Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04148859 |
| Other study ID # |
04-220 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 2004 |
| Est. completion date |
November 2025 |
Study information
| Verified date |
October 2019 |
| Source |
Tel-Aviv Sourasky Medical Center |
| Contact |
Zoya Gordon, PhD |
| Phone |
972-3-692-5759 |
| Email |
zoyag[@]tasmc.health.gov.il |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Objectives: Twin-to-twin transfusion syndrome (TTTS) generates high risk for one of the
twins, may lead to preterm delivery and is also associated with neurodevelopmental deficits.
The aim of this study was to explore a controlled amnioreduction (AR) procedure in which the
amniotic pressure is simultaneously measured with the removed volume of amniotic pressure.
Methods: Eleven patients with severe TTTS at stages II and III of Quintero classification
were enrolled to the study. The amniotic pressure was measured along with the removed volume
of the amniotic pressure between 17-34 weeks of gestation. The umbilical artery S/D ratio for
each twin was measured at the beginning and after every 500cc of removed amniotic fluid.
Long-term neurodevelopmental outcome of infants with TTTS was evaluated from a questionnaire
for assessing the overall health of the surviving twins.
Description:
The placentation of monozygotic twins depends on the stage at which duplication occurs. A
monochorionic diamniotic placenta type occurs when the blastocyst splits between days 3 8
after fertilization when the trophoblast but not the amniotic cavity has differentiated. The
blood vessels of the twins of such a placenta form superficial or deep anastomoses (Denbow et
al., 2000). The anastomoses may communicate between an artery of one twin to an artery of the
other one (A-A), vein to vein (V-V) or artery to vein (A-V). The superficial anastomoses are
the ones between fairly large vessels on the chorionic plate, where the majority of them are
A A. These anastomoses are bidirectional, and allow rapid flow between the twins, depending
on pressure gradient. The A-V anastomoses are usually deep and occur in a shared cotyledon
where the connection is via the capillary system. These anastomoses are unidirectional and
result in an asymmetric flow from one twin to another (Fox, 1997; Bajoria, 1998; Taylor et
al, 1999; De Paepe et al, 2002).
Monochorionic diamniotic placentas may be diagnosed by ultrasonography (US) at 8 10 weeks of
gestation in the presence of a single placenta, similar genitalia, an intrafetal septum <2 mm
thick, and the absence of a twin peak sign (Bajoria, 1998). Twin-twin transfusion syndrome
(TTTS) is a major complication of a monochorionic placenta which occurs in 10% 15% of
monochorionic multiple pregnancies (Sebire et al, 1997) due to blood transfusion from one
twin (the donor) to the other (the recipient) (Bajoria et al, 1995; Talbert et al, 1996). The
donor twin becomes anemic and the amount of its amniotic fluid decreases, while the recipient
becomes polycythemic, causing polyhydramnios. The cause for the development of TTTS accounts
for the types of anastomoses. Mild TTTS has a single deep A V anastomosis along with
superficial A-A and V-V anastomoses, whereas severe TTTS lacks the superficial anastomoses
(Bajoria, 1998; Denbow et al, 1998; Bermudez et al, 2002). It was postulated that a single,
deep A-V anastomosis causes asymmetric blood flow from one twin to the other (3)(Bajoria,
1998). The effect of an asymmetric blood flow is minimized when superficial anastomoses are
present together with an A-V anastomosis (Denbow et al, 2000). Superficial anastomoses are
clearly observed on the chorionic plate. Deep anastomoses, i.e., the A-V type, represent a
shared cotyledon in which the arterial supply is derived from one twin and the venous
drainage is to the other (Denbow et al., 1998). Thus, A-V anastomoses may be suspected by an
unpaired artery of one twin and an unpaired vein of the other twin being dipped closely into
the placenta at a distance <1 cm (De Paepe et al., 2002).
Monochorionic twins have an approximately 25% rate of perinatal morbidity and mortality,
which is much higher than singleton and dichorionic twins (Kaufman et al, 1998; De Catte et
al., 2002; Chow et al., 2001). No single therapy is associated with a uniformly improved
outcome for the involved twins and success is primarily related to gestational age and
severity at diagnosis. Treatment options for severe cases include serial amniocenteses,
septostomy, laser occlusion of placental vessels, digitalization, ligation of the umbilical
cord and selective feticide. These modalities are associated with significant risks of
complications, and variable results of fetal morbidity and mortality. Therefore, they should
be considered when risks of withholding treatment clearly outweigh those associated with
intervention (Ropacka et al, 2002).
The serial amnioreduction is currently the most widely used therapy because it is simple and
requires commonly available skilled and equipment. The excess amniotic fluid volume which can
vary from 0.5 to few liters are removed, reducing the excess amniotic fluid and pressure, and
potentially preventing or delaying rupture of the membranes or preterm labor. Amnioreduction
carries a related risk of delivery of 4% per procedure (Van Gemert et al, 2001).
Obliteration of placental anastomoses is the obvious causal therapy of TTTS, because
placental anastomoses cause oligo-polyhydramnios sequence of TTTS. The fetoscopic laser
coagulates placental vascular anastomoses along the inter-twin septum. However, few
anastomoses may be located at the donor side or hidden by the stuck twin and thus,
coagulation is limited. TTTS can worsen if compensating vessels (bidirectional) are
coagulated instead of significant AV. The risk of procedure-related spontaneous abortion is
greater after laser therapy than single amnioreduction. The advantage of amnioreduction
changes after three procedures (Van Gemert et al, 2001).
TTTS is not completely understood and is controversial which hampers development of
acceptable diagnostic and rational treatment strategies. In this research we would like to
investigate the mechanism which improves both twins blood flow after amnioreduction. Such
knowledge may improve future management of TTTS. We will recruit 11 women who have to undergo
amnioreduction due to TTTS. The amniotic fluid is drained via needle, which is stubbed in the
abdomen wall, connected to a tube into a plastic bag. The amniotic fluid pressure will be
measured by a water manometer. AT-shape connector will be connected to the tube on one side,
and to a short tube on the other side. The height of the fluid within the short tube will
indicate the pressure. All the fluid will be drained to the plastic bag. The pressure and the
blood flow of the fetuses will be measured during the procedure, depends on the drainage
rate. We will include cases of multiple pregnancies with TTTS who must undergo
amnioreduction. Pregnancies with malformations or genetic pathologies will be excluded. In
addition, we also will explore the long-term neurodevelopmental outcome of children born
following a pregnancy complicated by TTTS whose mothers underwent the controlled AR.
