Dons'koi Boris, Onyshchuk Oksana, Kononenko Iryna, Sirenko Vira, Bodnar Natalia, Serbyn Andrii, Kozachok Anzhela, Brovarska Yulia, Osypchuk Dariia, Anochko Yaroslava, Chernychov Viktor
Laboratory of Immunology, State Institution (Institute of Pediatrics, Obstetrics and Gynecology NAMED AFTER ACADEMICIAN O. Lukyanova of the National Academy of Medical Sciences of Ukraine), 04050 Kyiv, Ukraine.
Reproductive Medicine Clinic "DAHNO IRM", 04050 Kyiv, Ukraine.
Diagnostics (Basel). 2022 Apr 6;12(4):908. doi: 10.3390/diagnostics12040908.
Problem Many studies have demonstrated the negative impact of high rates of NK cytotoxicity (NKc) on reproductive processes, but there is no agreement as to the appropriateness and feasibility of using the NKc for routine diagnostic in IVF patients. This study conducted a retrospective analysis of embryo transfer (ET) success rates and live birth rates (LBR) in patients with different NKc values. Method of study 1854 cycles of ET were selected and divided into three groups according to NKc levels, and randomized by anamnesis and age: normal (nNKc, n = 871), elevated (eNKc, n = 759), and reduced NKc (rNKc, n = 123). ET with donors’ embryos (n = 101) were analyzed separately. NKc-to-K562 was measured in PBMC (peripheral blood mononuclear cells) by flow cytometry before ET. The patients did not obtain any additional treatments. Results Patients with eNKc, in addition to having reduced clinical pregnancy rates (OR1.59, p < 0.0001), had increased levels of subsequent pregnancy failures (OR2.545, p < 0.0001) when compared to nNKc patients. As a result, patients with eNKc had almost half the LBR than patients with nNKc (OR2.2, p < 0.0001). In patients with rNKc, LBR was also lowered. eNKc was equally unfavorable for implantation and delivery in cryo- or fresh cycles. Markedly, eNKc was much more unfavorable for reproduction than slightly elevated NKc. The donor’s embryos were implanted irrespective of the recipient’s NKc levels, but the later stages of pregnancy were worse in patients with eNKc. Conclusions Our findings highlighted the negative impact of high levels of NK cytotoxicity on pregnancy outcomes.
问题 许多研究已证明高自然杀伤细胞细胞毒性（NKc）率对生殖过程有负面影响，但对于将NKc用于体外受精（IVF）患者的常规诊断的适宜性和可行性尚无定论。本研究对不同NKc值患者的胚胎移植（ET）成功率和活产率（LBR）进行了回顾性分析。研究方法 选择1854个ET周期，根据NKc水平分为三组，并按病史和年龄进行随机分组：正常（nNKc，n = 871）、升高（eNKc，n = 759）和降低的NKc（rNKc，n = 123）。对使用供体胚胎的ET（n = 101）进行单独分析。在ET前通过流式细胞术检测外周血单个核细胞（PBMC）中NKc与K562的比值。患者未接受任何额外治疗。结果 与nNKc患者相比，eNKc患者不仅临床妊娠率降低（OR1.59，p < 0.0001），而且后续妊娠失败率升高（OR2.545，p < 0.0001）。因此，eNKc患者的LBR几乎是nNKc患者的一半（OR2.2，p < 0.0001）。rNKc患者的LBR也降低。eNKc对冷冻或新鲜周期的着床和分娩同样不利。值得注意的是，eNKc对生殖的不利影响远大于轻度升高的NKc。无论受体的NKc水平如何，供体胚胎均可着床，但eNKc患者的妊娠后期情况较差。结论 我们的研究结果突出了高水平NK细胞毒性对妊娠结局的负面影响。
