Meta-analysis Of TCM Bushen Huoxue Therapy In Recurrent Spontaneous Abortion

ObjectiveThis study adopts a meta-analysis method to systematically evaluate the efficacy and safety of TCM Bushen Huoxue therapy in recurrent spontaneous abortion,and statistically analyze the rule and characteristics of Bushen Huoxue method in recurrent spontaneous abortion,and provide evidence-based reference for clinical treatment of this disease.MethodsBy using different keywords such as "recurrent spontaneous abortion","recurrent miscarriage" "habitual abortion" "Bushen Huoxue",etc.,an extensive literature search was conducted to achieve local and overseas publications through China Knowledge Network Full-text Journal Database(CNKI),China Biomedical Literature Database(CBM),Weipu Chinese Stcience and Technology Periodical Database(VIP),Wanfang Database,Medline(PubMed),CENTRAL(The Cochrane Library)and other databases.Each database was searched from October 2002 to October 2018.Papers were screened according to the inclusion and exclusion criteria and the basic information of RCTs was extracted from the included literature.The methodological quality of included RCTs was evaluated according to the Cochrane Bias Risk Scale.The outcome measures of meta-analysis were analyzed by Review Manager version 5.3 statistical software provided by Cochrane.We used Microsoft Excel software to establish database from which the prescriptions and medication patterns of TCM Bushen Huoxue method for recurrent spontaneous abortion were statistically analyzed.ResultsBased on the above search results,a total of 33 studies were identified.All of the 33 trials were conducted in China,and published in Chinese journals.A total of 3,216 RSA patients participated,with an average sample size of 94.57,with a maximum of 188 and a minimum of 38.11 research projects reported funded by fund projects.The methodological quality of the included 33 RCTs literature was evaluated.It was found that 33 studies were randomized.14 RCTs have specific randomized methods,including 12 randomized digital tables,1 randomized control,and 1 randomly drawn.None of the 33 studies mentioned whether to hide the randomization protocol,nor did a study mention to blindness.Eight studies reported withdrawal,shedding,and exclusion during the trial,but none of them mentioned the use of Intension-to-treat Analysis.Therefore,there are various research methodological problems in the 33 research literatures,which may lead to high risk bias.For the 17 studies included,the meta-analysis of the pregnancy over the study for more than 12 weeks of pregnancy showed that the Bushen Huoxue experimental group found a superior effect over western medicine group(OR=2.22,95%CI[1.75,2.81],P<0.00001).The results of the subgroup showed that the efficacy of combination therapy with Chinese and Western medicine was significantly higher than that of western medicine(OR=2.98,95%CI[2.23,3.98],P<0.00001).After excluding one heterogeneity study,the Chinese medicine group was also superior to the western medicine(OR=1.72,95%CI[1.02,2.91],P=0.04).In the meta-analysis of early abortion,the results suggest the experimental group was better than that of the control group(OR=0.45,95%CI[0.36,0.57],P<0.00001).The subgroup analysis also showed that the efficacy of combination therapy with Chinese and Western medicine found a superior effect over western medicine(OR=0.34,95%CI[0.25,0.46],P<0.00001).However,the comparison of Chinese medicine alone and western medicine showed that Chinese medicine treatment was superior after excluding heterogeneity study(OR=0.57,95%CI[0.34,0.96],P=0.04).17 trials reported live birth rate,the meta-analysis showed that the Bushen Huoxue experimental group found a superior effect over western medicine group(OR=2.41,95%CI[1.89,3.07],P<0.00001).Subgroup analysis showed that the efficacy of combination therapy with Chinese and Western medicine was more advantageous than western medicine(OR=2.69,95%CI[1.98,3.65],P<0.00001).However,the comparison between Chinese medicine alone and western medicine showed that Chinese medicine treatment still had an advantage after excluding heterogeneity(OR=2.56,95%CI is[1.64,3.98],P<0.0001).In terms of laboratory indicators,7 trials reported the effect of ACA antibody.Meta-analysis showed that the Bushen Huoxue experimental group found a superior effect over western medicine group(OR=2.73,95%CI[1.72,4.33],P<0.0001),and the effect of combination therapy with Chinese and Western medicine is better than western medicine alone(OR=3.51,95%CI[1.82,6.79],P=0.0002).In terms of reducing the level of D-dimer in patients with recurrent spontaneous abortion,the results showed that compared with western medicine,there was no advantage in either Chinese medicine treatment or combination therapy with Chinese and Western medicine(Chinese medicine:SMD=-0.12,95%CI[-0.31,0.07],P=0.21;Chinese and Western medicine:SMD=-0.10,95%CI[-0.23,0.03],P=0.12).Safety evaluation:Only five studies specifically reported adverse events and drug side effects.However,the concerned information is too little to indicate what standardized monitoring is based on or whether patients voluntarily report to fill in the relevant results.In clinical trials,some incidents or serious negative events should be monitored through epidemiological observational studies.Due to the limited number of randomized controlled trials can be monitored by this system,and there is no placebo-controlled trials,and the time of treatment and follow-up is not long enough,there is no monitoring or report of adverse reactions.Therefore,the evaluation of safety of Bushen Huoxue therapy in recurrent spontaneous abortion could not draw definite conclusions.The frequency counting method was adopted to observe the medication pattern of Bushen Huoxue therapy for effective study cases.The treatment of RSA is mainly by nourishing of kidney-yang and activating of blood circulation and removing of blood stasis.Moreover,supplement treatments could be adopted through enriching of qi and blood,cooling of heat and blood,convergence to stop bleeding,regulating of liver-qi and diluting of water and dampness.The frequency counting method showed that a total of 59 herbal medicines were used in the treatment of RSA patients.The medicine with highest frequency use of nourishing kidney-yang,including Tusizi,Xuduan,Sangjisheng,DuZhong,while the second most frequently used medicine is blood stasis,sucha as Danshen,Angelica,Chuanxiong,Akasaka,etc.Conclusion1.According to the findings of systematic review and meta-analysis of 33 RCTs,with 3,216 participants included,the Bushen Huoxue therapy in combination with Western medicine treatment demonstrated potentially beneficial effect in improving pregnancy efficiency,reducing early abortion rate,as well as improving live birth rate and ACA antibody conversion rate for women with recurrent miscarriage.Due to the lack of information,the evaluation of safety of Bushen Huoxue therapy in recurrent spontaneous abortion cannot draw definite conclusions.2.Through the frequency counting method,it was found that the treatment of RSA was mainly by nourishing of kidney-yang and activating of blood circulation and removing of blood stasis.Moreover,supplement treatments could be adopted through enriching of qi and blood,cooling of heat and blood,convergence to stop bleeding,regulating of liver-qi and diluting of water and dampness.Among them,the most frequently used kidney-yang reinforcement medicines are Tusizi,Xuduan,SangJisheng,DuZhong,while the second most frequently used medicine is blood stasis,which including Danshen,Angelica,Chuanxiong,Akasaka,etc.