Table 1.
Summary of the current evidence with regard to the role of uterine natural killer cells in recurrent implantation failure, highlighting the examined parameters as well as the major findings of the analyzed studies.
| Publication | Study Design | Study Group | Control Group | Interventions | Examined Parameters | Major Findings |
|---|---|---|---|---|---|---|
| [54] | Controlled clinical study | 35 women with RIF after ET in IVF | 12 fertile women | Ultrasound evaluation and endometrial biopsy on day 20 | The balance between IL-12 and IL-18; the number of NK cells; and the vascular status | Distinct IL-12 and IL-18 patterns; significantly higher number of CD56 bright cells in patients with RIF |
| [17] | Pilot study | 37 women with unexplained RIF following ET in IVF | 8 fertile women | Ultrasonic evaluation and endometrial biopsy in luteal phase | Uterine artery Doppler; count of uterine CD56 bright cells/field; and quantification by real-time PCR to monitor IL-12 family, the IL-18 system (IL-18, IL-18R, IL18BP), and the IL-15 mRNA ratios. | Higher number of uNK CD56 bright cells/field in the preimplantation endometrium in RIF group; distinct IL-12/-15/-18 immune related mechanisms |
| [64] | Uncontrolled pilot study | 10 young (30–35 years old) women with unexplained RIF following ET in IVF | Data obtained from the literature | Endometrial biopsy >6 months following the last IVF cycle | The number of CD56bright uNK cells | The percentage of the uNK subpopulation of CD56+CD16– and CD56bright CD16– cells did not differ between RIF patients and normal human endometrium |
| [59] | Prospective observational study | 40 women with RIF | 15 women with no history of infertility | Endometrial biopsy | The number of CD56+, CD16+, and CD69+ cells in the unstimulated endometrium of women with RIF |
CD56+ cell density was significantly higher in the RIF group; there was no significant difference in the densities of CD16+ and CD69+ cells |
| [67] | Case-control study | 20 women with IVF failure | Healthy control women: 36 normal multiparous women and 7 women with successful IVF | Peripheral blood sample collection; NK cell cytotoxicity level assessment via lactate dehydrogenase (LDH) release assay | compare the percentage of peripheral blood CD56(+) (CD56(dim) and CD56(bright)) cells and the level of NK cell cytotoxicity | The percentage of CD56(dim) cells and the level of peripheral blood NK cell cytotoxicity in women with IVF failure were significantly higher compared with the control group |