Laboratory of Molecular Endocrinology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA.
Hum Reprod Update. 2014 Nov-Dec;20(6):822-39. doi: 10.1093/humupd/dmu032. Epub 2014 Jun 19.
The number of children conceived using assisted reproductive technologies (ART) has reached >5 million worldwide and continues to increase. Although the great majority of ART children are healthy, many reports suggest a forthcoming risk of metabolic complications, which is further supported by the Developmental Origins of Health and Disease hypothesis of suboptimal embryo/fetal conditions predisposing adult cardiometabolic pathologies. Accumulating evidence suggests that fetal and placental growth kinetics are important features predicting post-natal health, but the relationship between ART and intrauterine growth has not been systematically reviewed.
Relevant studies describing fetoplacental intrauterine phenotypes of concepti generated by in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and somatic cell nuclear transfer (SCNT) in the mouse, bovine and human were comprehensively researched using PubMed and Google Scholar. Intrauterine growth plots were created from tabular formatted data available in selected reports.
ART pregnancies display minor but noticeable alterations in fetal and placental growth curves across mammalian species. In all species, there is evidence of fetal growth restriction in the earlier stages of pregnancy, followed by significant increases in placental size and accelerated fetal growth toward the end of gestation. However, there is a species-specific effect of ART on birthweights, that additionally vary in a culture condition-, strain-, and/or stage at transfer-specific manner. We discuss the potential mechanisms that underlie these changes, and how they are affected by specific components of ART procedures.
ART may promote measurable alterations to intrauterine growth trajectory and placental function. Key findings include evidence that birthweight is not a reliable marker of fetal stress, and that increases in embryo manipulation result in more deviant fetal growth curves. Because growth kinetics in early life are particularly relevant to adult metabolic physiology, we advise more rigorous assessment of fetal growth and placental function in human ART pregnancies, as well as continued follow-up of ART offspring throughout post-natal life. Finally, strategies to minimize embryo manipulations should be adopted whenever possible.
全球范围内，通过辅助生殖技术（ART）受孕的儿童数量已超过 500 万，且这一数字还在不断增加。尽管绝大多数接受 ART 的儿童是健康的，但许多报告表明他们面临着即将出现的代谢并发症风险，而“健康与疾病的发育起源”假说认为胚胎/胎儿状况欠佳会导致成年后出现心血管代谢疾病，这进一步证实了这一观点。越来越多的证据表明，胎儿和胎盘生长动力学是预测出生后健康的重要特征，但 ART 与宫内生长之间的关系尚未得到系统评价。
使用 PubMed 和 Google Scholar 全面检索了描述体外受精（IVF）、胞浆内精子注射（ICSI）和体细胞核移植（SCNT）在小鼠、牛和人类中产生的胎儿胎盘宫内表型的相关研究。从选定报告中可用的表格格式数据创建了宫内生长图。
ART 妊娠在所有哺乳动物物种中，胎儿和胎盘生长曲线都存在微小但明显的改变。在所有物种中，妊娠早期都存在胎儿生长受限的证据，随后胎盘大小显著增加，并在妊娠晚期加速胎儿生长。然而，ART 对出生体重的影响具有种属特异性，并且还以培养条件、品系和/或转移阶段特异性的方式发生变化。我们讨论了这些变化背后的潜在机制，以及它们如何受到 ART 程序特定成分的影响。
ART 可能会导致宫内生长轨迹和胎盘功能发生可测量的改变。主要发现包括以下证据：出生体重不能可靠地作为胎儿应激的标志物，胚胎操作增加会导致胎儿生长曲线更偏离正常。由于生命早期的生长动力学与成年代谢生理学特别相关，因此我们建议对人类 ART 妊娠中的胎儿生长和胎盘功能进行更严格的评估，并在出生后对 ART 后代进行持续随访。最后，只要有可能，就应采取策略尽量减少胚胎操作。
