Selective Fetoscopic Laser Photocoagulation Research Articles

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.

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. 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. 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. 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.

Amniotic fluid biomarkers of fetal stress response to cardiac dysfunction in twin-twin transfusion syndrome

Recipient twin (RT) cardiovascular changes in twin-twin transfusion syndrome (TTTS) are associated with increased mortality. This relationship is likely related to a cascade of pathophysiologic changes in the RT progressing to multisystem organ failure. We sought to evaluate biomarkers of inflammation, stress, and tissue injury within amniotic fluid (AF) of RTs undergoing selective fetoscopic laser photocoagulation (SFLP) for TTTS and examine their relationship with fetal echocardiographic findings. AF samples from RTs were obtained from 39 monochorionic-diamniotic pregnancies complicated by TTTS. Those without preoperative fetal echocardiograms or evidence of selective intrauterine growth restriction were excluded from analysis with 24 remaining samples. 15 commonly utilized clinical biomarkers for inflammation, stress, and tissue injury were assessed using a flow-cytometry based multiplex immunoassay. Fetal echocardiograms were performed prior to SFLP with myocardial performance index (MPI) utilized as a measure of cardiac dysfunction. Pearson’s correlation was used for data analysis. RT Left ventricular MPI (LV-MPI) ranged from 0.28-0.74, with 11/24 RTs demonstrating abnormal MPI for GA (Z-score > 2). RT AF cortisol (r = 0.4527, p = 0.020), IL-6 (r = 0.44, p = 0.025), CRP (r = 0.431, p = 0.028), and myoglobin (r = 0.401, p = 0.042) levels correlated with recipient left ventricular MPI (LV-MPI). AF cortisol strongly correlated with AF myoglobin (r = 0.576, p < 0.001). RT with abnormal LV-MPI exhibited significantly higher AF cortisol levels compared to those with normal LV-MPI (p = 0.029). RT amniotic fluid demonstrates markers of inflammation, stress and cardiac injury in recipient twins with cardiac dysfunction. These markers may be indicators of disease progression in TTTS secondary to cardiac dysfunction. The presence of these markers implicate stress and the immune response in the pathophysiologic response to cardiac dysfunction in TTTS.

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

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. 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. 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. 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.

Selective Fetoscopic Laser Photocoagulation or Expectant Management for Stage I Twin-Twin Transfusion: A Cost-Effectiveness Analysis

Background: Selective fetoscopic laser photocoagulation (SFLP) is the preferred intervention for stage II-IV twin-twin transfusion syndrome (TTTS); however, there is no consensus on whether SFLP or expectant management (EM) is the preferred strategy to manage Quintero stage I TTTS. Objective: The objective of this study is to estimate whether SFLP or EM is the cost-effective strategy for management of Quintero stage I TTTS. Study Design: A decision-analysis (DA) model compared SFLP to EM for 1,000 pregnant people with monochorionic-diamniotic twins affected by stage I TTTS. All subjects were assumed to be appropriate candidates for either SFLP or EM. Probabilities, costs, and utilities were derived from the literature. The DA was conducted from a healthcare payor perspective, and the analytic horizon was over the course of an offspring’s lifetime, with primary outcomes of survivorship (i.e., no intrauterine fetal demise or neonatal death) and long-term neurodevelopmental impairment. The model incorporated Markov processes with 4-week cycles throughout pregnancy. Incremental cost-effectiveness ratios (ICER) for each strategy were calculated and compared to estimate marginal cost effectiveness. An ICER of USD 100,000 per quality-adjusted life year was used to define the cost-effectiveness threshold. One-way sensitivity and Monte Carlo analyses (MCA), as well as microsimulations, were performed. Results: For base-case estimates, SFLP was found to be cost-effective compared to EM in the management of stage I TTTS. In one-way sensitivity analysis, varying each variable along pre-specified ranges did not result in changes in the conclusion. MCA projects SFLP as the cost-effective strategy in 100% of runs. Conclusions: With base-case estimates, SFLP is estimated to be the cost-effective strategy for the treatment of Quintero stage I TTTS when compared with EM. This remained true across a wide range of inputs.

Solomon versus selective fetoscopic laser photocoagulation for twin-twin transfusion syndrome: A systematic review and meta-analysis.

This meta-analysis aims to compare the perinatal outcome of twin-twin transfusion syndrome (TTTS) pregnancies undergoing selective versus vascular equator (Solomon) fetoscopic laser photocoagulation (FLP). We performed a systematic search in PubMed and Web of Science from inception up to 25 July 2021. Studies comparing the Solomon and selective techniques of FLP for treatment of TTTS pregnancies were eligible. Random-effects or fixed-effect models were used to pool standardized mean differences (SMD) and log odds ratio. Seven studies with a total of 1664 TTTS pregnancies (n=671 undergoing Solomon and n=993 selective techniques) were included. As compared to the selective FLP, Solomon was associated with a lower risk of recurrent TTTS compared to the selective technique (Log odds ratio [OR]: -1.167; 95% credible interval [CrI]: -2.01, -0.33; p=0.021; I2 : 67%). In addition, Solomon was significantly associated with a higher risk of placental abruption than the selective technique (Log [OR]: 1.44; 95% CrI: 0.45, 2.47; p=0.012; I2 : 0.0%). Furthermore, a trend for the higher risk of preterm premature rupture of membranes was observed among those undergoing Solomon (Log [OR]: 0.581; 95% CrI: -0.43, 1.49; p=0.131; I2 : 17%). As compared to selective FLP, the Solomon technique for TTTS pregnancies is associated with a significantly lower recurrence of TTTS; however, it significantly increases the risk of placental abruption.

Mentoring a surgical team towards procedural competence in the early learning curve for selective fetoscopic laser photocoagulation.

Selective fetoscopic laser photocoagulation (SFLP) for twin-to-twin transfusion syndrome (TTTS) is challenging for new surgeons at the start of their learning curve. We described an approach utilising telementoring and team-based training to facilitate rapid attainment of the skills required for safe and efficient practice with a limited caseload. We conducted a prospective observational study of SFLP performed by the novice primary surgical team in three stages: under direct on-site supervision from an expert mentor (Group 1), with remote tele-guidance from that mentor (Group 2) and independently (Group 3), at an academic tertiary hospital in Singapore. The primary team undertook regular training on high-fidelity tissue models to accelerate skills acquisition and complement the surgical performance. 9 patients diagnosed with Stage 2 TTTS were assessed for procedural characteristics, surgical outcomes and perinatal survival following SFLP. There were no significant differences in operative duration, anastomoses ablated, gestational age or birth weight at delivery. The complications observed were: recurrent TTTS (22.2% of pregnancies), twin anaemia polycythaemia sequence (33.3%), preterm prelabour membrane rupture (22.2%) and delivery at < 32 weeks (44.4%). ≥ 1 twin was live-born in 88.9% of cases, while postnatal survival to six months of ≥ 1 twin occurred in 77.8% of cases. Systematic mentoring and specialised skills training are useful in aiding new surgeons to negotiate the steep learning curve and achieve good outcomes at the start of a new practice, particularly in the setting of low patient numbers. This is best paired with dedicated model training to achieve and maintain surgical dexterity for this complex procedure.

Twin-to-twin transfusion syndrome complicated with in utero limb ischemia of the donor twin \u2013 a case report

BackgroundIn utero limb ischemia is a rare complication of the monochorionic twin pregnancies complicated with twin to twin transfusion syndrome (TTTS). The condition is more often seen in recipient twins. There are few theories of the pathogenesis including in utero venous thromboembolism, but the cause remains unclear. However, limb ischemia is thought to be unrelated with any prenatal intervention.Case PresentationWe present a case of a monochorionic twin pregnancy complicated with TTTS admitted to the Clinic for selective fetoscopic laser photocoagulation. The invasive procedure failed due to poor visibility. In the following weeks of pregnancy, amnioreduction procedures were performed. At 28 weeks of gestation due to twin anemia-polycythemia sequence diagnosis the patient was qualified for cesarean section. Postnatally, the donor twin was diagnosed with lower right limb ischemic necrosis. The extremity was amputated 2 days later with an uncomplicated recovery. After speculations of the potential pathogeneses it was suggested that the ischemic limb occurred as a complication of the main condition – TTTS.ConclusionsIn literature, there have been no cases reported of TTTS stage I complicated with donor twin limb ischemia. The actual cause of the in utero limb ischemic necrosis in monochorionic twins remains unknown. Nevertheless, increased attention to the potential complication after failed invasive procedures or conservative treatment should be required.

Association of amnioinfusion and adverse outcomes at the time of surgery for TTTS

To evaluate if the volume of Ringer’s lactate amnioinfusion (AI) used during selective fetoscopic laser photocoagulation (SFLP) for treatment of twin-twin transfusion syndrome (TTTS) is associated with adverse pregnancy outcome.

Solomon versus selective fetoscopic laser photocoagulation for twin-twin transfusion syndrome: A systematic review and meta-analysis

This systematic review and meta-analysis aims to compare the perinatal outcomes of twin-twin transfusion syndrome (TTTS) pregnancies undergoing selective vs vascular equator (solomon) fetoscopic laser photocoagulation (FLP).

Abstract 12589: Fetoscopic Selective Laser Photocoagulation of Placental Anastomoses Leads to Early Reduction of Cardiovascular Burden in the Twin-Twin Transfusion Syndrome

Background: Twin-twin transfusion syndrome (TTTS) occurs with an incidence of 10-15% in monochorionic pregnancies. The Children’s Hospital of Philadelphia (CHOP) TTTS Cardiovascular Score (CVS) is a 20-point scale and encompasses evaluation of five domains: Recipient (R) abnormalities of 1) ventricular hypertrophy/systolic dysfunction, 2) atrioventricular valve insufficiency, 3) diastolic ventricular inflow, ductus venosus and umbilical vein flow patterns and 4) right ventricular outflow/pulmonary obstruction; Donor (D) abnormalities of 5) umbilical arterial (UA) flow. We explore the early impact of selective fetoscopic laser photocoagulation (SLPC) of placental anastomoses on fetal cardiovascular (CV) burden. Methods: Fetal echocardiograms performed prior to and one week post SLPC from 11/2012 to 6/2018 were reviewed. Pulsatility indices (PI) of the UA and middle cerebral artery (MCA), cerebroplacental ratio (CPR) and CHOP CVS elements were analyzed pre and post SLPC using paired t-tests. Results: SLPC was performed in 198 subjects; 17 excluded due to one twin demise post SLPC. Of the 181 analyzed, mean gestational age at SLPC was 19.8 (95% CI: ±0.3) weeks. Following SLPC, R demonstrated an increase in MCA PI and decrease in UA PI, with increase in CPR. D demonstrated a similar magnitude decrease in both MCA PI and UA PI, yielding no change in CPR. Following SLPC, mean CHOP CVS decreased. CHOP pre SLPC CVS was ≥6 in 62 (34%). The magnitude of change was greater in the subgroup with greater pre SLPC CV burden (CVS &gt; 6). Most common elements to improve were systolic dysfunction, tricuspid inflow, ductus venosus and umbilical vein flow patterns; least likely to improve was ventricular hypertrophy. Conclusions: Improvement in CV burden is seen as early as 1 week post SLPC, which supports acute alteration of loading conditions as contributing to the disease. Further study of the trajectory of CV alterations may provide insight into the complex mechanisms underlying TTTS.

Amniotic fluid microRNA profiles in twin-twin transfusion syndrome with and without severe recipient cardiomyopathy

Twin-twin transfusion syndrome presents many challenges for clinicians, and the optimal means of identifying pregnancies that will benefit most from intervention is controversial. There is currently no clinically available biomarker to detect twin-twin transfusion syndrome or to stratify cases based on the risk factors. microRNAs are small RNAs that regulate gene expression and are biomarkers for various disease processes, including adult and pediatric heart failure. To date, no studies have investigated amniotic fluid microRNAs as biomarkers for disease severity, specifically for severe recipient cardiomyopathy in twin-twin transfusion syndrome cases. This study aimed to assess whether amniotic fluid microRNAs could be useful as biomarkers to identify pregnancies at greatest risk for severe recipient cardiomyopathy associated with twin-twin transfusion syndrome. Amniotic fluid was collected at the time of amnioreduction or selective fetoscopic laser photocoagulation from monochorionic diamniotic twin pregnancies with twin-twin transfusion syndrome at any stage. Fetal echocardiography was performed on all twins before the procedure, and severe cardiomyopathy was defined as a right ventricular myocardial performance index of the recipient fetus of >4 Z-scores. microRNA was extracted from the amniotic fluid samples and analyzed using an array panel assessing 379 microRNAs (TaqMan Open Array, ThermoFisher). Student t tests were performed to determine significant differences in microRNA expression between pregnancies with severe recipient cardiomyopathy and those with preserved cardiac function. A stringent q value of <.0025 was used to determine differential microRNA expression. Random forest plots identified the top 3 microRNAs that separated the 2 groups, and hierarchical cluster analysis was used to determine if these microRNAs properly segregated the samples according to their clinical groups. A total of 14 amniotic fluid samples from pregnancies with twin-twin transfusion syndrome with severe cardiomyopathy were compared with samples from 12 twin-twin transfusion syndrome control cases with preserved cardiac function. A total of 110 microRNAs were identified in the amniotic fluid samples. Twenty microRNAs were differentially expressed, and the top 3 differentiating microRNAs were hsa-miR-200c-3p, hsa-miR-17-5p, and hsa-miR-539-5p. Hierarchical cluster analysis based on these top 3 microRNAs showed a strong ability to differentiate severe cardiomyopathy cases from controls. The top 3 microRNAs were used to investigate the sensitivity and specificity of these microRNAs to differentiate between the 2 groups with a receiver operating characteristic curve demonstrating sensitivity and specificity of 80.8%. All 20 differentially expressed microRNAs were down-regulated in the group with severe cardiomyopathy. Amniotic fluid microRNAs demonstrated differential expression between twin-twin transfusion syndrome recipient fetuses with severe cardiomyopathy and those without and have the potential to be important biomarkers of disease severity in this population.

334 Influence of cervical length change after laser surgery for twin-twin transfusion syndrome on pregnancy outcomes

Twin pregnancies complicated by twin-twin transfusion syndrome (TTTS) are at especially high risk of preterm birth. Cases that have selective fetoscopic laser photocoagulation (SFLP) at our institution undergo transvaginal ultrasound (TVUS) measurement of cervical length (CL) before and after SFLP to assess preterm birth risk during the perioperative period Retrospective cohort study comparing pre- and post-op TVUS CL in pregnancies that underwent SFLP at a single center from 4/2010-6/2019. Among 626 SFLP cases, 476 had data on both pre- and post-op CL and comprised the study cohort. Pre-op TVUS CL was obtained <30 days prior to SFLP, and post-op measure was obtained 0 to 5 days after SFLP. Change in cervical length was defined as pre-op CL minus post-op CL. No change in pre- to post-op CL was defined as a change of <0.5 mm Among 476 patients, n=309(64.9%) experienced net decrease in CL, 54(11.3%) had no change and 113(23.7%) had net increase in CL following SFLP. The mean pre-op CL was significantly longer in cases that had net increase in CL after SFLP compared to those that decreased, 4.59cm vs 3.53cm, p=0.0001. There was no difference in mean DVP of the recipient or latency to delivery among groups (mean 10 wks, p=0.606), Table 1. Cases with a net increase in CL after SFLP had lower rates of preterm birth (PTB) <28 and <32 wks. Decrease or no change in CL after SFLP had no significant influence on PTB rates even when accounting for short pre-op CL, Table 2. Short cervix pre-op in combination with CL change was not significantly associated with PTB Increase in cervical length after SFLP is associated with reduced risk of early preterm birth. It has previously been hypothesized that intraoperative amnioreduction of recipient polyhydramnios may decrease PTB by decreasing uterine stretch, however our data did not show differences in mean DVP with respect to CL change. The mechanisms that influence CL changes in the SFLP perioperative period and influence preterm parturition warrant further investigationView Large Image Figure ViewerDownload Hi-res image Download (PPT)

985 Influence of gestational age of treatment of twin-twin transfusion syndrome on latency-to-delivery and outcomes

The average latency to delivery after selective fetoscopic laser photocoagulation (SFLP) for treatment of pregnancies complicated by twin-twin transfusion syndrome (TTTS) has been reported as 10 weeks. We sought to determine the influence of the gestational age (GA) at the time of SFLP on latency to delivery and neonatal survival in patients with TTTS. This was a retrospective cohort study evaluating latency to delivery and survival of infants after SFLP in pregnancies complicated by TTTS at a single center from 4/2010 to 6/2019. A total of 637 patient were included. Latency was evaluated for each week that SFLP was performed. Primary and secondary outcomes were compared between three groups (16 0/7-17 6/7, 18 0/7-22 6/7, and 23 0/7-28 6/7 weeks) at time of SFLP. Primary outcomes were latency to delivery and neonatal survival after SFLP. Secondary outcomes were postoperative and pregnancy complications after SFLP. Data were analyzed using linear regression, ANOVA, and Chi2 as appropriate. Advancing GA is inversely related to latency from SFLP to delivery (See figure). Latency to delivery was longer the earlier SFLP was performed, mean (±SD) of 11.7 (±4.9) weeks at 16 0/7-17 6/7 weeks, 10.2 (±4) weeks at 18 0/7-22 6/7 weeks, and 6.3 (±3.4) weeks at 23 0/7-28 6/7 weeks (Table 1). Linear regression demonstrated an inverse relationship (coefficient -0.73, R2 0.19, p<0.001). Composite complications were increased the earlier SFLP was performed 55.6%, 40.3%, and 30.8% at 16 0/7-17 6/7, 18 0/7-22 6/7, and 23 0/7-28 6/7 weeks respectively (p=0.001). Neonatal survival for at least one twin to day of life 30 was 85.6%, 92.3%, and 94.7% (p=0.042) and dual neonatal survival to day of life 30 was 67.0%, 79.2%, and 81.2% (p=0.02) for the same groups. SFLP performed at earlier gestational age demonstrates longer latency until delivery. Despite this, SFLP at earlier gestational age is associated with an increase in complications and decreased neonatal survival for one or both twins.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

323 Selective fetoscopic laser or expectant management for quintero stage i twin-twin transfusion: a cost-effectiveness analysis

To determine whether selective fetoscopic laser photocoagulation (SFLP) or expectant management (EM) is a cost-effective strategy for management of Quintero stage I twin-twin transfusion syndrome (TTTS). A decision-analysis (DA) model compared SFLP to EM for 100000 pregnant people with monochorionic-diamniotic twins affected by stage I TTTS. All subjects were assumed to be appropriate candidates for either strategy. Probabilities, costs, and utilities were derived from the literature. The DA was conducted from a health care payor perspective and the analytic horizon was over the course of a child’s lifetime, with primary outcomes of survivorship (i.e., no intrauterine fetal demise or neonatal death) and long-term neurodevelopmental impairment (NDI). Markov processes were employed, cycling every 4 weeks throughout pregnancy. Incremental cost-effectiveness ratios (ICER) for each strategy were calculated and compared to determine marginal cost effectiveness. An ICER of $100,000 per quality-adjusted life year (QALY) was used to define the cost-effectiveness threshold. One-way sensitivity and Monte Carlo analyses (MCA) were performed. For base-case estimates, SFLP was found to be cost effective compared to EM in the management of stage I TTTS (Table). Compared to EM, SFLP resulted in 29184 fewer pregnancies affected with no survivors; 2346 more pregnancies with 1 survivor, and 26838 more pregnancies with 2 survivors. Furthermore, there were 4649 fewer cases of NDI. On one-way sensitivity analyses, if the probability of NDI after SFLP for pregnancies affected by stage I TTTS was above 0.078, then EM was the cost-effective strategy (Figure). MCA demonstrated that SFLP was cost-effective in 98.1% of runs. With base-case estimates, SFLP is a more cost-effective strategy than EM for the treatment of Stage I TTTS. However, given the limited data informing base-case estimates, further determination of outcome probabilities is needed to determine with high confidence which strategy is more cost-effective.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

546 Natural history of previable and periviable rupture of membranes after treatment of twin-twin transfusion syndrome

We aim to describe the natural history and outcomes of pre/periviable prelabor rupture of membranes (PROM) in TTTS after selective fetoscopic laser photocoagulation (SFLP). Retrospective cohort study at a single fetal center which included pregnancies from April 2010-June 2019 complicated by TTTS and were treated with SFLP and subsequently had PROM. Primary outcomes were latency from PROM to delivery and fetal survival. Exposure groups were pregnancies that developed PROM between 16-19 6/7 weeks, 20 -22 6/7 weeks, 23- 25 6/7 weeks and ≥ 26 weeks (referent group). Comparisons were made with t-test, Mann-Whitney U, Kruskall-Wallis, and chi-squared as appropriate, with significance reported as p < 0.05. A total of 33% (N=221/678) of patients had PROM post-SFLP. The average latency from SFLP to PROM was 7.5 weeks (95% CI 7.0 – 8.1) with overall 86% survival in setting of PROM. Eighteen patients (2.7%) experienced PROM within 7 days of surgery, with the mean gestational age (GA) at delivery of 23.4 weeks (95% CI 21.2-25.6 weeks) and 44% (8/18) of those patients delivering within 48 hrs. Baseline characteristic among those that experienced PROM < 26 weeks vs ≥ 26 weeks were non-significant except for GA at the time of surgery (19.5 ± 2.1 vs 20.6 ± 2.8 weeks respectively, p=0.005). The rates of PROM by GA were 0.7%, 2.7% and 6.1% at 16-19 6/7, 20-22 6/7, and 23-25 6/7 weeks, respectively. Linear regression demonstrated inverse correlation between GA at PPROM and latency, R = 0.25. Despite this longer latency, those with PROM after SFLP at less than 23 weeks demonstrated lower survival rates as delivery was more likely to occur in the periviable period (Table). These findings remained true when patients who delivered within 48 hours of PROM were excluded. GA at PROM after SFLP is inversely correlated with latency to delivery, however later GA at PROM is associated with improved live birth rates. When latency after PROM exceeds 48 hours, rates of live birth are significantly improved, with live birth of one or more fetuses exceeding 70% even with PROM < 20 weeks.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

338 The impact of total laser energy during selective-fetoscopic-laser-photocoagulation on outcomes of pregnancies affected by twin-twin-transfusion-syndrome

To quantify the influence of total laser energy on outcomes of TTTS treated with selective fetoscopic laser photocoagulation (SFLP) and to determine a critical energy threshold that is predictive of adverse outcome. This is a retrospective cohort study of monochorionic diamniotic twins treated with SFLP at the Cincinnati Fetal Center between April 2010 and June 2019. We excluded patients with triplets, short cervix (<2.8 cm), and incomplete procedures. Patients were stratified into groups with mean energy thresholds above and below the 75th percentile for energy among this cohort. Primary outcomes were latency from SFLP to delivery and gestational age at delivery. Secondary outcomes included postoperative complications and neonatal survival A total of 547 patients met inclusion criteria for this study. The 75th percentile of laser energy was 13,830 joules (J). At the time of SFLP, patients in the lower energy usage group were more likely to be earlier in gestation (20.4 vs 21.1wks, p=0.005), have a lower Quintero stage, and had less than 10 anastomoses. Latency from SFLP to delivery was longer in the lower energy group (10.4 vs 9.4wks, p=0.003). Latency from SFLP to PPROM was longer in the lower energy group but did not achieve statistical significance (p=0.057). Patients in the lower energy group had higher rates of composite complications (49.2% vs 39.6%, p= 0.031); which could be attributed to higher rates of PPROM (38.8% vs 29.6% p=0.026). There was also a significantly increased risk of delivery prior to 32 weeks in the higher energy group, even after adjusting for baseline differences between groups (aRR 1.74, 95% CI 1.18-2.58). There was no difference in rates of live births or neonatal survival Total laser energy above the 75th percentile was associated with a shorter latency from surgery to delivery and was associated with increased risk of delivery prior to 32 weeks, though overall survival rates were equivalent. Regard should be given to the lowest feasible energy usage at the time of SFLPView Large Image Figure ViewerDownload Hi-res image Download (PPT)

531 Evaluating surgical time in fetoscopic laser ablation. does a longer surgery equal a worse outcome?

A longer surgery is often perceived to be more challenging but the impact of increased operative time in outcomes after selective fetoscopic laser photocoagulation (SFLP) is unknown. Our objective is to evaluate pregnancy outcome in relation to surgical time. Retrospective cohort study at a single fetal center of TTTS patients treated with SFLP from April 2010 to June 2019. Data collected was maternal demographic data, pregnancy characteristics and outcomes, surgical characteristics, fetal survival, and postoperative complications. Surgical time (time from skin incision to closure) was normally distributed, and the 75th percentile (82 minutes [min]) was selected as the cut-off for increased surgical time. Primary outcomes were risk of preterm birth (PTD) at < 26, 28, and 32 weeks. Secondary analysis was performed with the 90th percentile (112 min). Data was analyzed using chi2, student’s t-test, multivariate logistic regression, and linear regression as appropriate. 538 pregnancies met inclusion criteria. SFLP mean time was 69 ± 9.8 min (range 9-220 min) and median was 63 min (IQR 49, 82). Amongst groups, baseline characteristics were similar with the exception of race. Surgical time > 82 min had higher laser time (641.9 ± 129.1 vs 340.0 ± 238.7 seconds, p <0.001) and laser energy exposure (12874.2 ± 9105.4 vs 10052.1 ± 6889.7 joules, p<0.001). There was no significant difference in fetal survival (Table). Time ≥ 82 min was not associated with any increased risk of PTD < 26, 28, and 32 weeks (Figure). Comparing surgical time ≥ 112 min (90%tile) to < 112 minutes, there is decreased mean gestational age at delivery (28.9 ± 3.9 vs 30.7 ± 3.9 weeks, p=0.002) , increased risk of PTD at < 26 weeks and nearly 3-fold increased risk of PTD < 32 weeks, even when adjusting for baseline differences (aRR 2.9, 95% CI 1.4-6.0) (Figure). SFLP surgical time >112 minutes was associated with significant decrease in gestational age at delivery and almost 3x increase in rate of PTD <26 and <32 weeks. These are important information in patient counseling and management postoperatively.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

543 Does the time of laser usage during surgery for twin-twin transfusion syndrome impact pregnancy outcomes?

Selective fetoscopic laser photocoagulation (SFLP) performed in twin-twin transfusion syndrome (TTTS) results in placental perfusion changes. Our objective is to evaluate pregnancy outcome in relation to the time of laser firing during surgery. Retrospective cohort study at a single fetal center of all TTTS patients treated with SFLP from April 2010 to June 2019. At the time of surgery, the time of laser firing was documented. Data collected was maternal demographic data, pregnancy characteristics and outcomes, surgical characteristics, fetal survival, and postoperative complications. Laser time was not normally distributed, thus the upper quartile (7.6 minutes (mins)) was selected as the cut-off for increased laser time. Primary outcomes were pregnancy outcomes, including survival and risk of preterm birth (PTB) at ≤26, 28, and 32 weeks. Data was analyzed using chi2, student’s t-test, multivariate logistic regression, and linear regression as appropriate. 580 patients met inclusion criteria. Median laser time was 4.9 min (range 0.2-22 min). Baseline characteristics were similar amongst groups (table). Surgery laser time >7.6 min was significantly associated with increase in number of total vessels ablated, higher rate of microseptostomy (39% vs 26%, p < 0.001), higher laser energy level (17298 vs 8608 joule, p < 0.001), and lower donor survival (71% vs 82% p = 0.004) as compared to time <7.6min respectively. Laser time <7.6min was also associated with higher rates of double survival (81.7% vs 70.1%, respectively, p = 0.034). Surgery laser time was not associated with any increased risk of PTB prior to 26, 28, and 32 weeks. Longer surgery laser time >7.6 min was associated with significant decrease in donor and double fetal survival rate. Surgery laser time did not impact gestational age at delivery. This information becomes important in surgical training for SFLP and patient counseling.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

630 Management of short cervix in twin-twin transfusion syndrome

There is no proven treatment for prevention of preterm birth (PTB) in twin-twin transfusion syndrome (TTTS). Our objective is to compare pregnancy and neonatal outcomes following cervical cerclage to cervical pessary in twin pregnancies complicated by TTTS and short cervix. We conducted a retrospective cohort study of all TTTS cases with a cervical length <30mm at time of evaluation managed in a single center between 2008 – 2018. The TTTS was managed with expectant management, amnioreduction, or selective fetoscopic laser photocoagulation (SFLP). Pregnancies with congenital abnormalities were excluded. Comparisons were made using the Student’s t, Mann-Whitney U, Kruskall-Wallis, and Chi-squared tests as appropriate, with significance reported as p < 0.05. Of 1,340 pregnancies with TTTS evaluated in our center during the study period, 122 had a cervical length <30mm and met inclusion criteria. Cervical cerclage was placed in 79 pregnancies, and cervical pessary in 29. There were no statistical differences in the baseline characteristics between the cerclage and pessary groups. No differences were noted in gestational age at delivery, indications for delivery, pregnancy complications, or survival between the cervical cerclage and pessary groups. In pregnancies complicated by TTTS and short cervix, similar outcomes were noted when treated with cervical cerclage or pessary. A pessary may offer a less invasive treatment option with similar results. Future studies are needed to determine the optimal treatment strategy in these complex pregnancies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

86 Amniotic fluid microRNA profiles in twin-twin transfusion syndrome with and without severe cardiomyopathy

Twin-twin transfusion syndrome (TTTS) presents many challenges for clinicians, and the optimal means of identifying which pregnancies will benefit most from intervention is controversial. There is currently no clinically significant biomarker to detect or risk-stratify TTTS. microRNAs (miRs) are small RNAs that regulate gene expression and are biomarkers in various disease processes, including adult and pediatric heart failure. To date no studies have investigated amniotic fluid (AF) miR as a biomarker for severe TTTS. This study aims to assess whether AF miRs could be useful as biomarkers to identify pregnancies at greatest risk of severe cardiomyopathy due to TTTS. AF was collected at the time of amniocentesis or selective fetoscopic laser photocoagulation from monochorionic diamniotic twin pregnancies with TTTS at any stage and stored at -80° C. Fetal echocardiography was available for all subjects, and right ventricular Tei index of the recipient fetus ≥ 0.64 was used to define severe cardiomyopathy. RNA was extracted from the AF samples using the miRNeasy Mini Kit (Qiagen) and miR arrays were performed using the TaqMan Open Array miR panel (ThermoFisher). Student’s t-test was performed between groups and a stringent q-value of <0.005 was used to determine differentially expressed miRs. Hierarchical cluster analysis (HCA) was used to determine if these miRs properly separated the two groups. A total of 11 AF samples from pregnancies with severe cardiomyopathy were compared to 12 control TTTS samples without severe cardiomyopathy. 40 miRs were differentially expressed. HCA (Fig 1) based on these 40 miRs show a strong ability to differentiate the two groups. All differentially expressed miRs were downregulated in the severe cardiomyopathy group with the exception of upregulation of miR-208 (Fig 2), which has previously been shown to be associated with adverse outcomes in dilated cardiomyopathy. AF miRs demonstrate differential expression in TTTS with and without severe cardiomyopathy, and can be an important biomarker of disease severity in this population.View Large Image Figure ViewerDownload Hi-res image Download (PPT)