Twin-Twin Transfusion Syndrome

William J. Polzin
Basics
Description
TTTS is a disease of reproductive-age women that affects monochorionic twin
pregnancies.
Affects 1020% of monochorionic twin pregnancies.

It is most commonly identified when polyhydramnios is seen in 1 twin's sac

and oligohydramnios is seen in the other twin's sac.

It can have an indolent course that becomes evident in the 3rd trimester and
requires no intervention except delivery close to term.

It can also arise in the early 2nd trimester and progress so rapidly that hydrops
and death of 1 or both twins occurs in a matter of weeks despite all treatment
attempts.

If present in the 2nd trimester and no treatment is rendered, the natural history
is such that mortality rates for both twins approximate 90%.

Staging
The Quintero staging system provides a useful shorthand for discussing the
disease:
o Stage I: Polyhydramnios/Oligohydramnios

Stage II: Urine not visible in the donor twin's bladder

Stage III: Abnormal Doppler velocimetry

Stage IV: Ascites or hydrops present in either twin

Stage V: Death of either or both twins

Modified staging system that stratifies Stage III is more descriptive of disease
severity:
o

Critical Doppler abnormalities (AEDF or REDF in UA, reverse flow in

DV, pulsatile UV)

Mild to moderate cardiomyopathy*

Severe cardiomyopathy*

Epidemiology
~1 in 100 pregnancies are twin gestations.
The prevalence of monochorionic twins is 1/400 pregnancies.

1020% of monochorionic twins develop TTTS.

80% of monochorionic twins have arteriovenous connections visible on the

placental surface:

These facts highlight the unknown etiology of TTTS

Pathophysiology
Unidirectional arteriovenous connections of placental circulations
Inadequate bidirectional compensation:

Hypervolemic, hypertensive cardiomyopathy in the larger (recipient)

twin

Hypovolemic, hypotensive circulatory pattern in the smaller (donor)

twin

Donor findings may be consistent with uteroplacental insufficiency:

o

Significant size differences can be seen

Abnormal umbilical artery and venous Doppler velocimetry

Recipient findings may be consistent with plethoric, hypervolemic state in

recipient:
o

Abnormal venous Doppler velocimetry in the ductus venosus

Cardiomyopathy

Neurodevelopmental injury in ~22% of survivors:

o

About equal distribution of injury in recipients and donors

Better long-term outcome if born as surviving twins rather than a

singleton survivor after a co-twin has died.

Associated Conditions
PPROM due to hydramnios
Preterm labor and delivery

IUGR in donor

Hemorrhagic or thrombotic brain lesions occurring antenatally

Cardiomyopathy in recipient

Hydrops fetalis in recipient

Death of 1 twin with 1550% morbidity or mortality in co-twin

>90% mortality of both twins, if TTTS is untreated

Diagnosis
Signs and Symptoms
Rapid change in FH
Premature contractions

Sudden onset of pelvic pressure

Shortness of breath

History
Known monochorionic twin gestation
Physical Exam
FH > dates
Rapid interval growth in FH
Tests
Labs

For diagnosis of hydramnios:

o TORCH titers in mother
o

Amniotic fluid culture and PCR evaluation

Thyroid function testing

Fetal karyotype

Imaging
Weekly US evaluation of AF volume beginning at 16 weeks
Monthly US evaluation of fetal size and changes in anatomy

Monthly Doppler velocimetry evaluation of umbilical artery

Differential Diagnosis
TTTS is readily identified, if it is anticipated and suspected in monochorionic twin
pregnancies. A number of other conditions should be considered and ruled out using
readily available US and laboratory testing.
Alert
Rule out premature labor. PROM and severe uteroplacental insufficiency can cause
oligohydramnios. Previously identified congenital anomalies such as TE fistulas can
cause hydramnios (see Hydramnios).
Infection
TORCH titers in mother
AF culture and PCR evaluation
Hematologic
Isoimmunization
Metabolic/Endocrine
Thyroid conditions in mother
Pregestational or gestational diabetes
Immunologic
SLE
Tumor/Malignancy
Placental or umbilical cord tumors
Trauma
Placental abruption
Drugs
Illicit drug use

Other/Miscellaneous
Congenital fetal anatomic abnormalities
Genetic syndromes

Karyotype abnormalities

Treatment
Pregnancy-Specific Issues
Bed rest is recommended:
Helps with discomfort of hydramnios
May be adjunct to treating PTL

May promote better circulation to the placenta of the smaller twin

P.431
Medication (Drugs)
Tocolytics for premature labor
Indomethacin to reduce degree of hydramnios:
o

Special caution to identify cardiovascular side-effects and discontinue

Surgery
Amnioreduction:
o May work effectively in up to 20% of cases

Survival of 1 or both twins approximates 60%; better than untreated

Little risk to mother

Chorioamnionic separation takes option of laser therapy off the table

Abruption or rupture of membranes may lead to pregnancy loss

Microseptostomy:
o

Has been used primarily

Has been used adjunctively

Often an unintentional result of amniocentesis

Laser photocoagulation of unidirectional arteriovenous anastomoses:

o

Bidirectional arterioarterial anastomoses may be protective

Performed through operating fetoscope

Selective treatment of 1-way anastomoses whether direct or via

cotyledons

Survival of 1 or both twins approximates 90%

Reduced survival with advancing stage of disease

Treatment risk borne more heavily by mother

Fewer abnormal head US findings (6% vs. 18% in amnioreduction)

No difference in long-term neurologic morbidity compared to

amnioreduction

Bipolar or radiofrequency ablation of a previable, dying twin's cord can be

protective of the surviving co-twin.

Followup
Disposition
Home bed rest is usually sufficient.
Evaluate response to therapy at least once a week.

Delivery usually occurs by 32 weeks' gestation.

Route of delivery determined by usual obstetric indications

Issues for Referral

Regional centers may offer more comprehensive evaluations and detect subtle
cardiovascular changes that may upstage the disease and change
recommendations for initiating or continuing treatment regimens.
Important to refer to an experienced treatment center if not available at the
primary care site:
o

Regional sites are available to evaluate, especially if laser is requested

by the patient or required due to failure of amnioreduction.

Detecting early cardiovascular changes requires an experienced fetal

echocardiographer.

Prognosis
Prognosis is poor (<10% survival) if disease occurs at a previable GA and is
untreated.
Prognosis with early-stage disease and aggressive treatment can improve
survival significantly.

Overall survival of 1 or both twins approximates 90% when treated

aggressively.

Patient Monitoring
Mother
Observe for PTL.
Fetus
The surviving neonates should be followed closely by physicians experienced in
detecting subtle variations from normal development. Early and aggressive
interventions can help mitigate the effects of injury from TTTS.
Bibliography

Banek CS, et al. Long-term neurodevelopmental outcome after intrauterine laser

treatment for severe twin-twin transfusion syndrome. Am J Obstet Gynecol.
2003;188:876880.
Harkness UF, et al. Twin-twin transfusion syndrome: Where do we go from here?
Semin Perinatol. 2005;29:296304.
Hecher K, et al. Endoscopic laser surgery versus serial amniocenteses in the treatment
of severe twin-twin transfusion syndrome. Am J Obstet Gynecol. 1999;180:717724.
Huber A, et al. Stage-related outcome in twin-twin transfusion syndrome treated by
fetoscopic laser coagulation. Obstet Gynecol. 2006;108:333337.
Quintero RA, et al. Staging of twin-twin transfusion syndrome. J Perinatol.
1999;19:550555.
Miscellaneous
Synonym(s)
Polyhydramnios/Oligohydramnios syndrome
Abbreviations
AEDFAbsent end diastolic flow
AFAmniotic fluid
AVAtrial ventricular
DVDuctus venosus
FHFundal height
IUGRIntrauterine growth restriction
PCRPolymerase chain reaction
PPROMPreterm premature rupture of membranes
PTLPreterm labor
REDFReverse end diastolic flow
SLESystemic lupus erythematosus
TORCHToxoplasmosis, other, rubella, CMV, HSV
TTTSTwin-twin transfusion syndrome
UAUmbilical artery
UVUmbilical vein
Codes
ICD9-CM
651.03 Twin pregnancy, antepartum
663.83 Other umbilical cord complications, antepartum
Patient Teaching
Instruct patient to report the following:
Rapid change in FH
Premature contractions
Sudden onset of pelvic pressure
Shortness of breath