Intrauterine Treatment of Monochorionic Triamniotic Triplet Pregnancy with Twin Reverse Arterial Perfusion Sequence

To editor: This case study reports a pregnant woman who was naturally conceived with monochorionic triamniotic (MCTA) combined with twin reversed arterial perfusion (TRAP). An ultrasound revealed that one of the fetuses had a cardiac malformation, and a connection between the umbilical arteries was suspected. To reduce the acardiac fetus, radiofrequency ablation was performed at 17 + 3 weeks of pregnancy. At 36 + 4 weeks, two healthy infants were delivered via elective cesarean section. Postoperative examination revealed a direct connection between the umbilical arteries, with the placental perfusion acting as a direct pump. It is essential to identify the intrauterine status of the blood-supplying infant and vascular connections in order to achieve successful outcomes in pregnancies with complications, such as edema and heart failure. The studies involving human participants were reviewed and approved by Human Research Ethics Committee of Tianjin Central Hospital of Obstetrics and Gynecology. The patient provided her written informed consent to participate in this study. Triplet pregnancies that occur naturally are quite uncommon, with a prevalence of about 1/7000; however, the exact rate of monochorionic triamniotic (MCTA) is yet to be ascertained, and there is a lack of reports in the literature. An exclusive complication of monochorionic multiple pregnancies is the twin reversed arterial perfusion (TRAP) sequence.1 Approximately 50% of intrauterine or neonatal deaths were linked to the high cardiac output status and subsequent heart failure in pumped infants in the TRAP sequence.2 The complexity of the hemodynamic changes in an MCTA with a TRAP sequence is quite intricate, due to the presence of one or more abnormal vascular connections between the fetuses, which are usually found on the surface of the placenta or within the umbilical cord. This affects the treatment methods that the doctor must take. In the case reported, a naturally conceived MCTA with TRAP was present, with one fetus pumping blood into an acardiac fetus. However, through careful monitoring and timely surgical intervention, two healthy newborns were successfully delivered. Case presentation The patient was a 28-year-old pregnant woman with one pregnancy and no deliveries. The first B-ultrasound showed three fetuses in the uterus, one placenta, and thin septations exhibiting a "T" shape between the three fetuses. Fetuses 1 and 2 were equivalent to 12 + 2 weeks of gestation, whereas Fetus 3 was equivalent to 10 + 1 weeks of pregnancy. Fetus 3 had no fetal head or skull, acardia, skin edema, and bilateral pleural effusion. Additionally, an artery and vein were observed emitting from Fetus 3, forming an umbilical cord. Based on the presence of a vascular connection between Fetus 3 and Fetus 2 via the umbilical arteries, a diagnosis of MCTA and triple pregnancy with TRAP (Fetus 2 and Fetus 3) was made (Fig. 1A–C). Ultrasounds were reviewed regularly until 16 weeks of pregnancy. The B-ultrasound at 15 + 5 weeks of pregnancy revealed that both Fetus 1 and Fetus 2 were in line with the gestational age. The abdominal circumference of Fetus 3 was 96 mm and 109 mm, respectively. At 16 + 5 weeks of gestation, a reexamination by B-ultrasound revealed that the acardiac Fetus (Fetus 3) had grown significantly, with an abdominal circumference of 128 mm and a maximum depth of amniotic fluid of 4.5 cm, as well as edematous skin and abundant blood flow in its artery. Fetus 2, which was adjacent to the pumping, had an abdominal circumference of 111 mm, a maximum depth of amniotic fluid of 4 cm, subcutaneous edema, pericardial effusion, cardiac enlargement, moderate tricuspid regurgitation, and a small amount of mitral regurgitation in heart failure (Fig. 1D–G). Fetuses 1, 2, and 3 weighed 159 g, 160 g, and 71 g, respectively, leading to the need for surgery. After considering the situation, the patient and family decided to proceed with radiofrequency ablation to reduce the acardiac fetus at 17 + 3 weeks of gestation. With the assistance of ultrasound, the radiofrequency ablation electrode was percutaneously punctured into the abdominal cavity of the acardiac fetus. The needle tip was placed close to the blood supply artery, and the umbrella-shaped needle tip was then deployed. Ultrasound was used to reconfirm the positioning. The power of the radiofrequency ablation was between 20 and 40 W, the duration was 2 minutes and 30 seconds, and the number of radiofrequency cycles was only one. Following this procedure, the umbilical cord blood flow of the acardiac fetus vanished, and the umbilical artery Doppler and fetal heart rate of the two remaining fetuses were normal. Amniocentesis was performed on the retained fetus (Fetus 2) to extract 20 mL of amniotic fluid for chromosome detection, such as chromosomal karyotype analysis and copy number variation (CNV) detection. After 24 hours of the operation, the B-ultrasound showed that the middle cerebral artery–peak systolic velocities (MCA-PSV) of the two retained fetuses (Fetus 1 and Fetus 2) were normal.Figure 1: Ultrasound image of the fetuses. (A) Monochorionic trimester, amniotic sac trimester, and Fetus 3 was acardiac at 12 + 4 weeks; (B) Fetus 3 showed an umbilical vein and artery at 12 + 4 weeks; (C) Fetus 3 umbilicoplacenta junction was closely related to Fetus 2 at 12 + 4 weeks; (D–G) Fetus 2 (pumping fetus) showed subcutaneous edema and pericardial effusion (D), fetal heart enlargement (E), mild mitral regurgitation (F), and moderate tricuspid regurgitation (G) 16 + 5 weeks.Two weeks after the fetal reduction procedure, B-ultrasound revealed a minimal amount of fluid had collected in the abdominal cavity of Fetus 2, along with minor tricuspid regurgitation, demonstrating a marked improvement. Chromosomal karyotype analysis and CNV evaluation of the amniotic fluid from Fetus 2 showed no abnormalities. At 36 + 4 weeks, two healthy male infants were born through an elective cesarean section. Fetus 1 weighed 2,450 g and had an Apgar score of 10/10 at 1 and 5 minutes, respectively. Fetus 2 weighed 2,930 g and had an Apgar score of 8/10 at 1 minute (lacking 1 point each for respiration and skin color) and 10/10 at 5 minutes. Upon postoperative examination of the placenta, it was found that a blood vessel extending from the umbilical artery of Fetus 2, approximately 1 cm away from the placental opening, had run about 3 cm inside the fetal membrane and ended up connecting freely to the abdomen of the acardiac fetus (Fig. 2A, B). Placental perfusion revealed there was no significant connection between Fetus 1 and the other two fetuses (Fig. 2C). The placental examination revealed two umbilical cords located 9 cm and 4 cm from the edge of the placenta. The placental tissue belonging to Fetus 1 and Fetus 2 accounted for 40% and 60% of the total volume, respectively. The maternal side of the placenta was poorly perfused, with evidence of multiple villous infarcts, calcifications, and partial villous adhesions (Fig. 2D). The two live fetuses had two arteries and one vein in the umbilical cord, with Wharton's jelly being edematous. The third fetus, which had an acardiac malformation, had one blood vessel on the fetal connection surface, with a degenerated wall and visible thrombus in the lumen (Fig. 2E).Figure 2: The vascular connection, placental perfusion, and pathological findings of the placenta in acardiac fetus. A The umbilical cord blood vessels of the acardiac fetus were directly connected to one of the umbilical arteries in the Fetus 2 (arrow); B The umbilical cord vessels of the acardiac fetus run within the fetal membrane (arrow); C Placental perfusion results (yellow pigment overflow was visible in the umbilical artery on the side of Fetus 2 at the junction of the fetal umbilical cord, arrow); D Multifocal villous infarction and calcification of the placenta (HE×40); E The cut section of the umbilical cord tissue of the acardiac (HE×100).Discussion It is essential to determine whether to reduce the acardiac fetus depends on the relative size of the acardiac fetuses and the pumping fetus, as well as the cardiac function of the pumping fetus. Close monitoring and accurate assessment of intrauterine intervention are essential to ensure a positive outcome for the healthy fetuses. This case was a naturally conceived MCTA with TRAP, and two healthy newborns were delivered through strict intrauterine monitoring and timely surgical intervention. Determining the connection mode of the pump in utero can be a useful guide for deciding whether to perform intrauterine treatments. It has been reported that, in monochorionic twin pregnancies with TRAP sequence, the risk of heart failure was higher when the acardiac fetus was 0.7-fold larger than the estimated fetal body weight (EFBW) of the pumping fetus.3 Kobori et al. reported a case of MCTA combined with TRAP sequence, where the estimated body weight of the acardiac fetus was twice that of the pumping fetus. Thus, having both indirect and direct pumps, or both fetuses providing blood flow to the acardiac fetus, may reduce the overall risk of fetal edema or intrauterine fetal death.1 Fetal A was found to have a direct pump and an indirect pump upon postoperative placental examination, which prevented Fetal B from experiencing heart failure. However, Fetal B did not show any signs of heart failure.4 In this case, the postoperative appearance of the placenta and placental perfusion indicated that the umbilicoplacenta junction of Fetus 3 was closely related to the umbilicoplacenta junction of Fetus 2. No vascular anastomosis was found between Fetus 1 and Fetus 2 or 3. This was in line with the preoperative ultrasound results, which showed that the second fetus was directly supplying the acardiac Fetus 3. Furthermore, the B-ultrasound at 16 + 5 weeks of gestation revealed that the pumping Fetus 2 had heart failure, likely due to the direct connection between the umbilical arteries. In this case, the EFBW ratio of Fetus 3/Fetus 2 was <0.7. However, Fetus 2 still had heart failure and edema. Therefore, apart from evaluating the EFBW ratio between acardiac fetuses and pumped fetuses, it is also important to consider the ultrasound performance of the fetuses. Thus, intrauterine intervention should be considered in a timely manner. It is by evaluating the connection of the intrauterine pump and performing the operation promptly that the risk of fetal intrauterine death can be minimized and pregnancies with issues can finally have positive outcomes. An adverse prognostic factor for fetal death in the uterus is the sudden enlargement of the pumped infant and the accompanying heart failure.5 In this case, after multiple ultrasounds and multidisciplinary consultations, it was believed that a direct connection existed between the umbilical cords of the two fetuses. Fetus 2 had already presented with heart failure and edema, and the decision was made to go ahead with a surgical procedure. The radiofrequency ablation operation to reduce the acardiac fetus was successful at 17 + 3 weeks of gestation. Compared with twin pregnancies with TRAP sequence, the treatment of MCTA combined with TRAP sequence is more difficult. It can be challenging to perform the invasive surgery, and it can also change the hemodynamics of all three fetuses after restricting the blood flow to the acardiac fetus. Unfortunately, the risks of fetal loss are high with MCTA radiofrequency ablation for fetal reduction. There have only been 5 reported cases of pregnant women with MCTA undergoing this procedure in the second trimester. In two of these cases, all three fetal hearts disappeared the next day, and one pregnancy lost two of the three fetal hearts after 19 weeks postfetal reduction.6 In this case, B-ultrasound examination showed that Fetus 1 was normal, and the heart function of Fetus 2 returned to normal. After 2 months of birth, no nervous system damage was observed. Thus, radiofrequency ablation was chosen for the fetal reduction surgery in a timely and successful manner, demonstrating the significance of ultrasound examination and the accurate understanding of vascular connections in utero. We summarized the published research on the intrauterine treatment of MCTA combined with TRAP (Table 1). In conclusion, it is essential to identify the placenta's vascular connections before surgery to determine the best treatment method and prognosis. Unfortunately, this is a complex process, making it difficult to achieve an accurate intrauterine diagnosis and treatment. However, early detection and intervention of risks such as edema and heart failure in the pumped fetus can lead to improved prognoses.8 To achieve this, not only do more advanced ultrasound techniques need to be developed, but also it is necessary for doctors to have the knowledge and experience to make the right decisions. With the limited number of reported cases, it is difficult to compare the outcomes of different "pump" intrauterine therapies. Thus, we contribute to the accumulation of these cases to provide more clinical experience for the diagnosis and treatment of MCTA combined with TRAP. Table 1 - Summary of published case reports of monochorionic triamniotic combined with twin reversed arterial perfusion. Patient number Gestational age at intervention (wk) Intervention method Gestational age (wk) Outcome of pregnancy 14 18 In utero radiofrequency ablation 37 Two live infants (2662 and 2031 g) 27 16 + 1 Fetoscopic laser surgery 28 + 4 Two live infants (917 and 713 g), 12 wk NICU stay 38 16 + 3 Unknown 29 + 3 Two live infants (1167 and 1237 g), NICU stay; one macerated acardiac fetus 49 23 + 4 In utero radiofrequency ablation 31 + 5 Two live infants (1515 and 1275 g), 3 wk NICU stay; one macerated acardiac fetus 510 Unknown Unknown None Two live infants (1821 and 1520 g); one acardiac fetus 611 17 Ultrasound-guided in utero thermogenic coil 35 Two live infants (2400 and 2600 g); one mummified acardiac fetus 712 17 Ultrasound-guided interstitial laser ablation 34 Two live infants (2305 and 1795 g); one acardiac fetus (14 g) 812 17 Ultrasound-guided interstitial laser ablation 37 One live infant (2730 g); one acardiac fetus; IUFD of pump fetus 6 d after laser ablation 912 Unknown Unknown 31 Two live infants (1320 and 1640 g); one acardiac fetus (80 g) 1012 Unknown Amniodrainage 32 One live infant (1660 g), discharged home on day 22; IUFD of pump fetus at 26 wk 1112 Unknown Unknown 12 One acardiac triplet; IUFD of the two normal fetuses at 12 wk 1213 Unknown Unknown 23 Intrauterine demise of all three fetuses