Christiansen Ole B, Steffensen Rudi, Nielsen Henriette S, Varming Kim
Fertility Clinic 4071, Rigshospitalet, Copenhagen, Denmark.
Gynecol Obstet Invest. 2008;66(4):257-67. doi: 10.1159/000149575. Epub 2008 Aug 1.
A considerable proportion of recurrent miscarriage (RM) cases are caused by recurrent chromosomally abnormal conceptions. However, in younger patients and patients with multiple miscarriages, maternal causes seem to dominate. No single biomarker with a high predictive value of maternally caused RM has been identified. Non-genetic biomarkers in RM may not reflect conditions in the pregnant uterus and we rarely know whether they are causes or consequences of miscarriage. Studies of genetic biomarkers are probably the best way to reveal the pathophysiological mechanisms behind RM. Epidemiological and genetic studies suggest that RM due to maternal causes has a multifactorial background. The risk of RM in each patient is probably determined by the interaction of many genetic variants and environmental factors but only few of these have so far been identified. The genetic biomarkers for RM can probably be classified into three groups: (1) variants associated with excessive inflammatory responses and autoimmunity; (2) variants of importance for insulin and androgen sensitivity and turn-over, and (3) variants associated with thrombophilia. Identification of these markers will require whole genome association studies comprising thousands of individuals. Acknowledgement of the multifactorial background for RM has important implications for the management of patients in clinical practice.
相当一部分复发性流产（RM）病例是由反复出现的染色体异常妊娠所致。然而，在年轻患者和有多次流产经历的患者中，母体因素似乎占主导。目前尚未发现单一的生物标志物对由母体因素导致的RM具有高预测价值。RM中的非遗传生物标志物可能无法反映妊娠子宫的状况，而且我们很少知道它们是流产的原因还是结果。对遗传生物标志物的研究可能是揭示RM背后病理生理机制的最佳方法。流行病学和遗传学研究表明，由母体因素导致的RM具有多因素背景。每位患者发生RM的风险可能由许多基因变异和环境因素的相互作用决定，但迄今为止仅识别出其中少数因素。RM的遗传生物标志物可能可分为三类：（1）与过度炎症反应和自身免疫相关的变异；（2）对胰岛素和雄激素敏感性及代谢具有重要意义的变异；（3）与血栓形成倾向相关的变异。识别这些标志物需要对数千名个体进行全基因组关联研究。认识到RM的多因素背景对临床实践中患者的管理具有重要意义。
