A Comparison of the Outcomes between Twin and Reduced Twin Pregnancies Produced through Assisted Reproduction

Objective: To compare the outcome of twin pregnancies, derived from IVF cycles, with and without fetal reduction. Design: A retrospective cohort study. Setting: The IVF Division of the Lee Women's Hospital, Taiwan. Patient(s): Seven hundred forty-two twin pregnancies, including 389 nonreduced pregnancies, 353 of which resulted from fetal reduction. Intervention(s): Selective fetal reduction for high-order multiple pregnancies. Main Outcome Measure(s): The rates of extreme prematurity and prematurity (i.e., less than 28 and 36 weeks gestational age, respectively), frequency of birth weight discordance, mean birth weight of twins, neonatal mortality, and morbidity. Result(s): The feral reduction group was associated with a higher incidence of extreme prematurity, prematurity, and lower birth weight that the nonreduced group, although the impact was relatively small. These findings were more pronounced among patients with a higher initial number of fetuses. The rates of discordant birth weights between the two groups were not significantly different. Conclusion(s): High-order multiple pregnancies after fetal reduction is still associated with a mild increased risk of premature delivery and low birth weight when compared to nonreduced twin pregnancies. These results provide as additional reason to limit the number of embryos transferred during IVF

Effects of growth hormone plus gonadotropins on controlled ovarian stimulation in infertile women of advanced age, poor responders, and previous in vitro fertilization failure patients

Objective: To investigate the effects of growth hormone (GH) cotreatment in ovarian stimulation in infertile women of advanced age, poor responders, and patients with one or more previous IVF treatment failures. Materials and methods: We conducted a retrospective observational study of 436 patients undergoing GH cotreatment in ovarian stimulation. The first arm included 134 infertile women of advanced age. The second arm included 236 patients with one or more IVF previous treatment failures, and the third arm included 66 younger poor responders. Main outcome measures were the number of oocytes and embryos, quality of embryos, and implantation and pregnancy rates. Results: In infertile women of advanced age, GH plus ovarian stimulation yielded no statistical differences in the numbers of oocytes and embryos, quality of embryo, and rates of implantation and pregnancy. In the second arm, the mature oocyte number (8.2 vs. 6.8), implantation rate (16.1% vs. 0%), and pregnancy rate (33.9% vs. 0%) in the GH cotreatment group differed significantly from those in the control group; the rate of good-quality embryos in the GH cotreatment group improved from 35.5% ± 31.1%–41.4% ± 30.6% in this arm. Similar results were observed in the third arm; in this arm, the clinical pregnancy rate was 30.3% in the GH cotreatment group and 6.1% in the control group. Conclusion: No significant differences were observed in infertile women of advanced age, which may be due to the low GH dose. The GH adjuvant therapy for patients with one or more previous IVF treatment failures and for poor responders significantly improved the oocyte and embryo numbers as well as implantation and pregnancy rates

The pregnancy health and birth outcomes of women who underwent assisted reproductive technology: Results of a national survey

Background: There is an upward trend for parents to resort to assisted reproductive technology (ART) treatment due to delayed childbirth or birth difficulties. Objective: This study investigates the pregnancy health and birth outcomes of women who underwent ART and analyzes the factors that influence birth weight to become<10 percentile when undergoing ART. Materials and Methods: This study analyzed results of the first wave of the Taiwan Birth Cohort study. Through stratified systematic sampling, 24,200 mother-and-child sampling pairs were obtained from a total of 206,741 live births in Taiwan in 2005; 366 of the babies were born with the use of ART. Results: During pregnancy, mothers who used ART suffered from higher risks of complication than the natural conception counterparts, including gestational diabetes mellitus (GDM), pregnancy induced hypertension (PIH), and placenta previa. Additionally, babies born through ART had poorer outcomes than the natural conception groups: the low birth weight (<2500g) was 33.1% compared to 6.4% for babies born naturally. Conclusion: Pregnancy health and birth outcomes of women who underwent ART were worse than those who got natural conception. Types of maternal complication among ART women included GDM, PIH, and placenta previa. Having multiple births was the most important factor that causes low birth weight in babies. The results of this study can be used as a reference for the health and care of mothers and babies who use ART

Upregulation of Protein Synthesis and Proteasome Degradation Confers Sensitivity to Proteasome Inhibitor Bortezomib in Myc-Atypical Teratoid/Rhabdoid Tumors.

Atypical teratoid rhabdoid tumors (ATRTs) are among the most malignant brain tumors in early childhood and remain incurable. Myc-ATRT is driven by the Myc oncogene, which directly controls the intracellular protein synthesis rate. Proteasome inhibitor bortezomib (BTZ) was approved by the Food and Drug Administration as a primary treatment for multiple myeloma. This study aimed to determine whether the upregulation of protein synthesis and proteasome degradation in Myc-ATRTs increases tumor cell sensitivity to BTZ. We performed differential gene expression and gene set enrichment analysis on matched primary and recurrent patient-derived xenograft (PDX) samples from an infant with ATRT. Concomitant upregulation of the Myc pathway, protein synthesis and proteasome degradation were identified in recurrent ATRTs. Additionally, we found the proteasome-encoding genes were highly expressed in ATRTs compared with in normal brain tissues, correlated with the malignancy of tumor cells and were essential for tumor cell survival. BTZ inhibited proliferation and induced apoptosis through the accumulation of p53 in three human Myc-ATRT cell lines (PDX-derived tumor cell line Re1-P6, BT-12 and CHLA-266). Furthermore, BTZ inhibited tumor growth and prolonged survival in Myc-ATRT orthotopic xenograft mice. Our findings suggest that BTZ may be a promising targeted therapy for Myc-ATRTs

Upregulation of Protein Synthesis and Proteasome Degradation Confers Sensitivity to Proteasome Inhibitor Bortezomib in Myc-Atypical Teratoid/Rhabdoid Tumors

Atypical teratoid rhabdoid tumors (ATRTs) are among the most malignant brain tumors in early childhood and remain incurable. Myc-ATRT is driven by the Myc oncogene, which directly controls the intracellular protein synthesis rate. Proteasome inhibitor bortezomib (BTZ) was approved by the Food and Drug Administration as a primary treatment for multiple myeloma. This study aimed to determine whether the upregulation of protein synthesis and proteasome degradation in Myc-ATRTs increases tumor cell sensitivity to BTZ. We performed differential gene expression and gene set enrichment analysis on matched primary and recurrent patient-derived xenograft (PDX) samples from an infant with ATRT. Concomitant upregulation of the Myc pathway, protein synthesis and proteasome degradation were identified in recurrent ATRTs. Additionally, we found the proteasome-encoding genes were highly expressed in ATRTs compared with in normal brain tissues, correlated with the malignancy of tumor cells and were essential for tumor cell survival. BTZ inhibited proliferation and induced apoptosis through the accumulation of p53 in three human Myc-ATRT cell lines (PDX-derived tumor cell line Re1-P6, BT-12 and CHLA-266). Furthermore, BTZ inhibited tumor growth and prolonged survival in Myc-ATRT orthotopic xenograft mice. Our findings suggest that BTZ may be a promising targeted therapy for Myc-ATRTs

Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan.

In 2016, a project was initiated in Taiwan to adopt molecular diagnosis of childhood medulloblastoma (MB). In this study, we aimed to identify a molecular-clinical correlation and somatic mutation for exploring risk-adapted treatment, drug targets, and potential genetic predisposition. In total, 52 frozen tumor tissues of childhood MBs were collected. RNA sequencing (RNA-Seq) and DNA methylation array data were generated. Molecular subgrouping and clinical correlation analysis were performed. An adjusted Heidelberg risk stratification scheme was defined for updated clinical risk stratification. We selected 51 genes for somatic variant calling using RNA-Seq data. Relevant clinical findings were defined. Potential drug targets and genetic predispositions were explored. Four core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Genetic backgrounds of metastasis at diagnosis and extent of tumor resection were observed. The adjusted Heidelberg scheme showed its applicability. Potential drug targets were detected in the pathways of DNA damage response. Among the 10 patients with SHH MBs analyzed using whole exome sequencing studies, five patients exhibited potential genetic predispositions and four patients had relevant germline mutations. The findings of this study provide valuable information for updated risk adapted treatment and personalized care of childhood MBs in our cohort series and in Taiwan