The limited cytotoxicity of immune cells facilitates a successful establishment of pregnancy. However, the association between cytotoxic granules and unexplained repeated implantation failure (uRIF) remains unkown. Twenty-one fertile controls and 54 patients with uRIF were included in this study. The pregnancy outcomes were monitored at different gestational periods. The peripheral blood lymphocytes were detected using specific monoclonal antibodies by flow cytometry. The percentage of perforin⁺ (Pfr⁺), granzyme B⁺ (GrB⁺), or granulysin⁺ (Gnly⁺) lymphocytes was not significantly different among fertile controls, uRIF patients with successful pregnancy outcomes, and uRIF patients with pregnancy failure. The percentage of GrB⁺ γδ-T cells in lymphocytes was markedly higher in uRIF patients with implantation failure and clinical pregnancy failure than that in uRIF patients with a corresponding successful pregnancy outcome. A four-tier risk model showed that the risk of suffering clinical pregnancy failure in uRIF patients among high risk tier (83.3 %), normal risk tier (65.0 %) and low risk tier (39.1 %) was elevated by 2–4 fold compared with uRIF patients among lowest risk tier (20.0 %). In addition, the percentage of GrB⁺ NK cells in lymphocytes tended to decrease in uRIF patients with pregnancy failure. The AUC of the combined indicator with GrB⁺ γδ-T cells and GrB⁺ NK cells was increased than that of GrB⁺ γδ-T cells and GrB⁺ NK cells for predicting clinical pregnancy failure. In conclusion, the frequency of GrB-expressing γδ-T and NK cells in peripheral blood could serve as a predictor of clinical pregnancy failure in patients with uRIF.

免疫细胞有限的细胞毒性有助于成功建立妊娠。然而，细胞毒性颗粒与无法解释的重复植入失败 (uRIF) 之间的关联仍然未知。本研究包括 21 名可育对照者和 54 名 uRIF 患者。在不同的妊娠期监测妊娠结局。通过流式细胞术使用特异性单克隆抗体检测外周血淋巴细胞。穿孔素的百分率⁺（PFR ⁺），粒酶B ⁺（GRB ⁺），或颗粒溶素⁺（GNLY ⁺) 淋巴细胞在可育对照、成功妊娠结果的 uRIF 患者和妊娠失败的 uRIF 患者之间没有显着差异。与相应的成功妊娠结局的uRIF患者相比，移植失败和临床妊娠失败的uRIF患者淋巴细胞中GrB ⁺ γδ-T细胞的百分比显着升高。四级风险模型显示，高风险级（83.3 %）、正常风险级（65.0 %）和低风险级（39.1 %）的uRIF患者临床妊娠失败的风险升高了2-4倍uRIF 患者属于最低风险等级 (20.0 %)。此外，GrB ⁺的百分比妊娠失败的uRIF患者淋巴细胞中的NK细胞趋于减少。用的GrB组合指示器的AUC ⁺ γδ-T细胞和的GrB ⁺ NK细胞比的GrB的增加⁺ γδ-T细胞和的GrB ⁺ NK细胞用于预测临床妊娠失败。总之，外周血中表达 GrB 的 γδ-T 和 NK 细胞的频率可以作为 uRIF 患者临床妊娠失败的预测指标。