Ben Willem J. Mol

C Farquhar

E Somigliana

EA Pritts

Frank J. Broekmans

Jan Bosteels

Jenneke Kasius

ML Casini

R Hart

Steven Weyers

T Pérez-Medina

Thomas M. D’Hooghe

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REVIEWARTICLETreating suspected uterine cavity abnormalities by hysteroscopyto improve reproductive outcome in women with unexplainedinfertility or prior to IUI, IVF, or ICSIJan Bosteels & Jenneke Kasius & Steven Weyers &Frank J. Broekmans & Ben Willem J. Mol &Thomas M. D’HoogheReceived: 5 March 2013 /Accepted: 23 April 2013 /Published online: 7 May 2013# The Author(s) 2013. This article is published with open access at Springerlink.comAbstract Endometrial polyps, submucous fibroids, uterinesepta, and intrauterine adhesions can be found by ultrasound(US), HSG, hysteroscopy, or any combined in 10–15 % ofinfertile women. Observational studies suggest a better re-productive outcome when these anomalies are removed byoperative hysteroscopy. The current Cochrane review as-sesses the effectiveness of hysteroscopy for treating thesesuspected anomalies in women with otherwise unexplainedinfertility or prior to intrauterine insemination, in vitro fer-tilization, or intracytoplasmic sperm injection.Keywords Hysteroscopy . Subfertility . Uterine cavityabnormalities . Randomized controlled trialBackgroundEndometrial polyps, submucous fibroids, uterine septa, andintrauterine adhesions can be found by ultrasound (US),HSG, hysteroscopy, or any combined in 10–15 % of infertilewomen. Observational studies suggest a better reproductiveoutcome, when these anomalies are removed by operativehysteroscopy. The current Cochrane review assesses theeffectiveness of hysteroscopy for treating these suspectedanomalies in women with otherwise unexplained infertilityor prior to intrauterine insemination (IUI), in vitro fertilization(IVF), or intracytoplasmic sperm injection (ICSI) [1].MethodsWe searched electronic databases including CENTRAL (TheCochrane Library 2012, Issue 7), MEDLINE (1950 to27 October 2012), and EMBASE (1974 to 27 October 2012)conference proceedings from the American Society for Repro-ductive Medicine through hand searching (from 2008 to 30October 2012) and reference lists of retrieved articles. Eligiblereports were parallel-design randomized trials (RCTs), compar-ing operative hysteroscopy with a control intervention in wom-en with suspected uterine cavity abnormalities and otherwiseunexplained infertility or undergoing IUI, IVF, or ICSI. Theprimary outcomes were live birth and hysteroscopy complica-tion rates. Secondary outcomes were ongoing or clinical preg-nancy and miscarriage rates. We expressed the dichotomousoutcome measures as Mantel–Haenszel odds ratios (ORs) with95 % confidence intervals (CIs) using a fixed-effect model.ResultsTrial qualityOnly two studies met the eligibility criteria for inclusion in thereview. One study included 94 women with otherwiseunexplained infertility and not more than two submucousJ. Bosteels (*)Imelda Hospital, Bonheiden, Belgiume-mail: jan.bosteels@hotmail.comJ. Kasius : F. J. BroekmansUniversity Medical Centre, Utrecht, the NetherlandsS. WeyersUniversity Hospital Ghent, Ghent, BelgiumB. W. J. MolAcademic Medical Centre University of Amsterdam, Amsterdam,the NetherlandsT. M. D’HoogheLeuven University Fertility Centre, University HospitalGasthuisberg, Leuven, BelgiumGynecol Surg (2013) 10:165–167DOI 10.1007/s10397-013-0798-0fibroids or one submucous fibroid combined with one intra-mural fibroid, all smaller than 40 mm [2]. The second trial [5]assessed the effectiveness of the hysteroscopic removal ofendometrial polyps with a mean diameter of 16 mm diagnosedby Doppler US in 215 women bound to undergo gonadotropintreatment and IUI for unexplained, male or female factorinfertility for at least 2 years. Both trials used computer-generated random number tables; in only one allocation con-cealment was adequate [5]. Blinding of patients, personnel,and outcome assessors was not assessed because these itemsare less relevant in the setting of a surgical trial with unequiv-ocal outcomes and a long follow-up period. Both studies wereat low risk for attrition bias but had some potential for selectiveoutcome reporting; no data for live birth rates were availabledespite long follow up periods of 86 [2] and 50 months [5].Wecould not do a formal assessment of publication bias, sinceonly two RCTs were included in the current review.Primary outcomes: live birth and hysteroscopy complicationratesWe retrieved no data for all primary outcomes.Secondary outcomesClinical pregnancy ratesRemoval of not more than two submucous fibroids or onesubmucous fibroid combined with one intramural fibroid, allsmaller than 40mm, in women with unexplained infertility forat least 1 year tends to increase the odds of clinical pregnancycompared to regular fertility-oriented intercourse. The differ-ences between both comparison groups fail to reach statisticalsignificance (OR 2.4, 95 % CI 0.97–6.2) (Fig. 1). Our resultsare not in accordance with the calculation of the authors in theprimary study report; they reported statistically significantdifferences between both comparison groups both in womenwith not more than two submucous fibroids only or onesubmucous combined with one intramural fibroid [2].The hysteroscopic removal of endometrial polyps with amean size of 16 mm increases the odds of clinical pregnancyprior to IUI for unexplained male or female factor infertilityfor at least 2 years, compared to diagnostic hysteroscopyand polyp biopsy only (OR 4.4, 95 % CI 2.5–8.0).Miscarriage ratesThere is no evidence for differences in the miscarriage ratesafter the hysteroscopic removal of not more than twosubmucous fibroids or one submucous fibroid with oneintramural fibroid in women with otherwise unexplainedinfertility for at least 1 year, compared to regular fertility-oriented intercourse (OR 1.5, 95 % CI 0.47–5.00).ConclusionsThe only randomized study published in the literature on thehysteroscopic removal of fibroids in infertile women hasclaimed statistically significant differences in the clinicalStudy or Subgroup1.1.1 Removal of submucous fibroids only vs regular fertility-oriented intercourseCasini 2006Subtotal (95% CI)Total eventsHeterogeneity: Not applicableTest for overall effect: Z = 1.18 (P = 0.24)1.1.2 Removal of mixed submucous-intramural fibroids vs regular fertility-oriented intercourseCasini 2006Subtotal (95% CI)Total eventsHeterogeneity: Not applicableTest for overall effect: Z = 1.53 (P = 0.13)Total (95% CI)Total eventsHeterogeneity: Chi² = 0.22, df = 1 (P = 0.64); I² = 0%Test for overall effect: Z = 1.89 (P = 0.06)Test for subgroup differences: Chi² = 0.22, df = 1 (P = 0.64), I² = 0%Events13138821Total3030222252Events66339Total2222202042Weight66.2%66.2%33.8%33.8%100.0%M-H, Fixed, 95% CI2.04 [0.62, 6.66]2.04 [0.62, 6.66]3.24 [0.72, 14.57]3.24 [0.72, 14.57]2.44 [0.97, 6.17]Operative hysteroscopy Control Odds Ratio Odds RatioM-H, Fixed, 95% CI0.01 0.1 1 10 100Favours intercourse Favours myomectomyFig. 1 Forest plot of comparison: 1 Hysteroscopic myomectomy vs. regular fertility-oriented intercourse in women with unexplained subfertility and notmore than two submucous fibroids or one submucous fibroid combinedwith one intramural fibroid, all smaller than 40mm.Outcome: 1.1Clinical pregnancy166 Gynecol Surg (2013) 10:165–167pregnancy rates between both comparison groups. Our ownrecalculation of the available data fails to demonstrate sta-tistically significant differences. This statistical error raisesconcerns about the validity of the published primary data.Moreover, we judged the overall study quality study to be verylow. This has implications for clinical research; additionalRCTs studying the effectiveness of hysteroscopic myomecto-my in infertile women are needed. The implications for dailypractice are more controversial. The gynecological professionwidely accepts that submucosal and intramural fibroids inter-fere with fertility in decreasing order of importance based onthe results and conclusions of a large systematic literaturereview with a meta-analysis of observational studies [6, 7].While conservative, medical, and surgical treatment are allconsidered as being appropriate for treating symptomatic fi-broids, myomectomy seems the only reasonable treatmentoption for women who wish to become pregnant. Womentreated by hysteroscopic myomectomy for submucosal fibroidsmight have similar reproductive outcomes as infertile womenwith normal uterine cavities [8]. According to one prospectivestudy, the surgical removal of large intramural fibroids inwomen with otherwise unexplained infertility prior to IVFtreatment might increase the likelihood of a successful repro-ductive outcome [4]. Our critical appraisal of the current evi-dence supports the conclusion published by others in the recentpast; at the present, there is still evidence of uncertainty on theeffectiveness of removing fibroids in infertile women [3].The hysteroscopic removal of endometrial polyps inwomen bound to undergo IUI for unexplained, male, orfemale factor infertility for at least 24 months increases theodds of clinical pregnancy compared to diagnostic hyster-oscopy and biopsy only. The level of evidence of this singlestudy was graded as high.More well-designed pragmatic RCTs are needed to assessthe effectiveness of the hysteroscopic removal of endometrialpolyps, submucous fibroids, uterine septa, or intrauterine ad-hesions in women with otherwise unexplained infertility orprior to IUI, ICSI, or IVF, preferably measuring live birth andadverse events as primary outcomes. The effects of the num-ber, size, and location of the intrauterine pathology as well asthe relationship between the timing of the hysteroscopy andsubsequent fertility treatment should be addressed bypredefined and sensible subgroup analyses.Open Access This article is distributed under the terms of the CreativeCommons Attribution License which permits any use, distribution, andreproduction in any medium, provided the original author(s) and thesource are credited.References1. Bosteels J, Kasius J, Weyers S, Broekmans FJ, Mol BWJ,D’Hooghe TM (2013) Hysteroscopy for treating subfertility associ-ated with suspected major uterine cavity abnormalities. CochraneDatabase of Systematic Reviews Issue 1. Art. No.:CD0094612. Casini ML, Rossi F, Agostini R, Unfer V (2006) Effects of theposition of fibroids on fertility. Gynecol Endocrinol 22(2):106–93. Farquhar C (2009) Do uterine fibroids cause infertility and shouldthey be removed to increase fertility? British Med J 338:b1264. Hart R, Khalaf Y, Yeong CT, Seed P, Taylor A, Braude P (2001)Prospective controlled study of the effects of uterine fibroids on theoutcome of assisted conception treatment. HumReprod 16:2411–24175. Pérez-Medina T, Bajo-Arenas J, Salazar F, Redondo T, Sanfrutos L,Alvarez P et al (2005) Endometrial polyps and their implication inthe pregnancy rates of patients undergoing intrauterine insemina-tion: a prospective, randomized study. Hum Reprod 20(6):1632–56. Pritts EA (2001) Fibroids and infertility: a systematic review of theevidence. Obstet Gynecol Surv 56:483–917. Pritts EA, Parker WH, Olive DL (2009) Fibroids and infertility: anupdated systematic review of the evidence. Fertil Steril 91:1215–238. Somigliana E, Vercellini P, Daguati R, Pasin R, De Giorgi O,Crosignani PG (2007) Fibroids and female reproduction: a criticalanalysis of the evidence. Hum Reprod Updat 13:465–76Gynecol Surg (2013) 10:165–167 167

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Treating suspected uterine cavity abnormalities by hysteroscopy to improve reproductive outcome in women with unexplained infertility or prior to IUI, IVF, or ICSI

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Treating suspected uterine cavity abnormalities by hysteroscopy to improve reproductive outcome in women with unexplained infertility or prior to IUI, IVF, or ICSI

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