Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis

Identifying the most effective Traditional... | F1000Research "use strict";function _typeof(t){return(_typeof="function"==typeof Symbol&&"symbol"==typeof Symbol.iterator?function(t){return typeof t}:function(t){return t&&"function"==typeof Symbol&&t.constructor===Symbol&&t!==Symbol.prototype?"symbol":typeof t})(t)}!function(){var t=function(){var t,e,o=[],n=window,r=n;for(;r;){try{if(r.frames.__tcfapiLocator){t=r;break}}catch(t){}if(r===n.top)break;r=r.parent}t||(!function t(){var e=n.document,o=!!n.frames.__tcfapiLocator;if(!o)if(e.body){var r=e.createElement("iframe");r.style.cssText="display:none",r.name="__tcfapiLocator",e.body.appendChild(r)}else setTimeout(t,5);return!o}(),n.__tcfapi=function(){for(var t=arguments.length,n=new Array(t),r=0;r 3&&2===parseInt(n[1],10)&&"boolean"==typeof n[3]&&(e=n[3],"function"==typeof n[2]&&n[2]("set",!0)):"ping"===n[0]?"function"==typeof n[2]&&n[2]({gdprApplies:e,cmpLoaded:!1,cmpStatus:"stub"}):o.push(n)},n.addEventListener("message",(function(t){var e="string"==typeof t.data,o={};if(e)try{o=JSON.parse(t.data)}catch(t){}else o=t.data;var n="object"===_typeof(o)&&null!==o?o.__tcfapiCall:null;n&&window.__tcfapi(n.command,n.version,(function(o,r){var a={__tcfapiReturn:{returnValue:o,success:r,callId:n.callId}};t&&t.source&&t.source.postMessage&&t.source.postMessage(e?JSON.stringify(a):a,"*")}),n.parameter)}),!1))};"undefined"!=typeof module?module.exports=t:t()}(); dataLayer = dataLayer || []; // Standard GTM initialization - Google Consent Mode handles consent automatically (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start': new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src= 'https://www.googletagmanager.com/gtm.js?id='+i+dl+ '>m_auth=hzk0Vc3qFsQYhCrIoHz68A>m_preview=env-1>m_cookies_win=x';f.parentNode.insertBefore(j,f); })(window,document,'script','dataLayer','GTM-MWFK8L5J'); ;window.NREUM||(NREUM={});NREUM.init={distributed_tracing:{enabled:true},privacy:{cookies_enabled:true},ajax:{deny_list:["bam.nr-data.net"]}}; ;NREUM.loader_config={accountID:"438030",trustKey:"438030",agentID:"772317073",licenseKey:"97f8f67f26",applicationID:"772317073"} ;NREUM.info={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net",licenseKey:"97f8f67f26",applicationID:"772317073",sa:1} ;/*! For license information please see nr-loader-spa-1.236.0.min.js.LICENSE.txt */ (()=>{"use strict";var e,t,r={5763:(e,t,r)=>{r.d(t,{P_:()=>l,Mt:()=>g,C5:()=>s,DL:()=>v,OP:()=>T,lF:()=>D,Yu:()=>y,Dg:()=>h,CX:()=>c,GE:()=>b,sU:()=>_});var n=r(8632),i=r(9567);const o={beacon:n.ce.beacon,errorBeacon:n.ce.errorBeacon,licenseKey:void 0,applicationID:void 0,sa:void 0,queueTime:void 0,applicationTime:void 0,ttGuid:void 0,user:void 0,account:void 0,product:void 0,extra:void 0,jsAttributes:{},userAttributes:void 0,atts:void 0,transactionName:void 0,tNamePlain:void 0},a={};function s(e){if(!e)throw new Error("All info objects require an agent identifier!");if(!a[e])throw new Error("Info for ".concat(e," was never set"));return a[e]}function c(e,t){if(!e)throw new Error("All info objects require an agent identifier!");a[e]=(0,i.D)(t,o),(0,n.Qy)(e,a[e],"info")}var u=r(7056);const d=()=>{const e={blockSelector:"[data-nr-block]",maskInputOptions:{password:!0}};return{allow_bfcache:!0,privacy:{cookies_enabled:!0},ajax:{deny_list:void 0,enabled:!0,harvestTimeSeconds:10},distributed_tracing:{enabled:void 0,exclude_newrelic_header:void 0,cors_use_newrelic_header:void 0,cors_use_tracecontext_headers:void 0,allowed_origins:void 0},session:{domain:void 0,expiresMs:u.oD,inactiveMs:u.Hb},ssl:void 0,obfuscate:void 0,jserrors:{enabled:!0,harvestTimeSeconds:10},metrics:{enabled:!0},page_action:{enabled:!0,harvestTimeSeconds:30},page_view_event:{enabled:!0},page_view_timing:{enabled:!0,harvestTimeSeconds:30,long_task:!1},session_trace:{enabled:!0,harvestTimeSeconds:10},harvest:{tooManyRequestsDelay:60},session_replay:{enabled:!1,harvestTimeSeconds:60,sampleRate:.1,errorSampleRate:.1,maskTextSelector:"*",maskAllInputs:!0,get blockClass(){return"nr-block"},get ignoreClass(){return"nr-ignore"},get maskTextClass(){return"nr-mask"},get blockSelector(){return e.blockSelector},set blockSelector(t){e.blockSelector+=",".concat(t)},get maskInputOptions(){return e.maskInputOptions},set maskInputOptions(t){e.maskInputOptions={...t,password:!0}}},spa:{enabled:!0,harvestTimeSeconds:10}}},f={};function l(e){if(!e)throw new Error("All configuration objects require an agent identifier!");if(!f[e])throw new Error("Configuration for ".concat(e," was never set"));return f[e]}function h(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");f[e]=(0,i.D)(t,d()),(0,n.Qy)(e,f[e],"config")}function g(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");var r=l(e);if(r){for(var n=t.split("."),i=0;i {r.d(t,{D:()=>i});var n=r(50);function i(e,t){try{if(!e||"object"!=typeof e)return(0,n.Z)("Setting a Configurable requires an object as input");if(!t||"object"!=typeof t)return(0,n.Z)("Setting a Configurable requires a model to set its initial properties");const r=Object.create(Object.getPrototypeOf(t),Object.getOwnPropertyDescriptors(t)),o=0===Object.keys(r).length?e:r;for(let a in o)if(void 0!==e[a])try{"object"==typeof e[a]&&"object"==typeof t[a]?r[a]=i(e[a],t[a]):r[a]=e[a]}catch(e){(0,n.Z)("An error occurred while setting a property of a Configurable",e)}return r}catch(e){(0,n.Z)("An error occured while setting a Configurable",e)}}},6818:(e,t,r)=>{r.d(t,{Re:()=>i,gF:()=>o,q4:()=>n});const n="1.236.0",i="PROD",o="CDN"},385:(e,t,r)=>{r.d(t,{FN:()=>a,IF:()=>u,Nk:()=>f,Tt:()=>s,_A:()=>o,il:()=>n,pL:()=>c,v6:()=>i,w1:()=>d});const n="undefined"!=typeof window&&!!window.document,i="undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self.navigator instanceof WorkerNavigator||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis.navigator instanceof WorkerNavigator),o=n?window:"undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis),a=""+o?.location,s=/iPad|iPhone|iPod/.test(navigator.userAgent),c=s&&"undefined"==typeof SharedWorker,u=(()=>{const e=navigator.userAgent.match(/Firefox[/\s](\d+\.\d+)/);return Array.isArray(e)&&e.length>=2?+e[1]:0})(),d=Boolean(n&&window.document.documentMode),f=!!navigator.sendBeacon},1117:(e,t,r)=>{r.d(t,{w:()=>o});var n=r(50);const i={agentIdentifier:"",ee:void 0};class o{constructor(e){try{if("object"!=typeof e)return(0,n.Z)("shared context requires an object as input");this.sharedContext={},Object.assign(this.sharedContext,i),Object.entries(e).forEach((e=>{let[t,r]=e;Object.keys(i).includes(t)&&(this.sharedContext[t]=r)}))}catch(e){(0,n.Z)("An error occured while setting SharedContext",e)}}}},8e3:(e,t,r)=>{r.d(t,{L:()=>d,R:()=>c});var n=r(2177),i=r(1284),o=r(4322),a=r(3325);const s={};function c(e,t){const r={staged:!1,priority:a.p[t]||0};u(e),s[e].get(t)||s[e].set(t,r)}function u(e){e&&(s[e]||(s[e]=new Map))}function d(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:"",t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:"feature";if(u(e),!e||!s[e].get(t))return a(t);s[e].get(t).staged=!0;const r=[...s[e]];function a(t){const r=e?n.ee.get(e):n.ee,a=o.X.handlers;if(r.backlog&&a){var s=r.backlog[t],c=a[t];if(c){for(var u=0;s&&u {let[t,r]=e;return r.staged}))&&(r.sort(((e,t)=>e[1].priority-t[1].priority)),r.forEach((e=>{let[t]=e;a(t)})))}function f(e,t){var r=e[1];(0,i.D)(t[r],(function(t,r){var n=e[0];if(r[0]===n){var i=r[1],o=e[3],a=e[2];i.apply(o,a)}}))}},2177:(e,t,r)=>{r.d(t,{c:()=>f,ee:()=>u});var n=r(8632),i=r(2210),o=r(1284),a=r(5763),s="nr@context";let c=(0,n.fP)();var u;function d(){}function f(e){return(0,i.X)(e,s,l)}function l(){return new d}function h(){u.aborted=!0,u.backlog={}}c.ee?u=c.ee:(u=function e(t,r){var n={},c={},f={},g=!1;try{g=16===r.length&&(0,a.OP)(r).isolatedBacklog}catch(e){}var p={on:b,addEventListener:b,removeEventListener:y,emit:v,get:x,listeners:w,context:m,buffer:A,abort:h,aborted:!1,isBuffering:E,debugId:r,backlog:g?{}:t&&"object"==typeof t.backlog?t.backlog:{}};return p;function m(e){return e&&e instanceof d?e:e?(0,i.X)(e,s,l):l()}function v(e,r,n,i,o){if(!1!==o&&(o=!0),!u.aborted||i){t&&o&&t.emit(e,r,n);for(var a=m(n),s=w(e),d=s.length,f=0;fn,p:()=>i});var n=r(2177).ee.get("handle");function i(e,t,r,i,o){o?(o.buffer([e],i),o.emit(e,t,r)):(n.buffer([e],i),n.emit(e,t,r))}},4322:(e,t,r)=>{r.d(t,{X:()=>o});var n=r(5546);o.on=a;var i=o.handlers={};function o(e,t,r,o){a(o||n.E,i,e,t,r)}function a(e,t,r,i,o){o||(o="feature"),e||(e=n.E);var a=t[o]=t[o]||{};(a[r]=a[r]||[]).push([e,i])}},3239:(e,t,r)=>{r.d(t,{bP:()=>s,iz:()=>c,m$:()=>a});var n=r(385);let i=!1,o=!1;try{const e={get passive(){return i=!0,!1},get signal(){return o=!0,!1}};n._A.addEventListener("test",null,e),n._A.removeEventListener("test",null,e)}catch(e){}function a(e,t){return i||o?{capture:!!e,passive:i,signal:t}:!!e}function s(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;window.addEventListener(e,t,a(r,n))}function c(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;document.addEventListener(e,t,a(r,n))}},4402:(e,t,r)=>{r.d(t,{Ht:()=>u,M:()=>c,Rl:()=>a,ky:()=>s});var n=r(385);const i="xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx";function o(e,t){return e?15&e[t]:16*Math.random()|0}function a(){const e=n._A?.crypto||n._A?.msCrypto;let t,r=0;return e&&e.getRandomValues&&(t=e.getRandomValues(new Uint8Array(31))),i.split("").map((e=>"x"===e?o(t,++r).toString(16):"y"===e?(3&o()|8).toString(16):e)).join("")}function s(e){const t=n._A?.crypto||n._A?.msCrypto;let r,i=0;t&&t.getRandomValues&&(r=t.getRandomValues(new Uint8Array(31)));const a=[];for(var s=0;s {r.d(t,{Bq:()=>n,Hb:()=>o,oD:()=>i});const n="NRBA",i=144e5,o=18e5},7894:(e,t,r)=>{function n(){return Math.round(performance.now())}r.d(t,{z:()=>n})},7243:(e,t,r)=>{r.d(t,{e:()=>o});var n=r(385),i={};function o(e){if(e in i)return i[e];if(0===(e||"").indexOf("data:"))return{protocol:"data"};let t;var r=n._A?.location,o={};if(n.il)t=document.createElement("a"),t.href=e;else try{t=new URL(e,r.href)}catch(e){return o}o.port=t.port;var a=t.href.split("://");!o.port&&a[1]&&(o.port=a[1].split("/")[0].split("@").pop().split(":")[1]),o.port&&"0"!==o.port||(o.port="https"===a[0]?"443":"80"),o.hostname=t.hostname||r.hostname,o.pathname=t.pathname,o.protocol=a[0],"/"!==o.pathname.charAt(0)&&(o.pathname="/"+o.pathname);var s=!t.protocol||":"===t.protocol||t.protocol===r.protocol,c=t.hostname===r.hostname&&t.port===r.port;return o.sameOrigin=s&&(!t.hostname||c),"/"===o.pathname&&(i[e]=o),o}},50:(e,t,r)=>{function n(e,t){"function"==typeof console.warn&&(console.warn("New Relic: ".concat(e)),t&&console.warn(t))}r.d(t,{Z:()=>n})},2587:(e,t,r)=>{r.d(t,{N:()=>c,T:()=>u});var n=r(2177),i=r(5546),o=r(8e3),a=r(3325);const s={stn:[a.D.sessionTrace],err:[a.D.jserrors,a.D.metrics],ins:[a.D.pageAction],spa:[a.D.spa],sr:[a.D.sessionReplay,a.D.sessionTrace]};function c(e,t){const r=n.ee.get(t);e&&"object"==typeof e&&(Object.entries(e).forEach((e=>{let[t,n]=e;void 0===u[t]&&(s[t]?s[t].forEach((e=>{n?(0,i.p)("feat-"+t,[],void 0,e,r):(0,i.p)("block-"+t,[],void 0,e,r),(0,i.p)("rumresp-"+t,[Boolean(n)],void 0,e,r)})):n&&(0,i.p)("feat-"+t,[],void 0,void 0,r),u[t]=Boolean(n))})),Object.keys(s).forEach((e=>{void 0===u[e]&&(s[e]?.forEach((t=>(0,i.p)("rumresp-"+e,[!1],void 0,t,r))),u[e]=!1)})),(0,o.L)(t,a.D.pageViewEvent))}const u={}},2210:(e,t,r)=>{r.d(t,{X:()=>i});var n=Object.prototype.hasOwnProperty;function i(e,t,r){if(n.call(e,t))return e[t];var i=r();if(Object.defineProperty&&Object.keys)try{return Object.defineProperty(e,t,{value:i,writable:!0,enumerable:!1}),i}catch(e){}return e[t]=i,i}},1284:(e,t,r)=>{r.d(t,{D:()=>n});const n=(e,t)=>Object.entries(e||{}).map((e=>{let[r,n]=e;return t(r,n)}))},4351:(e,t,r)=>{r.d(t,{P:()=>o});var n=r(2177);const i=()=>{const e=new WeakSet;return(t,r)=>{if("object"==typeof r&&null!==r){if(e.has(r))return;e.add(r)}return r}};function o(e){try{return JSON.stringify(e,i())}catch(e){try{n.ee.emit("internal-error",[e])}catch(e){}}}},3960:(e,t,r)=>{r.d(t,{K:()=>a,b:()=>o});var n=r(3239);function i(){return"undefined"==typeof document||"complete"===document.readyState}function o(e,t){if(i())return e();(0,n.bP)("load",e,t)}function a(e){if(i())return e();(0,n.iz)("DOMContentLoaded",e)}},8632:(e,t,r)=>{r.d(t,{EZ:()=>u,Qy:()=>c,ce:()=>o,fP:()=>a,gG:()=>d,mF:()=>s});var n=r(7894),i=r(385);const o={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net"};function a(){return i._A.NREUM||(i._A.NREUM={}),void 0===i._A.newrelic&&(i._A.newrelic=i._A.NREUM),i._A.NREUM}function s(){let e=a();return e.o||(e.o={ST:i._A.setTimeout,SI:i._A.setImmediate,CT:i._A.clearTimeout,XHR:i._A.XMLHttpRequest,REQ:i._A.Request,EV:i._A.Event,PR:i._A.Promise,MO:i._A.MutationObserver,FETCH:i._A.fetch}),e}function c(e,t,r){let i=a();const o=i.initializedAgents||{},s=o[e]||{};return Object.keys(s).length||(s.initializedAt={ms:(0,n.z)(),date:new Date}),i.initializedAgents={...o,[e]:{...s,[r]:t}},i}function u(e,t){a()[e]=t}function d(){return function(){let e=a();const t=e.info||{};e.info={beacon:o.beacon,errorBeacon:o.errorBeacon,...t}}(),function(){let e=a();const t=e.init||{};e.init={...t}}(),s(),function(){let e=a();const t=e.loader_config||{};e.loader_config={...t}}(),a()}},7956:(e,t,r)=>{r.d(t,{N:()=>i});var n=r(3239);function i(e){let t=arguments.length>1&&void 0!==arguments[1]&&arguments[1],r=arguments.length>2?arguments[2]:void 0,i=arguments.length>3?arguments[3]:void 0;return void(0,n.iz)("visibilitychange",(function(){if(t)return void("hidden"==document.visibilityState&&e());e(document.visibilityState)}),r,i)}},1214:(e,t,r)=>{r.d(t,{em:()=>v,u5:()=>N,QU:()=>S,_L:()=>I,Gm:()=>L,Lg:()=>M,gy:()=>U,BV:()=>Q,Kf:()=>ee});var n=r(2177);const i="nr@original";var o=Object.prototype.hasOwnProperty,a=!1;function s(e,t){return e||(e=n.ee),r.inPlace=function(e,t,n,i,o){n||(n="");var a,s,c,u="-"===n.charAt(0);for(c=0;c 2?n-2:0),o=2;o {r(A[T],e,w),r(E[T],e,w)})),r(l._A,"fetch",y),t.on(y+"end",(function(e,r){var n=this;if(r){var i=r.headers.get("content-length");null!==i&&(n.rxSize=i),t.emit(y+"done",[null,r],n)}else t.emit(y+"done",[e],n)})),t}const O={},j=["pushState","replaceState"];function S(e){const t=function(e){return(e||n.ee).get("history")}(e);return!l.il||O[t.debugId]++||(O[t.debugId]=1,s(t).inPlace(window.history,j,"-")),t}var P=r(3239);const C={},R=["appendChild","insertBefore","replaceChild"];function I(e){const t=function(e){return(e||n.ee).get("jsonp")}(e);if(!l.il||C[t.debugId])return t;C[t.debugId]=!0;var r=s(t),i=/[?&](?:callback|cb)=([^&#]+)/,o=/(.*)\.([^.]+)/,a=/^(\w+)(\.|$)(.*)$/;function c(e,t){var r=e.match(a),n=r[1],i=r[3];return i?c(i,t[n]):t[n]}return r.inPlace(Node.prototype,R,"dom-"),t.on("dom-start",(function(e){!function(e){if(!e||"string"!=typeof e.nodeName||"script"!==e.nodeName.toLowerCase())return;if("function"!=typeof e.addEventListener)return;var n=(a=e.src,s=a.match(i),s?s[1]:null);var a,s;if(!n)return;var u=function(e){var t=e.match(o);if(t&&t.length>=3)return{key:t[2],parent:c(t[1],window)};return{key:e,parent:window}}(n);if("function"!=typeof u.parent[u.key])return;var d={};function f(){t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}function l(){t.emit("jsonp-error",[],d),t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}r.inPlace(u.parent,[u.key],"cb-",d),e.addEventListener("load",f,(0,P.m$)(!1)),e.addEventListener("error",l,(0,P.m$)(!1)),t.emit("new-jsonp",[e.src],d)}(e[0])})),t}var k=r(5763);const H={};function L(e){const t=function(e){return(e||n.ee).get("mutation")}(e);if(!l.il||H[t.debugId])return t;H[t.debugId]=!0;var r=s(t),i=k.Yu.MO;return i&&(window.MutationObserver=function(e){return this instanceof i?new i(r(e,"fn-")):i.apply(this,arguments)},MutationObserver.prototype=i.prototype),t}const z={};function M(e){const t=function(e){return(e||n.ee).get("promise")}(e);if(z[t.debugId])return t;z[t.debugId]=!0;var r=n.c,o=s(t),a=k.Yu.PR;return a&&function(){function e(r){var n=t.context(),i=o(r,"executor-",n,null,!1);const s=Reflect.construct(a,[i],e);return t.context(s).getCtx=function(){return n},s}l._A.Promise=e,Object.defineProperty(e,"name",{value:"Promise"}),e.toString=function(){return a.toString()},Object.setPrototypeOf(e,a),["all","race"].forEach((function(r){const n=a[r];e[r]=function(e){let i=!1;[...e||[]].forEach((e=>{this.resolve(e).then(a("all"===r),a(!1))}));const o=n.apply(this,arguments);return o;function a(e){return function(){t.emit("propagate",[null,!i],o,!1,!1),i=i||!e}}}})),["resolve","reject"].forEach((function(r){const n=a[r];e[r]=function(e){const r=n.apply(this,arguments);return e!==r&&t.emit("propagate",[e,!0],r,!1,!1),r}})),e.prototype=a.prototype;const n=a.prototype.then;a.prototype.then=function(){var e=this,i=r(e);i.promise=e;for(var a=arguments.length,s=new Array(a),c=0;c e())),t};function m(e,t){i.inPlace(t,["onreadystatechange"],"fn-",E)}function b(){var e=this,t=r.context(e);e.readyState>3&&!t.resolved&&(t.resolved=!0,r.emit("xhr-resolved",[],e)),i.inPlace(e,f,"fn-",E)}if(function(e,t){for(var r in e)t[r]=e[r]}(o,p),p.prototype=o.prototype,i.inPlace(p.prototype,J,"-xhr-",E),r.on("send-xhr-start",(function(e,t){m(e,t),function(e){h.push(e),a&&(y?y.then(A):u?u(A):(w=-w,x.data=w))}(t)})),r.on("open-xhr-start",m),a){var y=c&&c.resolve();if(!u&&!c){var w=1,x=document.createTextNode(w);new a(A).observe(x,{characterData:!0})}}else t.on("fn-end",(function(e){e[0]&&e[0].type===d||A()}));function A(){for(var e=0;e {r.d(t,{t:()=>n});const n=r(3325).D.ajax},6660:(e,t,r)=>{r.d(t,{A:()=>i,t:()=>n});const n=r(3325).D.jserrors,i="nr@seenError"},3081:(e,t,r)=>{r.d(t,{gF:()=>o,mY:()=>i,t9:()=>n,vz:()=>s,xS:()=>a});const n=r(3325).D.metrics,i="sm",o="cm",a="storeSupportabilityMetrics",s="storeEventMetrics"},4649:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageAction},7633:(e,t,r)=>{r.d(t,{Dz:()=>i,OJ:()=>a,qw:()=>o,t9:()=>n});const n=r(3325).D.pageViewEvent,i="firstbyte",o="domcontent",a="windowload"},9251:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageViewTiming},3614:(e,t,r)=>{r.d(t,{BST_RESOURCE:()=>i,END:()=>s,FEATURE_NAME:()=>n,FN_END:()=>u,FN_START:()=>c,PUSH_STATE:()=>d,RESOURCE:()=>o,START:()=>a});const n=r(3325).D.sessionTrace,i="bstResource",o="resource",a="-start",s="-end",c="fn"+a,u="fn"+s,d="pushState"},7836:(e,t,r)=>{r.d(t,{BODY:()=>A,CB_END:()=>E,CB_START:()=>u,END:()=>x,FEATURE_NAME:()=>i,FETCH:()=>_,FETCH_BODY:()=>v,FETCH_DONE:()=>m,FETCH_START:()=>p,FN_END:()=>c,FN_START:()=>s,INTERACTION:()=>l,INTERACTION_API:()=>d,INTERACTION_EVENTS:()=>o,JSONP_END:()=>b,JSONP_NODE:()=>g,JS_TIME:()=>T,MAX_TIMER_BUDGET:()=>a,REMAINING:()=>f,SPA_NODE:()=>h,START:()=>w,originalSetTimeout:()=>y});var n=r(5763);const i=r(3325).D.spa,o=["click","submit","keypress","keydown","keyup","change"],a=999,s="fn-start",c="fn-end",u="cb-start",d="api-ixn-",f="remaining",l="interaction",h="spaNode",g="jsonpNode",p="fetch-start",m="fetch-done",v="fetch-body-",b="jsonp-end",y=n.Yu.ST,w="-start",x="-end",A="-body",E="cb"+x,T="jsTime",_="fetch"},5938:(e,t,r)=>{r.d(t,{W:()=>o});var n=r(5763),i=r(2177);class o{constructor(e,t,r){this.agentIdentifier=e,this.aggregator=t,this.ee=i.ee.get(e,(0,n.OP)(this.agentIdentifier).isolatedBacklog),this.featureName=r,this.blocked=!1}}},9144:(e,t,r)=>{r.d(t,{j:()=>m});var n=r(3325),i=r(5763),o=r(5546),a=r(2177),s=r(7894),c=r(8e3),u=r(3960),d=r(385),f=r(50),l=r(3081),h=r(8632);function g(){const e=(0,h.gG)();["setErrorHandler","finished","addToTrace","inlineHit","addRelease","addPageAction","setCurrentRouteName","setPageViewName","setCustomAttribute","interaction","noticeError","setUserId"].forEach((t=>{e[t]=function(){for(var r=arguments.length,n=new Array(r),i=0;i 1?r-1:0),i=1;i {e.exposed&&e.api[t]&&o.push(e.api[t](...n))})),o.length>1?o:o[0]}(t,...n)}}))}var p=r(2587);function m(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:{},m=arguments.length>2?arguments[2]:void 0,v=arguments.length>3?arguments[3]:void 0,{init:b,info:y,loader_config:w,runtime:x={loaderType:m},exposed:A=!0}=t;const E=(0,h.gG)();y||(b=E.init,y=E.info,w=E.loader_config),(0,i.Dg)(e,b||{}),(0,i.GE)(e,w||{}),(0,i.sU)(e,x),y.jsAttributes??={},d.v6&&(y.jsAttributes.isWorker=!0),(0,i.CX)(e,y),g();const T=function(e,t){t||(0,c.R)(e,"api");const h={};var g=a.ee.get(e),p=g.get("tracer"),m="api-",v=m+"ixn-";function b(t,r,n,o){const a=(0,i.C5)(e);return null===r?delete a.jsAttributes[t]:(0,i.CX)(e,{...a,jsAttributes:{...a.jsAttributes,[t]:r}}),x(m,n,!0,o||null===r?"session":void 0)(t,r)}function y(){}["setErrorHandler","finished","addToTrace","inlineHit","addRelease"].forEach((e=>h[e]=x(m,e,!0,"api"))),h.addPageAction=x(m,"addPageAction",!0,n.D.pageAction),h.setCurrentRouteName=x(m,"routeName",!0,n.D.spa),h.setPageViewName=function(t,r){if("string"==typeof t)return"/"!==t.charAt(0)&&(t="/"+t),(0,i.OP)(e).customTransaction=(r||"http://custom.transaction")+t,x(m,"setPageViewName",!0)()},h.setCustomAttribute=function(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2];if("string"==typeof e){if(["string","number"].includes(typeof t)||null===t)return b(e,t,"setCustomAttribute",r);(0,f.Z)("Failed to execute setCustomAttribute.\nNon-null value must be a string or number type, but a type of was provided."))}else(0,f.Z)("Failed to execute setCustomAttribute.\nName must be a string type, but a type of was provided."))},h.setUserId=function(e){if("string"==typeof e||null===e)return b("enduser.id",e,"setUserId",!0);(0,f.Z)("Failed to execute setUserId.\nNon-null value must be a string type, but a type of was provided."))},h.interaction=function(){return(new y).get()};var w=y.prototype={createTracer:function(e,t){var r={},i=this,a="function"==typeof t;return(0,o.p)(v+"tracer",[(0,s.z)(),e,r],i,n.D.spa,g),function(){if(p.emit((a?"":"no-")+"fn-start",[(0,s.z)(),i,a],r),a)try{return t.apply(this,arguments)}catch(e){throw p.emit("fn-err",[arguments,this,"string"==typeof e?new Error(e):e],r),e}finally{p.emit("fn-end",[(0,s.z)()],r)}}}};function x(e,t,r,i){return function(){return(0,o.p)(l.xS,["API/"+t+"/called"],void 0,n.D.metrics,g),i&&(0,o.p)(e+t,[(0,s.z)(),...arguments],r?null:this,i,g),r?void 0:this}}function A(){r.e(439).then(r.bind(r,7438)).then((t=>{let{setAPI:r}=t;r(e),(0,c.L)(e,"api")})).catch((()=>(0,f.Z)("Downloading runtime APIs failed...")))}return["actionText","setName","setAttribute","save","ignore","onEnd","getContext","end","get"].forEach((e=>{w[e]=x(v,e,void 0,n.D.spa)})),h.noticeError=function(e,t){"string"==typeof e&&(e=new Error(e)),(0,o.p)(l.xS,["API/noticeError/called"],void 0,n.D.metrics,g),(0,o.p)("err",[e,(0,s.z)(),!1,t],void 0,n.D.jserrors,g)},d.il?(0,u.b)((()=>A()),!0):A(),h}(e,v);return(0,h.Qy)(e,T,"api"),(0,h.Qy)(e,A,"exposed"),(0,h.EZ)("activatedFeatures",p.T),T}},3325:(e,t,r)=>{r.d(t,{D:()=>n,p:()=>i});const n={ajax:"ajax",jserrors:"jserrors",metrics:"metrics",pageAction:"page_action",pageViewEvent:"page_view_event",pageViewTiming:"page_view_timing",sessionReplay:"session_replay",sessionTrace:"session_trace",spa:"spa"},i={[n.pageViewEvent]:1,[n.pageViewTiming]:2,[n.metrics]:3,[n.jserrors]:4,[n.ajax]:5,[n.sessionTrace]:6,[n.pageAction]:7,[n.spa]:8,[n.sessionReplay]:9}}},n={};function i(e){var t=n[e];if(void 0!==t)return t.exports;var o=n[e]={exports:{}};return r[e](o,o.exports,i),o.exports}i.m=r,i.d=(e,t)=>{for(var r in t)i.o(t,r)&&!i.o(e,r)&&Object.defineProperty(e,r,{enumerable:!0,get:t[r]})},i.f={},i.e=e=>Promise.all(Object.keys(i.f).reduce(((t,r)=>(i.f[r](e,t),t)),[])),i.u=e=>(({78:"page_action-aggregate",147:"metrics-aggregate",242:"session-manager",317:"jserrors-aggregate",348:"page_view_timing-aggregate",412:"lazy-feature-loader",439:"async-api",538:"recorder",590:"session_replay-aggregate",675:"compressor",733:"session_trace-aggregate",786:"page_view_event-aggregate",873:"spa-aggregate",898:"ajax-aggregate"}[e]||e)+"."+{78:"ac76d497",147:"3dc53903",148:"1a20d5fe",242:"2a64278a",317:"49e41428",348:"bd6de33a",412:"2f55ce66",439:"30bd804e",538:"1b18459f",590:"cf0efb30",675:"ae9f91a8",733:"83105561",786:"06482edd",860:"03a8b7a5",873:"e6b09d52",898:"998ef92b"}[e]+"-1.236.0.min.js"),i.o=(e,t)=>Object.prototype.hasOwnProperty.call(e,t),e={},t="NRBA:",i.l=(r,n,o,a)=>{if(e[r])e[r].push(n);else{var s,c;if(void 0!==o)for(var u=document.getElementsByTagName("script"),d=0;d {s.onerror=s.onload=null,clearTimeout(h);var i=e[r];if(delete e[r],s.parentNode&&s.parentNode.removeChild(s),i&&i.forEach((e=>e(n))),t)return t(n)},h=setTimeout(l.bind(null,void 0,{type:"timeout",target:s}),12e4);s.onerror=l.bind(null,s.onerror),s.onload=l.bind(null,s.onload),c&&document.head.appendChild(s)}},i.r=e=>{"undefined"!=typeof Symbol&&Symbol.toStringTag&&Object.defineProperty(e,Symbol.toStringTag,{value:"Module"}),Object.defineProperty(e,"__esModule",{value:!0})},i.j=364,i.p="https://js-agent.newrelic.com/",(()=>{var e={364:0,953:0};i.f.j=(t,r)=>{var n=i.o(e,t)?e[t]:void 0;if(0!==n)if(n)r.push(n[2]);else{var o=new Promise(((r,i)=>n=e[t]=[r,i]));r.push(n[2]=o);var a=i.p+i.u(t),s=new Error;i.l(a,(r=>{if(i.o(e,t)&&(0!==(n=e[t])&&(e[t]=void 0),n)){var o=r&&("load"===r.type?"missing":r.type),a=r&&r.target&&r.target.src;s.message="Loading chunk "+t+" failed.\n("+o+": "+a+")",s.name="ChunkLoadError",s.type=o,s.request=a,n[1](s)}}),"chunk-"+t,t)}};var t=(t,r)=>{var n,o,[a,s,c]=r,u=0;if(a.some((t=>0!==e[t]))){for(n in s)i.o(s,n)&&(i.m[n]=s[n]);if(c)c(i)}for(t&&t(r);u {i.r(o);var e=i(3325),t=i(5763);const r=Object.values(e.D);function n(e){const n={};return r.forEach((r=>{n[r]=function(e,r){return!1!==(0,t.Mt)(r,"".concat(e,".enabled"))}(r,e)})),n}var a=i(9144);var s=i(5546),c=i(385),u=i(8e3),d=i(5938),f=i(3960),l=i(50);class h extends d.W{constructor(e,t,r){let n=!(arguments.length>3&&void 0!==arguments[3])||arguments[3];super(e,t,r),this.auto=n,this.abortHandler,this.featAggregate,this.onAggregateImported,n&&(0,u.R)(e,r)}importAggregator(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:{};if(this.featAggregate||!this.auto)return;const r=c.il&&!0===(0,t.Mt)(this.agentIdentifier,"privacy.cookies_enabled");let n;this.onAggregateImported=new Promise((e=>{n=e}));const o=async()=>{let t;try{if(r){const{setupAgentSession:e}=await Promise.all([i.e(860),i.e(242)]).then(i.bind(i,3228));t=e(this.agentIdentifier)}}catch(e){(0,l.Z)("A problem occurred when starting up session manager. This page will not start or extend any session.",e)}try{if(!this.shouldImportAgg(this.featureName,t))return void(0,u.L)(this.agentIdentifier,this.featureName);const{lazyFeatureLoader:r}=await i.e(412).then(i.bind(i,8582)),{Aggregate:o}=await r(this.featureName,"aggregate");this.featAggregate=new o(this.agentIdentifier,this.aggregator,e),n(!0)}catch(e){(0,l.Z)("Downloading and initializing ".concat(this.featureName," failed..."),e),this.abortHandler?.(),n(!1)}};c.il?(0,f.b)((()=>o()),!0):o()}shouldImportAgg(r,n){return r!==e.D.sessionReplay||!1!==(0,t.Mt)(this.agentIdentifier,"session_trace.enabled")&&(!!n?.isNew||!!n?.state.sessionReplay)}}var g=i(7633),p=i(7894);class m extends h{static featureName=g.t9;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];if(super(r,n,g.t9,i),("undefined"==typeof PerformanceNavigationTiming||c.Tt)&&"undefined"!=typeof PerformanceTiming){const n=(0,t.OP)(r);n[g.Dz]=Math.max(Date.now()-n.offset,0),(0,f.K)((()=>n[g.qw]=Math.max((0,p.z)()-n[g.Dz],0))),(0,f.b)((()=>{const t=(0,p.z)();n[g.OJ]=Math.max(t-n[g.Dz],0),(0,s.p)("timing",["load",t],void 0,e.D.pageViewTiming,this.ee)}))}this.importAggregator()}}var v=i(1117),b=i(1284);class y extends v.w{constructor(e){super(e),this.aggregatedData={}}store(e,t,r,n,i){var o=this.getBucket(e,t,r,i);return o.metrics=function(e,t){t||(t={count:0});return t.count+=1,(0,b.D)(e,(function(e,r){t[e]=w(r,t[e])})),t}(n,o.metrics),o}merge(e,t,r,n,i){var o=this.getBucket(e,t,n,i);if(o.metrics){var a=o.metrics;a.count+=r.count,(0,b.D)(r,(function(e,t){if("count"!==e){var n=a[e],i=r[e];i&&!i.c?a[e]=w(i.t,n):a[e]=function(e,t){if(!t)return e;t.c||(t=x(t.t));return t.min=Math.min(e.min,t.min),t.max=Math.max(e.max,t.max),t.t+=e.t,t.sos+=e.sos,t.c+=e.c,t}(i,a[e])}}))}else o.metrics=r}storeMetric(e,t,r,n){var i=this.getBucket(e,t,r);return i.stats=w(n,i.stats),i}getBucket(e,t,r,n){this.aggregatedData[e]||(this.aggregatedData[e]={});var i=this.aggregatedData[e][t];return i||(i=this.aggregatedData[e][t]={params:r||{}},n&&(i.custom=n)),i}get(e,t){return t?this.aggregatedData[e]&&this.aggregatedData[e][t]:this.aggregatedData[e]}take(e){for(var t={},r="",n=!1,i=0;i t.max&&(t.max=e),e 2&&void 0!==arguments[2])||arguments[2];super(e,r,j.t,n),c.il&&((0,t.OP)(e).initHidden=Boolean("hidden"===document.visibilityState),(0,N.N)((()=>(0,s.p)("docHidden",[(0,p.z)()],void 0,j.t,this.ee)),!0),(0,O.bP)("pagehide",(()=>(0,s.p)("winPagehide",[(0,p.z)()],void 0,j.t,this.ee))),this.importAggregator())}}var P=i(3081);class C extends h{static featureName=P.t9;constructor(e,t){let r=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(e,t,P.t9,r),this.importAggregator()}}var R,I=i(2210),k=i(1214),H=i(2177),L={};try{R=localStorage.getItem("__nr_flags").split(","),console&&"function"==typeof console.log&&(L.console=!0,-1!==R.indexOf("dev")&&(L.dev=!0),-1!==R.indexOf("nr_dev")&&(L.nrDev=!0))}catch(e){}function z(e){try{L.console&&z(e)}catch(e){}}L.nrDev&&H.ee.on("internal-error",(function(e){z(e.stack)})),L.dev&&H.ee.on("fn-err",(function(e,t,r){z(r.stack)})),L.dev&&(z("NR AGENT IN DEVELOPMENT MODE"),z("flags: "+(0,b.D)(L,(function(e,t){return e})).join(", ")));var M=i(6660);class B extends h{static featureName=M.t;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(r,n,M.t,i),this.skipNext=0;try{this.removeOnAbort=new AbortController}catch(e){}const o=this;o.ee.on("fn-start",(function(e,t,r){o.abortHandler&&(o.skipNext+=1)})),o.ee.on("fn-err",(function(t,r,n){o.abortHandler&&!n[M.A]&&((0,I.X)(n,M.A,(function(){return!0})),this.thrown=!0,(0,s.p)("err",[n,(0,p.z)()],void 0,e.D.jserrors,o.ee))})),o.ee.on("fn-end",(function(){o.abortHandler&&!this.thrown&&o.skipNext>0&&(o.skipNext-=1)})),o.ee.on("internal-error",(function(t){(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,o.ee)})),this.origOnerror=c._A.onerror,c._A.onerror=this.onerrorHandler.bind(this),c._A.addEventListener("unhandledrejection",(t=>{const r=function(e){let t="Unhandled Promise Rejection: ";if(e instanceof Error)try{return e.message=t+e.message,e}catch(t){return e}if(void 0===e)return new Error(t);try{return new Error(t+(0,D.P)(e))}catch(e){return new Error(t)}}(t.reason);(0,s.p)("err",[r,(0,p.z)(),!1,{unhandledPromiseRejection:1}],void 0,e.D.jserrors,this.ee)}),(0,O.m$)(!1,this.removeOnAbort?.signal)),(0,k.gy)(this.ee),(0,k.BV)(this.ee),(0,k.em)(this.ee),(0,t.OP)(r).xhrWrappable&&(0,k.Kf)(this.ee),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}onerrorHandler(t,r,n,i,o){"function"==typeof this.origOnerror&&this.origOnerror(...arguments);try{this.skipNext?this.skipNext-=1:(0,s.p)("err",[o||new F(t,r,n),(0,p.z)()],void 0,e.D.jserrors,this.ee)}catch(t){try{(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,this.ee)}catch(e){}}return!1}}function F(e,t,r){this.message=e||"Uncaught error with no additional information",this.sourceURL=t,this.line=r}let U=1;const q="nr@id";function G(e){const t=typeof e;return!e||"object"!==t&&"function"!==t?-1:e===c._A?0:(0,I.X)(e,q,(function(){return U++}))}function V(e){if("string"==typeof e&&e.length)return e.length;if("object"==typeof e){if("undefined"!=typeof ArrayBuffer&&e instanceof ArrayBuffer&&e.byteLength)return e.byteLength;if("undefined"!=typeof Blob&&e instanceof Blob&&e.size)return e.size;if(!("undefined"!=typeof FormData&&e instanceof FormData))try{return(0,D.P)(e).length}catch(e){return}}}var X=i(7243);class W{constructor(e){this.agentIdentifier=e,this.generateTracePayload=this.generateTracePayload.bind(this),this.shouldGenerateTrace=this.shouldGenerateTrace.bind(this)}generateTracePayload(e){if(!this.shouldGenerateTrace(e))return null;var r=(0,t.DL)(this.agentIdentifier);if(!r)return null;var n=(r.accountID||"").toString()||null,i=(r.agentID||"").toString()||null,o=(r.trustKey||"").toString()||null;if(!n||!i)return null;var a=(0,_.M)(),s=(0,_.Ht)(),c=Date.now(),u={spanId:a,traceId:s,timestamp:c};return(e.sameOrigin||this.isAllowedOrigin(e)&&this.useTraceContextHeadersForCors())&&(u.traceContextParentHeader=this.generateTraceContextParentHeader(a,s),u.traceContextStateHeader=this.generateTraceContextStateHeader(a,c,n,i,o)),(e.sameOrigin&&!this.excludeNewrelicHeader()||!e.sameOrigin&&this.isAllowedOrigin(e)&&this.useNewrelicHeaderForCors())&&(u.newrelicHeader=this.generateTraceHeader(a,s,c,n,i,o)),u}generateTraceContextParentHeader(e,t){return"00-"+t+"-"+e+"-01"}generateTraceContextStateHeader(e,t,r,n,i){return i+"@nr=0-1-"+r+"-"+n+"-"+e+"----"+t}generateTraceHeader(e,t,r,n,i,o){if(!("function"==typeof c._A?.btoa))return null;var a={v:[0,1],d:{ty:"Browser",ac:n,ap:i,id:e,tr:t,ti:r}};return o&&n!==o&&(a.d.tk=o),btoa((0,D.P)(a))}shouldGenerateTrace(e){return this.isDtEnabled()&&this.isAllowedOrigin(e)}isAllowedOrigin(e){var r=!1,n={};if((0,t.Mt)(this.agentIdentifier,"distributed_tracing")&&(n=(0,t.P_)(this.agentIdentifier).distributed_tracing),e.sameOrigin)r=!0;else if(n.allowed_origins instanceof Array)for(var i=0;i 2&&void 0!==arguments[2])||arguments[2];super(r,n,Z.t,i),(0,t.OP)(r).xhrWrappable&&(this.dt=new W(r),this.handler=(e,t,r,n)=>(0,s.p)(e,t,r,n,this.ee),(0,k.u5)(this.ee),(0,k.Kf)(this.ee),function(r,n,i,o){function a(e){var t=this;t.totalCbs=0,t.called=0,t.cbTime=0,t.end=E,t.ended=!1,t.xhrGuids={},t.lastSize=null,t.loadCaptureCalled=!1,t.params=this.params||{},t.metrics=this.metrics||{},e.addEventListener("load",(function(r){_(t,e)}),(0,O.m$)(!1)),c.IF||e.addEventListener("progress",(function(e){t.lastSize=e.loaded}),(0,O.m$)(!1))}function s(e){this.params={method:e[0]},T(this,e[1]),this.metrics={}}function u(e,n){var i=(0,t.DL)(r);i.xpid&&this.sameOrigin&&n.setRequestHeader("X-NewRelic-ID",i.xpid);var a=o.generateTracePayload(this.parsedOrigin);if(a){var s=!1;a.newrelicHeader&&(n.setRequestHeader("newrelic",a.newrelicHeader),s=!0),a.traceContextParentHeader&&(n.setRequestHeader("traceparent",a.traceContextParentHeader),a.traceContextStateHeader&&n.setRequestHeader("tracestate",a.traceContextStateHeader),s=!0),s&&(this.dt=a)}}function d(e,t){var r=this.metrics,i=e[0],o=this;if(r&&i){var a=V(i);a&&(r.txSize=a)}this.startTime=(0,p.z)(),this.listener=function(e){try{"abort"!==e.type||o.loadCaptureCalled||(o.params.aborted=!0),("load"!==e.type||o.called===o.totalCbs&&(o.onloadCalled||"function"!=typeof t.onload)&&"function"==typeof o.end)&&o.end(t)}catch(e){try{n.emit("internal-error",[e])}catch(e){}}};for(var s=0;s 1?e[1]=i:e.push(i)}else e[0]&&e[0].headers&&s(e[0].headers,n)&&(this.dt=n);function s(e,t){var r=!1;return t.newrelicHeader&&(e.set("newrelic",t.newrelicHeader),r=!0),t.traceContextParentHeader&&(e.set("traceparent",t.traceContextParentHeader),t.traceContextStateHeader&&e.set("tracestate",t.traceContextStateHeader),r=!0),r}}function x(e,t){this.params={},this.metrics={},this.startTime=(0,p.z)(),this.dt=t,e.length>=1&&(this.target=e[0]),e.length>=2&&(this.opts=e[1]);var r,n=this.opts||{},i=this.target;"string"==typeof i?r=i:"object"==typeof i&&i instanceof Y?r=i.url:c._A?.URL&&"object"==typeof i&&i instanceof URL&&(r=i.href),T(this,r);var o=(""+(i&&i instanceof Y&&i.method||n.method||"GET")).toUpperCase();this.params.method=o,this.txSize=V(n.body)||0}function A(t,r){var n;this.endTime=(0,p.z)(),this.params||(this.params={}),this.params.status=r?r.status:0,"string"==typeof this.rxSize&&this.rxSize.length>0&&(n=+this.rxSize);var o={txSize:this.txSize,rxSize:n,duration:(0,p.z)()-this.startTime};i("xhr",[this.params,o,this.startTime,this.endTime,"fetch"],this,e.D.ajax)}function E(t){var r=this.params,n=this.metrics;if(!this.ended){this.ended=!0;for(var o=0;o 2&&void 0!==arguments[2])||arguments[2];super(e,t,we.t,r),this.importAggregator()}}new class{constructor(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:(0,_.ky)(16);c._A?(this.agentIdentifier=t,this.sharedAggregator=new y({agentIdentifier:this.agentIdentifier}),this.features={},this.desiredFeatures=new Set(e.features||[]),this.desiredFeatures.add(m),Object.assign(this,(0,a.j)(this.agentIdentifier,e,e.loaderType||"agent")),this.start()):(0,l.Z)("Failed to initial the agent. Could not determine the runtime environment.")}get config(){return{info:(0,t.C5)(this.agentIdentifier),init:(0,t.P_)(this.agentIdentifier),loader_config:(0,t.DL)(this.agentIdentifier),runtime:(0,t.OP)(this.agentIdentifier)}}start(){const t="features";try{const r=n(this.agentIdentifier),i=[...this.desiredFeatures];i.sort(((t,r)=>e.p[t.featureName]-e.p[r.featureName])),i.forEach((t=>{if(r[t.featureName]||t.featureName===e.D.pageViewEvent){const n=function(t){switch(t){case e.D.ajax:return[e.D.jserrors];case e.D.sessionTrace:return[e.D.ajax,e.D.pageViewEvent];case e.D.sessionReplay:return[e.D.sessionTrace];case e.D.pageViewTiming:return[e.D.pageViewEvent];default:return[]}}(t.featureName);n.every((e=>r[e]))||(0,l.Z)("".concat(t.featureName," is enabled but one or more dependent features has been disabled (").concat((0,D.P)(n),"). This may cause unintended consequences or missing data...")),this.features[t.featureName]=new t(this.agentIdentifier,this.sharedAggregator)}})),(0,T.Qy)(this.agentIdentifier,this.features,t)}catch(e){(0,l.Z)("Failed to initialize all enabled instrument classes (agent aborted) -",e);for(const e in this.features)this.features[e].abortHandler?.();const r=(0,T.fP)();return delete r.initializedAgents[this.agentIdentifier]?.api,delete r.initializedAgents[this.agentIdentifier]?.[t],delete this.sharedAggregator,r.ee?.abort(),delete r.ee?.get(this.agentIdentifier),!1}}}({features:[J,m,S,class extends h{static featureName=oe;constructor(t,r){if(super(t,r,oe,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;const n=this.ee;let i;(0,k.QU)(n),this.eventsEE=(0,k.em)(n),this.eventsEE.on(se,(function(e,t){this.bstStart=(0,p.z)()})),this.eventsEE.on(ae,(function(t,r){(0,s.p)("bst",[t[0],r,this.bstStart,(0,p.z)()],void 0,e.D.sessionTrace,n)})),n.on(ce+ne,(function(e){this.time=(0,p.z)(),this.startPath=location.pathname+location.hash})),n.on(ce+ie,(function(t){(0,s.p)("bstHist",[location.pathname+location.hash,this.startPath,this.time],void 0,e.D.sessionTrace,n)}));try{i=new PerformanceObserver((t=>{const r=t.getEntries();(0,s.p)(te,[r],void 0,e.D.sessionTrace,n)})),i.observe({type:re,buffered:!0})}catch(e){}this.importAggregator({resourceObserver:i})}},C,xe,B,class extends h{static featureName=de;constructor(e,r){if(super(e,r,de,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;if(!(0,t.OP)(e).xhrWrappable)return;try{this.removeOnAbort=new AbortController}catch(e){}let n,i=0;const o=this.ee.get("tracer"),a=(0,k._L)(this.ee),s=(0,k.Lg)(this.ee),u=(0,k.BV)(this.ee),d=(0,k.Kf)(this.ee),f=this.ee.get("events"),l=(0,k.u5)(this.ee),h=(0,k.QU)(this.ee),g=(0,k.Gm)(this.ee);function m(e,t){h.emit("newURL",[""+window.location,t])}function v(){i++,n=window.location.hash,this[ve]=(0,p.z)()}function b(){i--,window.location.hash!==n&&m(0,!0);var e=(0,p.z)();this[pe]=~~this[pe]+e-this[ve],this[ye]=e}function y(e,t){e.on(t,(function(){this[t]=(0,p.z)()}))}this.ee.on(ve,v),s.on(be,v),a.on(be,v),this.ee.on(ye,b),s.on(ge,b),a.on(ge,b),this.ee.buffer([ve,ye,"xhr-resolved"],this.featureName),f.buffer([ve],this.featureName),u.buffer(["setTimeout"+le,"clearTimeout"+fe,ve],this.featureName),d.buffer([ve,"new-xhr","send-xhr"+fe],this.featureName),l.buffer([me+fe,me+"-done",me+he+fe,me+he+le],this.featureName),h.buffer(["newURL"],this.featureName),g.buffer([ve],this.featureName),s.buffer(["propagate",be,ge,"executor-err","resolve"+fe],this.featureName),o.buffer([ve,"no-"+ve],this.featureName),a.buffer(["new-jsonp","cb-start","jsonp-error","jsonp-end"],this.featureName),y(l,me+fe),y(l,me+"-done"),y(a,"new-jsonp"),y(a,"jsonp-end"),y(a,"cb-start"),h.on("pushState-end",m),h.on("replaceState-end",m),window.addEventListener("hashchange",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("load",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("popstate",(function(){m(0,i>1)}),(0,O.m$)(!0,this.removeOnAbort?.signal)),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}}],loaderType:"spa"})})(),window.NRBA=o})(); window.jQuery || document.write(' ') CKEDITOR_BASEPATH='https://f1000research.com/js/vendor/ckeditor/' window.reactTheme = 'research'; window.MathJax = { CommonHTML: { linebreaks: { automatic: true } }, 'HTML-CSS': { linebreaks: { automatic: true } }, SVG: { linebreaks: { automatic: true } }, AuthorInit: function() { MathJax.Hub.Register.MessageHook('End Process', function () { let timeout = false; // holder for timeout id const delay = 250; // delay after event is "complete" to run callback const reflowMath = function() { const dispFormulas = document.querySelectorAll('.disp-formula.panel'); if (!dispFormulas) { return; } for (const dispFormula of dispFormulas) { const child = dispFormula.querySelector('.MathJax_Preview').nextSibling.firstChild; const isMultiline = MathJax.Hub.getAllJax(dispFormula)[0].root.isMultiline; if (dispFormula.offsetWidth < child.offsetWidth || isMultiline) { MathJax.Hub.Queue(['Rerender', MathJax.Hub, dispFormula]); } } }; window.addEventListener('resize', function() { clearTimeout(timeout); // clear the timeout timeout = setTimeout(reflowMath, delay); // start timing for event "completion" }); }); }, }; if (window.location.hash == '#_=_'){ window.location = window.location.href.split('#')[0] } !function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function() {n.callMethod? n.callMethod.apply(n,arguments):n.queue.push(arguments)} ;if(!f._fbq)f._fbq=n; n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0; t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js'); fbq('init', '1641728616063202'); fbq('track', "PixelInitialized", {}); (function(h,o,t,j,a,r){ h.hj=h.hj||function(){(h.hj.q=h.hj.q||[]).push(arguments)}; h._hjSettings={hjid:2318163,hjsv:6}; a=o.getElementsByTagName('head')[0]; r=o.createElement('script');r.async=1; r.src=t+h._hjSettings.hjid+j+h._hjSettings.hjsv; a.appendChild(r); })(window,document,'https://static.hotjar.com/c/hotjar-','.js?sv='); search file_upload Submit your research search menu close search Browse Gateways & Collections How to Publish Submit your Research My Submissions Article Guidelines Article Guidelines (New Versions) Open Data, Software and Code Guidelines Open Data and Accessible Source Materials Guidelines (HSS) Open Data, Software and Code Guidelines (PSE) Prepublication Checks Production Process Posters and Slides Guidelines Document Guidelines Article Processing Charges Peer Review Finding Article Reviewers About How it Works For Reviewers Our Advisors Policies Glossary FAQs For Developers Newsroom Contact My Research Submissions Content and Tracking Alerts My Details Sign In file_upload Submit your research { "@context": "https://schema.org", "@type": "ScholarlyArticle", "mainEntityOfPage": { "@type": "WebPage", "@id": "https://f1000research.com/articles/12-450" }, "headline": "Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian...", "datePublished": "2023-04-27T15:35:32", "dateModified": "2023-04-27T15:35:32", "author": [ { "@type": "Person", "name": "Yen Suan Sin" }, { "@type": "Person", "name": "Min Chen" }, { "@type": "Person", "name": "Kim Sia Sng" }, { "@type": "Person", "name": "Jianwei Zhang" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": "Background: This study aimed to systematically evaluate and compare the clinical efficacy of different modalities of Traditional Chinese Medicine (TCM) for the treatment of premature ovarian insufficiency (POI) and identify the most effective treatment modality. Methods: Six electronic databases (PubMed, OVID, Scopus, CNKI, VIP and WanFang) were screened from their inception until 20/01/2022. This network meta-analysis (NMA) incorporated hormone replacement therapy (HRT) as the placebo and six different TCM treatment modalities as interventions. The primary outcome was total effective rate; the secondary outcomes were improvement in serum follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH) and anti-Müllerian hormone (AMH) levels. The Cochrane risk of bias tool was used to appraise the quality of the included studies. Random effect model was used for pairwise meta-analysis using RevMan 5.4. NMA was performed in STATA. The surface under the cumulative ranking curves (SUCRA) and mean rank (MR) were used as evaluation indexes. Results: Overall, 37 randomized clinical trials involving 2,597 subjects that conformed to the inclusion criteria were included. Herbal medicine combined with catgut-embedding therapy was concluded to achieve the highest total effective rate (MD 4.35; 95% CI 1.32, 14.38) and improvement in AMH level (MD 0.74; 95% CI -0.74, 2.22). HRT combined with herbal medicine and acupuncture was determined to be the most effective treatment model for POI in improving their FSH (MD -13.17; 95% CI -18.17, -8.17), E2 (MD 34.29; 95% CI 14.41, 54.18) and LH (MD -15.01; 95% CI -19.95, -10.06) levels. Conclusions: Combination of HRT, herbal medicine and acupuncture was the most effective treatment modality for patients with POI. We also found that combination of herbal medicine with conventional HRT for patients with POI could effectively improve the clinical effectiveness in all aspects. This result may provide guidance for future treatment guideline implementation for POI. Registration: PROSPERO (CRD42020163873; 28/04/2020)." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/12-450", "name": "Identifying the most effective Traditional Chinese Medicine treatment..." } } ] } Home Browse Identifying the most effective Traditional Chinese Medicine treatment... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Sin YS, Chen M, Sng KS and Zhang J. Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2023, 12 :450 ( https://doi.org/10.12688/f1000research.132981.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Systematic Review Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis [version 1; peer review: 1 approved with reservations, 1 not approved] Yen Suan Sin https://orcid.org/0000-0002-2392-0489 1,2 , Min Chen https://orcid.org/0000-0002-8074-897X 1 , Kim Sia Sng 2 , Jianwei Zhang https://orcid.org/0000-0002-0532-9580 3 Yen Suan Sin https://orcid.org/0000-0002-2392-0489 1,2 , Min Chen https://orcid.org/0000-0002-8074-897X 1 , Kim Sia Sng 2 , Jianwei Zhang https://orcid.org/0000-0002-0532-9580 3 PUBLISHED 27 Apr 2023 Author details Author details 1 Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 16369, China 2 Department of Chinese Medicine, International Medical University, Bukit Jalil, Kuala Lumpur, 57000, Malaysia 3 Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, Shandong, 250014, China Yen Suan Sin Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Writing – Original Draft Preparation, Writing – Review & Editing Min Chen Roles: Formal Analysis, Investigation, Methodology, Validation, Writing – Review & Editing Kim Sia Sng Roles: Data Curation, Investigation, Methodology, Validation, Writing – Review & Editing Jianwei Zhang Roles: Conceptualization, Supervision, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Global Public Health gateway. Abstract Background: This study aimed to systematically evaluate and compare the clinical efficacy of different modalities of Traditional Chinese Medicine (TCM) for the treatment of premature ovarian insufficiency (POI) and identify the most effective treatment modality. Methods: Six electronic databases (PubMed, OVID, Scopus, CNKI, VIP and WanFang) were screened from their inception until 20/01/2022. This network meta-analysis (NMA) incorporated hormone replacement therapy (HRT) as the placebo and six different TCM treatment modalities as interventions. The primary outcome was total effective rate; the secondary outcomes were improvement in serum follicle-stimulating hormone (FSH), estradiol (E 2 ), luteinizing hormone (LH) and anti-Müllerian hormone (AMH) levels. The Cochrane risk of bias tool was used to appraise the quality of the included studies. Random effect model was used for pairwise meta-analysis using RevMan 5.4. NMA was performed in STATA. The surface under the cumulative ranking curves (SUCRA) and mean rank (MR) were used as evaluation indexes. Results: Overall, 37 randomized clinical trials involving 2,597 subjects that conformed to the inclusion criteria were included. Herbal medicine combined with catgut-embedding therapy was concluded to achieve the highest total effective rate (MD 4.35; 95% CI 1.32, 14.38) and improvement in AMH level (MD 0.74; 95% CI -0.74, 2.22). HRT combined with herbal medicine and acupuncture was determined to be the most effective treatment model for POI in improving their FSH (MD -13.17; 95% CI -18.17, -8.17), E 2 (MD 34.29; 95% CI 14.41, 54.18) and LH (MD -15.01; 95% CI -19.95, -10.06) levels. Conclusions: Combination of HRT, herbal medicine and acupuncture was the most effective treatment modality for patients with POI. We also found that combination of herbal medicine with conventional HRT for patients with POI could effectively improve the clinical effectiveness in all aspects. This result may provide guidance for future treatment guideline implementation for POI. Registration: PROSPERO ( CRD42020163873 ; 28/04/2020). READ ALL READ LESS Keywords Premature ovarian insufficiency, Chinese medicine, Acupuncture, Network meta-analysis, Systematic review Corresponding Author(s) Jianwei Zhang ( [email protected] ) Close Corresponding author: Jianwei Zhang Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2023 Sin YS et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Sin YS, Chen M, Sng KS and Zhang J. Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2023, 12 :450 ( https://doi.org/10.12688/f1000research.132981.1 ) First published: 27 Apr 2023, 12 :450 ( https://doi.org/10.12688/f1000research.132981.1 ) Latest published: 27 Apr 2023, 12 :450 ( https://doi.org/10.12688/f1000research.132981.1 ) Introduction Premature ovarian insufficiency (POI) is a pathological state of a woman below the age of 40 years suffering from irreversible diminished ovarian function in her reproductive age, it mainly manifests as oligomenorrhoea, hypomenorrhea, amenorrhea, elevated follicle-stimulating hormone (FSH) level (>25 U/L) and short or long term effects of estrogen deficiency. 1 The ovarian reserve can be measured by serum anti-Müllerian hormone (AMH) levels. According to the Bologna criteria, a low ovarian reserve is defined as an AMH level below 0.5–1.1 ng/mL (3.6–7.9 pmol/L). 2 Review data from 2020 reported that the prevalence of POI is about 10% among women below 40 years old. 3 The occurrence of this disease has been increasing among populations living in urban cities. This has captured the attention of public health policy makers and a timely and appropriate preventive measure is urged to be implemented. Hormone replacement therapy (HRT) is the most recommended medical intervention for patients with POI, referring to the European Society of Human Reproduction and Embryology (ESHRE) and International Menopause Society (IMS) guidelines, as well as the Chinese Medical Experts’ Consensus on Clinical Diagnosis and Treatment of POI, stipulated by the Obstetrics and Gynecology Society of Chinese Medical Association. 1 , 4 – 6 However, there are risks of adverse reactions and associated diseases after HRT application. 7 , 8 Hence, patients often seek out complementary medicine to improve their ovarian functions and increase chances of conception. Various Traditional Chinese Medicine (TCM) treatments such as herbal medicine, acupuncture, moxibustion and catgut-embedding therapy have been applied as the treatment for patients with POI. These treatment modalities have been proven to be effective and safe to improve ovarian functions among patients with POI through numerous clinical trials and direct comparison by using meta-analysis. 9 – 11 However, there are inadequate direct and indirect comparisons between different TCM treatment modalities that contribute to clinical health promotion and selection of the optimal therapeutic procedure. Therefore, there is a need to systematically evaluate and analyze the efficacy of these alternatives in order to provide a strong theoretical basis and scientific evidence for clinical practice and research. In this study, we compared the efficacy of different TCM treatment modalities for patients with POI by conducting network meta-analysis (NMA) to rank the therapeutic measures in line with their treatment effect through direct and indirect comparisons of the means, with the prospective to provide an evidence-based guidance for future clinical guidelines. Methods The study method is compliant with the Cochrane Handbook for Systematic Reviews of Interventions 12 and the methods outlined in Lei Zhang et al. 13 It followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for network meta-analyses (PRISMA-NMA). 14 , 57 It was registered in the International Prospective Systematic Registration Review (PROSPERO) with registration number CRD42020163873 on 28 April 2020. Search strategy and literature screening Records identified from six electronic databases, which included three English databases ( PubMed (RRID:SCR_004846), OVID , Scopus (RRID:SCR_022559)) and three Chinese databases ( CNKI , VIP , WanFang ). Reported studies from the inception of each database until 20 January 2022 were screened. Search terms used were a combination of text words and medical subject headings (MeSH), including “Premature Ovarian Insufficiency”, “POI”, “Premature Ovarian Failure” or “Primary Ovarian Insufficiency”. Table 1 shows the search strategy details for each database. Only English and Chinese articles were included. Additionally, the reference lists of all eligible studies were screened to avoid missing eligible studies. The electronic search and literature screening were executed by two researchers (SYS and CM) independently. Any potential disagreement was assessed and discussed with a third reviewer (SKS). Table 1. Search strategy. Databases Search term PubMed (Premature ovarian insufficiency OR primary ovarian insufficiency OR premature ovarian failure OR primary ovarian failure OR ovarian insufficiency OR premature menopause OR premature ovarian dysfunction OR amenorrhoea OR “POI” OR “POF”) AND (Chinese medicine OR herbal medicine OR Chinese herb* OR Chinese drug OR traditional medicine OR alternative medicine OR complementary medicine OR acupuncture OR needling OR acupoint* OR “point, acupuncture” OR electroacupuncture OR warm* needle OR warm needling OR fire needling OR auricular acupressure OR auricular point* OR auricular needle OR ear acupuncture OR acupoint catgut embedding OR acusector OR moxibustion OR cupping OR massage OR tuina) Article type: Clinical trial OR randomized controlled trial Publication date: From the beginning until on 20 Jan 2022 Search result: 99 articles OVID MEDLINE ((Premature ovarian insufficiency or primary ovarian insufficiency or premature ovarian failure or primary ovarian failure or ovarian insufficiency or premature menopause or premature ovarian dysfunction or amenorrhoea or POI or POF) AND (Chinese medicine or herbal medicine or Chinese herb* or Chinese drug or traditional medicine or alternative medicine or complementary medicine or acupuncture or needling or acupoint* or electroacupuncture or warm* needle or warm needling or fire needling or auricular acupressure or auricular point* or auricular needle or ear acupuncture or acupoint catgut embedding or acusector or moxibustion or cupping or massage or tuina)) Publication type: Randomized controlled trial Search result: 22 articles Scopus ALL (((premature AND ovarian AND insufficiency OR primary AND ovarian AND insufficiency OR premature AND ovarian AND failure OR primary AND ovarian AND failure OR ovarian AND insufficiency OR premature AND menopause OR premature AND ovarian AND dysfunction OR amenorrhoea OR poi OR pof) AND (Chinese AND medicine OR herbal AND medicine OR Chinese AND herb* OR Chinese AND drug OR traditional AND medicine OR alternative AND medicine OR complementary AND medicine OR acupuncture OR needling OR acupoint* OR electroacupuncture OR warm* AND needle OR warm AND needling OR fire AND needling OR auricular AND acupressure OR auricular AND point* OR auricular AND needle OR ear AND acupuncture OR acupoint AND catgut AND embedding OR acusector OR moxibustion OR cupping OR massage OR tuina))) Document type: Clinical trial Search result: 0 articles CNKI Professional search: ((TI=premature ovarian insufficiency OR TI=premature ovarian failure OR TI=premature ovarian diminished OR TI=ovarian insufficiency OR TI=ovarian failure) OR (KY=premature ovarian insufficiency OR KY=premature ovarian failure OR KY=premature ovarian diminished OR KY=ovarian insufficiency OR KY=ovarian failure) OR (AB=premature ovarian insufficiency OR AB=premature ovarian failure OR AB=premature ovarian diminished OR AB=ovarian insufficiency OR AB=ovarian failure)) AND ((TI=Chinese medicine OR TI=herbal medicine OR TI=integrative medicine OR TI=herb OR TI=acupuncture OR TI=moxibustion OR TI=acupoint OR TI=tuina OR TI=catgut-embedding OR TI=cupping) OR (KY=Chinese medicine OR KY=herbal medicine OR KY=integrative medicine OR KY=herb OR KY=acupuncture OR KY=moxibustion OR KY=acupoint OR KY=tuina OR KY=catgut-embedding OR KY=cupping) OR (AB=Chinese medicine OR AB=herbal medicine OR AB=integrative medicine OR AB=herb OR AB=acupuncture OR AB=moxibustion OR AB=acupoint OR AB=tuina OR AB=catgut-embedding OR AB=cupping)) Search result: 1,135 articles (Note: Search was done in Chinese language.) WanFang ((TITLE=premature ovarian insufficiency OR TITLE=premature ovarian failure OR TITLE=premature ovarian diminished OR TITLE=ovarian insufficiency OR TITLE=ovarian failure) OR (KEYWORDS=premature ovarian insufficiency OR KEYWORDS=premature ovarian failure OR KEYWORDS=premature ovarian diminished OR KEYWORDS=ovarian insufficiency OR KEYWORDS=ovarian failure)) AND ((TITLE=Chinese medicine OR TITLE=herbal medicine OR TITLE=integrative medicine OR TITLE=herbal medicine OR TITLE=acupuncture OR TITLE=moxibustion OR TITLE=acupoint OR TITLE=tuina OR TITLE=catgut-embedding OR TITLE=cupping) OR (KEYWORDS=Chinese medicine OR KEYWORDS=herbal medicine OR KEYWORDS=integrative medicine OR KEYWORDS=herb OR KEYWORDS=acupuncture OR KEYWORDS=moxibustion OR KEYWORDS=acupoint OR KEYWORDS=tuina OR KEYWORDS=catgut-embedding OR KEYWORDS=cupping)) Source: Journal, conference report Search result: 978 articles (Note: Search was done in Chinese language.) VIP (M=(premature ovarian insufficiency OR premature ovarian failure OR premature ovarian diminished OR ovarian insufficiency OR ovarian failure) AND (herbal medicine OR herb OR integrative medicine OR acupuncture OR moxibustion OR acupoint OR tuina OR catgut-embedding OR cupping)) Search result: 368 articles (Note: Search was done in Chinese language.) Inclusion criteria All relevant TCM randomized controlled trials (RCTs) for POI were included according to the inclusion criteria. Types of participant (P): Patients diagnosed with POI according to the European Society of Human Reproduction and Embryology (ESHRE) guideline 1 or “Chinese expert consensus on premature ovarian insufficiency”. 4 Types of Intervention (I): The treatment group received TCM treatment modalities, such as herbal medicine, acupuncture, moxibustion and catgut embedding therapy alone or in combination. Comparisons (C): The control group received HRT or one of the aforementioned TCM treatments. Outcomes (O): • Primary outcome measurement: Total effective rate. Total effective rate = (number of recovery cases + number of effective cases + number of efficient cases)/total number of cases × 100%. (i) Recovery: clinical manifestations disappeared, menstrual cycle, serum FSH and E 2 levels returned to normal, total effective rate ≥95%; (ii) Effective: clinical manifestations were significantly improved, menstrual cycle, serum FSH and E 2 levels were significantly improved, total effective rate ≥70% and <95%; (iii) Efficient: clinical manifestations were slightly improved, menstrual cycle, serum FSH and E 2 levels were slightly improved, total effective rate ≥30% and <70%; (iv) Invalid: there was no improvement in clinical signs and symptoms, no improvement in menstrual cycle, no improvement in serum FSH and E 2 levels, total effective rate <30%. • Secondary outcome measurements: Serum FSH, E 2 , luteinizing hormone (LH) and AMH levels. Type of studies (S): RCTs. Exclusion criteria Studies were omitted if the studies did not meet the inclusion criteria, for instance animal studies, review articles, case reports, editorials, letters and comments. Data collection The name of authors, year of publication, subject age group, course of disease, types of TCM treatment modalities, number of subjects in intervention and comparison groups, were extracted into a spreadsheet. Two researchers (SYS and CM) performed the data extraction individually. In case of any discrepancies, another researcher (SKS) were asked to resolve the discrepancies via discussion. Literature quality evaluation The Cochrane risk of bias tool was used to appraise the quality and risk of bias of the included studies. The assessment was done independently by two researchers (SYS and CM). 15 In this tool, the random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome reporting, incomplete outcome data, selective reporting, and other items were being evaluated in all the included studies. Low, unclear and high risk of bias were used to evaluate each element. In case of discrepancies, discussion among the researchers (SYS, CM and SKS) were done to resolve it. Statistical analysis For pairwise meta-analysis of each intervention pair, a random effect model was used, with RevMan (RRID:SCR_003581) 5.4 (Nordic Cochrane Centre, Cochrane Collaboration, 2020) being employed. Continuous outcomes between intervention groups can be compared by using standard mean differences (SMDs), while dichotomous outcomes can be analyzed using odds ratios (OR). The relative treatment effectiveness between each intervention pair were estimated using 95% confidence intervals. A NMA was performed in Stata (RRID:SCR_012763) 14.0 (free alternative, RStudio) and the network evidence graph was generated using the ‘netplot’ command. To compare direct and indirect comparisons of each intervention, I 2 and P-value of the global consistency were evaluated, and then the node-splitting analysis method was applied to detect inconsistencies. The inconsistency factor within each closed loop of evidence was used to detect inconsistency among studies. The evaluation indexes included surface under the cumulative ranking curves (SUCRA) and mean rank (MR). The SUCRA value reflected the possibility of the intervention measures, and the intervention was considered more effective if the MR was closer to 0. P<0.05 was considered statistically significant. 11 To determine if there was a small sample effect or publication bias in the network, a comparison-adjusted funnel plot was used. Results Study selection The selection procedure was recorded in Figure 1 according to the most updated PRISMA 2020 flow diagram for new systematic review. 16 A total of 2,602 studies were firstly identified through six databases, including three English databases (PubMed, OVID and Scopus), as well as three Chinese databases (CNKI, VIP and WanFang). Of those, 586 duplicate records were eliminated using EndNote X9 (RRID:SCR_014001) (Clarivate Analytics, USA). By assessing the title and abstract, 1,940 studies were subsequently removed. Full articles of the remaining 76 studies were screened, of which 43 were removed for not reporting relevant outcome data, non-RCT, no full-text access, not relevant to TCM intervention, or intervention only included in one trial, which may lead to small study effects in a NMA. Eventually, 33 RCTs involving 2,597 subjects that conformed to the inclusion criteria were selected into this study and proceed with data extraction and analysis. Among them, all RCTs were Chinese articles. This NMA incorporated HRT as the placebo and six TCM treatment modalities. The characteristics and details of the included 33 RCTs are listed in Table 2 . Figure 1. PRISMA flowchart showing steps in the selection of relevant trials. Note: RCT, randomized controlled trials. Table 2. Characteristics and details of the included 33 RCTs. Author name, year (ref.) Admission time Sample size (T/C) Mean age/course of disease (T/C) Intervention group Control group Outcome Xie Q 2022 24 From Jan 2019 to Jan 2021 57/57 28.41±5.16/28.75±5.33 HRT + Herbal Medicine + Acupuncture HRT ①②③④ Peng YL 2022 25 From Jan 2019 to Dec 2020 46/46 28.54±3.66/28.21±3.85 Herbal Medicine + Acupuncture Herbal Medicine ①②③④ Huang YS 2021 26 From Mar 2018 to Mar 2020 30/30 31.43±4.48/30.80±5.12 Acupuncture + Moxibustion HRT ①②③⑤ Chen JM 2021 27 From May 2019 to Jan 2020 50/30 30.19±6.55/31.65±7.55 Herbal Medicine HRT ①②③⑤ Yuan F 2021 28 From Dec 2018 to Jun 2020 42/42 36.05±3.48/35.65±3.51 HRT + Herbal Medicine HRT ①②③④ Chen L 2021 29 From May 2017 to May 2019 35/35 38.97±5.52/38.80±4.96 HRT + Herbal Medicine HRT ①② Sui J 2021 30 From Oct 2017 to Jan 2019 60/62 32.45±0.93/34.61±0.61 Herbal Medicine HRT ①②③④⑤ Wang XW 2021 31 From Jul 2019 to Jun 2020 25/25 36.40±1.10/36.50±1.00 Herbal Medicine HRT ①②③④ Wang YY 2021 32 From Mar 2018 to Mar 2020 26/26 30.22±4.31/30.15±4.23 Herbal Medicine + Acupuncture HRT ①②③④ Tang HX 2021 33 From Oct 2019 to Oct 2020 40/40 31.63±3.46/32.57±3.60 Herbal Medicine HRT ①②③④⑤ Lin LL 2021 34 From Jan 2018 to Jan 2020 20/20 33.98±2.08/33.70±2.13 Herbal Medicine + Cat-gut Embedding Therapy HRT ①②③ Zhang H 2021 35 From Jan 2019 to Mar 2020 60/60 35.21±2.35/35.17±2.26 HRT + Herbal Medicine HRT ①②③④⑤ Hou M 2021 36 From Nov 2019 to Oct 2020 30/30 35.00±8.26/36.00±3.57 Acupuncture HRT ①②③ Wu Q 2021 37 From Mar 2019 to Oct 2019 30/30 31.57±5.04/31.63±4.54 HRT + Herbal Medicine HRT ①②③④⑤ Fu WJ 2021 38 From Sep 2019 to Nov 2020 30/30 36.43±2.18/35.29±2.43 HRT + Herbal Medicine HRT ①②③④ Ding AY 2021 39 From Mar 2019 to Nov 2019 40/40 35.40±2.50/35.10±2.80 HRT + Herbal Medicine HRT ①②③ Ma QW 2020 40 From Sep 2017 to Jan 2019 60/60 31.10±4.30/31.80±4.50 HRT + Herbal Medicine HRT ①②③④ Zhao JM 2020 41 From Aug 2017 to Dec 2018 52/52 31.17±3.69/31.62±3.75 HRT + Herbal Medicine HRT ①②③④ Luo C 2020 42 From Mar 2017 to Jan 2019 30/30 35.07±2.09/35.27±3.25 Herbal Medicine HRT ①②③④⑤ Wang TT 2020 43 From Mar 2019 to Aug 2020 30/30 32.45±4.15/32.44±4.12 Herbal Medicine + Acupuncture Herbal Medicine ① Chi L 2020 44 From Jun 2017 to Mar 2019 51/54 29.02±3.00/30.18±3.20 Herbal Medicine HRT ①②③⑤ Liu X 2020 45 From May 2017 to Oct 2018 35/35 31.55±3.16/30.81±3.25 HRT + Herbal Medicine HRT ① Ma K 2019 46 From Oct 2016 to Sep 2018 43/43 33.81±3.70/32.86±3.96 Herbal Medicine HRT ①②③④⑤ Zhong WP 2019 47 From Jun 2016 to Dec 2017 20/20 36.00±2.02/36.20±1.94 Herbal Medicine HRT ①②③④ Yuan YJ 2019 48 From Aug 2016 to Nov 2018 45/45 33.18±4.46/32.46±5.45 Herbal Medicine HRT ① Li J 2019 49 From Apr 2017 to Apr 2018 44/44 32.47±4.11/32.45±4.13 HRT + Herbal Medicine HRT ①②③④⑤ Zhang N 2019 50 From Dec 2016 to Jun 2018 45/45 28.20±4.60/30.20±4.10 HRT + Herbal Medicine + Acupuncture HRT + Herbal Medicine ①②③④ Zhou QY 2018 51 From Dec 2017 to May 2018 30/30 35.70±2.20/35.40±2.50 HRT + Herbal Medicine HRT ①②③ Li Xia 2018 52 From Mar 2015 to Jul 2018 30/30 22.40±9.08/25.71±7.12 Herbal Medicine + Acupuncture HRT ①②③④ Li Xiao 2018 53 From Feb 2015 to Dec 2016 40/40 31.81±4.29/31.78±4.26 Herbal Medicine HRT ①②③④ Yao L 2007 54 From Jan 1988 to Dec 2003 130/130 36.00±2.09/30.80±5.40 Herbal Medicine HRT ①②③④ Cui LL 2022 55 From Sep 2018 to Jan 2020 39/38 36.00±6.00/37.00±6.00 Herbal Medicine + Cat-gut Embedding Therapy Herbal Medicine ①②③④⑤ Zeng X 2021 56 From Dec 2019 to Jul 2020 48/48 32.60±3.90/33.20±3.90 HRT + Herbal Medicine HRT ①②③ Risk of bias of the included studies For the random sequence generation element, 21 studies reported an appropriate method for randomization, thus “low risk”. There were two studies allocated participants to interventions based on participants’ preference and hospital record number therefore “high risk”. The rest only reported random, so it is “unclear”. In terms of allocation concealment, 30 studies were judged as having “high risk” of bias as there were inadequate concealment of allocations prior to assignment. Only one study reported clear allocation concealment by using sequentially numbered, opaque and sealed envelope, therefore it was judged as “low risk”. There were two studies reported using assignment envelopes but sufficient details such as whether the envelopes were sequentially numbered, opaque and sealed were not mentioned, thus “unclear”. In terms of blinding of participants and personnel, only one study was stated as single-blinded design but did not address the outcome, therefore “unclear”. The rest of the studies were judged as “high risk” as there were no blinding and due to different treatment modalities, participants might have the wrong belief that the intervention was more effective for their treatment. In terms of outcome assessment, all studies were judged as “unclear” due to inadequate information for evaluation. In terms of incomplete outcome data, only one study was judged as “high risk” of bias as there were missing outcome data across the intervention groups. The rest were “low risk”. In terms of selective reporting, only one study was judged as “high risk” of bias due to incomplete outcome of interest in the study. The rest were “low risk”. In terms of other bias, all studies were “low risk” except two, in which there were incorrect reported data and discrepancies found in the studies. The graph and summary of the risk of bias are listed in Figure 2 . Figure 2. Graph and summary of the risk of bias. Risk of bias A) graph and B) summary. Results of NMA Pairwise meta-analysis Table 3 presents the results of the pairwise meta-analysis and heterogeneity estimates. All 33 studies reported total effective rate, 30 reported FSH, 29 reported E 2 , 20 reported LH and 13 reported AMH. Table 3. Pairwise meta-analysis. Outcome measurement Comparison N OR (95%CI) P I 2 (%) Total Effective Rate G vs. A 2 3.42 [1.02, 11.46] 0.05 0 D vs. A 11 2.34 [1.46, 3.76]* 0.0004 38 E vs. A 2 2.43 [0.16, 36.61] 0.52 80 F vs. A 1 10.32 [1.12, 93.34]* 0.04 N/A B vs. A 14 3.74 [2.61, 5.35]* <0.0001 0 C vs. A 1 5.17 [1.61, 16.64]* 0.006 N/A C vs. B 1 1.54 [0.24, 9.66] 0.65 N/A E vs. D 2 9.22 [2.02, 42.03]* 0.004 0 F vs. D 1 4.04 [1.17, 13.96]* 0.03 N/A Outcome measurement Comparison N SMD (95%CI) P I 2 (%) FSH G vs. A 2 3.70 [2.18, 5.23]* <0.00001 0 D vs. A 9 2.68 [0.48, 4.88]* 0.02 79 E vs. A 2 3.29 [0.51, 6.07]* 0.02 57 F vs. A 1 4.24 [-0.53, 9.01] 0.08 N/A B vs. A 13 4.82 [3.61, 6.02]* <0.00001 83 C vs. A 1 12.00 [8.43, 15.57]* <0.00001 N/A C vs. B 1 10.20 [4.96, 15.44]* 0.0001 N/A F vs. D 1 1.38 [-0.11, 2.87] 0.07 N/A E 2 G vs. A 2 -11.97 [-45.01, 21.08] 0.48 94 D vs. A 9 8.52 [0.53, 16.51]* 0.04 96 E vs. A 2 15.04 [1.06, 29.01]* 0.03 71 F vs. A 1 8.56 [3.44, 13.68]* 0.001 N/A B vs. A 12 9.09 [5.49, 12.70]* <0.00001 96 C vs. A 1 28.43 [25.92, 30.94]* <0.00001 N/A C vs. B 1 13.20 [9.06, 17.34]* <0.00001 N/A F vs. D 1 22.89 [20.44, 25.34]* <0.00001 N/A LH D vs. A 7 1.36 [0.36, 2.36]* 0.008 26 E vs. A 2 0.87 [0.14, 1.61]* 0.02 0 B vs. A 8 5.20 [2.51, 7.88]* 0.0001 92 C vs. A 1 18.10 [15.75, 20.45]* <0.00001 N/A C vs. B 1 5.90 [1.57, 10.23]* 0.008 N/A F vs. D 1 1.57 [1.12, 2.02]* <0.00001 N/A AMH G vs. A 1 0.09 [-0.12, 0.30] 0.39 N/A D vs. A 6 0.68 [0.22, 1.14]* 0.004 99 B vs. A 5 0.54 [-0.04, 1.13] 0.07 99 F vs. D 1 0.15 [0.02, 0.28]* 0.03 N/A The forest plot of total effective rate indicates that herbal medicine (OR 2.34, 1.46 to 3.76, I 2 =38%) and HRT + herbal medicine (OR 3.74, 2.61 to 5.35, I 2 =0%) were more effective than HRT alone. Herbal medicine and acupuncture (OR 9.22, 2.02 to 42.03, I 2 =0%) was more effective than herbal medicine alone. The forest plot of FSH indicates that acupuncture + moxibustion (MD 3.70, 2.18 to 5.23, I 2 =0%), herbal medicine (MD 2.68, 0.48 to 4.88, I 2 =79%), herbal medicine + acupuncture (MD 3.29, 0.51 to 6.07, I 2 =57%) and HRT + herbal medicine (MD 4.82, 3.61 to 6.02, I 2 =83%) were more effective in improving FSH levels compared to HRT alone. The forest plot of E 2 indicates that all treatment modalities involved herbal medicine, including HRT + herbal medicine (MD 9.09, 5.49 to 12.70, I 2 =96%), HRT + herbal medicine + acupuncture (MD 28.43, 25.92 to 30.94, I 2 =n/a), herbal medicine (MD 8.52, 0.53 to 16.51, I 2 =96) and herbal medicine + acupuncture (MD 15.04, 1.06 to 29.01, I 2 =71%) showed higher effectiveness than HRT alone to improve E 2 levels among patients with POI. The forest plot of LH indicates that therapeutic effects of HRT + herbal medicine (MD 5.20, 2.51 to 7.88, I 2 =92%), herbal medicine (MD 1.36, 0.36 to 2.36, I 2 =26%) and herbal medicine + acupuncture (MD 0.87, 0.14 to 1.61, I 2 =0%) were more superior than HRT alone. The forest plot of AMH indicates that herbal medicine (MD 0.68, 0.22 to 1.14, I 2 =99%) showed better efficacy compared to only HRT in improving AMH levels. NMA on total effective rate The results of the NMA showing comparisons of different treatments based on total effective rate are shown in Figure 3A . The total effective rate are presented in the form of a league table can be found in Figure 4A . A total of 33 RCTs (2,862 participants) with seven different treatment modalities were analyzed. The results of NMA indicate that herbal medicine combined with catgut-embedding therapy have the highest efficiency. According to the SUCRA, which presents treatment ranking to offer the most important benefit outcome (the highest total effective rate), herbal medicine combined with catgut-embedding therapy (87.8%) had the highest effective rate, followed by combination of HRT with herbal medicine and acupuncture (76.8%), HRT combined with herbal medicine (67.1%), acupuncture combined with moxibustion (63.1%), herbal medicine combined with acupuncture (27.3%), HRT alone (16.1%) and herbal medicine only (11.9%). This also showed that combination of TCM treatments with HRT are more effective than HRT alone. Table 4 (part A) and Figure 5A depict the rankings of these seven treatments. Figure 3. Network map results of treatment comparisons based on total effective rate, serum FSH, E 2 , LH and AMH levels. A) Total effective rate. B) FSH, C) E 2 , D) LH and E) AMH levels. Note: FSH, follicle-stimulating hormone; E 2 , estradiol; LH, luteinizing hormone; AMH, anti-Müllerian hormone; HRT, hormone replacement therapy; Herb, herbal medicine; Catgut, catgut-embedding therapy; Acu, acupuncture; Moxa, moxibustion. Figure 4. League table showing the results of network meta-analysis comparisons based on total effective rates, serum FSH, E 2 , LH and AMH levels of all TCM treatment modalities including odds ratios (OR) and 95% credible intervals. A) Total effective rate. B) FSH, C) E 2 , D) LH and E) AMH levels. OR>1 means the top-left treatment is better. Note: FSH, follicle-stimulating hormone; E 2 , estradiol; LH, luteinizing hormone; AMH, anti-Müllerian hormone; TCM, Traditional Chinese medicine; HRT, hormone replacement therapy; Herb, herbal medicine; Catgut, catgut-embedding therapy; Acu, acupuncture; Moxa, moxibustion. Table 4. SUCRA ranking probabilities of all TCM treatment modalities for POI based on total effective rate. Treatment SUCRA PrBest MeanRank A. Total effective rate HRT 16.1 0.0 6.0 HRT + Herb 67.1 3.9 3.0 HRT + Herb + Acu 76.8 21.4 2.4 Herb 11.9 0.0 6.3 Herb + Acu 27.3 0.1 5.4 Herb + Catgut 87.8 66.2 1.7 Acu + Moxa 63.1 8.5 3.2 B. FSH HRT 5.8 0.0 6.7 HRT + Herb 67.4 0.0 3.0 HRT + Herb + Acu 99.9 99.5 1.0 Herb 23.1 0.0 5.6 Herb + Acu 49.6 0.1 4.0 Herb + Catgut 49.3 0.2 4.0 Acu + Moxa 54.9 0.1 3.7 C. E 2 HRT 15.1 0.0 6.1 HRT + Herb 51.6 0.0 3.9 HRT + Herb + Acu 92.6 66.4 1.4 Herb 40.8 0.0 4.6 Herb + Acu 66.7 10.3 3.0 Herb + Catgut 80.1 23.3 2.2 Acu + Moxa 3.2 0.0 6.8 D. LH HRT 12.3 0.0 5.4 HRT + Herb 71.0 0.0 2.4 HRT + Herb + Acu 99.9 99.7 1.0 Herb 40.4 0.0 4.0 Herb + Acu 22.3 0.0 4.9 Herb + Catgut 53.9 0.3 3.3 E. AMH HRT 16.7 0.0 4.3 HRT + Herb 66.7 24.1 2.3 Herb 65.8 16.5 2.4 Herb + Catgut 67.2 45.5 2.3 Acu + Moxa 33.6 13.9 3.7 Figure 5. SUCRA ranking probabilities of total effective rate, serum FSH, E 2 , LH and AMH levels among all TCM treatment modalities. A) Total effective rate. B) FSH, C) E 2 , D) LH and E) AMH levels. Note: SUCRA, surface under the cumulative ranking curves; FSH, follicle-stimulating hormone; E 2 , estradiol; LH, luteinizing hormone; AMH, anti-Müllerian hormone; TCM, Traditional Chinese medicine; HRT, hormone replacement therapy; Herb, herbal medicine; Catgut, catgut-embedding therapy; Acu, acupuncture; Moxa, moxibustion. NMA on FSH levels The results of the NMA showing comparisons of different treatments based on improvements of FSH levels are shown in Figure 3B . The league table results of the NMA on FSH levels are presented in Figure 4B . A total of 28 RCTs (2,384 participants) with seven different treatment modalities were analyzed. The results of NMA indicate that the combination of HRT with herbal medicine and acupuncture achieved the highest efficiency in improving the FSH levels. According to SUCRA, the combination of HRT with herbal medicine and acupuncture (99.9%) had the highest effective rate, followed by HRT combined with herbal medicine (67.4%), acupuncture combined with moxibustion (54.9%), herbal medicine combined with acupuncture (49.6%), herbal medicine combined with catgut-embedding therapy (49.3%), herb alone (23.1%) and HRT only (5.8%). Table 4 (part B) and Figure 5B depict the rankings of these seven treatments. NMA on E 2 levels The results of the NMA showing comparisons of different treatments for the changes of E 2 levels are shown in Figure 3C . The league table results for the E 2 comparison are shown in Figure 4C . A total of 26 RCTs (2,108 participants) with seven different treatment modalities were analyzed. The results of NMA indicate that the combination of HRT with herbal medicine and acupuncture had the highest efficiency. It was also found that the combination of different treatment modalities pairing with herbal medicine were more effective than HRT alone. According to SUCRA, the combination of HRT with herbal medicine and acupuncture (92.6%) had the highest effective rate, followed by herbal medicine combined with catgut-embedding therapy (80.1%), herbal medicine combined with acupuncture (66.7%), HRT combined with herbal medicine (51.6%), herbal medicine alone (40.8%), HRT alone (15.1%) and acupuncture combined with moxibustion (3.2%). Table 4 (part C) and Figure 5C depict the rankings of these seven treatments. NMA on LH levels The results of the NMA showing treatment comparisons based on the difference of LH levels are shown in Figure 3D . The league table results of the NMA for LH levels are shown in Figure 4D . A total of 19 RCTs (1,505 participants) with six different treatment modalities were analyzed. The results of NMA indicate that the combination of HRT with herbal medicine and acupuncture have the highest efficacy. It was also discovered that treatment modalities combined with herbal medicine are more useful than HRT alone. According to SUCRA, the combination of HRT with herbal medicine and acupuncture (99.9%) had the highest effective rate, followed by HRT combined with herbal medicine (71.0%), herbal medicine combined with catgut-embedding therapy (53.9%), herbal medicine alone (40.4%), herbal medicine combined with acupuncture (22.3%) and HRT alone (12.3%). Table 4 (part D) and Figure 5D presents the ranking of these six treatments. NMA on AMH levels The results of the NMA showing treatment comparisons based on the improvement of AMH levels in five treatment modalities are shown in Figure 3E . The league table results regarding the comparison of the AMH levels are presented in Figure 4E . A total of 11 RCTs with reported AMH levels (1,030 participants) were analyzed. The results of NMA indicate that herbal medicine combined with catgut-embedding therapy had the highest efficiency and treatment modalities with the presence of herbal medicine are more effective compared to treatment without herbal medicine. According to SUCRA, herbal medicine combined with catgut-embedding therapy (67.2%) had the highest effective rate, followed by HRT combined with herbal medicine (66.7%), herbal medicine alone (65.8%), acupuncture combined with moxibustion (33.6%) and HRT alone (16.7%). Table 4 (part E) and Figure 5E depict the rankings of these five treatments. Evaluation of statistical inconsistency Although global inconsistency showed there that were no significant statistical differences for the outcomes, the node-splitting method was employed to further evaluate on the local inconsistency ( Table 5 ). Overall, no statistical inconsistency for the outcomes were seen from the node-splitting outcome, except between direct and indirect comparisons of HRT with combination of HRT and herbal medicine, HRT with herbal medicine, HRT with combination of herbal medicine and acupuncture, herbal medicine with combination of HRT and herbal medicine, herbal medicine with combination of herbal medicine and acupuncture, as P<0.05 indicates for local inconsistency between the local comparisons. These might be due to ineffective sample size for the particular treatment comparisons. Table 5. Side-splitting approach of total effective rate, serum FSH, E 2 , LH and AMH levels. Side Direct Indirect Difference P>|z| Coef. Std.Err Coef. Std.Err Coef. Std.Err A. Total effective rate A B 1.302018 0.1869113 2.694049 0.6192193 -1.392031 0.6308563 0.027 A C 1.643014 0.6890454 1.839627 1.020893 -0.1966132 1.231668 0.873 A D 0.7736507 0.2225935 -0.5922928 0.6084046 1.365943 0.6440799 0.034 A E 0.2745474 0.5314991 2.925095 0.8082094 -2.650548 0.9568743 0.006 A F 2.3254 1.177303 2.042871 0.7480681 0.2825286 1.394865 0.839 A G - - - - - - - B C 0.4290022 0.9997119 0.2323267 0.7194375 0.1966755 1.231671 0.873 B D -1.561014 0.4246506 -0.4012063 0.3030283 -1.159807 0.5189197 0.025 D E 2.221581 0.7822485 -0.4290057 0.551082 2.650587 0.9568655 0.006 D F 1.395881 0.7169363 1.678198 1.196491 -0.2823171 1.394837 0.840 B. FSH A B -4.385776 .8296878 -7.019813 3.360363 2.634038 3.463264 0.447 A C -12 3.379563 -14.80831 3.988823 2.808312 5.228016 0.591 A D -1.330655 1.152858 .4646895 3.094725 -1.795344 3.301872 0.587 A E - - - - - - - A F -4.24 3.754363 -2.397674 3.16034 -1.842325 4.907443 0.707 A G - - - - - - - B C -10.19999 3.902824 -7.3909 3.478562 -2.809093 5.228043 0.591 B D 5.876125 1.997919 2.04132 1.518885 3.834806 2.509528 0.126 D F -1.379984 2.959344 -3.219893 3.914674 1.839909 4.907389 0.708 C. E 2 A B 9.092383 2.721332 20.20191 9.597002 -11.10953 9.975317 0.265 A C 28.43 9.621474 22.89342 10.14843 5.536579 13.9844 0.692 A D 8.621667 3.561098 -1.652434 9.294642 10.2741 9.953024 0.302 A E - - - - - - - A F 8.560001 9.168995 31.61203 9.457669 -23.05203 13.17262 0.080 A G - - - - - - - B C 13.20007 9.767265 18.7195 10.00883 -5.519434 13.98484 0.693 B D -5.415176 6.761988 -1.062784 5.045681 -4.352393 8.437178 0.606 D F 22.89007 8.877762 -0.207172 9.733271 23.09724 13.17386 0.080 D. LH A B -4.632461 1.104242 -12.19775 4.807764 7.565293 4.932953 0.125 A C -18.1 3.135893 -10.5318 3.808109 -7.568203 4.933104 0.125 A D -2.089832 1.392677 0.7951949 31.73015 -2.885027 31.7607 0.928 A E - - - - - - - B C -5.899871 3.644604 -13.46706 3.32461 7.567194 4.93318 0.125 D F -1.57 3.060984 4.200054 63.4475 -5.770054 63.52132 0.928 E. AMH A B 0.5447631 0.326256 1.227886 1.155475 -0.6831228 1.200393 0.569 A C 0.68482 0.2711292 -0.9716826 1.105524 1.6565503 1.138173 0.146 A E - - - - - - - B C -0.4066692 0.4828313 0.4681092 0.5217627 -0.8747784 0.7108789 0.218 C D 0.15 0.7004296 -1.18702 18.80401 1.33702 18.81704 0.943 Small-study effects There was a lack of strong evidence on the small-study effects across outcomes based on total effective rate and FSH level ( Figure 6A and B ). Figure 6. Funnel plot of total effective rate, serum FSH, E 2 , LH and AMH levels. A) Total effective rate. B) FSH, C) E 2 , D) LH and E) AMH levels. Note: FSH, follicle-stimulating hormone; E 2 , estradiol; LH, luteinizing hormone; AMH, anti-Müllerian hormone. However, among the outcome indicators of E 2 , LH and AMH ( Figure 6C , D and E ), it could be inferred that heterogeneity between studies were one of the reasons for those studies located on the lateral side of the funnel plot. Comparison-correction funnel plots based on E 2 , LH and AMH levels were made upon 26, 19 and 11 included studies, respectively (involving seven, six and five interventions, respectively). The asymmetrical funnel plots suggest probability of small-study effects in this study. Sensitivity analysis For the paired studies with significant heterogeneity (I 2 > 50%), a sensitivity analysis was done by removing any single study one by one. Results showed that there were no significant changes, stipulating that the pooled results were consistent. Discussion Previous studies 9 , 10 , 17 have demonstrated the efficacy of herbal medicine and acupuncture in treating POI. In this study, we utilized the advantages of NMA method to compare the efficacy of various TCM treatment modalities for this condition. Our findings revealed the comparative efficacy of six treatment modalities: HRT combined with herbal medicine and acupuncture, HRT combined with herbal medicine, herbal medicine combined with acupuncture, herbal medicine combined with catgut-embedding therapy, acupuncture combined with moxibustion and herbal medicine alone. Table 6 shows the compilation of SUCRA rank for each outcome measurement in NMA. Our results indicated that the combination of HRT with herbal medicine and acupuncture was the most effective treatment modality for patients with POI in the present study. These findings suggest that TCM treatment approaches could be considered as a promising therapeutic option for women with POI. Table 6. Compilation of SUCRA Rank for each outcome measurement in NMA. SUCRA Rank Outcome measurement Total effective rate FSH E 2 LH AMH 1 Herb + Catgut HRT + Herb + Acu HRT + Herb + Acu HRT + Herb + Acu Herb + Catgut 2 HRT + Herb + Acu HRT + Herb Herb + Catgut HRT + Herb HRT + Herb 3 HRT + Herb Acu + Moxa Herb + Acu Herb + Catgut Herb 4 Acu + Moxa Herb + Acu HRT + Herb Herb Acu + Moxa 5 Herb + Acu Herb + Catgut Herb Herb + Acu HRT 6 HRT Herb HRT HRT 7 Herb HRT Acu + Moxa To the best of our knowledge, this study is the first systematic evaluation covering all treatment modalities in TCM to provide reliable evidence to determine the efficacy and feasibility of TCM treatment for patients with POI. There are a variety of different treatment modalities in TCM and all seem effective in treatment. 11 , 18 However, until now there have been no consensus or standard procedure of TCM treatment recommended for POI. This scientific direct and indirect comparison can provide important guidance on the pros and cons of each intervention and their treatment priority. There is no record about POI found in the TCM literature. However, comparing its clinical manifestations, POI can be categorized as “amenorrhoea”, “oligomenorrhoea” and “infertility” based on TCM perspective. The pathogenesis is mainly related to malnourishment of the thoroughfare and conception vessels, as well as the uterus, which might be due to congenital insufficiency, physical and mental overwork, or sexual overstrain. TCM treats a disease based on syndrome differentiation. Different treatment modalities such as oral administration of herbal decoction, acupuncture, catgut-embedding therapy, moxibustion, electroacupuncture, ear acupressure and herbal enema, are suitable for the treatment of POI. In our study, 33 clinical trials using TCM treatment were screened and the therapeutic effect of seven treatment modalities were analyzed. It has been proven that comprehensive treatment models are more effective in improving ovarian function, compared to just using HRT as sole treatment. This would provide clinical practitioners with strong and reliable evidence, as well as a useful alternative during clinical decision-making. We also found that the integration of herbal medicine into POI treatment, such as its combination with HRT, acupuncture or catgut-embedding therapy, can significantly improve the ovarian functions by observing on indicators including total effective rate, FSH, E 2 , LH and AMH levels. Therefore, herbal medicine may be considered as an intervention when HRT alone, the standard procedure recommended by recognized guidelines worldwide, 1 , 4 , 5 cannot effectively cure POI. This study possesses significance in providing clinical guidance. Acupuncture has been widely applied on POI treatment particularly in China. 10 , 11 , 18 It has been demonstrated that acupuncture is safe and effective. 19 – 21 Through early intervention of acupuncture, it has also been found that acupuncture can increase pregnancy rate significantly. 22 , 23 Our study has demonstrated that application of acupuncture in the treatment of POI is also useful to observe clinical improvement. However, it is suggested that acupuncture must be combined with herbal medicine and even HRT in order to optimize the therapeutic effects. This recommended treatment modality not only demonstrates the advantage of TCM treatment, it also provides a potential practical, safe and low-cost treatment option for both the patients and clinicians. In this study, we found a shortage of rigorous clinical trials adhering to the international requirements, as well as a paucity of heterogeneity of study candidates, interventions, controls, and outcome measures, which challenge the process of systematic review and NMA. Due to inadequate data from the included studies, the safety of each intervention could not be evaluated. The risk of bias assessment in this study indicates that most of the studies did not clearly state the blinding of outcome assessors, which might impact on the reliability of data analysis outcome. Conclusions In conclusion, herbal medicine combined with catgut-embedding therapy was shown to be the most effective treatment model to improve total effective rate and AMH levels in the present study. The combination of HRT, herbal medicine and acupuncture was demonstrated to be the most effective treatment model for improving serum FSH, E 2 and LH levels. An overview on SUCRA analysis outcomes showed that comprehensive treatment models with the integration of herbal medicine seemed more prone to improve ovarian functions. Monotherapies, such as solely using HRT or herbal medicine treatment, were found to have no obvious advantages on their curative effect for POI. The integration of herbal medicine to conventional HRT may be a favorable approach for enhancing the clinical utility of HRT in the management of POI. RCTs involving multiple centers and different countries are essential to further verify the conclusions of this study, which can also create international awareness on the efficacy of TCM treatments for POI. Data availability Underlying data All data underlying the results are available as part of the article and no additional source data are required. Reporting guidelines Figshare: PRISMA-NMA checklist for ‘Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis’. https://doi.org/10.6084/m9.figshare.22567846 . 57 Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). References 1. Webber L, Davies M, Anderson R, et al. : ESHRE Guideline: management of women with premature ovarian insufficiency. Human Reproduction. 2016; 31 (5): 926–937. PubMed Abstract | Publisher Full Text 2. Hvidman HW, Bentzen JG, Thuesen LL, et al. : Infertile women below the age of 40 have similar anti-Müllerian hormone levels and antral follicle count compared with women of the same age with no history of infertility. Human Reproduction. 2016; 31 (5): 1034–1045. PubMed Abstract | Publisher Full Text 3. Giri R, Vincent AJ: Prevalence and Risk Factors of Premature Ovarian Insufficiency/Early Menopause. Seminars in Reproductive Medicine. 2020; 38 (4-05): 237–246. PubMed Abstract | Publisher Full Text 4. Chen ZJ, Tian QJ, Qiao J: Chinese expert consensus on premature ovarian insufficiency. Zhonghua Fu Chan Ke Za Zhi. 2017; 52 (9): 577–581. 5. Panay N, Anderson RA, Nappi RE, et al. : Premature ovarian insufficiency: an International Menopause Society White Paper. Climacteric. 2020; 23 (5): 426–446. PubMed Abstract | Publisher Full Text 6. Sullivan SD, Sarrel PM, Nelson LM: Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertility and Sterility. 2016; 106 (7): 1588–1599. PubMed Abstract | Publisher Full Text | Free Full Text 7. Rovinski D, Ramos RB, Fighera TM, et al. : Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: A systematic review and meta-analysis. Thrombosis Research. 2018; 168 : 83–95. PubMed Abstract | Publisher Full Text 8. Marjoribanks J, Farquhar C, Roberts H, et al. : Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews. 2017; 1 (1): Cd004143. PubMed Abstract | Publisher Full Text 9. Li HF, Shen QH, Chen WJ, et al. : Efficacy of Traditional Chinese Medicine Tonifying Kidney (Bushen) and Activating Blood (Huoxue) Prescription for Premature Ovarian Insufficiency: A Systematic Review and Meta-Analysis. Evidence-Based Complementary and Alternative Medicine. 2020; 2020 : 1789304. 10. Li Y, Xia G, Tan Y, et al. : Acupoint stimulation and Chinese herbal medicines for the treatment of premature ovarian insufficiency: A systematic review and meta-analysis. Complementary Therapies in Clinical Practice. 2020; 41 : 101244. PubMed Abstract | Publisher Full Text 11. Zhang J, Huang X, Liu Y, et al. : A comparison of the effects of Chinese non-pharmaceutical therapies for premature ovarian failure: A PRISMA-compliant systematic review and network meta-analysis. Medicine. 2020; 99 (26): e20958. PubMed Abstract | Publisher Full Text | Free Full Text 12. Higgins JPTTJ, Chandler J, Cumpston M, et al. , editors: Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane; 2022. 13. Zhang L, Li H, Zhang J, et al. : A comparison of the efficacy and safety of complementary and alternative therapies for premature ovarian insufficiency: A protocol for network meta-analysis. Medicine. 2020; 99 (31): e21538. PubMed Abstract | Publisher Full Text | Free Full Text 14. Hutton B, Salanti G, Caldwell DM, et al. : The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Annals of Internal Medicine. 2015; 162 (11): 777–784. PubMed Abstract | Publisher Full Text 15. Sterne JAC, Savović J, Page MJ, et al. : RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ (Clinical research ed). 2019; 366 : l4898. Publisher Full Text 16. Page MJ, McKenzie JE, Bossuyt PM, et al. : The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ (Clinical research ed). 2021; 372 : n71. Publisher Full Text 17. Kou MJ, Ding XF, Chen JX, et al. : Traditional Chinese Medicine Combined with Hormone Therapy to Treat Premature Ovarian Failure: A Meta-analysis of Randomized Controlled Trials. African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM. 2016; 13 (5): 160–169. PubMed Abstract | Publisher Full Text | Free Full Text 18. Jin XF, Yan J, Zhao JY, et al. : Effect of penetrative needling of “Zhibian” (BL54) through “Shuidao” (ST28) on expression of TRAIL and its receptors in rats with premature ovarian insufficiency. Zhen ci yan jiu = Acupuncture Research. 2023; 48 (3): 259–266. PubMed Abstract | Publisher Full Text 19. Tao QF, Wang XY, Feng SJ, et al. : Efficacy of acupuncture for tension-type headache prophylaxis: systematic review and meta-analysis with trial sequential analysis. Journal of Neurology. 2023. PubMed Abstract | Publisher Full Text 20. Liu Y, Fan HY, Hu JQ, et al. : Effectiveness and safety of acupuncture for insulin resistance in women with polycystic ovary syndrome: A systematic review and meta-analysis. Heliyon. 2023; 9 (3): e13991. PubMed Abstract | Publisher Full Text | Free Full Text 21. Dietzel J, Habermann IV, Hörder S, et al. : Acupuncture in Patients with Diabetic Peripheral Neuropathy-Related Complaints: A Randomized Controlled Clinical Trial. Journal of Clinical Medicine. 2023; 12 (6). PubMed Abstract | Publisher Full Text | Free Full Text 22. Jiang D, Li L, Wan S, et al. : Acupuncture and Chinese Herbal Medicine Effects on Assisted Reproductive Technology: Six Cases and Their Clinical Significance. Medical Acupuncture. 2019; 31 (6): 395–406. PubMed Abstract | Publisher Full Text | Free Full Text 23. Xing LW, He Z, Sun YH, et al. : Effects of staged acupuncture on endometrial receptivity and anxiety in patients with recurrent implantation failure of thin endometrium based on “thoroughfare vessel is the sea of blood” theory. Zhongguo zhen jiu = Chinese Acupuncture & Moxibustion. 2023; 43 (3): 289–293. PubMed Abstract | Publisher Full Text 24. Xie Q, Tang Y, Fang J, et al. : Clinical efficacy of herbal medicine combined with acupuncture for the treatment of premature ovarian insufficiency due to Kidney Yin deficiency Syndrome and its effect on hormone levels. Zhejiang Journal of Traditional Chinese Medicine. 2022; 57 (01): 51–52. 25. Peng YL: Clinical Observation on Treatment of Premature Ovarian Insufficiency with Combined Acupuncture and Herbal Medicine. Journal of Practical Traditional Chinese Medicine. 2022; 38 (01): 5–6. 26. Huang YS, Zhuo YY, Huang XX, et al. : Clinical Observation on Treatment of Premature Ovarian Insufficiency by Acupuncture for Regulating Menstruation and Promoting Pregnancy Combined with Moxibustion. China's Naturopathy. 2021; 29 (07): 41–44. 27. Chen JM, Xu LP, Hao MH, et al. ; Clinical Study on Using Qizi Bushen Yuyan Decoction for 50 Cases of Premature Ovarian Insufficiency. Hebei Journal of Traditional Chinese Medicine. 2021; 43 (04): 588-91+637. 28. Yuan F, Guo HL, Xu YH: Integration of Chinese and Western Medicine Treatment for Premature Ovarian Insufficiency due to Kidney Deficiency and Liver Depression Syndrome. Acta Chinese Medicine. 2021; 36 (10): 2233–2238. 29. Chen L, Ji CR: Yuyin decoction combined with estradiol and dydrogesterone tablets in the treatment of premature ovarian insufficiency. Shenzhen Journal of Integrated Traditional Chinese and Western Medicine. 2021; 31 (02): 24–25. 30. Sui J, Dong L: Enhancing Effect of Zhushi Tiaojing Decoction on Ovarian Blood Supply in POI Patients with Kidney Deficiency and Blood Stasis Syndrome. Shanghai Journal of Traditional Chinese Medicine. 2021; 55 (11): 50-3+73. 31. Wang XW, Zhu JH, Gu ZH: Clinical efficacy of Yishen Shugan Decoction in the treatment of premature ovarian insufficiency (kidney deficiency and liver depression syndrome). Inner Mongolia Journal of Traditional Chinese Medicine. 2021; 40 (01): 47–48. 32. Wang YY, Shi XH: Clinical Effect of Bushen Huoxue Prescription combined with acupuncture on patients with premature ovarian insufficiency. China Medicine and Pharmacy. 2021; 11 (09): 5-8+14. 33. Tang HX, Zhou L, Chen XL, et al. : Efficacy and mechanism of Bushen Huoxue decoction combined with femotone in the treatment of premature ovarian insufficiency (kidney deficiency and blood stasis syndrome). Journal of Chinese Medicinal Materials. 2021; 44 (12): 2955–2959. 34. Lin LL: Clinical Analysis of Bushen Shugan Decoction Combined with Acupoint Catgut Embedding in Treatment of Premature Ovarian Insufficiency. Journal of Practical Traditional Chinese Medicine. 2021; 37 (01): 36–37. 35. Zhang H, Li WW, Zhang JT: Effects of Yishen Yangruan Decoction on ovarian reserve, expression of Bcl-2/Bax in ovarian granulosa cells and PI3K/AKT signaling pathway in patients with premature ovarian insufficiency. Guiding Journal of Traditional Chinese Medicine and Pharmacy. 2021; 27 (09): 108-11+16. 36. Hou M, Gao Y, Wang Y, et al. : Clinical effect of acupuncture and moxibustion combined with piercing to the bone in the treatment of premature ovarian insufficiency. Clinical Research and Practice. 2021; 6 (33): 135–137. 37. Wu Q, Liu HP, Li H, et al. : Clinical Observation of Bushenhuoxue Decoction in Treatment of Premature Ovarian Insufficiency of Kidney Deficiency Type. Hubei Journal of Traditional Chinese Medicine. 2021; 43 (01): 24–27. 38. Fu WJ, Han FJ, Xu JY, et al. : Clinical Study on Treatment of POI by Harmonizing Nutrient and Defensive. Information on Traditional Chinese Medicine. 2021; 38 (04): 63–66. 39. Ding AY, Cheng QL: Exploring the clinical effect of integrated traditional Chinese and Western medicine in the treatment of premature ovarian insufficiency. Diet Health. 2021; 1 : 61. 40. Ma QW, Tan Y: Clinical study on sequential therapy of nourishing Yin and tonifying Yang prescription combined with Femoston in the treatment of premature ovarian insufficiency. Guangxi Journal of Traditional Chinese Medicine. 2020; 43 (06): 7–10. 41. Zhao JM, Zhang AH: Clinical effect of Ziyin Shugan decoction combined with Clementine in the treatment of premature ovarian insufficiency. Henan Medical Research. 2020; 29 (14): 2617–2618. 42. Luo C: Clinical observation on 30 cases of premature ovarian insufficiency with liver depression and kidney deficiency type treated by Yijing Tang. Journal of Gansu University of Chinese Medicine. 2020; 37 (02): 61–66. 43. Wang TT: Effectiveness analysis of Zishen Qingxin decoction combined with acupuncture in treating premature ovarian insufficiency. Journal of Oriental Medicated Diet. 2020; 6 : 87. 44. Chi L, Zhang Q: The effects of Zishen Yugui decoction on serum anti-Mullerian hormone, estradiol and follicle stimulating hormone in patients with premature ovarian insufficiency. Tianjin Medical Journal. 2020; 48 (09): 886–890. 45. Liu X, Fan HF, Yang CG: Clinical effect of Bushen Yangxue Tiaojing Decoction on early-onset ovarian dysfunction. Chinese Community Doctors. 2020; 17 (10): 92–104. Publisher Full Text 46. Ma K, Yuan Y, Zhang HX: Clinical efficacy of Bushen Culuan Decoction in treating infertility due to premature ovarian insufficiency. China Journal of Chinese Materia Medica. 2019; 44 (06): 1075–1079. 47. Zhong WP, Ye YQ, Wang PJ, et al. : Curative effect of Bushen Huoxue decoction on premature ovarian insufficiency of type of kidney deficiency and blood stasis. Modern Journal of Integrated Traditional Chinese and Western Medicine. 2019; 28 (23): 2518–2522. 48. Yuan YJ, Wang XY, Lan L: Observation on the Therapeutic Effect of Erxian Decoction on Early-onset Ovarian Insufficiency of Spleen and Kidney Yang Deficiency Type. Systems Medicine. 2019; 4 (18): 130–132. 49. Li J, Zhang Y, Ding ZY: Exploration on the Efficacy and Partial Mechanism of Qingxin Zishen Decoction in Premature Ovarian Insufficiency of Heart-kidney Non-interaction Type Based on the Theory of “Heart-kidney-uterus Axis”. World Chinese Medicine. 2019; 14 (09): 2349–2353. 50. Zhang N, Li GR, Suo SL: 45 Cases of Premature Ovarian Insufficiency of Kidney Yin Deficiency Treated with Acupuncture and Medicine. Traditional Chinese Medicinal Research. 2019; 32 (10): 61–63. 51. Zhou QY, Luo NX, Chen WY, et al. : Clinical Observation on Treatment of Premature Ovarian Insufficiency with Combination of Traditional Chinese and Western Medicine. Chinese and Foreign Medical Research. 2018; 16 (36): 46–47. 52. Li X: 30 Cases of Premature Ovarian Insufficiency Treated by Zi Ni Bushen Tiaochong Decoction Combined with Acupuncture. China’s Naturopathy. 2018; 26 (13): 44–45. 53. Li X: Curative Effect Observation of Modified Erxian Decoction in Treatment of Early-onset Ovarian Insufficiency with Spleen-kidney Yang Deficiency Sydrome. Acta Chinese Medicine. 2018; 33 (07): 1340–1344. 54. Yao L, Liang DY: Influence of Traditional Chinese Medicine Decoction Series on the Treatment of Ovarian Function-related Infertility. Acta Chinese Medicine and Pharmacology. 2007; 02 : 34–36. 55. Cui LL, Kang MX, Peng B: Efficacy Observation of Acupoint Thread Embedding Combined with Yun Zhong Ding Kun Tang for Premature Ovarian Insufficiency. Shanghai Journal of Acupuncture and Moxibustion. 2022; 41 (06): 573–578. 56. Zeng X: Clinical Efficacy of Kuntai Capsules Combined with Estradiol Tablets/Estradiol and Dydrogesterone Tablets in the Treatment of Patients with Premature Ovarian Insufficiency. China Journal of Pharmaceutical Economics. 2021; 16 (10): 97–100. 57. Sin YS, Sng KS, Chen M, et al. : PRISMA checklist for ‘Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis’. [Dataset]. figshare. 2023. Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 27 Apr 2023 ADD YOUR COMMENT Comment Author details Author details 1 Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 16369, China 2 Department of Chinese Medicine, International Medical University, Bukit Jalil, Kuala Lumpur, 57000, Malaysia 3 Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, Shandong, 250014, China Yen Suan Sin Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Writing – Original Draft Preparation, Writing – Review & Editing Min Chen Roles: Formal Analysis, Investigation, Methodology, Validation, Writing – Review & Editing Kim Sia Sng Roles: Data Curation, Investigation, Methodology, Validation, Writing – Review & Editing Jianwei Zhang Roles: Conceptualization, Supervision, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 27 Apr 2023, 12:450 https://doi.org/10.12688/f1000research.132981.1 Copyright © 2023 Sin YS et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Sin YS, Chen M, Sng KS and Zhang J. Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2023, 12 :450 ( https://doi.org/10.12688/f1000research.132981.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 27 Apr 2023 Views 0 Cite How to cite this report: Laguna Benetti-Pinto C. Reviewer Report For: Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2023, 12 :450 ( https://doi.org/10.5256/f1000research.145942.r266528 ) The direct URL for this report is: https://f1000research.com/articles/12-450/v1#referee-response-266528 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 04 Jun 2024 Cristina Laguna Benetti-Pinto , Department of Obstetrics and Gynecology, Universidade Estadual de Campinas, Campinas, State of São Paulo, Brazil Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.145942.r266528 I reviewed the manuscript “ Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis” . The authors aimed to evaluate and compare the clinical efficacy of different modalities of Traditional ... Continue reading READ ALL I reviewed the manuscript “ Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis” . The authors aimed to evaluate and compare the clinical efficacy of different modalities of Traditional Chinese Medicine (TCM) for the treatment of POI and identify the most effective treatment. The authors registered the systematic review and declared to follow the PRISMA-NMA. They used 6 databases (three English databases and three Chinese databases). Only Traditional Chinese Medicine randomized controlled trials were included, with women treated with herbal medicine, acupuncture, moxibustion and catgut embedding therapy alone or in combination with conventional HT. The effectiveness of treatments was to be evaluated according to clinical manifestation, menstrual cycle, FSH and Estradiol levels, and LH and AMH levels. The issue is interesting and there are gaps in the knowledge of effectiveness of complementary IOF treatment. My major concern is on the outcomes of the treatments. It is not clear who were the POI-women investigated. Why analyze the AMH levels in POI due to gonadal dysgenesis or after an oophorectomy, for example? Is mandatory to identify the causes of POI in each study included. Furthermore, the reduction in FSH, LH are not good outcomes to evaluate the best treatment. The global consensus indicates to evaluate clinical aspects as hot flushes, improvement in sexual function or in vaginal dryness, improvement in bone mass. Theses aspects were not showed. Hence, my suggestion is to change the aim and the title of the reviewed to “Identifying the effectiveness of TCM treatment in changing some hormonal aspects related to POI” I have some other concerns that are listed below: 1.Title – see comments above 2.Abstract – see comments above and change 3.Introduction - -Page 3, first paragraph: the authors included a POI prevalence of about 10%. This rate is not in accordance with the literature or even with the reference cited [3]. Please review and correct (in reference number 3, the prevalence of POI is 1-3%). The authors also cited the use of AMH levels to measure ovarian reserve. AMH measurement is only indicated in specific cases of POI, if the final diagnosis is not completely certain, especially when FSH levels are not stable and above 25 U/L. I suggest a review of these concepts. Page 3: “Hence, patients often seek out complementary medicine to improve their ovarian functions and increase chances of conception” – what is the idea of ​​this paragraph? HT is the first and best treatment whenever the woman has no absolute contraindication, which is not frequent. In these cases, complementary treatment or alternative treatment generally aims to minimize the effects of hypoestrogenism. In most POI etiologies, it is unfortunately not possible to improve ovarian function. Please, clarify/rewrite the paragraph. 4.Methodology and Results Page 6, PRISMA flowchart – please, in the studies included, mention in the figure which database they are from. The authors mentioned that the diagnosis criteria were according to ESRHE guideline OR according Chinese expert consensus on POI. Please, include in the manuscript these criteria (the last article was published in Chinese. These criteria are important to comprehension of systematic review. Discussion: Page 19. “Our findings revealed the comparative efficacy of six treatment modalities: HRT combined with herbal medicine and acupuncture, HRT combined with herbal medicine, herbal medicine combined with acupuncture, herbal medicine combined with catgut-embedding therapy, acupuncture combined with moxibustion and herbal medicine alone.” - see “major concern”. And what kind of HT? Page 19: “However, comparing its clinical manifestations, POI can be categorized as “amenorrhoea”, “oligomenorrhoea” and “infertility” based on TCM perspective. The pathogenesis is mainly related to malnourishment of the thoroughfare and conception vessels, as well as the uterus, which might be due to congenital insufficiency, physical and mental overwork, or sexual overstrain. TCM treats a disease based on syndrome differentiation.” Please, make clear these concepts. I am not able to understand, according to global consensus of POI. Page 19. “Therefore, herbal medicine may be considered as an intervention when HRT alone, the standard procedure recommended by recognized guidelines worldwide,1,4,5 cannot effectively cure POI” – This conclusion is not supported bye the results of this review or by the global consensus. The idea is not clear to me. Please, reviewed. Although the systematic review was methodologically well done, there are conceptual errors, and conclusions aren’t in line with the recommendations of global consensus. If there is by the authors an extensive revision of the study, with changes in the concepts, aims and conclusions, the manuscript can be submitted to a new analysis. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? No Is the statistical analysis and its interpretation appropriate? Partly Are the conclusions drawn adequately supported by the results presented in the review? No If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: premature ovarian insufficiency I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Laguna Benetti-Pinto C. Reviewer Report For: Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2023, 12 :450 ( https://doi.org/10.5256/f1000research.145942.r266528 ) The direct URL for this report is: https://f1000research.com/articles/12-450/v1#referee-response-266528 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Aslam MS. Reviewer Report For: Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2023, 12 :450 ( https://doi.org/10.5256/f1000research.145942.r196644 ) The direct URL for this report is: https://f1000research.com/articles/12-450/v1#referee-response-196644 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 01 Sep 2023 Muhammad Shahzad Aslam , School of Traditional Chinese Medicine, Xiamen University Malaysia, Sepang, Malaysia Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.145942.r196644 According to authors: Acupuncture has been widely applied on POI treatment particularly in China. 10 , 11 , 18 It has been demonstrated that acupuncture is safe and effective. 19 – 21 I suggest to broaden the discussion in context to use of Acupuncture in Malaysia, US. We ... Continue reading READ ALL According to authors: Acupuncture has been widely applied on POI treatment particularly in China. 10 , 11 , 18 It has been demonstrated that acupuncture is safe and effective. 19 – 21 I suggest to broaden the discussion in context to use of Acupuncture in Malaysia, US. We all know its effectiveness on POI treatment in China. Please read literature and include more reference from different geography. If no study in other geography found then given give rational. Provide rational to use SUCRA Rank for each outcome measurement in NMA..I suggest to compare it with Bayesian Model and Averaging, Rank-Heat Plot. The study conclusion must present with future direction. Please include more paragraph. Is there any comparison given with best TCM TM for POI with pharmacotherapy? The discussion must contain a couple of paragraph to provide rational and treatment comparison. Please provide in-depth study limitation in separate paragraph. Please provide Prisma Checklist as supplementary file. Please suggest to include one heading how to improve the quality reporting of POI. Most of TCM treatment has similar issues. It is mandatory to provide solution. Please elaborate your discussion and specify to POI treatment. Acceptability of TCM treatment is a big issues. I hope you understand my point and add some heading inside discussion. If possible i recommend to include proposed Hypothetical mechanism of TCM TM in POI disease. Are the rationale for, and objectives of, the Systematic Review clearly stated? Partly Are sufficient details of the methods and analysis provided to allow replication by others? Partly Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? No Competing Interests: No competing interests were disclosed. Reviewer Expertise: Phytochemistry, Complementary and alternative medicine I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Aslam MS. Reviewer Report For: Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2023, 12 :450 ( https://doi.org/10.5256/f1000research.145942.r196644 ) The direct URL for this report is: https://f1000research.com/articles/12-450/v1#referee-response-196644 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 27 Apr 2023 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 27 Apr 23 read read Muhammad Shahzad Aslam , Xiamen University Malaysia, Sepang, Malaysia Cristina Laguna Benetti-Pinto , Universidade Estadual de Campinas, Campinas, Brazil Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Laguna Benetti-Pinto C. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 04 Jun 2024 | for Version 1 Cristina Laguna Benetti-Pinto , Department of Obstetrics and Gynecology, Universidade Estadual de Campinas, Campinas, State of São Paulo, Brazil 0 Views copyright © 2024 Laguna Benetti-Pinto C. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I reviewed the manuscript “ Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis” . The authors aimed to evaluate and compare the clinical efficacy of different modalities of Traditional Chinese Medicine (TCM) for the treatment of POI and identify the most effective treatment. The authors registered the systematic review and declared to follow the PRISMA-NMA. They used 6 databases (three English databases and three Chinese databases). Only Traditional Chinese Medicine randomized controlled trials were included, with women treated with herbal medicine, acupuncture, moxibustion and catgut embedding therapy alone or in combination with conventional HT. The effectiveness of treatments was to be evaluated according to clinical manifestation, menstrual cycle, FSH and Estradiol levels, and LH and AMH levels. The issue is interesting and there are gaps in the knowledge of effectiveness of complementary IOF treatment. My major concern is on the outcomes of the treatments. It is not clear who were the POI-women investigated. Why analyze the AMH levels in POI due to gonadal dysgenesis or after an oophorectomy, for example? Is mandatory to identify the causes of POI in each study included. Furthermore, the reduction in FSH, LH are not good outcomes to evaluate the best treatment. The global consensus indicates to evaluate clinical aspects as hot flushes, improvement in sexual function or in vaginal dryness, improvement in bone mass. Theses aspects were not showed. Hence, my suggestion is to change the aim and the title of the reviewed to “Identifying the effectiveness of TCM treatment in changing some hormonal aspects related to POI” I have some other concerns that are listed below: 1.Title – see comments above 2.Abstract – see comments above and change 3.Introduction - -Page 3, first paragraph: the authors included a POI prevalence of about 10%. This rate is not in accordance with the literature or even with the reference cited [3]. Please review and correct (in reference number 3, the prevalence of POI is 1-3%). The authors also cited the use of AMH levels to measure ovarian reserve. AMH measurement is only indicated in specific cases of POI, if the final diagnosis is not completely certain, especially when FSH levels are not stable and above 25 U/L. I suggest a review of these concepts. Page 3: “Hence, patients often seek out complementary medicine to improve their ovarian functions and increase chances of conception” – what is the idea of ​​this paragraph? HT is the first and best treatment whenever the woman has no absolute contraindication, which is not frequent. In these cases, complementary treatment or alternative treatment generally aims to minimize the effects of hypoestrogenism. In most POI etiologies, it is unfortunately not possible to improve ovarian function. Please, clarify/rewrite the paragraph. 4.Methodology and Results Page 6, PRISMA flowchart – please, in the studies included, mention in the figure which database they are from. The authors mentioned that the diagnosis criteria were according to ESRHE guideline OR according Chinese expert consensus on POI. Please, include in the manuscript these criteria (the last article was published in Chinese. These criteria are important to comprehension of systematic review. Discussion: Page 19. “Our findings revealed the comparative efficacy of six treatment modalities: HRT combined with herbal medicine and acupuncture, HRT combined with herbal medicine, herbal medicine combined with acupuncture, herbal medicine combined with catgut-embedding therapy, acupuncture combined with moxibustion and herbal medicine alone.” - see “major concern”. And what kind of HT? Page 19: “However, comparing its clinical manifestations, POI can be categorized as “amenorrhoea”, “oligomenorrhoea” and “infertility” based on TCM perspective. The pathogenesis is mainly related to malnourishment of the thoroughfare and conception vessels, as well as the uterus, which might be due to congenital insufficiency, physical and mental overwork, or sexual overstrain. TCM treats a disease based on syndrome differentiation.” Please, make clear these concepts. I am not able to understand, according to global consensus of POI. Page 19. “Therefore, herbal medicine may be considered as an intervention when HRT alone, the standard procedure recommended by recognized guidelines worldwide,1,4,5 cannot effectively cure POI” – This conclusion is not supported bye the results of this review or by the global consensus. The idea is not clear to me. Please, reviewed. Although the systematic review was methodologically well done, there are conceptual errors, and conclusions aren’t in line with the recommendations of global consensus. If there is by the authors an extensive revision of the study, with changes in the concepts, aims and conclusions, the manuscript can be submitted to a new analysis. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? No Is the statistical analysis and its interpretation appropriate? Partly Are the conclusions drawn adequately supported by the results presented in the review? No If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Yes Competing Interests No competing interests were disclosed. Reviewer Expertise premature ovarian insufficiency I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Laguna Benetti-Pinto C. Peer Review Report For: Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2023, 12 :450 ( https://doi.org/10.5256/f1000research.145942.r266528) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-450/v1#referee-response-266528 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2023 Aslam M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 01 Sep 2023 | for Version 1 Muhammad Shahzad Aslam , School of Traditional Chinese Medicine, Xiamen University Malaysia, Sepang, Malaysia 0 Views copyright © 2023 Aslam M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions According to authors: Acupuncture has been widely applied on POI treatment particularly in China. 10 , 11 , 18 It has been demonstrated that acupuncture is safe and effective. 19 – 21 I suggest to broaden the discussion in context to use of Acupuncture in Malaysia, US. We all know its effectiveness on POI treatment in China. Please read literature and include more reference from different geography. If no study in other geography found then given give rational. Provide rational to use SUCRA Rank for each outcome measurement in NMA..I suggest to compare it with Bayesian Model and Averaging, Rank-Heat Plot. The study conclusion must present with future direction. Please include more paragraph. Is there any comparison given with best TCM TM for POI with pharmacotherapy? The discussion must contain a couple of paragraph to provide rational and treatment comparison. Please provide in-depth study limitation in separate paragraph. Please provide Prisma Checklist as supplementary file. Please suggest to include one heading how to improve the quality reporting of POI. Most of TCM treatment has similar issues. It is mandatory to provide solution. Please elaborate your discussion and specify to POI treatment. Acceptability of TCM treatment is a big issues. I hope you understand my point and add some heading inside discussion. If possible i recommend to include proposed Hypothetical mechanism of TCM TM in POI disease. Are the rationale for, and objectives of, the Systematic Review clearly stated? Partly Are sufficient details of the methods and analysis provided to allow replication by others? Partly Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? No Competing Interests No competing interests were disclosed. Reviewer Expertise Phytochemistry, Complementary and alternative medicine I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Aslam MS. Peer Review Report For: Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2023, 12 :450 ( https://doi.org/10.5256/f1000research.145942.r196644) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-450/v1#referee-response-196644 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Stay Updated Sign up for content alerts and receive a weekly or monthly email with all newly published articles Register with F1000Research Already registered? Sign in Not now, thanks close PLEASE NOTE If you are an AUTHOR of this article, please check that you signed in with the account associated with this article otherwise we cannot automatically identify your role as an author and your comment will be labelled as a “User Comment”. If you are a REVIEWER of this article, please check that you have signed in with the account associated with this article and then go to your account to submit your report, please do not post your review here. If you do not have access to your original account, please contact us . All commenters must hold a formal affiliation as per our Policies . The information that you give us will be displayed next to your comment. User comments must be in English, comprehensible and relevant to the article under discussion. We reserve the right to remove any comments that we consider to be inappropriate, offensive or otherwise in breach of the User Comment Terms and Conditions . Commenters must not use a comment for personal attacks. When criticisms of the article are based on unpublished data, the data should be made available. I accept the User Comment Terms and Conditions Please confirm that you accept the User Comment Terms and Conditions. Affiliation ✕ refresh Please enter your institution. Note: To add your institution or organisation, start typing the name and then select the correct name from the list. Where applicable, the name will appear in both the original language and in English. Do not paste in the name. If the name does not appear in the drop-down list, we will display the information you have entered. ✕ refresh Country/Region * USA UK Canada China France Germany Afghanistan Aland Islands Albania Algeria American Samoa Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory British Virgin Islands Brunei Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Cook Islands Costa Rica Cote d'Ivoire Croatia Cuba Cyprus Czech Republic Democratic Republic of the Congo Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands Faroe Islands Federated States of Micronesia Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and Mcdonald Islands Holy See (Vatican City State) Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Kosovo (Serbia and Montenegro) Kuwait Kyrgyzstan Lao People's Democratic Republic Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Macao Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Minor Outlying Islands of the United States Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands Antilles New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island North Korea North Macedonia Northern Mariana Islands Norway Oman Pakistan Palau Palestinian Territory Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Puerto Rico Qatar Reunion Romania Russian Federation Rwanda Saint Helena Saint Kitts and Nevis Saint Lucia Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Is South Korea South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syria Taiwan Tajikistan Tanzania Thailand The Gambia The Netherlands Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu UK USA Uganda Ukraine United Arab Emirates United States Virgin Islands Uruguay Uzbekistan Vanuatu Venezuela Vietnam Wallis and Futuna West Bank and Gaza Strip Western Sahara Yemen Zambia Zimbabwe Please select your country/region. You must enter a comment. Competing Interests Please disclose any competing interests that might be construed to influence your judgment of the article's or peer review report's validity or importance. Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Please state your competing interests The comment has been saved. An error has occurred. Please try again. Cancel Post var lTitle = "Identifying the most effective Traditional...".replace("'", ''); var linkedInUrl = "http://www.linkedin.com/shareArticle?url=https://f1000research.com/articles/12-450/v1" + "&title=" + encodeURIComponent(lTitle) + "&summary=" + encodeURIComponent('Read the article by '); var deliciousUrl = "https://del.icio.us/post?url=https://f1000research.com/articles/12-450/v1&title=" + encodeURIComponent(lTitle); var redditUrl = "http://reddit.com/submit?url=https://f1000research.com/articles/12-450/v1" + "&title=" + encodeURIComponent(lTitle); linkedInUrl += encodeURIComponent('Sin YS et al.'); var offsetTop = /chrome/i.test( navigator.userAgent ) ? 4 : -10; var addthis_config = { ui_offset_top: offsetTop, services_compact : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_expanded : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_custom : [ { name: "LinkedIn", url: linkedInUrl, icon:"/img/icon/at_linkedin.svg" }, { name: "Mendeley", url: "http://www.mendeley.com/import/?url=https://f1000research.com/articles/12-450/v1/mendeley", icon:"/img/icon/at_mendeley.svg" }, { name: "Reddit", url: redditUrl, icon:"/img/icon/at_reddit.svg" }, ] }; var addthis_share = { url: "https://f1000research.com/articles/12-450", templates : { twitter : "Identifying the most effective Traditional Chinese Medicine treatment.... Sin YS et al., published by " + "@F1000Research" + ", https://f1000research.com/articles/12-450/v1" } }; if (typeof(addthis) != "undefined"){ addthis.addEventListener('addthis.ready', checkCount); addthis.addEventListener('addthis.menu.share', checkCount); } $(".f1r-shares-twitter").attr("href", "https://twitter.com/intent/tweet?text=" + addthis_share.templates.twitter); $(".f1r-shares-facebook").attr("href", "https://www.facebook.com/sharer/sharer.php?u=" + addthis_share.url); $(".f1r-shares-linkedin").attr("href", addthis_config.services_custom[0].url); $(".f1r-shares-reddit").attr("href", addthis_config.services_custom[2].url); $(".f1r-shares-mendelay").attr("href", addthis_config.services_custom[1].url); function checkCount(){ setTimeout(function(){ $(".addthis_button_expanded").each(function(){ var count = $(this).text(); if (count !== "" && count != "0") $(this).removeClass("is-hidden"); else $(this).addClass("is-hidden"); }); }, 1000); } close How to cite this report {{reportCitation}} Cancel Copy Citation Details $(function(){R.ui.buttonDropdowns('.dropdown-for-downloads');}); $(function(){R.ui.toolbarDropdowns('.toolbar-dropdown-for-downloads');}); $.get("/articles/acj/132981/145942") new F1000.Clipboard(); new F1000.ThesaurusTermsDisplay("articles", "article", "145942"); $(document).ready(function() { $( "#frame1" ).on('load', function() { var mydiv = $(this).contents().find("div"); var h = mydiv.height(); console.log(h) }); var tooltipLivingFigure = jQuery(".interactive-living-figure-label .icon-more-info"), titleLivingFigure = tooltipLivingFigure.attr("title"); tooltipLivingFigure.simpletip({ fixed: true, position: ["-115", "30"], baseClass: 'small-tooltip', content:titleLivingFigure + " " }); tooltipLivingFigure.removeAttr("title"); $("body").on("click", ".cite-living-figure", function(e) { e.preventDefault(); var ref = $(this).attr("data-ref"); $(this).closest(".living-figure-list-container").find("#" + ref).fadeIn(200); }); $("body").on("click", ".close-cite-living-figure", function(e) { e.preventDefault(); $(this).closest(".popup-window-wrapper").fadeOut(200); }); $(document).on("mouseup", function(e) { var metricsContainer = $(".article-metrics-popover-wrapper"); if (!metricsContainer.is(e.target) && metricsContainer.has(e.target).length === 0) { $(".article-metrics-close-button").click(); } }); var articleId = $('#articleId').val(); if($("#main-article-count-box").attachArticleMetrics) { $("#main-article-count-box").attachArticleMetrics(articleId, { articleMetricsView: true }); } }); var figshareWidget = $(".new_figshare_widget"); if (figshareWidget.length > 0) { window.figshare.load("f1000", function(Widget) { // Select a tag/tags defined in your page. In this tag we will place the widget. _.map(figshareWidget, function(el){ var widget = new Widget({ articleId: $(el).attr("figshare_articleId") //height:300 // this is the height of the viewer part. [Default: 550] }); widget.initialize(); // initialize the widget widget.mount(el); // mount it in a tag that's on your page // this will save the widget on the global scope for later use from // your JS scripts. This line is optional. //window.widget = widget; }); }); } close Error Close Add Reset F1000.MICROSERVICES.AFFILIATION = ''; $(document).ready(function () { $('.js-affiliations-form').each((index, form) => { new AffiliationForm({ formId: form.id, institutionErrorSelector: '.comment-enter-institution', departmentErrorSelector: '.comment-enter-department', placeSelector: '.js-add-comment-place', stateSelector: '.js-add-comment-state', zipCodeSelector: '.js-add-comment-zipcode', countrySelector: '.js-add-comment-country', countryErrorSelector: '.comment-enter-country', }); }); }); $(document).ready(function () { var reportIds = { "279424": 0, "252679": 0, "252682": 0, "252686": 0, "252690": 0, "266524": 0, "266525": 0, "192920": 0, "266526": 0, "192921": 0, "252696": 0, "266527": 0, "252703": 0, "178205": 0, "266523": 0, "266532": 0, "266528": 8, "266529": 0, "196645": 0, "252709": 0, "266530": 0, "266531": 0, "196644": 20, "274223": 0, "252720": 0, "260663": 0, "180150": 0, "252727": 0, "180151": 0, "180149": 0, "274227": 0, "260667": 0, "274236": 0, "260666": 0, "274237": 0, "252730": 0, "260665": 0, "180152": 0, "260664": 0, "209215": 0, "260670": 0, "260668": 0, "274235": 0, "260675": 0, "201795": 0, "201794": 0, "260673": 0, "260672": 0, "209216": 0, "173770": 0, "173771": 0, "173769": 0, "173772": 0, "171218": 0, "171219": 0, "171222": 0, "171220": 0, "171221": 0, "175839": 0, "248029": 0, "175840": 0, "248033": 0, "248038": 0, "248036": 0, "248043": 0, "248041": 0, "224751": 0, "248047": 0, "248049": 0, "224752": 0, "248055": 0, "248052": 0, "279423": 0, }; $(".referee-response-container,.js-referee-report").each(function(index, el) { var reportId = $(el).attr("data-reportid"), reportCount = reportIds[reportId] || 0; $(el).find(".comments-count-container,.js-referee-report-views").html(reportCount); }); var uuidInput = $("#article_uuid"), oldUUId = uuidInput.val(), newUUId = "4f04fc69-85c5-4a6d-a6b1-832e31cae415"; uuidInput.val(newUUId); $("a[href*='article_uuid=']").each(function(index, el) { var newHref = $(el).attr("href").replace(oldUUId, newUUId); $(el).attr("href", newHref); }); }); An innovative open access publishing platform offering rapid publication and open peer review, whilst supporting data deposition and sharing. Browse Gateways Collections How it Works Contact For Developers Cookie Notice Privacy Notice RSS Submit Your Research Follow us © 2012-2026 F1000 Research Ltd. ISSN 2046-1402 | Legal | Partner of Research4Life • CrossRef • ORCID • FAIRSharing R.templateTests.simpleTemplate = R.template(' $text $text $text $text $text '); R.templateTests.runTests(); var F1000platform = new F1000.Platform({ name: "f1000research", displayName: "F1000Research", hostName: "f1000research.com", id: "1", editorialEmail: "[email protected]", infoEmail: "[email protected]", usePmcStats: true }); $(function(){R.ui.dropdowns('.dropdown-for-authors, .dropdown-for-about, .dropdown-for-myresearch');}); // $(function(){R.ui.dropdowns('.dropdown-for-referees');}); $(document).ready(function () { if ($(".cookie-warning").is(":visible")) { $(".sticky").css("margin-bottom", "35px"); $(".devices").addClass("devices-and-cookie-warning"); } $(".cookie-warning .close-button").click(function (e) { $(".devices").removeClass("devices-and-cookie-warning"); $(".sticky").css("margin-bottom", "0"); }); $("#tweeter-feed .tweet-message").each(function (i, message) { var self = $(message); self.html(linkify(self.html())); }); $(".partner").on("mouseenter mouseleave", function() { $(this).find(".gray-scale, .colour").toggleClass("is-hidden"); }); }); Sign In Remember me Forgotten your password? Sign In Cancel Email or password not correct. Please try again Please wait... $(function(){ // Note: All the setup needs to run against a name attribute and *not* the id due the clonish // nature of facebox... $("a[id=googleSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("GOOGLE"); $("form[id=oAuthForm]").submit(); }); $("a[id=facebookSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("FACEBOOK"); $("form[id=oAuthForm]").submit(); }); $("a[id=orcidSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("ORCID"); $("form[id=oAuthForm]").submit(); }); }); If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password. The email address should be the one you originally registered with F1000. Email address not valid, please try again You registered with F1000 via Google, so we cannot reset your password. To sign in, please click here . If you still need help with your Google account password, please click here . You registered with F1000 via Facebook, so we cannot reset your password. To sign in, please click here . If you still need help with your Facebook account password, please click here . Code not correct, please try again Reset password Cancel Email us for further assistance. Server error, please try again. If your email address is registered with us, we will email you instructions to reset your password. If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance. Please wait... Register $(document).ready(function () { signIn.createSignInAsRow($("#sign-in-form-gfb-popup")); $(".target-field").each(function () { var uris = $(this).val().split("/"); if (uris.pop() === "login") { $(this).val(uris.toString().replace(",","/")); } }); });