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.

Patient empowerment improves follow-up data collection after fetal surgery for spina bifida: institutional audit.

OBJECTIVES: To define and grade fetal and maternal adverse events following fetal surgery for spina bifida and to report on the impact of engaging patients in collecting follow-up data. METHODS: This prospective single-center audit included 100 consecutive patients undergoing fetal surgery for spina bifida between January 2012 and December 2021. In our setting, patients return to their referring unit for further pregnancy care and delivery. On discharge, referring hospitals were requested to return outcome data. For this audit, we prompted patients and referring hospitals to provide data in cases of missing outcomes. Outcomes were categorized as missing, returned spontaneously or returned following additional request, by the patient and/or referring center. Postoperative maternal and fetal complications until delivery were defined and graded according to Maternal and Fetal Adverse Event Terminology (MFAET) and the Clavien-Dindo classification. RESULTS: There were no maternal deaths, but severe maternal complications occurred in seven women (anemia in pregnancy, postpartum hemorrhage, pulmonary edema, lung atelectasis, urinary tract obstruction and placental abruption). No cases of uterine rupture were reported. Perinatal death occurred in 3% of fetuses and other severe fetal complications in 15% (perioperative fetal bradycardia/cardiac dysfunction, fistula-related oligohydramnios, chorioamnionitis and preterm prelabor rupture of membranes (PPROM) before 32 weeks). PPROM occurred in 42% of patients and, overall, delivery took place at a median gestational age of 35.3 weeks (interquartile range, 34.0-36.6 weeks). Information provided following additional request, from both centers and patients but mainly from the latter, reduced missing data by 21% for gestational age at delivery, 56% for uterine-scar status at birth and 67% for shunt insertion at 12 months. Compared with the generic Clavien-Dindo classification, the MFAET system ranked complications in a more clinically relevant way. CONCLUSIONS: The nature and rate of severe complications following fetal surgery for spina bifida were similar to those reported in other large series. Spontaneous return of outcome data by referring centers was low, yet patient empowerment improved data collection. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetal endoscopic tracheal occlusion reverses the natural history of right-sided congenital diaphragmatic hernia: European multicenter experience.

OBJECTIVE: To evaluate the neonatal outcome of fetuses with isolated right-sided congenital diaphragmatic hernia (iRCDH) based on prenatal severity indicators and antenatal management. METHODS: This was a retrospective review of prospectively collected data on consecutive cases diagnosed with iRCDH before 30 weeks' gestation in four fetal therapy centers, between January 2008 and December 2018. Data on prenatal severity assessment, antenatal management and perinatal outcome were retrieved. Univariate and multivariate logistic regression analysis were used to identify predictors of survival at discharge and early neonatal morbidity. RESULTS: Of 265 patients assessed during the study period, we excluded 40 (15%) who underwent termination of pregnancy, two cases of unexplained fetal death, two that were lost to follow-up, one for which antenatal assessment of lung hypoplasia was not available and six cases which were found to have major associated anomalies or syndromes after birth. Of the 214 fetuses with iRCDH included in the neonatal outcome analysis, 86 were managed expectantly during pregnancy and 128 underwent fetal endoscopic tracheal occlusion (FETO) with a balloon. In the expectant-management group, lung size measured by ultrasound or by magnetic resonance imaging was the only independent predictor of survival (observed-to-expected lung-to-head ratio (o/e-LHR) odds ratio (OR), 1.06 (95% CI, 1.02-1.11); P = 0.003). Until now, stratification for severe lung hypoplasia has been based on an o/e-LHR cut-off of 45%. In cases managed expectantly, the survival rate was 15% (4/27) in those with o/e-LHR ≤ 45% and 61% (36/59) for o/e-LHR > 45% (P = 0.001). However, the best o/e-LHR cut-off for the prediction of survival at discharge was 50%, with a sensitivity of 78% and specificity of 72%. In the expectantly managed group, survivors with severe pulmonary hypoplasia stayed longer in the neonatal intensive care unit than did those with mildly hypoplastic lungs. In fetuses with an o/e-LHR ≤ 45% treated with FETO, survival rate was higher than in those with similar lung size managed expectantly (49/120 (41%) vs 4/27 (15%); P = 0.014), despite higher prematurity rates (gestational age at birth: 34.4 ± 2.7 weeks vs 36.8 ± 3.0 weeks; P < 0.0001). In fetuses treated with FETO, gestational age at birth was the only predictor of survival (OR, 1.25 (95% CI, 1.04-1.50); P = 0.02). CONCLUSIONS: Antenatal measurement of lung size can predict survival in iRCDH. In fetuses with severe lung hypoplasia, FETO was associated with a significant increase in survival without an associated increase in neonatal morbidity. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Outcome of monochorionic twin pregnancy complicated by Type-III selective intrauterine growth restriction.

OBJECTIVE: Type-III selective intrauterine growth restriction (sIUGR) is associated with a high and unpredictable risk of fetal death and fetal brain injury. The objective of this study was to describe the prospective risk of fetal death and the risk of adverse neonatal outcome in a cohort of twin pregnancies complicated by Type-III sIUGR and treated according to up-to-date guidelines. METHODS: We reviewed retrospectively all monochorionic diamniotic twin pregnancies complicated by Type-III sIUGR managed at nine fetal centers over a 12-year period. Higher-order multiple gestations and pregnancies with major fetal anomalies or other monochorionicity-related complications at initial presentation were excluded. Data on fetal and neonatal outcomes were collected and management strategies reviewed. Composite adverse neonatal outcome was defined as neonatal death, invasive ventilation beyond the resuscitation period, culture-proven sepsis, necrotizing enterocolitis requiring treatment, intraventricular hemorrhage Grade > I, retinopathy of prematurity Stage > II or cystic periventricular leukomalacia. The prospective risk of intrauterine death (IUD) and the risk of neonatal complications according to gestational age were evaluated. RESULTS: We collected data on 328 pregnancies (656 fetuses). After exclusion of pregnancies that underwent selective reduction (n = 18 (5.5%)), there were 51/620 (8.2%) non-iatrogenic IUDs in 35/310 (11.3%) pregnancies. Single IUD occurred in 19/328 (5.8%) pregnancies and double IUD in 16/328 (4.9%). The prospective risk of non-iatrogenic IUD per fetus declined from 8.1% (95% CI, 5.95-10.26%) at 16 weeks, to less than 2% (95% CI, 0.59-2.79%) after 28.4 weeks and to less than 1% (95% CI, -0.30 to 1.89%) beyond 32.6 weeks. In otherwise uncomplicated pregnancies with Type-III sIUGR, delivery was generally planned at 32 weeks, at which time the risk of composite adverse neonatal outcome was 29.0% (31/107 neonates). In twin pregnancies that continued to 34 weeks, there was a very low risk of IUD (0.7%) and a low risk of composite adverse neonatal outcome (11%). CONCLUSIONS: In this cohort of twin pregnancies complicated by Type-III sIUGR and treated at several tertiary fetal centers, the risk of fetal death was lower than that reported previously. Further efforts should be directed at identifying predictors of fetal death and optimal antenatal surveillance strategies to select a cohort of pregnancies that can continue safely beyond 33 weeks' gestation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

The vascular equator in monochorionic twin placentas.

INTRODUCTION: We aim to examine the location of the vascular equator according to the umbilical cord insertions in monochorionic twin placentas. METHODS: We combined two prospective series of monochorionic diamniotic twin placentas of patients included in the first trimester between 2004 and 2008, and between 2016 and 2019. We injected the placentas after birth and divided them into three groups, with respectively concordant (eccentric-eccentric, marginal-marginal, and velamentous-velamentous), intermediate (eccentric-marginal and marginal-velamentous) and discordant (eccentric-velamentous) cord insertions. For each unidirectional anastomosis, we determined the cord-anastomosis ratio and then calculated the mean ratio per placenta in each group. We also calculated the deviation from the midline in all groups. RESULTS: 195 placentas were included. In concordant placentas, the mean cord-anastomosis ratio was 0.957 (95% CI [0.908-1.009]). In placentas with intermediate discordance, the mean ratio was 0.886 (95% CI [0.828-0.948]) and in discordant placentas it was 0.797 (95% CI [0,708-0.897]) (p < 0.001). In concordant placentas, the equator was in the middle of the cord insertions with an average deviation of 0.2 cm (95% CI [-0.1 - 0.3]). In the intermediate placentas, the equator deviated on average 0.5 cm (95% CI [0.2-0.8]) and was displaced from the middle towards the most central cord insertion. In discordant placentas, there was an average displacement of 1.0 cm (95% CI [0.50-1.6]). DISCUSSION: In concordant placentas, the vascular equator lies in the middle between both cord insertions. In intermediate and discordant placentas, the equator is closer to the more central cord insertion.

Treatment and outcome of 370 cases with spontaneous or post-laser twin anemia-polycythemia sequence managed in 17 fetal therapy centers.

OBJECTIVE: To investigate the antenatal management and outcome in a large international cohort of monochorionic twin pregnancies with spontaneous or post-laser twin anemia-polycythemia sequence (TAPS). METHODS: This study analyzed data of monochorionic twin pregnancies diagnosed antenatally with spontaneous or post-laser TAPS in 17 fetal therapy centers, recorded in the TAPS Registry between 2014 and 2019. Antenatal diagnosis of TAPS was based on fetal middle cerebral artery peak systolic velocity > 1.5 multiples of the median (MoM) in the TAPS donor and < 1.0 MoM in the TAPS recipient. The following antenatal management groups were defined: expectant management, delivery within 7 days after diagnosis, intrauterine transfusion (IUT) (with or without partial exchange transfusion (PET)), laser surgery and selective feticide. Cases were assigned to the management groups based on the first treatment that was received after diagnosis of TAPS. The primary outcomes were perinatal mortality and severe neonatal morbidity. The secondary outcome was diagnosis-to-birth interval. RESULTS: In total, 370 monochorionic twin pregnancies were diagnosed antenatally with TAPS during the study period and included in the study. Of these, 31% (n = 113) were managed expectantly, 30% (n = 110) with laser surgery, 19% (n = 70) with IUT (± PET), 12% (n = 43) with delivery, 8% (n = 30) with selective feticide and 1% (n = 4) underwent termination of pregnancy. Perinatal mortality occurred in 17% (39/225) of pregnancies in the expectant-management group, 18% (38/215) in the laser group, 18% (25/140) in the IUT (± PET) group, 10% (9/86) in the delivery group and in 7% (2/30) of the cotwins in the selective-feticide group. The incidence of severe neonatal morbidity was 49% (41/84) in the delivery group, 46% (56/122) in the IUT (± PET) group, 31% (60/193) in the expectant-management group, 31% (57/182) in the laser-surgery group and 25% (7/28) in the selective-feticide group. Median diagnosis-to-birth interval was longest after selective feticide (10.5 (interquartile range (IQR), 4.2-14.9) weeks), followed by laser surgery (9.7 (IQR, 6.6-12.7) weeks), expectant management (7.8 (IQR, 3.8-14.4) weeks), IUT (± PET) (4.0 (IQR, 2.0-6.9) weeks) and delivery (0.3 (IQR, 0.0-0.5) weeks). Treatment choice for TAPS varied greatly within and between the 17 fetal therapy centers. CONCLUSIONS: Antenatal treatment for TAPS differs considerably amongst fetal therapy centers. Perinatal mortality and morbidity were high in all management groups. Prolongation of pregnancy was best achieved by expectant management, treatment by laser surgery or selective feticide. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Core outcome set for studies investigating management of selective fetal growth restriction in twins.

OBJECTIVE: Selective fetal growth restriction (sFGR) occurs in monochorionic twin pregnancies when unequal placental sharing leads to restriction in the growth of just one twin. Management options include laser separation of the fetal circulations, selective reduction or expectant management, but what constitutes the best treatment is not yet known. New trials in this area are urgently needed but, in this rare and complex group, maximizing the relevance and utility of clinical research design and outputs is paramount. A core outcome set ensures standardized outcome collection and reporting in future research. The objective of this study was to develop a core outcome set for studies evaluating treatments for sFGR in monochorionic twins. METHODS: An international steering group of clinicians, researchers and patients with experience of sFGR was established to oversee the process of development of a core outcome set for studies investigating the management of sFGR. Outcomes reported in the literature were identified through a systematic review and informed the design of a three-round Delphi survey. Clinicians, researchers, and patients and family representatives participated in the survey. Outcomes were scored on a Likert scale from 1 (limited importance for making a decision) to 9 (critical for making a decision). Consensus was defined a priori as a Likert score of ≥ 8 in the third round of the Delphi survey. Participants were then invited to take part in an international meeting of stakeholders in which the modified nominal group technique was used to consider the consensus outcomes and agree on a final core outcome set. RESULTS: Ninety-six outcomes were identified from 39 studies in the systematic review. One hundred and three participants from 23 countries completed the first round of the Delphi survey, of whom 88 completed all three rounds. Twenty-nine outcomes met the a priori criteria for consensus and, along with six additional outcomes, were prioritized in a consensus development meeting, using the modified nominal group technique. Twenty-five stakeholders participated in this meeting, including researchers (n = 3), fetal medicine specialists (n = 3), obstetricians (n = 2), neonatologists (n = 3), midwives (n = 4), parents and family members (n = 6), patient group representatives (n = 3), and a sonographer. Eleven core outcomes were agreed upon. These were live birth, gestational age at birth, birth weight, intertwin birth-weight discordance, death of surviving twin after death of cotwin, loss during pregnancy or before final hospital discharge, parental stress, procedure-related adverse maternal outcome, length of neonatal stay in hospital, neurological abnormality on postnatal imaging and childhood disability. CONCLUSIONS: This core outcome set for studies investigating the management of sFGR represents the consensus of a large and diverse group of international collaborators. Use of these outcomes in future trials should help to increase the clinical relevance of research on this condition. Consensus agreement on core outcome definitions and measures is now required. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

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.

Fertility, pregnancy and gynecological outcomes after fetoscopic surgery for congenital diaphragmatic hernia.

STUDY QUESTION: What is the impact of fetoscopic surgery for isolated Congenital Diaphragmatic Hernia (CDH) on future reproductive and gynecological outcomes? SUMMARY ANSWER: We did not observe an increase of obstetric or gynecological problems after fetoscopic surgery nor was there an increased risk for subsequent infertility. WHAT IS KNOWN ALREADY: The reproductive and gynecological outcomes of patients undergoing open maternal-fetal surgery are known. The most relevant counseling items are the elevated risk for uterine dehiscence and rupture (up to 14%). STUDY DESIGN, SIZE, DURATION: Bi-centric study over a 10-year period including 371 women carrying a fetus with isolated CDH either managed expectantly (n = 167) or operated in utero (n = 204). PARTICIPANTS/MATERIALS, SETTING, METHODS: Consenting patients filled out a survey with 23 questions (2 open and 21 multiple choice). Questionnaires were custom designed to obtain information on subsequent reproductive or gynecological problems as well as psychological impact. MAIN RESULTS AND THE ROLE OF CHANCE: The response rate was 40% (147/371). More women in the FETO group attempted a subsequent pregnancy: 70% (62/89) when compared with 47% (27/58) in controls (P = 0.009). This coincided with a longer follow-up in the FETO group (76 versus 59 months; P < 0.001) and a lower survival rate in the index pregnancy (53 versus 72%; P = 0.028). There was no difference in the number of nulliparous or parous women, neither in the conception rate. In total, there were 129 subsequent pregnancies. Nobody reported secondary fertility problems. Four women in the FETO group and one in the control reported a congenital anomaly in a subsequent pregnancy. Twenty-one pregnancies were reported with at least one complication (FETO: 23% (14/60), controls 27% (7/26)). During delivery or in the post-partum period 11 patients reported at least 1 complication (FETO 17% (10/59), controls 4% (1/24)). New onset gynecological problems occurred in 14 participants (10%). None of these events were more likely in one or the other group. Psychological and emotional impacts were frequent in both the FETO (41%) and the control groups (46%) (P = 0.691). LIMITATIONS, REASONS FOR CAUTION: The response rate was 40% (147/371), less than desired. The use of unvalidated self-reported outcomes may skew exact determination of the nature and severity of medical complications. The number of observations for uncommon events was low. The mean follow-up period to detect gynecological complications may be too short. WIDER IMPLICATIONS OF THE FINDINGS: This is the first evidence that fetoscopic surgery for CDH does not compromise future reproductive potential or obstetrical outcome when compared with expectant management. A pregnancy complicated by a serious congenital birth defect, such as CDH, frequently has a measurable psychological impact. STUDY FUNDING/COMPETING INTEREST: The authors have no conflicts to declare. J.D. receives a fundamental clinical research grant of the Fonds Wetenschappelijk Onderzoek - Vlaanderen (FWO; 18.01207). A.C.E. is supported by the Erasmus+Program of the European Union (Framework agreement number 2013-0040; contract 1011990). This was presented at the 61st meeting of the Society of Gynaecologic Investigation, in Florence, March 2014 (F-111).

Operator competence in fetoscopic laser surgery for twin-twin transfusion syndrome: validation of a procedure-specific evaluation tool.

OBJECTIVES: Fetoscopic laser surgery for twin-twin transfusion syndrome is a procedure for which no objective tools exist to assess technical skills. To ensure that future fetal surgeons reach competence prior to performing the procedure unsupervised, we developed a performance assessment tool. The aim of this study was to validate this assessment tool for reliability and construct validity. METHODS: We made use of a procedure-specific evaluation instrument containing all essential steps of the fetoscopic laser procedure, which was previously created using Delphi methodology. Eleven experts and 13 novices from three fetal medicine centers performed the procedure on the same simulator. Two independent observers assessed each surgery using the instrument (maximum score: 52). Interobserver reliability was assessed using Spearman correlation. We compared the performance of novices and experts to assess construct validity. RESULTS: The interobserver reliability was high (Rs = 0.974, P < 0.001). Checklist scores for experts and novices were significantly different; the median score for novices was 28/52 (54%), whereas that for experts was 47.5/52 (91%) (P < 0.001). The procedure time and fetoscopy time were significantly shorter (P < 0.001) for experts. Residual anastomoses were found in 1/11 (9%) procedures performed by experts and in 9/13 (69%) procedures performed by novices (P = 0.005). Multivariable analysis showed that the checklist score, independent of age and gender, predicted competence. CONCLUSIONS: The procedure-specific assessment tool for fetoscopic laser surgery shows good interobserver reliability and discriminates experts from novices. This instrument may therefore be a useful tool in the training curriculum for fetal surgeons. Further intervention studies with reassessment before and after training may increase the construct validity of the tool. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Simulator training in fetoscopic laser surgery for twin-twin transfusion syndrome: a pilot randomized controlled trial.

OBJECTIVE: To evaluate the effect of a newly developed training curriculum on the performance of fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS) using an advanced high-fidelity simulator model. METHODS: Ten novices were randomized to receive verbal instructions and either skills training using the simulator (study group; n = 5) or no training (control group; n = 5). Both groups were evaluated with a pre-training and post-training test on the simulator. Performance was assessed by two independent observers and comprised a 52-item checklist for surgical performance (SP) score, measurement of procedure time and number of anastomoses missed. Eleven experts set the benchmark level of performance. Face validity and educational value of the simulator were assessed using a questionnaire. RESULTS: Both groups showed an improvement in SP score at the post-training test compared with the pre-training test. The simulator-trained group significantly outperformed the control group, with a median SP score of 28 (54%) in the pre-test and 46 (88%) in the post-test vs 25 (48%) and 36 (69%), respectively (P = 0.008). Procedure time decreased by 11 min (from 44 to 33 min) in the study group vs 1 min (from 39 to 38 min) in the control group (P = 0.69). There was no significant difference in the number of missed anastomoses at the post-training test between the two groups (1 vs 0). Subsequent feedback provided by the participants indicated that training on the simulator was perceived as a useful educational activity. CONCLUSIONS: Proficiency-based simulator training improves performance, indicated by SP score, for fetoscopic laser therapy. Despite the small sample size of this study, practice on a simulator is recommended before trainees carry out laser therapy for TTTS in pregnant women.

Veno-venous anastomoses in twin-twin transfusion syndrome: A multicenter study.

INTRODUCTION: The aim of this study is to evaluate the prevalence of veno-venous (VV) anastomoses in a large cohort of monochorionic (MC) twin placentas with twin-twin transfusion syndrome (TTTS) compared to a control group of MC placentas without TTTS. METHODS: All TTTS placentas not treated with fetoscopic laser surgery (TTTS group) and examined at five international fetal therapy centers were included in this study and compared with a control group of MC placentas without TTTS (non-TTTS group). MC placentas were routinely injected with colored dye. We recorded the presence of VV and arterio-arterial (AA) anastomoses. RESULTS: A total of 414 MC placentas were included in this study (TTTS group, n = 106; non-TTTS group, n = 308). The prevalence of VV anastomoses was significantly higher in the TTTS group than in the non-TTTS group, 36% (38/106) and 25% (78/308), respectively (p = .04; odds ratio (OR) 1.65; 95% confidence interval (CI): 1.03-2.64). In the subgroup of MC placentas without AA anastomoses, the prevalence of VV anastomoses in the TTTS group and non-TTTS group was 32% (18/57) and 8% (2/25), respectively (p = .03; OR: 5.31; 95% CI: 1.13-24.98). DISCUSSION: VV anastomoses are detected more frequently in TTTS placentas than in MC placentas without TTTS and may thus play a role in the development of TTTS.

Identification of essential steps in laser procedure for twin-twin transfusion syndrome using the Delphi methodology: SILICONE study.

OBJECTIVE: To determine, by expert consensus, the essential substeps of fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) that could be used to create an authority-based curriculum for training in this procedure among fetal medicine specialists. METHODS: A Delphi survey was conducted among an international panel of experts (n = 98) in FLS. Experts rated the substeps of FLS on a five-point Likert-type scale to indicate whether they considered them to be essential, and were able to comment on each substep, using a dedicated online platform accessed by the invited tertiary care facilities that specialize in fetal therapy. Responses were returned to the panel until consensus was reached (Cronbach's α ≥ 0.80). All substeps that were rated ≥ 4 by 80% of the experts were included in the evaluation instrument. RESULTS: After the first iteration of the Delphi procedure, a response rate of 74% (73/98) was reached, and in the second and third iterations response rates of 90% (66/73) and 81% (59/73) were reached, respectively. Among a total of 81 substeps rated in the first round, 21 substeps had to be re-rated in the second round. Finally, from the initial list of substeps, 55 were agreed by experts to be essential. In the third round, the 18 categorized substeps were ranked in order of importance, with 'coagulation of all anastomoses that cross the equator' and 'determination of fetoscope insertion site' as the most important. CONCLUSIONS: A total of 55 substeps of FLS for TTTS were defined by a panel of experts to be essential in the procedure. This list is the first authority-based evidence to be used in the development of a final training model for future fetal surgeons.

Minimally invasive therapy for fetal sacrococcygeal teratoma: case series and systematic review of the literature.

OBJECTIVE: Large solid sacrococcygeal teratomas (SCT) can cause high-output cardiac failure and fetal or neonatal death. The aim of this study was to describe the outcomes of minimally invasive antenatal procedures for the treatment of fetal SCT. METHODS: A case review was performed of five fetuses with a large SCT treated antenatally using minimally invasive techniques, and a systematic literature review on fetal therapy for solid SCTs was carried out. RESULTS: Five women were referred between 17 + 5 and 26 + 4 weeks' gestation for a large fetal SCT with evidence of fetal cardiac failure. Vascular flow to the tumors was interrupted by fetoscopic laser ablation (n = 1), radiofrequency ablation (RFA; n = 2) or interstitial laser ablation ± vascular coiling (n = 2). There were two intrauterine fetal deaths. The other three cases resulted in preterm labor within 10 days of surgery. One neonate died. Two survived without procedure-related complications but had long-term morbidity related to prematurity. The systematic literature review revealed 16 SCTs treated minimally invasively for (early) hydrops. Including our cases, six of 20 hydropic fetuses survived after minimally invasive therapy (30%). Survival after RFA or interstitial laser ablation was 45% (5/11). Of 12 fetuses treated for SCT without obvious hydrops and for which perinatal survival data were available, eight (67%) survived. Mean gestational age at delivery after minimally invasive therapy was 29.7 ± 4.0 weeks. Survival after open fetal surgery in hydropic fetuses was 6/11 (55%), with a mean gestational age at delivery of 29.8 ± 2.9 weeks. CONCLUSIONS: Fetal therapy can potentially improve perinatal outcomes for hydropic fetuses with a solid SCT, but is often complicated by intrauterine death and preterm birth.

Collagen plug sealing of iatrogenic fetal membrane defects after fetoscopic surgery for congenital diaphragmatic hernia.

OBJECTIVES: To investigate the efficacy of collagen plugs at reducing the risk of preterm premature rupture of membranes (PPROM) after fetoscopic surgery for congenital diaphragmatic hernia (CDH). METHODS: This was a single-center cohort study on all consecutive cases undergoing fetoscopic endoluminal tracheal occlusion (FETO) for severe or moderate CDH, between April 2002 and May 2011 (n = 141). Cases either received a collagen plug for sealing the fetal membrane defect after FETO or did not, depending on the operating surgeon. The principal outcome measure was the time from fetal surgery to PPROM, further referred to as 'latency'. A multivariable Cox regression model was used to investigate the association between collagen plug and latency while adjusting for risk factors for PPROM. RESULTS: Of the 141 cases, 54 (38%) received a collagen plug and 87 (62%) did not. Sixty cases experienced PPROM, 26 among cases with and 34 among cases without a plug (48 vs 39%). The hazard ratio of plug use was 1.29 (95% CI, 0.76-2.19), which does not exclude a potentially increased risk for PPROM when a collagen plug is used. For cases with a plug, 24% had PPROM before balloon removal and 24% had PPROM after elective balloon removal. For cases without a plug, these rates were 30 and 9%, respectively. Perinatal outcomes were similar in both groups. CONCLUSIONS: No evidence was found that collagen plugs reduce the risk of PPROM after FETO for CDH.

Conservative surgery for left-sided isolated tubal torsion in pregnancy.

We report a case of severe lower abdominal pain in a pregnant woman at 35 weeks and 4 days of gestation. Early diagnosis of an isolated left-sided tubal torsion was established by ultrasound and emergency magnetic resonance imaging (MRI). Subsequent detorsion surgery was able to prevent the need for salpingectomy. The role of emergency imaging and conservative surgery in isolated tubal torsion is discussed.

[Amniopatch to treat iatrogenic rupture of the fetal membranes]. / Traitement de la rupture iatrogène des membranes fœtales par "patch" amniotique.

OBJECTIVE: With the increased use of invasive fetal procedures, the number of patients facing postprocedure membrane rupture is increasing. We aimed to describe the use of platelets and fresh frozen plasma for sealing iatrogenic fetal membrane defects. PATIENTS AND METHODS: We describe the mechanisms of action of the amniopatch procedure as well as published experience. RESULTS: Amniopatch effectively sealed the fetal membranes in over two thirds of published cases (n=44). There is a risk of 17% of in utero fetal death, which may occur remotely from the procedure and is often unexplained. DISCUSSION AND CONCLUSION: In case of early onset but persistent amniotic fluid leakage following an invasive fetal procedure, amniopatch may be offered.

Incidence and clinical implications of early inadvertent septostomy after laser therapy for twin-twin transfusion syndrome.

OBJECTIVE: To evaluate the incidence and clinical outcome of inadvertent septostomy after fetoscopic laser therapy for twin-twin transfusion syndrome (TTTS) and, particularly, to explore its association with the risk of developing pseudoamniotic band syndrome (PABS). METHODS: In a cohort of 414 consecutive monochorionic twin pregnancies with confirmed TTTS treated with laser, the incidence of postoperative septostomy within 1 week of the procedure was recorded prospectively. Rates of preterm delivery, preterm premature rupture of membranes (PPROM), intrauterine fetal demise (IUFD) and PABS were compared among cases with and without septostomy. RESULTS: The mean gestational age at laser therapy was 20.4 (range, 15.3-27.6) weeks. Postoperative septostomy occurred in 30 (7.2%) cases. Pregnancies complicated with septostomy had a significantly higher proportion of preterm delivery before 32 weeks (76.7% vs. 30.2%, P < 0.001), PPROM before 32 weeks (46.7% vs. 19.0%, P < 0.001), IUFD (43.3% vs. 25.8%, P < 0.05) and PABS (13.3% vs. 1.0%, P < 0.001), compared with pregnancies without septostomy. CONCLUSIONS: Inadvertent septostomy occurred in 7% of cases after fetoscopic laser therapy and was associated with a substantially increased risk of adverse perinatal outcome and PABS.

The fetal patient -- ethical aspects of fetal therapy.

The pregnant patient is a vulnerable subject, and even more so when a serious fetal condition is diagnosed. (Invasive) fetal therapy should only be offered when there is a good chance that the life of the fetus will be saved, or irreversible damage by the disease or disability is prevented. Following diagnosis of a potentially treatable condition, the patient needs to be referred to a center with sufficient expertise in diagnosis and all therapeutic options. Preferences of the physician towards one or another antenatal intervention is not at stake prior to that moment. When fetal therapy is justified--, it should be offered with full respect for maternal choice and individual assessment and perception of potential-- risks, and should be at the location where there is sufficient expertise. For therapies of unproven benefit, the absence of evidence must be disclosed, and therapy should only be undertaken with full voluntary consent of the mother. These ought to be undertaken within well designed and approved trials and only by experts in the treatment modality. Potential risks and eventual morbidities in case of therapeutic failure should be part of the counselling, neither-- should fetal therapy be presented as an alternative to termination of pregnancy.