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Unique Complications of Monochorionic Twins: Diagnosis and Management
R E V I E W A R T I C L E
Unique Complications of Monochorionic Twins: Diagnosis and Management Yao-Lung Chang* Monochorionic (MC) twins run the highest risk of complications and the wellbeing of one fetus crucially depends on that of the other because of vascular anastomoses in the common placenta. The management for unique complications of MC twins is also influenced by the vascular anastomoses on the chorionic plate. Those unique complications include twin–twin transfusion syndrome, twin reversed arterial perfusion, MC twin with selective intrauterine growth restriction, and MC twin with one anomaly. Diagnosis of the unique complications of MC twin pregnancy is heavily dependent on ultrasonography, and management would largely be dependent on the sonographic guide procedures. Such complications of MC twins are relatively rare but the management is somewhat complex; the obstetrician should be familiar with the diagnosis and the rationale of management.
KEY WORDS — intrauterine growth restriction, monochorionic twin, twin–twin transfusion syndrome, twin reversed arterial perfusion ■ J Med Ultrasound 2007;15(1):1–8 ■
Introduction Twins account for 10% of perinatal mortality, although they represent only 3.0% of pregnancies [1]. Twin pregnancy has a more complicated course in utero than singletons, and management is also complicated by the fact that more than one fetus must be taken into account. Approximately 30% of twins are monozygotic and 70% are dizygotic [2]. The key to management of multiple pregnancies is the accurate determination of chorionicity. This is best performed in the first trimester when accuracy rates approach 100% [3]. If monochorionic (MC)
twins have been confirmed, then some unique complications mentioned in this article should be kept in mind before performing sonographic examination. These complications include twin–twin transfusion syndrome (TTTS), twin reversed arterial perfusion (TRAP), MC twins with selective intrauterine growth restriction (IUGR), and MC twins with one anomaly. Common obstetric complications, such as preeclampsia, gestational diabetes, preterm labor, and intrauterine fetal growth restriction, occur more frequently in multiple gestations, yet the diagnosis and management of these conditions are similar to
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Tao-Yuan, Taiwan. *Address correspondence to: Dr. Yao-Lung Chang, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, 5 Fu-Shin Street, Kweishan, Taoyuan 333, Taiwan. E-mail: [email protected]
©Elsevier & CTSUM. All rights reserved.
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Y.L. Chang
The etiology of TTTS appears to result from a net unbalanced flow of blood between two MC fetuses through placental vascular communications, which results in a donor twin and a recipient twin. Although actual documentation of the unbalanced blood flow remains elusive [5], vascular anastomoses might be responsible for the development of TTTS if the vascular design is such that it forces a net flow from donor to recipient [5]. Alternatively, vascular anastomoses might play a passive role in the development of the syndrome, but nonetheless allow its development. This is the case with MC twins who are discordant for congenital heart disease, cardiomyopathies, cord anomalies, or other conditions associated with uneven hemodynamic competence [6]. When the onset of this condition occurs before 26 weeks of gestation, there is a significant associated risk of fetal loss, perinatal death, and subsequent handicap in survivors [7]. If untreated at its early onset, severe TTTS has a dismal prognosis, with perinatal mortality rates > 90% [8], and > 30% of survivors suffering from associated neurodevelopmental anomalies [8].
twin; (2) oligohydramnios, MVP ≤ 2 cm in the donor twin; (3) single placenta, thin dividing membrane, and similar external genitalia. In a study of 178 twin pairs [9], only four pairs had a hemoglobin difference > 5 g/dL and a weight difference > 20%, and none of those pregnancies showed evidence of polyhydramnios or oligohydramnios. Similarly, percutaneous umbilical blood sampling in six TTTS patients failed to show hemoglobin differences > 5 g/dL, except in one pregnancy [10]. Consequently, the previous pediatric criteria of a hemoglobin difference > 5 g/dL and a weight difference > 20% are no longer applicable [6]. The severity of TTTS depends on several prognostic factors, the most important of which is the Doppler flow of the two involved fetuses; the most widely used criteria for TTTS staging is that of Quintero et al [11], which is as follows: • Stage I — the bladder of the donor twin is still visible, and Doppler studies are still normal; • Stage II — the bladder of the donor twin is not visible (during the length of the examination, usually 1 hour), but Doppler studies are not critically abnormal; • Stage III — Doppler studies are critically abnormal in either twin and are characterized as absent or reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile umbilical venous flow; • Stage IV — presence of ascites, pericardial or pleural effusion, scalp edema, or overt hydrops; • Stage V — demise of one or both fetuses. There were about 80 cases of TTTS predicted to occur each year in Taiwan [12]; half of them would be the severe form (diagnosed before gestational age of 26 weeks). So familiarity with the diagnostic criteria of TTTS would be necessary for medics who would possibly manage the high-risk multiple pregnancy.
Diagnosis
Management
The diagnosis of TTTS is based on the following sonographic findings: (1) polyhydramnios, ≥ 8 cm of maximum vertical pocket (MVP) in the recipient
Undoubtedly, the most controversial aspect of TTTS is treatment [6]. Interpretation of published therapeutic results must be done with caution because
those in singleton pregnancies [4]. MC twins run the highest risk of complications and the wellbeing of one fetus crucially depends on that of the other because of the almost ever-present vascular anastomoses in the common placenta [3]. Management of the unique complications of MC twins are also influenced by the vascular anastomoses on the chorionic plate. These complications include TTTS, TRAP, IUGR, and MC twins with one anomaly. Diagnosis of these unique complications of MC twin pregnancy depend heavily on ultrasonography, and management would largely be dependent on the sonographic guide procedures.
TTTS
2
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Ultrasound Examination is Important for Monochorionic Twins not all investigators have adhered to standard diagnostic sonographic criteria [6]. Treatment options include serial amniocentesis, laser therapy, umbilical cord occlusion, and septostomy. Serial amniocentesis and endoscopic laser ablation of vascular anastomoses have both been shown to reduce perinatal mortality in an uncontrolled series [13]. After the first and only randomized trial on interventions for TTTS was published, comparing laser to amnioreduction [14], it was proved that the laser group had a higher likelihood of survival of at least one twin to 28 days of age (76% vs. 56%; relative risk of the death of both fetuses, 0.63; 95% confidence interval, 0.25–0.93; p = 0.009) and to 6 months of age (p = 0.002) [14]. Recently, a clinical trial was conducted to compare the efficacy of septostomy and amnioreduction in treating TTTS [15], and the conclusion was that septostomy and amnioreduction were equally efficacious for early onset TTTS. But later, there were differing comments about the conclusion of this paper [16]. So in addition to laser therapy and serial amnioreduction, I will also introduce the method of septostomy in this section.
Serial amniocentesis Serial amniocentesis could also be called amnioreduction. The goal of this therapy is to decrease the likelihood of miscarriage or preterm labor by reducing the amniotic fluid volume in the sac of the recipient twin [6]. There is no standard technique for performing serial amniocentesis. How much fluid should be removed, at what rate, what needle, or what type of anesthesia should be used are among the issues that could benefit from standardization [6]. In Chang Gung Memorial Hospital, we only perform serial amniocentesis in cases of TTTS with gestational age ≥ 27 weeks. The patients treated by serial amniocentesis before this have been reported to have had 14% cases of leukomalacia in the surviving fetuses and 76% risk of death of both fetuses [14]. So amnioreduction is not considered as the first line of therapy for TTTS diagnosed before 26 weeks of gestation. Sonography is very important in the procedure of amnioreduction, because you need to evaluate the
position of the placenta, the position of the recipient, and the amount of amniotic fluid before and after this procedure.
Laser therapy Fetoscopic laser therapy for TTTS performed percutaneously before 26 weeks of gestation is a minimally invasive treatment with few maternal complications, with premature rupture of membranes becoming the main source of neonatal complications [17]. It has been recognized that laser surgery for TTTS should be available in fetal medicine units that are managing at least 20 cases per year [13]. Sonography is very important before, during, and after this procedure. Before the procedure, you have to locate the position of the placenta, the position of the fetuses, the amount of amniotic fluid, and the ideal position for insertion of the fetoscope. A good evaluation is crucial for a successful operation. The insertion of the fetoscope is usually not difficult in mainly posterior placenta (Fig. 1); you just need to choose the site of entry directly into the sac of the recipient. The risk of septostomy is low in such cases. But in cases of mainly anterior placenta (Fig. 2), to choose an ideal site for entry is not always easy. In cases where the free space for entry is located near the sac of the donor, the risk of septostomy is high. During operation, you have to identify whether there are uterine wall vessels
Fig. 1. Mainly posterior wall placenta, the 0 degree fetoscope can be inserted to see the placenta directly. J Med Ultrasound 2007 • Vol 15 • No 1
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Fig. 2. Mainly anterior placenta, the 30 degree reverse scope needs to be inserted to see the vascular anastomoses. on the site that you choose for entry so as to avoid bleeding caused by trocar insertion. Because the laser therapy for TTTS is usually one-port surgery, the location of the fetoscope needs to be identified by continuous sonographic monitoring. The uterine cavity space is not so large in midtrimester even in cases of polyhydramnios and multiple pregnancies. The fetoscope could easily touch the uterine wall if it is not monitored by sonography and there will be a loss of the visual field in the endoscope. In extreme conditions and unfamiliar hands, the fetoscope could leave the uterine cavity unintentionally. At the end of laser therapy, amnioreduction to reduce MVP to below 8 cm is still performed under sonographic guidance.
Umbilical cord occlusion The goal of the umbilical cord occlusion technique is to stop blood exchange between the fetuses at the level of the umbilical cord of one of the twins; the procedure is reserved for severe cases in which spontaneous fetal death of one of the twins is likely to happen, particularly in the presence of hydrops or intracranial hemorrhage found in one fetus [6].
produced by the recipient is one explanation for the extreme rarity of TTTS in monoamniotic twins. The procedure is done by using a 22-gauge needle to perforate the intertwin membrane with a single puncture under ultrasound guidance. This is usually introduced through the donor twin’s gestational sac into the recipient twin’s amniotic cavity. If the needle was introduced from the recipient’s sac, it would be harder to puncture the donor’s sac due to oligohydramnios and there is a risk of hurting the donor. In view of the lack of mathematically or clinically evidenced benefit of septostomy vs. amnioreduction and the significant risk of cord entanglement, amnioreduction but not septostomy should be the continued procedure of choice after the occurrence of fetal viability (at which time laser therapy is generally not offered) [16].
TRAP The TRAP sequence is a rare complication of monozygotic multiple gestations that affects 1% of monozygotic twins or 1 in 35,000 births [19]. The pathophysiologic mechanism that is responsible for the syndrome is not well known [20]; it has been hypothesized that blood is perfused by the hemodynamically advantaged twin (‘’pump’’ twin) into the other twin (‘’acardiac’’ twin) by means of retrograde blood flow through an arterioarterial and a venovenous anastomosis in a MC placenta [20]. Thus, the acardiac twin receives deoxygenated arterial blood from the pump twin. This inadequate perfusion of the acardiac twin is responsible for a spectrum of characteristic and invariably lethal set of anomalies, which include acardia, acephalus, severe maldevelopment of the upper body, variable limb and organ reductions, malformations, and a relative excess of edematous connective tissue [21].
Septostomy In 1998, Saade et al [18] proposed the concept of intentionally perforating the intertwin membrane (septostomy) to allow equilibration of the amniotic fluid volume in severe cases of TTTS. Indeed, allowing the donor twin to swallow excess amniotic fluid
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Diagnosis The prenatal diagnosis of acardiac twins should be suspected when a grossly malformed fetus is seen in the setting of a MC twin pregnancy (Fig. 3) [22]. Features visualized on ultrasound that point to the
Ultrasound Examination is Important for Monochorionic Twins
Pump twin
Acardiac twin
Fig. 3. Grossly malformed acardiac twin and normal structure pump twin.
Fig. 4. Umbilical flow at the acardiac; the umbilical artery is pumping into the acardiac twin. diagnosis include biometric discordance between the twins, the absence of identifiable cardiac pulsation in one twin, poor definition of the head, trunk, and upper extremities, deformed lower extremities, marked and diffuse subcutaneous edema, and abnormal cystic areas in the upper part of the body of the affected twin. The presence of cardiac motion does not exclude the diagnosis, as it may result from a rudimentary heart or transmitted pulsation from the cardiac function of the pump twin. Retrograde perfusion from the pump twin to the acardiac twin is the key point for diagnosis of TRAP (Fig. 4).
Management Management of TRAP should be tailored [23]. The classification of TRAP has been done mainly according to the prognostic factors [24], but even in the
same stage of the classification system, characteristics including the flow amount and diameter of the vessel of the communicating flow between the TRAP and acardiac twin are different. The criteria for surgery are: (1) abdominal circumference of the acardiac twin is equal to or greater than that of the pump twin (i.e. acardiac/pump twin ratio ≥ 1.0; the measurement is taken at the level of the stomach including the skin); (2) polyhydramnios (MVP ≥ 8 cm); (3) critically abnormal Doppler studies in the pump twin (persistent absent or reversed diastolic blood flow in the umbilical artery, pulsatile blood flow in the umbilical vein, and/or reversed blood flow in the ductus venosus); (4) fetal hydrops of the pump twin, defined as ≥ 2 fetal compartments with fluid; and (5) monoamniotic twins (high risk for cord entanglement) [21]. In a review paper [24], intrafetal laser was chosen as the best management for TRAP. But further publications [21,24,25] showed that fetoscopic guide therapy is also effective in such cases and many more cases were studied in those papers compared to the previous study. The first successful umbilical cord ligation of a TRAP twin in 1994 using custom-designed instruments and combined endoscopic and ultrasound guidance was done by Quintero et al [26]. Recently, Quintero et al [21] analyzed 74 cases of TRAP in a single institution and suggested that patients with TRAP sequence who are treated with umbilical cord occlusion have a more favorable outcome relative to surgical candidates who do not undergo surgery, provided that the dividing membrane is not disrupted. That is because if the dividing membrane is disrupted, the risk of cord accident and ruptures of membrane would increase.
Selective IUGR MC twins with selective IUGR of one twin was defined as an estimated fetal weight below the 10th percentile for gestational age [27]. Selective IUGR of one twin usually presents as a large and small twin with significant discordant sizes; they are MC same as in TTTS. So they are J Med Ultrasound 2007 • Vol 15 • No 1
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Y.L. Chang usually recognized as TTTS in the first impression. About 25% of cases transferred to the Florida Institute for Fetal Diagnosis and Therapy with a suspected diagnosis of TTTS later turned out not to fulfill the TTTS criteria. Those cases varied from simple amniotic fluid volume discordance to isolated polyhydramnios and isolated oligohydramnios [6]. Since September 2005, there were about 16 cases transferred to Chang Gung Memorial Hospital, Linkou Medical Center under the impression of TTTS, four of the 16 cases were MC twins with selective IUGR, one of the four cases eventually met the criteria for TTTS after 2 weeks. The main pathophysiologic basis of MC twins with selective IUGR is the territory factor; it arises from unequal sharing of the placenta in MC twins. It differs from the vascular communicating factor in TTTS. The diagnosis of MC twins with selective IUGR in ultrasound is: 1. MC placenta; 2. IUGR of the small twin, estimated fetal weight below the 10th percentile in one twin of MC pregnancy; 3. Lack of polyhydramnios/oligohydramnios sequel. They can present as oligohydramnios in the small twin but lack polyhydramnios in the appropriate for gestational age (AGA) twin, or polyhydramnios in the AGA twin but lack oligohydramnios in the small twin. Selective IUGR occurs in about 12% of twin pregnancies [28]. The incidence of this process is similar in dichorionic (DC) and MC twin pregnancies, but the risk of neurologic damage may be greater in MC twins [29]. Spontaneous demise of the twin with selective IUGR may result in the concomitant demise of the twin who is AGA in up to 40% of cases or in neurologic damage of the AGA twin in up to 30% of cases [27]. However, even in the absence of single intrauterine fetal death, the risk of neurologic damage may be increased in MC as compared with DC twin pregnancies [29]. Current treatment of selective IUGR in MC twins involves expectant management and early delivery (if warranted), termination of pregnancy,
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or umbilical cord occlusion [27]. The prognosis of MC twins with selective IUGR is highly influenced by the umbilical artery Doppler of the small twin. If the small twin suffers from absence or reversal of end-diastolic velocity of the umbilical artery, it would display a relatively high perinatal mortality rate. Quintero et al [27] conducted a pioneer study using laser therapy to convert the MC placenta to a functionally DC one. They claimed that the neurologic deficit in the IUGR twin would decrease but the mortality rate of the small twin would remain the same. The technique to laser the communicating vessels in MC twins with selective IUGR is more difficult than in TTTS usually because of the lack of polyhydramios. In unfamiliar hands, it could make the condition worse.
Congenital Malformations in Twins The incidence of malformations in twins varies by chorionicity. The overall risk of congenital malformation in twins is 600/10,000 twin births. Monozygotic twinning is associated with midline defects such as holoprosencephaly, neural tube defects, and cloaca extrophy [3]. Overall, MC twins have a two- to three-fold higher rate than DC twins [3]. In a congenital anomaly that is lethal, fetocide is unnecessary except unless polyhydramnios or TTTS occurs, and expectant management is the sensible option. For example, in anencephaly, if fetocide is considered, bipolar cord occlusion is the choice because potassium chloride injection is not feasible due to the communicating vessels that almost always exist between the two twins. The bipolar could be inserted into the uterus via a 2.5–3.5 mm trocar. Cord insertion near the fetus is better than near the placenta to be coagulated to prevent thrombosis or thermo damage to another twin.
Conclusion Sonography has made a dramatic impact on the obstetric diagnosis and management of complicated
Ultrasound Examination is Important for Monochorionic Twins MC twin pregnancies [30]. Since these relatively rare complications are unique to MC twins, obstetricians, especially those dedicated to high-risk pregnancies, should be familiar with the diagnosis. The management of such complications should be left in expert hands.
References 1. Leduc L, Takser L, Rinfret D. Persistance of adverse obstetric and neonatal outcomes in monochorionic twins after exclusion of disorders unique to monochorionic placentation. Am J Obstet Gynecol 2005;193: 1670–5. 2. Lewi L, Jani J, Deprest J. Invasive antenatal interventions in complicated multiple pregnancies. Obstet Gynecol Clin North Am 2005;32:105–26. 3. Taylor MJ. The management of multiple pregnancy. Early Hum Dev 2006;82:365–70. 4. Graham GM III, Gaddipati S. Diagnosis and management of obstetrical complications unique to multiple gestations. Semin Perinatol 2005;29:282–95. 5. Quintero R, Quintero L, Bornick P, et al. The donorrecipient (D-R) score: in vivo endoscopic evidence to support the hypothesis of a net transfer of blood from donor to recipient in twin–twin transfusion syndrome. Prenat Neonat Med 2000;5:84–91. 6. Quintero RA. Twin–twin transfusion syndrome. Clin Perinatol 2003;30:591–600. 7. Gaziano EP, De Lia JE, Kuhlmann RS. Diamnionic monochorionic twin gestations: an overview. J Matern Fetal Med 2000;9:89–96. 8. Machin GA. Some causes of genotypic and phenotypic discordance in monozygotic twin pairs. Am J Med Genet A 1996;61:216–28. 9. Danskin FH, Neilson JP. Twin-to-twin transfusion syndrome: what are appropriate diagnostic criteria? Am J Obstet Gynecol 1989;161:365–9. 10. Fisk NM, Borrell A, Hubinont C, et al. Fetofetal transfusion syndrome: do the neonatal criteria apply in utero? Arch Dis Child 1990;65:657–61. 11. Quintero RA, Morales WJ, Allen MH, et al. Staging of twin–twin transfusion syndrome. J Perinatol 1999;19: 550–5. 12. Chang YL. Fetoscopic laser therapy for twin–twin transfusion syndrome. Taiwan J Obstet Gynecol 2006; 45:294–301.
13. Robyr R, Quarello E, Ville Y. Management of fetofetal transfusion syndrome. Prenat Diagn 2005;25:786–95. 14. Senat MV, Deprest J, Boulvain M, et al. Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome. N Engl J Med 2004; 351:136–44. 15. Moise KJ Jr, Dorman K, Lamvu G, et al. A randomized trial of amnioreduction versus septostomy in the treatment of twin–twin transfusion syndrome. Am J Obstet Gynecol 2005;193:701–7. 16. Ross MG, van den Wijngaard JP, van Gemert MJ. TTTS amnioreduction versus septostomy. Am J Obstet Gynecol 2006;195:881–2. 17. Yamamoto M, El ML, Robyr R, et al. Incidence and impact of perioperative complications in 175 fetoscopy-guided laser coagulations of chorionic plate anastomoses in fetofetal transfusion syndrome before 26 weeks of gestation. Am J Obstet Gynecol 2005;193: 1110–6. 18. Saade GR, Belfort MA, Berry DL, et al. Amniotic septostomy for the treatment of twin oligohydramniospolyhydramnios sequence. Fetal Diagn Ther 1998;13: 86–93. 19. James WH. A note on the epidemiology of acardiac monsters. Teratology 1977;16:211–6. 20. Van Allen MI, Smith DW, Shepard TH. Twin reversed arterial perfusion (TRAP) sequence: a study of 14 twin pregnancies with acardius. Semin Perinatol 1983;7: 285–93. 21. Quintero RA, Chmait RH, Murakoshi T, et al. Surgical management of twin reversed arterial perfusion sequence. Am J Obstet Gynecol 2006;194:982–91. 22. Sepulveda WH, Quiroz VH, Giuliano A, Henriquez R. Prenatal ultrasonographic diagnosis of acardiac twin. J Perinat Med 1993;21:241–6. 23. Weisz B, Peltz R, Chayen B, et al. Tailored management of twin reversed arterial perfusion (TRAP) sequence. Ultrasound Obstet Gynecol 2004;23:451–5. 24. Wong AE, Sepulveda W. Acardiac anomaly: current issues in prenatal assessment and treatment. Prenat Diagn 2005;25:796–806. 25. Hecher K, Lewi L, Gratacos E, et al. Twin reversed arterial perfusion: fetoscopic laser coagulation of placental anastomoses or the umbilical cord. Ultrasound Obstet Gynecol 2006;28:688–91. 26. Quintero RA, Reich H, Puder KS, et al. Brief report: umbilical-cord ligation of an acardiac twin by fetoscopy at 19 weeks of gestation. N Engl J Med 1994;330: 469–71.
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Y.L. Chang 27. Quintero RA, Bornick PW, Morales WJ, et al. Selective photocoagulation of communicating vessels in the treatment of monochorionic twins with selective growth retardation. Am J Obstet Gynecol 2001; 185:689–96. 28. Sebire NJ, Snijders RJ, Hughes K, et al. The hidden mortality of monochorionic twin pregnancies. Br J Obstet Gynaecol 1997;104:1203–7.
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29. Gratacos E, Carreras E, Becker J, et al. Prevalence of neurological damage in monochorionic twins with selective intrauterine growth restriction and intermittent absent or reversed end-diastolic umbilical artery flow. Ultrasound Obstet Gynecol 2004;24: 159–63. 30. Feldstein VA, Filly RA. Complications of monochorionic twins. Radiol Clin North Am 2003;41:709–27.
Unique Complications of Monochorionic Twins: Diagnosis and Management Yao-Lung Chang* Monochorionic (MC) twins run the highest risk of complications and the wellbeing of one fetus crucially depends on that of the other because of vascular anastomoses in the common placenta. The management for unique complications of MC twins is also influenced by the vascular anastomoses on the chorionic plate. Those unique complications include twin–twin transfusion syndrome, twin reversed arterial perfusion, MC twin with selective intrauterine growth restriction, and MC twin with one anomaly. Diagnosis of the unique complications of MC twin pregnancy is heavily dependent on ultrasonography, and management would largely be dependent on the sonographic guide procedures. Such complications of MC twins are relatively rare but the management is somewhat complex; the obstetrician should be familiar with the diagnosis and the rationale of management.
KEY WORDS — intrauterine growth restriction, monochorionic twin, twin–twin transfusion syndrome, twin reversed arterial perfusion ■ J Med Ultrasound 2007;15(1):1–8 ■
Introduction Twins account for 10% of perinatal mortality, although they represent only 3.0% of pregnancies [1]. Twin pregnancy has a more complicated course in utero than singletons, and management is also complicated by the fact that more than one fetus must be taken into account. Approximately 30% of twins are monozygotic and 70% are dizygotic [2]. The key to management of multiple pregnancies is the accurate determination of chorionicity. This is best performed in the first trimester when accuracy rates approach 100% [3]. If monochorionic (MC)
twins have been confirmed, then some unique complications mentioned in this article should be kept in mind before performing sonographic examination. These complications include twin–twin transfusion syndrome (TTTS), twin reversed arterial perfusion (TRAP), MC twins with selective intrauterine growth restriction (IUGR), and MC twins with one anomaly. Common obstetric complications, such as preeclampsia, gestational diabetes, preterm labor, and intrauterine fetal growth restriction, occur more frequently in multiple gestations, yet the diagnosis and management of these conditions are similar to
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Tao-Yuan, Taiwan. *Address correspondence to: Dr. Yao-Lung Chang, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, 5 Fu-Shin Street, Kweishan, Taoyuan 333, Taiwan. E-mail: [email protected]
©Elsevier & CTSUM. All rights reserved.
J Med Ultrasound 2007 • Vol 15 • No 1
1
Y.L. Chang
The etiology of TTTS appears to result from a net unbalanced flow of blood between two MC fetuses through placental vascular communications, which results in a donor twin and a recipient twin. Although actual documentation of the unbalanced blood flow remains elusive [5], vascular anastomoses might be responsible for the development of TTTS if the vascular design is such that it forces a net flow from donor to recipient [5]. Alternatively, vascular anastomoses might play a passive role in the development of the syndrome, but nonetheless allow its development. This is the case with MC twins who are discordant for congenital heart disease, cardiomyopathies, cord anomalies, or other conditions associated with uneven hemodynamic competence [6]. When the onset of this condition occurs before 26 weeks of gestation, there is a significant associated risk of fetal loss, perinatal death, and subsequent handicap in survivors [7]. If untreated at its early onset, severe TTTS has a dismal prognosis, with perinatal mortality rates > 90% [8], and > 30% of survivors suffering from associated neurodevelopmental anomalies [8].
twin; (2) oligohydramnios, MVP ≤ 2 cm in the donor twin; (3) single placenta, thin dividing membrane, and similar external genitalia. In a study of 178 twin pairs [9], only four pairs had a hemoglobin difference > 5 g/dL and a weight difference > 20%, and none of those pregnancies showed evidence of polyhydramnios or oligohydramnios. Similarly, percutaneous umbilical blood sampling in six TTTS patients failed to show hemoglobin differences > 5 g/dL, except in one pregnancy [10]. Consequently, the previous pediatric criteria of a hemoglobin difference > 5 g/dL and a weight difference > 20% are no longer applicable [6]. The severity of TTTS depends on several prognostic factors, the most important of which is the Doppler flow of the two involved fetuses; the most widely used criteria for TTTS staging is that of Quintero et al [11], which is as follows: • Stage I — the bladder of the donor twin is still visible, and Doppler studies are still normal; • Stage II — the bladder of the donor twin is not visible (during the length of the examination, usually 1 hour), but Doppler studies are not critically abnormal; • Stage III — Doppler studies are critically abnormal in either twin and are characterized as absent or reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile umbilical venous flow; • Stage IV — presence of ascites, pericardial or pleural effusion, scalp edema, or overt hydrops; • Stage V — demise of one or both fetuses. There were about 80 cases of TTTS predicted to occur each year in Taiwan [12]; half of them would be the severe form (diagnosed before gestational age of 26 weeks). So familiarity with the diagnostic criteria of TTTS would be necessary for medics who would possibly manage the high-risk multiple pregnancy.
Diagnosis
Management
The diagnosis of TTTS is based on the following sonographic findings: (1) polyhydramnios, ≥ 8 cm of maximum vertical pocket (MVP) in the recipient
Undoubtedly, the most controversial aspect of TTTS is treatment [6]. Interpretation of published therapeutic results must be done with caution because
those in singleton pregnancies [4]. MC twins run the highest risk of complications and the wellbeing of one fetus crucially depends on that of the other because of the almost ever-present vascular anastomoses in the common placenta [3]. Management of the unique complications of MC twins are also influenced by the vascular anastomoses on the chorionic plate. These complications include TTTS, TRAP, IUGR, and MC twins with one anomaly. Diagnosis of these unique complications of MC twin pregnancy depend heavily on ultrasonography, and management would largely be dependent on the sonographic guide procedures.
TTTS
2
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Ultrasound Examination is Important for Monochorionic Twins not all investigators have adhered to standard diagnostic sonographic criteria [6]. Treatment options include serial amniocentesis, laser therapy, umbilical cord occlusion, and septostomy. Serial amniocentesis and endoscopic laser ablation of vascular anastomoses have both been shown to reduce perinatal mortality in an uncontrolled series [13]. After the first and only randomized trial on interventions for TTTS was published, comparing laser to amnioreduction [14], it was proved that the laser group had a higher likelihood of survival of at least one twin to 28 days of age (76% vs. 56%; relative risk of the death of both fetuses, 0.63; 95% confidence interval, 0.25–0.93; p = 0.009) and to 6 months of age (p = 0.002) [14]. Recently, a clinical trial was conducted to compare the efficacy of septostomy and amnioreduction in treating TTTS [15], and the conclusion was that septostomy and amnioreduction were equally efficacious for early onset TTTS. But later, there were differing comments about the conclusion of this paper [16]. So in addition to laser therapy and serial amnioreduction, I will also introduce the method of septostomy in this section.
Serial amniocentesis Serial amniocentesis could also be called amnioreduction. The goal of this therapy is to decrease the likelihood of miscarriage or preterm labor by reducing the amniotic fluid volume in the sac of the recipient twin [6]. There is no standard technique for performing serial amniocentesis. How much fluid should be removed, at what rate, what needle, or what type of anesthesia should be used are among the issues that could benefit from standardization [6]. In Chang Gung Memorial Hospital, we only perform serial amniocentesis in cases of TTTS with gestational age ≥ 27 weeks. The patients treated by serial amniocentesis before this have been reported to have had 14% cases of leukomalacia in the surviving fetuses and 76% risk of death of both fetuses [14]. So amnioreduction is not considered as the first line of therapy for TTTS diagnosed before 26 weeks of gestation. Sonography is very important in the procedure of amnioreduction, because you need to evaluate the
position of the placenta, the position of the recipient, and the amount of amniotic fluid before and after this procedure.
Laser therapy Fetoscopic laser therapy for TTTS performed percutaneously before 26 weeks of gestation is a minimally invasive treatment with few maternal complications, with premature rupture of membranes becoming the main source of neonatal complications [17]. It has been recognized that laser surgery for TTTS should be available in fetal medicine units that are managing at least 20 cases per year [13]. Sonography is very important before, during, and after this procedure. Before the procedure, you have to locate the position of the placenta, the position of the fetuses, the amount of amniotic fluid, and the ideal position for insertion of the fetoscope. A good evaluation is crucial for a successful operation. The insertion of the fetoscope is usually not difficult in mainly posterior placenta (Fig. 1); you just need to choose the site of entry directly into the sac of the recipient. The risk of septostomy is low in such cases. But in cases of mainly anterior placenta (Fig. 2), to choose an ideal site for entry is not always easy. In cases where the free space for entry is located near the sac of the donor, the risk of septostomy is high. During operation, you have to identify whether there are uterine wall vessels
Fig. 1. Mainly posterior wall placenta, the 0 degree fetoscope can be inserted to see the placenta directly. J Med Ultrasound 2007 • Vol 15 • No 1
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Fig. 2. Mainly anterior placenta, the 30 degree reverse scope needs to be inserted to see the vascular anastomoses. on the site that you choose for entry so as to avoid bleeding caused by trocar insertion. Because the laser therapy for TTTS is usually one-port surgery, the location of the fetoscope needs to be identified by continuous sonographic monitoring. The uterine cavity space is not so large in midtrimester even in cases of polyhydramnios and multiple pregnancies. The fetoscope could easily touch the uterine wall if it is not monitored by sonography and there will be a loss of the visual field in the endoscope. In extreme conditions and unfamiliar hands, the fetoscope could leave the uterine cavity unintentionally. At the end of laser therapy, amnioreduction to reduce MVP to below 8 cm is still performed under sonographic guidance.
Umbilical cord occlusion The goal of the umbilical cord occlusion technique is to stop blood exchange between the fetuses at the level of the umbilical cord of one of the twins; the procedure is reserved for severe cases in which spontaneous fetal death of one of the twins is likely to happen, particularly in the presence of hydrops or intracranial hemorrhage found in one fetus [6].
produced by the recipient is one explanation for the extreme rarity of TTTS in monoamniotic twins. The procedure is done by using a 22-gauge needle to perforate the intertwin membrane with a single puncture under ultrasound guidance. This is usually introduced through the donor twin’s gestational sac into the recipient twin’s amniotic cavity. If the needle was introduced from the recipient’s sac, it would be harder to puncture the donor’s sac due to oligohydramnios and there is a risk of hurting the donor. In view of the lack of mathematically or clinically evidenced benefit of septostomy vs. amnioreduction and the significant risk of cord entanglement, amnioreduction but not septostomy should be the continued procedure of choice after the occurrence of fetal viability (at which time laser therapy is generally not offered) [16].
TRAP The TRAP sequence is a rare complication of monozygotic multiple gestations that affects 1% of monozygotic twins or 1 in 35,000 births [19]. The pathophysiologic mechanism that is responsible for the syndrome is not well known [20]; it has been hypothesized that blood is perfused by the hemodynamically advantaged twin (‘’pump’’ twin) into the other twin (‘’acardiac’’ twin) by means of retrograde blood flow through an arterioarterial and a venovenous anastomosis in a MC placenta [20]. Thus, the acardiac twin receives deoxygenated arterial blood from the pump twin. This inadequate perfusion of the acardiac twin is responsible for a spectrum of characteristic and invariably lethal set of anomalies, which include acardia, acephalus, severe maldevelopment of the upper body, variable limb and organ reductions, malformations, and a relative excess of edematous connective tissue [21].
Septostomy In 1998, Saade et al [18] proposed the concept of intentionally perforating the intertwin membrane (septostomy) to allow equilibration of the amniotic fluid volume in severe cases of TTTS. Indeed, allowing the donor twin to swallow excess amniotic fluid
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Diagnosis The prenatal diagnosis of acardiac twins should be suspected when a grossly malformed fetus is seen in the setting of a MC twin pregnancy (Fig. 3) [22]. Features visualized on ultrasound that point to the
Ultrasound Examination is Important for Monochorionic Twins
Pump twin
Acardiac twin
Fig. 3. Grossly malformed acardiac twin and normal structure pump twin.
Fig. 4. Umbilical flow at the acardiac; the umbilical artery is pumping into the acardiac twin. diagnosis include biometric discordance between the twins, the absence of identifiable cardiac pulsation in one twin, poor definition of the head, trunk, and upper extremities, deformed lower extremities, marked and diffuse subcutaneous edema, and abnormal cystic areas in the upper part of the body of the affected twin. The presence of cardiac motion does not exclude the diagnosis, as it may result from a rudimentary heart or transmitted pulsation from the cardiac function of the pump twin. Retrograde perfusion from the pump twin to the acardiac twin is the key point for diagnosis of TRAP (Fig. 4).
Management Management of TRAP should be tailored [23]. The classification of TRAP has been done mainly according to the prognostic factors [24], but even in the
same stage of the classification system, characteristics including the flow amount and diameter of the vessel of the communicating flow between the TRAP and acardiac twin are different. The criteria for surgery are: (1) abdominal circumference of the acardiac twin is equal to or greater than that of the pump twin (i.e. acardiac/pump twin ratio ≥ 1.0; the measurement is taken at the level of the stomach including the skin); (2) polyhydramnios (MVP ≥ 8 cm); (3) critically abnormal Doppler studies in the pump twin (persistent absent or reversed diastolic blood flow in the umbilical artery, pulsatile blood flow in the umbilical vein, and/or reversed blood flow in the ductus venosus); (4) fetal hydrops of the pump twin, defined as ≥ 2 fetal compartments with fluid; and (5) monoamniotic twins (high risk for cord entanglement) [21]. In a review paper [24], intrafetal laser was chosen as the best management for TRAP. But further publications [21,24,25] showed that fetoscopic guide therapy is also effective in such cases and many more cases were studied in those papers compared to the previous study. The first successful umbilical cord ligation of a TRAP twin in 1994 using custom-designed instruments and combined endoscopic and ultrasound guidance was done by Quintero et al [26]. Recently, Quintero et al [21] analyzed 74 cases of TRAP in a single institution and suggested that patients with TRAP sequence who are treated with umbilical cord occlusion have a more favorable outcome relative to surgical candidates who do not undergo surgery, provided that the dividing membrane is not disrupted. That is because if the dividing membrane is disrupted, the risk of cord accident and ruptures of membrane would increase.
Selective IUGR MC twins with selective IUGR of one twin was defined as an estimated fetal weight below the 10th percentile for gestational age [27]. Selective IUGR of one twin usually presents as a large and small twin with significant discordant sizes; they are MC same as in TTTS. So they are J Med Ultrasound 2007 • Vol 15 • No 1
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Y.L. Chang usually recognized as TTTS in the first impression. About 25% of cases transferred to the Florida Institute for Fetal Diagnosis and Therapy with a suspected diagnosis of TTTS later turned out not to fulfill the TTTS criteria. Those cases varied from simple amniotic fluid volume discordance to isolated polyhydramnios and isolated oligohydramnios [6]. Since September 2005, there were about 16 cases transferred to Chang Gung Memorial Hospital, Linkou Medical Center under the impression of TTTS, four of the 16 cases were MC twins with selective IUGR, one of the four cases eventually met the criteria for TTTS after 2 weeks. The main pathophysiologic basis of MC twins with selective IUGR is the territory factor; it arises from unequal sharing of the placenta in MC twins. It differs from the vascular communicating factor in TTTS. The diagnosis of MC twins with selective IUGR in ultrasound is: 1. MC placenta; 2. IUGR of the small twin, estimated fetal weight below the 10th percentile in one twin of MC pregnancy; 3. Lack of polyhydramnios/oligohydramnios sequel. They can present as oligohydramnios in the small twin but lack polyhydramnios in the appropriate for gestational age (AGA) twin, or polyhydramnios in the AGA twin but lack oligohydramnios in the small twin. Selective IUGR occurs in about 12% of twin pregnancies [28]. The incidence of this process is similar in dichorionic (DC) and MC twin pregnancies, but the risk of neurologic damage may be greater in MC twins [29]. Spontaneous demise of the twin with selective IUGR may result in the concomitant demise of the twin who is AGA in up to 40% of cases or in neurologic damage of the AGA twin in up to 30% of cases [27]. However, even in the absence of single intrauterine fetal death, the risk of neurologic damage may be increased in MC as compared with DC twin pregnancies [29]. Current treatment of selective IUGR in MC twins involves expectant management and early delivery (if warranted), termination of pregnancy,
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or umbilical cord occlusion [27]. The prognosis of MC twins with selective IUGR is highly influenced by the umbilical artery Doppler of the small twin. If the small twin suffers from absence or reversal of end-diastolic velocity of the umbilical artery, it would display a relatively high perinatal mortality rate. Quintero et al [27] conducted a pioneer study using laser therapy to convert the MC placenta to a functionally DC one. They claimed that the neurologic deficit in the IUGR twin would decrease but the mortality rate of the small twin would remain the same. The technique to laser the communicating vessels in MC twins with selective IUGR is more difficult than in TTTS usually because of the lack of polyhydramios. In unfamiliar hands, it could make the condition worse.
Congenital Malformations in Twins The incidence of malformations in twins varies by chorionicity. The overall risk of congenital malformation in twins is 600/10,000 twin births. Monozygotic twinning is associated with midline defects such as holoprosencephaly, neural tube defects, and cloaca extrophy [3]. Overall, MC twins have a two- to three-fold higher rate than DC twins [3]. In a congenital anomaly that is lethal, fetocide is unnecessary except unless polyhydramnios or TTTS occurs, and expectant management is the sensible option. For example, in anencephaly, if fetocide is considered, bipolar cord occlusion is the choice because potassium chloride injection is not feasible due to the communicating vessels that almost always exist between the two twins. The bipolar could be inserted into the uterus via a 2.5–3.5 mm trocar. Cord insertion near the fetus is better than near the placenta to be coagulated to prevent thrombosis or thermo damage to another twin.
Conclusion Sonography has made a dramatic impact on the obstetric diagnosis and management of complicated
Ultrasound Examination is Important for Monochorionic Twins MC twin pregnancies [30]. Since these relatively rare complications are unique to MC twins, obstetricians, especially those dedicated to high-risk pregnancies, should be familiar with the diagnosis. The management of such complications should be left in expert hands.
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13. Robyr R, Quarello E, Ville Y. Management of fetofetal transfusion syndrome. Prenat Diagn 2005;25:786–95. 14. Senat MV, Deprest J, Boulvain M, et al. Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome. N Engl J Med 2004; 351:136–44. 15. Moise KJ Jr, Dorman K, Lamvu G, et al. A randomized trial of amnioreduction versus septostomy in the treatment of twin–twin transfusion syndrome. Am J Obstet Gynecol 2005;193:701–7. 16. Ross MG, van den Wijngaard JP, van Gemert MJ. TTTS amnioreduction versus septostomy. Am J Obstet Gynecol 2006;195:881–2. 17. Yamamoto M, El ML, Robyr R, et al. Incidence and impact of perioperative complications in 175 fetoscopy-guided laser coagulations of chorionic plate anastomoses in fetofetal transfusion syndrome before 26 weeks of gestation. Am J Obstet Gynecol 2005;193: 1110–6. 18. Saade GR, Belfort MA, Berry DL, et al. Amniotic septostomy for the treatment of twin oligohydramniospolyhydramnios sequence. Fetal Diagn Ther 1998;13: 86–93. 19. James WH. A note on the epidemiology of acardiac monsters. Teratology 1977;16:211–6. 20. Van Allen MI, Smith DW, Shepard TH. Twin reversed arterial perfusion (TRAP) sequence: a study of 14 twin pregnancies with acardius. Semin Perinatol 1983;7: 285–93. 21. Quintero RA, Chmait RH, Murakoshi T, et al. Surgical management of twin reversed arterial perfusion sequence. Am J Obstet Gynecol 2006;194:982–91. 22. Sepulveda WH, Quiroz VH, Giuliano A, Henriquez R. Prenatal ultrasonographic diagnosis of acardiac twin. J Perinat Med 1993;21:241–6. 23. Weisz B, Peltz R, Chayen B, et al. Tailored management of twin reversed arterial perfusion (TRAP) sequence. Ultrasound Obstet Gynecol 2004;23:451–5. 24. Wong AE, Sepulveda W. Acardiac anomaly: current issues in prenatal assessment and treatment. Prenat Diagn 2005;25:796–806. 25. Hecher K, Lewi L, Gratacos E, et al. Twin reversed arterial perfusion: fetoscopic laser coagulation of placental anastomoses or the umbilical cord. Ultrasound Obstet Gynecol 2006;28:688–91. 26. Quintero RA, Reich H, Puder KS, et al. Brief report: umbilical-cord ligation of an acardiac twin by fetoscopy at 19 weeks of gestation. N Engl J Med 1994;330: 469–71.
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29. Gratacos E, Carreras E, Becker J, et al. Prevalence of neurological damage in monochorionic twins with selective intrauterine growth restriction and intermittent absent or reversed end-diastolic umbilical artery flow. Ultrasound Obstet Gynecol 2004;24: 159–63. 30. Feldstein VA, Filly RA. Complications of monochorionic twins. Radiol Clin North Am 2003;41:709–27.