Twin-to-Twin Transfusion Syndrome 

Updated: Apr 02, 2020
Author: Lisa E Moore, MD, MS, FACOG, RDMS; Chief Editor: Ronald M Ramus, MD 


Practice Essentials

Twin-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twinning. If TTTS is left untreated, mortality is 80-100% in severe cases.[1] Fetoscopic laser photocoagulation (FLP) of placental anastomoses is the standard treatment of TTTS. (See the image below.)

A monochorionic placenta with the vasculature of t A monochorionic placenta with the vasculature of twin A in blue/red and that of twin B in green/yellow. This placenta is shown after laser ablation of shared vessels. Close examination reveals the line of photocoagulation using the Solomon technique. Courtesy of Anthony Johnson, DO.

Signs and symptoms

Fundal height larger than dates is a common finding because of the production of excess amniotic fluid by the recipient twin.

See Presentation for more detail.


Chorionicity is best determined prior to 14 weeks' gestation. From 16 weeks until delivery, monochorionic twin pregnancies should be screened for TTTS every 2 weeks.

TTTS is defined as polyhydramnios (single deepest pocket [SDP] >8 cm) in one twin and oligohydramnios (SDP < 2 cm ) in the co-twin.

The Quintero system is used to stage twin-twin transfusion[2, 3] :

  • Stage I: Polyhydramnios (deepest pocket >8 cm)/oligohydramnios (deepest pocket < 2 cm )
  • Stage II: Donor bladder not visualized
  • Stage III: Doppler abnormalities
  • Stage IV: Hydrops in either twin
  • Stage V: Death of one or both twin

See Workup for more detail.


Patients with TTTS before 26 weeks' gestation should be referred to a center for fetal intervention for FLP.

Serial amnioreduction may have a role in TTTS identified too late for fetoscopic laser treatment. Septostomy has no role in the treatment of TTTS. 

The demise of one twin places the surviving twin at risk for death (15%) and significant neurologic morbidity (26%); however, once the death of one twin is identifed, immediate delivery of the surviving twin has not been shown to improve outcomes.

See Treatment for more detail.


Twin-twin transfusion syndrome (TTTS) is a serious complication of monozygotic monochorionic twinning in which shared placental blood vessels allow shunting of blood away from one twin (the donor) to the co-twin (the recipient).

Monozygotic twinning occurs when a single fertilized egg divides to form 2 embryos. The timing of the division determines the degree of differentiation between the 2 embryos. The earlier the split occurs, the greater the differentiation. Twins that split between days 0 and 3 have 2 amnions and 2 placentas (diamniotic dichorionic). Between days 4 and 7 the twins will share a placenta but will have separate amniotic sacs (diamniotic monochorionic). (See the images below.) Between days 7 and 13 the twins will share both a placenta and an amniotic sac (monoamniotic monochorionic), and after day 13 the twins will be conjoined.


The 2 separate amniotic sacs of diamniotic twins a The 2 separate amniotic sacs of diamniotic twins are prominent in this image.


This image of diamniotic monochorionic twins shows This image of diamniotic monochorionic twins shows the dividing membrane and a single placenta.


When twins share a placenta, there will always be vascular anastomoses between the circulations of the twins. When the anastomoses are unbalanced, with preferential shunting from one twin to the other, TTTS is the result. The donor twin is usually smaller and has oligohydramnios due to decreased urine production, whereas the recipient is larger with polyhydramnios due to polyuria. 

Left untreated, TTTS has high morbidity and mortality.


Monochorionic placentas have anastomotic vascular connections between the twins. These anastomoses can be artery to artery (AA), vein to vein (VV), or artery to vein (AV).

AA and VV anastomoses are on the surface of the placenta and usually have bidirectional flow. AV anastomoses are typically within the placenta and are at least partially responsible for unbalanced transfer of fluid volume to the recipient twin because they only allow flow in one direction. AA anastomoses are believed to compensate for AV anastomoses.[1, 4]  Placental dye injection studies show that monochorionic placentas in pregnancies that develop TTTS have fewer AA anastomoses.[5]

Over time, the unbalanced transfer of fluid volume has significant but different effects on both twins. As the donor twin becomes hypovolemic, decreased renal perfusion causes decreased urine output and oligohydramnios. The renin-angiotensin system is activated to increase reabsorption in the renal tubules, and angiotensin-2 causes vasoconstriction in an attempt to maintain circulating volume in the donor twin.

Vasoconstriction leads to uteroplacental insufficiency and intrauterine growth restriction (IUGR) of the donor twin. Blood flow is redistributed to protect the brain, and vasoconstriction results in abnormal umbilical artery Doppler studies. The donor may develop hydrops because of severe anemia.

The recipient twin experiences an increase in circulating volume, which causes synthesis of atrial natriuretic peptide. Glomerular filtration is increased, and reabsorption from the renal tubules decreases. Urine production is increased, which results in polyhydramnios. Hydrops may occur because of volume overload and high output failure.

The cardiovascular system of the recipient twin experiences changes in overall function and in preload and afterload. In Quintero stages I and II TTTS, left ventricular filling pressures are increased with decreased systolic function. In stages III and IV TTTS, right ventricular filling pressures become elevated. This finding demonstrates that the heart of the recipient twin is affected even in the early stages of the disease.[6, 7]  

Twin anemia polycythemia sequence (TAPS) is a variant of TTTS. TAPS differs from TTTS in that polyhydramnios and oligohydramnios do not occur. TAPS may occur spontaneously (3-6%) or as a side effect of incomplete ablation of an anastomosis during laser photocoagulation (16%). Use of the Solomon technique reduces the postablation rate to 3%.[8]  

TAPS is the result of chronic, slow, unidirectional transfusion of blood from one twin to the other via a few small (< 1 mm in diameter) anastomoses. One fetus becomes anemic and the other polycythemic, but no difference in the amount of amniotic fluid occurs. In contrast to TAPS, the flow in TTTS is bidirectional though unbalanced and the anastomoses are larger.

TAPS is generally unrecognized because no recommendation exists to screen for TAPS in monochorionic diamniotic pregnancies. Screening is done by evaluating the peak systolic velocity (PSV) in the middle cerebral artery (MCA). Criteria for diagnosis are based on the difference between twins (the delta) in the MCA-PSV.[9]  The table below lists the stages of TAPS.

Table 1. Stages of Twin Anemia Polycythemia Sequence (TAPS) (Open Table in a new window)

Stage 1

Delta MCA-PSV >0.5 MOM; no signs of fetal compromise

Stage 2

Delta MCA-PSV >0.7 MOM; no signs of fetal compromise

Stage 3

Stage 1 or 2 with hydrops of the donor

Stage 4

Hydrops of the donor

Stage 5

Death of one or both twins preceded by TAPS

MCA-PSV = middle cerebral artery peak systolic velocity; MOM = multiples of the median.

Intervention is recommended for stage 2 and higher TAPS, with intrauterine transfusion or laser photocoagulation.





United States data

Monozygotic twins occur in 3-5 per 1000 pregnancies. Approximately 75% of monozygotic twins are monochorionic. TTTS occurs in 10-15% of monochorionic twins.[10, 11]




Untreated severe TTTS (stage 3 or higher) has a 60-100% fetal or neonatal mortality rate. Mild to moderate TTTS (stage 2) is frequently associated with premature delivery. Fetal demise of one twin is associated with neurologic sequelae in 25% of surviving twins. Fetal blood pressure instability can lead to brain ischemia in either the donor or the recipient twin. Periventricular leukomalacia, porencephaly, microcephaly, and cerebral palsy have all been identified in survivors of TTTS.[1, 12]

Survival of at least one twin approaches 75% with treatment by fetoscopic laser photocoagulation (FLP).[13]

In a review of 135 monochorionic twin pregnancies with single intrauterine death (sIUD), whether spontaneous or procedure related, O'Donoghue et al found that death of the co-twin followed in 22.9% of cases.[14] In the pregnancies that continued after sIUD, the frequency of antenatally acquired brain injury in the co-twin was significantly lower after procedure-related than spontaneous sIUD: 2.6% versus 22.2% (P = .003). The investigators concluded that the risk of brain injury is reduced but not negated by procedures that restrict inter-twin transfusion. 

The risk of prematurity continues after FLP treatment and is as high as 50% for birth before 34 weeks. The risk of preterm premature rupture of the membranes (PPROM) before 34 weeks ranges between 20% and 30%.[15]


Heart disease

Heart disease is a major cause of death in TTTS, representing 50% of the fetal deaths that occur in the postnatal period. If TTTS is treated with amnioreduction rather than fetoscopic laser photocoagulation (FLP), the risk of heart failure in the recipient twin is 2.7-fold higher.[16]  This increased risk is due to the fact that FLP corrects the underlying placental pathology whereas amnioreduction does not. Among patients who survive after undergoing FLP, up to 85-87% will have a normal cardiac evaluation.[17]

When patients are treated with FLP, cardiac function usually normalizes by about 15 months of age. However, these patients are at higher risk for long-term cardiac pathology than the general population. The recipient twin has a 4.46% increased risk of pulmonary stenosis compared with the general population. The risk of atrial septal defects is also higher than in the general population, most likely because of pressure differences that result from volume overload.[18]

Neurologic sequelae

Neurologic abnormalities related to TTTS include periventricular leukomalacia and intraventricular hemorrhage. During childhood, neurologic sequelae include mental retardation, language delay, strabismus, and cerebral palsy.[17, 19]  It is theorized that placental abnormalities such as arteriovenous malformations lead to hemodynamic disturbances. These disturbances disrupt normal blood flow and may lead to hemorrhagic brain lesions and ischemia.[12, 20]  Other complications associated with TTTS result from low birth weight and prematurity. 

After FLP, the rate of significant neurologic impairment is 10% at 2 years of age. A higher Quintero stage and a lower gestational age at birth are associated with worse cognitive performance.[10, 17]







The following clinical features raise suspicion for twin-twin transfusion syndrome (TTTS):

  • Known monochorionic-diamniotic gestation
  • Known or suspected difference in fetal weights
  • Known or suspected difference in the amount of amniotic fluid in each amniotic sac
  • Rapidly expanding abdomen as fluid accumulates in the sac of the recipient twin

Physical Examination

Fundal height larger than dates is a common finding because of the production of excess amniotic fluid by the recipient twin.



Diagnostic Considerations

The diagnosis of twin-twin transfusion is made by ultrasound. In a known monochorionic-diamniotic pregnancy, the finding of polyhydramnios of one twin with a single deepest pocket >8 cm and oligohydramnios in the co-twin with a single deepest pocket < 2 cm is diagnostic.

Growth failure may also be noted in the twin with oligohydramnios, but this finding is not part of the diagnostic criteria.

Differential Diagnoses

  • Fetal Growth Restriction

  • Premature Rupture of Membranes

  • Rupture of the amniotic sac of one twin

    Rupture of the amniotic sac of one twin can present a picture of oligohydramnios or even "stuck twin" appearance. A careful history is important to rule out an event that might have been an unrecognized rupture of the membranes. If questions remain, testing for membrane rupture should be performed.

  • Selective fetal growth restriction

    Selective fetal growth restriction occurs in monochorionic pregnancies in which unequal division of the placenta between the twins results in suboptimal growth in the twin with the lesser share of the placenta. About 10% of monochorionic pregnancies are affected. The growth-restricted twin may develop abnormalities on Doppler studies.



Approach Considerations

Chorionicity is best identified by ultrasound before 14 weeks' gestation. Monochorionic twin gestations should be screened for twin-twin transfusion syndrome (TTTS) every 2 weeks starting at 16 weeks and continuing until delivery. Screening consists of determination of the single deepest pocket of amniotic fluid in each sac and visualization of the fetal bladders.

Growth scans should concomitantly be performed every 3-4 weeks to detect growth failure.

Middle cerebral artery–peak systolic velocity (MCA-PSV) screening for twin anemia polycythemia syndrome (TAPS) is not recommended except after fetoscopic laser photocoagulation (FLP).


Laboratory Studies

There are no laboratory studies to diagnose or to rule out TTTS. Routine prenatal laboratory studies are recommended.

Imaging Studies


Amniotic fluid measurement

In twin pregnancies, the maximum vertical amniotic fluid pocket in each sac is measured rather than the 4-quadrant amniotic fluid index (AFI).

The diagnosis of TTTS is based on the finding of oligohydramnios, usually defined as a deepest vertical pocket of < 2 cm, and polyhydramnios, which is usually defined as a deepest vertical pocket of >8 cm. Some experts use gestational age-based criteria for defining polyhydramnios (≥6 cm at 15-17 weeks, ≥8 cm at 18-20 weeks, and >10 cm at ≥20 weeks)

Bladder visualization

The bladders of both twins should be visualized at each ultrasound visit. Absence of visualization of the bladder of the donor twin is characteristic of stage 2 TTTS. 


Hydrops fetalis is a condition that consists of ascites, pleural or pericardial effusions, and skin edema. Because of volume overload and heart failure, the recipient twin is most likely to develop hydrops. (See the image below.) The donor twin may develop hydrops in cases of severe anemia.

A recipient twin with hydrops at 22 weeks' gestati A recipient twin with hydrops at 22 weeks' gestation. Fluid surrounds the heart and lungs, and the skin is thickened.

Growth restriction

Growth restriction occurs in about 50% of donor twins. Fetal growth restriction or intrauterine growth restriction (IUGR) is defined as an estimated fetal weight of < 10% of normal or an abdominal circumference (AC) of < 5% of normal in the setting of otherwise normal fetal growth.

Fetal echocardiography

TTTS commonly leads to right heart anomalies. Fetal circulation depends primarily on the right heart. Pulmonary stenosis is a common right ventricular anomaly and has been identified most frequently in the recipient twin. In one study, prior to FLP, the recipient twin demonstrated typical signs of volume overload in utero, which led to cardiac dysfunction in 55% of cases.[1]  

Peak systolic velocity of the middle cerebral artery

Middle cerebral artery–peak systolic flow velocity (MCA-PSV) may be obtained to rule out twin anemia polycythemia sequence (TAPS). An inter-twin difference (delta) in MCA-PSV greater than 0.5 multiples of median is diagnostic of TAPS. Screening for TAPS is currently not recommended by the Society for Maternal-Fetal Medicine except after FLP.[21]

Other Tests

The risk of aneuploidy in monochorionic twin gestations is not higher than the risk associated with a singleton gestation at the same maternal age.



The most useful staging system for TTTS was developed by Quintero[2, 3] :

Table 2. Twin-Twin Transfusion Syndrome (TTTS) Staging System (Open Table in a new window)




Absent Urine in Donor Bladder

Abnormal Doppler Blood Flows

Hydrops Fetalis

Fetal Demise































Histologic Findings

Gross evaluation of the placenta after delivery will confirm monochorionic placentation. Dye injection studies of the placenta may help to show the extent of anastomoses.



Approach Considerations

Fetoscopic laser photocoagulation

Fetoscopic laser photocoagulation (FLP) of anastomotic vessels is considered the gold standard of treatment for twin-twin transfusion syndrome (TTTS). First described in 1990, this procedure is performed in specialized centers across the United States and in Europe.   

Abnormal vessels are mapped by following them from origin to termination. A vessel that originates with one fetus, inserts into a cotyledon, and then travels to the other fetus is considered pathologic and is photocoagulated. Vessels that exit the cord as an artery, enter a cotyledon, and return to the same fetus as a vein are not pathologic and are not treated. This procedure is called selective photocoagulation.[22]

An additional modification of the procedure is sequential selective photocoagulation, in which pathologic vessels are ablated in the following order of the type of connections:

  • Donor artery–recipient vein
  • Recipient artery–donor vein
  • Artery-artery
  • Vein-vein

Theoretically, the sequential selective technique reduces hypotension in the donor twin.[23, 24]

The Solomon technique creates a dichorionic placenta by photocoagulating the surface of the placenta from one edge to the other edge in a straight line. (See the image below.) This procedure is done after selective photocoagulation and has been shown to decrease the rate of recurrent TTTS.[10]


A monochorionic placenta with the vasculature of t A monochorionic placenta with the vasculature of twin A in blue/red and that of twin B in green/yellow. This placenta is shown after laser ablation of shared vessels. Close examination reveals the line of photocoagulation using the Solomon technique. Courtesy of Anthony Johnson, DO.


Referral to a specialized center for laser treatment is recommended once the diagnosis is made. Patients between 16 and 26 weeks' gestation are considered candidates for the procedure, although several studies report successful outcomes at later gestations.

Fetal complications of FLP

Fetal complications of FLP include the following[15, 10, 5] :

  • Preterm  premature rupture of membranes (10%); 3-6% within 7 days and 7-9% within 28 days; as high as 30% in some studies.
  • Persistent TTTS (7% reduced to 1% using the Solomon technique).
  • Twin anemia polycythemia sequence (16% reduced to 3% using the Solomon technique).
  • Preterm delivery (50% prior to 34 weeks).
  • Demise of one twin (13-33%).
  • Demise of both twins (22%); studies report survival of at least one twin in 75-88% of cases.
  • Severe long-term neurologic impairment (3-18%).

Maternal complications of FLP

Maternal complications of FLP include the following[25] :

  • Placental abruption: Separation of the placenta from the uterine wall.
  • Amniotic fluid embolism: A serious complication that occurs when fetal cells and other material enter the maternal circulation and cause a severe anaphylactic reaction.
  • Mirror syndrome: A rare life-threatening condition in which the mother develops hypertension and edema that "mirrors" edema in the placenta or the fetus.

Other complications include chorioamnionitis, abdominal pain, and development of pulmonary edema.[10]

Serial amnioreduction

The goal of serial amnioreduction is to reduce hydrostatic pressure on the smaller twin. An ultrasound-guided amniocentesis is performed on the sac of the recipient twin, and as much fluid as possible is removed. Before the use of laser photocoagulation, this procedure was the treatment of choice for TTTS.

The Eurofetus trial enrolled women from 6 countries in a randomized comparison of serial amnioreduction versus laser surgery.[16] The study was discontinued early because a planned interim analysis showed significant benefit in the laser group. 

There may still be a role for serial amnioreduction, particularly in late gestation, to alleviate maternal discomfort, or in cases after 26 weeks, when elective delivery may be considered safer than laser surgery on the placenta.


Septostomy is the deliberate creation of a hole in the dividing membrane. This allows equilibration of hydrostatic pressure and relieves the compression on the placenta of the donor twin.  Effectively, a monoamniotic pregnancy is iatrogenically created. A limitation of the procedure is that it does not address the underlying problem of the unbalanced transfer of fluid volume. Cord entanglement is the major complication. Septostomy is no longer recommended as a treatment for TTTS.[1]

Selective cord occlusion

In monochorionic twins, when one twin dies, the remaining twin may exsanguinate to the dead twin. In cases of TTTS in which the death of one twin is considered imminent and unavoidable, cord occlusion interrupts blood flow to the distressed twin and laser ablation of anastomoses prevents exsanguination of the survivor.

A meta-analysis showed survival was improved in the remaining twin if cord occlusion was performed after 18 weeks. The survival rate among the remaining twins was 79%. No significant difference was found between the death of the donor and the death of the recipient.[26]

Expectant management

Controversy exists regarding the treatment of stage 1 TTTS. Many cases identified at stage 1 either do not progress or regress.  Treatment by laser photocoagulation is recommended for stage 2 TTTS or higher. Consideration can be given to expectant management in stage 1.



A specialist in maternal-fetal medicine should confirm the diagnosis of monochorionic twinning and initiate follow-up every 2 weeks for TTTS screening. The perinatologist will typically make referrals to an interventionist if needed.

Fetal interventionist

If TTTS is diagnosed, referral should be made to a center for fetal intervention for laser photocoagulation.


Referral to a neonatologist is recommended for neonatal care after delivery.


Recommendations for multiple gestations are extrapolated from singleton gestations. With a twin gestation, it is estimated that 40% more calories are needed than in a singleton gestation, which would mean an additional 476-632 Kcal/day in the second and third trimesters. One recommendation for macronutrients is 20% protein, 40% carbohydrates, and 40% fat.[27]

Twins have a 2- to 4-fold increase in iron deficiency anemia and an 8-fold increase in folate deficiency. Micronutrient recommendations include iron and folate supplementation.


Physical activity during pregnancy is encouraged. Regular physical activity helps control weight gain, is beneficial in managing diabetes, and has been shown to enhance well-being during pregnancy.

Multiple gestations and twins affected by TTTS have not been specifically studied; however, it is known that a twin gestation is associated with anatomic and physiologic changes that should be considered when choosing an exercise regimen. 

During pregnancy, a shift in the center of gravity due to the pregnant abdomen and increased pressure on the spine and joints result in low back pain. The ability to tolerate aerobic exercise is impaired because of a decrease in pulmonary reserve and the increased work load of the weight of the pregnancy.[28]

A multiple gestation at risk for premature labor is an absolute contraindication to aerobic exercise during pregnancy.

Intrauterine growth restriction is a relative contraindication to aerobic exercise, indicating that the decision to exercise should be weighed on a case-by-case basis.