Beaumont Hospital, Dublin, Ireland.
Rotunda IVF, Parnell Square, Dublin 1, Ireland.
Ir J Med Sci. 2019 Aug;188(3):893-901. doi: 10.1007/s11845-018-1933-8. Epub 2018 Nov 27.
A complete reproductive immunophenotype is poorly described, with most focus on peripheral blood natural killer cells rather than uterine populations. There is debate regarding normal endometrial levels, with no consensus, and much controversy on correlation with implantation/miscarriage.
Development and validation of a rapid endometrial assessment flow cytometry (FCM) technique, allowing determination of local lymphocyte subset ranges, comparison to peripheral blood, and patient subgroup analysis.
Prospective pilot, assessing patients with prior implantation, failure offered endometrial biopsy before subsequent ART cycle, functioning as therapeutic scratch. HRT regime administered to standardise environment, and progesterone-primed mid-luteal biopsy (five completed days progestogen, P+5) analysed using comprehensive flow panel to identify lymphocyte subsets.
Two hundred patients were recruited in a tertiary university-affiliated ART centre. FCM identified differing lymphocyte ranges between peripheral blood and biopsy. Uterine/decidual natural killer cells are the dominant endometrial subtype. Patients with repeated implantation failure had higher uNK levels (52.4 vs 43.7%, p = 0.01). Conversely, B lymphocytes (0.87 vs 0.72%, p = 0.032), pNK (1.21 vs 0.8%, p = 0.041), and NK-T (2.68 vs 2.26, p = 0.031) cells were higher in recurrent pregnancy loss.
FCM is widely used to assess cellular populations, but not typically employed for endometrial evaluation. FCM provides a rapid, detailed, and quantitative analysis and reduces inter-observer subjectivity bias. Detailed understanding of the normal endometrial immunophenotype, and associated deviations, may provide insight into the aetiology of infertile patients labelled "unexplained". Failure despite transfer of high grade, or proven euploid blastocysts, is a difficult problem, and endometrial profiling may help identify research areas to determine potential future therapeutic interventions for this difficult to treat population.
完整的生殖免疫表型描述不完整，大多数研究集中在外周血自然杀伤细胞上，而不是子宫内的细胞群体。对于正常子宫内膜水平存在争议，尚无共识，而且对于其与着床/流产的相关性也存在很多争议。
开发和验证一种快速的子宫内膜评估流式细胞术（FCM）技术，该技术可确定局部淋巴细胞亚群范围，与外周血进行比较，并对患者亚组进行分析。
前瞻性试点研究，评估有既往着床失败史的患者，在随后的 ART 周期前提供子宫内膜活检，作为治疗性搔刮。给予激素替代治疗（HRT）方案以标准化环境，并对孕激素预激的黄体中期活检（使用孕激素 5 天，P+5）进行分析，使用综合流式细胞仪面板来识别淋巴细胞亚群。
在一家三级大学附属的 ART 中心招募了 200 名患者。FCM 鉴定出外周血和活检之间不同的淋巴细胞范围。子宫/蜕膜自然杀伤细胞是子宫内膜的主要亚型。反复着床失败患者的 uNK 水平较高（52.4%比 43.7%，p=0.01）。相反，B 淋巴细胞（0.87%比 0.72%，p=0.032）、pNK（1.21%比 0.8%，p=0.041）和 NK-T（2.68%比 2.26%，p=0.031）细胞在复发性流产患者中较高。
FCM 广泛用于评估细胞群体，但通常不用于子宫内膜评估。FCM 提供快速、详细和定量的分析，并减少了观察者之间的主观偏见。详细了解正常子宫内膜免疫表型及其相关偏差，可能有助于深入了解被标记为“不明原因”的不孕患者的病因。尽管移植了高等级或已证实的整倍体胚胎仍失败是一个难题，而子宫内膜分析可能有助于确定研究领域，为这一难以治疗的人群确定潜在的未来治疗干预措施。
