RARE DISEASE
Twin to twin transfusion syndrome
Twin to twin transfusion syndrome
Twin to twin transfusion syndrome
Synonyms: Feto-fetal transfusion syndrome
Synonyms: Feto-fetal transfusion syndrome
Synonyms: Feto-fetal transfusion syndrome
Drug discovery
0
drugs
With orphan designations
Overview
Twin-to-Twin Transfusion Syndrome (TTTS) is a progressive placental disorder in monochorionic twins, characterized by imbalanced blood flow through vascular anastomoses. The donor twin develops oligohydramnios and growth restriction due to hypovolemia, while the recipient experiences polyhydramnios, cardiac overload, and risks of hydrops. Diagnosed via ultrasound (Quintero staging I-V), untreated TTTS carries >90% mortality. Laser photocoagulation of anastomotic vessels is the gold-standard intervention, improving survival and reducing neurodevelopmental morbidity [1][4][6][18].
Therapies
Fetoscopic laser photocoagulation: First-line for stages II–IV, with 66–85% dual survival and reduced TAPS risk using the Solomon technique [2][13][18].
Serial amnioreduction: Temporizes polyhydramnios but does not address underlying pathophysiology [3][8].
Selective fetal reduction or septostomy: Reserved for severe cases or laser contraindications [3][19].
Categories: rare gynecological and obstetric diseases, rare immunological diseases
Research Papers
1,023 drug discovery papers about Twin to twin transfusion syndrome, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,023 drug discovery papers about Twin to twin transfusion syndrome, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-06-05 | Intrathecal fentanyl and intraoperative pain during fetoscopic laser photocoagulation: a single-center retrospective cohort study (2020-2025).
Intrathecal fentanyl is used as an adjunct to spinal anesthesia for cesarean delivery; however, its role during fetoscopic laser photocoagulation has not been studied. We evaluated its association with intraoperative pain during fetoscopic laser photocoagulation. In this retrospective study, patients who underwent fetoscopic laser photocoagulation under spinal anesthesia were grouped according to intrathecal fentanyl use. The primary outcome was intraoperative pain, which was defined as patient-reported pain. Multivariable logistic regression was performed to adjust for potential confounders. Among 172 patients, intraoperative pain occurred less frequently with intrathecal fentanyl (22.9% vs. 40.4%; P = 0.015). Multivariable analysis showed that intrathecal fentanyl was independently associated with a reduced risk of intraoperative pain (odds ratio, 0.33; 95% confidence interval, 0.15-0.71; P = 0.005). Maternal and fetal adverse events did not differ between the groups. Intrathecal fentanyl was associated with reduced intraoperative pain during fetoscopic laser photocoagulation without an increase in adverse events.
2026-04-05 | Interventions and Perinatal Outcomes Associated With Recipient Twin Cardiomyopathy in the Setting of Twin-To-Twin Transfusion Syndrome: A Systematic Review.
To determine (1) Whether the presence and severity of recipient twin cardiomyopathy in the setting of twin-to-twin transfusion syndrome are associated with worse perinatal outcomes when compared to recipient twins without evidence of cardiomyopathy and (2) The optimal management strategy to reduce the likelihood of adverse perinatal outcomes when recipient twin cardiomyopathy is present. We included observational studies and randomized controlled trials of monochorionic-diamniotic twin gestations affected by twin-to-twin transfusion syndrome, which reported the relationship between recipient twin cardiomyopathy and adverse perinatal outcomes. PubMed, CINAHAL, Scopus, Embase, and the Cochrane Central Register of Controlled Trials were queried from January 2004 to December 2025. The primary outcome was single and dual twin survival at 6 months of life. The secondary outcomes were the frequency of live birth of one or both twins; gestational age at the time of delivery; latency from diagnosis of twin-to-twin transfusion syndrome to delivery; birthweight of living twins; newborn length(s) of stay; need for neonatal intensive care unit admission; single and dual twin survival at 0 and 1 month of life; postnatal recipient twin cardiomyopathy (inclusive of right ventricular outflow tract obstruction); and frequency of neonatal complications at 6 months of life. Assessment of bias was performed using the Cochrane Risk-of-Bias and Newcastle-Ottawa tools. Of 207 abstracts available, 13 met the inclusion criteria. None of the studies reported the primary outcome defined by the systematic review, but did report on multiple secondary outcomes. Most manuscripts (10/13) used the Myocardial Performance Index to define recipient twin cardiomyopathy. One manuscript reported on the use of calcium channel blockers in addition to selective fetoscopic photocoagulation, and its relationship with adverse perinatal outcomes. Most studies exhibited a low risk of bias. Three out of 10 manuscripts using the Myocardial Performance Index demonstrated a relationship between the presence and severity of recipient twin cardiomyopathy and adverse perinatal outcomes. Two manuscripts demonstrated that the use of calcium channel blockers perioperatively may be associated with a reduced frequency of adverse perinatal outcomes. A small number of studies have assessed recipient twin cardiomyopathy's role in the risk of adverse perinatal outcomes or whether unique forms of treatment may improve the risk of perinatal outcomes. Further, studies suffer from a lack of long-term neonatal follow-up. Future studies should investigate whether other markers of recipient twin cardiac compromise are associated with adverse perinatal outcomes.
2025-12-13 | Short-Term Indomethacin Use Reduces Preterm Premature Rupture of Membranes After Fetoscopic Laser Surgery for Twin-to-Twin Transfusion Syndrome.
Preterm labor is a severe problem after fetoscopic laser surgery (FLS), which often requires multiple tocolytic agents. We investigated the utility of indomethacin as a tocolytic agent after FLS. This study included monochorionic diamniotic twin pregnancies who underwent FLS for twin-to-twin transfusion syndrome at our hospital from 2015 to 2023. Medical records of all cases were reviewed retrospectively. Since indomethacin has been used routinely since 2020, all cases were divided into the control group (without indomethacin) and IND group (with indomethacin). Indomethacin was administered until 48 h postoperatively. This study was approved by the ethics committee of our hospital, and written informed consent for indomethacin use was obtained from all patients. Fifty-seven patients were in the IND group and 97 were in the control group. No fetal adverse effects were observed in the IND group. Median gestational age at delivery did not differ between the groups (p = 0.670). pPROM within 14 days after FLS occurred more frequently in the control group (8.2%) than in the IND group (0%) (p = 0.022). The IND group had a shorter median duration of magnesium sulfate use (3 days [2-12]) than the control group (8 days [2-81]) (p < 0.001), and less frequent use of nifedipine (42% vs. 80%, p < 0.001). The short-term administration of indomethacin was not associated with fetal adverse events, and it may be useful in postoperative management by reducing immediate postoperative pPROM and the need for other tocolytic agents.
2025-05-30 | TWIN-TWIN TRANSFUSION SYNDROME ASSOCIATED MATERNAL HYPERTHYROIDISM
INTRODUCTION/BACKGROUNDPregnancies complicated by twin-twin transfusion syndrome (TTTS) are associated with elevated human chorionic gonadotropin (hCG) compared to uncomplicated twin pregnancies. Studies have shown a positive correlation between hCG and free thyroxine (FT4) in TTTS, thereby increasing the risk of maternal hyperthyroidism. This case report describes a twin pregnancy complicated by TTTS, where maternal hyperthyroidism developed prior to fetoscopic laser ablation (FLA). CASEWe present a 36-year-old female with a twin pregnancy complicated by TTTS. She was diagnosed with gestational transient thyrotoxicosis (GTT) at 10 weeks of gestation with thyroid stimulating hormone (TSH) of 0.01 mIU/L, FT4 of 24.8 pmol/L and triiodothyronine (T3) of 3.8 pmol/L. She had negative thyroid-stimulating hormone receptor antibodies and a normal neck ultrasound. Clinically, she has no goitre or thyroid eye disease. At 15 weeks of gestation, her FT4 decreased to 14.3 pmol/L while TSH remained suppressed. She did not receive any anti-thyroid drugs (ATDs) during the first trimester. She was admitted at 22 weeks of gestation for FLA due to TTTS stage 1. Upon admission, she complained of palpitations, and the cardiac monitor showed sinus tachycardia with a heart rate of 123 bpm. Her TSH was <0.008 mIU/L, FT4 was increased to 21 pmol/L and hCG of >225,000 U/L. Due to hyperthyroid symptoms, she was treated with carbimazole and beta-blocker prior to FLA. Her carbimazole dose was reduced at 25 weeks of gestation as FT4 dropped to 13.2 pmol/L. It was then discontinued at 28 weeks of gestation (FT4 11.25 pmol/L; TSH 0.11 mIU/L). She underwent emergency hysterectomy at 28 weeks of gestation due to TTTS progression to stage 4. CONCLUSIONGTT in twin pregnancies typically resolve by the end of the first trimester. A sustained FT4 increase should raise suspicion for TTTS. ATDs should be considered due to the risk of TTTS-associated maternal hyperthyroidism, as it may persist until successful FLA.
2025-04-24 | Bronchopulmonary sequestration in a monochorionic diamniotic preterm twin.
This is a unique case with an initial suspicion of twin-to-twin transfusion syndrome in monochorionic twins, leading to hydrops fetalis. The recurrence of left pleural effusion complicated the initial diagnosis. An incidental finding of a lung lesion revealed bronchopulmonary sequestration on further investigation. A customised dexamethasone regimen successfully managed the recurrent pleural effusion, avoiding the need for early thoracic surgery.
cell therapies
2026-05-25 | Does the order of ablation of vein-to-vein placental connections during fetoscopic laser photocoagulation affect outcomes in twin-twin transfusion syndrome?
To assess whether the sequence of laser occlusion of vein-to-vein placental anastomoses is associated with fetal survival after laser photocoagulation for twin-twin transfusion syndrome. This post hoc analysis used data from the Sequential Trial, a randomized controlled trial comparing sequential vs selective laser photocoagulation techniques. Within this trial, a nested randomization assigned patients with superficial anastomoses (ie, artery-to-artery or vein-to-vein) to ablation of these anastomoses either at the beginning or at the end of surgery. For this analysis, we compared survival in patients with vein-to-vein anastomoses with a reference group lacking superficial anastomoses. Variables associated with survival were included in multiple logistic regression models, including the nested assignment to "Ablated First" vs "Ablated Last." Of 642 trial patients, 64 (10%) had at least one vein-to-vein anastomosis (range, 1-3). Donor live birth was 421/466 (90.3%) in the No Superficial Anastomoses group and 48/64 (75.0%) in the vein-to-vein group (P=.001). Among the 64 patients with vein-to-vein anastomoses, 28 (43.8%) were randomized to Ablated First and 36 (56.3%) to Ablated Last. Donor survival in the No Superficial Anastomoses, Ablated First, and Ablated Last groups was 90.3%, 82.1%, and 69.4%, respectively (P<.001). Recipient survival was 94.2%, 96.4%, and 86.1% (P=.128). In adjusted models, the Ablated Last group had lower odds of donor survival (adjusted odds ratio, 0.24 [0.10-0.58]; P=.002) and recipient survival (adjusted odds ratio, 0.30 [0.10-0.92]; P=.035) compared with the No Superficial Anastomoses group. In this post hoc exploratory analysis, end-of-procedure treatment of vein-to-vein anastomoses for twin-twin transfusion syndrome was associated with lower donor and recipient survival.
2026-03-01 | Comment on “Single Fetal Demise in Twin Anemia–Polycythemia Sequence: Perinatal Outcome of Surviving Cotwin”
When blood flow between the two fetuses in a monochorionic twin pregnancy is imbalanced, serious complications can arise, including twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia (TAPS). TTTS involves relatively large placental anastomoses between the twins and can lead to amniotic fluid imbalance, whereas TAPS results from small intertwin placental anastomoses that cause chronic anemia in the donor twin and chronic polycythemia in the recipient. Prior studies show that single intrauterine fetal demise (IUFD) in monochorionic twin pregnancies with intertwin anastomoses can result in acute exsanguination of the surviving twin, potentially leading to brain injury or death. It is plausible that this effect may be attenuated in cases complicated by TAPS due to the small size and high resistance of the intertwin vessels, but this remains understudied. This study aims to better characterize the risk of adverse perinatal outcomes for the surviving fetus following IUFD in monochorionic twin pregnancies complicated by TAPS. This retrospective cohort study used data from twin pregnancies recorded in the international TAPS Registry between 2014 and 2023. Inclusion criteria were active TAPS and spontaneous single IUFD, while cases managed with selective reduction, termination of pregnancy, or preterm delivery were excluded. For each case, antenatal characteristics and obstetric, fetal, and neonatal outcomes were abstracted from medical records. The primary outcomes were mortality and severe neonatal cerebral injury in the surviving twin. A total of 432 twin pregnancies complicated by TAPS were identified, of which 39 involved a single IUFD. Most cases (n = 30, 77%) developed after laser surgery to treat TTTS, while the remainder (n = 9, 23%) occurred spontaneously. Management strategies included expectant management in 27 cases (69%), intrauterine transfusion in 10 cases (26%), and fetoscopic laser surgery in 2 cases (5%). Most IUFDs occurred in the donor twin (90%), and new-onset anemia was not observed in any surviving cotwins. Cotwin demise occurred in one case, attributed to suspected intrauterine fetal infection following premature rupture of membranes. No cases of neonatal cerebral injury were identified in surviving cotwins measured one day after delivery. Severe neonatal morbidity occurred in 8 cases (22%), most commonly due to respiratory distress syndrome. One case of perinatal asphyxiation occurred, but was attributed to pulmonary hypoplasia rather than fetal exsanguination. Previous studies have reported rates of severe cerebral injury of ∼25% following single IUFD in monochorionic twin pregnancies overall. In contrast, these findings suggest that the risks of mortality and brain injury in pregnancies complicated by TAPS are low. The authors suggest that these results could inform clinical decision-making when weighing the risks and benefits of rescue intrauterine transfusion versus expectant management. They caveat that the study is limited by a retrospective design, small sample size, short follow-up period, and the potential for underreporting in cases of double IUFD. (Summarized from van de Sande MJA, Lopriore E, Lanna M, et al. Single fetal demise in twin anemia-polycythemia sequence: Perinatal outcome of surviving cotwin. Ultrasound Obstet Gynecol. 2025;66(1):51–55. doi: https://doi.org/10.1002/uog.29242)
2026-02-24 | Fetoscopic Laser Therapy for Twin-to-Twin Transfusion Syndrome: Learning Curve and Perinatal Outcomes in a Brazilian Public Tertiary Center
Abstract Background To describe the institutional learning curve and neonatal outcomes of fetoscopic laser photocoagulation for Twin-to-Twin Transfusion Syndrome (TTTS) following the implementation of a fetal therapy program in a tertiary reference center in Brazil. Materials and methods This retrospective cohort study analyzed 31 monochorionic diamniotic twin pregnancies complicated by TTTS that underwent fetoscopic laser ablation between January 2019 and December 2024. Procedures were classified as complete Solomon, incomplete Solomon, or selective photocoagulation. Primary outcome was neonatal survival (double, single, or none). Secondary outcomes assessed associations with Quintero stage, coexisting complications (selective fetal growth restriction—sFGR or twin anemia–polycythemia sequence—TAPS), and Solomon completeness. Results The mean maternal age was 29 years, and the mean gestational ages at TTTS diagnosis and fetoscopy were 20.5 and 21.4 weeks, respectively. Most cases presented in Quintero Stage III (61.3%). sFGR occurred in 20 pregnancies and TAPS in five. Complete Solomon ablation was achieved in 84% of cases. Dual survival occurred in 6.4% of complete procedures and single survival in 38.7%. No significant difference in survival was found between complete and incomplete Solomon techniques ( p = 0.356). Survival outcomes differed significantly across Quintero stages, with all Stage I and II cases achieving survival of at least one fetus ( p = 0.002). Conclusion Fetoscopic laser ablation for TTTS is feasible and yields acceptable perinatal outcomes within a public tertiary hospital, even during the program’s early learning phase. Early diagnosis, efficient referral pathways, and continued team training are essential to optimize results and strengthen fetal therapy services in resource-limited settings.
2026-01-01 | Advancing Robotic Fetal Surgery: A Preclinical Platform for Treating Twin-to-Twin Transfusion Syndrome
Twin-to-twin transfusion syndrome is a life-threatening disease affecting monochorionic twin fetuses before they are even born. It is characterized by an imbalanced blood flow between the fetuses through shared vessels in the placenta as well as a severe amniotic fluid discrepancy. The gold standard treatment is fetoscopic laser coagulation (FLC), a minimally invasive fetal surgery, which aims to stop the blood flow between the twins. The surgeon enters the uterus with an endoscope, identifies all shared vessels and ablates them using a surgical laser. This complex procedure requires highly trained and experienced surgeons, as it presents various challenges: the placental vasculature must be memorized to identify the shared vessels, as only a small part of the placenta is visible in the endoscopic images at any given time. Visualization and access to the vessels can be a major challenge depending on the placental location due to the lack of dexterity of current instruments, and the precision of the ablations relies on the surgeon’s ability to hold the instrument steady. Flexible surgical robots have the potential to overcome these challenges by providing superior dexterity, precise control, and safe tissue interaction. This thesis demonstrates this through the development of a robotic platform designed for FLC and its validation in realistic settings. The platform combines a magnetically actuated flexible endoscope with teleoperated and semiautonomous navigation capabilities to facilitate this surgery. To enhance scene awareness, the platform generates real-time mosaics of the endoscopic images, enabling improved surgical planning, tool localization, and characterization of areas of interest. The platform is validated in vivo in an ovine model, demonstrating its feasibility and effectiveness. The navigation and mapping algorithms developed in this work have potential beyond FLC. Their versatility is validated in vitro and ex vivo for cystoscopies and gastroscopies under various conditions with different magnetic endoscopes. This thesis thereby contributes to advancing minimally invasive surgeries in open organs.
2025-12-13 | The Impact of Maternal Body Mass Index on Fetoscopic Laser Surgery for Twin-Twin Transfusion Syndrome.
Both a low and an increased body mass index (BMI) are risk factors for surgical complications. It is less clear whether they also affect the outcomes of fetoscopic procedures. In this manuscript, we aimed to assess the effect of maternal BMI on operative and pregnancy outcomes following fetoscopic laser ablation of placental anastomoses for twin-twin transfusion syndrome (TTTS). We retrospectively reviewed all patients with twin pregnancies complicated by TTTS treated with fetoscopic laser surgery at the Ontario Fetal Centre, Toronto, over a 24-year period. Demographic and procedural data as well as pregnancy and delivery outcomes were prospectively collected as part of our quality control program. Patients were divided into 6 groups for BMI at the time of surgery: BMI <20, 20-24.9, 25-29.9, 30-34.9, 35-39.9, and ≥40 kg/m2. Collected variables included demographics, operative characteristics, operative complications, obstetric complications, twin anemia-polycythemia sequence, TTTS recurrence, intrauterine (fetal) death, gestational age at delivery, and survival. Outcomes of all groups were compared to the "normal weight" reference cohort (BMI: 20-24.9 kg/m2). Of 1,012 patients in our database, 859 were twin pregnancies treated with laser for TTTS. Pregnancy outcomes were available for 515. Of all patients, 47% were categorized as normal weight, 3% were underweight, 25% were obese, and 5% had a BMI of >40 kg/m2. Patients with a higher BMI had higher parity (p = 0.0001), longer cervical length (p = 0.008), and a significantly higher TTTS stage (p = 0.0003) at the time of surgery. There were no significant differences between groups in terms of surgical or anesthetic characteristics or perinatal complications. BMI does not significantly affect operative or perinatal outcomes in patients undergoing fetoscopic laser ablation for severe TTTS, despite being at a higher stage at diagnosis.
proteins
2025-12-26 | Proteomic comparison of intact and fetoscopy-induced fetal membrane defect sites
Background: Iatrogenic preterm premature rupture of fetal membranes (iPPROM) following fetoscopic interventions remains a major barrier to the advancement of fetal therapies. The mechanisms underlying iPPROM are poorly understood, but the inability of fetal membrane (FM) defects to heal spontaneously likely plays a key role, contrasting with the regenerative potential of amniotic membranes in other contexts. Methods: To assess the impact of fetoscopic procedures on FMs, tissue samples from patients who underwent laser surgery for twin-to-twin transfusion syndrome (16-27 weeks gestation, n = 8) were collected after cesarean delivery at 29-35 weeks. Samples were categorized by proximity to the trocar site and analyzed using proteomic and histological methods. Results: While differential expression analysis in the amnion revealed no significant changes, pathway enrichment indicated increased collagen deposition at defect sites. In the chorion, seven differentially expressed proteins were identified, largely linked to enhanced intercellular contact stability. These findings suggest the amnion may respond to mechanical stress by reinforcing structural integrity through collagen deposition, while the chorion may attempt to stabilize cell junctions. However, no other signs of tissue regeneration were observed. Conclusion: This study provides molecular and cellular evidence that FMs lack a substantial healing response post-surgery, underscoring the need for biologically informed repair strategies. Impact: By combining untargeted proteomics with histological and qPCR evaluations, this study demonstrates subtle molecular and cellular changes in fetoscopy-induced fetal membrane defects at the time of delivery. This indicates minimal molecular and cellular healing mechanisms in the fetal membranes. This underscores the potential for sealing FM defects after fetoscopy to prevent amniotic fluid leakage, thereby reducing the incidence of intra-amniotic preterm rupture of membranes.
2001-09-06 | Prolonged use of tissue plasminogen activator for bilateral lower limb arterial occlusion in a neonate.
The authors report the case of a 29-week-gestation twin with very severe vascular compromise of both lower limbs secondary to premature twin-twin transfusion. A tissue plasminogen activator (tPA) infusion was used locally for 13 days with complete recovery of perfusion to both legs, demonstrated by serial angiograms, thereby avoiding bilateral amputation. There were no side effects as a result of the continuous administration of tPA. The authors therefore suggest that the benefits of thrombolysis from a local infusion of tPA in neonates may outweigh the potential risks. This case report thus supports the view that under certain circumstances infusion of tPA in neonates may offer significant benefits. J Pediatr Surg 36:654-656.
antibodies
2026-06-07 | Impact of preimplantation genetic testing on the incidence of monochorionic diamniotic pregnancies in single blastocyst frozen-thawed embryo transfers: a retrospective cohort study spanning 10 years.
This study aimed to explore the associations between assisted reproductive technology (ART) modality and chorionicity in monozygotic twinning pregnancies following single blastocyst frozen-thawed embryo transfer. This retrospective cohort study analyzed 30,121 single embryo transfer cycles from January 2013 to December 2022 but focused on 251 monozygotic twinning pregnancies following single blastocyst frozen-thawed embryo transfer, including 144 monochorionic diamniotic (MCDA) twins and 107 dichorionic diamniotic (DCDA) twins. Regression analysis was performed to determine the risk factors for the subtypes of monozygotic twinning pregnancies after ART. Pregnancy complications and neonatal outcomes of the MCDA and DCDA groups were compared, and subgroup analyses among the in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and preimplantation genetic testing (PGT) groups were performed. The overall monozygotic twinning rate was 1.97%, without a significant difference between D5/6 and D3 embryos in frozen cycles (1.95% vs. 1.56%, p = 0.55). IVF and ICSI were associated with a lower incidence of MCDA twins than observed in the PGT group (IVF: adjusted odds ratio [aOR] = 0.40, p = 0.009; ICSI: aOR = 0.38, p = 0.011). The incidence rates of specific severe complications in MCDA twins, such as twin‒twin transfusion syndrome, selective intrauterine growth restriction, and twin anemia polycythemia sequence, were 2.78%, 2.78%, and 0.69%, respectively. No significant differences were observed in other adverse pregnancy or neonatal outcomes among the MCDA, DCDA, and ART modalities. PGT may be associated with an increased incidence of MCDA twins following single blastocyst frozen-thawed embryo transfer. The incidence of specific maternal-fetal complications for MCDA twins, such as twin‒twin transfusion syndrome and selective intrauterine growth restriction, remains noteworthy. However, the occurrence rates of other adverse pregnancy complications and neonatal outcomes of MCDA twins and DCDA twins are comparable.
2025-12-26 | Double trouble: A case series exploring the complications of twin pregnancy
Monochorionic twin pregnancies are associated with unique and serious complications due to shared placental circulation, including twin-to-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), and twin reversed arterial perfusion (TRAP) sequence. This case series presents four monochorionic diamniotic pregnancies complicated by TAPS, TTTS (Quintero stages I and IV), and TRAP. Diagnostic features such as intertwin discrepancies in middle cerebral artery peak systolic velocity, amniotic fluid discordance, and Doppler studies were critical in identifying these conditions. Management strategies included conservative monitoring, radiofrequency ablation, and, in one case, termination due to poor prognosis. Outcomes varied, highlighting the unpredictable nature of these conditions despite timely intervention. This study underscores the importance of early chorionicity determination, regular ultrasound monitoring, and individualized multidisciplinary care in optimizing outcomes for monochorionic twin pregnancies.
2025-11-05 | Preoperative factors associated with donor twin demise in 1602 pregnancies complicated by twin-twin transfusion syndrome.
To identify preoperative risk factors associated with postlaser fetal death of the donor twin in a large cohort of pregnancies complicated by twin-twin transfusion syndrome (TTTS). This retrospective cohort study of prospectively collected data included monochorionic diamniotic pregnancies complicated by TTTS that underwent laser surgery between March 2006 and May 2024 at two specialized referral centers. Patients underwent a comprehensive ultrasound examination, including fetal Doppler evaluation, to assign a Quintero stage and to obtain the middle cerebral artery (MCA) peak systolic velocity (PSV) for each twin within 24 h before laser surgery. An isolated elevation of the donor MCA-PSV was defined as having an MCA-PSV > 1.5 multiples of the median (MoM) in the absence of twin anemia-polycythemia sequence (TAPS). TAPS was defined as donor MCA-PSV > 1.5 MoM and recipient MCA-PSV < 1.0 MoM or intertwin MCA-PSV difference of > 0.5 MoM. Patients underwent postoperative ultrasound the day after surgery to document cardiac activity in each twin. Univariate logistic and multivariable Poisson (Zou's method) regression models were used to estimate the odds ratio and adjusted relative risk (aRR) for donor twin demise, adjusted for TAPS, TTTS stage, selective fetal growth restriction (sFGR), donor MCA pulsatility index < 10th percentile, gestational age < 18 weeks at surgery and other risk factors. Fetal demise of the donor twin was noted in 14.3% (229/1602) of the study population. Preoperative isolated elevation of donor MCA-PSV conferred the highest aRR of any risk factor for postlaser donor fetal demise (aRR, 2.69 (95% CI, 1.91-3.81); P < 0.001) compared with Stage-III TTTS (aRR, 2.34 (95% CI, 1.36-4.02); P = 0.002), MCA pulsatility index < 10th percentile (aRR, 1.91 (95% CI, 1.48-2.46); P < 0.001), velamentous cord insertion in the donor twin (aRR, 1.86 (95% CI, 1.43-2.41); P < 0.001), TAPS (aRR, 1.63 (95% CI, 1.19-2.23); P = 0.001), gestational age < 18 weeks at laser surgery (aRR, 1.59 (95% CI, 1.21-2.08); P = 0.001) and sFGR (aRR, 1.58 (95% CI, 1.19-2.07); P = 0.001). The observed frequency of fetal demise of the donor twin increased with each additional concomitant risk factor included. Isolated elevation of donor MCA-PSV prior to laser surgery for TTTS conferred the highest aRR for donor fetal demise among risk factors including TAPS, TTTS staging, sFGR and other covariates. This risk increased progressively when more than one risk factor was present in pregnancies complicated by TTTS. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.
2025-10-21 | Predictors of Adverse Perinatal Outcome in Twin Anemia Polycythemia Sequence: Evidence From a Single Center Cohort Study.
To evaluate the perinatal outcome of monochorionic pregnancies complicated by Twin Anemia-Polycythemia Sequence (TAPS) and identify prognostic factors associated with adverse outcomes. A retrospective study (2012-2024) analyzed TAPS cases at a tertiary center. Demographic, obstetric, and neonatal outcomes were compared between conservative management and interventions (intrauterine transfusion, laser surgery, or selective feticide). TAPS characteristics were also analyzed in three subgroups: deliveries before/after 32 weeks, CNS findings on MRI, and dual versus single/no survival. Of 32 TAPS cases, 68.75% were spontaneous, and 31.25% followed TTTS laser treatment. Conservative management was used in 62.5%, while 21.9% received intrauterine transfusions, 9.4% underwent laser treatment, and 9.4% had selective feticide. Gestational age at diagnosis and delivery was earlier in the intervention group (25 vs. 27 weeks, p = 0.05; 30.6 vs. 32.6 weeks, p = 0.04). CNS abnormalities (25%) were linked to earlier diagnosis. Perinatal survival was 86%, with dual, single, and no survival rates of 78.1%, 15.6%, and 6.2%, respectively. Patients with single/no survival were characterized by an earlier gestational age at diagnosis of TAPS compared to those with dual survival (21 vs. 27 weeks, p < 0.01). Earlier TAPS diagnosis is associated with poorer outcomes, including reduced survival and increased risk of brain injury.
2025-10-12 | Complications in monochorionic twin pregnancies.
Monochorionic placentas occur in two-thirds of identical (monozygotic) twin pregnancies and typically feature inter-fetal vascular anastomoses on their surface. These anastomoses can cause very specific complications including twin-to-twin transfusion syndrome (TTTS) in about 10 %, TAPS in 5 %, twin reversed arterial perfusion (TRAP) sequence in 2.5 % and spontaneous intrauterine fetal death (IUFD) in 2 % of monochorionic-diamniotic twin pregnancies. Moreover, unequal sharing of placental territories can lead to selective fetal growth restriction (sFGR) in about 15 %. Monochorionic multiples affected by such complications are at increased risk of mortality, brain abnormalities and neurodevelopmental disorders. This narrative review provides insight into prenatal detection and management of specific complications of monochorionic twin pregnancies.
small molecules
2026-06-05 | Intrathecal fentanyl and intraoperative pain during fetoscopic laser photocoagulation: a single-center retrospective cohort study (2020-2025).
Intrathecal fentanyl is used as an adjunct to spinal anesthesia for cesarean delivery; however, its role during fetoscopic laser photocoagulation has not been studied. We evaluated its association with intraoperative pain during fetoscopic laser photocoagulation. In this retrospective study, patients who underwent fetoscopic laser photocoagulation under spinal anesthesia were grouped according to intrathecal fentanyl use. The primary outcome was intraoperative pain, which was defined as patient-reported pain. Multivariable logistic regression was performed to adjust for potential confounders. Among 172 patients, intraoperative pain occurred less frequently with intrathecal fentanyl (22.9% vs. 40.4%; P = 0.015). Multivariable analysis showed that intrathecal fentanyl was independently associated with a reduced risk of intraoperative pain (odds ratio, 0.33; 95% confidence interval, 0.15-0.71; P = 0.005). Maternal and fetal adverse events did not differ between the groups. Intrathecal fentanyl was associated with reduced intraoperative pain during fetoscopic laser photocoagulation without an increase in adverse events.
2026-04-05 | Interventions and Perinatal Outcomes Associated With Recipient Twin Cardiomyopathy in the Setting of Twin-To-Twin Transfusion Syndrome: A Systematic Review.
To determine (1) Whether the presence and severity of recipient twin cardiomyopathy in the setting of twin-to-twin transfusion syndrome are associated with worse perinatal outcomes when compared to recipient twins without evidence of cardiomyopathy and (2) The optimal management strategy to reduce the likelihood of adverse perinatal outcomes when recipient twin cardiomyopathy is present. We included observational studies and randomized controlled trials of monochorionic-diamniotic twin gestations affected by twin-to-twin transfusion syndrome, which reported the relationship between recipient twin cardiomyopathy and adverse perinatal outcomes. PubMed, CINAHAL, Scopus, Embase, and the Cochrane Central Register of Controlled Trials were queried from January 2004 to December 2025. The primary outcome was single and dual twin survival at 6 months of life. The secondary outcomes were the frequency of live birth of one or both twins; gestational age at the time of delivery; latency from diagnosis of twin-to-twin transfusion syndrome to delivery; birthweight of living twins; newborn length(s) of stay; need for neonatal intensive care unit admission; single and dual twin survival at 0 and 1 month of life; postnatal recipient twin cardiomyopathy (inclusive of right ventricular outflow tract obstruction); and frequency of neonatal complications at 6 months of life. Assessment of bias was performed using the Cochrane Risk-of-Bias and Newcastle-Ottawa tools. Of 207 abstracts available, 13 met the inclusion criteria. None of the studies reported the primary outcome defined by the systematic review, but did report on multiple secondary outcomes. Most manuscripts (10/13) used the Myocardial Performance Index to define recipient twin cardiomyopathy. One manuscript reported on the use of calcium channel blockers in addition to selective fetoscopic photocoagulation, and its relationship with adverse perinatal outcomes. Most studies exhibited a low risk of bias. Three out of 10 manuscripts using the Myocardial Performance Index demonstrated a relationship between the presence and severity of recipient twin cardiomyopathy and adverse perinatal outcomes. Two manuscripts demonstrated that the use of calcium channel blockers perioperatively may be associated with a reduced frequency of adverse perinatal outcomes. A small number of studies have assessed recipient twin cardiomyopathy's role in the risk of adverse perinatal outcomes or whether unique forms of treatment may improve the risk of perinatal outcomes. Further, studies suffer from a lack of long-term neonatal follow-up. Future studies should investigate whether other markers of recipient twin cardiac compromise are associated with adverse perinatal outcomes.
2025-12-13 | Short-Term Indomethacin Use Reduces Preterm Premature Rupture of Membranes After Fetoscopic Laser Surgery for Twin-to-Twin Transfusion Syndrome.
Preterm labor is a severe problem after fetoscopic laser surgery (FLS), which often requires multiple tocolytic agents. We investigated the utility of indomethacin as a tocolytic agent after FLS. This study included monochorionic diamniotic twin pregnancies who underwent FLS for twin-to-twin transfusion syndrome at our hospital from 2015 to 2023. Medical records of all cases were reviewed retrospectively. Since indomethacin has been used routinely since 2020, all cases were divided into the control group (without indomethacin) and IND group (with indomethacin). Indomethacin was administered until 48 h postoperatively. This study was approved by the ethics committee of our hospital, and written informed consent for indomethacin use was obtained from all patients. Fifty-seven patients were in the IND group and 97 were in the control group. No fetal adverse effects were observed in the IND group. Median gestational age at delivery did not differ between the groups (p = 0.670). pPROM within 14 days after FLS occurred more frequently in the control group (8.2%) than in the IND group (0%) (p = 0.022). The IND group had a shorter median duration of magnesium sulfate use (3 days [2-12]) than the control group (8 days [2-81]) (p < 0.001), and less frequent use of nifedipine (42% vs. 80%, p < 0.001). The short-term administration of indomethacin was not associated with fetal adverse events, and it may be useful in postoperative management by reducing immediate postoperative pPROM and the need for other tocolytic agents.
2025-05-30 | TWIN-TWIN TRANSFUSION SYNDROME ASSOCIATED MATERNAL HYPERTHYROIDISM
INTRODUCTION/BACKGROUNDPregnancies complicated by twin-twin transfusion syndrome (TTTS) are associated with elevated human chorionic gonadotropin (hCG) compared to uncomplicated twin pregnancies. Studies have shown a positive correlation between hCG and free thyroxine (FT4) in TTTS, thereby increasing the risk of maternal hyperthyroidism. This case report describes a twin pregnancy complicated by TTTS, where maternal hyperthyroidism developed prior to fetoscopic laser ablation (FLA). CASEWe present a 36-year-old female with a twin pregnancy complicated by TTTS. She was diagnosed with gestational transient thyrotoxicosis (GTT) at 10 weeks of gestation with thyroid stimulating hormone (TSH) of 0.01 mIU/L, FT4 of 24.8 pmol/L and triiodothyronine (T3) of 3.8 pmol/L. She had negative thyroid-stimulating hormone receptor antibodies and a normal neck ultrasound. Clinically, she has no goitre or thyroid eye disease. At 15 weeks of gestation, her FT4 decreased to 14.3 pmol/L while TSH remained suppressed. She did not receive any anti-thyroid drugs (ATDs) during the first trimester. She was admitted at 22 weeks of gestation for FLA due to TTTS stage 1. Upon admission, she complained of palpitations, and the cardiac monitor showed sinus tachycardia with a heart rate of 123 bpm. Her TSH was <0.008 mIU/L, FT4 was increased to 21 pmol/L and hCG of >225,000 U/L. Due to hyperthyroid symptoms, she was treated with carbimazole and beta-blocker prior to FLA. Her carbimazole dose was reduced at 25 weeks of gestation as FT4 dropped to 13.2 pmol/L. It was then discontinued at 28 weeks of gestation (FT4 11.25 pmol/L; TSH 0.11 mIU/L). She underwent emergency hysterectomy at 28 weeks of gestation due to TTTS progression to stage 4. CONCLUSIONGTT in twin pregnancies typically resolve by the end of the first trimester. A sustained FT4 increase should raise suspicion for TTTS. ATDs should be considered due to the risk of TTTS-associated maternal hyperthyroidism, as it may persist until successful FLA.
2025-04-24 | Bronchopulmonary sequestration in a monochorionic diamniotic preterm twin.
This is a unique case with an initial suspicion of twin-to-twin transfusion syndrome in monochorionic twins, leading to hydrops fetalis. The recurrence of left pleural effusion complicated the initial diagnosis. An incidental finding of a lung lesion revealed bronchopulmonary sequestration on further investigation. A customised dexamethasone regimen successfully managed the recurrent pleural effusion, avoiding the need for early thoracic surgery.
cell therapies
2026-05-25 | Does the order of ablation of vein-to-vein placental connections during fetoscopic laser photocoagulation affect outcomes in twin-twin transfusion syndrome?
To assess whether the sequence of laser occlusion of vein-to-vein placental anastomoses is associated with fetal survival after laser photocoagulation for twin-twin transfusion syndrome. This post hoc analysis used data from the Sequential Trial, a randomized controlled trial comparing sequential vs selective laser photocoagulation techniques. Within this trial, a nested randomization assigned patients with superficial anastomoses (ie, artery-to-artery or vein-to-vein) to ablation of these anastomoses either at the beginning or at the end of surgery. For this analysis, we compared survival in patients with vein-to-vein anastomoses with a reference group lacking superficial anastomoses. Variables associated with survival were included in multiple logistic regression models, including the nested assignment to "Ablated First" vs "Ablated Last." Of 642 trial patients, 64 (10%) had at least one vein-to-vein anastomosis (range, 1-3). Donor live birth was 421/466 (90.3%) in the No Superficial Anastomoses group and 48/64 (75.0%) in the vein-to-vein group (P=.001). Among the 64 patients with vein-to-vein anastomoses, 28 (43.8%) were randomized to Ablated First and 36 (56.3%) to Ablated Last. Donor survival in the No Superficial Anastomoses, Ablated First, and Ablated Last groups was 90.3%, 82.1%, and 69.4%, respectively (P<.001). Recipient survival was 94.2%, 96.4%, and 86.1% (P=.128). In adjusted models, the Ablated Last group had lower odds of donor survival (adjusted odds ratio, 0.24 [0.10-0.58]; P=.002) and recipient survival (adjusted odds ratio, 0.30 [0.10-0.92]; P=.035) compared with the No Superficial Anastomoses group. In this post hoc exploratory analysis, end-of-procedure treatment of vein-to-vein anastomoses for twin-twin transfusion syndrome was associated with lower donor and recipient survival.
2026-03-01 | Comment on “Single Fetal Demise in Twin Anemia–Polycythemia Sequence: Perinatal Outcome of Surviving Cotwin”
When blood flow between the two fetuses in a monochorionic twin pregnancy is imbalanced, serious complications can arise, including twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia (TAPS). TTTS involves relatively large placental anastomoses between the twins and can lead to amniotic fluid imbalance, whereas TAPS results from small intertwin placental anastomoses that cause chronic anemia in the donor twin and chronic polycythemia in the recipient. Prior studies show that single intrauterine fetal demise (IUFD) in monochorionic twin pregnancies with intertwin anastomoses can result in acute exsanguination of the surviving twin, potentially leading to brain injury or death. It is plausible that this effect may be attenuated in cases complicated by TAPS due to the small size and high resistance of the intertwin vessels, but this remains understudied. This study aims to better characterize the risk of adverse perinatal outcomes for the surviving fetus following IUFD in monochorionic twin pregnancies complicated by TAPS. This retrospective cohort study used data from twin pregnancies recorded in the international TAPS Registry between 2014 and 2023. Inclusion criteria were active TAPS and spontaneous single IUFD, while cases managed with selective reduction, termination of pregnancy, or preterm delivery were excluded. For each case, antenatal characteristics and obstetric, fetal, and neonatal outcomes were abstracted from medical records. The primary outcomes were mortality and severe neonatal cerebral injury in the surviving twin. A total of 432 twin pregnancies complicated by TAPS were identified, of which 39 involved a single IUFD. Most cases (n = 30, 77%) developed after laser surgery to treat TTTS, while the remainder (n = 9, 23%) occurred spontaneously. Management strategies included expectant management in 27 cases (69%), intrauterine transfusion in 10 cases (26%), and fetoscopic laser surgery in 2 cases (5%). Most IUFDs occurred in the donor twin (90%), and new-onset anemia was not observed in any surviving cotwins. Cotwin demise occurred in one case, attributed to suspected intrauterine fetal infection following premature rupture of membranes. No cases of neonatal cerebral injury were identified in surviving cotwins measured one day after delivery. Severe neonatal morbidity occurred in 8 cases (22%), most commonly due to respiratory distress syndrome. One case of perinatal asphyxiation occurred, but was attributed to pulmonary hypoplasia rather than fetal exsanguination. Previous studies have reported rates of severe cerebral injury of ∼25% following single IUFD in monochorionic twin pregnancies overall. In contrast, these findings suggest that the risks of mortality and brain injury in pregnancies complicated by TAPS are low. The authors suggest that these results could inform clinical decision-making when weighing the risks and benefits of rescue intrauterine transfusion versus expectant management. They caveat that the study is limited by a retrospective design, small sample size, short follow-up period, and the potential for underreporting in cases of double IUFD. (Summarized from van de Sande MJA, Lopriore E, Lanna M, et al. Single fetal demise in twin anemia-polycythemia sequence: Perinatal outcome of surviving cotwin. Ultrasound Obstet Gynecol. 2025;66(1):51–55. doi: https://doi.org/10.1002/uog.29242)
2026-02-24 | Fetoscopic Laser Therapy for Twin-to-Twin Transfusion Syndrome: Learning Curve and Perinatal Outcomes in a Brazilian Public Tertiary Center
Abstract Background To describe the institutional learning curve and neonatal outcomes of fetoscopic laser photocoagulation for Twin-to-Twin Transfusion Syndrome (TTTS) following the implementation of a fetal therapy program in a tertiary reference center in Brazil. Materials and methods This retrospective cohort study analyzed 31 monochorionic diamniotic twin pregnancies complicated by TTTS that underwent fetoscopic laser ablation between January 2019 and December 2024. Procedures were classified as complete Solomon, incomplete Solomon, or selective photocoagulation. Primary outcome was neonatal survival (double, single, or none). Secondary outcomes assessed associations with Quintero stage, coexisting complications (selective fetal growth restriction—sFGR or twin anemia–polycythemia sequence—TAPS), and Solomon completeness. Results The mean maternal age was 29 years, and the mean gestational ages at TTTS diagnosis and fetoscopy were 20.5 and 21.4 weeks, respectively. Most cases presented in Quintero Stage III (61.3%). sFGR occurred in 20 pregnancies and TAPS in five. Complete Solomon ablation was achieved in 84% of cases. Dual survival occurred in 6.4% of complete procedures and single survival in 38.7%. No significant difference in survival was found between complete and incomplete Solomon techniques ( p = 0.356). Survival outcomes differed significantly across Quintero stages, with all Stage I and II cases achieving survival of at least one fetus ( p = 0.002). Conclusion Fetoscopic laser ablation for TTTS is feasible and yields acceptable perinatal outcomes within a public tertiary hospital, even during the program’s early learning phase. Early diagnosis, efficient referral pathways, and continued team training are essential to optimize results and strengthen fetal therapy services in resource-limited settings.
2026-01-01 | Advancing Robotic Fetal Surgery: A Preclinical Platform for Treating Twin-to-Twin Transfusion Syndrome
Twin-to-twin transfusion syndrome is a life-threatening disease affecting monochorionic twin fetuses before they are even born. It is characterized by an imbalanced blood flow between the fetuses through shared vessels in the placenta as well as a severe amniotic fluid discrepancy. The gold standard treatment is fetoscopic laser coagulation (FLC), a minimally invasive fetal surgery, which aims to stop the blood flow between the twins. The surgeon enters the uterus with an endoscope, identifies all shared vessels and ablates them using a surgical laser. This complex procedure requires highly trained and experienced surgeons, as it presents various challenges: the placental vasculature must be memorized to identify the shared vessels, as only a small part of the placenta is visible in the endoscopic images at any given time. Visualization and access to the vessels can be a major challenge depending on the placental location due to the lack of dexterity of current instruments, and the precision of the ablations relies on the surgeon’s ability to hold the instrument steady. Flexible surgical robots have the potential to overcome these challenges by providing superior dexterity, precise control, and safe tissue interaction. This thesis demonstrates this through the development of a robotic platform designed for FLC and its validation in realistic settings. The platform combines a magnetically actuated flexible endoscope with teleoperated and semiautonomous navigation capabilities to facilitate this surgery. To enhance scene awareness, the platform generates real-time mosaics of the endoscopic images, enabling improved surgical planning, tool localization, and characterization of areas of interest. The platform is validated in vivo in an ovine model, demonstrating its feasibility and effectiveness. The navigation and mapping algorithms developed in this work have potential beyond FLC. Their versatility is validated in vitro and ex vivo for cystoscopies and gastroscopies under various conditions with different magnetic endoscopes. This thesis thereby contributes to advancing minimally invasive surgeries in open organs.
2025-12-13 | The Impact of Maternal Body Mass Index on Fetoscopic Laser Surgery for Twin-Twin Transfusion Syndrome.
Both a low and an increased body mass index (BMI) are risk factors for surgical complications. It is less clear whether they also affect the outcomes of fetoscopic procedures. In this manuscript, we aimed to assess the effect of maternal BMI on operative and pregnancy outcomes following fetoscopic laser ablation of placental anastomoses for twin-twin transfusion syndrome (TTTS). We retrospectively reviewed all patients with twin pregnancies complicated by TTTS treated with fetoscopic laser surgery at the Ontario Fetal Centre, Toronto, over a 24-year period. Demographic and procedural data as well as pregnancy and delivery outcomes were prospectively collected as part of our quality control program. Patients were divided into 6 groups for BMI at the time of surgery: BMI <20, 20-24.9, 25-29.9, 30-34.9, 35-39.9, and ≥40 kg/m2. Collected variables included demographics, operative characteristics, operative complications, obstetric complications, twin anemia-polycythemia sequence, TTTS recurrence, intrauterine (fetal) death, gestational age at delivery, and survival. Outcomes of all groups were compared to the "normal weight" reference cohort (BMI: 20-24.9 kg/m2). Of 1,012 patients in our database, 859 were twin pregnancies treated with laser for TTTS. Pregnancy outcomes were available for 515. Of all patients, 47% were categorized as normal weight, 3% were underweight, 25% were obese, and 5% had a BMI of >40 kg/m2. Patients with a higher BMI had higher parity (p = 0.0001), longer cervical length (p = 0.008), and a significantly higher TTTS stage (p = 0.0003) at the time of surgery. There were no significant differences between groups in terms of surgical or anesthetic characteristics or perinatal complications. BMI does not significantly affect operative or perinatal outcomes in patients undergoing fetoscopic laser ablation for severe TTTS, despite being at a higher stage at diagnosis.
proteins
2025-12-26 | Proteomic comparison of intact and fetoscopy-induced fetal membrane defect sites
Background: Iatrogenic preterm premature rupture of fetal membranes (iPPROM) following fetoscopic interventions remains a major barrier to the advancement of fetal therapies. The mechanisms underlying iPPROM are poorly understood, but the inability of fetal membrane (FM) defects to heal spontaneously likely plays a key role, contrasting with the regenerative potential of amniotic membranes in other contexts. Methods: To assess the impact of fetoscopic procedures on FMs, tissue samples from patients who underwent laser surgery for twin-to-twin transfusion syndrome (16-27 weeks gestation, n = 8) were collected after cesarean delivery at 29-35 weeks. Samples were categorized by proximity to the trocar site and analyzed using proteomic and histological methods. Results: While differential expression analysis in the amnion revealed no significant changes, pathway enrichment indicated increased collagen deposition at defect sites. In the chorion, seven differentially expressed proteins were identified, largely linked to enhanced intercellular contact stability. These findings suggest the amnion may respond to mechanical stress by reinforcing structural integrity through collagen deposition, while the chorion may attempt to stabilize cell junctions. However, no other signs of tissue regeneration were observed. Conclusion: This study provides molecular and cellular evidence that FMs lack a substantial healing response post-surgery, underscoring the need for biologically informed repair strategies. Impact: By combining untargeted proteomics with histological and qPCR evaluations, this study demonstrates subtle molecular and cellular changes in fetoscopy-induced fetal membrane defects at the time of delivery. This indicates minimal molecular and cellular healing mechanisms in the fetal membranes. This underscores the potential for sealing FM defects after fetoscopy to prevent amniotic fluid leakage, thereby reducing the incidence of intra-amniotic preterm rupture of membranes.
2001-09-06 | Prolonged use of tissue plasminogen activator for bilateral lower limb arterial occlusion in a neonate.
The authors report the case of a 29-week-gestation twin with very severe vascular compromise of both lower limbs secondary to premature twin-twin transfusion. A tissue plasminogen activator (tPA) infusion was used locally for 13 days with complete recovery of perfusion to both legs, demonstrated by serial angiograms, thereby avoiding bilateral amputation. There were no side effects as a result of the continuous administration of tPA. The authors therefore suggest that the benefits of thrombolysis from a local infusion of tPA in neonates may outweigh the potential risks. This case report thus supports the view that under certain circumstances infusion of tPA in neonates may offer significant benefits. J Pediatr Surg 36:654-656.
antibodies
2026-06-07 | Impact of preimplantation genetic testing on the incidence of monochorionic diamniotic pregnancies in single blastocyst frozen-thawed embryo transfers: a retrospective cohort study spanning 10 years.
This study aimed to explore the associations between assisted reproductive technology (ART) modality and chorionicity in monozygotic twinning pregnancies following single blastocyst frozen-thawed embryo transfer. This retrospective cohort study analyzed 30,121 single embryo transfer cycles from January 2013 to December 2022 but focused on 251 monozygotic twinning pregnancies following single blastocyst frozen-thawed embryo transfer, including 144 monochorionic diamniotic (MCDA) twins and 107 dichorionic diamniotic (DCDA) twins. Regression analysis was performed to determine the risk factors for the subtypes of monozygotic twinning pregnancies after ART. Pregnancy complications and neonatal outcomes of the MCDA and DCDA groups were compared, and subgroup analyses among the in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and preimplantation genetic testing (PGT) groups were performed. The overall monozygotic twinning rate was 1.97%, without a significant difference between D5/6 and D3 embryos in frozen cycles (1.95% vs. 1.56%, p = 0.55). IVF and ICSI were associated with a lower incidence of MCDA twins than observed in the PGT group (IVF: adjusted odds ratio [aOR] = 0.40, p = 0.009; ICSI: aOR = 0.38, p = 0.011). The incidence rates of specific severe complications in MCDA twins, such as twin‒twin transfusion syndrome, selective intrauterine growth restriction, and twin anemia polycythemia sequence, were 2.78%, 2.78%, and 0.69%, respectively. No significant differences were observed in other adverse pregnancy or neonatal outcomes among the MCDA, DCDA, and ART modalities. PGT may be associated with an increased incidence of MCDA twins following single blastocyst frozen-thawed embryo transfer. The incidence of specific maternal-fetal complications for MCDA twins, such as twin‒twin transfusion syndrome and selective intrauterine growth restriction, remains noteworthy. However, the occurrence rates of other adverse pregnancy complications and neonatal outcomes of MCDA twins and DCDA twins are comparable.
2025-12-26 | Double trouble: A case series exploring the complications of twin pregnancy
Monochorionic twin pregnancies are associated with unique and serious complications due to shared placental circulation, including twin-to-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), and twin reversed arterial perfusion (TRAP) sequence. This case series presents four monochorionic diamniotic pregnancies complicated by TAPS, TTTS (Quintero stages I and IV), and TRAP. Diagnostic features such as intertwin discrepancies in middle cerebral artery peak systolic velocity, amniotic fluid discordance, and Doppler studies were critical in identifying these conditions. Management strategies included conservative monitoring, radiofrequency ablation, and, in one case, termination due to poor prognosis. Outcomes varied, highlighting the unpredictable nature of these conditions despite timely intervention. This study underscores the importance of early chorionicity determination, regular ultrasound monitoring, and individualized multidisciplinary care in optimizing outcomes for monochorionic twin pregnancies.
2025-11-05 | Preoperative factors associated with donor twin demise in 1602 pregnancies complicated by twin-twin transfusion syndrome.
To identify preoperative risk factors associated with postlaser fetal death of the donor twin in a large cohort of pregnancies complicated by twin-twin transfusion syndrome (TTTS). This retrospective cohort study of prospectively collected data included monochorionic diamniotic pregnancies complicated by TTTS that underwent laser surgery between March 2006 and May 2024 at two specialized referral centers. Patients underwent a comprehensive ultrasound examination, including fetal Doppler evaluation, to assign a Quintero stage and to obtain the middle cerebral artery (MCA) peak systolic velocity (PSV) for each twin within 24 h before laser surgery. An isolated elevation of the donor MCA-PSV was defined as having an MCA-PSV > 1.5 multiples of the median (MoM) in the absence of twin anemia-polycythemia sequence (TAPS). TAPS was defined as donor MCA-PSV > 1.5 MoM and recipient MCA-PSV < 1.0 MoM or intertwin MCA-PSV difference of > 0.5 MoM. Patients underwent postoperative ultrasound the day after surgery to document cardiac activity in each twin. Univariate logistic and multivariable Poisson (Zou's method) regression models were used to estimate the odds ratio and adjusted relative risk (aRR) for donor twin demise, adjusted for TAPS, TTTS stage, selective fetal growth restriction (sFGR), donor MCA pulsatility index < 10th percentile, gestational age < 18 weeks at surgery and other risk factors. Fetal demise of the donor twin was noted in 14.3% (229/1602) of the study population. Preoperative isolated elevation of donor MCA-PSV conferred the highest aRR of any risk factor for postlaser donor fetal demise (aRR, 2.69 (95% CI, 1.91-3.81); P < 0.001) compared with Stage-III TTTS (aRR, 2.34 (95% CI, 1.36-4.02); P = 0.002), MCA pulsatility index < 10th percentile (aRR, 1.91 (95% CI, 1.48-2.46); P < 0.001), velamentous cord insertion in the donor twin (aRR, 1.86 (95% CI, 1.43-2.41); P < 0.001), TAPS (aRR, 1.63 (95% CI, 1.19-2.23); P = 0.001), gestational age < 18 weeks at laser surgery (aRR, 1.59 (95% CI, 1.21-2.08); P = 0.001) and sFGR (aRR, 1.58 (95% CI, 1.19-2.07); P = 0.001). The observed frequency of fetal demise of the donor twin increased with each additional concomitant risk factor included. Isolated elevation of donor MCA-PSV prior to laser surgery for TTTS conferred the highest aRR for donor fetal demise among risk factors including TAPS, TTTS staging, sFGR and other covariates. This risk increased progressively when more than one risk factor was present in pregnancies complicated by TTTS. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.
2025-10-21 | Predictors of Adverse Perinatal Outcome in Twin Anemia Polycythemia Sequence: Evidence From a Single Center Cohort Study.
To evaluate the perinatal outcome of monochorionic pregnancies complicated by Twin Anemia-Polycythemia Sequence (TAPS) and identify prognostic factors associated with adverse outcomes. A retrospective study (2012-2024) analyzed TAPS cases at a tertiary center. Demographic, obstetric, and neonatal outcomes were compared between conservative management and interventions (intrauterine transfusion, laser surgery, or selective feticide). TAPS characteristics were also analyzed in three subgroups: deliveries before/after 32 weeks, CNS findings on MRI, and dual versus single/no survival. Of 32 TAPS cases, 68.75% were spontaneous, and 31.25% followed TTTS laser treatment. Conservative management was used in 62.5%, while 21.9% received intrauterine transfusions, 9.4% underwent laser treatment, and 9.4% had selective feticide. Gestational age at diagnosis and delivery was earlier in the intervention group (25 vs. 27 weeks, p = 0.05; 30.6 vs. 32.6 weeks, p = 0.04). CNS abnormalities (25%) were linked to earlier diagnosis. Perinatal survival was 86%, with dual, single, and no survival rates of 78.1%, 15.6%, and 6.2%, respectively. Patients with single/no survival were characterized by an earlier gestational age at diagnosis of TAPS compared to those with dual survival (21 vs. 27 weeks, p < 0.01). Earlier TAPS diagnosis is associated with poorer outcomes, including reduced survival and increased risk of brain injury.
2025-10-12 | Complications in monochorionic twin pregnancies.
Monochorionic placentas occur in two-thirds of identical (monozygotic) twin pregnancies and typically feature inter-fetal vascular anastomoses on their surface. These anastomoses can cause very specific complications including twin-to-twin transfusion syndrome (TTTS) in about 10 %, TAPS in 5 %, twin reversed arterial perfusion (TRAP) sequence in 2.5 % and spontaneous intrauterine fetal death (IUFD) in 2 % of monochorionic-diamniotic twin pregnancies. Moreover, unequal sharing of placental territories can lead to selective fetal growth restriction (sFGR) in about 15 %. Monochorionic multiples affected by such complications are at increased risk of mortality, brain abnormalities and neurodevelopmental disorders. This narrative review provides insight into prenatal detection and management of specific complications of monochorionic twin pregnancies.
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