BACKGROUND: The use of transvaginal mesh and biological graft material in prolapse surgery is controversial and has led to a number of enquiries into their safety and efficacy. Existing trials of these augmentations are individually too small to be conclusive. We aimed to compare the outcomes of prolapse repair involving either synthetic mesh inlays or biological grafts against standard repair in women.
METHODS: We did two pragmatic, parallel-group, multicentre, randomised controlled trials for our study (PROSPECT [PROlapse Surgery: Pragmatic Evaluation and randomised Controlled Trials]) in 35 centres (a mix of secondary and tertiary referral hospitals) in the UK. We recruited women undergoing primary transvaginal anterior or posterior compartment prolapse surgery by 65 gynaecological surgeons in these centres. We randomly assigned participants by a remote web-based randomisation system to one of the two trials: comparing standard (native tissue) repair alone with standard repair augmented with either synthetic mesh (the mesh trial) or biological graft (the graft trial). We assigned women (1:1:1 or 1:1) within three strata: assigned to one of the three treatment options, comparison of standard repair with mesh, and comparison of standard repair with graft. Participants, ward staff, and outcome assessors were masked to randomisation where possible; masking was obviously not possible for the surgeon. Follow-up was for 2 years after the surgery; the primary outcomes, measured at 1 year and 2 years, were participant-reported prolapse symptoms (i.e. the Pelvic Organ Prolapse Symptom Score [POP-SS]) and condition-specific (ie, prolapse-related) quality-of-life scores, analysed in the modified intention-to-treat population. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN60695184.
FINDINGS: Between Jan 8, 2010, and Aug 30, 2013, we randomly allocated 1352 women to treatment, of whom 1348 were included in the analysis. 865 women were included in the mesh trial (430 to standard repair alone, 435 to mesh augmentation) and 735 were included in the graft trial (367 to standard repair alone, 368 to graft augmentation). Because the analyses were carried out separately for each trial (mesh trial and graft trial) some women in the standard repair arm assigned to all treatment options were included in the standard repair group of both trials. 23 of these women did not receive any surgery (15 in the mesh trial, 13 in the graft trial; five were included in both trials) and were included in the baseline analyses only. Mean POP-SS at 1 year did not differ substantially between comparisons (standard 5.4 [SD 5.5] vs mesh 5.5 [5.1], mean difference 0.00, 95% CI -0.70 to 0.71; p=0.99; standard 5.5 [SD 5.6] vs graft 5.6 [5.6]; mean difference -0.15, -0.93 to 0.63; p=0.71). Mean prolapse-related quality-of-life scores also did not differ between groups at 1 year (standard 2.0 [SD 2.7] vs mesh 2.2 [2.7], mean difference 0.13, 95% CI -0.25 to 0.51; p=0.50; standard 2.2 [SD 2.8] vs graft 2.4 [2.9]; mean difference 0.13, -0.30 to 0.56; p=0.54). Mean POP-SS at 2 years were: standard 4.9 (SD 5.1) versus mesh 5.3 (5.1), mean difference 0.32, 95% CI -0.39 to 1.03; p=0.37; standard 4.9 (SD 5.1) versus graft 5.5 (5.7); mean difference 0.32, -0.48 to 1.12; p=0.43. Prolapse-related quality-of-life scores at 2 years were: standard 1.9 (SD 2.5) versus mesh 2.2 (2.6), mean difference 0.15, 95% CI -0.23 to 0.54; p=0.44; standard 2.0 (2.5) versus graft 2.2 (2.8); mean difference 0.10, -0.33 to 0.52; p=0.66. Serious adverse events such as infection, urinary retention, or dyspareunia or other pain, excluding mesh complications, occurred with similar frequency in the groups over 1 year (mesh trial: 31/430 [7%] with standard repair vs 34/435 [8%] with mesh, risk ratio [RR] 1.08, 95% CI 0.68 to 1.72; p=0.73; graft trial: 23/367 [6%] with standard repair vs 36/368 [10%] with graft, RR 1.57, 0.95 to 2.59; p=0.08). The cumulative number of women with a mesh complication over 2 years in women actually exposed to synthetic mesh was 51 (12%) of 434.
INTERPRETATION: Augmentation of a vaginal repair with mesh or graft material did not improve women's outcomes in terms of effectiveness, quality of life, adverse effects, or any other outcome in the short term, but more than one in ten women had a mesh complication. Therefore, follow-up is vital to identify any longer-term potential benefits and serious adverse effects of mesh or graft reinforcement in vaginal prolapse surgery.
FUNDING: UK National Institute of Health Research.