Twin-Twin Transfusion Syndrome

Other Names

• Twin-twin transfusion syndrome
• twin to twin transfusion syndrome, TTTS
• polyhydramnios-oligohydramnios sequence

Signs and Symptoms

In monochorionic twins, even though there is one single placenta, it is, in fact, functionally divided into two portions that support each twin separately. Mechanisms that maintain this functional separation are not yet fully understood. In approximately 10 to 15% of monochorionic diamniotic twins (a twin pregnancy with one placenta and two separate amniotic sacs), this functional separation fails to develop properly resulting in an imbalanced distribution of blood between the two fetuses and is called Twin-to-Twin Transfusion Syndrome (TTTS).

Diagnosis

TTTS is caused by the imbalanced blood distribution in the shared placenta. The fetus that receives the most blood is called the RECIPIENT and the one that gets the smaller amount of blood is called the DONOR. Both conditions may be detrimental to fetal wellbeing. This imbalance can initially manifest as oligohydramnios, where the amount of the amniotic fluid is less than expected (Maximum Vertical Pocket [MVP] measured on ultrasound < 2cm) in the donor’s sac and/or polyhydramnios, where the amount of the amniotic fluid is more than expected (MVP > 8 cm if gestational age <20 weeks or MVP >10 cm if gestational age > 20 weeks) in the recipient’s sac. Later in the course of the pregnancy, underperfusion of the kidneys in the donor results in an inability to visualize the urinary bladder. If the disease progresses further, the cardiovascular system starts failing in the recipient as documented by abnormal Doppler findings. Before fetal demise occurs, worsening cardiovascular compromise may result in hydrops in the recipient twin. Eventually fetal demise ensues in either or both twins if the imbalance is not corrected. Quintero et al ^[1] developed a clinical staging system for TTTS which has been confirmed to correlate with the severity and the outcome of the disease. (Table)

• Absent end diastolic flow or reverse end diastolic flow in umbilical artery; abnormal blood flow in ductus venosus.

Treatment

When left untreated, advanced stage TTTS diagnosed before 24 weeks of gestation almost universally ends with perinatal mortality of one or both fetuses. Serial amnioreduction or septostomy had been the only two therapeutic approaches available to treat this disorder until the early 1990’s when the first placental laser ablation procedure (selective laser photocoagulation - S-LPC) was reported.^[2] Currently, the options for managing TTTS include expectant medical management, amnioreduction, septostomy, laser ablation or selective fetacide techniques such as umbilical cord occlusion. In some cases the treatment aim is to enable one twin to survive if the chances for both surviving are extremely poor. Some women may choose to terminate the pregnancy completely because of the high risk of perinatal morbidity and mortality in both twins.

Expectant management is only appropriate in a few mild cases because of the high perinatal mortality and morbidity when TTTS is left untreated. Amnioreduction is a well-established procedure which aims to reduce amniotic fluid volume in the recipient polyhydramiotic twin and to prevent extremely preterm delivery. It does not treat the underlying pathophysiological cause (i.e. abnormal communications between vessels in the shared placenta) nor allow the amniotic fluid volume to normalize around the donor twin.

Selective Laser Photocoagulation (S-LPC) Since the first laser ablation procedure was performed, multiple studies have compared serial amnioreduction with laser ablation of the communicating placental vessels. The multinational-multicenter EUROFETUS^[3] trial was the first well designed randomized study comparing pregnancy outcomes among those treated with laser ablation versus serial amnioreduction. In this study procedure related complications were similar between the laser and amnioreduction groups. When compared to serial amnioreduction, S-LPC provided significant survival advantage.

Outcome

Survival In a systematic review^[4] overall perinatal survival ranged from 61% to 70% ^{[5] [6]} with at least one twin survival rates ranging from 61% - 83% ^{[7] [8]}. Randomized controlled trial included in the review found that compared with the amnioreduction group, those treated with laser had a greater likelihood of at least one twin surviving to 28 days (76% vs. 56% p=0.002). This difference was also maintained to 6 months of age (p=0.01) ^[9]. Similar results were also reported in two non-randomized trials.

Neurological impairment The incidence of neurological morbidity range from 1.2% to 7.6% ^[10] among fetuses born alive. Long term follow up studies reported major neurological abnormalities in 6% and 11% of twins treated with laser and followed up to a median post-natal follow-up of 22 and 38 months respectively.^[11] Studies comparing laser and amnioreduction found that neurological morbidity was reduced following laser compared with amnioreduction.^[12]

Safety The evidence on safety is based on a review of two trials (one randomized, one non-randomized) and two case series. The most common maternal complication following laser surgery was premature rupture of the membranes. In one of the case series evaluating perioperative complications following laser ablation, premature rupture of the membranes occurred in 28% of women, with 43% occurring within 3 weeks of the procedure. ^[13] Placental abruption and pregnancy losses (miscarriage) were also reported, occurring in 2% and 7% of women respectively.^[14] In the randomized controlled trial, premature rupture of the membranes within 28 days of the procedure occurred equally (9%) in the two groups (laser ablation vs. amnioreduction).^[15] Placental abruption occurred in one woman in the laser group 1% (1/69) and two women in the amnioreduction group 3% (2/68).^[16] Pregnancy loss within seven days after the procedure was reported in 17% (12/69) of women in the laser group and 4% (3/68) in the amnioreduction group (p = 0.1). Other complications reported in the studies included amniotic fluid leakage and vaginal bleeding. Only one study (n=101) reported recurrence of TTTS (14%) following the procedure.^[17]

Notable Experts

Organizations

North American Fetal Therapy Network

EuroFetus

US Fetus

References

1. QUINTERO RA, MORALES WJ, ALLEN MH, BORNICK PW, JOHNSON PK, KRUGER M. Staging of twin-twin transfusion syndrome. Journal of Perinatology 1999;19:550-5.

2. DE LIA JE, CRUIKSHANK DP, KEYE WR, JR. Fetoscopic neodymium:YAG laser occlusion of placental vessels in severe twin-twin transfusion syndrome. Obstetrics & Gynecology 1990;75:1046-53.

3. SENAT M-V, DEPREST J, BOULVAIN M, PAUPE A, WINER N, VILLE Y. Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome.[see comment]. New England Journal of Medicine 2004;351:136-44.

4. ROBYR R, QUARELLO E, VILLE Y. Management of fetofetal transfusion syndrome. Prenatal Diagnosis 2005;25:786-95.

5. QUINTERO RA, COMAS C, BORNICK PW, ALLEN MH, KRUGER M. Selective versus non-selective laser photocoagulation of placental vessels in twin-to-twin transfusion syndrome. Ultrasound in Obstetrics & Gynecology 2000;16:230-6.

6. HUBER A, HECHER K. How can we diagnose and manage twin-twin transfusion syndrome? Best Practice & Research in Clinical Obstetrics & Gynaecology 2004;18:543-56.

7. GRAEF C, ELLENRIEDER B, HECHER K, HACKELOER BJ, HUBER A, BARTMANN P. Long-term neurodevelopmental outcome of 167 children after intrauterine laser treatment for severe twin-twin transfusion syndrome. American Journal of Obstetrics & Gynecology 2006;194:303-8.

8. BANEK CS, HECHER K, HACKELOER BJ, BARTMANN P. Long-term neurodevelopmental outcome after intrauterine laser treatment for severe twin-twin transfusion syndrome.[see comment]. American Journal of Obstetrics & Gynecology 2003;188:876-80.

9. QUINTERO RA, DICKINSON JE, MORALES WJ, et al. Stage-based treatment of twin-twin transfusion syndrome. American Journal of Obstetrics & Gynecology 2003;188:1333-40.

10. HECHER K, PLATH H, BREGENZER T, HANSMANN M, HACKELOER BJ. Endoscopic laser surgery versus serial amniocenteses in the treatment of severe twin-twin transfusion syndrome. American Journal of Obstetrics & Gynecology 1999;180:717-24.

11. YAMAMOTO M, EL MURR L, ROBYR R, LELEU F, TAKAHASHI Y, VILLE Y. Incidence and impact of perioperative complications in 175 fetoscopy-guided laser coagulations of chorionic plate anastomoses in fetofetal transfusion syndrome before 26 weeks of gestation. American Journal of Obstetrics & Gynecology 2005;193:1110-6.

12. ROBYR R, LEWI L, SALOMON LJ, et al. Prevalence and management of late fetal complications following successful selective laser coagulation of chorionic plate anastomoses in twin-to-twin transfusion syndrome. American Journal of Obstetrics & G