TY - JOUR
T1 - Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility
AU - Bosteels, Jan
AU - Weyers, Steven
AU - D'Hooghe, Thomas M.
AU - Torrance, Helen
AU - Broekmans, Frank J.
AU - Chua, Su Jen
AU - Mol, Ben Willem J.
N1 - Funding Information:
Computer generated randomisation list. 2. Can you describe the method that you used to make the surgeons unaware of the treatment allocation? Did you use sequentially numbered opaque sealed envelopes? Did you phone to a central randomisation trial office? Other method? Sequentially numbered opaque sealed envelops. 3. Were the outcome assessor who evaluated the HSG or did the second look hysteroscopy in case of abnormal HSG the same surgeons that performed the septum resection? Yes, they were the same surgeons that performed the septum resection. 4. Do you have any baseline characteristics data of both comparison groups e.g. mean age of women in either group, length of septum, etc…? Unfortunately I am unable to retrieve these data. The study was completed almost 30 years ago. 5. Two women had their IUD removed early in the intervention group and in 1 woman in the control group a balloon catheter was left in situ for 24 hours because of bleeding. What was the outcome regarding normality of the cavity in these 3 women? See reply to point 4. 6. Is it correct that this is a single centre study conducted at 1.a. Clinica Ostetrica e Ginecologica ”L. Mangiagalli” dell Università di Milano? Yes, it is correct. 7. Were the study participants all women of proven fertility or did the study also include women with infertility with two miscarriages? Do you have data on the proportions of infertile women in both comparison groups? The study participants were all fertile. 8. Was there IRB/Ethical committee approval for this clinical trial? Yes, the study was approved by the Council of the Institute of the First Obstetrics and Gynecologic Department of the Università degli Studi, Milan. 9. Was the study funded by a research grant or was it an investigator-driven noncommercial study? It was an investigator-driven non-commercial study. 10. Was a power calculation done before the conduct of the study? It was a pilot study and no pre-planned power calculation was performed. Thank you for your interest in our study and best wishes for your work. Paolo Vercellini Department of Clinical Sciences and Community Health, Università degli Studi di Milano and Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122 Milan, Italy.
Funding Information:
Parallel-group randomised controlled trial. Single centre, Department of Minimally Invasive Gynecologic Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China Protocol approved by IRB: yes. Study protocol registered as NCT02496052 in ClinicalTrials.gov Statistical power calculation reported; sample size determined based on findings of a pilot study External funding: supported by grants from Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (Grant No. ZYLX201406), Capital Health Research and Development of Special (Grant No. 2014-1-2112) and National Science and Technology Infrastructure Program (Grant No. 2014BAI05B03) Conflicts of interest reported: authors had no conflicts of interest Number recruited: 88 women. Number randomly assigned: 88 women. Number excluded: 2 women; 1 per treatment arm; reason: protocol violation Number lost to follow-up: 6 women. Intervention group: 3 women lost to follow-up; 2 not undergo second hysteroscopy and 1 had incomplete data collection for defaulted follow-up. Control group: 3 women lost to follow-up; 3 did not undergo second hysteroscopy Number analysed: 80 women. Consecutive series of women who fulfilled the recruitment criteria were invited to participate in the study until the enrolment target was met. All women had severe IUAs confirmed by outpatient diagnostic hysteroscopy and AFS IUA score ≥ 8 Inclusion criteria: • age < 40 years; • hypomenorrhoea or amenorrhoea; • infertility or spontaneous abortion (≥ 1); • baseline AFS IUA score ≥ 8. Exclusion criteria: • premature menopause; • presence of other intrauterine lesions (e.g. polyps, myoma or septa); • severe intercurrent disease (e.g. systemic disease, coagulation disorders or severe disease of the kidneys or liver). Precise proportion of women with infertility not reported in this mixed population of women with infertility or ≥ 1 spontaneous miscarriage Study duration: 12 months. Mean age (± SD) in intervention group: 29.6 (± 3.7) years. Mean age (± SD) in control group: 30.8 (± 3.7) years.
PY - 2017/11/27
Y1 - 2017/11/27
N2 - Background: Observational evidence suggests a potential benefit with several anti-adhesion therapies in women undergoing operative hysteroscopy (e.g. insertion of an intrauterine device or balloon, hormonal treatment, barrier gels or human amniotic membrane grafting) for decreasing 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 June 2017: the Cochrane Gynaecology and Fertility Group Specialised Register; the Cochrane Central Register of Studies (CRSO); MEDLINE; Embase; 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. We also searched reference lists of appropriate papers. Selection criteria: Randomised controlled trials (RCTs) of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy following operative hysteroscopy in subfertile women. The primary outcome was live birth. Secondary outcomes were clinical pregnancy, miscarriage and IUAs present at second-look hysteroscopy, along with mean adhesion scores and severity of IUAs. Data collection and analysis: Two review authors independently selected studies, assessed risk of bias, extracted data and evaluated quality of evidence using the GRADE method. Main results: The overall quality of the evidence was low to very low. The main limitations were serious risk of bias related to blinding of participants and personnel, indirectness and imprecision. We identified 16 RCTs comparing a device versus no treatment (two studies; 90 women), hormonal treatment versus no treatment or placebo (two studies; 136 women), device combined with hormonal treatment versus no treatment (one study; 20 women), barrier gel versus no treatment (five studies; 464 women), device with graft versus device without graft (three studies; 190 women), one type of device versus another device (one study; 201 women), gel combined with hormonal treatment and antibiotics versus hormonal treatment with antibiotics (one study; 52 women) and device combined with gel versus device (one study; 120 women). The total number of participants was 1273, but data on 1133 women were available for analysis. Only two of 16 studies included 100% infertile women; in all other studies, the proportion was variable or unknown. No study reported live birth, but some (five studies) reported outcomes that were used as surrogate outcomes for live birth (term delivery or ongoing pregnancy). Anti-adhesion therapy versus placebo or no treatment following operative hysteroscopy. There was insufficient evidence to determine whether there was a difference between the use of a device or hormonal treatment compared to no treatment or placebo with respect to term delivery or ongoing pregnancy rates (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.42 to 2.12; 107 women; 2 studies; I2 = 0%; very-low-quality evidence). There were fewer IUAs at second-look hysteroscopy using a device with or without hormonal treatment or hormonal treatment or barrier gels compared with no treatment or placebo (OR 0.35, 95% CI 0.21 to 0.60; 560 women; 8 studies; I2 = 0%; low-quality evidence). The number needed to treat for an additional beneficial outcome (NNTB) was 9 (95% CI 5 to 17). Comparisons of different anti-adhesion therapies following operative hysteroscopy It was unclear whether there was a difference between the use of a device combined with graft versus device only for the outcome of ongoing pregnancy (OR 1.48, 95% CI 0.57 to 3.83; 180 women; 3 studies; I2 = 0%; low-quality evidence). There were fewer IUAs at second-look hysteroscopy using a device with or without graft/gel or gel combined with hormonal treatment and antibiotics compared with using a device only or hormonal treatment combined with antibiotics, but the findings of this meta-analysis were affected by evidence quality (OR 0.55, 95% CI 0.36 to 0.83; 451 women; 5 studies; I2 = 0%; low-quality evidence). Authors' conclusions: Implications for clinical practice The quality of the evidence ranged from very low to low. The effectiveness of anti-adhesion treatment for improving key reproductive outcomes or for decreasing IUAs following operative hysteroscopy in subfertile women remains uncertain. Implications for research More research is needed to assess the comparative safety and (cost-)effectiveness of different anti-adhesion treatments compared to no treatment or other interventions for improving key reproductive outcomes in subfertile women.
AB - Background: Observational evidence suggests a potential benefit with several anti-adhesion therapies in women undergoing operative hysteroscopy (e.g. insertion of an intrauterine device or balloon, hormonal treatment, barrier gels or human amniotic membrane grafting) for decreasing 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 June 2017: the Cochrane Gynaecology and Fertility Group Specialised Register; the Cochrane Central Register of Studies (CRSO); MEDLINE; Embase; 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. We also searched reference lists of appropriate papers. Selection criteria: Randomised controlled trials (RCTs) of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy following operative hysteroscopy in subfertile women. The primary outcome was live birth. Secondary outcomes were clinical pregnancy, miscarriage and IUAs present at second-look hysteroscopy, along with mean adhesion scores and severity of IUAs. Data collection and analysis: Two review authors independently selected studies, assessed risk of bias, extracted data and evaluated quality of evidence using the GRADE method. Main results: The overall quality of the evidence was low to very low. The main limitations were serious risk of bias related to blinding of participants and personnel, indirectness and imprecision. We identified 16 RCTs comparing a device versus no treatment (two studies; 90 women), hormonal treatment versus no treatment or placebo (two studies; 136 women), device combined with hormonal treatment versus no treatment (one study; 20 women), barrier gel versus no treatment (five studies; 464 women), device with graft versus device without graft (three studies; 190 women), one type of device versus another device (one study; 201 women), gel combined with hormonal treatment and antibiotics versus hormonal treatment with antibiotics (one study; 52 women) and device combined with gel versus device (one study; 120 women). The total number of participants was 1273, but data on 1133 women were available for analysis. Only two of 16 studies included 100% infertile women; in all other studies, the proportion was variable or unknown. No study reported live birth, but some (five studies) reported outcomes that were used as surrogate outcomes for live birth (term delivery or ongoing pregnancy). Anti-adhesion therapy versus placebo or no treatment following operative hysteroscopy. There was insufficient evidence to determine whether there was a difference between the use of a device or hormonal treatment compared to no treatment or placebo with respect to term delivery or ongoing pregnancy rates (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.42 to 2.12; 107 women; 2 studies; I2 = 0%; very-low-quality evidence). There were fewer IUAs at second-look hysteroscopy using a device with or without hormonal treatment or hormonal treatment or barrier gels compared with no treatment or placebo (OR 0.35, 95% CI 0.21 to 0.60; 560 women; 8 studies; I2 = 0%; low-quality evidence). The number needed to treat for an additional beneficial outcome (NNTB) was 9 (95% CI 5 to 17). Comparisons of different anti-adhesion therapies following operative hysteroscopy It was unclear whether there was a difference between the use of a device combined with graft versus device only for the outcome of ongoing pregnancy (OR 1.48, 95% CI 0.57 to 3.83; 180 women; 3 studies; I2 = 0%; low-quality evidence). There were fewer IUAs at second-look hysteroscopy using a device with or without graft/gel or gel combined with hormonal treatment and antibiotics compared with using a device only or hormonal treatment combined with antibiotics, but the findings of this meta-analysis were affected by evidence quality (OR 0.55, 95% CI 0.36 to 0.83; 451 women; 5 studies; I2 = 0%; low-quality evidence). Authors' conclusions: Implications for clinical practice The quality of the evidence ranged from very low to low. The effectiveness of anti-adhesion treatment for improving key reproductive outcomes or for decreasing IUAs following operative hysteroscopy in subfertile women remains uncertain. Implications for research More research is needed to assess the comparative safety and (cost-)effectiveness of different anti-adhesion treatments compared to no treatment or other interventions for improving key reproductive outcomes in subfertile women.
UR - http://www.scopus.com/inward/record.url?scp=85035139373&partnerID=8YFLogxK
U2 - 10.1002/14651858.CD011110.pub3
DO - 10.1002/14651858.CD011110.pub3
M3 - Review article
C2 - 29178172
AN - SCOPUS:85035139373
VL - 2017
JO - The Cochrane database of systematic reviews
JF - The Cochrane database of systematic reviews
SN - 1469-493X
IS - 11
M1 - CD011110
ER -