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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., (Copyright © 2015. Published by Elsevier B.V.)

Objective: To report a case of mifepristone-induced abortion in only one horn but a growing fetus in another horn for a twin pregnancy in a bicornuate uterus., Design: Case report., Setting: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taiwan., Patient(s): A 31-year-old woman who conceived spontaneously presented with 37 days' gestation., Intervention(s): Mifepristone 600 mg orally followed by misoprostol 400 mug orally 2 days later., Main Outcome Measure(s): Termination of pregnancy., Result(s): Induced abortion in only one horn but a growing fetus in another horn for a twin pregnancy in the bicornuate uterus detected by ultrasound. Surgical abortion with vacuum curettage was performed, and menstruation resumed 1 month later., Conclusion(s): As medical abortion with mifepristone and misoprostol becomes more prevalent, more studies are necessary to establish the dosage and regimens for multiple pregnancies associated with uterine anomalies.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the relationship among umbilical venous volume flow, birthweight and placental share in monochorionic twins with or without selective growth restriction. Having excluded cases complicated with twin-to-twin transfusion syndrome and one co-twin suffering intrauterine fetal death, a total of 51 monochorionic twin pregnancies were divided into two groups as with (group 1) and without (group 2) selective intrauterine growth restriction. Umbilical venous volume flow was calculated by multiplying the umbilical vein cross-sectional area by half of the maximal velocity around mid-trimester. The placentas were cut along the vascular equator into two individual placental masses. The discordance of birthweight was calculated as [(birthweight of larger twin-birthweight of smaller twin)/birthweight of larger twin 100%]. The discordances of umbilical venous volume flow and placental share were calculated in a similar fashion. The median umbilical venous volume flow discordances (68.4% and 15.3% in groups 1 and 2 monochorionic twins, respectively) were similar and correlated well with the placental share discordances (66.6% and 18.5% in groups 1 and 2 monochorionic twins, respectively) but not with the birthweight discordance (28.6% and 6.4% in groups 1 and 2 monochorionic twins, respectively) in both groups. We concluded that the umbilical venous volume flow discordance reflects the placental share discordance rather than the birthweight discordance in monochorionic twin pregnancies. [ABSTRACT FROM AUTHOR]

Background: We previously reported that fetal plasma erythropoietin (EPO) concentrations are significantly increased in growth-restricted fetuses with abnormal umbilical artery (UA) Doppler. During hypoxia in an ovine model, the primary site of fetal EPO synthesis was switched from the kidneys to the placenta. Therefore, we designed this study to evaluate human placental EPO gene expression and the correlation to fetal serum EPO concentration in growth-restricted fetuses in a monochorionic (MC) twin model.Methods: In MC twin pairs, selective intrauterine growth restriction (sIUGR) was defined as the presence of (i) birth weight discordance of > 20% and (ii) a smaller twin with a birth weight less than the 10th percentile. Fetal UA and middle cerebral artery (MCA) Doppler were checked within 1 week before delivery. An abnormal UA Doppler was defined as persistently absent or reverse end-diastolic flow. Cerebroplacental ratio (CPR) was defined as MCA-pulsatility index (PI)/UA-PI. Fetal plasma EPO concentrations were measured in cord blood, and EPO gene expression was assayed in each twin's placental territory. The intertwin plasma EPO ratio was calculated as the cord plasma EPO level of the smaller (or sIUGR) twin divided by the EPO concentration of the larger (or appropriate-for-gestational-age (AGA)) twin, and the intertwin placental EPO gene expression ratio was calculated similarly.Results: Twenty-six MC twins were analyzed, including normal twins (Group 1, n = 9), twins with sIUGR without UA Doppler abnormalities (Group 2, n = 9), and twins with sIUGR and UA Doppler abnormalities (Group 3, n = 8). The CPRs of smaller (sIUGR) fetuses were significantly decreased in Group 3 MC twins (p < 0.001), but not significantly different between Group 1 and Group 2. The highest fetal plasma EPO ratio and placental EPO gene expression ratio were identified in Group 3 MC twins (p < 0.001). The placental EPO gene expression ratios were significantly correlated with the fetal plasma EPO ratios (Pearson's correlation test, p = 0.004).Conclusion: This study provides evidence of increased placental EPO expression in MC twin fetuses with sIUGR and abnormal UA Doppler. Future studies are needed to confirm the similar role of placental EPO in severe IUGR singletons. [ABSTRACT FROM AUTHOR]

Objective: To study the regulatory mechanisms of selective intrauterine growth restriction (sIUGR) independent of confounding ge-netic factors, monochorionic (MC) twins are the ideal model, because they have identical genomic DNA. We hypothesize that the in-trauterine growth restriction fetus has mitochondrial activation compared with its larger counterpart, and sought to demonstrate this using the MC twin model. Design: Fetal cord blood and amniotic fluid of MC twins were prospectively collected during delivery. Mitochondrial DNA of cord blood was measured using real-time quantitative polymerase chain reaction (PCR), and mitochondria in amniotic fluid mesenchymal stem cells (AFMSCs) were analyzed with MitoTracker staining. Setting: Tertiary referring center. Patient(s): Forty-three pairs of MC twins, including 24 pairs with sIUGR and 19 pairs without. Intervention(s): None. Main Outcome Measure(s): Mitochondrial DNA contents were measured and presented as fold difference between the small and large fetuses. After staining with MitoTracker, mitochondrial intensity in AFMSCs was analyzed with the Image J program. Result(s): The fold differences of the cord blood mitochondrial DNA content between the small and large twins were significantly higher in the MC twins with sIGUR (2.5 ± 1.2, n = 24 pairs) than in those without sIUGR (1.2 ± 0.3, n = 19 pairs). In addition, mito-chondrial staining intensities were significantly higher in the AFMSCs derived from growth-restricted fetuses than from control fetuses. Conclusion(s): Mitochondrial activation in the sIUGR fetus of MC twins was likely regulated by locally adverse placental and blood flow conditions, instead of genetic factors. [ABSTRACT FROM AUTHOR]

• The transcriptome array of the MZ twins discordant for trisomy 21 from AFMSCs showed dysregulated genes. • The predominance of dysregulated genes was on chromosome 21. • The cluster pattern of dysregulation was on chromosomes 1, 6, 11, 16, 17, 19, and 21. • The genes were associated with extracellular matrix organization and central nervous system development. Down syndrome is one of the most common chromosomal disorders and yet our understanding about the dysregulated genes in this disease is limited. Through this case study, we investigated the gene expression profile of primary amniotic fluid mesenchymal stem cells (AFMSCs) isolated from the amniotic sac of monozygotic twins discordant for trisomy 21 with one fetal hydrops at 17 weeks of gestation. AFMSCs were cultured to analyze the gene expression profiles for the human transcriptome array. Gene ontology was used to evaluate dysregulated gene functions. Total 25,799 genes were identified such that 65 were up-regulated (0.25%) and 111 were down-regulated (0.43%) with a log 2 fold change trisomy 21/euploidy (log 2 [FC]) > 1, p < 0.01). 16 genes were selected and verified by qRT-PCR, which showed compatible result with transcriptome array. At the chromosome level, chromosome 21 was found to carry the highest percentage of up-regulated genes (2.13%, 7/329 genes) with the highest mean log 2 [FC] (0.23, p < 10−5), particularly on 21q22.3. There were eight segments with significant mean log 2 [FC] on chromosomes 1, 6, 11, and 21 for upregulation, and on chromosomes 16, 17, and 19 for downregulation, indicating a pattern of dysregulated genes clustering in domains along the genome. Gene ontology showed the identified genes associated with extracellular matrix organization (11 genes, p = 5.1 × 10−6) and central nervous system development (8 genes, p = 6.0 × 10−5). Using transcriptome analysis of the AFMSCs of monozygotic twins discordant for trisomy 21, we report the dysregulated genes involved in Down syndrome, their predominance on chromosome 21, and the cluster pattern on the whole genome. [ABSTRACT FROM AUTHOR]