Clinical Literature Research Of Traditional Chinese Medicine And Western Medicine Combine Cycle Treatment For Infertility With PCOS In The Past 20 Years

ObjectiveTo include the integrated traditional Chinese medicine and Western medicine cycle therapy for the treatment of infertility caused by PCOS as subjects,to collect and collate the literature data of the past 20 years,to summarize and conclude the syndrome,method,prescription and medicine of the disease,and to explore the development law of symptoms,therefore providing systematic ideas and objective data for future treatment and clinical use.MethodIn this study,the frequency analysis was used as a main tool to compare the frequency of syndrome,method,prescription and medicine of infertility caused by PCOS with the application of integrated traditional Chinese medicine and Western medicine cycle therapy,then explore the application of different kinds of drugs and methods in Chinese and Western medicines;finally to systematically present evidence for the treatment patterns of infertility caused by PCOS through cluster analysis and to deduce the dominant trend of medication.Subjects:The keywords used to search for literatures from January 1998 to December 2018 were cycle therapy,traditional Chinese medicine and Western medicine,polycystic ovary syndrome,ovulation disorders and infertility.Research methods:1.Meta-analysis:review of systems mainly based on the "risk of bias assessment tool" recommended by the Cochrane Collaboration for RCT literature quality evaluation;the content of RCT literature,including inclusion and exclusion criteria,efficacy criteria,randomization method,sample content,comparison of balance variables between groups,blind method,treatment method,statistical methods,follow-up,participant withdrawals and loss of follow-up were descriptively analysed in SPSS 25.0 software.2.Distribution of traditional Chinese medicine(TCM)syndromes and frequency and regularity of drug use:statistical analysis was carried out on the literatures that complied with the inclusion criteria.Excel software and SPSS 25.0 statistical software were mainly used to establish a database for frequency analysis and cluster analysis.Database:China Journal Full-text Database,Weipu Journal Database,Wanfang Database and Medical Literature Search Service System,and the Baptist University Library's literatures on the treatment of PCOS infertility with traditional Chinese medicine and Western medicine cycle therapy.The methods and medicines referred in the Western medical literature would be included.The treatment rules,prescriptions,specific medications,channel tropism,acupuncture points,meridians and other data from the literature of traditional Chinese medicine were normalised into tables to establish database for statistical analysis,class comparison,summary of phased treatment and prescription of infertility caused by PCOS in each menstrual cycle.Statistical analysis:to apply Review Manager,Excel software and statistical software,and to perform risk of bias assessment,cluster analysis,and frequency analysis on the data.Results:1.Meta-analysis:77 studies included(total of 58 pieces from traditional Chinese medicine and Western medicine/surgery combined;19 pieces from Western medicine combined with acupuncture).In the production of random sequence,19 studies(accounting for 24.68%)were rated as"medium risk" by using random number table,coin method,and draw-lots method respectively,and 2 of them(accounting for 3.00%)which were in accordance with the treatment sequence of random method,were rated as“high risk”;none of the assigned hidden items was mentioned and was then rated as "risk unknown";2 studies(accounting for 3.00%)mentioned blind method,but did not give any detailed discussion,and no other research mentioned whether blinded experiments were performed on researchers(included patients and surveyors for blinded experiments),and were rated as "risk unknown";5 studies(accounting for 6.49%)included experimental description on missing or exclusion situations,the number of missing persons was<20%,and thus rated as "low risk";the included studies did not mention whether there were other potential risks,such as early termination of research and deceptive behaviour,and was rated as“risk unknown".In conclusion,the 77 pieces of literatures included in this study were of middle level,and the overall literature quality was moderate.58 experimental results involved a total of 3540 cases from an integrated traditional Chinese medicine and Western medicine/surgery,and there were homogeneity between each study(P=0.04,I2-25%).The total effective rate of the experimental group as compared to the control group in the treatment of PCOS infertility was[OR=3.78,95%CI(3.29,4.34,P<0.00001)].Acupuncture combined with Western medicine as compared to Western medical treatment to treat PCOS infertility,19 experimental results involved a total of 1814 cases,and there were homogeneity in each study(P=0.31,I 2=11%),with total effective rate of[OR=2.64,95%CI(2.14,3.25,P<0.00001)].Integrated traditional Chinese medicine and Western medicine was used to treat PCOS infertility as compared to Western medical treatment,51 experimental results involved a total of 4350 cases,and there were homogeneity between each study(P=0.47,I2=0%),and the pregnancy rate was[OR=2.76,95%CI(2.43,3.13,P<0.00001)].16 experimental results involved a total of 1582 cases,and there were homogeneity between each study(P=0.50,I2=0%),and the pregnancy rate of acupuncture combined with Western medicine was[OR=2.45,95%CI(1.98,3.04,P<0.00001))].26(Traditional Chinese medicine and Western medicine/surgery combination)experimental results involved a total of 2228 cases,and the heterogeneity between each study was acceptable(P=0.00005,I2=55%),the experimental group compared with the control group for the treatment of PCOS infertility's ovulation rate was[OR=2.88,95%CI(2.39,3.50,P<0.00001)].10 experimental results involved a total of 1022 cases,and there were homogeneity between each study(P=0.62,I2=0%),ovulation rate of acupuncture combined with Western medicine was[OR=2.70,95%CI(2.00,3.66,P<0.00001)].The law of treatment:According to the research objectives and inclusion criteria,84 literatures that met the literature inclusion criteria were selected as subjects.66 of them were integrated traditional Chinese medicine and Western medicine cycle therapy literatures and the remaining 18 were combination of acupuncture and Western medicine cycle therapy literatures.(1)Etiologic and pathologic analysisAmong the 84 literatures,73 of them referred to the syndromes,and the first 3 traditional Chinese medicine syndromes with the highest frequency were liver depression and kidney deficiency(17),kidney yin and yang deficiency(10),kidney yin deficiency(4),and the relationship with kidney was the closest.(2)Analysis of medication and prescriptionIn the 84 literatures regarding the traditional Chinese medicine used for the treatment of PCOS infertility with cycle method in this study,there were four cycles involving 93 kinds of medicines(Table 4-7).The total usage frequency was 2557 times,833 times in the follicular phase,851 times in the ovulation period,653 times in the luteal phase,and 242 times in the menstrual period,respectively.There were 67 kinds of medicines in the follicular phase with usage frequency>=2,and have appeared for a total of 815 times,accounting for 97.83%of the total drug usage frequency,18 kinds of medicines with usage frequency<2,appearing for 18 times,accounting for 2.16%of the total drug usage frequency;there were 72 kinds of medicines in the ovulation period with usage frequency>=2,and have appeared for a total of 829 times,accounting for 97.41%of the total drug usage frequency;23 kinds of medicines with usage frequency<2,appearing for 23 times,accounting for 2.70%of the total drug usage frequency;there were 57 kinds of medicines in the luteal phase with usage frequency>=2,and have appeared for a total of 639 times,accounting for 97.86%of the total drug usage frequency,14 kinds of medicines with usage frequency<2,appearing for 14 times,accounting for 2.14%of the total drug usage frequency;there were 30 kinds of medicines in the menstrual period with usage frequency>=2,and have appeared for a total of 210 times,accounting for 84.71%of the total drug usage frequency,31 kinds of medicines with usage frequency<2,appearing for 31 times,accounting for 15.29%of the total drug usage frequency.The classification specification was based on "Science of Chinese Pharmacology"(edited by Huang Zhaosheng,People's Medical Publishing House,2002,1st edition).The following are the classifications:solution medicine,tonic medicine,heat-clearing medicine,laxative,damp-relieving medicine,rheumatism medicine,diuresis-promoting medicine,qi-regulating medicine,Wenli medicine,phlegm,cough and asthma relieving medicine,blood circulation medicine,hemostyptic,tranquilizer,secreting medicine,enlightening medicine,digestion medicine,Pinggan Xifeng medicine,detoxification and insecticide dampness and antipruritic drugs.The rankings for medicine categories with highest frequency are:follicular phase:tonic class(61.94%)commonly used drugs are Fructus Ligustri Lucidi,wolfberry,Eclipta Prostrata,dodder,Epimedium,Angelica sinensis,Dioscorea polystachya,Cornu Cervi Degelatinatum,Himalayan Teasel Root,Amethyst,Cistanche Deserticola,Paeonia lactiflora,Fallopia multi flora,Astragalus,and Atractylodes.Commonly used medicines for promoting blood circulation(9.84%)include Ligusticum striatum,Salvia miltiorrhiza,Achyranthes,peach kernel,and safflower.The commonly used drugs for qi(5.16%)include Cyperus Rotundus,Chenpi and Poncirus Trifoliata.Commonly used drugs for astringent(4.92%)include Cornus Officinalis,Rubus Idaeus,and Schisandra Chinensis.Commonly used drugs for diuresis-promoting(4.08%)are Wolfiporia Extensa,Alisma Plantago-aquatica and Plantago asiatica.Commonly used drugs for phlegm,cough and asthma relieving(4.08%)are Pinellia Ternata,Arisaema Cum Bile,and Chinese Honeylocust Spine.Commonly used drugs for heat-clearing(3.60%)include peony bark,Paeonia Anomala,and Rehmannia Glutinosa.Ovulation period:The commonly used drugs for promoting blood circulation(23.85%)include Salvia Miltiorrhiza,peach kernel,Lycopus Asper,Ligusticum Striatum,safflower,Spatholobus,and Achyranthes.The common drugs used in Bu Yang(19.62%)are Cuscuta,Epimedium,Dipsacaceae,Amethyst,Cornu Cervi Degelatinatum,Curculigo,and Psoralea Corylifolia.The most commonly used drugs for blood supplementation(11.52%)are Angelica,Rehmannia,and Paeonia lactiflora.The most commonly used drugs for qi(6.93%)are Dioscorea polystachya,Atractylodes,Glycyrrhiza Uralensis,Astragalus,and Codonopsis Pilosula.The most commonly used drugs for heat-clearing(6.46%)are Paeonia Anomala,Rehmannia glutinosa,peony bark,and Phellodendron.The most commonly used drugs for qi(6.35%)are Cyperus Rotundus,Chenpi,Poncirus Trifoliata,and Saussurea Costus.The most commonly used drugs for yin(5.52%)are Wolfberry,Ligustrum Lucidum,Fructus Leonuri,Eclipta Prostrata,and Carapax Trionycis.Luteal phase:the most commonly used drugs for Bu Yang(33.69%)are dodder,Dipsacaceae,Epimedium,Gynochthodes officinalis,Curculigo,Amethyst,and Cistanche.The most commonly used drugs for blood supplementation(16.69%)are Angelica,Rehmannia,Paeonia Lactiflora,Fallopia multiflora,and Donkey-hide gelatin.The most commonly used drugs for qi(9.34%)are Dioscorea Polystachya,Scutellaria,Atractylodes,Codonopsis,and Glycyrrhiza Uralensis.The most commonly used drugs for activating blood circulation(7.81%)are Achyranthes,Astragalus,Salvia,Motherwort,and peach kernel.The most commonly used drugs for yin(6.89%)are Fructus Ligustri Lucidi,wolfberry and Eclipta.The most commonly used drugs for qi(4.44%)are Chenpi,Cyperus rotundus and rose.The most commonly used drugs for phlegm,cough and asthma relieving(3.22%)are Pinellia,Arisaema Cum Bile,and Fritillaria.Menstrual period:The most commonly used drugs for promoting blood circulation(42.98%)are Ligusticum Striatum,Lycopus Asper,Leonurus Japonicus,peach kernel,Salvia,safflower and Achyranthes.The most commonly used drugs for blood supplementation(16.12%)are Angelica,Rehmannia and Paeonia Lactiflora.The most commonly used drugs for qi(12.40%)are Cyperus Rotundus,Chenpi,Poncirus Trifoliata,and Lindera Aggregata.The most commonly used drugs for heat-clearing(7.85%)are Paeonia Anomala and Rehmannia Glutinosa.The most commonly used drugs for qi(5.37%)are Glycyrrhiza Uralensis,Dioscorea polystachya and Chinese liquorice.The most commonly used drugs for Bu Yang(5.37%)are Cuscuta Chinensis and Epimedium.The most commonly used types of dampness-removing(1.65%)are Atractylodes Lancea and Magnolia.Conclusion:Clinical research literatures within the period of 1998-2018 on the treatment of PCOS infertility with integrated traditional Chinese medicine and Western medicine cycle therapy were examined and a total of 562 articles were retrieved.The quality of these literatures were evaluated.77 literatures were included for META analysis,and 84 papers were used to examine the use of traditional Chinese medicine and Western medicine,use of cavity and the law of treatment.1.Meta analysis:(1)Combination of traditional Chinese medicine and Western medicine,combination of acupuncture and Western medicine are better than Western medicine treatment.(2)The combination of traditional Chinese medicine and Western medicine,and the combination of acupuncture and Western medicine treatment in treating the pregnancy rate and ovulation rate of PCOS infertility were better than Western medicine treatment.(3)The combination of traditional Chinese medicine and Western medicine,and the combination of acupuncture and Western medicine treatment in treating PCOS infertility were one of the effective methods,but the quality of methodology of clinical randomized controlled trials was moderate,and there was a certain risk of bias;future research should strictly follow the principle of medicine and strictly control the medical quality.2.Traditional Chinese medicine and Western medicine's pathogenesis and treatment rules:(1)Kidney deficiency is the basic pathogenesis of infertility caused by polycystic ovary syndrome.(2)The treatment of infertility caused by polycystic ovary syndrome should mainly base on tonic medicine and blood circulation-promoting medicine.In terms of meridian,it is based on Ren Meridian and the three yin channel of the foot.(3)Follicular phase and ovulation period are the key opportunities for treatment.(4)The combination of traditional Chinese medicine and Western medicine can increase pregnancy rate.