Twin-twin transfusion syndrome

Diagnosis/definition: The diagnosis of TTTS requires 2 criteria: (1) the presence of a monochorionic diamniotic (MCDA) pregnancy; and (2) the presence of oligohydramnios (defined as a maximal vertical pocket < 2cm) in one sac and polyhydramnios (defined as a maximal vertical pocket >8 cm) in the other sac. The Quintero staging system (Table 1) appears to be a useful tool for describing the severity of TTTS in a standardized fashion.

Epidemiology/Incidence: TTTS complicates about 8-10% of MCDA pregnancies. The prevalence of TTTS is approximately 1-3 per 10,000 births.

Pathophysiology: The primary etiology of TTTS is thought to involve intertwin vascular connections within the placenta (Figure 4). An imbalance of blood flow through placental anastemoses leads to volume depletion in the donor twin, with oliguria and oligohydramnios, and to volume overload in the recipient twin, with polyuria and polyhydramnios. Complex interactions of the renin-angiotensin system in the twins also appear to be involved in the development of this disorder.

Risk factors/associations: There are several second- and even first-trimester sonographic findings that have been associated with TTTS (Table 3).

Complications: The presentation of TTTS is highly variable and often does not progress in a predictable manner. Single twin survival rates in TTTS vary widely between 15-70%, depending on gestational age at diagnosis and severity of disease. 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. Scoring systems that include cardiac dysfunction have been developed, but their usefulness to predict outcome in TTTS remains controversial. 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. Even laser-treated TTTS is associated with a perinatal mortality rate of 30-50% (Table 7), and a 5-20% chance of long-term neurologic handicap (Table 8). 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.

Management: (Figure 10)
Screening/Work-up: 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. Serial sonographic evaluation should be considered for all twins with MCDA placentation, beginning at around 16 weeks and continuing about every 2 weeks until delivery (Figure 5).  Screening for congenital heart disease is warranted in all monochorionic twins, in particular those complicated by TTTS.
Counseling: 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.
Stage I: 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 be managed expectantly. Stages I and II TTTS have been shown to regress following amnioreduction in up to 20-30% of cases, a rate that is not significantly different than with expectant management, especially for stage I.  
Stages II, III, IV:

• Fetoscopic laser photocoagulation of placental anastemoses is considered by most experts to be the best available approach for states II, III, and IV TTTS in continuing pregnancies at < 26 weeks, but the meta-analysis data show no significant survival benefit, and the long-term neurologic outcomes in the Eurofetus trial were not different than in nonlaser-treated controls. Survival rates of 50-70% can be expected after fetoscopic laser for the treatment of TTTS (Table 7).
• Expectant management and amnioreduction remain 2 options in cases if TTTS > stage I at <26 weeks of gestation in which the patient does not have the ability to travel to a center that performs fetoscopic laser photocoagulation.
• In cases complicated by severe unequal placental sharing with marked discordant growth and IUGR, major malformation affecting 1 twin, or evidence of brain injury either before or subsequent to laser, selective reduction by cord occlusion or by termination of the entire pregnancy may be reasonable management choices for the patient and her family < 24 weeks’ gestation.

Stage V: In cases of death of 1 MCDA twin, the risks to the cotwin include a 10% risk of death and 10-30% risk of neurologic complications. No intervention has been evaluated in randomized trials to try to ameliorate outcome.
Antepartum: 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.

Delivery: Optimal timing of delivery for TTTS pregnancies depends on several factors, including disease stage and severity, progression, effect of interventions (if any), and results of antenatal testing. Timing of delivery at around 34-36 weeks may be reasonable in selected cases.    

Last Reaffirmed: Aug 1, 2017