Twin-Twin Transfusion Syndrome

What is twin-twin transfusion syndrome (TTTS)?

The different types of twins or higher multiples are classified depending on the number of placentas and the number of sacs present. In the case of twins, the different types include: 2 placentas and 2 sacs (dichorionic-diamniotic), 1 placenta and 2 sacs (monochorionic-diamniotic), or 1 placenta and 1 sac (monochorionic-monoamniotic, also called “mono-mono.” All monochorionic fetuses derive from the splitting of a common fertilized egg (zygote). Dichorionic fetuses may derive from the fertilization of separate eggs, or from very early splitting of a zygote.

The placenta of all monochorionic pregnancies contains blood vessels that allow blood exchange between the fetuses. Ordinarily, the blood exchange between the fetuses via these placental vessels is balanced, such that the same amount volume of blood given off or received by any fetus is the same. However, in approximately 5-15% of cases, the blood exchange between the fetuses is uneven. This results in a donor fetus (one that gives off more blood) and a recipient fetus (one that receives more blood and sends less blood back to the donor fetus). In the case of higher multiples (triplets, quadruplets) sharing the same placenta, one or more donor or recipient fetuses may exist. The condition, where two or more fetuses exchange blood unevenly through placental vessels is called Twin-Twin Transfusion Syndrome (TTTS) or Feto-Fetal Transfusion Syndrome (FFTS).

What is the effect of TTTS on each fetus?

The response of each fetus to the unbalanced blood exchange is different. The recipient fetus increases its urinary production, which results in increased amniotic fluid volume, but may also cause signs of volume overload, overt heart failure, or death of this fetus. On the other hand, the donor fetus, presumed to be hypotensive, decreases its urinary production and thus its amniotic fluid volume. It may also develop anemia, growth restriction, abnormal blood flow studies, or ultimately die from the condition.

What is the effect of TTTS on the mother?

The excessive accumulation of fluid (polyhydramnios) in the sac of the recipient fetus may produce a marked distension of the uterus that may result in shortening of the cervix, uterine contractions, premature rupture of membranes and miscarriage or premature delivery. Rarely, if one of the fetuses develops hydrops, the mother may also show signs of accumulation of fluid (so-called “Mirror” or Ballantyne syndrome). Ballantyne syndrome is an extremely serious maternal complication that requires interruption of the pregnancy, regardless of the gestational age at which the diagnosis is made.

How is TTTS diagnosed?

TTTS is diagnosed with ultrasound by noting a significant difference in the amniotic fluid volume between the sacs of two monochorionic-diamniotic twins. By convention, for the definition of TTTS, the deepest pocket of amniotic fluid in the sac of the recipient twin should be equal to or greater than 8 cm, independent of the gestational age, and the deepest pocket of fluid in the donor twin should be 2 cm of less. This is the so-called >8<2 motto="" p="">

In the case of monochorionic-monoamniotic twins (one placenta, one sac), TTTS is suspected if the deepest vertical pocket of the common sac is > 8cm, particularly if other ultrasound signs (abnormal blood flow studies, non-visible bladder in one twin, etc) are present. TTTS may also affect triplet or higher order multiples. If all fetuses share a common placenta, more than one donor or more than one recipient may be exist. If TTTS occurs in a triplet pregnancy (or higher order) that includes 2 or more fetuses sharing the same placenta and 1 or more fetuses with separate placentas, only the fetuses sharing the common placenta will show the ultrasound features of TTTS, while the fetus(es) with their own placenta will not.

How is a common placenta diagnosed with ultrasound?

Essential to the diagnosis of TTTS is the presence of a single, common placenta between the fetuses involved. On ultrasound, a thin dividing membrane that makes the shape of a “T” when it reaches the placenta is indicative of the presence of a single, common placenta. If on the other hand, the dividing membrane makes the shape of a “Y” when it reaches the placenta, this is indicative of the presence of 2 placentas abutting (yuxtaposed) against each other. The ultrasound identification of a “Y” shaped membrane has been dubbed “The Twin-Peak Sign.” Therefore, a single, common placenta is one where a twin-peak sign does not exist.

Staging of TTTS.

Quintero and collaborators proposed a classification of TTTS to categorize the different degrees of severity that can occur in TTTS:

Quintero TTTS Staging System

Stage I: The fetal bladder of the donor twin remains visible on ultrasound.

Stage II: The bladder of the donor twin is not visible on ultrasound.

Stage III: Doppler studies in either twin are critically abnormal fetal. These include: absent or reverse end-diastolic velocity (AREDV) in the umbilical artery, absent or reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein.

Stage IV: Fetal hydrops is noted. Stage V: Demise of one or both twins.

What is the course of a pregnancy diagnosed with TTTS?

The course of a pregnancy with TTTS is unpredictable. However, untreated, most pregnancies are lost from one or two mechanisms: either one or both fetuses die, or the mother miscarries or delivers prematurely from the adverse effects of the polyhydramnios of the recipient twin.

Can TTTS be treated antenatally?

The underlying mechanism for the development of TTTS can be halted altogether by identifying and occluding with laser energy the placental vessels responsible for the uneven blood exchange between the fetuses. This surgery is called generically “Laser Surgery” or “Laser Therapy” for TTTS. The surgery is done by inserting a thin medical telescope (endoscope) through the mother’s abdomen and uterus into the sac of the recipient twin. Once inside the amniotic cavity of the recipient twin, the surgeon proceeds to identify each and every one of the communicating vessels, following which, they are occluded with laser energy. The surgical technique that occludes only the culprit vessels is called “The Selective” technique (“Selective Laser Photocoagulation of Communicating Vessels, or SLPCV), described by Quintero and collaborators. This is in contrast to previous techniques in which the communicating vessels and other vessels that did not partake in the development of the syndrome, were occluded, based on their location along the dividing membrane (non-selective technique). At the end of the procedure, the excess amniotic fluid is removed from the sac of the recipient twin. In experienced hands, SLPCV is associated with survival or one or both twins in more than 90% of cases, and survival of both twins in approximately 75% of cases. Neurological damage of TTTS pregnancies treated with SLPCV is approximately 4-5%, compared to 11-18% of other laser techniques. Similarly, the rate of communicating vessels that are shown to be patent on placental examination after birth is <5% with SLPCV, whereas it is 19-33% with other techiques.

What other management options are there for patients with TTTS?

Standard counseling of patients with TTTS includes discussion of other management alternatives, including:

Expectant Management. In this option, the pregnancy is followed with serial ultrasound examinations. In some cases, the condition may regress. However, in most cases, either the pregnancy is lost or the babies are delivered at an extremely premature age.
Amnioreduction. In this option, a needle is inserted in the amniotic cavity of the recipient twin under ultrasound guidance to drain the excess amniotic fluid present in this sac. Occasionally, a single amniocentesis may result in stabilization and non-progression of the syndrome. However, in most cases, either the polyhydramnios recurs, or the condition of the fetuses worsens and the pregnancy may be either lost or delivered prematurely. If the procedure is repeated, the term “serial amnioreduction” is used. Because with amnioreduction the underlying cause is not treated, the survival rate of this tecnique is less than with laser therapy and the rate of neurological complications (brain damage) is higher compared to laser therapy. This was shown in a decisive study conducted in Europe, where laser therapy was compared with amnioreduction in a group of patients randomly assigned to either treatment. Occasionally, an amnioreduction is performed in patients wishing to undergo laser therapy, but that are not stable enough to travel to a laser center because of significant polyhydramnios, shortened cervix, or threatened preterm labor (contemporizing amnioreduction).
Umbilical Cord Occlusion. In this option, the umbilical cord of one of the fetuses is occluded. The corresponding fetus dies and the other fetus continues the pregnancy. The fetus that dies remains inside the uterus for the duration of the pregnancy. This option has no advantage over laser therapy, since the likelihood of survival of the remaining fetus is also approximately >90% and the risk of brain damage is also approximately 5%. Therefore, we do not recommend occlusion of the umbilical cord for the treatment of TTTS, unless of one fetus is also affected by another condition (for example, a severe congenital anomaly).
Interruption of the Pregnancy. In countries and states where is legally permitted, patients may elect not to continue the pregnancy within the legal parameters allowed.

Other treatments of TTTS have been proposed, but are only of historical interest. These include the use of medications to assist the cardiac function of the recipient twin, or the purposeful disruption of the dividing membrane with a needle (so-called “septostomy” or “microseptostomy”). The latter procedure is particularly discouraged, because the passive transfer of fluid from one sac to the other through the defect created in the membrane does not allow subsequent proper assessment of the amniotic fluid volume in the donor twin. Thus, if the condition of the donor twin worsens, the presence of normal fluid in its sac will mask this. The small hole created originally with the needle can extend along the dividing membrane, allowing the fetuses to come in contact with each other. This can produce entanglement of the umbilical cords and death of one or both fetuses.

What can be expected after laser therapy for TTTS?

Successful completion of the laser therapy should result in complete resolution of the syndrome. The amniotic fluid volume of both fetuses normalizes and the abnormal Doppler studies, if present before the surgery, may also disappear. Hydrops also typically resolves. If the ultrasound signs of TTTS persist after surgery, this is due to communicating vessels that were either not occluded or were only partially occluded during the surgery. These cases are labeled as “persistent” TTTS. The condition may also show reversal of the roles, where the former donor becomes the new recipient with polyhydramnios, and the former recipient becomes the new donor with oligohydramnios. Such cases are labeled as “reverse” TTTS. The incidence of persistent or reverse TTTS after SLPCV is <1%.

The mean gestational age at the time of laser surgery for TTTS is approximately 20 weeks. The mean gestational age at delivery is approximately 34 weeks. Extremely premature delivery may occur is some cases, and in others, the pregnancy may be allowed to continue until term.

What is the difference between TTTS and selective intrauterine growth restriction?

Monochorionic twins may also show growth restriction of one of the fetuses. This condition is called “Selective Intrauterine Growth Restriction” or SIUGR. If both fetuses are growth restricted, the condition is called double growth restriction. SIUGR is defined as an estimated fetal weight (EFW) less than the 10th percentile for gestational age. In contrast, TTTS is defined as a difference of amniotic fluid volume deepest.