Toshimitsu Maemura

Quantitative evaluation of the influence of ovarian steroids on plasminogen activators and inhibitors in human endometrial cells and trophoblasts

INTRODUCTION Plasminogen activators and inhibitors were quantitated in cultured human endometrial and trophoblast cells under the influence of ovarian steroids in order to investigate the role of the fibrinolytic system for trophoblast invasion and anchorage. MATERIALS AND METHODS Plasminogen activators (t-PA and u-PA) and their inhibitors (PAI-1 and PAI-2) secretions were assayed in cultures of epithelial, stromal, and trophoblast cells. These cells were also cultured on a fibrin substrate for microscopic examination of the fibrinolytic degradation. RESULTS The u-PA from epithelial cells was predominant among PAs and PAI-1 in endometrial cells. Estradiol (E2) enhanced t-PA production in stromal cells and PAI-1 production in epithelial cells. Progesterone (P4) suppressed u-PA production in epithelial cells and enhanced PAI-1 production in both epithelial and stromal cells. Trophoblasts produced PAI-1, PAI-2, and small quantities of t-PA and u-PA, none of which were notably influenced by E2 or P4. The PAI-1 production in trophoblasts was more than four-fold greater than the u-PA production in epithelial cells. Epithelial and stromal cells initially grew on fibrin substrate but were gradually detached from the substrate with fibrinolytic degradation, with the exception of the stromal cells grown in the presence of P4 (or E2+P4). Trophoblasts grew well on fibrin substrate without fibrinolytic degradation both in the presence and absence of the steroids tested. CONCLUSIONS Fibrinolytic balance seemed to be basically maintained between the endometrial PAs and the relative excess of trophoblasts-derived PAI-1. This balance might be regulated principally by P4 and focally by E2 in the endometrial tissue for placental implantation.

OC18.03: The relationship between recipient twin's hemodynamic deterioration and ductus venosus Doppler flow in Twin-twin transfusion syndrome

Objectives: Cardiac dysfunction among recipient twins is a well-established complication in Twin–twin transfusion syndrome (TTTS). Abnormal Doppler flow of ductus venosus (DV) also complicates well in recipient twins. However, how recipient’s hemodynamic deterioration associates DV flow remains to be fully elucidated. We investigated the relationship between recipient’s DV flow and amniotic fluid N-terminal-prohormone BNP (NT-proBNP) levels as a biomarker of ventricular wall stress or fetal E/e’ as an indicator of diastolic function. Methods: This prospective study included monochorionic twin pregnancies complicated with TTTS from 2015 to 2018. Pulsed Doppler evaluation of DV flow was performed, and its pulsatility index (PI) was measured. Abnormal DV flow was defined as absent or reverse end-diastolic flow. The relationships between DV flow and amniotic fluid NT-proBNP level or E/e’ [left ventricle (LV)and right ventricle (RV)-E/e’] were analysed. Recipient’s amniotic fluid samples were obtained at the time of fetoscopic laser surgery, and NT-proBNP level was corrected by amniotic fluid total protein (TP) levels. Results: Fifty-five TTTS cases participated in this study. Twelve recipients (22%) showed abnormal DV flow. DV-PI showed a strong positive correlation with amniotic fluid NT-proBNP/TP level (r = 0.720, p < 0.001), and abnormal DV flow was related with significantly higher NT-proBNP/TP level than those without abnormal DV flow [5,305 (860-17,800) ng/g vs. 564 (101-9,050) ng/g, p < 0.001]. Recipients with elevated RV-E/e’ (z-score > 2) had significant higher DV-PI than those without elevated RV-E/e’, and abnormal DV flow was also related with the elevation of bilateral E/e’ (p < 0.05). Conclusions: In TTTS recipient twins, DV flow was associated with amniotic fluid NT-proBNP and E/e’. It appeared that the more ventricular wall stress and pressure increase, the higher end-diastolic resistance of DV flow become, and subsequently DV flow shows absent or reverse flow.

Utility of fetal anteroposterior to transverse cerebellar diameter ratio to exclude cerebellar hypoplasia in trisomy 18

This study was aimed to determine reference ranges for fetal cerebellar hemisphere biometry, including the transverse cerebellar diameter (TCD), anteroposterior cerebellar diameter (APCD) and APCD/TCD ratio in normal fetuses. In addition, we investigated which parameter would be useful for cerebellar hypoplasia in trisomy 18.

OP26.04: Low cerebroplacental ratio can predict subsequent fetal demise of donor or smaller twin with abnormal umbilical artery flow after fetoscopic laser surgery

Objectives: To evaluate the utility of cerebroplacental ratio (CPR) for prediction of subsequent fetal demise (FD) after fetoscopic laser photocoagulation of placental communication (FLP) in cases with Twin–twin transfusion (TTTS) or selective intrauterine growth restriction (sIUGR), complicated with absent end-diastolic flow in umbilical artery (UA-AEDF). Methods: FLP were performed from 2015 to 2017. CPR (MCA-PI/UA-PI) was recorded within 24 hours before FLP and postoperative 1, 4-7 or 9-15 days. All patient was followed until neonatal period. Relation between the perinatal outcome, especially FD of smaller twin, and values of CPR were analysed. Results: Three cases of TTTS stage 3 and 10 cases of sIUGR were treated with FLP. Median gestational age at FLP was 19.3 (16.0-23.1). Eight case (62%) showed two neonatal survivals and other 5 twins (38%) were complicated with FD of donor or smaller twin at 31, 39, 80, 84 and 105 days after FLP, respectively. All recipient or larger twins survived after FLP. Preoperative CPR showed no significant difference between two groups with or without FD of donor or smaller twin. CPR of 8 survived donor or smaller twin showed marked increases after FLP, in which all CPR values increased at least more than 0.57 at the point of around 2 weeks after FLP. On the other hand, all 5 twins resulted in FD showed low CRP value, which remained less than 0.57 until 2 weeks after FLP. Conclusions: In compromised monochorionic twins showing UA-AEDF in donor or smaller twin, continuation of lower CPR in donor or smaller twin after laser surgery can predict the subsequent fetal demise. Such low CPR value might reflect severe insufficient placental function of remained placental territory in donor or smaller twins.