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Evidence for the use of complementary and alternative medicines during fertility treatment: a scoping… Miner, Skye A; Robins, Stephanie; Zhu, Yu J; Keeren, Kathelijne; Gu, Vivian; Read, Suzanne C; Zelkowitz, Phyllis May 15, 2018

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RESEARCH ARTICLE Open AccessEvidence for the use of complementaryand alternative medicines during fertilitytreatment: a scoping reviewSkye A. Miner1,2, Stephanie Robins2, Yu Jia Zhu2,3, Kathelijne Keeren2, Vivian Gu2,4, Suzanne C. Read2and Phyllis Zelkowitz2,5,6*AbstractBackground: Complementary and alternative medicines (CAM) are sometimes used by individuals who desire toimprove the outcomes of their fertility treatment and/or mental health during fertility treatment. However, there islittle comprehensive information available that analyzes various CAM methods across treatment outcomes andincludes information that is published in languages other than English.Method: This scoping review examines the evidence for 12 different CAM methods used to improve female and malefertility outcomes as well as their association with improving mental health outcomes during fertility treatment. Usingpredefined key words, online medical databases were searched for articles (n = 270). After exclusion criteria wereapplied, 148 articles were analyzed in terms of their level of evidence and the potential for methodological andauthor bias.Results: Surveying the literature on a range of techniques, this scoping review finds a lack of high qualityevidence that complementary and alternative medicine (CAM) improves fertility or mental health outcomes formen or women. Acupuncture has the highest level of evidence for its use in improving male and female fertilityoutcomes although this evidence is inconclusive.Conclusion: Overall, the quality of the evidence across CAM methods was poor not only because of the use ofresearch designs that do not yield conclusive results, but also because results were contradictory. There is a needfor more research using strong methods such as randomized controlled trials to determine the effectiveness ofCAM in relation to fertility treatment, and to help physicians and patients make evidence-based decisions aboutCAM use during fertility treatment.Keywords: Complementary and alternative medicine, Infertility treatment, Mental health, Acupuncture, Reproductivehealth, Scoping reviewBackgroundPeople facing infertility concerns are increasingly turningto the use of assisted reproductive technologies. However,successful treatment outcomes are far from certainbecause 68.5% of IVF cycles do not result in a live birth[1]. These high failure rates lead many couples to look forways to improve their chances of achieving conception.Complementary and alternative medicines (CAM) pur-portedly offer couples a way to improve outcomes and/ordecrease stress and anxiety levels during treatment [2–4].CAM are also used to incorporate cultural traditions ofhealth and fertility as well as increase feelings of hope andcontrol during a biomedicalized fertility treatment plan[5]. Some patients also use CAM as an alternative toassisted reproductive technologies, although most fertilitypatients use CAM in addition to biomedical fertility treat-ment [6, 7]. However, little comprehensive informationexists on the effectiveness of these methods, leaving bothpatients and physicians lacking the necessary knowledge* Correspondence: phyllis.zelkowitz@mcgill.ca2Department of Psychiatry, Jewish General Hospital, 4333 Chemin de laCote-Ste-Catherine, Room 223, Montreal, QC H3T 1E4, Canada5Lady Davis Institute, 3755 Chemin de la Cote-Ste-Catherine, Montreal, QCH3T 1E2, CanadaFull list of author information is available at the end of the article© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Miner et al. BMC Complementary and Alternative Medicine  (2018) 18:158 https://doi.org/10.1186/s12906-018-2224-7to make evidence-based decisions about whether to useCAM during fertility treatment.CAM is defined by the Centers for Disease Control(CDC) as a “group of diverse medical and health caresystems, practices, and products that are not presentlyconsidered to be part of conventional medicine” [8]. Thecurrent definition of CAM is broad but inclusive,encompassing acupuncture, body work (e.g. massage),energy healing (e.g. reiki), herbal medicines (e.g. natur-opathy), mind-body techniques (e.g. meditation, yoga),and traditional medicines (e.g. Chinese medicine). SomeCAM relies on alternative practitioners to administerthese methods (e.g. acupuncture) while others require achange in behavior by the individual using CAM (e.g.meditation). The various types of CAM offered, alongwith the increasing market for alternative fertility prod-ucts, makes it pertinent to have a broader understandingof the effectiveness of these treatments.The stigma, costs, and uncertainty associated with bio-medical fertility treatments often entice those who arehaving problems conceiving to use CAM as a first lineof treatment before engaging in more medically invasivetreatments [6, 9]. Recent studies suggest that fertilitypatients often see CAM methods as a safe and effectiveway to increase their fertility [2], and are thus willing totry alternative treatments and remedies to supplementconventional approaches to fertility treatment. Theholistic approach that many CAM methods purport alsooffers a way for current fertility patients to offset somepotential negative side-effects of biomedical treatments[2]. Additionally, the patient-centered focus of CAMprovides fertility patients a feeling of control over thetreatment process [4, 7]. While these “fertility-enhan-cing” treatments are often sold and marketed to couplesattempting to conceive naturally or through biomedicalprocesses, their effectiveness is often unknown.CAM is not only used to increase fertility, but also todecrease patient levels of stress and anxiety during thetaxing process of treatment [2, 10]. A lack of knowledgesurrounding CAM’s effectiveness and potential negativeeffects along with the belief that CAM makes one psycho-logically stronger contributes to the prevalence of CAMuse during fertility treatment; 29–91% of fertility patientsreport using a CAM method during treatment [4].The wide range of fertility patients reporting CAM useis partially due to differing definitions of CAM in the lit-erature. The review of CAM by Rayner, Willis and Burgess[4] reports on eight different studies and found the highestprevalence of use was 91%. A 2013 study by Clark reportsa similar prevalence of CAM use by fertility patients inthe US where 91.3% reported using CAM with 73% ofthese patients believing CAM had beneficial effects ontheir fertility [10]. The high rates of CAM endorsementmay be due to a number of factors: their broad definition(e.g. including exercise as a CAM method), and the sam-ple bias (i.e. those who use CAM are potentially morelikely to answer a survey examining CAM-seeking behav-iors). On the other hand, more restrictive definitions ofCAM that exclude more common practices such asprayer, or consider only a subset of CAM treatments suchas herbal or alternative medicine, report a lower preva-lence of use 8.3–29% [11, 12], suggesting that reportedprevalence of CAM use is highly dependent on definition.Rayner, Willis and Burgess [4] found that the mostcommonly used CAM methods for promoting fertilityinclude herbal medicine, acupuncture and nutritionaladvice/supplements while the most rarely used includereligious intervention, spiritual healing1, fertility acces-sories (e.g. necklaces, rocks) and changes in attire/sexualpractices. The differences in popularity of these methodsmay be due not only to patients’ personal preferences,but also to the perception that some methods have bet-ter outcomes. However, the benefits of CAM have notbeen systematically evaluated across CAM methods asmost comprehensive reviews focus on why people useCAM, and prevalence and types of CAM used.This paper provides a scoping review of the potentialbenefits of various CAM methods, while describing thequality of that evidence. This paper advances the litera-ture in this field by a) looking at a wider variety of CAMmethods by including methods such as Ayurveda, herbalmedicine, osteopathy, and hypnosis that have not beenpreviously summarized in the literature; b) assessingCAM effectiveness in relation to female and male factorinfertility as well as mental health outcomes; c) review-ing articles in multiple languages including Chinese,English, French and Korean; d) not limiting the evidenceto randomized clinical trials or previously compiledmeta-analyses.The specific research questions were: 1) What is theavailable evidence written in English, French, Chineseand/or Korean on the use of CAM in conjunction withmale and female factor medical fertility treatment? 2)What evidence exists on using CAM for reducingpsychological distress, including, stress, anxiety, anddepression during men’s and women’s medical fertilitytreatment? 3) What is the quality of the evidence avail-able on using CAM for improving fertility outcomes andfertility-related mental distress for both men and womenexperiencing infertility? Based on the review of the evi-dence, the conclusion contains recommendations aboutthe potential benefits of particular CAM for both maleand female fertility patients.MethodsType of reviewA scoping review was conducted to compile and evalu-ate the evidence available for the use of CAM duringMiner et al. BMC Complementary and Alternative Medicine  (2018) 18:158 Page 2 of 12fertility treatment. A scoping review is “a form of know-ledge synthesis that addresses an exploratory researchquestion aimed at mapping key concepts, types of evi-dence and gaps in research related to a defined area orfield by systematically searching, selecting, and synthe-sizing existing knowledge” [13]. Scoping reviews help toprovide information surrounding the effectiveness oftreatments and are becoming increasingly important inproviding information to determine evidence based-treatments (EBT) [14]. They are useful for reviewingtopics where there is limited information and the meth-odologies used are disparate across studies [15]. Theability to comprehensively analyze information withvarious outcomes and measures offers an advantage overthe more traditional systematic reviews such as meta-analyses. Scoping reviews also identify potential gaps inthe evidence, pointing to areas where further researchshould be conducted [14, 15]. The stages set out byArksey and O’Malley [14] were used to conduct ascoping review of the different types of CAM used inconjunction with infertility treatment: stage one identi-fies the research question; stage two identifies relevantstudies; stage three involves study selection; stage fourcharts the data; stage five collates, summarizes andreports the results.Stage 1-identifying the research questionThe research questions (see above) were identified whilecollecting evidence surrounding the effectiveness of CAM.During this process, it became clear that there was nocomprehensive review of the effectiveness of CAM in rela-tion to specific fertility outcomes.Stage 2-identifying relevant studiesOn the basis of the National Center for Complementaryand Alternative Medicine’s (NCCAM) review of popularCAM methods, the following methods were included:acupressure, acupuncture, Ayurveda, homeopathy, hyp-nosis, Chinese medicine, chiropractory, massage therapy,meditation, Mercier Therapy, mindfulness, naturopathy,relaxation, reflexology, reiki, touch therapy, yoga (seeTable 1 for the search terms used and see Additional file 1for definitions of methods). We categorized these com-mon CAM methods according to the NCCAM classifi-cation system: alternative medicine systems (AMS; e.g.acupuncture), biological-based therapies (BBT; e.g.herbal supplements), manipulative and body-basedtherapies (MBBT; e.g. chiropractic care), and mind–body therapies (MBT; e.g. meditation) [8]. Althoughthe NCCAM includes nutrition, diet and supplementsin their definition of CAM, we chose not to includenutrition and supplements in our scoping review asdietary and nutritional advice is often viewed to bepart of biomedical fertility treatments [16]. We did notinclude treatments such as Chelation therapy as itspurpose is not intended for infertility. Some of theCAM methods identified by NCCAM like traditionalhealers were included by searching for “herbal medi-cine” rather than the title of the practitioner in anattempt to identify the mechanism of action (i.e., theherb). These common CAM methods were thencombined with the search terms for our populationsand outcomes of interest. Population terms includedmale infertility/subfertility/fertility, female infertility/subfertility/fertility. The outcomes of interest wereemotional distress AND infertility/subfertility/fertility,anxiety AND infertility/subfertility/fertility, depressionAND infertility/subfertility/fertility, infertility-relateddistress, IVF, ICSI, assisted reproduction, fertility treat-ment, and infertility treatment (see Table 1).The CAM method, population terms and outcomesof interest were combined using “AND,” and searchesTable 1 Search Terms UsedPopulation Terms Outcomes of Interest Type of CAMGeneralinfertility, subfertility, fertilityType of Treatmentassisted reproduction, fertility treatment,infertility treatment, IVF, ICSIGeneral CAM Termsalternative medicine, complementary alternative medicine,complementary medicine, alternative medicineFemalefemale infertility, female subfertility,female fertilityMental Healthanxiety, depression, infertility-relateddistress, emotional distressAlternative Medicine Systemsacupressure, acupuncture, moxibustion, naturopathy,homeopathy, Ayurveda, Traditional Chinese Medicine,traditional medicineMalemale infertility, male subfertility,male fertilityBiologically Based Therapies (BBT)Chinese herbal medicine, herbal medicine, herbalsupplementsManipulative-and-Body Based Therapies (MBBT)chiropractory, healing touch, massage therapy, Merciertherapy, osteopathy, reflexology, reiki, shiatsu, therapeutictouch, touch therapyMind-Body Therapies (MBT)hypnosis, meditation, relaxation, yogaMiner et al. BMC Complementary and Alternative Medicine  (2018) 18:158 Page 3 of 12were undertaken in the following databases: CochraneLibrary, Medline Ovid, Pubmed, and PsycInfo.Stage 3-study selection The search was limited to stud-ies published from January 2006–June 2016. Both quali-tative and quantitative articles were included for review.Articles were excluded if they were not written inEnglish, Spanish, French, Chinese or Korean, if they didnot contain data points that measured the specified out-comes (female fertility, male fertility and/or psycho-logical distress), and/or if the full-text articles could notbe located using the Colombo Interlibrary Loan system(see Fig. 1).Stage 4-charting the dataEach article was read independently by one of the au-thors. The following information was recorded abouteach article: language of the article and the abstract, typeof CAM, type of study (see Table 2 for the types of stud-ies included), the research question, the fertility outcomeassessed, how the fertility outcome was assessed, thenumber of participants, the description of the controland treatment groups, the results including statisticalsignificance of the findings (p < 0.05), the accuracy of theabstract (i.e. if the abstract contained correct findingsand/or interpretation of results), and any bias (i.e. aprejudice in favor of the authors’ hypotheses and/orconflicts of interest reported or omitted by the studyauthors) (see Additional file 2). After this informationwas recorded, the first author assessed the level of evidenceof each individual article using Australia’s National Healthand Medical Research Council’s Evidence Hierarchy(NHMRC) [17, 18]. This tool was developed by a team ofresearchers and clinical practitioners to evaluate theFig. 1 Exclusion CriteriaMiner et al. BMC Complementary and Alternative Medicine  (2018) 18:158 Page 4 of 12clinical effectiveness of medical evidence (see Table 2).Level I evidence includes studies that are obtained from asystematic evaluation of randomized control trials; level IIevidence is “evidence obtained from at least one properly-designed randomized trial;” level III-1 evidence is “evidenceobtained from well-designed pseudorandomized controlledtrials;” level III-2 evidence is “evidence obtained from com-parative studies with concurrent controls and allocation isnot randomized, cohort studies, case-control studies, orinterrupted time series with a control group;” level III-3 is“evidence obtained from comparative studies with histor-ical control, two or more single arm studies, or interruptedtime series without a parallel control group;” and level IVevidence is “evidence obtained from case series, eitherpost-test or pre-test/post-test” [18].ResultsA total of 148 out of 270 articles were determined to berelevant to review after applying the exclusion criteria(see Table 3). 101 articles were written in English, forty-four articles were written in Chinese with forty-threehaving an English abstract, and three articles were writ-ten in Korean all having English abstracts. Only one art-icle of forty-four (2.3%) written in Chinese had anabstract that did not accurately describe the results whilethirteen of the 101 (12.9%) articles in English had ab-stracts that did not accurately represent the findings ofthe study. All of the articles written in Korean hadaccurate abstracts. Articles that contained informationabout two methods (n = 17) were reviewed in both areas.The following results describe the rated evidence as perAustralia’s National Health and Medical Research(NHRMC). The risk of bias was assessed for each article.Articles with lower levels of evidence had increased riskfor author bias. Table 4 describes how many articleswere found in relationship to each CAM area. No arti-cles were found in relation to chiropractic medicine,reiki, reflexology, shiatsu, therapeutic touch therapy, ortouch therapy.AcupunctureForty-four articles were reviewed with evidence rangingfrom level I to level IV. Some articles evaluated multipleoutcomes. Five articles were written in Chinese, one art-icle was written in Korean, and thirty-eight were writtenin English. Eight of the forty-four studies (18.2%) wererated as having level I evidence (with one study assessingmultiple outcomes). Five level I studies showed animprovement in fertility outcomes: two showed animprovement in female fertility, two showed an improve-ment in male fertility, and two showed an improvementin mental health (see Table 4). The number of studies ofacupuncture that had level II evidence was fifteen offorty-four (34.1%). Seven of the twelve (58%) level IIstudies evaluating acupuncture in relationship to femalefertility showed an improvement in outcome while theonly level II study evaluating male fertility showed animprovement in outcome (see Table 5). Additionally, thethree level II studies evaluating mental health outcomeswith the use of acupuncture showed an improvement inoutcomes (see Table 5). The remaining twenty-two stud-ies ranged in their levels of evidence from level III-1 tolevel IV with a minority showing improvement in out-comes (see Table 4).AyurvedaEighteen articles were reviewed with evidence rangingfrom level II to level IV. Some articles examinedmultiple outcomes. All articles were written in English.Six of the eighteen studies (33.3%) were rated as havinglevel II evidence. All five (100%) of the level II studiesTable 2 Types of Studies by Evidence LevelLevel of Evidence Types of StudiesLevel I systematic review of level II studies, meta-analysisLevel II randomized control trialLevel III-1 pseudorandomized control trialLevel III-2 comparative studies including non-randomizedexperimental trials, cohort studies, case-controlstudies, interrupted time series with controlsLevel III-3 comparative studies without controls includinghistorical control studies, two or more single-armstudies, interrupted time series without a parallelcontrol group, cross-sectionalLevel IV case series, nonsystematic review, survey,qualitative interviewsTable 3 Number of Studies by CAM Method (N = 147)Alternative Medicine Systems(AMS)Biological Based Therapies(BBT)Manipulative and Body-Based Therapies(MBBT)Mind-Body Therapies(MBT)Acupuncture (n = 44)a Herbal Medicine (n = 16)b Massage (n = 3) Hypnosis (n = 2)Ayurveda (n = 17) Homeopathy (n = 1) Osteopathy (n = 1) Relaxation (n = 8)Traditional Chinese Medicine (n = 71)a,b Naturopathy (n = 1) Chiropractic medicine, reiki, reflexology,shiatsu, therapeutic touch, touch therapy(n = 0)Yoga (n = 3)aThere were 11 articles that contained evidence for both acupuncture and Traditional Chinese Medicine. Duplicate articles were reviewed in all categoriesbThere were 6 articles that contained evidence for both acupuncture and herbal medicine. Duplicate articles were reviewed in all categoriesMiner et al. BMC Complementary and Alternative Medicine  (2018) 18:158 Page 5 of 12showed an improvement in fertility outcomes: threeshowed an improvement in female fertility, two showedan improvement in male fertility, and one showed animprovement in mental health (with one study evaluat-ing two outcomes) (see Table 5). There was only onestudy that had level III-1 evidence which showed animprovement in male fertility outcomes. While therewere three level III-2 studies, only two showed animprovement in male fertility outcomes (see Table 5).The remaining eight studies were level IV studies withsix studies showing an improvement in female fertilityand two studies showing an improvement in male fer-tility (see Table 4). The risk of bias for female fertilityoutcomes was very high as study protocols were notstandardized.Chinese herbal medicineSeventy-two articles were reviewed with evidence ran-ging from level I to level IV. Some articles examinedmultiple outcomes. Forty-two articles were written inChinese with thirty-six of those articles providing anEnglish abstract. Twenty-nine articles were written inEnglish. Fourteen of the seventy-two articles (19.4%)were level I studies with twelve (16.6%) evaluatingfemale fertility outcomes and two (2.7%) rating malefertility outcomes. Nine of these level I studies showedan improvement in female fertility outcomes and twoshowed an improvement in male fertility outcomes (seeTable 5). Thirty-one of the seventy-two articles (43.1%)were rated as having level II evidence; twenty-one of thethirty-one articles (67.8%) showed an improvement infemale fertility outcomes and six showed an improve-ment in male fertility outcomes (see Table 5). Therewere only two articles that evaluated mental health out-comes. Although both studies showed an improvementin mental health outcomes, the evidence for this im-provement was very low (level-IV).Herbal medicineSeventeen articles were reviewed with evidence rangingfrom level I to level IV. Some articles examined multipleoutcomes. All articles were written in English. Three ofthe seventeen articles (17.6%) were level I studies withone evaluating female fertility outcomes and two evalu-ating male fertility health outcomes (see Table 5). Themajority of the studies (nine out of seventeen articles,52.9%) evaluating herbal medicine had the lowest levelof evidence. Two of the three (66.7%) level IV studiesthat evaluated female fertility outcomes showed an im-provement in outcome while four of the six (66.7%) levelIV studies that evaluated male fertility outcomes showedan improvement in outcome. The only study related toTable 4 Rating the EvidenceMethod Type of Outcome Level I Level II Level III-1 Level III-2 Level III-3 Level IVAcupuncture Female Fertility (n = 32) 5 (15.6%) 12 (37.5%) 1 (3.1%) 3 (9.4%) 4 (12.5%) 7 (21.9%)Male Fertility (n = 9) 3 (33.3%) 1 (11.1%) 0 (0.0%) 0 (0.0%) 1 (11.1%) 4 (44.4%)Mental Health (n = 8) 1 (12.5%) 3 (37.5%) 0 (0.0%) 1 (12.5%) 1 (12.5%) 2 (25.0%)Ayurveda Female fertility (n = 9) 0 (0.0%) 3 (33.3%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 6 (66.7%)Male fertility (n = 8) 0 (0.0%) 2 (25.0%) 1 (12.5%) 3 (37.5%) 0 (0.0%) 2 (25.0%)Mental health (n = 1) 0 (0.0%) 1 (100.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)Chinese Herbal Medicine Female fertility (n = 53) 12 (22.6%) 25 (47.2%) 2 (3.8%) 3 (5.7%) 3 (5.7%) 8 (15.1%)Male fertility (n = 17) 2 (11.8%) 6 (35.3%) 7 (41.2%) 1 (5.9%) 0 (0.0%) 1 (5.9%)Mental health (n = 2) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 2 (100%)Herbal Medicine Female fertility (n = 6) 1 (16.7%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 2 (33.3%) 3 (50.0%)Male fertility (n = 10) 2 (20%) 1 (10%) 0 (0.0%) 0 (0.0%) 1 (10%) 6 (60.0%)Mental health (n = 1) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (100%) 0 (0.0%)Homeopathy Female fertility (n = 1) 0 (0.0%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (100%)Hypnosis Female fertility (n = 2) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (50.0%) 0 (0.0%) 1 (50.0%)Massage Female fertility (n = 3) 0 (0.0%) 1 (33.3%) 1 (33.3%) 0 (0.0%) 0 (0.0%) 1 (33.3%)Naturopathy Female fertility (n = 1) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (100%)Osteopathy Female fertility (n = 1) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (100%)Relaxation Mental health (n = 8) 0 (0.0%) 1 (12.5%) 1 (12.5%) 3 (37.5%) 0 (0.0%) 3 (37.5%)Yoga Mental health (n = 3) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (33.3%) 0 (0.0%) 2 (66.7%)n = number of studies, CAM methods which had no studies (n = 0) evaluating specific fertility outcomes were removed from the table; n.b. Articles could evaluatemultiple outcomes (e.g. some articles that evaluated female fertility outcomes also evaluated male fertility outcomes)Miner et al. BMC Complementary and Alternative Medicine  (2018) 18:158 Page 6 of 12mental health was rated as having level III-3 evidenceand it showed an improvement in outcomes.HomeopathyThere was only one article found that evaluated the useof homeopathy. It was written in English, and examinedfemale fertility outcomes. While the study showed animprovement in outcomes, it was rated as having thelowest level of evidence, level IV (see Tables 4 and 5).There was a high risk of bias in this study as there wasnot standardized recruitment or predefined outcomes.HypnosisThere were two articles found that evaluated the use ofhypnosis and fertility treatment. They were both writtenin English and examined female fertility outcomes. Onestudy was rated as having level III-2 evidence and theother as having level IV evidence (see Table 4). Bothshowed an improvement in outcomes (see Table 5). TheTable 5 Evidence for Positive OutcomesMethod Type of Outcome Level IImprovedOutcomeLevel IIImprovedOutcomeLevel III-1ImprovedOutcomeLevel III-2ImprovedOutcomeLevel III-3ImprovedOutcomeLevel IVImprovedOutcomeAcupuncture Female Fertility 40%(2/5)58%(7/12)0%(0/1)33.3%(1/3)100%(4/4)(14.3%)1/7Male Fertility 66.7%(2/3)100%(1/1)0%(0/1)–(0/0)100%(1/1)100%(4/4)Mental Health 100%(1/1)100%(3/3)–(0/0)0%(0/1)0%0/1100%(2/2)Ayurveda Female Fertility –(0/0)67%(2/3)–(0/0)–(0/0)–(0/0)100%(6/6)Male Fertility –(0/0)100%(2/2)100%(1/1)66.7%(2/3)–(0/0)100%(2/2)Mental Health –(0/0)100%(1/1)–(0/0)–(0/0)–(0/0)–(0/0)Chinese Herbal Medicine Female fertility 75%(9/12)84%(21/25)100%(2/2)66.7%(2/3)66.7%(2/3)37.5%(3/8)Male fertility 100%2/2100%(6/6)85.7%(6/7)100%(1/1)–(0/0)100%(1/1)Mental health –(0/0)–(0/0)–(0/0)–(0/0)–(0/0)100%(2/2)Herbal Medicine Female fertility 0%(0/1)–(0/0)–(0/0)–(0/0)100%(2/2)66.7%(2/3)Male fertility 50%(1/2)100%(1/1)–(0/0)–(0/0)100%(1/1)66.7%(4/6)Mental health –(0/0)–(0/0)–(0/0)–(0/0)0%(0/1)–(0/0)Homeopathy Female fertility –(0/0)–(0/0)–(0/0)–(0/0)–(0/0)100%(1/1)Hypnosis Female fertility –(0/0)–(0/0)–(0/0)100%(1/1)–(0/0)100%(1/1)Massage Femalefertility–(0/0)100%(1/1)100%(1/1)–(0/0)–(0/0)100%(1/1)Naturopathy Femalefertility–(0/0)–(0/0)–(0/0)–(0/0)–(0/0)100%(1/1)Osteopathy Female fertility –(0/0)–(0/0)–(0/0)–(0/0)–(0/0)100%(1/1)Relaxation Mental health –(0/0)100%(1/1)100%(1/1)100%(3/3)–(0/0)100%(3/3)Yoga Mental health –(0/0)–(0/0)–(0/0)100%(1/1)–(0/0)100%(2/2)Fractions in parenthesis represent the number of studies that improve the outcome over the total number of studies in that area. CAM methods which had nostudies (n = 0) evaluating specific fertility outcomes were removed from the tableMiner et al. BMC Complementary and Alternative Medicine  (2018) 18:158 Page 7 of 12risk of bias is moderate as the study did have a controlgroup, but it is uncertain whether or not the effectscould be replicated.MassageThere were three articles found that evaluated the use ofmassage and fertility outcomes. They were all written inEnglish and evaluated female fertility outcomes. Onestudy had level II evidence, one had level III-1 evidenceand one had level IV evidence (see Table 4). All showedan improvement in outcomes. All studies had a high riskof bias as there was a lack of a real control group andnonstandardized definitions of fertility were used.NaturopathyThere was only one article found that evaluated the useof naturopathy through a nonsystematic review. It waswritten in English, and examined female fertility out-comes. While the review showed an improvement inoutcomes, it was rated as having the lowest level of evi-dence, level IV (see Tables 4 and 5). This nonsystematicreview has a high risk for bias as it was unclear how thearticles were found.OsteopathyThere was only one article found that evaluated the useof osteopathy. It was written in English, and examinedfemale fertility outcomes. While the study showed animprovement in outcomes, it was rated as having thelowest level of evidence, level IV (see Tables 4 and 5).Since the observational case study was written, per-formed and qualitatively evaluated by the sole author ofthe publication, the results have a high risk for bias.RelaxationThere were eight studies that evaluated the use of relax-ation techniques and fertility outcomes. All articles werewritten in English, and examined mental health out-comes. The studies ranged in levels of evidence fromlevel II to level IV with level III-2 and level IV havingthree articles each (see Table 4). All studies showed animprovement in mental health outcomes.YogaThere were three studies that evaluated the use of yogaand fertility outcomes. All articles were written in English,and examined mental health outcomes. All three articlesshowed an improvement in mental health outcomes withone article having level III-2 evidence while the two arti-cles had level IV evidence.DiscussionWhile numerous studies (n = 148) examined the use ofCAM in relation to female fertility, male fertility and/ormental health outcomes, the body of evidence is not evenlydistributed amongst different types of CAM methods.Most studies focused on acupuncture and Chinese HerbalMedicine. Both acupuncture and Chinese Herbal Medicineare considered Alternative Medicine Systems (AMS) bythe National Center for Complementary and AlternativeMedicine (NCCAM). However, there was much lessevidence for biological-based therapies (BBTs), manipula-tive and body based therapies (MBBTs), and mind-bodytherapies (MBT) (see Table 3). Additionally, female fertilityoutcomes were evaluated more frequently than both malefertility outcomes and mental health outcomes with theleast amount of evidence for alternative treatments (e.g.treatments outside of psychotherapy or cognitive basedtherapy) in relation to mental health outcomes.There was a large body of evidence found written inChinese for both acupuncture and Chinese HerbalMedicine (n = 44). There was a smaller body of evidencewritten in Korean (n = 3). Most of these articles hadEnglish abstracts (n = 47); in all but one case, the Englishabstract contained information that was consistent withthe results presented in the body of the paper. Thisfinding suggests that researchers could safely rely onabstracts written in English to capture the findings ofstudies written in languages that they do not read.Attention should be given to English abstracts where thearticle is also written in English as there was a certainnumber of English abstracts for English-language papers(13/101, 12.9%) which contained inaccurate informationsuch as incorrect reporting of sample size or results thatsuggested a more positive outcome than what waspresented in the discussion. If possible, researchersand clinicians assessing the evidence provided by aparticular study should verify that the abstract andfull-text are congruent.Studies that discussed acupuncture and fertility treat-ment were the most numerous and had the highestlevels of evidence, especially for female and male fertilityoutcomes. While there was some level I evidence thatshowed that acupuncture did improve female and malefertility outcomes, there is still no conclusive evidencethat the use of acupuncture in conjunction with conven-tional fertility treatment will improve fertility outcomesbecause not all studies showed improvements in out-comes and for some outcomes (e.g. mental health) therewere few studies with high levels of evidence (seeTable 6). Many treatments had lower levels of evidenceincluding homeopathy, hypnosis, massage, naturopathy,osteopathy, relaxation and yoga. In addition to the lowlevels of evidence, there were few studies surroundingthese CAM treatments. While there is a smaller body ofevidence surrounding Ayurvedic medicine and malefactor fertility outcomes, the existing evidence is promis-ing for outcomes such as improving sperm parametersMiner et al. BMC Complementary and Alternative Medicine  (2018) 18:158 Page 8 of 12in men. Additionally, the large body of mostly positiveevidence for the use of Chinese Herbal Medicine (CHM)for female factor infertility may suggest that Chineseherbs could be used as an effective supplement; however,more meta-analyses of the current randomized controltrials are needed in order to gain a more adequateunderstanding of the particular type of female factorinfertility CHM could promote.There were few studies that assessed mental healthoutcomes. While many of these studies do show animprovement in mental health outcomes, the studiesthat do exist are of low quality and have high risks forbias. This lack of assessment is problematic becauseCAM practitioners promote the use of CAM as a holis-tic treatment to improve “emotional outcomes” and pro-mote “healthy lifestyles” [19]. The evidence that existsgenerally focuses on improved measures of perceivedstress and depression, rather than employing standard-ized scales assessing quality of life during fertility treat-ment (i.e FertiQoL). Future research should considerquality of life as an outcome of CAM in order to capturehow the use of CAM may improve a person’s overallwell-being during fertility treatment.Overall, there was a lack of level I and level II studies inevaluating specific CAM therapies in relation to fertilitytreatment. This may be due to lack of funding provided toCAM researchers, and also due to the difficulty conduct-ing randomized control trials for treatments that requireholistic and individualistic approaches. For example, inacupuncture there is a debate about which type of placeboto use (i.e. sham at acupoints, sham at nonacupoints, nointervention, etc.), and doses are often individualized [20].These individual differences in study design and treatmentprotocol have led to the development of standardizedways of evaluating and performing control-trials foracupuncture (i.e. STRICTA), [21], Chinese herbal medicine[22], and herbal medicine, [23]; however, guidelines forreporting other CAM methods are less standardized. Thisresults in a variety of ways of performing and reportingtrial outcomes, which creates difficulty in comparing dataacross studies. Additionally, most articles (outside ofRCTs) suggested a possible placebo effect where individ-uals who believed the CAM treatments were helping weremore likely to have improved outcomes.The mechanisms of actions of the variety of CAM tech-niques are largely unknown. It was difficult to determinehow each specific CAM technique affected the specificoutcome measured as within various CAM methods thereare different types of interventions used. For example, inAyurvedic medicine, oils were used to attempt to clearfallopian tubes while in other cases roots were given inorder to improve pregnancy rates. Additionally, the stud-ies analyzed did not necessarily investigate the mechanismthat may have caused improvement, but were more inter-ested in the outcome itself. Future studies of CAM shouldconsider the mechanism of action of these methods toproduce better quality of evidence.Strengths and limitationsA scoping review of the literature was performed toevaluate twelve different CAM methods. The review wasnot confined to the English literature but rather includedarticles that were written in four different languages.Although the individual study results were not statisti-cally combined, the collating of various outcomes allowsfor a determination of which methods may improve fertilityTable 6 Overall Summary of CAM OutcomesType of CAM Female Factor Male Factor May reduce stressAcupuncture ? ? ?Ayurveda X ? XChinese Herbal Medicine ? X XHerbal Medicine X X XChiropractic Medicine X X XMassage X X ✓Osteopathy X X XHomeopathy X X XNaturopathy X X XHypnosis X X XYoga X X ✓Key Level of EvidenceX There is a lack of good scientific evidence that this CAM technique improves the outcome.? Evidence is conflicting. While some studies show that there is an improved outcome, others show no change in outcome.✓ There is evidence that this CAM technique may improve the outcome.Miner et al. BMC Complementary and Alternative Medicine  (2018) 18:158 Page 9 of 12outcomes and/or need more statistical evidence. The articlealso evaluates multiple CAM methods, some of which werenot previously systematically reviewed (e.g. hypnosis).This scoping review was only performed on publishedstudies. Therefore, we may have a publication bias towardspositive results, suggesting that the results of our scopingreview be interpreted with caution. There may also havebeen articles that our English search terms missed thatwere not evaluated. Additionally, we were not able to havemultiple authors read the individual articles to determinethe accuracy of the levels of evidence as we only had oneauthor who could read and interpret the Chinese articles.However, author one did confirm that the type of studywritten by each author correctly matched the level ofevidence. When the type of study was unclear, authorsconferred about the type of study and the level of evidencewas interpreted conservatively. Since there was a broadvariety of fertility outcomes identified, sometimes withconflicting definitions, the review could not both assessthe entire body of evidence and the individual fertility out-comes identified by every article.Future research directionsThis scoping review has highlighted the lack of strongevidence for CAM methods to improve fertility outcomes.However, this lack of evidence should not mean that nofuture studies be performed on CAM and fertility out-comes. We suggest that future research should look to-wards the most promising areas of CAM (i.e. Ayurveda formale factor infertility, Chinese Herbal Medicine for femalefertility and relaxation techniques for promoting mentalhealth during fertility treatment), and subsequently, imple-ment studies with more purposeful and valid researchdesigns in order to form conclusions that are based onhigher levels of evidence. In order to discourage publicationbias, publishers should also be willing to publish evidencethat shows negative or no effects as this is importantevidence in determining the effectiveness of CAM. In otherwords, scientists and practitioners of CAM should moresystematically research CAM therapies that have alreadybeen proven to be effective (e.g. relaxation techniques forimproving mental health outcomes). Additionally, morestandard definitions should be applied to articles assessingfertility outcomes so that results are statistically comparableacross studies. For example, we suggest that measurementsof improvement in female fertility outcomes should followthe BESST (Birth Emphasizing a Successful Singleton atTerm) endpoints, which define assisted reproductive suc-cess based on live full-term singleton births [24].ConclusionsThere is a lack of evidence for the use of CAM to improvefertility outcomes as most techniques are not evaluated bystudies that produce high levels of evidence (i.e. level Iand level II). Additionally, across fertility outcomes andCAM techniques, studies do not always show a significantimprovement in fertility outcomes. Rather, the overall evi-dence points to CAM having no significant effect on thefertility outcome of interest. Although there has been anincrease in the use of CAM use over time [25], despite thefact that this increase is not necessarily supported by em-pirical evidence. However, some individuals may chooseto use CAM methods to feel more in control of theirfertility treatment [5]. This potential feeling of empower-ment, however, is not adequately captured by the existingstudies involving CAM and mental health as most of themental health studies found were of poor quality, and didnot measure the quality of life of the participants or theirfeelings of empowerment. Thus, there remain questions asto whether CAM does improve fertility patients’ quality oflife and/or their feelings of control over treatment.Fertility physicians should inform their patients aboutthe lack of standardized empirical evidence for all CAMmethods with the realization that patients may choose toengage in CAM despite the lack of evidence. Since nomethods were found to negatively impact fertility ormental health outcomes, there should be less concernwith patients engaging in CAM that may hinder theirfertility outcomes. However, physicians and patientsshould consider the evidence base for treatments thatclaim to significantly improve fertility and/or mentalhealth in order to manage expectations regarding theirefficacy. It should also be acknowledged that patientsmay choose to undergo a particular CAM procedurebecause it helps them feel more empowered in theirtreatment. The widespread use of CAM among fertilitypatients should provide an impetus for the design andimplementation of high-quality studies of their effects.Endnotes1Rayner, Willis and Burgess [4] do not provide a def-inition of how religious intervention and spiritualhealing differ. We have listed them as separate typesof CAM to reflect the findings that Rayner, Willis andBurgess [4] present.Additional filesAdditional file 1: Definitions of CAM Methods-Definition of CAM methodsanalyzed. (DOCX 14 kb)Additional file 2: CAM Review Sheet-Copy of the Google review sheetused to record the information from the articles. (PDF 90 kb)AbbreviationAMS: Alternative medicine systems; BBT: Biological-based therapies;CAM: Complementary and alternative medicine; CDC: Center for DiseaseControl; CHM: Chinese Herbal Medicine; IVF: In vitro fertilization;MBBT: Manipulative and body-based therapiesMBTMind-body therapies;NCCAM: National Center for Complementary and Alternative Medicine;NHMRC: National Health and Medical Research CouncilMiner et al. BMC Complementary and Alternative Medicine  (2018) 18:158 Page 10 of 12AcknowledgmentsThe authors would like to thank Angie Lee for her work on translating theKorean articles.FundingCanadian Institutes for Health Research Team Grant: CIHR Grant #TE1–138296.This work was supported by CIHR Grant #TE1–138296.Availability of data and materialsThe compilation of articles analyzed and the document showing how eacharticle was analyzed are available through Googledrive, http://bit.ly/2AaGD0RAuthors’ contributionsSAM— Performed search of articles based on keywords for some CAM methods,collected and analyzed articles, created the database for inputting results, oversawarticle analysis, compiled results, primary author of the manuscript, approved finalmanuscript, submitted article for publication. SR— Performed search of articlesbased on keywords for some CAM methods, collected and analyzed articles,contributed to the creation of the database, contributed to manuscript writing,approved final manuscript. YJZ—Collected and analyzed articles, translated articleswritten in Chinese, made minor edits to the manuscript, approved finalmanuscript. KK—Performed search of articles based on keywords forsome CAM methods, collected and analyzed articles, made minor editsto the manuscript, approved final manuscript. VG— Collected andanalyzed articles, made minor edits to the manuscript, approved finalmanuscript. SCR—Created search terms and selected databases tosearch, performed first search, approved final manuscript. PZ—Oversawresearch process, approved research design, gave feedback regardinginterpretation of results, made significant edits to the manuscript,approved final manuscript, corresponding author.Author informationSkye A. Miner is a PhD student in Sociology at McGill University. As part of theCIHR Fertility Health Lab (PI: Dr. Phyllis Zelkowitz), Skye is working on creatingevidence-based content on fertility treatments for the use in a mobile healthapplication for fertility patients. Her other research interests includeunderstanding the ethical and social issues surrounding egg donation.Ethics approval and consent to participateNot applicable.Competing interestsThe authors declare that they have no competing interests.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.Author details1Department of Sociology, McGill University, Room 712, Leacock Building,855 Sherbrooke Street West, Montreal, QC H3A 2T7, Canada. 2Department ofPsychiatry, Jewish General Hospital, 4333 Chemin de la Cote-Ste-Catherine,Room 223, Montreal, QC H3T 1E4, Canada. 3Department of Dentistry, McGillUniversity, 2001 McGill College Ave, Montreal, QC H3A 1G1, Canada.4Department of Medicine, University of British Columbia Medical School,2275 Laurel Street, 10th Floor, British Columbia, BC V5Z 1M9, Canada. 5LadyDavis Institute, 3755 Chemin de la Cote-Ste-Catherine, Montreal, QC H3T 1E2,Canada. 6Department of Psychiatry, McGill University, Ludmer Research andTraining Building, 1033 Pine Ave. West., Montreal, QC H3A 1A1, Canada.Received: 27 November 2017 Accepted: 30 April 2018References1. Dhillon RK, McLernon DJ, Smith PP, Fishel S, Dowell K, Deeks JJ,Bhattacharya S, Coomarasamy A. Predicting the chance of live birth forwomen undergoing IVF: a novel pretreatment counselling tool. HumanReproduction 2016; 31:84–92.2. Aelion A, Barbieri E, Shastri S, Grill E, Chung P, Rosenwaks Z. The use ofcomplementary medical therapies (CMT) in infertility patients. Fertil Steril.2009;92:S33–4.3. Coulson C, Jenkins J. Complementary and alternative medicineutilisation in NHS and private clinic settings: a United Kingdom surveyof 400 infertility patients. Journal of Experimental and Clinical AssistedReproduction. 2005;24. Rayner J, Willis K, Burgess R. Women's use of complementary andalternative medicine for fertiity enhancement: a review of the literature. TheJournal of Alternative and Complementary Medicine. 2011;17:685–90.5. Read SC, Carrier M-E, Whitley R, Gold I, Tulandi T, Zelkowitz P.Complementary and alternative medicine use in infertility: cultural andreligious influences in a multicultural Canadian setting. J AlternComplement Med. 2014;20:686–92.6. Perry TE, Hirshfeld-Cytron J. Role of complementary and alternativemedicine to achieve fertility in uninsured patients. Obstetrical &gynecological survey. 2013;68:305–11.7. Ried K, Alfred A. Quality of life, coping strategies and support needs ofwomen seeking traditional Chinese medicine for infertility and viablepregnancy in Australia: a mixed methods approach. BMC WomensHealth. 2013;138. Barnes P, Bloom B, Nahin R. Complementary and alternative medicine useamong adults and children, vol. 12. CDC National Health Statistics: UnitedStates; 2008.9. Rayner J, McLachlan H, Forster D, Cramer R. Australian women's use ofcomplementary and alternative medicines to enhance fertility: exploring theexperiences of women and practitioners. BMC Complement Altern Med.2009;9:52.10. Clark NA, Will M, Moravek MB, Fisseha S. A systematic review of theevidence for complementary and alternative medicine in infertility. Int JGynaecol Obstet. 2013;122:202–6.11. Charaf S, Wardle JL, Sibbritt DW, Lal S, Callaway LK. Women's use of herbaland alternative medicines for preconception care. Australia and NewZealand Journal of Obstetrics and Gynaecology. 2015;55:222–6.12. Ghazeeri GS, Awwad JT, Alameddine M, Younes ZM, Naja F. Prevalence anddeterminants of complementary and alternative medicine use amonginfertile patients in Lebanon: a cross sectional study. BMC ComplementAltern Med. 2012;12:129.13. Colquhoun HL, Levac D, O'Brien KK, Straus S, Tricco AC, Perrier L, Kastner M,Moher D. Scoping reviews: time for clarity in definition, methods, andreporting. J Clin Epidemiol. 2014;67:1291–4.14. Arksey H, O'Malley L. Scoping studies: towards a methodological framework.Int J Soc Res Methodol. 2005;8:19–32.15. Levac D, Colquhoun H, O'Brien KK. Scoping studies: advancing themethodology. Implement Sci. 2010;5:69.16. Twigt JM, Bolhuis MEC, Steegers EAP, Hammiche F, van Inzen WG, LavenJSE, Steegers-Theunissen RPM. The preconception diet is associated withthe chance of ongoing pregnancy in women undergoing IVF/ICSItreatment. Hum Reprod. 2012;27:2526–31.17. NHMRC. NHMRC levels of evidence and grades for recommendation fordevelopers of guidelines. National Health and Medical Research Council:Australia; 2009.18. Merlin T, Weston A, Tooher R. Extending an evidence hierarchy to includetopics other than treatment: revising the Australian 'levels of evidence'. BMCMed Res Methodol. 2009;9:34.19. O'Reilly E, Sevigny M, Sabarre KA, Phillips KP. Perspectives of complementaryand alternative medicine (CAM) practitioners in the support and treatmentof infertility. BMC Complement Altern Med. 2014;14:394.20. Manheimer E. Selecting a control for in vitro fertilization andacupuncture randomized controlled trials (RCTs): how sham controlsmay unnecessarily complicate the RCT evidence base. Fertility Sterility.2011;95:2456–61.21. MacPherson H, Altman DG, Hammerschlag R, Youping L, Taixiang W, WhiteA, Moher D. Revised standards for reporting interventions in clinical trials ofacupuncture (STRICTA): extending the CONSORT statement. MedicalAcupuncture. 2010;22:167–80.22. Cheng CW, Wu TX, Shang HC, Li YP, Altman DG, Moher D, Bian ZX.CONSORT extension for Chinese herbal medicine formulas 2017:recommendations, explanation, and elaboration. Ann Intern Med. 2017;23. Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J, Bombardier C. Reportingrandomized, controlled trials of herbal interventions: an elaboratedCONSORT statement. Ann Intern Med. 2006;144:364–7.24. Min JK, Breheny SA, MacLachlan V, Healy DL. What is the most relevantstandard of success in assisted reproduction? The singleton, term gestation,Miner et al. BMC Complementary and Alternative Medicine  (2018) 18:158 Page 11 of 12live birth rate per cycle initiated: the BESST endpoint for assistedreproduction. Hum Reprod. 2004;19:3–7.25. Smith CA, de Lacey S, Chapman M, Ratcliffe J, Norman RJ, Johnson N, SacksG, Lyttleton J, Boothroyd C. Acupuncture to improve live birth rates forwomen undergoing in vitro fertilization: a protocol for a randomizedcontrolled trial. Trials. 2012;13:60.Miner et al. BMC Complementary and Alternative Medicine  (2018) 18:158 Page 12 of 12

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