Brown University

Fetal Medicine @ Brown

The Warren Alpert Medical School of Brown University

Twin to Twin Transfusion Syndrome
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Embargoed for release at 5 p.m. July 7, 2004

Summary: Performing laser surgery in utero on identical twins suffering from twin-to-twin transfusion syndrome leads to significantly better outcomes than traditional treatment, according to a study that involves physicians from Rhode Island Hospital, Women & Infants' Hospital and Brown Medical School. The results of the study, which was led by investigators in France and Belgium, will appear in the July 8 issue of New England Journal of Medicine. The Rhode Island site is the only one in North America that performed fetal surgery as part of the study.

Proof of efficacy of laser therapy for Twin-Twin Transfusion Syndrome (TTTS), a complication unique to identical twins

Providence, RI/Paris, France/Leuven, Belgium - The majority of identical twins have only one placenta. In a number of these, blood may flow disproportionately from one baby to the other through connecting blood vessels in their shared placenta. This condition is called Twin-Twin Transfusion Syndrome, and has an incidence of about 1 per 1,000 pregnancies. If it occurs early in pregnancy and is left untreated, it is likely to cause loss of both babies. Until recently, the only available treatment consisted in repeated drainage of excess amniotic fluid (a consequence of the condition), but the results of this method are less than optimal. A new, more cause-oriented approach was therefore introduced, whereby a surgical separation of the connecting vessels on the placenta is performed by means of laser. Pioneering centers in keyhole surgery inside the womb ("fetoscopic surgery"), together with a number of "Fetal Treatment" centers throughout Europe, just finished a study comparing the two treatments. Using the most powerful form of medical research, whereby patients are randomly assigned by a computer to one or the other therapy, they have demonstrated that fetoscopic laser coagulation improves survival chances by 25 % and reduces the risks of neurologic problems by half, compared with drainage of amniotic fluid alone. These results will be published this week in the New England Journal of Medicine and are expected to have an impact on modern management of this disease.


There are two types of twin pregnancies. Those resulting from two fertilized eggs are called fraternal twins: they are like any other siblings, who just happen to occupy the same womb at the same time. They may or may not have a different gender. Twins resulting from the fertilization of a single egg or "zygote" are called identical or "monozygotic" twins. These children look identical and always have the same gender.
While most people are only interested in whether twins are identical or not, this is irrelevant from an obstetrical viewpoint. In terms of outcome of the pregnancy, the number of placentas is the most important factor. Fraternal twins always have their own placenta, but monozygotic or identical twins each have their own placenta in only 30 % of cases. 70 % of identical twins will have to share a single placenta throughout pregnancy, a situation that is much riskier.

Figure 1: Schematic drawing of TTTS. The smaller fetus is the donor, who has almost no amniotic fluid and is stuck to the wall of the womb, whereas the larger fetus is the recipient, who has too much amniotic fluid. Both babies share a single placenta.


Most identical twins experience no problems from the shared circulation and placenta. This remains true as long as the exchange of blood between the fetuses is well balanced. In 15%, however, more blood flows from one fetus towards the other, leading to what is called Twin-Twin Transfusion Syndrome (TTTS). The first fetus is called the "donor," as he pumps blood into the second fetus, who is therefore called the "recipient." This leads to too little blood (anemia), too little urine production and too little amniotic fluid production in the donor, who is frequently smaller. Doctors can document the lack of urine and amniotic fluid production using ultrasound, showing a nearly empty gestational sac, which may eventually not be visible at all. The recipient receives too much blood and eliminates the excess fluid by increasing his urine production (Figure.1). This leads to too much amniotic fluid around the recipient (polyhydramnios) and a rapid and excessive distension of the womb, leading to early delivery or rupture of the membranes. The condition itself can be easily demonstrated by ultrasound.

Figure 2: Drawing of the shared placenta in TTTS. Multiple vessels connect both fetuses through so-called "anastomoses" (open circles). These anastomoses are the sites for laser coagulation.

Importantly, TTTS is essentially a disease of the placenta, while the twins themselves are normal. However, unborn babies are fully dependent on the placenta for oxygen and nutrition, and any disease of the placenta will invariably affect their well-being. When TTTS occurs before 26 weeks gestational age (the normal duration of pregnancy is 40 weeks), it will have dramatic implications. It is estimated that the chance of survival is less than 1 in 5. Of the surviving fetuses, approximately 25% will sustain severe damage of the brain, liver, kidneys or other organs.
Given this high risk for losing the entire pregnancy, treatment is highly desirable. Certainly, the excess of amniotic fluid should be evacuated. This is done by needle puncture of the mother's pregnant uterus and is called amniodrainage. Amniodrainage does not remove the cause of the disease (the communicating blood vessels on the placenta), but it reduces the pressure in the womb and the risk of early delivery. The removal of fluid is repeated as often as required, usually 5 to 6 times. In the study that is to be published, one or both babies survived in only half the mothers who were treated with amniodrainage only. Babies were also born very prematurely, i.e. at 29 weeks on average. While this is certainly better than without any therapy at all, it leaves room for improvement.

Figure 3: Illustration of fetoscopic laser treatment. A cannula has been placed through the abdominal wall, through which a telescope and laser beam have been passed. The connecting vessels are identified and subsequently destroyed.



In 1995 an operation to separate the two blood circulations was introduced. By means of an endoscope (a tiny telescope of 3 mm diameter) the physician inspects the placenta and uses a laser to separate the connecting blood vessels on the placenta (Figure 2). This operation usually lasts less than an hour and causes no pain to the fetuses, who are not touched by it. At the end of the operation, the excess amniotic fluid is evacuated, down to normal levels; thus, it combines laser with the previously described therapy. In the study, 76 % of pregnancies ended up with one or two babies; this is an improvement of 25 % when compared with amniodrainage alone. In addition to that, laser therapy reduced the occurrence of serious brain damage by the age of 6 months from 10.3 to 4.5 %. This may be in part due to the later gestational age at birth (babies in the laser group were born at a mean of 33 weeks).
With this study, a long-lasting quarrel between "believers" and "non-believers" in this new method may be settled in favor of the more modern and causative approach to this disease. At this stage there are only a limited number of centers that have enough experience with the operation. The results of this study suggest that patients diagnosed with severe TTTS should be offered laser intervention, or should be offered the option to travel to a center familiar with this form of therapy.

For further information contact:
François I. Luks, MD, Rhode Island Hospital, Brown Medical School, Providence, RI
Stephen R. Carr, MD, Women & Infants' Hospital, Brown Medical School, Providence, RI
Prof Yves Ville, C.H.R. de Poissy-St Germain Paris, Dept. of Obstetrics and Gynaecology (Principal Investigator)
Prof Jan Deprest, University Hospital Leuven, Dept. of Obstetrics and Gynaecology (Eurofoetus General Project Manager)

Figures: K Dalkowski, with permission of Karl Storz Endoskope.


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