Treatment

Twin-Twin Transfusion Syndrome Treatment

Because twin-twin transfusion syndrome is a progressive disorder, early treatment may prevent complications, including preterm labor and premature rupture of membranes secondary to polyhydramnios. The most commonly used treatment is amnioreduction (serial large-volume amniocenteses), in which large volumes of amniotic fluid are drained with a needle placed through the abdomen of the mother into the sac of the recipient twin. This procedure may be repeated, if necessary. Survival rates with this treatment reach about 70%. Although it is not known exactly how amnioreduction improves the state of both twins, it is effective in many cases.

However, some cases of TTTS do not respond to amnioreduction, and will be lost if other methods are not tried. These cases are appropriately treated with a direct approach to try to stop transfusion in the abnormal arterio-venous connection. This can be achieved by introducing a thin fiber-optic scope through the mother's abdomen, through the wall of the uterus and into the amniotic cavity of the recipient. By examining the surface placental vessels directly, the abnormal vascular connections can be found and eliminated by directing a laser beam at them. The procedure should be as selective as possible, and detailed ultrasound examination prior to the procedure may help locate the causative abnormal connection, making it quicker and easier to locate with the fetoscope.
We have experience in fetoscopic examination of MC twin pregnancies, and are offering a variety of therapeutic procedures, including laser therapy for TTTS. The service relies for its success on close multidisciplinary collaboration between many experienced specialists. This work is a natural extension of many years of experience in treating malformed fetuses with surgical procedures months before they are born.

If not treated, severe Twin-Twin Transfusion Syndrome has a mortality rate close to 100%. 

Current treatment methods include:

• Serial Amniocentesis
• Amniotic Septostomy
• Umbilical Cord Ligation
• Laser photocoagulation of the communicating vessels
• Termination of the pregnancy.

What is it?

Twin ReversedArterial Perfusion (TRAP) sequence occurs only in monochorionic pregnancy. This condition occurs approximately 1% of monochorionic twin gestations and 1 in 35,000 births, overall. This disease is complicated by a normal developing twin and a twin that fails to develop a heart (acardiac twin) In the TRAP sequence, the acardiac twin receives all of its blood supply from the normal, or so-called "pump twin".

Serial Amniocentesis

In this procedure, extra fluid is removed from the amniotic sac of the Recipient (larger) twin with a needle. Repeated removal of fluid may be needed. Each time fluid is removed, 1 - 3 liters (quarts) may be obtained. How often fluid is withdrawn depends upon how severe the case. It may need to be done as often as every other day.

Pregnancies that develop signs of TTTS after 26 weeks gestation are usually managed by Serial Amniocentesis as the fetuses are at a viable age (able to live outside the womb). The success rate for this technique varies, but may be as high as 50 - 60 %.

The advantage of Serial Amniocentesis is that it may prevent pre-term labor and thereby extend the pregnancy for a few more weeks. Also, there are trained doctors at many centers throughout the country who may perform this procedure.

The main disadvantages of this approach are that it does not fix the basic problem (unequal sharing of blood), therefore making repeat removal of fluid necessary, each with its own risk of trauma, infection, or pregnancy loss. It may be related to a relatively high occurrence of cerebral palsy (up to 25%). Also, if one baby dies from the disease, the shared blood flow between the babies may allow for the second twin to bleed into the dead twin. This may cause brain or neurological damage (15 - 25%) or death (up to 40%). Serial amniocentesis may cause membranes to detach from the uterine wall. This would make any other form of therapy contraindicated.

Amniotic Septostomy

There are mixed feelings in the medical practice about performing an amniotic septostomy.

Report 1
Needling of the dividing membrane (fetal septostomy): This procedure consists of purposely disrupting the dividing membrane between the fetuses with a needle. This results in equalization of the fluid volumes between the sacs. From our point of view, this procedure is both ill founded and dangerous. We have recently published data showing that the amniotic fluid pressures are similar in both sacs, despite large differences in the fluid volumes. Artificial normalization of the fluid volumes with septostomy does not change the volume of blood each of the fetuses receives. Moreover, the disruption of the membranes may lead to death of the fetuses from cord entanglement. For these reasons we strongly advise against this procedure. Dr. Ruben Quintero

Report 2
Recently needle septostomy has been reported as a treatment for TTTS. While preliminary results are encouraging with 80% survival in one small series of 12 patients, no neurologic outcome has been available. In addition, the septostomy may expose both fetuses to the risks of cord entanglement.

Report 3

ABSTRACT December 1997

OBJECTIVE: To report our experience with intentional puncture of the intervening membrane ("septostomy") for the treatment of the twin oligohydramnios-polyhydramnios sequence (TOPS)

METHODS: 12 patients were diagnosed with TOPS based on ultrasonographic findings. A 20 to 22-gauge spinal needle was used to puncture the membrane between the twins without any attempt at amnioreduction in 9 patients, while the procedure was combined with amnioreductions in 3 patients

RESULTS: Gestational age was 23.1 +/- 3.3 weeks at the time of septostomy and 31.1 +/- 4.4 weeks at delivery. Rapid accumulation of fluid around the "stuck" fetus occurred in all cases following a single procedure. Three of the 24 fetuses died in utero and one died on the fifth day of life, for a combined survival of 83.3%. In the survivors, the septostomy to delivery interval ranged between 0.6 and 13 weeks (mean + SD: 8.3 +/- 4.8 weeks)

CONCLUSION: Amniotic septostomy is a promising new method for the management of TOPS and is associated with survival rates that are better than, or comparable to, more invasive modalities. A multicenter trial comparing septostomy to other modalities is warranted.

Extract from the report:

The finding of markedly increased amniotic fluid in the gestational sac of one twin and virtual absence of fluid in the other's is an ominous complication of monochorionic-diamniotic twin pregnancies. Because of the belief that this derangement is caused by placental vascular communications (chorioangiopagus) the condition has been referred to as twin-twin transfusion syndrome. Actual shunting of blood between the twins, however, has not been documented in all cases which have fulfilled the ultrasonographic criteria. For this reason, some investigators prefer to use descriptive terms such as the "stuck twin syndrome" or "twin oligohydramios-polyhydramnios sequence" (TOPS) to refer to this condition.

Due to differing diagnostic criteria and ascertainment bias, the estimated incidence of this syndrome in twin gestations has ranged widely between 1 - 26%. The data on perinatal mortality have also been affected by diagnostic inconsistencies and the general improvements in perinatal survival through the years. In the untreated condition, the mortality rate approaches 100%, and prognosis is especially poor when diagnosed in the second trimester. Given this high perinatal mortality, several aggressive treatment modalities have been attempted including selective feticide, hysterotomy for umbilical cord ligation or extirpation of one twin, bloodletting from a placental vessel, and maternal digoxin therapy. More recently, fetoscopic-guided laser ablation of the chorioangiopagus placental vessels has been reported to improve survival. Serial decompression amniocentesis, however, remains the most widely used therapy.

In a recent review of the literature, Moise reported an overall survival rate of 49% with serial amnioreduction. In most cases, the polyhydramnios recurs after a few days to weeks and repeated decompression amniocenteses are required. However, several reported series include a number of cases in which the stuck twin syndrome resolved after a single amniocentesis or suddenly following an amniocentesis that was the last in a series, with no need for additional therapy. Equalization of amniotic fluid volumes following a single amniocentesis was first reported by Wax et al. in a patient diagnosed at 27 4/7 weeks' gestation. An ultrasound performed five days after removal of 1,300 ml of amniotic fluid revealed polyhydramnios in both sacs. The ascites that was present in the recipient twin had disappeared. By the 11th day after amniocentesis, the amniotic fluid in both sacs had normalized and remained as such until delivery at 35 5/7 weeks. The sudden resolution of the syndrome after one or more amniocenteses, and the failure to document an increase in urine production in the stuck twin in the few cases where it was measured, are not consistent with the explanation that the post procedural increase in the amniotic fluid around the stuck twin is always the direct result of improved fetal renal perfusion. We propose that, in cases where resolution of the syndrome occurred unexpectedly, the amnion separating the twins was inadvertently punctured at the time of amniocentesis. This resulted in movement of fluid along a hydrostatic pressure gradient from the sac with polyhydramnios into the stuck twin's sac. At first, it would seem implausible that the intervening membrane could be unintentionally perforated despite continuous ultrasonographic visualization of the needle within the sac with polyhydramnios. Figure 1, however, shows that the operator may be unaware that the intervening membrane is being traversed by the needle. Before one of the twins becomes stuck to one side of the uterus, the separating membrane floats freely between the two sacs. As the amniotic fluid increases in one sac, this membrane bulges toward the other sac and is ultimately pushed against the stuck twin and the uterine wall. Therefore, this membrane which is formed by the amnions of both twins does not only envelop the stuck twin, but also covers part of the internal uterine wall surface. Visualization of the intervening membrane along the inner uterine wall would not be possible given the limitations of our current ultrasound imaging equipment. This finding, however, was described by De Lia et al. during endoscopic laser treatment for twin-twin transfusion: "During the operation, it was apparent that the amniotic membrane septum between the twins had maintained its location over the vascular equator and was compressed onto the chorionic plate of the smaller twin by the expanding sac of the polyhydramniotic twin.". Since the membranes covering the uterine wall are not easily identified by ultrasound, one cannot be certain of the exact position of the separating membrane. When the needle happens to be placed over the uterine area covered by this membrane, as in position 1 in figure 1, both amniotic sacs will be punctured. If the needle placement happens to be in an area such as position 2 in figure 1, then only the amnion of the sac with polyhydramnios is punctured and no connection between the two sacs is created.

We therefore hypothesized that the deliberate creation of a needle puncture in the intervening membrane, a procedure for which we coined the term septostomy, would allow equilibration of the fluid between the two sacs and improve survival of the twins without the need, in most cases, for decompression amniocentesis. The purpose of this report was to review the experience of five centers using this technique.

Umbilical Cord Ligation

In severe cases of TTTS, one of the fetuses may be extremely sick at the time of presentation. Attempts to save both fetuses in this case may be futile, as the sicker fetus may die despite all efforts. Spontaneous death of the unhealthy fetus may in turn cause death or neurological damage to the co-twin. An umbilical cord ligation may be performed to spare the co-twin from harm.

The success rate (the percent of remaining fetuses that survive) with this technique is approximately 90%. Other means of occluding the blood flow to the fetus (injection of alcohol, superglue, etc.) are unreliable and may result in the death of both twins. These techniques are no longer recommended.

Umbilical cord ligation is offered only in severe cases and the intent is to save the life of the other twin.

Selective Laser Photocoagulation of Communicating Vessels (S-LPCV)

Laser surgery may be performed to stop the sharing of vessels between the two fetuses. In this method of treatment, important advances have made in recent years.

Dr. Ruben Quintero revolutionized the surgical method used to treat TTTS by developing a way to laser specific vessels that cause the problem of blood sharing in this syndrome and spare the remainder of the vessels. The laser is used to seal the vessels to stop the blood flow. The previous method lasered all vessels crossing the dividing membrane, many of them not being involved in the problem.

The Florida Institute for Fetal Diagnosis and Therapy at St. Joseph Women's Hospital was founded by Dr. Quintero in 1996 and is today, one of the leading referral centers for fetal conditions worldwide. He is internationally recognized for his work in TTTS.

Currently, Dr. Quintero is one of only a few doctors performing this procedure throughout the world. He has performed more than 200 laser surgeries (as of August 2001) with an 84% survival rate for at least one baby and 50 percent for both. The center's incidence of neurological complications is 2%. The worldwide average of 5% is reported by all fetal surgeons.

The surgery is done under general anesthesia, which limits the fetuses from moving and interfering with the delicate procedure. A small incision (1/10 inch) is made in the mother's belly to insert an endoscope and laser fiber, under combined ultrasound and endoscopic guidance. The endoscope is a long, narrow tube with a light and camera on the end. An ultrasound is also known as a sonogram. It uses sound waves to image and look closely at structures in the body. The blood vessels are identified and sealed through the endoscope. For patients who have an anterior placenta (located in front of the uterus), they use flexible endoscopes that curve upwards and are still able to perform the surgery through a 1/10" skin incision. They do not perform a laparotomy (large incision in the abdomen of the mother).

The main advantage to this method is that the disease is corrected during a single intervention. In addition, cerebral palsy and other complications caused by the death of one of the twins are less likely to occur (approximately 5%) than with serial amniocentesis. If one fetus dies, the other twin is not affected.

For more information, refer to the reference: Selective Photocoagulation of Communicating Vessels (S-LPCV) (Quintero et al. Obstetrical and Gynecological Survey, 1997; 53 (12): s97-103).

One or Two Babies?

The purpose of surgery is to separate the circulation between the babies by using the laser to seal the vessels connecting the two. In essence, these babies are now like fraternal twins. They are no longer sharing blood and each has its own portion of the placenta. The question raised is why, in some cases, only one baby survives? This depends on how much placenta each baby receives when the egg splits. At the time of surgery, we cannot give more placenta to either baby nor can we tell how much placenta each baby has. According to research on placentas inspected after birth, each baby needs approximately 30% of the placenta to survive. If there is a loss after surgery, the other baby will not be affected since they are no longer sharing blood vessels. Loss can occur anytime from the time of surgery through delivery time. If both babies are doing well after one month, both are likely to survive.

Termination of Pregnancy

After reviewing all information and options, you may decide you do not want to continue this pregnancy. This option is available until the 24th week of pregnancy in most states.

How We Treat It 

Currently, UCSF offers a minimally-invasive approach in treating TRAP sequence. Since the treatment goal is to stop the blood flow to the acardiac twin, a high energy device is utilized to destroy the blood vessels and surrounding tissue at the site where they enter the acardiac twin. This device, known as Radiofrequency Ablation (RFA), utilizes a 3 mm needle to precisely deploy energy to the desired site. The needle is placed through the mother's skin and into the fetus by ultrasound guidance. Then, by using color Doppler, the energy is applied until blood flow is completely halted. This approach has eliminated the need for open surgery or using larger Fetoscopes into the uterus.

Steroids For Fetal Lung Maturity

During pregnancy the mother may be given steroids for fetal lung maturity should an early delivery be anticipated.  These steroids may be given from 24 weeks gestation.

• When a baby is born, the lungs need to expand with air.
• Phospholipids are soapy substances that are made by the lungs. They help the lungs expand easier.
• Fetuses do not make enough phospholipids for lung expansion until about 35 weeks.
• Respiratory distress syndrome (RDS), also known as hyaline membrane disease occurs when the lungs do not expand properly
• RDS is treated by helping the baby breathe with mechanical ventilation (a tube that goes into the baby’s lungs and is attached to a breathing machine).
• Steroids that cross the placenta are given to help the baby make phospholipids earlier.
• Two steroids are used in the United States: Betamethasone and Dexamethasone. Betamethasone is used more frequently, because fewer doses are needed.
• Two shots, usually 24 hours apart are given. The shots are given into the muscle.
• Sometimes repeat shots are given after 1 week.
• The number of repeat shots that are needed, or even necessity of the repeat shots is unknown.
• These steroids will not cause growth of facial hair or muscle development.
• Women with diabetes often have very high blood sugars after the steroid shots. This is not a reason to avoid the shots. However, blood sugars will need to be tested frequently, and more insulin may be needed.