Tzu-Hao Wang

Clinical outcome and placental territory ratio of monochorionic twin pregnancies and selective intrauterine growth restriction with different types of umbilical artery Doppler

To evaluate the clinical outcome and placental territory ratio in monochorionic diamniotic (MCDA) twin pregnancies and selective intrauterine growth restrictions (sIUGR) with different types of umbilical artery (UA) Doppler.

Increased autophagy in the placental territory of selective intrauterine growth-restricted monochorionic twins

This study investigates the placental autophagic activity in growth‐restricted fetuses in the monochorionic (MC) twin model.

Differential proteomics analysis of amniotic fluid in pregnancies of increased nuchal translucency with normal karyotype.

To investigate the functional roles of differentially expressed proteins in amniotic fluid supernatant (AFS) from normal karyotype pregnancies with increased nuchal translucency (NT).

The use of human amniotic fluid mesenchymal stem cells as the feeder layer to establish human embryonic stem cell lines

Human embryonic stem cells (hESCs) are pluripotent cells that have the potential to differentiate into the three germ layers and possibly all tissues of the human body. To fulfil the clinical potentials for cell‐based therapy, banks of hESC lines that express different combinations of the major histocompatibility genes should be established, preferably without exposing such cells to animal cells and proteins. In this study, we tested human amniotic fluid mesenchymal stem cells (AFMSCs) as feeder cells to support the growth of hESCs. Our results indicated that mitomycin‐treated AFMSCs were able to support the newly established hESC lines CGLK‐1 and CGLK‐2. The hESC colonies cultured on AFMSCs expressed alkaline phosphatase (ALK‐P), SSEA‐4, TRA‐1‐60, TRA‐1‐81, Oct‐4, Nanog and Sox‐2, which are markers for undifferentiated hESCs. Chromosomal analyses of both hESC lines, CGLK‐1 and CGLK‐2, which were cultured on AFMSC feeders for 22 and 14 passages, respectively, were confirmed to be normal karyotypes (46, XX). The ability of AFMSCs as feeder cells to maintain the undifferentiated growth and pluripotency of hESCs was confirmed by in vivo formation of teratomas derived on AFMSC hESCs in severe combined immune‐compromised mice. The use of AFMSCs for feeder cells to culture hESCs has several advantages, in that AFMSCs are not tumourigenic and can be expanded extensively with a short doubling time. Copyright

Placenta Share Discordance and Umbilical Artery Doppler Change After Antenatal Betamethasone Administration in Monochorionic Twins With Selective Intrauterine Growth Restriction: Is There a Link?

This study was designed to evaluate the degree of placenta share discordance in relation to the betamethasone-induced return of positive end-diastolic flow in monochorionic twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery Doppler. Monochorionic twins with sIUGR was defined as one twin having an estimated fetal weight below the 10th percentile combined with an estimated fetal weight discordance >25%. The umbilical artery Doppler directly prior to (D0) and 24 hours (D1) and 48 hours (D2) after the first dose of betamethasone administration was recorded. The estimated individual placental weight in monochorionic twins was obtained by cutting the placenta along the vascular equator into two territories; the placenta share discordance was calculated as [(estimated individual placental weight of appropriated for gestational age twin- estimated individual placental weight of growth restricted twin)/estimated individual placental weight of appropriated for gestational age twin] × 100%. Six (23.1%) of the 26 included cases achieved betamethasone-induced return of positive umbilical artery end-diastolic flow. The difference of placenta share discordance and birth weight discordance were not significantly different between twins with and without betamethasone-induced return of positive umbilical artery end-diastolic flow. Thus, according to our study results, it was proposed that although the placenta share discordance correlated with the abnormal umbilical artery Doppler in the IUGR fetus in monochorionic twin, the betamethasone-induced return of positive umbilical artery end-diastolic flow, however, did not reveal the similar relationship with the severity of placenta share discordance.

Fetal hemodynamic changes following maternal betamethasone administration in monochorionic twin pregnancies featuring one twin with selective growth restriction and abnormal umbilical artery Doppler

Aim:  To evaluate fetal hemodynamic changes following maternal betamethasone administration in monochorionic twin pregnancies featuring one twin with selective intrauterine growth restriction (sIUGR) and absence of end‐diastolic velocity in umbilical artery (UA) Doppler.

Increased Fetal Plasma Erythropoietin in Monochorionic Twin Pregnancies With Selective Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler.

Hypoxia is the primary stimulus for the production of erythropoietin (EPO) in both fetal and adult life. Here, we investigated fetal plasma EPO concentrations in monochorionic (MC) twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery (UA) Doppler. We diagnosed sIUGR in presence of (1) birth-weight discordance >20% and (2) either twin with a birth weight <10th percentile. An abnormal UA Doppler was defined as a persistent absent-reverse end diastolic flow (AREDF). The intertwin EPO ratio was calculated as the plasma EPO level of the smaller (or small-for-gestational-age) twin divided by the EPO concentration of the larger (or appropriate-for-gestational-age (AGA)) twin. Thirty-two MC twin pairs were included. Of these, 17 pairs were normal twins (Group 1), seven pairs were twins with sIUGR without UA Doppler abnormalities (Group 2), and eight pairs were twins with sIUGR and UA Doppler abnormalities (Group 3). The highest EPO ratio was identified in Group 3 (p < .001) but no significant differences were observed between Groups 1 and 2. Fetal hemoglobin levels did not differ significantly in the three groups, and fetal EPO concentration did not correlate with gestational age at birth. We conclude that fetal plasma EPO concentrations are selectively increased in MC twin pregnancies with sIUGR and abnormal UA Doppler, possibly as a result of uncompensated hypoxia.

Early anti-angiogenic proteins expression in amniotic fluid of twin fetuses.

Multiple pregnancies are thought to be associated with a high incidence of perinatal complications such as preterm labor, preeclampsia and low birth weight. But the true mechanisms of these obstetric complications are still uncertain. The components of amniotic fluid reflect the pathophysiology features of the fetus. Amniotic fluid soluble fms-like tyrosine kinase 1(sFLT1), soluble endoglin (sENG), and adiponectin reflect the oxidative stress and pro-inflammatory status and are associated with preeclampsia and fetal growth restriction. We prospectively collected amniotic fluids during amniocentesis from singleton and twin pregnancies. Samples were analyzed for levels of sFLT1, sENG, and adiponectin by enzyme-linked immunosorbent assay. The levels of sENG and sFLT1 were significantly increased in twin pregnancies. Adiponectin was not significantly different between the two groups. These findings would suggest that twin fetuses suffer from more oxidative stress and pro-inflammatory status from the early trimesters.

Outcome of twin–twin transfusion syndrome treated by laser therapy in Taiwan’s single center: Role of Quintero staging system

OBJECTIVE To evaluate the outcome of twin-twin transfusion syndrome (TTTS) treated by fetoscopic laser therapy (FLT) stratified by Quintero staging. MATERIALS AND METHODS A total of 100 TTTS cases treated by FLT, from October 2005 to August 2014, were included in this study. Cases were divided into first and second half periods to evaluate the learning effect-related outcomes, and logistic regression was applied to determine the independent factors in predicting the perinatal outcomes. RESULTS The total fetal survival rate was 68.5%, two fetal survival rate was 55%, and at least one fetal survival rate was 82%. High Quintero stage (Stages III and IV) and small gestational age at delivery were two independent factors predicting lower two fetal survivals. Gestational age at delivery was the only independent factor predicting at least one survival. The odds ratios of high Quintero stage predicting lower two fetal survivals were 11.3 (p<0.001) and 4.8 (p=0.043) in the first and second periods, respectively. CONCLUSION High Quintero stage and small gestational age at delivery were associated with low two survival rate in TTTS treated by FLT; after gaining experience with FLT, the effect of high Quintero stage on lower two survival rate would decrease.

Fetoscopic laser coagulation of intertwin anastomoses reduces discordant placental autophagic activities in discordant twin growth.

OBJECTIVES To investigate placental autophagic activity in cases of twin-twin transfusion syndrome (TTTS) after successful laser therapy and to evaluate the effect of intertwin anastomoses on discordant placenta autophagic activity in monochorionic twins with one twin exhibiting selective intrauterine growth restriction. MATERIALS AND METHODS Placenta samples were prospectively obtained from 11 cases of successful TTTS post-laser therapy with two living babies. Among these infants, five infants had selective intrauterine growth restriction (sIUGR), based on the definition of a birth weight below the 10(th) percentile. After protein extraction, western blot tests were used to determine the amount of placenta microtubule-associated protein 1A/1B-light chain 3 (LC3)-II protein in the two individual placenta territories of the twin pair. The LC3-II protein fold change ratio (FCR) in a twin pair was defined as the LC3-II protein fold value over β-actin of the smaller twin divided by the LC3-II protein fold value over β-actin of the larger twin. RESULTS The LC3-II FCRs were not significantly different between TTTS with sIUGR and TTTS without sIUGR, after successful laser therapy. CONCLUSION The discordance of placenta autophagic activity in the monochorionic twin with sIUGR was reduced after laser coagulation of the intertwin anastomoses, which may result from the effect of correction of the discordant intertwin placenta perfusion.