Study on level of CD56⁺ CD16⁺ natural killer cell in patients with repeated implantation failure complicated with chronic endometritis

Objective To observe the expression level of uterine natural killer (uNK) cell in patients with repeated implantation failure (RIF) complicated with chronic endometritis (CE).

Methods A total of 82 RIF patients treated in the Reproductive Medicine Center from October 2018 to February 2023 were selected as RIF group; 82 cases with history of IVF-assisted pregnancy and willing of assisted pregnancy again in the same period who underwent in vitro fertilization-embryo transfer (IVF-ET) in the center were selected as control group. Two samples of endometrial tissues were taken from both groups during the mid-luteal phase, one sample was used for detection of endometrial CD56⁺CD16⁺ uNK cell level by flow cytometry, and another sample was used for detection of CD138 by immunohistochemistry. A sample of 3 to 4 mL peripheral blood was collected, and flow cytometry was used to detect the level of CD56⁺CD16⁺ peripheral blood natural killer (CD56⁺CD16⁺PbNK) cell and blood routine. Patients with positive CE were asked to take a course of oral antibiotic therapy. In the luteal phase of the next menstrual cycle after the end of anti-inflammatory treatment, a small amount of endometrial tissues was taken again, and CD138 was detected by immunohistochemistry. Clinical pregnancy rate and embryo implantation rate before and after treatment were compared between the two groups.

Results The level of CD56⁺CD16⁺uNK cell was (34.23±17.01)% in the RIF group, which was significantly lower than (45.41±20.90)% in the control group (P < 0.05); the level of CD56⁺CD16⁺PbNK cell in the peripheral blood of the mid-luteal phase in the RIF group was (14.38±5.36)%, which showed no significant difference compared to (13.58±4.34)% in the control group (P>0.05); there were no significant differences in white blood cell count, lymphocyte percentage, and neutrophil percentage between the RIF group and the control group (P>0.05). There was no correlation between the level of endometrial CD56⁺CD16⁺uNK cell and the level of CD56⁺CD16⁺PbNK cell in peripheral blood (r=0.06). There were no significant differences in the levels of endometrial CD56⁺CD16⁺uNK cell and peripheral blood CD56⁺CD16⁺PbNK cell in mid-luteal phase between cases with CE and without CE in the RIF group and the control group (P>0.05). In the patients complicating CE in the RIF group and the control group, the clinical pregnancy rate and implantation rate of cases with negative CE after treatment were significantly higher than those with positive CE after treatment, while the early abortion rate of cases with negative CE after treatment was significantly lower (P < 0.05).

Conclusion Low expression of CD56⁺CD16⁺uNK cell may lead to immune disorders at the maternal-fetal interface, thereby increasing the risk of RIF; there is no correlation between peripheral blood CD56⁺CD16⁺PbNK cell and endometrial CD56⁺CD16⁺uNK cell; antibiotic treatment for CE can significantly improve the pregnancy outcome of RIF, and the diagnosis and treatment of CE should be considered as an important factor in the evaluation of RIF.