Consensus protocol for management of early and late twin-twin transfusion syndrome: Delphi study.

OBJECTIVE: Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 and 26 weeks' gestation. High-quality evidence and guidelines regarding the optimal clinical management of very early (prior to 16 weeks), early (between 16 and 18 weeks) and late (after 26 weeks) TTTS are lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS. METHODS: A Delphi procedure was conducted among an international panel of experts. Participants were chosen based on their clinical expertise, affiliation and relevant publications. A four-round Delphi survey was conducted using an online platform and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the second and third rounds, participants were asked to grade each statement on a Likert scale (1, completely disagree; 5, completely agree) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of 5 without suggestions for change were accepted as the consensus. Statements with a median grade of 3 or less were excluded from the Delphi process. Statements with a median grade of 4 were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree with the statements, and those with more than 70% agreement without suggestions for change were considered the consensus. RESULTS: A total of 122 experts met the inclusion criteria and were invited to participate, of whom 53 (43.4%) agreed to take part in the study. Of those, 75.5% completed all four rounds. A consensus on the optimal management of early and late TTTS was obtained. FLP can be offered as early as 15 weeks' gestation for selected cases, and can be considered up to 28 weeks. Between 16 and 18 weeks, management should be tailored according to Doppler findings. CONCLUSIONS: A consensus-based treatment protocol for early and late TTTS was agreed upon by a panel of experts. This protocol should be modified at the discretion of the operator, according to their experience and the specific demands of each case. This should advance the quality of future studies, guide clinical practice and improve patient care. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Human fetal membranes release a Ca++ channel inhibitor.

OBJECTIVE: Our purpose was to test the hypothesis that an inhibitor of uterine contractions released by human fetal membranes acts on the dihydropyridine site of the myometrial voltage-dependent Ca++ L channel. STUDY DESIGN: Initial experiments established the time course of release of the inhibitor from term, fetal membranes. Both a competitive binding assay and a uterine contraction bioassay were used to detect the inhibitor. After optimal time of release of inhibitor was determined, a dose-response experiment was performed with the competitive binding assay. To determine the source of the inhibitor, membranes are separated into component layers to generate inhibitor, and the competitive binding assay was used to measure the inhibitor. RESULTS: An inhibitor released from fetal membranes competes with 3H-isradipine at the Ca++ L channel dihydropyridine binding site. There is a time-dependent release of the inhibitor from membranes, which is maximal at 20 minutes (P < or = .05, n = 4). A dose effect of the inhibitor is present because greater amounts of inhibitor produce greater competition at the dihydropyridine site (P < or = .005, n = 3). The data are consistent with 1-site binding. Inhibition is restricted to the chorion (64% specific inhibition) and decidua (52% specific inhibition) with little competition seen in amnion alone (4% specific inhibition) (P < or = .03, n = 3). CONCLUSIONS: These studies support the hypothesis that human chorion/decidua releases an inhibitor of uterine contractions that acts specifically at the dihydropyridine site of the myometrial Ca++ L channel.