Pelvic Floor Clinical Support

Transcription

1 Pelvic Floor Clinical Support

2 Contents Select bibliography (listed chronologically) 3 Advantage System 3 Advantage System/Obtryx System 4 Obtryx System 4 Lynx System 4 Solyx (Single-Incision Sling System) 5 Coaptite Injectable Implant 6 Advantage System 10 Advantage System/Obtryx System 11 Obtryx System 13 Lynx System 15 Solyx (Single-Incision Sling System) 16 Coaptite Injectable Implant Pelvic Floor Reconstruction Select bibliography (listed chronologically) 17 Uphold /Uphold LITE System Pelvic Floor Reconstruction 19 Uphold /Uphold LITE System Commitment to Clinical Research (Investigator-Sponsored Research program) Pelvic Floor Reconstruction

3 Select bibliography (listed chronologically) Please note: Other relevant articles on topic may exist, as there is an extensive body of medical literature. In addition, the clinical information provided in this brochure has been summarized from original articles. For complete information, refer to each article in its entirety. Advantage System Chevrot A, et al. Long-term efficacy and safety of tension free vaginal tape in a historic cohort of 463 women with stress urinary incontinence Int Urogynecol J Balachandran A, et al. Does the diagnosis of detrusor overactivity affect the long-term prognosis of patients treated with a retropubic midurethral sling? Int Urogynecol J Basu M, et al. Three-year results from a randomised trial of a retropubic mid-urethral sling vs the Miniarc single incision sling for SUI Int Urogynecol J Renganathan A, et al. A series of advantage suburethral slings J Obstet Gynaecol Basu M, et al. A randomised trial of a retropubic tension-free vaginal tape versus a mini-sling for stress incontinence BJOG Lim YN, et al. Do the Advantage slings work as well as the tension-free vaginal tapes? Int Urogynecol J Moalli PA, et al. Tensile properties of five commonly used mid-urethral slings relative to the tvt Int Urogynecol J Pelvic Floor Dysfunct Advantage System/Obtryx System Brennand EA, et al. Five years after midurethral sling surgery for stress incontinence: obesity continues to have an impact on outcomes Int Urogynecol J Ross S, et al. Transobturator tape versus retropubic tension-free vaginal tape for stress urinary incontinence: 5-year safety and effectiveness outcomes following a randomised trial Int Urogynecol J Brennand EA, et al. Twelve-month outcomes following midurethral sling procedures for stress incontinence: impact of obesity BJOG Tarcan T, et al. Safety and efficacy of retropubic or transobturator midurethral slings in a randomized cohort of Turkish women Urol Int Arunkalaivanan A, et al. Efficacy and safety of transobturator tape (Obtryx) in women with stress urinary incontinence and intrinsic sphincter deficiency: Results from International Obtryx Registry ICS Meeting 2010 Costa P. Comparisons of safety and efficacy of the Obtryx Sling and Advantage Mid-Urethral Sling for the treatment of stress urinary incontinence: Propensity matching results in a large international registry AAGL 2010 Cholhan HJ, et al. Dyspareunia associated with paraurethral banding in the transobturator sling Am J Obstet Gynecol Ross S, et al. Transobturator tape compared with tension-free vaginal tape for stress incontinence: a randomized controlled trial Obstet Gynecol Robert M, et al. Patient expectations, subjective improvement and objective cure: Is there a difference between the transobturator tape and the tension free vaginal tape procedure? Neurourology and Urodynamics 2009 Costa P. Safety of sub-mid urethral tapes: Report on 3 and 12 months follow-up on 1198 patients in an international registry J Urol Pelvic Floor Clinical Support 3

4 Select bibliography (listed chronologically) Costa P. Results of retropubic and transobturator placement of sub-mid urethral tapes (M.U.T.) in first international registry: Results on 984 patients at 3 and 12 months ICS 2007 Costa P. First international registry on sub-mid urethral tapes (M.U.T.) implanted by retro pubic of trans-obturator route: Preliminary results on 700 patients EAU 2007 Obtryx System Aygül C, et al. Evaluation of the efficacy of transobturator tape surgery in the treatment of stress urinary incontinence using urodynamics and questionnaires Turk J Obstet Gynecol Hogston P, et al. Medium term follow-up of women who underwent transobturator suburethral tape insertion for the treatment of urinary stress incontinence BJOG Smith P, et al. Comparison of single-incision mid-urethral tape (Ophira ) and transobturator tape (Obtryx ) suburethral sling procedures for female stress urinary incontinence J Clin Med and Research 2013 May J, et al. Outcome of Obtryx Transobturator Sling for stress incontinence in Scottish women Int Journal Gynecol Obstet Hogston P. Single surgeon experience with 125 transobturator sling procedures Int Urogynecol J./IUGA 2011 Wilson C, et al. Short-term efficacy of a transobturator sling in women veterans with a history of sexual trauma MAAUA 2010 Litwiller SE. Long term efficacy and safety of the Obtryx Sling (Boston Scientific Corp.) for treatment of stress urinary incontinence in a community setting: an analysis of outcomes and quality of life. J Pelvic Med Surg Tahseen S, et al. Effect of transobturator tape on overactive bladder symptoms and urge urinary incontinence in women with mixed urinary incontinence Obstet Gynecol./MAAUA 2009 Dati S. Obtryx System: Transobturator out-in sling in the treatment of isolated or POP-associated urinary incontinence Int Urogynecol J Lynx System Agarwala N. A randomized comparison of two synthetic mid-urethral tension-free slings UroToday International Journal 2008 Noblett KL, et al. Lynx midurethral sling system: a 1-year prospective study on efficacy and safety Int Urogynecol J Pelvic Floor Dysfunct Solyx (Single-Incision Sling System) Serels S, et al. Long term follow up of the Solyx Single Incision Sling in the treatment of female stress urinary incontinence (SUI) Open Journal of Urology 2014 Serels S, et al. Safety and efficacy of the Solyx Single Incision Sling System for the treatment of SUI: Preliminary results UroToday International Journal 2011 Serels S, et al. Preliminary findings with the Solyx single-incision sling system in female stress urinary incontinence Int Urogynecol J Pelvic Floor Clinical Support 4

5 Select bibliography (listed chronologically) Coaptite Injectable Implant Mayer RD, et al. Multicenter prospective randomized 52-week trial of calcium hydroxylapatite versus bovine dermal collagen for treatment of stress urinary incontinence Urology 2007 Mayer R, et al. Preliminary Evaluation of Calcium Hydroxylapatite as a Transurethral Bulking Agent for Stress Urinary Incontinence Urology 2001 Pelvic Floor Clinical Support 5

6 Advantage System Chevrot A, Droupy S, Coffin G, Soustelle L, Boukaram M, Fatton B, de Tayrac R, Wagner L, Costa P. Long-term efficacy and safety of tension free vaginal tape in a historic cohort of 463 women with stress urinary incontinence. Int Urogynecol J. 2017;28(6): To investigate the long-term safety and efficacy of the retropubic midurethral sling (Advantage) in a large series of women with stress urinary incontinence. A retrospective cohort of 517 consecutive women who underwent placement of an Advantage retropubic sling at a single center in France was analyzed. Data was obtained from the patient s chart, and the mailed validated Urinary Symptom Profile (USP) and the Patient Global Improvement (PGI) Questionnaires as well as telephone interviews. Women were considered subjectively cured if there was a total absence of any involuntary leakage during physical activity, coughing, sneezing, house cleaning or walking (USP score 0), a feeling of improvement (PGI score 6), the use of a maximum of 1 pad per day, and no need for further SUI treatment. The rate of operative, early (<30 days), and late postoperative complications were obtained. 463 patients were evaluable at a mean (±SD) follow-up of 71±23 months. At the last follow-up: 74.3% (344) of patients demonstrated subjective cure 11.9% (55) of patients were improved 13.8% (64) of patients had treatment failure Preoperative ISD (p=0.0006) and previous incontinence surgery (p=0.0336) were significant risk factors for failure. Bladder perforations occurred in 7.1% (33) of patients and were significantly more frequent in patients with previous incontinence or prolapse surgery (p<0.05). Temporary, intermittent self-catheterization was required in 2.2% (10) of patients due to voiding difficulties. Two of these patients required tape loosening in the operating room. The most frequent long-term complication (>30 days after surgery) was de novo urge incontinence reported in 12.7% (59) of patients. Other long-term complications included pelvic and groin pain reported in 5.6% and 2.6% of patients. Bladder, urethral, and vaginal erosion occurred in 0.4%, 0.2% and 0.2% of patients respectively. In long-term follow-up, 1.5% (7) of patients needed tape excision due to voiding difficulties and 1.3% (6) due to erosion or chronic pain. The Advantage sling has a high success/improvement rate of 86.2% at a mean follow-up of 71 ± 23 months, with a low erosion and tape excision/ revision rate and no serious long-term tape related adverse effects. Pelvic Floor Clinical Support 6

7 Advantage System Basu M, Duckett J. Three-year results from a randomised trial of a retropubic mid-urethral sling versus the Miniarc single incision sling for stress urinary incontinence. Int Urogynecol J. 2013; 24: To evaluate the success rate of the Miniarc single-incision sling versus a retropubic mid-urethral tape (Advantage) for cure of SUI at 3 years follow-up to assess if there is a deterioration in efficacy over time. This study is a 3-year questionnaire-based follow-up of a prospective, parallel group, randomized trial at a single center in the UK. 61 patients completed the 3-year King s Health Questionnaire; 26/33 (79%) of patients in the Advantage group and 35/38 (92.1%) patients in the MiniArc group. Patients were considered failures if they documented stress incontinence on the symptom domain of the King s Health Questionnaire or had undergone repeat surgery for stress incontinence. Patients were also asked about any late adverse events, such as treatment for mesh exposure. At 3-years, 21% (8/38) of patients in the MiniArc group had undergone a repeat continence procedure vs. 0 (0/33) in the Advantage group. Of the remaining 30 patients in the Miniarc group, 34% (11/30) had SUI symptoms. In the Advantage group, 9% (3/33) had SUI symptoms. The overall 3-year failure rate was 52.6% (20/38) in the Miniarc group and 9% (3/33) in the Advantage group (OR 10.0, 95 % CI ). In the Miniarc group, the failure rate increased from 40.5% at 6-months to 52.6% at 3-years. In the Advantage group, the failure rate increased from 3% to 9% (P=0.21). No late adverse events were identified in either group. This study found that the single-incision slings had a significantly higher 3-year failure and re-operation rate than the retropubic slings. However, both procedures had reduced efficacy from 6 months to 3 years follow-up. Pelvic Floor Clinical Support 7

8 Advantage System Lim Y, Dwyer P, Muller R, Rosamilia A, Lee J, Stav K. Do the Advantage slings work as well as the tension-free vaginal tapes? Int Urogynecol J. 2010; 21(9): To compare the efficiency and safety outcome data of the Advantage sling to tension-free vaginal tape (TVT). A retrospective chart review was conducted at a single center in Australia. Data from 556 tension-free vaginal tape (TVT) and 108 Advantage sling cases were compared after assessing for potential confounding factors. Identified subjects were interviewed by phone with a structured questionnaire to examine urinary symptoms, pain, and the need for additional anti-incontinence surgery. Women were considered subjectively cured if they did not have subsequent anti-incontinence surgery and responded no to the question of leaking urine during physical activity, coughing or sneezing. The two groups proved comparable. The Advantage group had significantly shorter follow-up than the TVT group (111 vs. 235 weeks, p <0.001); however, additional analysis revealed that outcome parameters were not influenced by the duration of follow-up in the overall sample. Bladder injury rates were 4.6% for the Advantage group and 2.9% for the TVT group (p=0.36). Subjective stress incontinence cure was 83.3% for the Advantage group and 85.3% for the TVT group (p=0.66). Incidences of de novo urgency, urge incontinence, and voiding difficulties were 22.2% vs. 14.7% (p=0.06), 9.3% vs. 7.4% (p=0.55), and 11.1% vs. 6.7% (p=0.11) for the Advantage and TVT groups respectively. There were no sling erosions in the Advantage group and a 1.43% erosion rate in the TVT group. 93.2% of the TVT group would recommend the procedure to a friend compared to 92.6% of the Advantage group. This study found the Advantage sling to be as effective as the TVT sling. There is a non-significant trend towards more de novo urgency and voiding difficulty symptoms in the Advantage group, but the author thinks this may be due to the slightly stiffer nature of the Advantage sling which may require them to be left slightly looser than TVT slings. Pelvic Floor Clinical Support 8

9 Advantage System Moalli PA, Papas N, Menefee S, Albo M, Meyn L, Abramowitch SD. Tensile properties of five commonly used mid-urethral slings relative to the TVT Int Urogynecol J Pelvic Floor Dysfunct May; 19(5): To assess physical and mechanical characteristics and characterize tensile properties of six commonly used mid urethral slings. Slings were subjected to loading to failure and to three step cyclic loading protocol to determine how samples permanently elongate under repetitive loading. Textile properties measured for all slings show Boston Scientific, AMS, and Gynecare meshes to be very similar. Coloplast (Mentor) mesh was distinct with small pore, fiber size, and smooth edges. Coloplast had tightest knit pattern followed by Caldera. Load to failure curves of the Coloplast and Caldera slings were completely dissimilar to others. Coloplast mesh was distinct with minimal elongation even at high loads. Mesh tensile and loading behavior was similar between Boston Scientific, AMS, and Gynecare. Gynecare TVT mesh has a unique tensile behavior. Mesh permanently elongated by more than 10% of its initial length, confirming the easy permanent deformability of the mesh observed clinically during placement. High stiffness material may not elongate with the application of even high loads (a very heavy cough) and consequently would have an increased likelihood of erosion into the bladder or urethra. Low stiffness material may also make the sling less likely to obstruct the urethra or cause postoperative voiding dysfunction. The two main takeaways from this study are: The three most commonly used and studied slings are very similar in textile properties and behavior under load and those are Gynecare, Boston Scientific, and AMS. Coloplast (Mentor) and Caldera have distinctly different properties and behavior. High stiffness meshes such as those for Coloplast and Caldera do not elongate and may present higher risk of erosion or voiding dysfunction. Pelvic Floor Clinical Support 9

10 Advantage System/Obtryx System Ross S, Tang S, Eliasziw M, Lier D, Girard I, Brennand E, Dederer L, Jacobs P, Magali R. Transobturator tape versus retropubic tension-free vaginal tape for stress urinary incontinence: 5-year safety and effectiveness outcomes following a randomised trial. Int Urogynecol J. 2016; 27(6): To clarify whether the transobturator tape (Obtryx) approach was safe and effective compared to tension-free vaginal tape (Advantage) using outcomes designed to reflect choices in usual clinic practice. This is a 5-year extension study of a multicenter randomized controlled trial. In the original trial, 199 women were randomly assigned to receive either Obtryx (94) or Advantage (105) and followed for 12 months after surgery. All women in the initial RCT study were eligible to participate in the 5-year follow-up. The primary composite outcome was the occurrence of one or more of the following: Vaginal mesh exposure, urinary retention, repeat continence surgery, and moderate to severe pelvic pain. Objective evidence of SUI was obtained by a standardized pad test with test failure defined as 1g over the test period. A patient was considered to have a subjective failure if urine loss was reported as a big problem over the past 7-days when the patient coughed, laughed, sneezed, lifted, exercised, etc. 88.4% (176/199) of the original patients participated; 83 Obtryx and 93 Advantage. 93.8% (165/176) had sufficient data to determine primary study outcome. The primary composite outcome occurred in 21.8% of the Obtryx group and 27.6% of the Advantage group (P=0.39). Except for mesh exposure in 9% of the Obtryx group vs. 2.3% of the Advantage group (p=0.06) all other component outcomes favored the Obtryx group (urine retention 5.1% vs. 6.9% (p=0.63), repeat surgery 1.3% vs. 3.4% (p=0.37) and pain 12.8% vs. 24.1% (p=0.06)). Objective failure was observed in 13.6% of Obtryx patients and 24.3% of Advantage patients (p=0.11). Subjective failure was observed in 3.7% of Obtryx patients and 9.9% of Advantage patients (P=0.11). Women in the Obtryx group continued to have more palpable tapes than in the Advantage group (48.5% vs. 22.4%, p < 0.001). Both groups reported better scores on average for UDI-6 and IIQ-7, compared with baseline, the difference between the groups was marginal. The study suggests that the outcomes at 5-years post-procedure for transobturator tape patients may be more favorable than for TVT patients. Overall serious adverse events did not differ between the groups, but transobturator patients continue to have a palpable tape which is a concern for additional adverse events. Pelvic Floor Clinical Support 10

11 Obtryx System Smith P, Dhillon R, Baptiste M, Arunkalaivanan A. Comparison of single-incision mid-urethral tape (Ophira ) and transobturator tape (Obtryx ) suburethral sling procedures for female stress urinary incontinence. J Clin Med and Research. Aug 2013; 5(5): To assess the efficacy and patient satisfaction of single incision mid-urethral tape (Ophira) against transobturator tape (Obtryx). This is a prospective single-center observational study with 12 month follow-up. 61 women self-selected to receive either Obtryx (31) or Ophira (30) based upon anesthesia preference. Objective cure was defined as a negative cough stress test. Subjective cure was based on the patient s perception of improvement in stress urinary incontinence symptoms using the ICIQ-SF Questionnaire. No significant intergroup differences were found at baseline. Objective cure was 90% in the Ophira group and 93.5% in the Obtryx group. Subjective cure (significantly improved) was reported in 93.3% of the Ophira group and 93.5% of the Obtryx group. Comparing peri-procedural complications, the only significant difference was found in blood loss. Obtryx patients had more than average blood loss in 3 patients compared to 1 Ophira patient (p=0.04) Women reported a significant improvement in quality of life, as measured by the ICIQ-SF, regardless of treatment received (pre-procedure 16.5±5.2 Ophira vs. 17.1±1.69 Obtryx (p=0.79); post-procedure 4.2±1.8 Ophira vs. 4.1±2.1 Obtryx (p0.56)). Twelve-month follow-up showed the procedures were comparable in objective and subjective cure rates. Pelvic Floor Clinical Support 11

12 Obtryx System Litwiller SE. Long term efficacy and safety of the Obtryx Sling (Boston Scientific Corp.) for treatment of stress urinary incontinence in a community setting: an analysis of outcomes and quality of life. J Pelvic Med Surg. 2009; 12(5): 353. To report the objective results and quality of life indices of the Obtryx sling in a private practice setting. This is a retrospective study of 954 patients who received an Obtryx sling for genuine stress incontinence by two private practitioners. Chart review was used to evaluate surgical details, post-operative exam parameters, and pad use. Blinded validated quality of life questionnaires (UDI-6, IIQ-7, and VAS Quality of life) were used to assess subjective outcomes. At a median follow-up of 21 months: 98% of patients reported no stress incontinence. 93% of patients never wear pads. Urge incontinence resolved in 66% of patients with 22% of patients reporting urgency post op. Median postoperative UDI-6, IIQ-7 and QOL parameters were 3, 1 and 1 respectively (P<0.005). Postoperative post-void residual (PVR) was unchanged (median 10mL). There were no complications involving bladder or urethral perforation and no thigh or groin pain. One patient suffered a vaginal sling exposure which resolved with topical estrogen therapy. There was no postoperative retention, and no patient required postoperative sling incision or urethral dilation. Obtryx represents an effective and safe long-term option for the treatment of SUI. Significant objective and quality of life improvements can be expected. Pelvic Floor Clinical Support 12

13 Lynx System Agarwala N. A randomized comparison of two synthetic mid-urethral tension-free slings. UroToday International Journal. 2008; 1(4). To compare the efficacy, intraoperative and postoperative complication rates, and ease of procedure and training for two synthetic mid-urethral slings (Gynecare TVT and Lynx) in patients with stress urinary incontinence. This is a single center, prospective, randomized study of 96 women with stress urinary incontinence who were consecutively assigned to Gynecare TVT or Boston Scientific Lynx mid-urethral slings (n=48 in each group). Intraoperative complications and early and late postoperative complications were recorded. Ease of training was assessed by the level of difficulty in passing the trocars. Objective cure was defined as a negative standing cough stress test. Subjective cure was defined as the absence of any symptoms of involuntary urine loss with stress or Valsalva at the postoperative evaluation. Both groups were similar in baseline characteristics. Intraoperative injuries were higher in the Lynx group with 3 (6%) trocar injuries vs. 2 (4%) for TVT (p=0.21). Postoperative voiding dysfunction was higher in the TVT group at 21% (10/48) vs. the Lynx group at 15% (7/48) (p<0.001). The need for prolonged catheterization for days was similar for both at 4% (2 patients each). The UTI rate was 13% (6/48) in the Lynx group vs. 10% (5/48) in the TVT group (p=0.12). The vaginal sling exposure rate was 4% (2/48) in the Lynx group vs. 0% in the TVT group (p=0.45). Objective cure was 94% (45/48) for the Lynx group vs. 96% (46/48) for the TVT group (p=0.07). Subjective cure was 92% (44/48) in the Lynx group vs. 94% (45/48) in the TVT group (p=0.08). The residents favored the Lynx sling giving it better scores for ease, technicality, and stability but preferred TVT in cases where the tissue was scared from previous surgeries. The Lynx and TVT patients have similar efficacy, complication, and failure rates. The incidence of post-operative voiding difficulties was better with Lynx, but there was an increased rate of tape exposures in these patients. Residents rated the Lynx sling better for ease, technicality, and stability but favored the TVT in patients with prior surgeries. Pelvic Floor Clinical Support 13

14 Lynx System Noblett K, Shen B, Lane F. Lynx midurethral sling system: a 1-year prospective study on efficacy and safety. Int Urogynecol J Pelvic Floor Dysfunct. 2008; 19: To evaluate the efficacy and safety of the Lynx midurethral sling system. This is a prospective, descriptive, single-center study of 118 patients with urodynamic stress incontinence who underwent a Lynx midurethral sling procedure. Subjects were considered cured if they were subjectively dry by history and objectively dry by standing stress test. Intraoperative and postoperative complications were documented. Complete information was available on 102 (86%) subjects at 1-year. 90% (92/102) of patients were considered cured by subjective report and objective negative CST, and 10% (10/102) were failures. Of those that failed (10%, 10/102) all but one patient had one or more risk factors for failure which include previous incontinence surgery, BMI > 30, MUCP < 20 cm H2O, age > 70 years, and COPD/asthma. There were 4 (3.4%) intraoperative bladder perforations and five (4.2%) erosions. Two patients developed urinary retention. One resolved at 31 days, and the other underwent take down at 6-months, but both remain dry at 12-months. The Lynx sling system shows high subjective and objective success rates at 1-year follow-up with low rates of intraoperative and postoperative complications. Pelvic Floor Clinical Support 14

15 Solyx (Single-Incision Sling System) Serels S, Douso M. Long term follow up of the Solyx single incision sling in the treatment of female stress urinary incontinence (SUI). Open Journal of Urology. 2014; 4: To retrospectively assess the long-term safety and efficacy of the Solyx SIS Sling System in women with SUI. This is a retrospective study of 69 patients at two centers in the United States with a mean follow-up of 48 (range, 39-49) months. Subject charts were reviewed and follow-up, study specific, telephone questionnaires were obtained from all patients. 93% (64/69) of patients were subjectively dry & satisfied with their outcome. 1:1 correlation of subjective outcome and standing CST results. 91% (63/69) of patients would have the procedure again. There were 4 cases of de novo urge incontinence and 2 reports of transient retention. No serious adverse events reported including: No bladder, bowel, vessel or nerve perforation No erosions or extrusions No pain reported attributed to the implant This study shows that the Solyx SIS has a high rate of sustainable subjective and objective efficacy at an average of 43 months follow-up. Pelvic Floor Clinical Support 15

16 Coaptite Injectable Implant Mayer RD, Dmochowski RR, Appell RA, Sand PK, Klimberg IW, Jacoby K, Graham CW, Snyder JA, Nitti VW, Winters JC. Multicenter prospective randomized 52-week trial of calcium hydroxylapatite versus bovine dermal collagen for treatment of stress urinary incontinence. Urology May;69(5): To evaluate the safety and efficacy of calcium hydroxylapatite (CaHA; Coaptite) compared with glutaraldehyde cross-linked bovine collagen (Contigen) in female patients with SUI due to intrinsic sphincter deficiency (ISD). This is a prospective, randomized, single-blinded study of 296 patients at 14 sites in the United States. Patients were randomized to receive either Coaptite or Contigen and were permitted up to five injections during the first 6-months of the study. No treatments were allowed after 6-months and patients were followed for 12-months post-injection. The primary efficacy endpoint was defined as an improvement of one or more grades on the Stamey Urinary Incontinence Scale at 12-months. The secondary endpoints evaluated the patient for improvement of more than one Stamey grade, a reduction in 24-hour pad weight, and quality of life changes. Safety was based on adverse events, physical exam findings, and laboratory tests. 231 patients (78%) had 12-month Stamey grades available (131 Coaptite and 100 Contigen). At 6-months, 74% of Coaptite and 71% of Contigen patients improved by one Stamey grade (P=0.57). At 12-months, 63.4% (83/131) of Coaptite and 57% (57/100) of Contigen patients sustained at least one Stamey grade improvement (P=0.34). The cure rate or Stamey grade 0 at 12-months was 39% for Coaptite patients vs. 37% for Contigen patients (P=0.78). The proportion of patients with substantial improvement, defined as improvement of two Stamey grades or being dry, was 50% in the Coaptite group vs. 46% in the Contigen group (P=0.59). Both groups experienced a significant improvement in quality of life at 12-months as demonstrated on the IQOL assessment (mean IQOL improvement for Coaptite patients was 31 (range -41 to +87) vs. 26 (range -44 to +91) for the Contigen patients (P< for each group)). More patients in the Coaptite group required only one injection (38%) compared to Contigen patients (26.1%) (P=0.03). The average total volume of material injected during the study was less for Coaptite patients than for Contigen patients (4.0ml vs. 6.6ml; P<0.0001) No permanent retention was noted in either group. Transient retention occurred in 41% of the Coaptite group and 33% of the Contigen group. After treatment urge incontinence was noted in 5.7% of the Coaptite group and 12% of the Contigen group (p <0.05). A total of 33 serious Adverse Events were reported in 23 patients (11 Coaptite and 12 Contigen) at 9 sites. Two of the serious adverse events in the Coaptite group were considered to be treatment related. The results of the study show that Coaptite is as effective as Contigen treating incontinence in patients with ISD. Coaptite patients were more likely to be treated successfully with a single injection compared to Contigen patients. No permanent retention was noted, and transient retention occurred in both groups which were not significant. Pelvic Floor Clinical Support 16

17 Pelvic Floor Reconstruction Select bibliography (listed chronologically) Please note: other relevant articles on topic may exist, as there is an extensive body of medical literature. In addition, the clinical information provided in this brochure has been summarized from original articles. For complete information, refer to each article in its entirety. Uphold /Uphold LITE System Altman D, et al. (2017) Pelvic organ prolapse repair using the Uphold Vaginal Support System: 5-year follow-up Gutman RE, et al. Vaginal and laproscopic mesh hysteropexy for uterovaginal prolapse: a parallel cohort study Am J Obstet Gynecol (Uphold or Uphold LITE Vaginal Support System) Morcos E, et al. Comparison of single- versus multicenter outcomes for pelvic organ prolapse repair using a meshcapturing device Int Urogynecol J (Uphold LITE Vaginal Support System) Rahkola-Soisalo P, et al. Quality of life after Uphold Vaginal Support System surgery for apical pelvic organ prolapse A prospective multicenter study Eur J Obstet Gynecol Reprod Biol (Uphold Vaginal Support System) Pahwa AK, et al. Management of arterial and venous hemorrhage during sacrospinous ligament fixation: cases and review of the literature Int Urogynecol J (Uphold LITE Vaginal Support System) Gillingham A. Comparison of perioperative and short-term postoperative outcomes in two transvaginal mesh systems used in the treatment of pelvic organ prolapse Female Pelvic Medicine & Reconstructive Surgery/AUGS 2015 (Uphold LITE Vaginal Support System) Jirschele K, et al. A multicenter, prospective trial to evaluate mesh-augmented sacrospinous hysteropexy for uterovaginal prolapse Int Urogynecol J (Uphold Vaginal Support System) Larouche M, et al. Outcomes of trocar-guided Gynemesh PS versus single-incision trocarless Polyform transvaginal mesh procedures Int Urogynecol J (Polyform) Letouzey V, et al. Utero-vaginal suspension using a bilateral vaginal anterior sacrospinous fixation with mesh: intermediate results of a cohort study Int Urogynecol J (Uphold Vaginal Support System) Altman D, et al. Intra and perioperative morbidity following pelvic organ prolapse repair using a transvaginal suture capturing mesh device compared to trocar guided transvaginal mesh and traditional colporrhaphy Neurology and Urodynamics/ICS 2013 (Uphold LITE Vaginal Support System) Evans J. Native tissue suture repair vs mesh augmented vaginal repair for primary or recurrent POP: long-term outcomes and complications Int Urogynecol J./IUGA 2013 (Uphold Vaginal Support System) Letko J, et al. Comparison of surgical outcomes after augmented anterior/apical repair using two different materials: dermal graft and polypropelene mesh Female Pelvic Med Reconstr Surg./ICS 2013 (Uphold Vaginal Support System) Robinson BL, et al. Robotic versus vaginal urogynecologic surgery: A retrospective cohort study of perioperative complications in elderly women Female Pelvic Med Reconstr Surg (Uphold Vaginal Support System) Rusavy Z, et al. Voiding difficulties after vaginal mesh cystocele repair: does the perivesical dissection matter? Int Urogynecol J (Uphold Vaginal Support System, Polyform Synthetic Mesh) de Tayrac R, et al. Analysis of the learning curve of bilateral anterior sacrospinous ligament suspension associated with anterior mesh repair Eur J Obstet Gynecol Reprod Biol (Polyform Synthetic Mesh, Pinnacle mesh, Capio, Uphold Vaginal Support System) Letko J, et al. Postoperative pain and perception of recuperation after mesh based vs suture based sacrospinous suspension Female Pelvic Med Reconstr Surg (Uphold Vaginal Support System) Rivaux G, et al. Utero-vaginal suspension using a bilateral vaginal anterior sacrospinous fixation with mesh. Preliminary results Prog Urol (Uphold Vaginal Support System) Pelvic Floor Clinical Support 17

18 Pelvic Floor Reconstruction Select bibliography (listed chronologically) Tipton, A. Uphold Vaginal Support System in the surgical management of POP Female Pelvic Med Reconstr Surg (Uphold Vaginal Support System) Vu MK, et al. Minimal mesh repair for apical and anterior prolapse: initial anatomical and subjective outcomes Int Urogynecol J (Uphold Vaginal Support System) Ghoneim G. Uterine preservation: Early experience with vaginal sacrospinous suspension using polypropylene mesh Int Urogynecol J./IUGA 2011 (Uphold Vaginal Support System) Mobley J. Feasibility and short-term outcomes following the use of the Uphold vaginal support system for treatment of symptomatic vaginal prolapse Neurology and Urodynamics/SUFU 2011 (Uphold Vaginal Support System) Zoorob D. Vaginal colpopexy using a trocar less mesh kit vs traditional uterosacral ligament suspension: A retrospective cohort study AUGS 2011 (Uphold Vaginal Support System) de Tayrac, R. Bilateral anterior sacrospinous ligament suspension associated with a paravaginal repair with mesh short-term clinical results of a pilot study Int Urogynecol J (Polyform, Capio) Vu M. A new minimal mesh anterior-apical repair: Results for the first 140 cases performed at 2 urogynecology centers Female Pelvic Med Reconstr Surg./AUGS 2010 (Uphold Vaginal Support System) Goldberg R. Minimal mesh anterior-apical prolapse repair: A new alternative for uterine preservation Int Urogynecol J./IUGA 2009 (Uphold Vaginal Support System) Vu M. A new minimal mesh anterior-apical repair. Initial outcomes in a uterine preservation cohort J Pelvic Med Surg (Uphold Vaginal Support System) Pelvic Floor Clinical Support 18

19 Pelvic Floor Reconstruction Uphold /Uphold LITE System Altman D, Mikkola T, Bek K, Rahkola-Soisalo P, Gunnersson J, Engh M, Falconer C (2017) Pelvic organ prolapse repair using the Uphold Vaginal Support System: 5-year follow-up To assess the long term (5 year) outcomes of the Uphold Vaginal Support System for symptomatic vaginal apical prolapse with or without anterior colporhphy. This is a prospective, multicenter, cohort study performed throughout 24 centers in Sweden, Finland, Denmark, and Norway. In total 164 (81.2%) of 202 women operated on were reached for follow-up. Outcomes were assessed by Pelvic Organ Prolapse Quantification (POP-Q) objectively and by Pelvic floor Distress Inventory 20, and the Pelvic Organ Prolapse/urinary Incontinence Sexual Q questionnaires subjectively. Pain in pelvic area was evaluated using a visual analogy scale (VAS). Apical outcome was optimal in 83.5% of women. There was no significant difference between 1 and 5 year follow-up. Rate of extrusion at 5 years was 1.4% with all treated with local estrogen and none required surgical intervention Study reported 19.7% reoperation rate between 1 and 5 year with most common being 38.4% (15) for mid urethral sling, 15.4% (6) for posterior repairs, 10.2 % (4) for hysterectomy Mesh removal was performed in 3 women because of pain. Mesh related pain persisted in those three patients over 5 years with a VAS score over 7. Patient information shows one with history of prolonged pain after previous operations, another with a base line VAS score of 3.9 with possible pudendal nerve injury during surgery, and last shown to have had rheumatism with baseline VAS score of 3 and a VAS score of 0.4 at discharge. That patient had a mid-urethral sling inserted sometime between 1 and 5 years post-surgery. Subjective outcomes showed no difference between 1 and 5 years Total score points from questionnaires exceeded baseline points in 89.4% of patients Minimal clinically important difference (>23 points) was reached in 78.8% of patients Bother from urge incontinence decreased between 1 to 5 years follow up while bother from stress incontinence increased At 5 year visit, sexual satisfaction had improved in all domains compared to baseline and 1 year Dyspareunia rates decreased from 59.2% at baseline to 42.9% at 1 year to 36.4% at 5 year Number of women with any pain decreased from 1 to 5 years (65.8% to 42.4%) and both showed significant decrease from baseline Apical objective and subjective outcomes were sustained after 5 years in women operated on for apical compartment prolapse by the Uphold Vaginal Support System. Pelvic Floor Clinical Support 19

20 Pelvic Floor Reconstruction Uphold /Uphold LITE System Gutman RE, Rardin CR, Sokol ER, Matthews C, Park AJ, Iglesia CB, Geoffrion R, Sokol AI, Karram M, Cundiff GW, Blomquist JL, Barber MD. Vaginal and laproscopic mesh hysteropexy for uterovaginal prolapse: a parallel cohort study. Am J Obstet Gynecol Jan; 216(1):38.e1-38.e11. To compare 1-year efficacy and safety of laparoscopic sacral hysteropexy (LSHP) and vaginal mesh hysteropexy (VMHP). This is a prospective, multicenter, parallel cohort study conducted at 8 centers; 7 in the United States and 1 in Canada. 150 women (74 LSHP, 76 VMHP) with stage 2-4 symptomatic anterior/apical prolapse who desired uterine conservation and were undergoing one of the two identified procedures were included. LSHP was performed using an anterior and posterior lightweight, type 1, polypropylene mesh. Anterior colporrhaphy was performed after LSHP for anterior prolapse (Ba -1) following apical suspension or at the surgeon s discretion. VMHP was performed using Uphold or Uphold LITE. The primary outcome was a composite of anatomic and symptomatic cure at 12 months. Cure was defined as no prolapse beyond the hymen and cervix above mid-vagina, no reoperations or pessary use (anatomic) and no vaginal bulge sensation (symptomatic). 1 year data was collected for 64 (83%) LSHP and 61 (80%) VMHP patients. LSHP patients were younger (p<0.001), had lower parity (p=0.006), and were more commonly premenopausal (p=0.008) with more advanced prolapse (p=0.02) involving the cervix and posterior wall. There were no other baseline differences. Half of all LSHP procedures used robotic assistance and the total procedure time (174 vs. 64 min, p <0.001) and total operating time (239 vs. 112 min, p <0.001) was longer than for the VMHP group. After adjusting for baseline differences, there was no difference in: Composite cure (72% LSHP vs. 74% VMHP; adjusted OR, 0.58; 95% CI, ; P=0.27) Anatomic cure (77% LSHP vs. 80% VMHP; adjusted OR, 0.48; 95% CI, ; P=0.20) Symptomatic cure (90% LSHP vs. 95% VMHP; adjusted OR, 0.4; 95% CI, ; P=0.22) The majority of failures were apical (19% LSHP vs. 16% VMHP) compared to anterior (9% LSHP vs. 6% VMHP). Two patients in the VMHP group underwent prolapse reoperation. Mesh erosions occurred in 2.7% (2/74) of the LSHP and 6.6% (5/77) of the VMHP groups. The most common adverse event was UTI which occurred in 11% (8/74) of the LSHP. Satisfaction, as measured by the Patient Global Impression of Improvement (PGII), was 95% in each group. Laparoscopic sacral hysteropexy and vaginal mesh hysteropexy had similar cure rates and high satisfaction at 1-year postprocedure. The vaginal mesh hysteropexy group had shorter surgical time compared to the laparoscopic group. Both reported improvement in pelvic floor symptoms and sexual function with no differences between the groups. Pelvic Floor Clinical Support 20

21 Pelvic Floor Reconstruction Uphold /Uphold LITE System Letouzey V, Ulrich D, Balenbois E, Cornille A, de Tayrac R, Fatton B. Utero-vaginal suspension using a bilateral vaginal anterior sacrospinous fixation with mesh. Intermediate results of a cohort study. Int Urogynecol J. 2015; 26: To report the medium-term results of the Uphold Vaginal Mesh Kit procedure for a combined treatment of POP of the anterior and apical compartments. This study is a longitudinal cases series of patients with symptomatic stage 2 prolapse who were operated on with the Uphold System at a single center in France. Anatomical success was defined as prolapse POP-Q stage -1 for both the anterior and apical compartments. Evaluation of subjective bother of POP was measured by the visual analog scale (VAS). Patients were also asked to rate their subjective outcome on the Patient Global Impression of Improvement (PGII) Questionnaire. Patients who did not complete at least 12 months of follow-up were excluded from the analysis. 115 subjects completed a mean follow-up of 23 ±10months. Anatomical success was 93% in both the anterior and apical compartments. 92% success in the anterior compartment 100% success in the apical compartment The median preoperative VAS bother score was 6 (0-10) and improved significantly postoperatively to 0 (0-7; p=<0.0001). The patient satisfaction rate was 96%. The reoperation rate for mesh-related complications was 3.4% (4/115). 1 (1%) due to pudendal neuralgia 3 (2.7%) due to vaginal mesh exposure Four patients (8%) experienced de novo dyspareunia related to the mesh. There were no re-operations due to POP recurrence. The subjective and objective cure rates were high at 96% and 93% respectively. The reoperation rate for mesh-related complications was 3.4% with no surgery required for POP recurrence. Pelvic Floor Clinical Support 21

22 Pelvic Floor Reconstruction Uphold /Uphold LITE System Vu MK, Letko J, Jirschele K, Gafni-Kane A, Nguyen A, Du H, Goldberg RP. Minimal mesh repair for apical and anterior prolapse: initial anatomical and subjective outcomes. Int Urogynecol J Dec; 23(12): To report objective and subjective outcomes on a center s first 2.5 years using a reduced mesh implant size and apex only fixation for anterior and apical compartment defects. This is a retrospective cohort study of the first 115 consecutive subjects undergoing the Uphold repair procedure by a single surgeon at a single center. Objective outcomes were based on POP-Q measurements, with recurrence defined as any anterior and/or apical points reaching 0, and secondary analyses -1. Complications were recorded and subjective outcome measures consisted of pre and postoperative dyspareunia according to a 0-4 Likert scale, Pelvic Floor Distress Inventory (PFDI) and Surgical Satisfaction (SSQ) questionnaires. The procedures performed in this study were done with one 34cm 2 type 1 polypropylene mesh implant and the Capio Suture Capturing Device. The technique and mesh implant size and shape were eventually commercialized as Uphold. Recurrence with whole cohort: Anterior: One (0.8 %) defined as Ba 0 Five (4.4 %) defined as Ba 1 Apical: Two (1.7 %) defined as C 0 Three (2.6 %) defined as C 1 The rate of mesh exposure was 2.6% (3/115). 1 uterus in situ (1.9%) 2 with concurrent hysterectomy (8.3%) Dyspareunia more common preoperatively (13.4%) than postoperatively (9.3%). PFDI-20 summary scores significantly decreased from 202.3±41.9 pre-operatively to 50.7±49 post-operatively (p <0.0001). 93% completing the SSQ reported they were satisfied and would choose the surgery again. This technique resulted in few POP recurrences (<5 %), a low rate of mesh complications (2.6%), and high rates of patient satisfaction and improved condition-specific quality of life. Pelvic Floor Clinical Support 22

23 Commitment to Clinical Research (Investigator-Sponsored Research program) Boston Scientific is committed to providing clinical data to support our key products. This sample list reflects some of the clinical research we are supporting through our Investigator-Sponsored Research program and internal-sponsored trials as we partner with the physician community to achieve clinical excellence. Lead Investigator Study Objective Primary Endpoint Target Completion White, A, Schaffer, J 1 Prospectively compare objective and subjective outcomes of Solyx SIS System to Obtryx II System for treatment of SUI Negative cough stress test and patient improvement (PGI-I) 2018 Brennand, E Evaluate two standardized techniques of Retropubic sling tensioning Abnormal post-operative bladder function at 12 months 2018 Oliveira Brito, L Prospectively compare Solyx SIS System to Obtryx II System in stress urinary incontinent (SUI) women Subjective cure (yes or no to loss, satisfaction yes/no) and objective cure (Valsalva maneuver) at 12 months 2019 García Gamón Valero, M RCT comparing Solyx to Obtryx II 24 hour pad test + PROMs 2025 Pelvic Floor Reconstruction Lead Investigator Study Objective Primary Endpoint Target Completion de Tayrac, R 2 Prospectively assess anatomic outcomes of Uphold LITE System (Anterior/Apical) for treatment of POP POP-Q score at 12 months, no bulge symptoms, no retreatment of POP 2017 Geller, E Evaluate the impact of Colpassist on individual procedure steps during RASCP and to assess surgeon satisfaction Procedural time, surgeon satisfaction, impact on operative cost 2017 Reboul, Q Retrospective study of Uphold vaginal mesh for sacrocolpopexy Day-case acceptability of surgery by patients, safety measures 2017 Gantz, M, PFDN/NICHD 3 Prospectively compare objective and subjective outcomes of Uphold LITE System (Anterior/Apical) to Hysterectomy with Uterosacral Ligament Suspension for treatment of POP POP leading edge at/ beyond hymen, bulge with bother, retreatment for failed POP repair 2018 Pelvic Floor Clinical Support 23

24 Commitment to Clinical Research (Investigator-Sponsored Research program) Lead Investigator Study Objective Primary Endpoint Target Completion Geller, E Compare vaginal mesh or suture exposure rates in women undergoing robotic total hysterectomy and sacrocolpopexy with UPsylon Y-Mesh using permanent vs delayed absorbable sutures Anatomic, subjective evaluations, additional surgical procedures for recurrent anterior or apical repair, feeling of bulge, QoL questionnaires, complications 2019 Noblett, K 4 Prospectively assess objective and subjective outcomes of Uphold LITE System (Anterior/Apical) for treatment of POP POP leading edge at/ beyond hymen, bulge with bother, retreatment for failed POP repair 2019 Rosenblatt, P 5 Prospectively assess objective and subjective outcomes of Xenform Soft Tissue Matrix for treatment of POP POP leading edge at/ beyond hymen, bulge with bother, retreatment for failed POP repair 2019 Siddighi, S Prospectively compare the effectiveness of abdominal RASCP with UPsylon Y-Mesh vs vaginal High Uterosacral Ligament Suspension POP-Q measurements at 12 months 2019 Lee, J Prospectively compare anatomic/ symptomatic outcomes of Uphold LITE System (Anterior/Apical) vs. Vaginal Hysterectomy for treatment of POP POP-Q scores at 12 months 2020 de Tayrac, R RCT of Uphold Lite vs LSC PFDI 20 and other PROMS + POP-Q 2021 * The following trials have been registered at 1. NCT NCT NCT NCT NCT Pelvic Floor Clinical Support 24

25 Products and clinical study publications listed for INFORMATION purposes only. Products may not be approved or cleared for sale in certain countries. Please check availability with your local sales representative or contact customer service. CAUTION: The law restricts these devices to sale by or on the order of a physician. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for use only in countries with applicable health authority registrations. Material not intended for use in France. For FEMALE Mid-Urethral Slings: CAUTION: U.S. Federal law restricts this device to sale by or on the order of a physician trained in use of surgical mesh for repair of stress urinary incontinence. For Coaptite Injectable Implant: INDICATIONS: Coaptite Injectable Implant is indicated for soft tissue augmentation in the treatment of stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (lsd) in adult females. CONTRAINDICATIONS: The Coaptite Injectable Implant is contraindicated for use in a patient: who has significant history of urinary tract infections without resolution; who has current or acute conditions of cystitis or urethritis; who has fragile urethral mucosal lining. POTENTIAL ADVERSE EFFECTS that may occur include: genitourinary adverse events (i.e., urinary retention, hematuria, dysuria, UTI, urinary urgency and frequency), erosion, erythema, embolic phenomena, and vascular occlusion. WARNING: Following injection of Coaptite Implant, dissection of the device through tissue may lead to 1) tissue erosion and may require corrective surgery or 2) elevation of the bladder wall causing ureteral obstruction. This may be caused by improper injection technique using Coaptite Implant. (See adverse event section in IFU for further information.) WARNING: Women with peripheral vascular disease and prior pelvic surgery may be at increased risk for tissue erosion following injection of Coaptite Implant. (See adverse event section in IFU for further information.) Please refer to complete instructions for use for a complete listing of all warnings and potential adverse effect. CAUTION: Federal Law (USA) restricts this device to sale by or on the order of a physician trained in diagnostic and therapeutic cystoscopy. For Repliform Soft Tissue Repair: Repliform Tissue Regeneration Matrix complies with US regulations in 21 CFR part 1271 Human Tissue Intended for Transplantation and is distributed exclusively by Boston Scientific. For Xenform Soft Tissue Repair Matrix: CAUTION: U.S. Federal law restricts this device to sale by or on the order of a physician trained in use of surgical mesh for repair of pelvic organ prolapse. For Uphold LITE Vaginal Support System: CAUTION: U.S. Federal law restricts this device to sale by or on the order of a physician trained in use of surgical mesh for transvaginal repair of pelvic organ prolapse. For UPsylon Y-Mesh: CAUTION: U.S. Federal law restricts this device to sale by or on the order of a physician trained in performing mesh procedures for surgical repair of pelvic organ prolapse. Accordingly for medical devices: CAUTION: U.S. Federal law restricts this device to sale by or on the order of a physician. Refer to package insert provided with this product for complete Indications for Use, Contraindications, Warnings, Precautions, Adverse Events, and Instructions prior to using this product. Results from case studies are not necessarily predictive of results in other cases. Results in other cases may vary. All trademarks are the property of their respective owners. All images are owned by Boston Scientific. Boston Scientific Corporation 300 Boston Scientific Way Marlborough, MA Ordering Information Boston Scientific Corporation or its affiliates. All rights reserved. WH AC FEB 2018