Twin-twin transfusion syndrome

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.

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 FIGURE 2, FIGURE 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.^, 

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Laser involves photocoagulating the vascular anastomoses crossing from one side of the placenta to the other. This is usually performed by placing a sheath and passing an endoscope under ultrasound guidance. Ultrasound is also used to map the vasculature to determine the placental angioarchitecture. The primary theoretical advantage of laser coagulation is that it is designed to interrupt the placental anastomoses that give rise to TTTS. The goal of laser ablation is to functionally separate the placenta into 2 regions, each supplying one of the twins. This unlinking of the circulations of the twins is often referred to as “dichorionization” of the monochorionic placenta. Adequate visualization of the vascular equator that separates the cotyledons of one twin from the other is critical for laser photocoagulation. Selective coagulation of AV as well as AA and VV anastomoses is preferred over nonselective ablation of all vessels crossing the separating membrane as it appears to lead to fewer procedure-related fetal losses. Sequential coagulation of the donor artery to recipient vein followed by recipient artery to donor vein may theoretically allow some return of fluid from the recipient to the donor prior to severing other connections.^,  Criteria for laser have included MCDA pregnancies between about 15-26 weeks with the recipient twin having MVP ≥8.0 cm at ≤20 weeks or ≥10.0 cm at >20 weeks and a distended fetal bladder, and donor twin having MVP ≤2.0 cm in 1 trial, and MCDA pregnancies at <24 weeks with the recipient twin having MVP >8 cm, and donor twin having MVP ≤2 cm and nonvisualized fetal bladder in the other. There is insufficient evidence to recommend management in MCDA pairs with TTTS in higher-order multiple gestations, but laser has been proposed as feasible and effective.

Selective reduction involves purposefully interrupting umbilical cord blood flow of 1 twin, causing the death of this twin, with the purpose of improving the outcome of the other surviving twin. Usually the cord occlusion is performed with radiofrequency ablation or cord coagulation, but other procedures have been employed. Obviously this option can be associated with a maximum of 50% overall survival, so, if ever considered, it is usually reserved for stages III or IV TTTS only.

In general, overall survival rates of 50-70% can be expected after fetoscopic laser for the treatment of TTTS. Overall perinatal survival of fetuses with TTTS treated with laser was 56% in the Eurofetus trial at 6 months of age, and 45% in the NICHD trial at 30 days (TABLE 5, TABLE 6, respectively). The Eurofetus trial reported an 86% survival rate of at least 1 fetus for combined stage I and II disease treated with laser, decreasing to 66% for combined stage III and IV. In recent nonrandomized large series, summarizing >1000 cases of TTTS (about 86% with stages II and III) treated with laser, the overall perinatal survival was about 65% (Table 7). Given publication bias, these data probably represent the best current possible outcomes with this procedure.

Although the risk of membrane rupture may be as low as 10% in experienced centers, there remains a 10-30% procedure-associated fetal loss with laser.^{,  ,  ,}  Both double and single fetal demise are common complications in advanced stages of TTTS treated with laser (Table 7). In a multicenter observational study, fetal demise occurred in 24% of donors and in 17% of recipients after laser. Survival of 1 or 2 fetuses after laser may depend on coexisting unequal placental sharing that may not be visible before or even at the time of fetoscopy. Preoperative IUGR with absent or reversed end-diastolic flow in the umbilical artery has a 20-40% increased risk of postoperative donor demise.^,  Recipient twin demise after laser is more common when the recipient has IUGR, reversed a-wave in the ductus venosus, or hydrops. Improved recipient twin survival has been reported with the maternal administration of nifedipine 24-48 hours prior to laser photocoagulation in cases of TTTS cardiomyopathy, but more data are needed to suggest its use in this clinical situation. After successful laser photocoagulation, the cardiac function of recipient twins tends to normalize in about 4 weeks. Pulmonic valve abnormalities, affecting about 20% of recipient twins with advanced TTTS, have also been observed to improve after laser with less than a third of surviving twins having persistent pulmonic valve defects requiring treatment after birth. Overall, 87% of postlaser recipient twins who survived were reported to have normal echocardiograms at a median age just under 2 years.

Although procedure-related fetal loss is a recognized complication of fetoscopic laser photocoagulation, survival with neurologic handicap is also a serious long-term sequela of TTTS, with or without treatment. While the gestational age at delivery is a significant risk factor for adverse neurologic outcome, initial studies suggested that neurologic outcomes may be better for those cases managed with laser photocoagulation, compared to amnioreduction. Infants in the laser group of the Eurofetus trial had a lower incidence of cystic periventricular leukomalacia and were more likely to be free of neurologic complications at 6 months of age compared to those treated with amnioreduction (Table 6). However, 6-year follow-up of 120 children from this trial found that laser therapy conferred no significant benefit in terms of difference in major neurologic handicap among TTTS survivors treated with laser vs amnioreduction. Another recent study also reported no difference in neurodevelopmental outcome at 2 years of age among donors and recipients treated with laser or amnioreduction, although they did observe a trend of increased major neurologic impairment in survivors after amnioreduction compared to those treated with laser (9.5% vs 4.6%).

Overall, rates of long-term neurologic sequelae in laser-treated stage I TTTS are reported to be about ≤3%, with rates of about 5-20% in survivors of any stage TTTS (Table 8).^{,  ,  ,  ,}  The risk of abnormal neurodevelopment seems to be similar in donor and recipient survivors, and not drastically different between those treated with laser or amnioreduction. Antenatally acquired severe brain lesions, including cystic periventricular leukomalacia and grade-3 or -4 intraventricular hemorrhage, affect 10% of TTTS compared to 2% of MCDA twins without TTTS (P = .02); this difference was seen to persist in findings seen on cranial ultrasounds at the time of hospital discharge (14% vs 6%, P = .04). Other risk factors for neurodevelopmental impairment in TTTS survivors are advanced gestational age at laser surgery, low birth weight, and severe TTTS. Both ultrasound and magnetic resonance imaging (MRI) can be used to evaluate abnormalities of the fetal brain. In general, fetal MRI to evaluate cortical development and assess for ischemic injury is best in the third trimester. Following single twin demise in a MCDA gestation, neurologic injury, when present in the surviving twin, may be detected by ultrasound in about 1-2 weeks, and by MRI as early as 1-2 days after the demise of the other twin.^,  Routine neuroimaging with MRI cannot yet be recommended given the limited data on benefit, although this has been suggested by some authors for TTTS both prior to and after therapeutic interventions, or in cases complicated by single twin demise.^{,  ,  ,}  Follow-up studies of all survivors of TTTS are critical to determine accurate long-term outcomes and stage-specific rates of neurologic handicap of these complicated MCDA pregnancies.

In summary, even with the laser treatment option available, TTTS is still a severe condition in terms of perinatal outcomes. Given the 30-50% chance of overall perinatal death and 5-20% chance of neurologic handicap long-term, twin death or neurologic handicap is the outcome in up to two thirds of laser-treated TTTS.

There are no randomized trials to evaluate the effectiveness of antenatal monitoring for pregnancies complicated by TTTS. Weekly monitoring of the umbilical artery Doppler flow and MVP of amniotic fluid of each fetus may be considered. The evidence for effectiveness of serial (eg, weekly or twice/wk) nonstress tests, biophysical profiles, and other antenatal testing modalities is insufficient to make a recommendation, but these tests can be considered.

One reason for surveillance, even following laser therapy, is that not all anastomoses are ablated at the time of laser.^,  Residual anastomoses, either initially undetected, missed, or revascularized after laser, have been observed in up to a third of cases.^,  Placental casting has also demonstrated the presence of deep, atypical AV anastomoses beneath the chorionic plate that would not be visible by fetoscopy. Failure to coagulate all AV anastomoses can lead to persistent, recurrent or reversed TTTS. Persistent or recurrent TTTS has been reported in 14% of cases postlaser and reversed TTTS, with the recipient becoming anemic and the donor polycythemic, in 13% of cases.^,  While TAPS can occur spontaneously in a MCDA gestation, it is a known iatrogenic complication of laser.