Objective: To provide an up-to-date comparison of pregnancy-related complications and adverse pregnancy outcomes of multiple pregnancies generated with assisted reproductive technology (ART) vs. spontaneous conception. Design: Meta-analysis. Setting: University-affiliated teaching hospital. Patient(s): Multiple pregnancies conceived by ART or naturally. Intervention(s): Searches through October 2014 were conducted on PubMed, Google Scholar, Cochrane Libraries, China Biology Medicine disc, Chinese Scientific Journals Fulltext Database, China National Knowledge Infrastructure, and Wanfang Data, to identify studies that met prestated inclusion criteria. Either a fixed-or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators. Main Outcome Measure(s): Pregnancy-related complications and adverse pregnancy outcomes. Result(s): Thirty-nine cohort studies involving 146,008 multiple births were included in the meta-analysis. Multiple pregnancies from ART were associated with a higher risk of premature rupture of membranes (relative risk [RR] = 1.20, 95% confidence interval [CI]: 1.05-1.37; I-2 = 15%); pregnancy-induced hypertension (RR = 1.11, 95% CI: 1.04-1.19; I-2 = 6%); gestational diabetes mellitus (RR = 1.78, 95% CI: 1.25-2.55; I-2 = 42%); preterm birth (RR = 1.08, 95% CI: 1.03-1.14; I-2 = 83%); very preterm birth (RR = 1.18, 95% CI: 1.04-1.34; I-2 = 79%); low birth weight (RR = 1.04, 95% CI: 1.01-1.07; I-2 = 47%); very low birth weight (RR = 1.13, 95% CI: 1.01-1.25; I-2 = 62%); and congenital malformation (RR = 1.11, 95% CI: 1.02-1.22; I-2 = 30%). The relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded similar results. No evidence of publication bias was observed. Conclusion(s): Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, the present study suggests that multiple pregnancies generated via ART, vs. spontaneous conception, are associated with higher risks of pregnancy-related complications and adverse pregnancy outcomes. Further research is needed to determine which aspect of ART poses the most risk and how this risk can be minimized. (C) 2015 by American Society for Reproductive Medicine.
BACKGROUND: Genetic modification is a prerequisite to realizing the full potential of human embryonic stem cells (hESCs) in human genetic research and regenerative medicine. Unfortunately, the random integration methods that have been the primary techniques used keep creating problems, and the primary alternative method, gene targeting, has been effective in manipulating mouse embryonic stem cells (mESCs) but poorly in hESCs. METHODOLOGY/PRINCIPAL FINDINGS: Human ribosomal DNA (rDNA) repeats are clustered on the short arm of acrocentric chromosomes. They consist of approximately 400 copies of the 45S pre-RNA (rRNA) gene per haploid. In the present study, we targeted a physiological gene, human coagulation factor IX, into the rDNA locus of hESCs via homologous recombination. The relative gene targeting efficiency (>50%) and homologous recombination frequency (>10(-5)) were more than 10-fold higher than those of loci targeted in previous reports. Meanwhile, the targeted clones retained both a normal karyotype and the main characteristics of ES cells. The transgene was found to be stably and ectopically expressed in targeted hESCs. CONCLUSION/SIGNIFICANCE: This is the first targeting of a human physiological gene at a defined locus on the hESC genome. Our findings indicate that the rDNA locus may serve as an ideal harbor for transgenes in hESCs.
Gene therapy has emerged as a promising approach for the lethal disorder of Duchenne muscular dystrophy (DMD). Using a novel non-viral delivery system, the human ribosomal DNA (hrDNA) targeting vector, we targeted a minidystrophin-GFP fusion gene into the hrDNA locus of HT1080 cells with a high site-specific integrated efficiency of 10~(-5), in which the transgene could express efficiently and continuously. The minidystrophin-GFP fusion protein was easily found to localize on the plasma membrane of HT1080 cells, indicating its possible physiologic performance. Our findings showed that the hrDNA-targeting vector might be highly useful for DMD gene therapy study.
[Hu You-Jin; Xia Kun; Xue Zhi-Gang; Wu Ling-Qian; Pan Qian; He Qiang; Yang Jun-Lin; Long Zhi-Gao; Liang De-Sheng; Xia Jia-Hui; Li Zhuo; Liu Xiong-Hao; Xue Jin-Feng; Gao Ting] Cent S Univ, State Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China.
[Liang De-Sheng] Cent S Univ, State Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China.
[王冰; 吕国华; 胡冬煦] Department of Surgery, Second Affiliated Xiangya Hospital, Central South University, Changsha, Hunan 410011, China;[夏家辉; 李崎] Natl. Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410011, China
Department of Surgery, Second Affiliated Xiangya Hospital, Central South University, China