HexafluOride, a Contrast Agent for Placenta Echo-angiography
Condition: Pregnancy
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to quantify the placental perfusion during the first trimester
      of pregnancy by 3D Doppler ultrasound angiography without a contrast agent and by ultrasound
      with a contrast agent: SonoVue®
    

Detailed description: 
      The quality of the utero-placental vascularization is a major point for the foetal healthy
      development and for the healthy pregnancy. Pre-eclampsia (PE) and the Intra-Uterine Growth
      Retardation (IUGR) are currently two of the major pregnancy complications in the West. Those
      placental pathologies cause more than 30 per cent of the foetal and maternal
      morbidity-mortality. The relationship between these pathologies, affecting 4 to 7 per cent of
      pregnancies, and a chronic utero-placental hypoperfusion, which is caused by a failure of
      implantation during the first trimester of pregnancy, has been confirmed.

      A hypoxic environment surrounds the embryonic implantation and the first steps of the
      placental development into uterus. Moreover, the maternal-foetal exchanges space (the
      Inter-Villi Space or IVS) is so maternal-bloodless. At the pregnancy first period are
      released there uterine secretions and a plasmatic ultra-filtrate. Indeed, the ends of the
      uterine arteries are plugged by trophoblastic plugs.

      It was also accepted that the disappearance of these plugs, a major step in the
      implementation of the mother-fetal interface, occurred around 10 weeks of amenorrhea (10 SA).
      However, a recent study questions this dogma since the presence of blood in the intervilleous
      chamber has just been detected as early as 6 weeks of amenorrhea (6SA). In addition, an
      increase in blood flow within the IVS is found between 6 and 13 SA. Thus, it would appear
      that chronic placental hypoperfusion phenomena are more related to a vascular flow defect
      within the IVS than to the disappearance of endovascular plugs.

      These new advances come from a single recent publication which was carried out on a small
      number of people (maximum 4 women per group).

      It is therefore essential to carry out further studies to confirm that the infusion of IVS
      occurs very early and to evaluate the evolution of infusion kinetics with gestational age.

      The detection of blood in the IVS from 6 SA was made possible by the injection of an
      ultrasound vascular contrast agent. This contrast agent does not have marketing authorization
      in women and its use is therefore not possible during the course of the progressive desired
      pregnancies. This study can therefore only be conducted in women who have confirmed a desire
      for voluntary interruption of pregnancy.

      Since 2004, the quantification of the placental and uterine vascularization is possible by
      Doppler 3D ultrasound angiography but this technique has only been evaluated from 11SA. The
      advantage of this technique is that it does not require the injection of contrast agent, but
      the main limitation is that the Doppler signal observed is not necessarily specific to a
      blood flow. Thus, it would be interesting to evaluate whether 3D Doppler ultrasound
      angiography would make it possible to quantify the perfusion of the IVS early, compared to
      contrast ultrasound. If this is the case, the use of contrast media would no longer be
      necessary to evaluate the evolution of placental flux in future studies.

      Recent data challenge ideas that have been accepted for decades. It is crucial to continue
      early exploration in order to understand the kinetics of maternal blood development in the
      IVS.

      This kinetic would have a major impact on the progression of pregnancy and it analysis may
      permit a screening test and an early diagnosis for PE- or IUGR-risky pregnancies.
    

Intervention name(s): Contrast agent: SonoVue®.
Intervention type(s): Drug
Intervention description(s): SonoVue® Injection: will be done through the peripheral venous way already set up by the anesthetist for its injection. None venous dedicated way will be established. The injection will take place when the woman will be under general anesthesia, ventilated and under constant cardio-respiratory monitoring.
Other intervention name(s): hexafluoride
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other