86/102) in the TTTS-only group (p = 0.001). However, the survival of at least one twin did not differ between the two groups: 93.6% (44/47) in the TTTS + sFGR group versus 92.2% (94/102) in the TTTS-only group (p = 0.751). The presence of type 2-3 sFGR (OR = 0.56; 95% CI 0.32-0.96, p = 0.033) and gestational age at laser therapy (OR = 1.17; 95% CI 1.01 = 1.36, p = 0.036) were independently associated with dual survival. CONCLUSION: sFGR is independently associated with decreased double survivorship at the expense of the donor in TTTS undergoing laser therapy. Type 2 or 3 sFGR and early gestational age at treatment are especially at risk. A larger cohort is needed to validate our results.

Flexible Video Fetoscopy: Feasibility and Outcomes of a Novel Modality for Laser Therapy in Twin-to-Twin Transfusion Syndrome Presenting with Inaccessible Anterior Placenta.

INTRODUCTION: Identification of intertwin anastomosis may be challenging during fetoscopy in cases with complete anterior placenta. The aim of this study was to describe the technique, feasibility, and outcomes of flexible video fetoscopy for laser coagulation in monochorionic (MC) twin pregnancies with twin-to-twin transfusion syndrome (TTTS) presenting with inaccessible anterior placenta. METHODS: From April 2021 to March 2022, a prospective cohort of consecutive MC twin pregnancies complicated with TTTS presenting with anterior placenta after 20 weeks was recruited. Cases with inaccessible anterior placenta during standard technique were converted into flexible video fetoscopy for completion of laser coagulation of placental anastomoses using a 270° flexible video endoscope through the same uterine port. Descriptive analysis includes feasibility, remaining anastomoses requiring laser photocoagulation, and perinatal outcomes. RESULTS: A total of 45 pregnancies with TTTS were treated with fetoscopic laser therapy during the 1-year study period. Twenty-one pregnancies presented with anterior placenta after 20 weeks, in which an inaccessible vascular equator was observed in 33.3% (7/21). Flexible video fetoscopy was successfully performed in all 7 cases at a median gestational age of 22+2 (20+0-27+1) weeks+days. Visualization of the entire placental surface, coagulation of selected vessels, and exploration of the entire vascular equator were achieved in all cases. Six cases (85.7%) required additional laser coagulation due to either vascular patency despite initial coagulation with conventional fetoscopy (1/6, 16.7%) and/or remaining noncoagulated anastomoses (5/6, 83.3%). Perinatal survival of at least one twin and both twins was achieved in 85.7% and 57.1%, respectively. DISCUSSION: Flexible video fetoscopy for completion of laser coagulation of placental anastomoses is feasible and represents a good option for TTTS cases presenting after 20 weeks with inaccessible anterior placenta.

Intertwin Membrane Perforation and Umbilical Cord Entanglement after Laser Surgery for Twin-Twin Transfusion Syndrome: Prevalence, Risk Factors, and Outcome.

INTRODUCTION: Perforation of the intertwin membrane can occur as a complication of fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS). Data on the occurrence and the risk of subsequent cord entanglement are limited. The objective of this study was to assess the prevalence, risk factors and outcome of intertwin membrane perforation, and cord entanglement after laser surgery for TTTS. METHODS: In this multicenter retrospective study, we included all TTTS pregnancies treated with laser surgery in two fetal therapy centers, Shanghai (China) and Leiden (the Netherlands) between 2002 and 2020. We evaluated the occurrence of intertwin membrane perforation and cord entanglement after laser, based on routine fortnightly ultrasound examination and investigated the risk factors and the association with adverse short- and long-term outcomes. RESULTS: Perforation of the intertwin membrane occurred in 118 (16%) of the 761 TTTS pregnancies treated with laser surgery and was followed by cord entanglement in 21% (25/118). Perforation of the intertwin membrane was associated with higher laser power settings, 45.8 Watt versus 42.2 Watt (p = 0.029) and a second fetal surgery procedure 17% versus 6% (p < 0.001). The group with intertwin membrane perforation had a higher rate of caesarean section (77% vs. 31%, p < 0.001) and a lower gestational age at birth (30.7 vs. 33.3 weeks of gestation, p < 0.001) compared to the group with an intact intertwin membrane. Severe cerebral injury occurred more often in the group with intertwin membrane perforation, 9% (17/185) versus 5% (42/930), respectively (p = 0.019). Neurodevelopmental outcome at 2 years of age was similar between the groups with and without perforation of the intertwin membrane and between the subgroups with and without cord entanglement. CONCLUSION: Perforation of the intertwin membrane after laser occurred in 16% of TTTS cases treated with laser and led to cord entanglement in at least 1 in 5 cases. Intertwin membrane perforation was associated with a lower gestational age at birth and a higher rate of severe cerebral injury in surviving neonates.