{"paper_id":"9a140500-2c20-4099-a7c4-bbc9dd7fa4e7","body_text":"Submit Manuscript | http://medcraveonline.com\nIntroduction\nInfertility is defined as an absence of successful pregnancy in a \ncouple where the woman is 35 years and younger, with at least one \nyear of regular intercourses without using birth control methods. \nFertility decreases with age. 1 Estimated infertility from 782 couples \nrecruited from seven European centres is 8% for women aged 19-26 \nyears, 13-14% for women aged 27-34 years, and 18% for women aged \n35-39 years.2 women aged 15-44 in the USA with impaired fertility \nis 12.3%. 3 Common reasons causing female infertility are tubal \nblockage, pelvic inflammatory disease caused by infections such as \ntuberculosis, uterine problems, previous tubal ligation; endometriosis, \nand advanced maternal age. 4 Up to 20% of infertile couples have \nunexplained infertility. In these cases, abnormalities are likely to \nbe present but not detected by current methods, or only functional \ndisorders are apparent.5\nMedical treatment of infertility generally involves the use of \nfertility medication[follicle-stimulating hormone (FSH), human \nchorionic gonadotropin (hCG), gonadotropin-releasing hormone \n(GnRH) analogues], ovarian stimulating medication [clomiphene \ncitrate, human menopausal gonadotropin (hMG), Letrozole).6 surgery \n(tuboplasty, salpingectomy, oophorectomy, unilateral or bilateral \nsalpingo-oophorectomy (USO).7,8 or assisted reproductive technology \n(ART) techniques such as in vitro fertilization (IVF) and related \ntechniques (ICSI, ZIFT, GIFT).9\nThese therapies can treat some causes of infertility but results are \nnot always satisfactory. Although the overall live birth rate per embryo \ntransfer has increased from 19.2% in 2002 to 23.3% in 2013 (21.9-\n24.3% for fresh embryo transfers and 14.6-23.3% for frozen/thaw \nembryo transfers).9,10 the result still falls short of the expectations of \nthe infertile woman/couple. Furthermore side effects from hormonal \ntreatment are not without risk, such as overstimulated ovaries. 11 or \npsychiatric disorders.12\nDue to the lack of a perfectly satisfactory outcome from standard \nmedical treatment, patients are looking to alternative therapies to \nimprove their results. Acupuncture has been proven by many different \nstudies from both laboratory and clinic to play an important role in \nsupporting infertility treatment. 13-15 Chinese Herbal Medicine is an \nintegral part of Traditional Chinese Medicine, in which acupuncture, \ndiet, exercise (Taiji)and Qigong are involved together as a whole \nsystem of health maintenance. Do they play an important role in \nsupporting infertility treatment? As a traditional medical system, how \ncan this system of TCM be used to give the best result or infertility \ntreatment? In this chapter we perform a thorough review of papers.\nKey words “Chinese Herbal Medicine, or TCM, and Infertility” were \nused in the Pubmed, Cochrane, Medline, Google Scholar, CINAHL \nand Wanfang databases to search for papers published between 2001-\n2016.The resultant papers were evaluated closely and summarised \nbelow. In general most of research on the mechanism of infertility \ntreatment using CHM or TCM have come from research teams in \nChina, as well as other Asian countries such as Japan. 17,18 Korea. 19 \nand Taiwan.20 However increasingly more papers are being published \nfrom Western countries such as Australia, the USA, and Europe..  \nBelow is a summary of the findings from literature review:\nPre-clinic and laboratory research:\nThere are many studies which aim to elucidate the mechanism \nof Chinese Herbal Medicine in treating infertility in rat models of \ncommon diseases associated with infertility.\nTo promote endometrial receptivity in the uterus : To conceive \neither naturally or using an assisted pregnancy technique, a receptive \nuterine state is required. Poor endometrial receptivity is the commonest \nreason for infertility and prevents embryo implantation into the uterus. \nCHM has been found to promote a receptive uterine state.\nIn Y Nan’s study using a mouse model,163 female pregnant \nkunming mice were randomly divided into six groups, comprising \nthe A control group; B ovulation stimulation (OS) group; C \nOS+TCM (Chinese herbal medicine Pregnancy-supporting Recipe \n– the Zhuyun Recipe, Table 1) group; D embryo implantation \nObstet Gynecol Int J. 2017;8(1):380‒388. 380\n©2017 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which \npermits unrestrited use, distribution, and build upon your work non-commercially.\nEffect of chinese herbal medicine on female \ninfertility\nVolume 8 Issue 1 - 2017\nDan Jiang,1 Lily Li2\n1Hallam Institute of TCM, UK\n2St Marys Hospital Paddington, UK\nCorrespondence: Ms Dan Jiang, Fellow of BAcC, Fellow of \nATCM, TCM Consultant (be awarded by WFCMS), Principal of \nHallam Institute of TCM UK, Vice Principal of Asante Academy \nof Chinese Medicine UK, Visiting Professor of Beijing University \nof Chinese Medicine in China. Email \nReceived: August 28, 2017 | Published: September 27, 2017\nAbstract\nInfertility is the inability of a sexually active, non-contracepting couple to achieve pregnancy \nin one year. In recent years, more couples are looking to alternative and complementary \nmedicine (CAM) to achieve a satisfactory result, although conventional treatment possesses \nmany effective therapies to treat infertility. Chinese Herbal Medicine (CHM) can be a very \neffective treatment. Through combining multiple therapies from within this traditional \nmedical system, such as CHM and acupuncture together, CHM, otherwise known as TCM, \ncan enhance the natural pregnancy rate two-fold, which is remarkably higher than through \nroutine hormonal treatment. Evidence has also shown that CHM can increase the success \nrate of Assistant Reproductive Techniques (ART) from 33% to 60%. Authors here have \nreviewed CHM research papers from China, Asia, Europe and America which explain how \nto treat infertility using CHM based on clinical experience, how CHM supports ART, and \nalso pre-clinical research which seeks to prove CHM’s effectiveness, and demonstrate its \nmechanism of action from laboratory and animal tests. The key techniques of CHM are \neither using a tried-and-tested formula composed of a mixture of several herbs according \nto classical theory or clinical experience of a famous doctor, or by using a combination of \nmultiple traditional therapies together. Some researchers advocate integrating CHM with \nsurgery to encourage post-operative healing and promote early patient recovery.\nKeywords: Infertility; Chinese Herbal Medicine; TCM\nObstetrics & Gynecology International Journal\nResearch Article\n Open Access\n\n\nEffect of chinese herbal medicine on female infertility\n381\nCopyright:\n©2017 Jiang et al.\nCitation: Jiang D, Li L. Effect of chinese herbal medicine on female infertility. Obstet Gynecol Int J. 2017;8(1):380‒388. DOI: 10.15406/ogij.2017.08.00274\ndysfunction (EID) group; E, EID+TCM group; F TCM-only group. \nUterine samples were collected at gestation day four and detected \nwith immunohistochemistry and Real Time-PCR analyses. Uterine \nhorns were excised to determine the number of pregnant mice and \nimplantation sites on day eight post-coitus.\nThe study found that OS group and EID group showed a significant \ndecrease in pregnancy rate and the expression of both endometrial \nleukaemia inhibitory factor (LIF) and integrin β3 subunit during \nthe implantation window. The OS+TCM and EID+TCM groups \nshowed a higher pregnant rate and endometrial LIF and integrin β3 \nsubunit expression compared to the OS and EID groups. The number \nof implanted embryos in EID group was lower than in the control \ngroup, but higher in the EID+TCM group than in the EID group. \nTheir research indicates that TCM appears to reverse the expression \nof endometrial LIF and integrin β3 subunit, improves the uterine \nreceptivity in mice, and increases pregnancy rate and embryonic \nimplantation.21\nX Gong’s team showed that Leukemia-inhibitory factor (LIF) and \nAngiopoietin-2 (Ang-2) are important factors in fertility. Bu Shen \nHuoXue Decoction (BSHXD, an established CHM recipe, Table 1) \nwas investigated for its effect on the number of implantation sites \nand live births in rats. Uteri were collected on day (D) 3, 4 and 5 of \npregnancy, and LIF and Ang-2 protein and mRNA expression were \ndetected using Western blot analysis and quantitative polymerase chain \nreaction. On pregnancy D10, the average number of implantation sites \nwas observed, and the number of live births from each group was \nrecorded. The study found that BSHXD treatment markedly increased \nthe number of live births by restoring endometrial LIF expression and \nthe implantation capacity in the rat model. In addition, no association \nwas identified between LIF and Ang-2 expression. The author s \nconcluded that BSHXD may be useful in female reproduction.22\nTo stimulate ovulated inhibition and to treat ovary failure, and \nto raise hormonal levels: Premature ovarian failure and insufficient \nstorage function of the ovaries are both common reasons for infertility. \nThey can be a result of a variety of hormonal disorders. Established \nrecipes of CHM have been found to effectively stimulate ovaries and \nraise low hormone level. \nS Luo’s research team used rat models where ovulation was \ninhibited (by hydroxyl urea), which matched Shen deficiency and \ndampness-accumulation patterns in TCM. They showed that Luo’s \nestablished recipe (Table 1) increased ovulation, levels of FSH, LH \nand oestrogen, and promoted pregnancy rate when compared to the \ncontrol group.23\nX Teng’s team gave 60 female rats Tripterygium wilfordii tablets \norally to establish a rat model of premature ovarian failure. The rats \nwere randomly divided into a control group (n=10), and model group \n(n=50). The latter group were given Yulin Formula which is a classical \nestablished CHM recipe for treating Shen deficiency and blood stasis \n(Table 1). The test group was also sub-divided into groups of low, \nmiddle, and high dose Yulin formula. Their results showed that Yulin \nformula increased ovarian wet weight in rats with premature ovarian \nfailure and increased the ovarian index. The study also showed that \nYulin formula reduced FSH and LH levels, and raised oestrogen \nlevels, They found also that Yulin formula promoted follicle growth \nand repair, thus improving ovarian function.24\nTo relax the uterus and to prevent spontaneous abortion: Luo’s \nteam designedrat models of abortion using hydroxyurea and \nmifepristone to mimic Kidney deficiency and Spleen deficiency \nrespectively for observing the effect of ZY3 (CHM recipe for \nPregnancy-support:Zhuyun No3, an establised formula for preventing \nmiscarriage, Table 1) on Progesterone (P) and Estradiol (E2) and their \nreceptors (PR and ER). They found that ZY3 could significant increase \npositive rates of PR in decidua models of two types: its water abstract \nand drug serum can decrease the potency of contractility of the uterus \nin vivo, and isolated uterus smooth muscle in vitro respectively. They \nconcluded that the major mechanism of ZY3 in reinforcing Kidney \nand strengthening Spleen in protecting pregnancy is to elevate target \ncell PR and relax uterine smooth muscle.25.26\nTo comprehensive observation to embryo embedding condition \nof uterus for increase a natural pregnancy and IVF’s successful \nrates which is supported by CHM: H Du et al. [27] studied the effect \nof recipes for reinforcing Kidney and dredging Liver on strengthening \nendometrial receptivity to improve pregnancy rates. They found that \ntwo-thirds of pregnancy failure was caused by poor uterine receptivity. \nThey designed a mouse model with recurrent failure of IVF-ET. After \ngiving injection of hCG to the test and control groups of mice, they \nobserved levels of E2, LH, and progesterone, the thickening of the \nendometrium, and expression of angiogenic proteins at the endometrial \nsurface. They found that the Bushenzhuyun Recipe (Table 1) \nincreased hormone levels and thicked the endometrium. It also down-\nregulated the expression of ER, PR, and up-regulated expression of \nVEGF, VEGFR-2, eNOS, PCNA, MMP-9, and CyclinD1, which are \ninvolved in promoting cellular growth, increasing vasculogenesis, and \nincreasing vascular permeability. They concluded that CHM could \ncorrect uterus receptivity.27\nChinese Herbal Medicine can increase pregnancy rate in clinical \nresearch:  K Ried’s team performed a systematic review in 2011 \nlooking at Chinese herbal medicine in infertility. They identified eight \nrandomised controlled trials (RCTs), 13 cohort studies, three case \nseries, and six case studies involving 1851 women with infertility. \nMeta-analysis of the RCTs suggested a 3.5 greater likelihood of \nachieving pregnancy with CHM therapy over a four-month period \ncompared with Western drug (clomiphene) therapy alone. They \nsuggested that management of female infertility with Chinese Herbal \nMedicine could improve pregnancy rates two-fold .28 They also found \nthat assessment of the quality of the menstrual cycle, integral to \nTCM diagnosis, appears to be fundamental to successful treatment of \nfemale infertility.29 \nThe same group published an updated review of the same topic in \n2015, where they collected data from 40 RCTs involving 4247 women \nwith infertility into a systematic review. Meta-analysis suggested a \n1.74 higher probability of achieving pregnancy with CHM therapy \nthan with Western therapy alone. In addition the authors concluded \nthat fertility indicators such as ovulation rates, cervical mucus \nscore, biphasic basal body temperature, and appropriate thickness \nof the endometrial lining are positively influenced by CHM therapy, \nindicating an ameliorating physiological effect for viable pregnancy.30\nTo promote ovulation rate: L Tan.31 published a meta-analysis where \n1659 participants were involved in 15 studies showing the efficacy \nof CHM treatment of infertility caused by anovulation as compared \nto clomiphene. Analysis indicated that CHM significantly increased \nthe pregnancy rate. There were also no significant adverse effects \nidentified from the use of CHM in this review.31\nY Huang’s team divided 60 patients with anovulatory infertility \ninto a Chinese medicine treatment group and a Western medicine \ncontrol group where the groups were equally matched in their general \nand anovulatory condition. The treatment group was treated with \nLEL (an established CHM recipe, Table 1), and the control group was \ngiven clomiphene. Ovulation rates and pregnant rates were observed \nand compared. They found that the total effective rate in the treatment \ngroup was 96.7%, which was significantly higher than that in the \n\nEffect of chinese herbal medicine on female infertility\n382\nCopyright:\n©2017 Jiang et al.\nCitation: Jiang D, Li L. Effect of chinese herbal medicine on female infertility. Obstet Gynecol Int J. 2017;8(1):380‒388. DOI: 10.15406/ogij.2017.08.00274\ncontrol group (53.3%, p < 0.05). The abortion rate was 10.0% in the \ntreatment group, which was significantly lower than that in the control \ngroup (54.6%, p<0.05). The symptom score decrease significantly in \nthe treatment group after treatment (P < 0.01), but remained unchanged \nin the control group. The authors were able to conclude that LEL had \ngood effect in treating anovulatory infertility. Q Chen and X Li’s team \nhave made similar studies with positive results.32-34\nT able 1 The established CHM formulae mentioned in this review, and the constituent herbs.\nReference number \n& Author Name of formula Herbs in  formula Latin names of herbs Pattern of TCM Research form\nX Gong.6\nBushenhuoxue \nRecipe (T onifying Kid and \nActivating Blood Formula)\nSheng Di Huang \nDan Shen \nDang Gui\nChuanDuan \nDu Zhong\nShan Yao \nMei Gui-hua\nChuanXiong \nYi Yi-ren\nRehmannia Rehmanniae \nSalviaemiltiorrhizae Bge. \nRadix Angelica sinensis (Oliv.) \nDipsacusAsperoides  Diels., \nEucommiaulmoides Oliv., \ncRhizomaDioscorea \nFlosRosa rugosa \nLigusticum \nRhizomachuanxiong \nSemen Coicis\nKidney Deficiency \n& Blood \nstasis\nRat Model\nS Luo.7 Luo’s recipe\nT uisizi \nDangshen \nGouqizi \nBajitian \nShudihuang \nYinyanghuo \nDangui \nFuzi \nZhigancao\nSemen Cuscutae \nRadix Codonopsis \nFructusLycii Chinensis \nRadix Morindae Officinalis \nRadix Glutinosa Libosch \nHerba Epimedi \nRadix Angelicae Sinensis \nRadix Aconiti Lateralis Preparata \nAngelica Sinensis (Oliv.)Diels \nAconitum Carmichaeli Debx \nRadix Glycyrrhizae Preparata\nKidney deficiency \n& \nDampness \naccumulation\nRat Model\nX T eng.8 Yulin Formula \n(A classical recipe 39)\nRenshen, \nBaizhu, \nFuling, \nBaishao, \nChuanxiong, \nDanggui, \nShudihuang, \nT usizi,\nDuzhong, \nLujiaoshuang \nChuanjiao \nZhigancao\nRanax Ginseng C.A.Mey \nAtractylodes Macrocephala Koidz \nPoria Cocos (Schw)Wolf \nPaeonia Laciflora Pall \nLigusticum ChuanxionHort \nAngelica Sinensis (Oliv.)Diels \nRehmannia Glutinosa Libosch \nCuscuta Chinensis Lam \nEucommia UlmoidesOliv \nZanthoxylum Bungeanum Maximl \nRadix Glycyrrhizae Preparata\nKidney deficiency \n& \nBlood deficiency\nRat \nModel\nS Luo.9\nZhuyun Recipe No3 \n(Promoting conceive \nrecipe)\nT usizi, \nSangjisheng \nHunagqi, \nDangshen, \nXuduan, \nNvzhenzi\nCuscutaChinensis Lam \nTaxillus Chinensis (DC.) Danser \nAstragalus Membranaceus (Fisch) \nCodonopsis Pilosula (Franch.) Nannf \nDipsacus Asperoides \nLigustrum Lucidum Ait.\nKidney& \nSpleen deficiencies, \nBlood stasis\n \nH Du.11\nBushenzhuyun recipe \n(T onifying Kid & promoting \nconceive\nShudihuang \nDangui \nBaishao \nShanyao \nShanyurou \nGouqizi \nYinyanghuo \nHuangqi \nT usizi\nRehmannia Glutinosa Libosch \nAngelica Sinensis (Oliv.)Diels \nPaeonia Laciflora Pall \nDiosacorea OppositaThunb. \nCornus Officinalis Sieb \nFructus LyciiChinensis \nEpimedium Brevicornum Maxim. \nAstragalus Membranaceus (Fisch \nCuscuta Chinensis Lam\nKidney deficiency \n& \nLiver stagnation\nRat Model\nQ Chen.16\nTiaojingyunyu Recipe \n(regulating menstrual circle \nand promoting conceive \nformula 39)\nDangui, \nChuanxiong \nShudihuang \nFuling \nChenpi \nXiangfu \nWuzhuyu \nRougui \nGanjiang \nMudanpi, \nYanhusuo, \nAiye\nRadix Angelica sinensis (Oliv.) \nLigusticum ChuanxionHort \nRadix Glutinosa Libosch \nPoria Cocos (Schw)Wolf \nCitrus Reticulata Blanco \nCyperus Rotundus L. \nEvodia Rutaecarpa (Juss.) Benth. \nCinnamomum Cassia Presl \nZingiber OfficinaleRosc. \nPaeonia SuffruticosaAndr. \nCordalis Vanhusuo \nArtemisia ArgyiLevl.\nBlood deficiency \n& stasis Clinic\n\nEffect of chinese herbal medicine on female infertility\n383\nCopyright:\n©2017 Jiang et al.\nCitation: Jiang D, Li L. Effect of chinese herbal medicine on female infertility. Obstet Gynecol Int J. 2017;8(1):380‒388. DOI: 10.15406/ogij.2017.08.00274\nReference number \n& Author Name of formula Herbs in  formula Latin names of herbs Pattern of TCM Research form\n \n \nY Huang.18\nLin’ erlai Recipe\nGuoqizi \nT usizi\nFupenzi \nWuweizi \nCheqianzi, \nShudihuang \nBaishao \nDanggui \nChuanxiong\nLyciumBarbarum L. \nCuscutaChinensis Lam \nRubusChingii Hu \nSchisandra Sphenanthera \nPlantago Asiatica L. \nCuscuta Chinensis Lam \nPaeonia Laciflora Pall \nAngelica Sinensis (Oliv.)Diels \nLigusticum ChuanxionHort\nKidney & \nBlood deficiencies Clinic\nJ Zhou.20 Y Jiang.23 J \nGuo .32\nT onifying Kid and Activating \nblood Recipe\nHuangqi \nDanshen \nBaizhu \nSanyao \nShanzhuyu \nNvzhenzi \nHanliancao \nXianmao \nYinyanghuo \nChuanxiong \nFuling \nHonghua \nDanggui \nT usizi \nChenpi \nMuxiang \nZexie\nAstragalus Membranaceus(Fisch) \nSalviaemiltiorrhizae Bge. \nAtractylodes MacrocephalaKoidz \nDiosacorea OppositaThunb. \nCornus Officinalis Sieb \nLigustrum Lucidum Ait. \nEclipta Prostrata L. \nCurculigo OrchioidesGaeth \nEpimedium Brevicornum Maxim. \nLigusticum Chuanxion Hort. \nPoria Cocos (Schw.)Wolf \nCarpesiumTinctorins L \nAngelica Sinensis (Oliv.)Diels \nCuscutaChinensis Lam \nCitrus Reticulata Blanco \nVladimiria Souliei (Franch.) Ling \nAlisma Orientalis (Sam) Juzep\nKidney deficiency \n& \nBlood stasis\nClinic\nF Liang.24 F Lian.31 ErzhiTiangui Granule Nvzhenzi \nHanliancao\nLigustrum Lucidum Ait. \nEclipta Prostrata L.\nKidney Yin \ndeficiency Clinic\nC Lu.25\nBushenHua \ntan Recipe (T onifying Kid \nand Cleansing Phlegm \nformula  )\nHuangqi \nCanzhu \nFuling \nYinyanghuo \nDanshen\nAstragalus Membranaceus (Fisch) \nXanthium Sibiricum Part. \nPoria Cocos (Schw.) Wolf \nEpimedium Brevicornum Maxim. \nSalvia MiltiorrhizaBge\nKidney deficiency \n& Phlegm \naccumulation\nClinic\nY Chen.26\nBushenantai Recipe \n(T onifying Kid to protect \nembryo )\nBaishao \nChuanduan \nSangjisheng \nLonggu \nMuli \nGancao \nEjiao\nPaeonia Laciflora Pall \nDipsacus Asperoides \nTaxillus Chinensis (DC.) Danser \n(Fossilised Bone) \n(Oyster Shell) \nGlycyrrhizae Uralensis Fisch \nAsini Gelatinun,\nKidney &Spleen \ndeficiency Clinic\nJ Yu.28 Yupingfeng Recipe (A \nclassical formula)\nHuangqi \nBaizhu \nFangfeng\nAstragalus Membranaceus (Fisch) \nAtractylodes MacrocephalaKoidz \nSaposhnikovia Divaricata (Turcz) \nSchischk\nLung and Spleen \ndeficiencies Clinic\nT able 2  Periodic Herbal Managements from G Xia’s experience.20,21,34,39,40\nPeriodic stage Treating Principle Xia’s herbal management39,44\nDuring Menstruation\nT o move Qi’s stagnation and activity \nblood for supporting follicle’s \ngrowth.\nCangzhu / Xanthium Sibiricum Part. \nXiangfu / CyperusRotundus L. \nMudanpi /PaeoniaSuffruticosaAndr. \nDanshen /Salviaemiltiorrhizae Bge \nChishao / PaeoniaLactiflora Pall. \nWulingzhi \nZelan / LycopusLucidusT urcz var. \nHirtus Regel \nZishiying / \nShanzha / CrataegusPinnatifidaBge \nYimucao / LeonurusJaponicus Hoult \nFuling / Poria Cocos (Schw.) Wolf\nTable Continued...\n\nEffect of chinese herbal medicine on female infertility\n384\nCopyright:\n©2017 Jiang et al.\nCitation: Jiang D, Li L. Effect of chinese herbal medicine on female infertility. Obstet Gynecol Int J. 2017;8(1):380‒388. DOI: 10.15406/ogij.2017.08.00274\nPeriodic stage Treating Principle Xia’s herbal management39,44\nPost of Menstruation\nT o nourish Yin and blood for \npromoting essence (egg)’s growing \nup and bursting out\nDanggui / Angelica Sinensis (Oliv.)Diels \nChishao / PaeoniaLactiflora Pall \nShudihuang / RadixGlutinosaLibosch \nMudanpi /PaeoniaSuffruticosaAndr \nFuling / Poria Cocos (Schw.)Wolf \nShanyao / DioscoreaOppositaThunb \nShanyurou / Cornus Officinalis Sieb et. \nZucc \nZhizi / Gardenia Jasminoides Ellis \nChuanduan / DipsacusAsperoides C.Y. \nCheng et \nT usizi / CuscutaGlabraRoxb \nFupenzi / RubusChingi Hu\nOvulation\nT o tonify Kidney Yang & to nourish \nYin essence and blood for preparing \na pregnancy\nDanggui / Angelica Sinensis (Oliv.)Diels \nDanshen /Salviaemiltiorrhizae Bge \nChishao / PaeoniaLactiflora Pall. \nZelan / LycopusLucidusT urcz var. \nHirtus Regel \nChongweizi / LeonurusHeterophyllus \nSweet \nHonghua / CarpesiumTinctorins L. \nXiangfu / CyperusRotundus L\nBefore of Menstruation\nT o move Liver Qi stagnation & \nnourish blood for feeding embryo \nand preventing a miscarriage\nChaihu / BupleurumChinense DC \nXiangfu / CyperusRotundus L \nAiye / Artemisisia Argyi Levl.et Vant \nXuduan / Dipsacus Asperoides C.Y. \nCheng et \nDuzhong / EucommiaUlmoidesOliv. \nEjiao / AsiniGelatinum, ComiAsiniColla \nSangjisheng / TaxillusChinensis (DC.) Danser\nTable Continued...\nHowever a review published by J Zhang. 35 indicated a different \nopinion that there is limited evidence that the addition of CHM to \nclomiphene is associated with improved clinical pregnancy outcomes, \nand found no evidence of any other effect.35\nTo treat ovulation failure and insufficiency of stored ova: J Zhou’s \nteam observed the curative effect of CHM of Tonifying the Kidney and \nActivating the Blood on improving ovulation failure, and the effect on \nincidence rate of luteinized unruptured follicle (LUF) and luteal phase \ndefect (LPD). 52 patients with ovulation disorder were randomly \ndivided into two groups; one group was treated with traditional \nChinese medicine (n=32, Table 1), and the other group, as the control, \nwas treated with Western drugs (n=20). In the treatment group, the \npatients were given various herbal formulae according to the patients’ \nstages of the menstrual circle; the Western drug control group patients \nwere given clomiphene 50-100 mg per day on day 5 of menstrual or \nwithdrawal of flavolutan. The two groups were all treated for three to \nsix cycles. All 52 patients completed the treatment. The authors found \nthat during the 156 cycles of 32 patients in the TCM group, ovulation \nwas found in 133 cycles, and the ovulation rate was significantly \nhigher than in the Western drug control group (85.26% versus 58.7%, \np<0.05). They found that the occurrence rates of LUF and LPD in the \nTCM group were lower than in the Western drug control group. The \nauthors concluded that CHM, by the Tonifying kidney and Activating \nBlood method improved ovulation rate and lowered incidence rate of \nLUF and LPD when compared with clomiphene.36 (Table 2).\nPeriodic treatment method of CHM is a particular TCM technique \nusing various herbal formulae in different stages of the menstrual \ncircle to promote ovarian function and following the cyclical hormonal \nchanges. It has been observed to be more effective than the standard \nTCM treatment methods. This method was created by Prof G Xia, 39 \nand was developed by D Jiang into a regime which is suitable to be \nused in the West.37 (Table 2).\nTo treat Fallopian tube obstruction : J Kang’s team studied an \neffective and practical treatment to Fallopian tube obstruction (OvO). \n120 patients with OVO were randomly divided into three groups: the \nTCM-WM group, treated with integrative Chinese herbal medicine (an \nestablished CHM formula) and Western medicine (salpingectomy); \nthe TCM group, treated with Chinese herbal medicine alone; and \nthe WM group treated with Western medicine alone. The therapeutic \neffect as well as the effect of treatment on serum C-reactive protein \n(CRP) and interleukin-1 beta (IL-1 beta) were observed. The authors \nfound that after treatment, Fallopian tube patency rate rose to 86.7% \nand pregnancy rate to 85.0% in the TCM-WM group, while in the \nTCM group rates were 66.7% and 63.3% respectively, and in the WM \ngroup 53.3% and 50.0% respectively. Comparison among the three \ngroups show that the effect in the TCM-WM group was significantly \nsuperior to that in the other two groups (P < 0.01). The levels of CRP \nand IL-1 beta were all lowered after three courses of treatment, and \nthe effect was more evident in the TCM-WM group (P < 0.01). They \nauthors concluded that TCM-WM treatment was a good and practical \nmethod in treating Fallopian tube obstruction.38\nY Jiang’s team also compared the effect of treatment of \nFallopian tube obstructive infertility by salpingectomy alone and in \ncombination with TCM drugs for BushenHuoxue (invigorating Shen \nand promoting blood circulation, an established CHM formula, Table \n1). To all the patients, salpingostomy was performed three to seven \ndays after menstruation, and hydrotubation with Xiangdan Injection \n(XI) was applied once in the next menstrual cycle. BushenHuoxue \nDecoction (BHD) was administrated additionally to patients in the \ntreatment group, one dose every day starting from the fifth day of \n\nEffect of chinese herbal medicine on female infertility\n385\nCopyright:\n©2017 Jiang et al.\nCitation: Jiang D, Li L. Effect of chinese herbal medicine on female infertility. Obstet Gynecol Int J. 2017;8(1):380‒388. DOI: 10.15406/ogij.2017.08.00274\nmenstrual cycle for 14 days. Three months’ treatment was taken as one \ntherapeutic course, and the observation lasted for four courses. The \nauthors confirmed the combined therapy of salpingostomy and CHM \nwas an effective therapy for Fallopian tube obstructive infertility \nby enhancing follicular development and increasing thickness of \nendometrium, and could elevate the pregnancy rate in patients.39\nTo treat PCO＆PCOS: F Lian ‘s team found that CHM-ErzhiTiangui \nGranule (Table 1) could increase anti-Müllerian hormone (AMH) and \noocyte quality for patients with polycystic ovarian syndrome. The \ndrug’s mechanisms of action are correlated with regulating AMH \nlevels in the serum and follicular fluid, adjusting androgen levels, \nimproving the pathophysiological changes of PCOS patients, and \nactivating the ovarian microenvironment.40\nC Lu’ team divided 30 patients with PCOS into a normoinsulinaemic \ngroup (NI=13), and an hyperinsulinaemic group (HI=17). Both \ngroups were treated for three menstrual cycles with the TCM Formula \nBushenHuatan Formula (an established CHMformula for tonifying \nkidney and activating blood, Table1). A metabolomics-approach based \non ultra-high-performance liquid chromatography (UPLC) coupled \nwith linear ion trap Orbi-trap mass spectrometer (LTQ Orbi-trap MS) \nwas used to investigate serum metabolic changes of TCM intervention \nto PCOS. After BHF intervention for three menstrual cycles, the \nserum levels of glycerophosphoryl ethanolamine (GPEA), creatine, \nand creatinine decreased in both NI and HI groups. Furthermore in \nthe NI group, the main manifestation were changes in phospholipid \nmetabolism. While in the HI group, lysine, phenol sulfate, phe-phe \netc. were decreased, and ornithine, proline, betaine, acetylcholine etc. \nwere increased. Combined with clinical biochemical data, BHF was \nproved effective in treatment of PCOS by reducing the inflammatory \nreaction and oxidative stress. This study also illustrated that the LC-\nMS-based metabolomics approach was a helpful tool to evaluate \ncurative effect and to understand the mechanisms of TCM.41\nTo reduce and to treat miscarriage : Recurrent spontaneous \nmiscarriage (RSM) is one of the commonest and complicated medical \nconditions amongst pregnant women. In recent years miscarriage \nrates have been progressively increasing, due to women trying to \nconceive later in life and the higher risk of pregnancy loss from in \nvitro fertilisation (IVF) and intrauterine insemination (IUI). TCM is \noften able to treat and prevent RSM.\nY Chen’s team observed the effect produced by the Gushenantai \nrecipe (a classical formula to prevent and treat miscarriage, Table 1) \nto women with recurrent spontaneous miscarriage without obvious \ncause, and its influence on T-lymphocytes. 90 patients were separated \ninto two groups where routine treatment of Progesterone was given, \nand Gushenantai recipe given to the half in the treatment group. No \nherbs were given to the other half in the control group. The authors \nfound that miscarriage was prevented and pregnancy proceeded in \n71.1% in the control group, and 86.7% in the treatment group. The \nteam also observed that B-HCG, HPL. P, CD4, CD8, CD4/CD8 \nlevels were different before and after treatment. They were able to \nconfirm that Gushenantai recipe was effective in reducing recurrent \nspontaneous miscarriage, and could correct immunological disorders \nand increase hormone levels.42\nTo treat mycoplasma infection: Y Lou’s team investigated the \nchanges in cytokines (IL-1beta, IL-2, TNF-alpha) in the peripheral \nblood and cervical mucus of infertile women with mycoplasma \ninfection and the effect of intervention of TCM. 72 patients with \npositive genital mycoplasma cultures were randomly divided into \na TCM group (38 cases) and a Western medicine group (34 cases). \nThe Western medicine group was treated with 0.5 g azithromycin \nfor three days and consecutively underwent six courses of treatment, \neach course of treatment of four days’ duration. The TCM group was \ntreated with Xiaozhi decoction (an established CHM formula) twice \nevery day for six weeks. Cytokines (IL-1beta, IL-2, TNF-alpha) in \nthe peripheral blood and cervical mucus were found to increase, \nsuggesting that TCM could effectively inhibit the levels of IL-1beta, \nIL-2, TNF-alpha in the peripheral blood, and IL-1beta, TNF-alpha in \ncervical mucus. The authors concluded that Xiaozhi decoction could \nbe used to treat infertile women with mycoplasma infection.43\nTo re-regulate immunology disorder: J Yu studied the effect of \nYupingfeng Formula (a classic CHM formula)to treat infertility in \nwomen with immunological disorders. Table 1). 72 patients with \nimmunological infertility were randomly assigned into two groups of \n36. The observed group was given Yupingfeng granule; the control \ngroup was given oral Prednisone. Levels of AsAb, AEmAb, AOV Ab \nand AbCGAb were markedly more reduced in the observed group \nthan in the controlled group (p< 0.05). Yu concluded that Yupingfeng \ngranule was able to significantly affect immunological infertility.44\nTo treat many abnormal physical and psychiatric symptoms, \nSuch as anxiety, stress, and insomnia: K Ried et al. 28 designed \nquestionnaires and interviewed women with infertility with the aim \nof identifying their quality of life. They found high level of distress, \nguilt, grief, and frustration caused by infertility. However, these \nwomen represented a highly motivated sample, who were actively \nseeking alternative support methods. Traditional Chinese Medicine \naddresses some of these. The group recommended that more peer-\nled and professional-led support groups were greatly needed \nfor women experiencing infertility to help break isolation and raise \nawareness of integrative approaches to fertility managemen. 45\nChinese Herbal Medicine can increase the success \nrate of in-vitro fertilisation and embryo transfer (IVF-\nET) outcomes\nA review series by J Liu et al. found that CHM could \nincrease success rates from 33% to 60% in IVF and IVF-\nET treatment. The authors’ results are summarised below:  \nTwenty trials involving 1721 women were included in the meta-\nanalysis. Three trials were evaluated as having an unclear risk of bias. \nThe remaining trials were evaluated as having a high risk of bias. \nDespite this the authors found that the combination of CHM and IVF \nsignificantly increased clinical pregnancy rates (OR 2.04, 95%CI 1.67 \nto 2.49, p<0.00001), and ongoing pregnancy rates (OR 1.91, 95%CI \n1.17 to 3.10, p = 0.009). Use of CHM after embryo transfer had no \nbetter outcome in reducing the rate of ovarian hyperstimulation \nsyndrome (OR 0.39, 95%CI 0.14 to 1.11, p = 0.08). This meta-analysis \nshowed that combination of IVF and CHM used in the included trials \nimprove IVF success, however due to the high risk of bias observed \nwith the trials, the significant differences found were felt to be unlikely \nto be accurate. The authors also mentioned that no conclusion could \nbe made with respect to the reproductive toxicity of CHM. Further \nlarge randomized placebo controlled trials were recommended to \nconfirm these findings before recommending women to take CHM to \nimprove their IVF success.47\nF Lian’s team conducted a series of studies to confirm the \neffectiveness of CHM in promoting IVF and increasing pregnancy \nrates:\nTo promote pregnancy uterus receptivity: Lian et al..48 found that for \ninfertile patients undergoing IVF, the recipe for tonifying the Kidney \n(Table 1) as an adjunct to standard Western treatment could reduce \nGn dosage and treatment duration, alleviate clinical symptoms, and \n\nEffect of chinese herbal medicine on female infertility\n386\nCopyright:\n©2017 Jiang et al.\nCitation: Jiang D, Li L. Effect of chinese herbal medicine on female infertility. Obstet Gynecol Int J. 2017;8(1):380‒388. DOI: 10.15406/ogij.2017.08.00274\nimprove pregnancy rate. The authors felt that the improvement could \nbe explained by an increased level of DNMT1 protein expression after \ntreatment, leading to enhanced endometrial receptivity.48\nTo improve the quality of oocytes and leukemia inhibitory factor \nin follicular fluid : The established CHM formula Erzhitiangui \nGranule ETG (Table 1) was found to distinctively increase the amount \nof oocytes, elevate the quality of embryos, and raise the success \nrate of IVF-ET. The authors speculated that the mechanism maybe \ncorrelated to the increase of LIF level in FF and the activating of \nmicroenvironment for its full expression.49\nTo improve endometrial blood flow in the uterus: Endometrial blood \nflow is directly related to endometrial receptivity, thereby affecting \nin-vitro fertilization and embryo transfer (IVF-ET) outcomes. J Guo \nteam’s studies confirmed that CHM formulae (Table 1) based on \nreinforcing kidney and activating blood can promote the formation of \nuterine endometrial blood vessels by adjusting expression of a variety \nof angiogenic growth factors, and regulating nitric oxide levels for \nthe inhibition of vascular smooth muscle contraction of the uterus. \nTreatments based on differentiation of syndromes are key to the \ntheory of TCM. Differentiation of syndromes should be combined \nwith biomedical disease diagnosis. The authors also felt that it was \nnecessary to further clarify other endometrial blood flow disorders \nusing TCM diagnostic methods.50\nTo decrease FSH level for making a good preparation to IVF \ntreatment: Elliott reported that Follicle stimulating hormone (FSH) \nlevels are routinely tested during biomedical investigations into \nfemale fertility. An appropriately low FSH level is frequently required \nby fertility clinics as an entry requirement for women wishing to \nreceive assisted reproductive technology (ART) treatment such as in-\nvitro fertilisation (IVF). The author asserts that with the appropriate \ntreatment using acupuncture and Chinese herbal medicine, the proper \nfunctioning of the ovaries and anterior pituitary gland, in cases where \nthey have been pathologically affected, can be restored. This process \ndoes not, however, necessarily imply that treatment has reversed the \nageing process or affected the quality of eggs produced.49\nTo support patients who have failed IVF treatment: X X’s team \nexplored the effect of traditional Chinese comprehensive therapy \n(TCCT) on promoting gestation in patients with previously failed in-\nvitro fertilisation and embryo transfer (IVF-ET) because of kidney \ndeficiency, liver stagnation, and blood stasis (KLB). 37 patients were \nenrolled in this study and divided into two groups: a trial group with \n35 patients, and a control group with 32 patients. The trial group was \ngiven TCCT for three months, then administered IVF-ET or natural \npregnancy was awaited. The control group was administered IVF--\nET without TCCT three months after the previous IVF-ET or natural \npregnancy attempt. The patterns of KLB were observed both before \nand after treatment. The natural pregnancy rate of the two groups was \ncalculated after treatment.\nAfter treatment with TCM comprehensive therapy, seven patients \nin the treatment group became pregnant, while there were no \nsuccessful conceptions in the control group. The difference in clinical \npregnancy rate in the initial cycle and transfer cycle of IVF were \nsignificantly different (p < 0.05). The trial group had a significantly \nhigher conception rate than the control group (P < 0.05).The authors \nconcluded that TCCT can promote natural pregnancy rate in patients \nwith previously failed IVF-ET. TCCT could increase the number \nof fertilised eggs, the fertilisation rate, pregnancy rate, and clinical \npregnancy rate after another IVF-ET treatment.50\nWhole Systematic TCM Treatment for Infertility and \nIVF Treatment\nTCM is a traditional medical system with a thousand years of \nexperience which should be combined with herbal medicine and \nacupuncture together. From the evidence it appears that using \nwhole TCM treatment may achieve the best results for both natural \npregnancy and IVF.\nK Sela et al.. 51 observed the effect of combining acupuncture and \nmedicinal herbs as a therapeutic adjuvant to ovulation induction \nwith intrauterine insemination (IUI) procedures, and evaluated \nits contribution to pregnancy and “take-home baby” rates. The \nretrospective study was carried out in a university – affiliated \nmunicipal hospital. All women undergoing artificial insemination by \ndonor spermatozoa (AID) and concomitantly treated with TCM were \ninvited to participate. The enrolled women underwent weekly TCM in \nparallel with standard Western therapy. The treatment lasted between \ntwo and 36 cycles (equivalent to a time period ranging from one \nmonth to one year). The control group was comprised of women who \nunderwent AID without TCM and whose data were retrospectively \nretrieved from hospital files. Pregnancy was assessed by human \nchorionic gonadotropin findings in blood 12–14 days after IUI. The \nbirth rate was calculated during follow-up. A total of 29 women \naged 30–45 years were enrolled in the study. The historical control \ngroup include 94 women aged 28–46 years. The results showed that \nwomen who combined TCM with procedures for undergoing IUI had \nsignificantly higher pregnancy (OR=4.403, 95% CI 1.51–12.835, \np=0.007) and birth rates (OR=3.905, 95% CI 1.321–11.549, p=0.014) \nthan the control group. The group concluded that TCM appeared \nto be beneficial as an adjunctive treatment in IUI procedures. They \ncalled for randomised controlled trials to further assess the role of \nacupuncture and herbs in this setting.51 \nE Lee et al. 52 observed that whole-systems traditional Chinese \nmedicine (WS-TCM) was a multi-dimensional intervention that \ncould include any combination of modalities classified under the \nsystem of TCM. They describe these as including any combination \nof acupuncture (the insertion of sterile, filiform needles in the body), \nmoxibustion (the burning of the processed herb A rtemesia argyi on \nor near the body), and Chinese herbal medicine (granule, powder or \ndry herbal forms). The authors compared the reproductive outcomes \nof women who elected for WS-TCM treatment in addition to their \nusual IVF care, and compared them with those who received the \nusual IVF care alone, and to those who received two standardised \nacupuncture treatments on the day of embryo transfer acupuncture \nonly. They compared the three groups on the outcome of live birth, \nand found evidence that the addition of WS-TCM to non-donor \nIVF cycles increased the odds of achieving a live birth over usual \nIVF care alone or two standardized treatments administered around \nembryo transfer. They found that the effects of WS-TCM were less \nclear compared with usual donor IVF care alone but showed a non-\nsignificant trend towards increased odds of a live birth in this cycle \ntype. This retrospective cohort study suggested that WS-TCM as an \nadjuvant IVF treatment may be associated with improved live birth \nrates.52\nConclusion\nFrom searching and reviewing the above information, some \nconclusions can be drawn:\n\nEffect of chinese herbal medicine on female infertility\n387\nCopyright:\n©2017 Jiang et al.\nCitation: Jiang D, Li L. Effect of chinese herbal medicine on female infertility. Obstet Gynecol Int J. 2017;8(1):380‒388. DOI: 10.15406/ogij.2017.08.00274\ni. Chinese Herbal medicine is an effective therapy which appears \nto be show ability to support infertility treatment. Much research \nhas been done in China to explain the mechanism of action \nof CHM in treating Infertility, and some utilise very modern \ntechniques and high levels of expertise. 21-27 However they are \nlimited in circulation and impact due to being in Chinese only.\nii. A mature and established CHM formula may be the key to high \nefficacy, and effective and experienced herbal formulae should \nbe designed according to diagnostic patterns within TCM. 53,54 \nNo paper described effects produced by a single herb to treat \nInfertility.\niii. Combining the whole system of TCM together, such as \ncombining acupuncture and CHM, acupuncture, moxibustion \nand CHM, massage and CHM, gives better treatment power than \nindividual therapy modalities.55,56\niv. The shortcoming of CHM may still be its weaker treatment level. \nSome researchers observe that combining CHM with Western \nmedical technology or drugs can give better effects than either \nCHM or Western drug alone.38,39,42\nAcknowledgments\nNone.\nConflicts of Interset\nNone.\nReferences\n1. Clinic Specialization Gynaecology handbook Oxford University \npublisher.\n2. Dunson DB, Baird DD, Colombo B Increased infertility with age in men \nand women. Obstet Gynecol. 2004;103(1):51-56.\n3. National Centre for health statistics: Infertility.\n4. Wikipedia, Infertility Females.\n5. Richard S, Unexplained Infertility Background, Tests and Treatment \nOptions. Advanced Fertility Centre of Chicago, USA.\n6. Williams T, Mortada R, Porter S Diagnosis and Treatment of Polycystic \nOvary Syndrome. Am Fam Physician. 2016; 94(2):106-113.\n7. Sotrel G Is Surgical Repair of the Fallopian Tubes Ever Appropriate? \nRev Obstet Gynecol. 2009; 2(3):176-185.\n8. 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G Xia Female and Men infertility and regulation in menstrual circles. \nPeople Health Publishing House, Beijing, The secondary publishing \nissue. 2001\n56. Z Dong The Experienced formulae of TCM on Infertility Beijing. \nPublishing House of Science and Technology Beijing. 1990.","source_license":"CC0","license_restricted":false}