| Background and ObjectiveMiscarriage is one of the most common pregnancy-related diseases in women,and almost 25% of women would experience one or more abortions in their lifetime.About 1% to 5% of women might have experienced two or more repeated abortions,called recurrent miscarriage(RM).Usually,recurrent miscarriage that occurs before 10 weeks of gestation defines as early recurrent miscarriage.There are many etiologies of recurrent miscarriage such as chromosomal abnormalities,reproductive system malformations,endocrine dysfunction,immune dysfunction,coagulopathy,and social factors.However,some patients still cannot find the cause,called unexplained recurrent miscarriage.A lot of researches indicates that early r unexplained recurrent miscarriage is associated with a specific immune system dysfunction during the pregnancy.The balance of the maternal-fetal interface immune system is an important condition for the successful establishment and maintenance of pregnancy.Immune dysfunction is a research hotspot of unexplained early recurrent miscarriage,and various diagnostic and therapeutic programs are carried out around it.Granulocyte-colony stimulating factor(G-CSF)is a cytokine that stimulates neutrophil proliferation and differentiation,promotes trophoblastic growth,regulates Th1/Th2 cytokine network.The immune function plays an important regulatory role in the maternal-fetal interface.Therefore,granulocyte colony-stimulating factor is potentially used in the treatment of unexplained early recurrent miscarriage immunomodulation.This study provided a new promising evaluation that the peripheral neutrophils combined with interleukin-10(IL-10)to assume the efficacy of G-CSF in the treatment of early recurrent miscarriage.Materials and Methods 1 MaterialsWe got the clinical data of 232 patients diagnosed with unexplained early recurrent abortion in the second affiliated hospital of Zhengzhou University from January 2015 to December 2018.All of Patients were divided into two groups--the G-CSF group contains 185 patients who received G-CSF treatment and the control group that 47 patients who got conventional anti-abortion treatment.The records contained the uterine artery resistance,Peripheral white blood cell count,Peripheral neutrophil count,Th1/Th2 cytokine group,and lymphocyte subset percentage in the early pregnancy The abortion rate in each group was followed up to 10 weeks.2 Statistic Analysisstatistical analysis and data visualization of data were performed using SPSS 21.0(IBM Corp,Armonk,NY)and GraphPad Prism 7.01(GraphPad Software,La Jolla California USA,www.graphpad.com).The mean ± standard deviation(`x ± s)of the measurement data in accordance with the normal distribution was used,and the t test was used for comparison between the two groups.The median M(first quartile Q1,third quartile Q3)consistent with the skewed distribution was expressed using the Mann-Whitney U test.Count data were expressed as ratios and composition ratios,and comparisons between groups were made using the ? 2 test or Fisher's exact test.Receiver operating characteristic(ROC)was used to evaluate the predictive value of granulocyte count combined with interleukin-6(IL-6)in assessing the clinical efficacy of G-CSF in patients with unexplained early recurrent spontaneous abortion,using GraphPad Prism7 The.01 statistical software plots the ROC curve and calculates the Yoden's index and the best cutoff value.All statistical tests were 2-tailed and The difference was statistically significant at P < 0.05.Results1 the abortion rate of G-CSF group39 patients in the G-CSF group occurred miscarriage before 10 weeks of gestation with the abortion rate 21.08%(39/185),and the miscarriage week 7.43(6.43,8.14)weeks.,17 patients Among the control group occurred miscarriage with the abortion rate 36.17%(17/47)and the abortion week 7.00(6.14,8.87)weeks.There was a statistically significant difference in the abortion rate between the two groups(P=0.0309),and there was no statistical difference in the gestational age of abortion(P=0.3826).2 Peripheral blood biochemical indicator testIn the G-CSF group,the white blood cell count,neutrophil count,IL-10,and CD4+ T cells in the peripheral blood were significantly higher than those in the control group(P<0.05);the percentage of NK cells was lower than that of the control group.Statistical difference(P=0.0016),the other results were not statistically different(P>0.05).3 The uterine artery resistanceThe S/D values of the left and right side of the uterine artery in the G-CSF group were 6.62±2.74,5.81±2.22,12.43±3.32.The control group was 7.10±2.70,6.85±2.63,13.96±3.43.The difference was statistically significant(P < 0.05).The rate of uterine artery resistance decreased 61.62%(114/185),which was significantly higher than that of the control group(44.68%(21/47)).The difference was statistically significant(P=0.0331).4 Neutrophil combined with interleukin-10(IL-10)to assess pregnancy outcome in patients with G-CSFThe neutrophil count and interleukin-10 levels in the G-CSF group continued to be higher than those in the abortion group(P<0.05).the ROC curve Analysis of the neutrophil count and IL-10 in the G-CSF group showed that the neutrophil count(NEUTC)AUC=0.689,the best cutoff value was 8.54*109/L,the sensitivity was 0.721,the specificity was 0.677,the Yoden index was 0.397,and the IL-10 AUC= 0.838,the best truncation.the best cutoff value 2.79 pg/ml,the sensitivity 0.767,the specificity 0.821,and the Yoden index was 0.588.The combined NEUTC with IL-6 AUC=0.865,the best cutoff value 0.78,the sensitivity 0.808,the specificity 0.846,and the Yoden Results index was 0.654.The predicted value of IL-10 is significantly higher than that of neutrophils,but slightly lower than the combined predictive value of the combination Conclusions1 G-CSF could increase peripheral blood TH2 cytokines,reduce the percentage of NK cells,decrease the resistance of uterine arteries and improve the pregnancy success rate of RM patients in the first trimester.It is suggested that G-CSF can be used as an immunomodulatory to treat recurrent miscarriage.2 It is the first time to propose that peripheral blood neutrophils combined with interleukin-10(IL-10)can predict the clinical efficacy of G-CSF in RM patients with pregnancy.That provides clinic value for G-CSF in the treatment of recurrence miscarriage. |
PDF Full Text Request