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The influence of the young microbiome on inflammatory diseases—Lessons from animal studies 年轻微生物群对炎症性疾病的影响——来自动物研究的教训
Q Medicine Pub Date : 2015-12-13 DOI: 10.1002/bdrc.21116
Katja M. Bendtsen, Line Fisker, Axel K. Hansen, Camilla H.F. Hansen, Dennis S. Nielsen

Chronic inflammatory diseases are on the rise in the Westernized world. This rise has been correlated to a range of environmental factors, such as birth mode, rural versus urban living conditions, and use of antibiotics. Such environmental factors also influence early life gut microbiota (GM) colonization and maturation—and there is growing evidence that the negative effects of these factors on human health are mediated via GM alterations. Colonization of the gut initiates priming of the immune system from birth, driving tolerance towards non-harmful microorganisms and dietary antigens and proper reactions towards invading pathogens. This early colonization is crucial for the establishment of a healthy GM, and throughout life the balanced interaction of GM and immune system is a key element in maintaining health. An immune system out of balance increases the risk for later life inflammatory diseases. Animal models are indispensable in the studies of GM influence on disease mechanisms and progression, and focus points include studies of GM modification during pregnancy and perinatal life. Here, we present an overview of animal studies which have contributed to our understanding of GM functions in early life and how alterations affect risk and expression of certain inflammatory diseases with juvenile onset, including interventions, such as birth mode, antibiotics, and probiotics. Birth Defects Research (Part C) 105:278–295, 2015. © 2015 Wiley Periodicals, Inc.

慢性炎症性疾病在西方化世界呈上升趋势。这种上升与一系列环境因素有关,如出生方式、农村与城市生活条件以及抗生素的使用。这些环境因素也会影响生命早期肠道微生物群(GM)的定植和成熟,越来越多的证据表明,这些因素对人类健康的负面影响是通过转基因改变介导的。肠道的定植从出生开始启动免疫系统,推动对无害微生物和饮食抗原的耐受性,以及对入侵病原体的适当反应。这种早期的定植对于建立健康的转基因至关重要,并且在整个生命过程中,转基因和免疫系统的平衡相互作用是维持健康的关键因素。免疫系统失衡会增加晚年罹患炎症性疾病的风险。在研究转基因对疾病机制和进展的影响中,动物模型是必不可少的,重点包括对妊娠期和围产期转基因修饰的研究。在这里,我们提出了动物研究的概述,这些研究有助于我们了解转基因在生命早期的功能,以及改变如何影响某些幼年发病炎症性疾病的风险和表达,包括干预措施,如出生模式、抗生素和益生菌。出生缺陷研究(C辑)105:278 - 29,2015。©2015 Wiley期刊公司
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引用次数: 29
Development of the infant intestinal microbiome: A bird's eye view of a complex process 婴儿肠道微生物群的发育:一个复杂过程的鸟瞰图
Q Medicine Pub Date : 2015-12-11 DOI: 10.1002/bdrc.21114
Sharon B. Meropol, Amy Edwards

Infants undergo profound shifts in colonizing intestinal microorganisms during their first year, especially during and after birth and during weaning. Microbiota are passed to infants through the placenta, during the vaginal birth process, and from early diet and other environmental exposures. These microbiota play an active role in the development of healthy infant metabolic and immunologic systems; profound shifts in microbiotal populations can be persistent, are associated with immediate alterations in gene expression, metabolic, immunologic, and neurologic function, and with downstream metabolic and immunologic consequences such as obesity, allergies, asthma, autoimmune diseases, and potentially neurologic conditions. Many modern exposures, including Cesarean section, formula feeding, and antibiotics, have been associated with microbiome shifts, and also with downstream diseases; while many published studies considered exposures individually, a more comprehensive understanding of their interaction and impact will consider the entirety of the infant's environment. It is not possible, nor desirable, to return to a world without toilets, sewers, tap water, delivery room antisepsis, Cesarean sections, antibiotics, immunizations, and refrigerators; our other alternative is to better understand these complex changes in infant developmental and molecular physiology. Protecting and repairing the developmental processes of the healthy infant microbiome is the modern medical frontier. Birth Defects Research (Part C) 105:228–239, 2015. © 2015 Wiley Periodicals, Inc.

婴儿在出生的第一年,特别是在出生期间和之后以及断奶期间,肠道微生物的定植会发生深刻的变化。微生物群通过胎盘、阴道分娩过程、早期饮食和其他环境暴露传递给婴儿。这些微生物群在健康婴儿代谢和免疫系统的发育中发挥积极作用;微生物种群的深刻变化可能是持续性的,与基因表达、代谢、免疫和神经功能的直接改变有关,并与下游代谢和免疫后果有关,如肥胖、过敏、哮喘、自身免疫性疾病和潜在的神经系统疾病。许多现代暴露,包括剖宫产、配方奶喂养和抗生素,都与微生物群的变化有关,也与下游疾病有关;虽然许多已发表的研究考虑的是单独的暴露,但对它们的相互作用和影响的更全面的理解将考虑婴儿的整个环境。回到一个没有厕所、下水道、自来水、产房消毒、剖宫产、抗生素、免疫和冰箱的世界是不可能的,也是不可取的;我们的另一个选择是更好地理解婴儿发育和分子生理学中的这些复杂变化。保护和修复健康婴儿微生物群的发育过程是现代医学的前沿。出生缺陷研究(C辑)105:228-239,2015。©2015 Wiley期刊公司
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引用次数: 37
Microbial programming of health and disease starts during fetal life 微生物对健康和疾病的规划始于胎儿时期
Q Medicine Pub Date : 2015-12-10 DOI: 10.1002/bdrc.21117
Petya T. Koleva, Ji-Sun Kim, James A. Scott, Anita L. Kozyrskyj

The pioneer microbiota of the neonatal gut are essential for gut maturation, and metabolic and immunologic programming. Recent research has shown that early bacterial colonization may impact the occurrence of disease later in life (microbial programming). Despite early conflicting evidence, it has long been considered that the womb is a sterile environment and human microbial colonization begins at birth. In the last few years, several findings have reiterated the presence of microbes in infant first stool (meconium) and pointed to the existence of in utero microbial colonization of the infant gut. The dominant bacterial taxa detected in meconium specimens belong to the Enterobacteriaceae family (Escherichia genus) and lactic acid bacteria (notably members of the genera Leuconostoc, Enterococcus, and Lactococcus). Maternal atopy promotes dominance of Enterobacteriaceae in newborn meconium, which in turn may lead to respiratory problems in the infant. This microbial interaction with the host immune system may in fact, originate during fetal life. Our review evaluates the evidence for an intrauterine origin of meconium microbiota, their composition and influences, and potential clinical implications on infant health. Birth Defects Research (Part C) 105:265–277, 2015. © 2015 Wiley Periodicals, Inc.

新生儿肠道的先锋微生物群对肠道成熟,代谢和免疫程序是必不可少的。最近的研究表明,早期细菌定植可能会影响生命后期疾病的发生(微生物编程)。尽管早期的证据相互矛盾,但长期以来人们一直认为子宫是一个无菌环境,人类微生物的定植始于出生。在过去的几年里,一些研究结果重申了婴儿首便(胎便)中微生物的存在,并指出婴儿肠道中存在子宫内微生物定植。在粪标本中检测到的优势细菌类群属于肠杆菌科(埃希氏菌属)和乳酸菌(特别是白菌属、肠球菌属和乳球菌属)。母体特应性促进肠杆菌科在新生儿胎便中的优势,这反过来可能导致婴儿的呼吸问题。事实上,这种微生物与宿主免疫系统的相互作用可能起源于胎儿时期。我们的综述评估了子宫内胎粪微生物群起源的证据,它们的组成和影响,以及对婴儿健康的潜在临床意义。出生缺陷研究(C辑),2015。©2015 Wiley期刊公司
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引用次数: 102
The very low birth weight infant microbiome and childhood health 极低出生体重婴儿微生物群与儿童健康
Q Medicine Pub Date : 2015-12-10 DOI: 10.1002/bdrc.21115
Maureen W. Groer, Katherine E. Gregory, Adetola Louis-Jacques, Shelley Thibeau, W. Allan Walker

This review describes current understandings about the nature of the very low birth weight infant (VLBW) gut microbiome. VLBW infants often experience disruptive pregnancies and births, and prenatal factors can influence the maturity of the gut and immune system, and disturb microbial balance and succession. Many VLBWs experience rapid vaginal or Caesarean births. After birth these infants often have delays in enteral feeding, and many receive little or no mother's own milk. Furthermore the stressors of neonatal life in the hospital environment, common use of antibiotics, invasive procedures and maternal separation can contribute to dysbiosis. These infants experience gastrointestinal dysfunction, sepsis, transfusions, necrotizing enterocolitis, oxygen toxicity, and other pathophysiological consditions that affect the normal microbiota. The skin is susceptible to dysbiosis, due to its fragility and contact with NICU organisms. Dysbiosis in early life may resolve but little is known about the timing of the development of the signature gut microbiome in VLBWs. Dysbiosis has been associated with a number of physical and behavioral problems, including autism spectrum disorders, allergy and asthma, gastrointestinal disease, obesity, depression, and anxiety. Dysbiosis may be prevented or ameliorated in part by prenatal care, breast milk feeding, skin to skin contact, use of antibiotics only when necessary, and vigilance during infancy and early childhood. Birth Defects Research (Part C) 105:252–264, 2015. © 2015 Wiley Periodicals, Inc.

这篇综述描述了目前对极低出生体重婴儿(VLBW)肠道微生物群性质的理解。VLBW婴儿经常经历破坏性的怀孕和分娩,产前因素可以影响肠道和免疫系统的成熟,扰乱微生物的平衡和继承。许多VLBWs经历了快速阴道分娩或剖腹产。出生后,这些婴儿往往在肠内喂养方面有延迟,许多婴儿很少或根本没有母乳。此外,医院环境中新生儿生活的压力因素、抗生素的普遍使用、侵入性手术和产妇分离都可能导致生态失调。这些婴儿会经历胃肠道功能障碍、败血症、输血、坏死性小肠结肠炎、氧中毒和其他影响正常微生物群的病理生理状况。由于皮肤的脆弱性和与新生儿重症监护病房的生物接触,皮肤容易受到生态失调的影响。生命早期的生态失调可能会解决,但对于VLBWs中标志性肠道微生物群的发育时间知之甚少。生态失调与许多身体和行为问题有关,包括自闭症谱系障碍、过敏和哮喘、胃肠道疾病、肥胖、抑郁和焦虑。通过产前护理、母乳喂养、皮肤对皮肤接触、仅在必要时使用抗生素以及在婴儿期和幼儿期保持警惕,可以预防或部分改善生态失调。出生缺陷研究(C辑)(5):562 - 564,2015。©2015 Wiley期刊公司
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引用次数: 81
The influence of the young microbiome on inflammatory diseases--Lessons from animal studies. 年轻微生物群对炎症性疾病的影响——来自动物研究的经验教训。
Q Medicine Pub Date : 2015-12-01 DOI: 10.1002/bdrc.21116
K. M. Bendtsen, Line Fisker, A. K. Hansen, C. H. Hansen, D. Nielsen
Chronic inflammatory diseases are on the rise in the Westernized world. This rise has been correlated to a range of environmental factors, such as birth mode, rural versus urban living conditions, and use of antibiotics. Such environmental factors also influence early life gut microbiota (GM) colonization and maturation--and there is growing evidence that the negative effects of these factors on human health are mediated via GM alterations. Colonization of the gut initiates priming of the immune system from birth, driving tolerance towards non-harmful microorganisms and dietary antigens and proper reactions towards invading pathogens. This early colonization is crucial for the establishment of a healthy GM, and throughout life the balanced interaction of GM and immune system is a key element in maintaining health. An immune system out of balance increases the risk for later life inflammatory diseases. Animal models are indispensable in the studies of GM influence on disease mechanisms and progression, and focus points include studies of GM modification during pregnancy and perinatal life. Here, we present an overview of animal studies which have contributed to our understanding of GM functions in early life and how alterations affect risk and expression of certain inflammatory diseases with juvenile onset, including interventions, such as birth mode, antibiotics, and probiotics.
慢性炎症性疾病在西方化世界呈上升趋势。这种上升与一系列环境因素有关,如出生方式、农村与城市生活条件以及抗生素的使用。这些环境因素也会影响生命早期肠道微生物群(GM)的定植和成熟——越来越多的证据表明,这些因素对人类健康的负面影响是通过转基因改变介导的。肠道的定植从出生开始启动免疫系统,推动对无害微生物和饮食抗原的耐受性,以及对入侵病原体的适当反应。这种早期的定植对于建立健康的转基因至关重要,并且在整个生命过程中,转基因和免疫系统的平衡相互作用是维持健康的关键因素。免疫系统失衡会增加晚年罹患炎症性疾病的风险。在研究转基因对疾病机制和进展的影响中,动物模型是必不可少的,重点包括对妊娠期和围产期转基因修饰的研究。在这里,我们提出了动物研究的概述,这些研究有助于我们了解转基因在生命早期的功能,以及改变如何影响某些幼年发病炎症性疾病的风险和表达,包括干预措施,如出生模式、抗生素和益生菌。
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引用次数: 27
Microbial programming of health and disease starts during fetal life. 微生物对健康和疾病的规划始于胎儿时期。
Q Medicine Pub Date : 2015-12-01 DOI: 10.1002/bdrc.21117
P. Koleva, Ji-sun Kim, J. Scott, A. Kozyrskyj
The pioneer microbiota of the neonatal gut are essential for gut maturation, and metabolic and immunologic programming. Recent research has shown that early bacterial colonization may impact the occurrence of disease later in life (microbial programming). Despite early conflicting evidence, it has long been considered that the womb is a sterile environment and human microbial colonization begins at birth. In the last few years, several findings have reiterated the presence of microbes in infant first stool (meconium) and pointed to the existence of in utero microbial colonization of the infant gut. The dominant bacterial taxa detected in meconium specimens belong to the Enterobacteriaceae family (Escherichia genus) and lactic acid bacteria (notably members of the genera Leuconostoc, Enterococcus, and Lactococcus). Maternal atopy promotes dominance of Enterobacteriaceae in newborn meconium, which in turn may lead to respiratory problems in the infant. This microbial interaction with the host immune system may in fact, originate during fetal life. Our review evaluates the evidence for an intrauterine origin of meconium microbiota, their composition and influences, and potential clinical implications on infant health.
新生儿肠道的先锋微生物群对肠道成熟,代谢和免疫程序是必不可少的。最近的研究表明,早期细菌定植可能会影响生命后期疾病的发生(微生物编程)。尽管早期的证据相互矛盾,但长期以来人们一直认为子宫是一个无菌环境,人类微生物的定植始于出生。在过去的几年里,一些研究结果重申了婴儿首便(胎便)中微生物的存在,并指出婴儿肠道中存在子宫内微生物定植。在粪标本中检测到的优势细菌类群属于肠杆菌科(埃希氏菌属)和乳酸菌(特别是白菌属、肠球菌属和乳球菌属)。母体特应性促进肠杆菌科在新生儿胎便中的优势,这反过来可能导致婴儿的呼吸问题。事实上,这种微生物与宿主免疫系统的相互作用可能起源于胎儿时期。我们的综述评估了子宫内胎粪微生物群起源的证据,它们的组成和影响,以及对婴儿健康的潜在临床意义。
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引用次数: 106
The very low birth weight infant microbiome and childhood health. 极低出生体重婴儿微生物群与儿童健康。
Q Medicine Pub Date : 2015-12-01 DOI: 10.1002/bdrc.21115
M. Groer, K. Gregory, A. Louis-Jacques, S. Thibeau, W. Walker
This review describes current understandings about the nature of the very low birth weight infant (VLBW) gut microbiome. VLBW infants often experience disruptive pregnancies and births, and prenatal factors can influence the maturity of the gut and immune system, and disturb microbial balance and succession. Many VLBWs experience rapid vaginal or Caesarean births. After birth these infants often have delays in enteral feeding, and many receive little or no mother's own milk. Furthermore the stressors of neonatal life in the hospital environment, common use of antibiotics, invasive procedures and maternal separation can contribute to dysbiosis. These infants experience gastrointestinal dysfunction, sepsis, transfusions, necrotizing enterocolitis, oxygen toxicity, and other pathophysiological conditions that affect the normal microbiota. The skin is susceptible to dysbiosis, due to its fragility and contact with NICU organisms. Dysbiosis in early life may resolve but little is known about the timing of the development of the signature gut microbiome in VLBWs. Dysbiosis has been associated with a number of physical and behavioral problems, including autism spectrum disorders, allergy and asthma, gastrointestinal disease, obesity, depression, and anxiety. Dysbiosis may be prevented or ameliorated in part by prenatal care, breast milk feeding, skin to skin contact, use of antibiotics only when necessary, and vigilance during infancy and early childhood.
这篇综述描述了目前对极低出生体重婴儿(VLBW)肠道微生物群性质的理解。VLBW婴儿经常经历破坏性的怀孕和分娩,产前因素可以影响肠道和免疫系统的成熟,扰乱微生物的平衡和继承。许多VLBWs经历了快速阴道分娩或剖腹产。出生后,这些婴儿往往在肠内喂养方面有延迟,许多婴儿很少或根本没有母乳。此外,医院环境中新生儿生活的压力因素、抗生素的普遍使用、侵入性手术和产妇分离都可能导致生态失调。这些婴儿会经历胃肠道功能障碍、败血症、输血、坏死性小肠结肠炎、氧中毒和其他影响正常微生物群的病理生理状况。由于皮肤的脆弱性和与新生儿重症监护病房的生物接触,皮肤容易受到生态失调的影响。生命早期的生态失调可能会解决,但对于VLBWs中标志性肠道微生物群的发育时间知之甚少。生态失调与许多身体和行为问题有关,包括自闭症谱系障碍、过敏和哮喘、胃肠道疾病、肥胖、抑郁和焦虑。通过产前护理、母乳喂养、皮肤对皮肤接触、仅在必要时使用抗生素以及在婴儿期和幼儿期保持警惕,可以预防或部分改善生态失调。
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引用次数: 81
On the origin of species: Factors shaping the establishment of infant's gut microbiota. 物种起源:影响婴儿肠道菌群形成的因素。
Q Medicine Pub Date : 2015-12-01 DOI: 10.1002/bdrc.21113
N. van Best, M. Hornef, P. Savelkoul, J. Penders
The human gut microbiota is a complex and dynamic ecosystem, which naturally lives in a symbiotic relationship with the host. Perturbations of the microbial composition (dysbiosis) and reduced diversity may promote disease susceptibility and recurrence. In contrast to the mature intestinal microbiota of healthy adults, which appears relatively stable over time, the infant's microbiome only establishes and matures during the first years of life. In this respect, early childhood seems to represent a crucial age-window in disease prevention, since microbial diversification and maturation of the microbiome primarily occurs during this period of life. A better understanding of ecological processes and pioneer consortia in microbial development is crucial, in order to support the development of a beneficial microbiota. Various deterministic and stochastic aspects seem to shape the microbiome in early life, including maternal, environmental, and host factors. Here, we review the current understanding of the origin of pioneer bacteria and the evolutionary factors that influence the development of the gut microbiota in infants. In addition, future perspectives, including manipulating and promoting the succession of initial bacteria during infancy, will be highlighted.
人体肠道菌群是一个复杂而动态的生态系统,它与宿主自然存在共生关系。微生物组成的扰动(生态失调)和多样性的减少可能促进疾病的易感性和复发。健康成年人成熟的肠道微生物群随着时间的推移相对稳定,与之相反,婴儿的微生物群只在生命的头几年建立和成熟。在这方面,幼儿期似乎是预防疾病的关键年龄窗口,因为微生物的多样化和微生物组的成熟主要发生在生命的这一时期。为了支持有益微生物群的发展,更好地了解微生物发展的生态过程和先驱财团是至关重要的。各种确定性和随机因素似乎塑造了生命早期的微生物群,包括母亲、环境和宿主因素。在这里,我们回顾了目前对先锋细菌的起源和影响婴儿肠道微生物群发育的进化因素的理解。此外,未来的观点,包括在婴儿期操纵和促进初始细菌的继承,将被强调。
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引用次数: 78
On the origin of species: Factors shaping the establishment of infant's gut microbiota 物种起源:影响婴儿肠道菌群形成的因素
Q Medicine Pub Date : 2015-11-26 DOI: 10.1002/bdrc.21113
Niels van Best, Mathias W. Hornef, Paul H. M. Savelkoul, John Penders

The human gut microbiota is a complex and dynamic ecosystem, which naturally lives in a symbiotic relationship with the host. Perturbations of the microbial composition (dysbiosis) and reduced diversity may promote disease susceptibility and recurrence. In contrast to the mature intestinal microbiota of healthy adults, which appears relatively stable over time, the infant's microbiome only establishes and matures during the first years of life. In this respect, early childhood seems to represent a crucial age-window in disease prevention, since microbial diversification and maturation of the microbiome primarily occurs during this period of life. A better understanding of ecological processes and pioneer consortia in microbial development is crucial, in order to support the development of a beneficial microbiota. Various deterministic and stochastic aspects seem to shape the microbiome in early life, including maternal, environmental, and host factors. Here, we review the current understanding of the origin of pioneer bacteria and the evolutionary factors that influence the development of the gut microbiota in infants. In addition, future perspectives, including manipulating and promoting the succession of initial bacteria during infancy, will be highlighted. Birth Defects Research (Part C) 105:240–251, 2015. © 2015 Wiley Periodicals, Inc.

人体肠道菌群是一个复杂而动态的生态系统,它与宿主自然存在共生关系。微生物组成的扰动(生态失调)和多样性的减少可能促进疾病的易感性和复发。健康成年人成熟的肠道微生物群随着时间的推移相对稳定,与之相反,婴儿的微生物群只在生命的头几年建立和成熟。在这方面,幼儿期似乎是预防疾病的关键年龄窗口,因为微生物的多样化和微生物组的成熟主要发生在生命的这一时期。为了支持有益微生物群的发展,更好地了解微生物发展的生态过程和先驱财团是至关重要的。各种确定性和随机因素似乎塑造了生命早期的微生物群,包括母亲、环境和宿主因素。在这里,我们回顾了目前对先锋细菌的起源和影响婴儿肠道微生物群发育的进化因素的理解。此外,未来的观点,包括在婴儿期操纵和促进初始细菌的继承,将被强调。出生缺陷研究(C辑)(5):344 - 344,2015。©2015 Wiley期刊公司
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引用次数: 72
Gestational surrogacy and the role of routine embryo screening: Current challenges and future directions for preimplantation genetic testing 妊娠代孕和常规胚胎筛查的作用:胚胎植入前基因检测的当前挑战和未来方向
Q Medicine Pub Date : 2015-11-23 DOI: 10.1002/bdrc.21112
E. Scott Sills, Robert E. Anderson, Mary McCaffrey, Xiang Li, Nabil Arrach, Samuel H. Wood

Preimplantation genetic screening (PGS) is a component of IVF entailing selection of an embryo for transfer on the basis of chromosomal normalcy. If PGS were integrated with single embryo transfer (SET) in a surrogacy setting, this approach could improve pregnancy rates, minimize miscarriage risk, and limit multiple gestations. Even without PGS, pregnancy rates for IVF surrogacy cases are generally satisfactory, especially when treatment utilizes embryos derived from young oocytes and transferred to a healthy surrogate. However, there could be a more general role for PGS in surrogacy, since background aneuploidy in embryos remains a major factor driving implantation failure and miscarriage for all infertility patients. At present, the proportion of IVF cases involving GS is limited, while the number of IVF patients requesting PGS appears to be increasing. In this report, the relevance of PGS for surrogacy in the rapidly changing field of assisted fertility medicine is discussed. Birth Defects Research (Part C) 108:98–102, 2016. © 2015 Wiley Periodicals, Inc.

胚胎植入前遗传学筛查(PGS)是体外受精的一个组成部分,需要在染色体正常的基础上选择胚胎进行移植。如果PGS与代孕中的单胚胎移植(SET)相结合,这种方法可以提高妊娠率,减少流产风险,并限制多胎妊娠。即使没有PGS, IVF代孕病例的妊娠率通常也是令人满意的,特别是当治疗使用来自年轻卵母细胞的胚胎并将其转移到健康的代孕母亲时。然而,PGS在代孕中可能有更广泛的作用,因为胚胎的背景非整倍体仍然是导致所有不孕症患者植入失败和流产的主要因素。目前,IVF病例中涉及GS的比例有限,而IVF患者要求PGS的数量似乎在增加。在本报告中,在快速变化的辅助生育医学领域中,PGS与代孕的相关性被讨论。出生缺陷研究(C辑)108:98-102,2016。©2015 Wiley期刊公司
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引用次数: 3
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Birth Defects Research Part C-Embryo Today-Reviews
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