Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, People's Republic of China.
Office of Clinical Epidemiology, Obstetrics and Gynaecology Hospital of Fudan University, Shanghai, People's Republic of China.
Fertil Steril. 2020 Aug;114(2):426-435. doi: 10.1016/j.fertnstert.2019.12.022. Epub 2020 Mar 18.
To compare the changing peripheral levels of immune checkpoint proteins T-cell immunoglobulin mucin-3 (Tim-3)/galectin-9 (Gal-9), and programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) over a 9-day period after blastocyst transfer between women who did and did not conceive.
Prospective observational study.
University teaching hospital.
PATIENTS(S): Fifty-one infertile women undergoing day-5 blastocyst transfer.
INTERVENTION(S): Serial blood samples obtained on the day of embryo transfer (ET), and 3, 6, and 9 days afterward for measurement of membranous Tim-3 and PD-1 expression on various peripheral lymphocytes by flow cytometry, and serum concentrations of ligands Gal-9 and PD-L1 by ELISA.
MAIN OUTCOME MEASURE(S): Membranous Tim-3 and PD-1 expression on lymphocytes and serum Gal-9 and PD-L1 concentrations and comparison of results between pregnant and nonpregnant women.
RESULT(S): In women who conceived, the measurements exhibited three different types of response: [1] a transient and statistically significant reduction of Tim-3NK-like T cells, Tim-3/PD-1CD8 T cells, and Tim-3/PD-1CD4 T cells that returned back to baseline level 9 days after ET; [2] a reduction followed by steady increase to above baseline level on day 9 (Tim-3CD56NK cells); [3] a steady increase in expression after ET to reach a level statistically significantly higher than that of the baseline by day 9 (Tim-3CD56NK cells). Women who did not conceive showed no statistically significant fluctuation in any of the parameters measured across the four time pointswith exception of increased Tim-3 expression on NK cells on day 9.
CONCLUSION(S): Successful blastocyst implantation is associated with a reduction of Tim-3 and PD-1 expression in peripheral lymphocytes on days 3 and 6 that is no longer apparent on day 9.
比较胚胎移植后 9 天内着床和未着床的女性外周免疫检查点蛋白 T 细胞免疫球蛋白粘蛋白-3（Tim-3）/半乳糖凝集素-9（Gal-9）和程序性细胞死亡-1（PD-1）/程序性死亡配体 1（PD-L1）水平的变化。
前瞻性观察性研究。
大学教学医院。
51 名接受第 5 天囊胚移植的不孕女性。
胚胎移植（ET）当天及之后第 3、6 和 9 天，通过流式细胞术检测外周淋巴细胞表面膜 Tim-3 和 PD-1 的表达，ELISA 法检测血清中配体 Gal-9 和 PD-L1 的浓度。
淋巴细胞表面膜 Tim-3 和 PD-1 的表达、血清 Gal-9 和 PD-L1 浓度，以及妊娠和非妊娠妇女的结果比较。
在着床的女性中，这些指标表现出三种不同的反应类型：[1] 短暂且具有统计学意义的 Tim-3NK 样 T 细胞、Tim-3/PD-1CD8 T 细胞和 Tim-3/PD-1CD4 T 细胞减少，这些细胞在 ET 后 9 天恢复到基线水平；[2] 在第 9 天减少后稳定增加至高于基线水平（Tim-3CD56NK 细胞）；[3] 在 ET 后持续增加，到第 9 天达到统计学上显著高于基线水平的水平（Tim-3CD56NK 细胞）。未妊娠的女性在四个时间点测量的所有参数均无统计学意义的波动，除了第 9 天 NK 细胞上的 Tim-3 表达增加。
成功的囊胚着床与胚胎移植后第 3 和第 6 天外周淋巴细胞中 Tim-3 和 PD-1 表达减少有关，第 9 天这种减少不再明显。
