Mukherjee Nupur, Sharma Richa, Modi Deepak
Molecular and Cellular Biology Laboratory, ICMR-National Institute for Research in Reproductive and Child Health, Indian Council of Medical Research (ICMR), Parel, Mumbai, Maharashtra, India.
Am J Reprod Immunol. 2023 Feb;89(2):e13563. doi: 10.1111/aji.13563. Epub 2022 May 29.
A failure to achieve pregnancy after three or more embryo transfer cycles with high-quality blastocysts is referred to as recurrent implantation failure (RIF). RIF can be due to altered uterine factors or male factors or embryo factors. Disrupted endometrial receptivity, altered expression of genes in several pathways, immunologic disturbances in the peripheral blood and/or the endometrium, and epigenetic alterations are associated with RIF. Amongst the immunologic disturbances, altered Th1/Th2 ratio, altered NK cell and macrophage numbers are observed in women with RIF. However, not all women with RIF have the same kind of immune dysfunction suggesting that RIF is a heterogeneous condition associated with varied immune responses and one size may not fit all. Thus, personalized therapies based on the immune status of the patient are being tested in women with RIF. In general, women with a high Th1/Th2 ratio are offered Tacrolimus, while intravenous IgG is recommended in women with high NK cell numbers/HLA mismatch. Women with hyperactivated immune status in the uterus are offered progesterone support, prednisolone, vitamin E, and intralipid treatment to suppress inflammation and oxidative stress, while endometrial scratching and intrauterine hCG administration are offered to women with hypo-active immune status. There is a need for standardized tests for evaluation of immune status in patients and sufficiently powered randomized controlled trials for personalized therapies to determine which of these will be beneficial in women with RIF. Till then, the ART community should limit the use of such add-on interventions in women with RIF.
在进行三次或更多次高质量囊胚移植周期后仍未实现妊娠被称为反复种植失败（RIF）。RIF可能归因于子宫因素改变、男性因素或胚胎因素。子宫内膜容受性破坏、多种信号通路中基因表达改变、外周血和/或子宫内膜的免疫紊乱以及表观遗传改变都与RIF相关。在免疫紊乱中，RIF女性中观察到Th1/Th2比值改变、NK细胞和巨噬细胞数量改变。然而，并非所有RIF女性都有相同类型的免疫功能障碍，这表明RIF是一种与多种免疫反应相关的异质性疾病，不能一概而论。因此，基于患者免疫状态的个性化治疗正在RIF女性中进行测试。一般来说，Th1/Th2比值高的女性给予他克莫司，而NK细胞数量高/HLA不匹配的女性推荐静脉注射免疫球蛋白。子宫免疫状态过度激活的女性给予孕激素支持、泼尼松龙、维生素E和脂肪乳治疗以抑制炎症和氧化应激，而免疫状态低下的女性给予子宫内膜搔刮和子宫内注射hCG。需要有标准化的检测来评估患者的免疫状态，以及有足够效力的随机对照试验来验证个性化治疗，以确定哪些治疗方法对RIF女性有益。在此之前，辅助生殖领域应限制对RIF女性使用此类附加干预措施。
