Twin-twin transfusion syndrome




Objective


We sought to review the natural history, pathophysiology, diagnosis, and treatment options for twin-twin transfusion syndrome (TTTS).


Methods


A systematic review was performed using MEDLINE database, PubMed, EMBASE, and Cochrane Library. The search was restricted to English-language articles published from 1966 through July 2012. Priority was given to articles reporting original research, in particular randomized controlled trials, although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document. Evidence reports and guidelines published by organizations or institutions such as the National Institutes of Health, Agency for Health Research and Quality, American College of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence, and recommendations were graded accordingly.


Results and Recommendations


TTTS is a serious condition that can complicate 8-10% of twin pregnancies with monochorionic diamniotic (MCDA) placentation. The diagnosis of TTTS requires 2 criteria: (1) the presence of a MCDA pregnancy; and (2) the presence of oligohydramnios (defined as a maximal vertical pocket of <2 cm) in one sac, and of polyhydramnios (a maximal vertical pocket of >8 cm) in the other sac. The Quintero staging system appears to be a useful tool for describing the severity of TTTS in a standardized fashion. Serial sonographic evaluation should be considered for all twins with MCDA placentation, usually beginning at around 16 weeks and continuing about every 2 weeks until delivery. Screening for congenital heart disease is warranted in all monochorionic twins, in particular those complicated by TTTS. Extensive counseling should be provided to patients with pregnancies complicated by TTTS including natural history of the disease, as well as management options and their risks and benefits. The natural history of stage I TTTS is that more than three-fourths of cases remain stable or regress without invasive intervention, with perinatal survival of about 86%. Therefore, many patients with stage I TTTS may often be managed expectantly. The natural history of advanced (eg, stage ≥III) TTTS is bleak, with a reported perinatal loss rate of 70-100%, particularly when it presents <26 weeks. Fetoscopic laser photocoagulation of placental anastomoses is considered by most experts to be the best available approach for stages II, III, and IV TTTS in continuing pregnancies at <26 weeks, but the metaanalysis data show no significant survival benefit, and the long-term neurologic outcomes in the Eurofetus trial were not different than in nonlaser-treated controls. Even laser-treated TTTS is associated with a perinatal mortality rate of 30-50%, and a 5-20% chance of long-term neurologic handicap. Steroids for fetal maturation should be considered at 24 0/7 to 33 6/7 weeks, particularly in pregnancies complicated by stage ≥III TTTS, and those undergoing invasive interventions.


Question 1. How is the diagnosis of twin-twin transfusion syndrome made and how is it staged? (Levels II and III)


Twin-twin transfusion syndrome (TTTS) is diagnosed prenatally by ultrasound. The diagnosis requires 2 criteria: (1) the presence of a monochorionic diamniotic (MCDA) pregnancy; and (2) the presence of oligohydramnios (defined as a maximal vertical pocket [MVP] of <2 cm) in one sac, and of polyhydramnios (a MVP of >8 cm) in the other sac ( Figure 1 ). MVP of 2 cm and 8 cm represent the 5th and 95th percentiles for amniotic fluid measurements, respectively, and the presence of both is used to define stage I TTTS. If there is a subjective difference in amniotic fluid in the 2 sacs that fails to meet these criteria, progression to TTTS occurs in <15% of cases. Although growth discordance (usually defined as >20%) and intrauterine growth restriction (IUGR) (estimated fetal weight <10% for gestational age) often complicate TTTS, growth discordance itself or IUGR itself are not diagnostic criteria. The differential diagnosis may include selective IUGR, or possibly an anomaly in 1 twin causing amniotic fluid abnormality. Twin anemia-polycythemia sequence (TAPS) has been recently described in MCDA gestations, and is defined as the presence of anemia in the donor and polycythemia in the recipient, diagnosed antenatally by middle cerebral artery (MCA)–peak systolic velocity (PSV) >1.5 multiples of median in the donor and MCA PSV <1.0 multiples of median in the recipient, in the absence of oligohydramnios-polyhydramnios. Further studies are required to determine the natural history and possible management of TAPS. TTTS can occur in a MCDA twin pair in triplet or higher-order pregnancies.




FIGURE 1


Polyhydramnios-oligohydramnios sequence

Monochorionic diamniotic twins with twin-twin transfusion syndrome demonstrating polyhydramnios in recipient’s sac (twin A) while donor (twin B) was stuck to anterior uterine wall due to marked oligohydramnios.

SMFM. Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013.

Reproduced with permission from Simpson.


The most commonly used TTTS staging system was developed by Quintero et al in 1999, and is based on sonographic findings. The TTTS Quintero staging system includes 5 stages, ranging from mild disease with isolated discordant amniotic fluid volume to severe disease with demise of one or both twins ( Table 1 and Figures 2 and 3 ). This system has some prognostic significance and provides a method to compare outcome data using different therapeutic interventions. Although the stages do not correlate perfectly with perinatal survival, it is relatively straightforward to apply, may improve communication between patients and providers, and identifies the subset of cases most likely to benefit from treatment.



TABLE 1

Staging of twin-twin transfusion syndrome




























Stage Ultrasound parameter Categorical criteria
I MVP of amniotic fluid MVP <2 cm in donor sac; MVP >8 cm in recipient sac
II Fetal bladder Nonvisualization of fetal bladder in donor twin over 60 min of observation ( Figure 2 )
III Umbilical artery, ductus venosus, and umbilical vein Doppler waveforms Absent or reversed umbilical artery diastolic flow, reversed ductus venosus a-wave flow, pulsatile umbilical vein flow ( Figure 3 )
IV Fetal hydrops Hydrops in one or both twins
V Absent fetal cardiac activity Fetal demise in one or both twins

MVP, maximal vertical pocket.

SMFM. Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013.



FIGURE 2


Stage II twin-twin transfusion syndrome

Nonvisualization of fetal bladder ( arrow ) between umbilical arteries in donor twin.

SMFM. Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013.

Reproduced with permission from Simpson.



FIGURE 3


Stage III twin-twin transfusion syndrome

Absent end-diastolic flow ( arrows ) in umbilical artery of donor twin.

SMFM. Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013.

Reproduced with permission from Simpson.


Since the development of the Quintero staging system, much has been learned about the changes in fetal cardiovascular physiology that accompany disease progression (discussed below). Myocardial performance abnormalities have been described, particularly in recipient twins, including those with only stage I or II TTTS. Several groups of investigators have attempted to use assessment of fetal cardiac function to either modify the Quintero TTTS stage or develop a new scoring system. While this approach has some benefits, the models have not yet been prospectively validated. As a result, a recent expert panel concluded that there were insufficient data to recommend modifying the Quintero staging system or adopting a new system. Thus, despite debate over the merits of the Quintero system, at this time it appears to be a useful tool for the diagnosis of TTTS, as well as for describing its severity, in a standardized fashion.




Question 2. How often does TTTS complicate monochorionic twins and what is its natural history? (Levels II and III)


Approximately one-third of twins are monozygotic (MZ), and three-fourths of MZ twins are MCDA. In general, only twin gestations with MCDA placentation are at significant risk for TTTS, which complicates about 8-10% of MCDA pregnancies. TTTS is very uncommon in MZ twins with dichorionic or monoamniotic placentation. Although most twins conceived with in vitro fertilization (IVF) are dichorionic, it is important to remember that there is a 2- to 12-fold increase in MZ twinning in embryos conceived with IVF, and TTTS can therefore occur for IVF MCDA pregnancies. In current practice, the prevalence of TTTS is approximately 1-3 per 10,000 births.


The presentation of TTTS is highly variable. Because pregnancies with TTTS often receive care at referral centers, data about the stage of TTTS at initial presentation (ie, to nonreferral centers) are lacking in the literature. Fetal therapy centers report that about 11-15% of their cases at referral were Quintero stage I (probably underestimated as some referral centers did not report stage I TTTS cases), 20-40% were stage II, 38-60% were stage III, 6-7% were stage IV, and 2% were stage V. Although TTTS may develop at any time in gestation, the majority of cases are diagnosed in the second trimester. Stage I may progress to a nonvisualized fetal bladder in the donor (stage II) ( Figure 2 ), and absent or reversed end-diastolic flow in the umbilical artery of donor or recipient twins may subsequently develop (stage III) ( Figure 3 ), followed by hydrops (stage IV). However, TTTS often does not progress in a predictable manner. Natural history data by stage are limited, especially for stages II-V, as staging was initially proposed in 1999. This is because most natural history data were published before 1999, and therefore was not stratified by stage ( Table 2 ). Over three fourths of stage I TTTS cases remain stable or regress without invasive interventions ( Table 2 ). The natural history of advanced (eg, stage ≥III) TTTS is bleak, with a reported perinatal loss rate of 70-100%, particularly when it presents <26 weeks. It is estimated that TTTS accounts for up to 17% of the total perinatal mortality in twins, and for about half of all perinatal deaths in MCDA twins. Without treatment, the loss of at least 1 fetus is common, with demise of the remaining twin occurring in about 10% of cases of twin demise, and neurologic handicap affecting 10-30% of cotwin remaining survivors. Overall, single twin survival rates in TTTS vary widely between 15-70%, depending on the gestational age at diagnosis and severity of disease. The lack of a predictable natural history, and therefore the uncertain prognosis for TTTS, pose a significant challenge to the clinician caring for MCDA twins.



TABLE 2

Natural history of stage I twin-twin transfusion syndrome














Stage Incidence of progression to higher stage Incidence of resolution, regression to lower stage, or stability Overall survival
I 6/39 (15%) 33/39 (85%) 102/118 (86%)

SMFM. Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013.




Question 2. How often does TTTS complicate monochorionic twins and what is its natural history? (Levels II and III)


Approximately one-third of twins are monozygotic (MZ), and three-fourths of MZ twins are MCDA. In general, only twin gestations with MCDA placentation are at significant risk for TTTS, which complicates about 8-10% of MCDA pregnancies. TTTS is very uncommon in MZ twins with dichorionic or monoamniotic placentation. Although most twins conceived with in vitro fertilization (IVF) are dichorionic, it is important to remember that there is a 2- to 12-fold increase in MZ twinning in embryos conceived with IVF, and TTTS can therefore occur for IVF MCDA pregnancies. In current practice, the prevalence of TTTS is approximately 1-3 per 10,000 births.


The presentation of TTTS is highly variable. Because pregnancies with TTTS often receive care at referral centers, data about the stage of TTTS at initial presentation (ie, to nonreferral centers) are lacking in the literature. Fetal therapy centers report that about 11-15% of their cases at referral were Quintero stage I (probably underestimated as some referral centers did not report stage I TTTS cases), 20-40% were stage II, 38-60% were stage III, 6-7% were stage IV, and 2% were stage V. Although TTTS may develop at any time in gestation, the majority of cases are diagnosed in the second trimester. Stage I may progress to a nonvisualized fetal bladder in the donor (stage II) ( Figure 2 ), and absent or reversed end-diastolic flow in the umbilical artery of donor or recipient twins may subsequently develop (stage III) ( Figure 3 ), followed by hydrops (stage IV). However, TTTS often does not progress in a predictable manner. Natural history data by stage are limited, especially for stages II-V, as staging was initially proposed in 1999. This is because most natural history data were published before 1999, and therefore was not stratified by stage ( Table 2 ). Over three fourths of stage I TTTS cases remain stable or regress without invasive interventions ( Table 2 ). The natural history of advanced (eg, stage ≥III) TTTS is bleak, with a reported perinatal loss rate of 70-100%, particularly when it presents <26 weeks. It is estimated that TTTS accounts for up to 17% of the total perinatal mortality in twins, and for about half of all perinatal deaths in MCDA twins. Without treatment, the loss of at least 1 fetus is common, with demise of the remaining twin occurring in about 10% of cases of twin demise, and neurologic handicap affecting 10-30% of cotwin remaining survivors. Overall, single twin survival rates in TTTS vary widely between 15-70%, depending on the gestational age at diagnosis and severity of disease. The lack of a predictable natural history, and therefore the uncertain prognosis for TTTS, pose a significant challenge to the clinician caring for MCDA twins.



TABLE 2

Natural history of stage I twin-twin transfusion syndrome














Stage Incidence of progression to higher stage Incidence of resolution, regression to lower stage, or stability Overall survival
I 6/39 (15%) 33/39 (85%) 102/118 (86%)

SMFM. Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013.




Question 3. What is the underlying pathophysiology of TTTS? (Levels II and III)


The primary etiologic problem underlying TTTS is thought to lie within the architecture of the placenta, as intertwin vascular connections within the placenta are critical for the development of TTTS. Virtually all MCDA placentas have anastomoses that link the circulations of the twins, yet not all MCDA twins develop TTTS. There are 3 main types of anastomoses in monochorionic placentas: venovenous (VV), arterioarterial (AA), and arteriovenous (AV). AV anastomoses are found in 90-95% of MCDA placentas, AA in 85-90%, and VV in 15-20%. Both AA and VV anastomoses are direct superficial connections on the surface of the placenta with the potential for bidirectional flow ( Figure 4 ). In AV anastomoses, while the vessels themselves are on the surface of the placenta, the actual anastomotic connections occur in a cotyledon, deep within the placenta ( Figure 4 ). AV anastomoses can result in unidirectional flow from one twin to the other, and if uncompensated, may lead to an imbalance of volume between the twins. Unlike AA and VV, which are direct vessel-to-vessel connections, AV connections are linked through large capillary beds deep within the cotyledon. AV anastomoses are usually multiple and overall balanced in both directions so that TTTS does not occur. While the number of AV anastomoses from donor to recipient may be important, their size as well as placental resistance likely influences the volume of intertwin transfusion that occurs. Placentas in twins affected with TTTS are reportedly more likely to have VV, but less likely to have AA anastomoses. It is thought that these bidirectional anastomoses may compensate for the unidirectional flow through AV connections, thereby preventing the development of TTTS or decreasing its severity when it does occur. Mortality is highest in the absence of AA and lowest when these anastomoses are present (42% vs 15%). However, the presence of AA is not completely protective, as about 25-30% of TTTS cases may also have these anastomoses. The imbalance of blood flow through the placental anastomoses leads to volume depletion in the donor twin, with oliguria and oligohydramnios, and to volume overload in the recipient twin, with polyuria and polyhydramnios.




FIGURE 4


Selected anastomoses in monochorionic placentas

Courtesy of Vickie Feldstein, University of California, San Francisco.

a-a, arterioarterial anastomosis; a-v, arteriovenous anastomosis; v-a, venous-arterial anastomosis.

SMFM. Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013.


There also appear to be additional factors beyond placental morphology, such as complex interactions of the renin-angiotensin system in the twins, involved in the development of this disorder.




Question 4. How should monochorionic twin pregnancies be monitored for the development of TTTS? (Levels II and III)


All women with a twin pregnancy should be offered an ultrasound examination at 10-13 weeks of gestation to assess viability, chorionicity, crown-rump length, and nuchal translucency. TTTS usually presents in the second trimester, and is a dynamic condition that can remain stable throughout gestation, occasionally regress spontaneously, progress slowly over a number of weeks, or develop quickly within a period of days with rapid deterioration in the well-being of the twins. There have been no randomized trials of the optimal frequency of ultrasound surveillance of MCDA pregnancies to detect TTTS. Although twin pregnancies are often followed up with sonography every 4 weeks, sonography as often as every 2 weeks has been proposed for monitoring of MCDA twins for the development of TTTS. This is in part because, while stage I TTTS has been observed to remain stable or resolve in most cases, when progression does occur it can happen quickly. However, studies that have focused on progression of early-stage TTTS may not be applicable to the question of disease development in apparently unaffected pregnancies.


Given the risk of progression from stage I or II to more advanced stages, and that TTTS usually presents in the second trimester, serial sonographic evaluations about every 2 weeks, beginning usually around 16 weeks of gestation, until delivery, should be considered for all twins with MCDA placentation, until more data are available allowing better risk stratification ( Figure 5 ). Sonographic surveillance less often than every 2 weeks has been associated with a higher incidences of late-stage diagnosis of TTTS. This underscores the importance of establishing chorionicity in twin pregnancies as early as possible. These serial sonographic evaluations to screen for TTTS should include at least MVP of each sac, and the presence of the bladder in each fetus. Umbilical artery Doppler flow assessment, especially if there is discordance in fluid or growth, is not unreasonable, but data on the utility of this added screening parameter are limited. There is no evidence that monitoring for TAPS with MCA PSV Doppler at any time, including >26 weeks, improves outcomes, so that this additional screening cannot be recommended at this time.




FIGURE 5


Algorithm for screening for TTTS

MCDA, monochorionic diamniotic; MVP, maximum vertical pocket; NT, nuchal translucency; TTTS, twin-twin transfusion syndrome.

SMFM. Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013.


In addition to monitoring MCDA pregnancies for development of amniotic fluid abnormalities, there are several second- and even first-trimester sonographic findings that have been associated with TTTS. These findings are listed in Table 3 . Before 14 weeks, MCDA twins can be evaluated with nuchal translucency and crown-lump length. Nuchal translucency abnormalities and crown-lump length discrepancy have been associated with an increased risk of TTTS. If such findings ( Table 3 ) are encountered, it may be reasonable to perform more frequent surveillance (eg, weekly instead of every 2 weeks) for TTTS. Velamentous placental cord insertion ( Figure 6 ) has been found in approximately one third of placentas with TTTS. Intertwin membrane folding ( Figure 7 ) has been associated with development of TTTS in more than a third of cases. The clinical utility of the sonographic findings listed in Table 3 has not been prospectively evaluated, and several require Doppler evaluation not typically performed in otherwise uncomplicated MCDA gestations. Thus, while they are associated with TTTS and may potentially improve TTTS detection, they are not specifically recommended as part of routine surveillance.



TABLE 3

First- and second-trimester sonographic findings associated with twin-twin transfusion syndrome





















First-trimester findings
Crown-rump length discordance
Nuchal translucency >95th percentile or discordance >20% between twins
Reversal or absence of ductus venosus A-wave
Second-trimester findings
Abdominal circumference discordance
Membrane folding
Velamentous placental cord insertion (donor twin)
Placental echogenicity (donor portion hyperechoic)

SMFM. Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013.



FIGURE 6


Abnormal placental cord insertion

A , Velamentous or membranous placental cord insertion (PCI) ( arrow ) of monochorionic diamniotic twin detected by color Doppler. B , Velamentous PCI confirmed on examination of placenta with identification of anastomosis ( arrows ) passing beneath separating membrane and joining circulations of twins.

SMFM. Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013.

Reproduced with permission from Simpson.



FIGURE 7


Membrane folding

Membrane folding ( arrow ) suggestive of discordant amniotic fluid volume in monochorionic diamniotic twin gestation.

SMFM. Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013.

Reproduced with permission from Simpson.


In addition to TTTS, MCDA gestations are at risk for discordant twin growth or discordant IUGR. When compared to MCDA twins with concordant growth, velamentous placental cord insertion (22% vs 8%, P < .001) and unequal placental sharing (56% vs 19%, P < .0001) are seen more commonly in cases with discordant growth. Unequal placental sharing occurs in about 20% of MCDA gestations and can coexist with TTTS, complicating the diagnosis and management of the pregnancy. For example, abnormal umbilical artery waveforms in MCDA twins may represent placental insufficiency, but may also be secondary to the presence of intertwin anastomoses and changes in vascular reactivity typical of TTTS ( Figure 3 ). Overall, the development of abnormal end-diastolic flow in the umbilical artery, especially absent or reversed, has been associated with later deterioration of fetal testing necessitating delivery in MCDA twins, but latency between Doppler and other fetal testing changes is increased in these gestations compared to singletons. Frequent, eg, twice weekly, fetal surveillance is suggested for MCDA pregnancies with abnormal umbilical artery Doppler once viability is reached.




Question 5. Is there a role for fetal echocardiography in TTTS? (Levels II and III)


Screening for congenital heart disease with fetal echocardiography is warranted in all monochorionic twins as the risk of cardiac anomalies is increased 9-fold in MCDA twins and up to 14-fold in cases of TTTS, above the population prevalence of approximately 0.5%. Specifically, the prevalence of congenital cardiac anomalies has been reported to be 2% in otherwise uncomplicated MCDA gestations and 5% in cases of TTTS, particularly among recipient twins. Although many cases are minor septal defects, an increase in right ventricular outflow tract obstruction has also been reported. It is theorized that the abnormal placentation that occurs in monochorionic twins, particularly in cases that develop TTTS, contributes to abnormal fetal heart formation.


The functional cardiac abnormalities that complicate TTTS occur primarily in recipient twins. Volume overload causes increased pulmonary and aortic velocities, cardiomegaly, and atrioventricular valve regurgitation ( Figure 8 ). Over time, recipient twins can develop progressive biventricular hypertrophy and diastolic dysfunction as well as poor right ventricular systolic function that can lead to functional right ventricular outflow tract obstruction and pulmonic stenosis ( Figure 9 ). The development of right ventricular outflow obstruction, observed in close to 10% of all recipient twins, is likely multifactorial, a consequence of increased preload, afterload, and circulating factors such as renin, angiotensin, endothelin, and atrial and brain natriuretic peptides. The cardiovascular response to TTTS contributes to the poor outcome of recipient twins while recipients with normal cardiac function have improved survival.




FIGURE 8


Cardiac dysfunction in recipient twin

Color flow imaging demonstrating forward flow across atrioventricular valves in diastole and severe tricuspid regurgitation ( arrow ) during systole in recipient twin.

SMFM. Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013.

Reproduced with permission from Simpson.



FIGURE 9


Recipient twin cardiomyopathy

SMFM. Twin-twin transfusion syndrome. Am J Obstet Gynecol 2013.

Reproduced with permission from Simpson.


A functional assessment of the fetal heart may be useful in identifying cases that would benefit from therapy and in evaluating the response to treatment. The myocardial performance index or Tei index, an index of global ventricular performance by Doppler velocimetry, is a measure of both systolic and diastolic function, and has been used to monitor fetuses with TTTS. Donor twins with TTTS tend to have normal cardiac function, whereas recipient twins may develop ventricular hypertrophy (61%), atrioventricular valve regurgitation (21%), and abnormal right ventricular (50%) or left ventricular (58%) function. Overall, two thirds of recipient twins show diastolic dysfunction, as indicated by a prolonged ventricular isovolumetric relaxation time, which is associated with an increased risk of fetal death.


Although fetal cardiac findings are not officially part of the TTTS staging system, many centers routinely perform fetal echocardiography in cases of TTTS and have observed worsening cardiac function in advanced stages. However, cardiac dysfunction can also be detected in up to 10% of apparently early-stage TTTS. It has been theorized that the early diagnosis of recipient twin cardiomyopathy may identify those MCDA gestations that would benefit from early intervention. In summary, scoring systems that include cardiac dysfunction have been developed, but their usefulness to predict outcome in TTTS remains controversial. Further evaluation of functional fetal echocardiography as a tool for decision-making about intervention and management in TTTS is needed.




Question 6. What management options are available for TTTS? (Levels I, II, and III)


The management options described for TTTS include expectant management, amnioreduction, intentional septostomy of the intervening membrane, fetoscopic laser photocoagulation of placental anastomoses, and selective reduction. The interventions that have been evaluated in randomized controlled trials (RCTs) include intentional septostomy of the intervening membrane to equalize the fluid in both sacs, amnioreduction of the excess fluid in the recipient’s sac, and laser ablation of placental anastomoses. There have been 3 randomized trials designed to evaluate some of the different treatment modalities for TTTS, all of which were terminated prior to recruitment of the planned subject number after interim analyses, as discussed below. Despite the limitations and early termination of these clinical trials, they represent the best available data upon which to judge the various treatments for TTTS. Consultation with a maternal-fetal medicine specialist is recommended, particularly if the patient is at a gestational age at which laser therapy is potentially an option. In evaluating the data, considerations include the stage of TTTS, the details of the intervention, and the perinatal outcome. The most important outcomes reported are overall perinatal mortality, survival of at least 1 twin, and, if available, long-term outcomes of the babies, including neurologic outcome. Extensive counseling should be provided to patients with pregnancies complicated by TTTS, including natural history of the disease, as well as management options and their risks and benefits.


Expectant management involves no intervention. This natural history of TTTS, also called conservative management, has limited outcome data according to stage, particularly for advanced disease ( Table 2 ). It is important that the limitations in the available data are discussed with the patient with TTTS, and compared with available outcome data for interventions.


Amnioreduction involves the removal of amniotic fluid from the polyhydramniotic sac of the recipient. It is usually done only when the MVP is >8 cm, with an aim to correct it to a MVP of <8 cm, often to <5 cm or <6 cm. Usually an 18- or 20 -gauge needle is used. Some practitioners use aspiration with syringes, while some use vacuum containers. Amnioreduction can be performed either as a 1-time procedure, as at times this can resolve stage I or II TTTS, or serially, eg, every time the MVP is >8 cm. It can be performed any time >14 weeks. Amnioreduction is hypothesized to reduce the intraamniotic and placental intravascular pressures, potentially facilitating placental blood flow, and/or to possibly reduce the incidence of preterm labor and birth related to polyhydramnios. Amnioreduction may be used also >26 weeks, particularly in cases with maternal respiratory distress or preterm contractions from polyhydramnios. Amnioreduction has been associated with average survival rates of 50%, with large registries reporting 60-65% overall survival. However, serial amnioreduction is often necessary, and repeated procedures increase the likelihood of complications such as preterm premature rupture of the membranes, preterm labor, abruption, infection, and fetal death. Another consideration is that any invasive procedure prior to fetoscopy may decrease the feasibility and success of laser due to bleeding, chorioamnion separation, inadvertent septostomy, or membrane rupture.


Septostomy involves intentionally puncturing with a needle the amniotic membranes between the 2 MCDA sacs, theoretically allowing equilibration of amniotic fluid volume in the 2 sacs. In the 1 randomized trial in which it was evaluated, the intertwin membrane was purposefully perforated under ultrasound guidance with a single puncture using a 22-gauge needle. This was usually introduced through the donor’s twin gestational sac into the recipient twin’s amniotic cavity. If reaccumulation of amniotic fluid in the donor twin sac was not seen in about 48 hours, a repeat septostomy was undertaken. Intentional septostomy is mentioned only to note that it has generally been abandoned as a treatment for TTTS. It is believed to offer no significant therapeutic advantage, and may lead to disruption of the membrane and a functional monoamniotic situation. A randomized trial of amnioreduction vs septostomy ended after an interim analysis found that the rate of survival of at least 1 twin was similar between the 2 groups, and that recruitment had been slower than anticipated ( Table 4 ). In all, 97% of the enrolled pregnancies had stages I-III TTTS, and results were not otherwise reported by stage. In 40% of the septostomy cases, additional procedures were needed. No data on neurologic outcome are available.


May 13, 2017 | Posted by in GYNECOLOGY | Comments Off on Twin-twin transfusion syndrome

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