Research On Combined Chinese And Western Medical Treatment Guideline For Ovulatory Disorders Of Infertility

Research Purpose1.Following the evidence-based principle,we combed through the research on polycystic ovary syndrome(PCOS),hyperprolactinemia(HPRL),luteal insufficiency(LPD),premature ovarian insufficiency(POI)/premature ovarian failure(POF)/decreased ovarian reserve function(DOR)/low ovarian response(POR),anovulatory abnormal uterine bleeding(AUB-O),luteinized unruptured follicle syndrome(LUFS).The existing guidelines do not yet reflect the advantages of combining Chinese and Western medicine in the diagnosis and treatment of ovulatory disorders,therefore,the "Guidelines for Combining Chinese and Western Medicine in the Treatment of Ovulatory Disorders" have been formulated to provide medical practitioners of gynecology,reproductive medicine,Chinese medicine,combined Chinese and Western medicine,and related nursing staff at all levels of health care institutions with the opportunity to discuss and discuss the issues related to ovulatory disorders.2.Based on the preliminary study of the guidelines,one of the diseases POI leading to ovulatory disorders of infertility was selected to provide a paradigm for subsequent relevant clinical research protocols.Research Method一、Guideline Study1.Establishment of the guideline project team:the project team involved in guideline development was identified according to the principle of equal emphasis on Chinese and Western medicine.2.Construction of clinical problems:clinical problems were identified according to the expert consensus method by means of expert interview studies and clinical questionnaire research,combined with clinical reality.3.Determination of evidence and evidence elements:according to the results of expert interview studies and clinical research,combined with clinical reality,and after discussion by the expert group.4.Screening and synthesis of evidence:develop a reasonable search strategy,systematically search both English and Chinese databases,search time frame from the establishment of the database to 2022.7.20,according to the evidence pyramid,according to the nadir criteria to screen the last two years of systematic evaluation and randomized controlled trials,if the retrieved systematic evaluation is of high quality,it can be directly applied;if it is determined that there is no systematic evaluation of high relevance and or high methodological quality.If it was determined that there were no systematic evaluations of high relevance or methodological quality,they were recreated.For studies with high homogeneity of homologous study diseases,interventions,controls and outcome indicators,Meta-analysis was performed using the RevMan 5.3 software provided by the Cochrane Collaboration Network.5.Evidence quality evaluation:Grading of evidence and strength of recommendation were classified using the GRADE method,an internationally accepted system for evaluating evidence,and the Recommendations for Grading Clinical Evidence in Chinese Medicine Based on Body of Evidence.For the recommended drugs that are not applicable to the GRADE method and have already been recommended in the guideline recommendations,relevant works are used to make recommendations,and if recommendations lacking research evidence are presented by expert consensus.6.Formation of recommendations and consensus methods:Based on the inclusion of research evidence,attention is paid to patient preferences and values,and the balance of costs and pros and cons of interventions is paid attention to,and a preliminary recommendation suitable for China is prepared.The draft recommendations were discussed and validated using the nominal group method and the Delphi method in the formal expert consensus method,and consensus was reached.二、Clinical protocolThe content analysis and quality evaluation of the included clinical study protocols,based on the study of the Guidelines for Combination of Chinese and Western Medicine in the Diagnosis and Treatment of Ovulatory Disorders of Infertility,showed that there were problems of low quality level.Therefore,following the clinical trial report specifications,a standardized design of the clinical study of combined Chinese and Western medicine diagnosis and treatment of POI infertility was conducted,and some key issues that need attention in the protocol design were optimized with reference to the discussion suggestions of the clinical study protocol in the guidelines.Research Results一、Guideline Study1.Clinical questions:10 clinical questions were identified based on expert interviews and clinical questionnaire research.2.Evidence type and evidence elements:common evidence of ovulatory disorders of infertility were:kidney qi deficiency,kidney yang deficiency,kidney yin deficiency,liver stagnation,phlegm-dampness,blood stasis,and kidney deficiency and blood stasis;evidence elements of disease location category were kidney and liver;evidence elements of disease nature category were:qi deficiency,yang deficiency,yin deficiency,qi stagnation,phlegm-dampness,and blood stasis.3.Evidence screening and synthesis:441 items were retrieved from the systematic evaluation literature search,and 2853 items were retrieved from the randomized controlled trial literature search.The final systematic evaluation included 21,due to the absence of correlation high and or higher methodological quality of the systematic evaluation,reformulated Meta-analysis 25,single randomized controlled trial data 156.4.Quality evaluation:In terms of the quality of the included literature,most of the included studies were of low quality level,3 systematic studies were moderate quality evidence,1 Meta-analysis was very low quality evidence,and the rest were low quality Evidence.5.Recommendations:Disease categories:disorders of ovulatory infertility mainly include PCOS,HPRL,LPD,POI/POF/DOR/POR,AUB-O,LUFS(level IV evidence,expert consensus degree:100%).Western medicine diagnosis:the currently accepted guidelines or expert consensus were used to determine the diagnostic criteria for the 6 diseases causing ovulatory disorders of infertility(level IV evidence,expert consensus:92.86%).Traditional Chinese medicine diagnosis:the "Questionnaire on Chinese medical evidence and evidence elements of ovulatory disorders" was used to determine the evidence elements,and the evidence types were kidney qi deficiency,kidney yin deficiency,kidney yang deficiency,liver depression,phlegm-dampness,stasis,and kidney deficiency and blood stasis(level Ⅳ evidence,expert consensus:85.71%).Outcome indicators:mainly include ovulation rate,pregnancy rate,and live birth rate(level Ⅳ evidence,expert consensus:92.86%).Daily regimen:Patients are recommended to regulate in four aspects:psycho-emotional,exercise,weight and diet(level Ⅳ evidence,expert consensus:96.43%).Treatment principle:It is recommended that on the basis of holistic diagnosis treatment in TCM,a Western ovulation promotion program(or medication)should be chosen starting from day 5 of the menstrual cycle(or day 5 of withdrawal bleeding)for 3 consecutive menstrual cycles as a course of treatment(level Ⅳ evidence,expert consensus:85.71%).Treatment options:A total of 33 recommendations.(1)Ovulation disorder infertility:Jin Kui Kidney Qi Pill for kidney qi deficiency(level Ⅳ evidence,strong recommendation),Right Return Pill for kidney yang deficiency(level Ⅳ evidence,strong recommendation),Letrozole combined with Kuntai Capsule for kidney yin deficiency(level C evidence,strong recommendation)or Letrozole combined with Gynecological Reclamation Capsule(level C evidence,strong recommendation),Letrozole combined with Ding Kun Dan for liver depression(level C evidence,weak recommendation),Phlegm-Damp(levelⅣ,strong recommendation),Gui Zhi Fu Ling Wan(level Ⅳ,strong recommendation)for stasis,and Zuo Gui Wan(level Ⅳ,weak recommendation)or Jin Kui Kidney Qi Wan(level Ⅳ,weak recommendation)for kidney deficiency and blood stasis overlaid with Blood Mansions and Stasis Capsules(level Ⅳ,weak recommendation).(2)Obstructed ovulation infertility due to PCOS:for phlegm-damp type,use ethinyl estradiol cyproterone tablets/clomiphene/metformin/drospirenone ethinyl estradiol tablets in combination with Cang Zhi Gui Phlegm Pill/Tang(Class C evidence,strong recommendation),for stasis type,use ethinyl estradiol cyproterone tablets/clomiphene/human chorionic gonadotropin in combination with Gui Zhi Fu Ling Wan(Class C evidence,weak recommendation),for kidney-yin deficiency type,use letrozole in combination with Kun Tai Capsule(Class Ⅳ evidence,strong recommendation).The main acupuncture points recommended for acupuncture are San Yin Jiao,Guan Yuan,Zhong Ji,Zi Gong,Qi Hai,Foot San Li,and Sanyu.The main acupuncture points recommended are Sanyinjiao,Guan Yuan,Zhongji,Zi Gong,Qi Hai,Shu San Li,Feng Long,Kidney Yu,Tai Chong,Yin Ling Quan,,and Blood Sea(frequency>10 times)(Grade Ⅳ evidence,weak recommendation).(3)Ovulatory infertility due to HPRL:use bromocriptine combined with prolotherapy(Class C evidence,strong recommendation)or Dingkun Dan(Class Ⅳ evidence,weak recommendation)for liver-depression type.(4)Ovulatory infertility due to LPD:use bromocriptine combined with compound Xuanju capsule(Class C evidence,weakly recommended)or progesterone capsule combined with Nuanguangzi capsule(Class C evidence,weakly recommended)for kidney yang deficiency.(5)Ovulation disorders caused by POI:Estradiol Tablets/Estradiol Digestrol Tablets combined with Yi Jing Tang for Kidney Yin-Yang deficiency(Grade C evidence,weakly recommended);Ovulation disorders caused by DOR:Estradiol Valerate Tablets and Progesterone combined with Kidney Return Pill for Kidney Yin deficiency(Grade C evidence,strongly recommended);Ovulation disorders caused by POR:Desogestrel Estradiol Tablets and Gonadotropin Releasing Capsules for Kidney Yin deficiency(Grade C evidence,strongly recommended).In POR-induced ovulatory infertility,the use of desogestrel estradiol tablets and gonadotropin-releasing hormone agonist combined with Zuo Gui Pill(Level C evidence,strong recommendation)is recommended,as is the use of acupuncture combined with assisted reproductive technology(in vitro fertilization embryo transfer)(Level C evidence,strong recommendation).(6)Ovulation disorder infertility due to LUFS:for the type of stasis,the combination of Hemifu and Yu Tang with clomiphene and human chorionic gonadotropin and Hemifu and Yu Capsule/Tang with human chorionic gonadotropin(Level C evidence,strong recommendation),and for the type of kidney qi deficiency,the combination of clomiphene and human chorionic gonadotropin with Jin Kui Kidney Qi Pill Plus(Level C evidence,strong recommendation).二、Clinical protocolThe clinical study of combined Chinese and Western medicine diagnosis and treatment of POI infertility was designed and key elements were discussed in terms of study background,study objectives,study methods,study subjects,interventions,observation indexes and observation time points,efficacy and safety criteria,documentation of adverse events,medical ethics requirements,quality control,data management and statistical analysis.Research ConclusionCombination of Chinese and Western medicine has unique advantages and definite efficacy in the treatment of ovulatory disorders.The "Guidelines for the Treatment of Ovulatory Infertility with Integrative Chinese and Western Medicine"adheres to evidence-based principles,standardizes systematic searches of the literature on ovulatory infertility,strictly follows the relevant rules of drafting,selects the best evidence,formulates recommendations for the treatment of integrative Chinese and Western medicine,and designs relevant clinical research protocols to provide preliminary evidence support,opening up new ideas for the study of ovulatory infertility.