Clinical Research into Treating Unexplained Recurrent Spontaneous Abortion during Early Pregnancy with the Qing Yi Tiao Mian Formula.

OBJECTIVE: The present study aims to analyze the clinical effect of the Qing Yi Tiao Mian (QYTM) formula on unexplained recurrent spontaneous abortion (URSA) during early pregnancy and the immune balance of T lymphocytes. METHODS: With their consent, 45 patients with URSA in weeks 4-9 of pregnancy were separated into three groups, i.e., the conventional fetal protection (n = 15), prednisone treatment (n = 10), and QYTM formula treatment (n = 20) groups. These patients received treatment once they had been diagnosed with an intrauterine pregnancy. The conventional fetal protection group was given progesterone (20 ∼ 40 mg daily injection) for four weeks. The prednisone treatment group was given progesterone (20 ∼ 40 mg daily injection) + prednisone (5 mg/d) for four weeks. The QYTM formula treatment group was given progesterone (20 ∼ 40 mg daily injection) + QYTM formula (one dose per day) for four weeks. In addition, women who had previously had a normal pregnancy were enrolled as a control group (n = 18). The success rate of the pregnancy in the first trimester was observed in each group, and the proportion of T lymphocytes in the peripheral blood before and after treatment was recorded. RESULTS: Among the 20 patients with URSA in the QYTM formula treatment group, 19 remained pregnant. Thus, the success rate during early pregnancy was 95%, which was significantly higher than the conventional fetal protection (53.33%) and prednisone treatment (70%) groups. The CD8+ T and natural killer (NK) cells population in the URSA groups was higher compared with the control group (P < 0.01). The QYTM formula treatment significantly decreased the ratio of CD8+ T lymphocytes (P < 0.01) and NK cells (P < 0.01). CONCLUSION: The QYTM formula significantly decreased the spontaneous abortion rate in patients with URSA during early pregnancy. The mechanism may be closely related to the inhibition of the killer lymphocytes' proliferation by CD8+ T lymphocytes and NK cells.

Polarization disorder of decidual NK cells in unexplained recurrent spontaneous abortion revealed by single-cell transcriptome analysis.

BACKGROUND: Unexplained recurrent spontaneous abortion (URSA) is one of the most common diseases in pregnancy and is mainly caused by immune disorders. The foetus is similar to semiallogeneic maternal tissue, so the balance of immune tolerance must be dynamically maintained during pregnancy. Decidual natural killer (dNK) cells primarily mediate the immune tolerance microenvironment at the maternal-fetal interface. By using single-cell RNA sequencing (scRNA-seq) and high-throughput transcriptome sequencing analysis, we explored the characteristic distribution of dNK cells in URSA patients. METHODS: Control maternal-fetal interface tissue (from normal pregnant women, n = 3) and case maternal-fetal interface tissue (from patients with URSA, n = 3) samples were analysed by scRNA-seq and high-throughput transcriptome sequencing. RESULTS: By scRNA-seq, we demonstrated the maturation process of the transition of dNK cells from cytotoxic characteristics to immune tolerance in transcriptome analysis. Moreover, compared with normal pregnant women, serious disturbances in the polarization process of dNK cells were found in URSA. Simultaneously, the transcriptional level of the extracellular matrix (ECM) in URSA patients showed a significant decrease. The dNK cells interacted with extravillous trophoblasts to achieve immune-tolerant polarization. CONCLUSIONS: Insufficient expression of KIRs during dNK cell differentiation might be a key reason why polarized dNK cells still had high cytotoxic reactivity in URSA patients. Abnormal expression of ECM may affect the interaction of dNK cells with EVTs, making dNK cells immature. Both resulted in maternal immune intolerance to the foetus during pregnancy.