Background The role of autoantibodies in recurrent miscarriage (RM) is unclear. Commonly studied autoimmune markers in RM include anti-nuclear (ANA), thyroid peroxidase (TPO-Ab), and anti-thyroid globulin antibodies (Tg-Ab) and peripheral blood natural killer (pbNK) cells. The correlation between autoimmune markers (TPO-Ab, Tg-Ab, ANA) and pbNK cells in women with unexplained recurrent miscarriage (uRM) is unexamined. Because NK cells are associated with the adaptive immune response, we hypothesized that the change in pbNK cell number might be a result of the immune response to autoimmunity in women with RM rather than a cause of RM. We aimed to explore whether the pbNK count is significantly different in women testing positive than in those testing negative for autoantibodies. Methods The clinical data and performed pbNK cell measurements of patients who visited the specialist clinic for RM of the First Affiliated Hospital between May 2014 and August 2021 were analyzed. Eligible patients were divided into two groups: High-pbNK group (n=118) and Normal-pbNK group (n=184). Results The positive rates of TPO-Ab in High-pbNK group were significantly higher than in Normal-pbNK group (20.3% vs. 10.9%, p=0.04), and the positive rates of ANA in Normal-pbNK group were significantly higher than in High-pbNK group (22.3% vs. 11.9%, p=0.02). There was a statistically significant positive association between TPO-Ab positivity and high pbNK cells (p=0.016, OR=5.097, 95% CI 1.356–19.159), while there was a statistically significant negative association between ANA positivity and high pbNK cells (p=0.013, OR=0.293, 95% CI 0.111–0.773). Conclusion Our results indicated that changes in pbNK cell count are a result of the miscarriage-associated autoimmune response rather than a causal factor for RM. Hence, the increased number of pbNK cells cannot be applied as a therapeutic index for immunological abnormalities in patients with uRM.

Study objective The current knowledge on recurrent pregnancy loss (RPL) is largely limited, with up to 70% of RPL cases still classified as unexplained. More than 30% of patients with unexplained recurrent pregnancy loss (uRPL) will suffer an additional pregnancy loss. The majority of scholars are supportive of an immune basis, while clinical data fail to support established therapies. In addition, the effectiveness of immunotherapies is difficult to evaluate because of the lack of diagnostic and predictive indicators. Natural Killer (NK) cells are the largest population of lymphocytes in the endometrium during early pregnancy and play a key regulatory rather than participatory role in the cytotoxic killing reaction to embryos at the maternal-fetal interface. Specifically, they support the invasion of trophoblast cells and embryo implantation. Previous studies on the roles of NK cells with distinct phenotypes in pregnancy loss were based on NK cells derived from the peripheral blood or decidua, and it is difficult to determine whether the reported changes in decidual NK cells are causes or consequences of pregnancy loss. Hence, whether the results of these studies are applicable to the interaction between NK cells and embryonic trophoblast cells during the earliest pregnancy stage remains unknown.Design This study evaluated the expression of 9 receptors and cytokines after coculture of the HTR-8/SVneo human chorionic trophoblast cell line with peripheral blood NK (pbNK) cells and uterine NK (uNK) cells collected during the same embryo implantation window. Then the phenotypes of NK cells during this period were analyzed, and the associations of NK cell functional features with early pregnancy outcomes were explored.Results We found that a decrease in the CD3-CD56 + CD27 + uNK cell population and increases in the frequencies of CD3-CD56 + CD107a + NK cells in women with the recurrence of pregnancy loss.Conclusions CD3-CD56 + IFN-γ + pbNK cells and CD3-CD56 + IFN-γ + uNK cells were immunological risk factors associated with the recurrence of pregnancy loss in uRPL.

Introduction Current knowledge on the association of uric acid (UA) as a scavenger of free radicals with the reproductive outcomes of in vitro fertilization is largely limited, since most of the available data are focused on pregnancy complications, and high UA concentration was proposed as a risk indicator for adverse maternal and even infant risks. In the reproductive system, several studies have revealed that UA is involved in female reproductive diseases and that UA accumulation may cause reproductive disorders. However, the effect of UA on the progression of the evolution and quality of oocytes or embryos remains unexplored and unknown. This study aimed to explore the relationship between serum uric acid and reproductive outcomes in women undergoing in vitro fertilization procedures. Methods 1027 women without any intervention on serum UA levels who underwent the COH procedure and treatment with PGT-M and PGT-A were included, leaving a total of 1,177 samples available for analysis. Finally, 1,177 subjects were further divided into 3 groups according to the serum UA levels: the ≤250 μmol/L group (N=347), the 251-360 μmol/L group (N=669), and the >360 μmol/L group (N=161). Results The number of retrieved oocytes, mature oocyte rate and good-quality blastocyst rate were individually negatively related to hyperuricemia. Conclusions The presence of high serum uric acid could lead to a change in the follicular microenvironment, insufficient ovarian blood supply and overexposure of ovarian follicles and embryos to hypoxia and inflammation responses, which strengthened the utility of uric acid as a promising biomarker in clinical practice, particularly in in vitro fertilization procedures, that could contribute to early detection, decision-making about intervention, and improvement of reproductive treatment outcomes.