Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility (Review) Bosteels J, Weyers S, Kasius J, Broekmans FJ, Mol BWJ, D’Hooghe TM This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2015, Issue 11 http://www.thecochranelibrary.com For Preview Only Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 4 BACKGROUND .................................... 7 OBJECTIVES ..................................... 9 METHODS ...................................... 9 RESULTS....................................... 13 Figure1. ..................................... 15 Figure2. ..................................... 17 Figure3. ..................................... 18 Figure4. ..................................... 27 Figure5. ..................................... 28 Figure6. ..................................... 30 ADDITIONALSUMMARYOFFINDINGS . 30 DISCUSSION ..................................... 33 Figure7. ..................................... 34 AUTHORS’CONCLUSIONS . 36 ACKNOWLEDGEMENTS . 36 REFERENCES ..................................... 37 CHARACTERISTICSOFSTUDIES . 42 DATAANDANALYSES. 82 Analysis 1.1. Comparison 1 Inserted device vs no treatment, Outcome 1 Live birth. 85 Analysis 1.2. Comparison 1 Inserted device vs no treatment, Outcome 2 Clinical pregnancy. 85 Analysis 1.3. Comparison 1 Inserted device vs no treatment, Outcome 3 Miscarriage. 86 Analysis 1.4. Comparison 1 Inserted device vs no treatment, Outcome 4 Presence of intrauterine adhesions at second-look hysteroscopy................................... 87 Analysis 2.1. Comparison 2 Inserted device vs another inserted device, Outcome 1 Presence of intrauterine adhesions at second-lookhysteroscopy. 87 Analysis 3.1. Comparison 3 Hormonal treatment vs no treatment or placebo, Outcome 1 Live birth. 88 Analysis 3.2. Comparison 3 Hormonal treatment vs no treatment or placebo, Outcome 2 Clinical pregnancy. 89 Analysis 3.3. Comparison 3 Hormonal treatment vs no treatment or placebo, Outcome 3 Miscarriage. 90 Analysis 3.4. Comparison 3 Hormonal treatment vs no treatment or placebo, Outcome 4 Presence of intrauterine adhesions atsecond-lookhysteroscopy.. 91 Analysis 4.1. Comparison 4 Gel vs no treatment, Outcome 1 Clinical pregnancy. 92 Analysis 4.2. Comparison 4 Gel vs no treatment, Outcome 2 Presence of intrauterine adhesions at second-look hysteroscopy................................... 93 Analysis 4.3. Comparison 4 Gel vs no treatment, Outcome 3 Mean adhesion scores at 12 weeks. 94 Analysis 4.4. Comparison 4 Gel vs no treatment, Outcome 4 Mild adhesions at second-look hysteroscopy. 95 Analysis 4.5. Comparison 4 Gel vs no treatment, Outcome 5 Moderate or severe adhesions at second-look hysteroscopy. 96 Analysis 6.1. Comparison 6 Graft vs no graft, Outcome 1 Live birth.................. 97 Analysis 6.2. Comparison 6 Graft vs no graft, Outcome 2 Clinical pregnancy. 97 Analysis 6.3. Comparison 6 Graft vs no graft, Outcome 3 Miscarriage. ................ 98 Analysis 7.1. Comparison 7 Any therapy vs no treatment or placebo, Outcome 1 Live birth. 98 Analysis 7.2. ComparisonFor 7 Any therapyPreview vs no treatment or placebo, Outcome 2Only Clinical pregnancy. 99 Analysis 7.3. Comparison 7 Any therapy vs no treatment or placebo, Outcome 3 Miscarriage. 100 Analysis 7.4. Comparison 7 Any therapy vs no treatment or placebo, Outcome 4 Presence of intrauterine adhesions at second-lookhysteroscopy. 101 Analysis 7.5. Comparison 7 Any therapy vs no treatment or placebo, Outcome 5 Mean adhesion scores. 102 Analysis 7.6. Comparison 7 Any therapy vs no treatment or placebo, Outcome 6 Mild adhesions at second-look hysteroscopy................................... 103 Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility (Review) i Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Analysis 7.7. Comparison 7 Any therapy vs no treatment or placebo, Outcome 7 Moderate or severe adhesions at second- lookhysteroscopy. 104 Analysis 8.1. Comparison 8 Any therapy vs any other therapy, Outcome 1 Presence of intrauterine adhesions at second- lookhysteroscopy. 105 APPENDICES ..................................... 105 CONTRIBUTIONSOFAUTHORS . 112 DECLARATIONSOFINTEREST . 112 SOURCESOFSUPPORT . 112 DIFFERENCES BETWEEN PROTOCOL AND REVIEW . .... 113 For Preview Only Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility (Review) ii Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. [Intervention Review] Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility Jan Bosteels1, Steven Weyers2, Jenneke Kasius3, Frank J Broekmans3, Ben Willem J Mol4, Thomas M D’Hooghe5 1Belgian Branch of the Dutch Cochrane Centre, Leuven, Belgium. 2Obstetrics and Gynaecology, University Hospital Ghent, Ghent, Belgium. 3Department of Reproductive Medicine and Gynecology, University Medical Center, Utrecht, Netherlands. 4The Robinson Institute, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, Australia. 5Leuven University Fertility Centre, University Hospital Gasthuisberg, Leuven, Belgium Contact address: Jan Bosteels, Belgian Branch of the Dutch Cochrane Centre, Kapucijnenvoer 33 blok J bus 7001, 3000 Leuven, Leuven, Belgium. [email protected]. [email protected]. Editorial group: Cochrane Gynaecology and Fertility Group. Publication status and date: New, published in Issue 11, 2015. Review content assessed as up-to-date: 1 March 2015. Citation: Bosteels J, Weyers S, Kasius J, Broekmans FJ, Mol BWJ, D’Hooghe TM. Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility. Cochrane Database of Systematic Reviews 2015, Issue 11. Art. No.: CD011110. DOI: 10.1002/14651858.CD011110.pub2. Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ABSTRACT Background Limited observational evidence suggests potential benefit for subfertile women undergoing operative hysteroscopy with several anti- adhesion therapies (e.g. insertion of an intrauterine device (IUD) or balloon, hormonal treatment, barrier gels or human amniotic membrane grafting) to decrease intrauterine adhesions (IUAs). Objectives To assess the effectiveness of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility. Search methods We searched the following databases from inception to March 2015: the Cochrane Menstrual Disorders and Subfertility Specialised Register, the Cochrane Central Register of Controlled Trials (2015, Issue 2), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and other electronic sources of trials, including trial registers, sources of unpublished literature and reference lists. We handsearched The Journal of Minimally Invasive Gynecology, and we contacted experts in the field. Selection criteria Randomised comparisonsFor of anti-adhesion Preview therapies versus placebo, no treatment or anyOnly other anti-adhesion therapy following operative hysteroscopy in subfertile women. The primary outcome was live birth or ongoing pregnancy. Secondary outcomes were clinical pregnancy, miscarriage and IUAs present at second look, along with their mean adhesion scores or severity. Data collection and analysis Two review authors independently selected studies, assessed risk of bias, extracted data and evaluated quality of the evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) method. Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility (Review) 1 Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Main results We included 11 randomised studies on use of an inserted device versus no treatment (two studies; 84 women) or another inserted device (one study; 162 women), hormonal treatment versus no treatment or placebo (two studies; 131 women), gel versus no treatment (five studies; 383 women) and graft versus no graft (one study; 43 women). The total number of women randomly assigned was 924, but data on only 803 participants were available for analysis. The proportion of subfertile women varied from 0% (one study; 41 women), to less than 50% (six studies; 487 women), to 100% (one study; 43 women); the proportion was unknown in three studies (232 women). Most studies (9/11) were at high risk of bias with respect to one or more methodological criteria. We found no evidence of differences between anti-adhesion therapy and no treatment or placebo with respect to live birth rates (odds ratio (OR) 0.99, 95% confidence interval (CI) 0.46 to 2.13, P value = 0.98, three studies, 150 women; low-quality evidence) and no statistical heterogeneity (Chi2 = 0.14, df = 2 (P value = 0.93), I2 = 0%). Anti-adhesion therapy was associated with fewer IUAs at any second-look hysteroscopy when compared with no treatment or placebo (OR 0.36, 95% CI 0.20 to 0.64, P value = 0.0005, seven studies, 528 women; very low-quality evidence). We found no statistical