Summary of Evidence

Injectable bulking agents may offer an alternative to other interventions for individuals with urinary and fecal incontinence. For individuals with urinary incontinence, the evidence includes randomized controlled trials (RCTs) and systematic reviews. The outcome measures considered are symptoms, quality of life (QoL), morbidity, sexual function and other functional outcomes. For individuals suffering from fecal incontinence, the evidence includes RCTs and systematic reviews. Available evidence is insufficient to permit conclusions concerning the safety and efficacy of injectable bulking agents especially for fecal incontinence. Most of the evidence takes into consideration subjective outcome measures instead of objective outcomes. Well-designed large randomized controlled trials that study long-term follow-up and provide direct comparative evidence with standard therapies are needed to determine long-term efficacy and safety of injectable bulking agents.

Rationale

Several injectable bulking agents have received FDA approval for urinary incontinence. Bulkamid urethral bulking system received market approval from the FDA in 2022. Before that, the FDA granted market approval to Macroplastique in 2006, Coaptite in 2005, and Tegress in 2005, which was later removed from the market voluntarily in 2007 due to safety concerns. Previously, Durasphere was granted approval by FDA in 1999. FDA granted market approval to NASHA Dx in 2011 for fecal incontinence.

Injectable bulking agents for urinary incontinence

Siddiqui et al (2017) published a systematic review to assess the efficacy and safety of urethral bulking agents (UBA), principally Macroplastique and Bulkamid, in the treatment of female stress urinary incontinence (SUI). MEDLINE® and EMBASE® databases were systematically searched up to June 2016. Year of publication, study type, outcome measures, urodynamics before and after the procedure, number of participants, procedure complications, proportion requiring repeat injections or surgical procedures, frequency of follow-up, and results were analyzed. The use of Bulkamid and Macroplastique for the treatment of female SUI was described in 26 studies. Studies used modalities including the visual analogue scale, Likert scale, International Consultation on Incontinence Modular Questionnaire (ICIQ), Patient Global Improvement Questionnaire (PGIQ) and Incontinence Impact Questionnaire (IIQ) and showed success rates ranging from 66% to 89.7% at 12 months follow-up. Objective improvements in patient symptoms were measured using urodynamics, 24-h pad tests, cough tests and voiding diaries. Studies showed variable objective success rates ranging from 25.4% to 73.3%. Objective findings for UBAs remain less well documented than those for the midurethral sling procedure. The authors conclude that there are a range of complications associated with UBAs, the most common being urinary tract infection. However, it remains a very well tolerated procedure in the majority of patients. UBAs should be considered as an alternative in patients unsuitable for more invasive procedures and those willing to accept the need for repeat injections.

Hoe et al (2021) published a systematic review assessing and comparing the efficacy and safety of all urethral bulking agents (UBAs) available for the treatment of stress urinary incontinence (SUI) in women. This systematic review was conducted in accordance with the PRISMA guideline. A systematic search was conducted using the Ovid Medline, Embase and PubMed databases. Studies were included if they involved women who underwent either Bulkamid®, Macroplastique®, Durasphere®, Coaptite®, or Urolastic® injections for the treatment of SUI. A total of 583 articles were screened with 56 articles included. A qualitative analysis was performed. The newer synthetic UBAs are not inferior to Contigen®, with variable mean success rates of 30%-80% in the short-term. Better long-term success rates were found with Bulkamid® (42%-70%), Coaptite® (60%-75%), and Macroplastique® (21%-80%) on qualitative review. Urinary tract infection rates were similar between bulking agents (4%-10.6%) although temporary acute urinary retention was more commonly associated with Coaptite® (mean: 34.2%), and de novo urgency in Durasphere® (mean: 24.7%). Significant complications such as migration into lymph nodes was reported with Durasphere®. Erosion was reported with Macroplastique®, Coaptite®, and Urolastic®, with a rate as high as 24.6% in one study of Urolastic®. The authors concluded that available data support the use of Bulkamid® and Macroplastique®, which has shown a short-term efficacy of 30%-90% and 40%-85% respectively, and long-term efficacy of 42%-70%, and 21%-80%, respectively and that Bulkamid® appears to have a more favorable safety profile, with no cases of erosion or migration of product associated with its use. Direct comparisons of UBAs have not been performed.

Braga et al (2022) published a systematic review to summarize the findings on the use of urethral bulking agents (UBAs) in the management of rSUI after the failure of a mid-urethral sling (MUSs). They performed a systematic review and meta-analysis, according to PRISMA 2020 guidelines, and selected eleven publications for inclusion in the analysis. The overall cure and improvement rate ranged from 64% to 85% in the included studies, with a pooled value of 75%, compared with pooled failure and re-operation rates of 32% (95% CI: 22%-43%) and 25% (95% CI: 17%-34%), respectively. The I2 test indicated significant statistical heterogeneity among the studies in relation to all the outcome measures; however, no risk of publication bias was found. To explore this heterogeneity in more depth, the authors performed a sub-group analysis of the two most commonly used bulking agents (Bulkamid and Macroplastique). The pooled values of the cure and improvement rate were 84% (95% CI: 77.0%-90.0%) and 80% (95% CI: 74.0%-85.0%) for Macroplastique and Bulkamid, respectively. The authors did not find significant heterogeneity or significant differences in the outcome measures in either group. Future studies with shared protocols are needed in order to recommend the use of UBAs in the treatment of recurrent cases.

Itkonen Freitas et al (2020) published a randomized clinical trial evaluating whether polyacrylamide hydrogel is noninferior to tension-free vaginal tape to treat women with primary stress urinary incontinence. In this controlled noninferiority clinical trial patients with primary stress urinary incontinence were randomized to tension-free vaginal tape or polyacrylamide hydrogel treatment. The primary outcome was patient satisfaction and secondary outcomes were effectiveness in reducing urinary leakage and complications at 1-year follow up. For statistical power significance was considered at 5%, power was set at 80% and the noninferiority limit was 20% with a 10% expected dropout rate. A total of 224 women with primary stress urinary incontinence entered the study between September 28, 2015, and March 1, 2017. Of the women 111 were randomized to tension-free vaginal tape and 113 were randomized to polyacrylamide hydrogel. At 1 year a satisfaction score of 80 or greater on a visual analogue scale of 0 to 100 was reached in 95.0% and 59.8% of patients treated with tension-free vaginal tape and polyacrylamide hydrogel, respectively. Thus, polyacrylamide hydrogel did not meet the noninferiority criteria set in our study. As secondary outcomes, the cough stress test was negative in 95.0% of tension-free vaginal tape cases vs 66.4% of polyacrylamide hydrogel cases (difference 28.6%, 95% CI 18.4-38.5). However, most perioperative complications, including those in 19 tension-free vaginal tape cases vs 3 polyacrylamide hydrogel cases (difference 16.0%, 95% CI 7.8-24.9), and all 6 reoperations due to complications (difference 5.9%, 95% CI 1.2-12.4) were associated with tension-free vaginal tape. The authors concluded that mid urethral tension-free vaginal tape slings were associated with better satisfaction and cure rates than polyacrylamide hydrogel in women with primary stress urinary incontinence. However, complications were mainly associated with tension-free vaginal tape. Thus, tension-free vaginal tape should be offered as first line treatment in women who expect to be completely cured by the initial treatment and are willing to accept the complication risks. Since polyacrylamide hydrogel treatment also provides high satisfaction and cure rates, women with primary stress urinary incontinence can be offered polyacrylamide hydrogel as an alternative treatment.

Itkonen Freitas et al (2022) published a 3-year follow up from the randomized controlled trial seeking to determine whether polyacrylamide hydrogel (PAHG) is noninferior to tension-free vaginal tape (TVT) in the treatment of women with primary stress urinary incontinence (SUI). In this noninferiority trial, 223 women eligible for operative SUI treatment were randomized for TVT (110) or PAHG (113). Primary outcome was patient satisfaction and the noninferiority margin for the difference was 20%. Secondary outcomes were effectiveness and complications. At 3 years, 188 (84.3%) women attended the follow up. The satisfaction score (visual analogue scale 0-100) median was 98.5 (IQR 90-100) in the TVT group and 90.0 (IQR 70-100) in the PAHG group, whereas a score ≥80 was reached in 87 (94.6%) and 65 (67.7%), respectively (difference 26.9%, 95% CI 16.7% to 36.8%). Thus, PAHG did not meet the noninferiority criteria set in our study. The cough stress test was negative in 88 (95.7%) of TVT patients vs 75 (78.1%) of PAHG patients (difference 17.5%, 95% CI 8.6% to 26.9%). Any peri- or postoperative complication before crossover between the groups was detected in 40 (43.5%) women in the TVT group and 23 (24.0%) women in the PAHG group (difference 19.5%, 95% CI 6.8% to 31.4%). In midterm follow up, PAHG did not reach in patient satisfaction the noninferiority set in this study. Furthermore, mid urethral TVT slings show better subjective and objective cure rates than PAHG. However, complications were more often associated with TVT. The authors concluded that since the majority of PAHG treated women were also cured or improved, primary SUI women can be offered PAHG as a safe and durable alternative treatment.

Clark et al (2022) published a randomized controlled trial that aimed to determine whether surgical treatment is superior to endoscopic bulking injections. A two-arm trial, set in at least 20 National Health Service (NHS) urology and urogynaecology referral units in the UK, randomizing 250 adult women with recurrent or persistent SUI 1:1 to receive either an endoscopic intervention (endoscopic bulking injections) or a standard NHS surgical intervention, currently colposuspension, autologous fascial sling or artificial urinary sphincter. Symptom severity at 1 year after randomization was the primary outcome measured using the patient-reported International Consultation on Incontinence Questionnaire - Urinary Incontinence - Short Form (ICIQ-UI-SF). Secondary outcomes include assessment of longer-term clinical impact, improvement of symptoms, safety, operative assessments, sexual function, cost-effectiveness and an evaluation of patients' and clinicians' views and experiences of the interventions. The authors believed that the PURSUIT study will benefit healthcare professionals and patients and provide robust evidence to guide further treatment and improve symptoms and quality of life for women with this condition.

Injectable bulking agents for fecal incontinence

Silillis et al (2019) published a systematic review comparing the clinical outcomes and effectiveness of treatments available for FI. Forty-seven RCTs were included comparing 37 treatments and reporting on 3748 participants. No treatment ranked best or worst with high probability for any outcome of interest. No significant difference was identified between treatments for frequency of FI per week, or in changing the resting pressure, maximum resting pressure, squeeze pressure, and maximum squeeze pressure. Radiofrequency resulted in more adverse events compared to placebo. Sacral nerve stimulation (SNS) and zinc-aluminium improved the fecal incontinence quality of life questionnaire (FIQL) lifestyle, coping, and embarrassment domains compared to placebo. Transcutaneous posterior tibial nerve stimulation (TPTNS) improved the FIQL embarrassment domain compared to placebo. Autologous myoblasts and zinc-aluminium improved the FIQL depression domain compared to placebo. SNS, artificial bowel sphincter (ABS), and zinc-aluminium significantly improved incontinence scores compared to placebo. Injection of non-animal stabilized hyaluronic acid/dextranomer (NASHA/Dx) resulted in more patients with ≥50% reduction in FI episodes compared to placebo. SNS, ABS, TPTNS, NASHA/Dx, zinc-aluminium, and autologous myoblasts resulted in isolated improvements in specific outcomes of interest. No difference was identified in incontinence episodes, no treatment ranked best persistently or persistently improved outcomes, and many included treatments did not significantly benefit patients compared to placebo. To compare the outcomes and effectiveness of treatments for FI, large multicentre RCTs with long-term follow-up and standardized inclusion criteria and outcome measures are needed.

Forte et al (2016) from Agency for Healthcare Research and Quality (AHRQ) published a comparative effectiveness review assessing the efficacy and comparative effectiveness of surgical and nonsurgical treatments for fecal incontinence (FI) in adults. Two investigators screened abstracts of identified references for eligibility (examined treatments in adults with FI published from 1980 to the present that had a control/comparator group; case series were included for surgical interventions). Full-text articles were reviewed to identify patient-reported outcomes (FI episodes, FI severity, quality of life, urgency, pain, other). The authors extracted data, assessed risk of bias of individual studies, and evaluated strength of evidence for each comparison and outcome. Sixty-three unique studies met inclusion criteria; an additional 53 surgical case series were examined for adverse effects. Enrolled adults were mostly female with mixed FI etiologies. Most randomized controlled trials (RCTs) were nonsurgical (n = 38); 13 examined pelvic floor muscle training (PFMT) and PFMT with biofeedback (PFMT-BF). Meta-analysis was not possible because numerous outcomes were used. Low-strength evidence suggests that dietary fiber (psyllium) decreases FI episodes (-2.5 per week) at 1 month; clonidine has no effect; and PFMT-BF with electrostimulation is no more effective than PFMT-BF for FI severity and the FI Quality of Life scale (FIQL) over 2 to 3 months. Low-strength evidence at 6 months suggests that dextranomer anal bulking injections are more effective than sham injections on the FIQL, the number of FI-free days, and the percent of adults with at least 50-percent reduction from baseline in FI episodes, but no more effective than PFMT-BF with or without electrostimulation on FI severity (PFMT-BF -5.4 vs. dextranomer -4.6 point Vaizey score improvements) and the FIQL, and no more effective than sham injection on FI severity (-2.5 vs. -1.7 point sham improvement in Cleveland Clinic FI score [CCFIS]) or FI episode frequency. Moderate-strength evidence suggests that Durasphere® (off label) bulking injections reduce FI severity up to 6 months (-4 to -5 points CCFIS), but gains diminish thereafter. Evidence was insufficient for all other surgical and nonsurgical comparisons. Surgical improvements varied. Noninvasive nonsurgical treatments had few minor adverse effects (AEs). Surgical treatments were associated with more frequent and more severe complications than nonsurgical interventions. AEs were most frequent for the artificial bowel sphincter (22–100% of adults). Surgical AEs ranged from minor to major (infection, bowel obstruction, perforation, fistula). Major surgical complications often required reoperation, fewer required permanent colostomy. Only 12 percent of RCTs were high quality.

Graf et al (2011) published a randomized, double-blind, sham-controlled trial assessing the efficacy of injection of dextranomer in stabilized hyaluronic acid (NASHA Dx) for treatment of fecal incontinence. In this trial, patients aged 18-75 years from centres in USA and Europe were randomly assigned (2:1) to receive either transanal submucosal injections of NASHA Dx or sham injections. Randomization was stratified by sex and region in blocks of six, and managed with a computer generated, real-time, web-based system. Patients and investigators were masked to assignment for 6 months when the effect on severity of faecal incontinence and quality of life was assessed with a 2-week diary and clinical assessments. The primary endpoint was response to treatment based on the number of incontinence episodes. A response to treatment was defined as a reduction in number of episodes by 50% or more. 278 patients were screened for inclusion, of whom 206 were randomised assigned to receive NASHA Dx (n=136) or sham treatment (n=70). 71 patients who received NASHA Dx (52%) had a 50% or more reduction in the number of incontinence episode, compared with 22 patients who received sham treatment (31%; odds ratio 2·36, 95% CI 1·24-4·47, p=0·0089). The authors recorded 128 treatment-related adverse events, of which two were serious (1 rectal abscess and 1 prostatic abscess). They interpreted that anal injection of NASHA Dx is an effective treatment for faecal incontinence. The authors reported strong placebo effect observed in this study and other studies assessing treatments for FI. They also report that the optimum amount of NASHA Dx to inject and the best location for injection have not been established. The study lacked long-term follow up. Also, the authors pointed that a refinement of selection criteria for patients, optimum injected dose, ideal site of injection, and long-term results might increase the acceptance of this minimally invasive treatment.

Mellgren et al (2014) evaluated the long-term (36-month) clinical effectiveness and safety of injection of non-animal stabilized hyaluronic acid/dextranomer from the NASHA Dx RCT published by Graft et al (2011) on FI symptoms. In this prospective multicenter trial, 136 patients with FI received the NASHA Dx bulking agent. Treatment success defined as a reduction in number of FI episodes by 50% or more compared with baseline (Responder50 ). Change from baseline in Cleveland Clinic Florida Fecal Incontinence Score (CCFIS) and Fecal Incontinence Quality of Life Scale (FIQL), and adverse events were also evaluated. A decrease in symptoms was achieved in 52% of patients at 6 months and this was sustained at 12 months (57%) and 36 months (52%). Mean CCFIS decreased from 14 at baseline to 11 at 36 months (p < 0.001). Quality-of-life scores for all four domains improved significantly between baseline and 36 months of follow-up. Severe adverse events were rare and most adverse events were transient and pertained to minor bleeding and pain or discomfort.  The authors conclude that submucosal injection of NASHA Dx provided a significant improvement of FI symptoms in a majority of patients and this effect was stable during the course of the follow-up and maintained for 3 years. They also found an unexpectedly high rate of success in the sham injection arm. This underlines that effects of any treatment modality should be interpreted with caution.

Dehli et al (2013) published a randomized controlled trial evaluating the efficacy and safety of injection of a bulking agent in the anal canal in comparison to sphincter training with biofeedback in the treatment of anal incontinence. 126 adult patients with anal incontinence were randomly assigned to a transanal, submucosal injection of 4 x 1 mL of dextranomer in hyaluronic acid or to sphincter training with biofeedback. The primary outcome was severity of incontinence, evaluated by St Mark's score for incontinence (0 = continence to 24 = complete incontinence) assessed at 2 years after the start of treatment. A mixed models analysis was applied. Of the 126 participants, 64 patients were randomly assigned to anal injections, and among them the mean St Mark's score improved from 12.9 (95% CI: 11.8-14.0) at baseline to 8.3 (95% CI: 6.7-9.8) at the end of follow up. Among the 62 patients who were assigned to sphincter training with biofeedback, there was a corresponding improvement in St Mark's score from 12.6 (95% CI: 11.4-13.8) to 7.2 (95% CI: 7.2-8.8). Comparisons of St Mark's scores between the groups showed no differences in effect between treatments. The efficacy of anal injections and biofeedback in treating anal incontinence did not differ in this randomized, single-blinded, controlled trial.

Dodi et al (2010) published an open-Label, noncomparative, multicenter study evaluating efficacy and safety of NASHA/Dx Gel as a Bulking Agent for the Treatment of Fecal Incontinence.  115 eligible patients suffering from FI received 4 injections of 1 mL NASHA/Dx gel. Primary efficacy was based on data from 86 patients that completed the study. This study demonstrated a ≥50% reduction from baseline in the number of FI episodes in 57.1% of patients at 6 months, and 64.0% at 12 months. Statistically significant improvements (P < .001) were also noted in total number of both solid and loose FI episodes, FI free days, CCFIS, and FIQL scores in all 4 domains. Most of the treatment related AEs (94.9%) were mild or moderate intensity, and (98.7%) of AEs resolved spontaneously, or following treatment, without sequelae. The authors concluded that treatment effect was significant both in reduction of number of FI episodes and disease specific quality of life at 6 months and lasted up to 12 months after treatment. The study is limited by a lack of blinding and absence of comparators along with a short-term follow-up period. Although the authors mentioned that the AEs were mild or moderate intensity there were a significant number of AEs (154) reported. 24 patients were lost to follow-up over the 12-month period. Some of the authors received support in the form of research grants from QMed AB,the manufacturer of NASHA Dx.

La Torre et al (2013) evaluated the long-term efficacy and safety of NASHA/Dx. This study was a 24-month follow-up assessment of patients treated with NASHA/Dx under open-label conditions and published by Dodi et al (2010). Data on FI episodes and quality of life measures were collected from diaries over the 28-day period immediately preceding the 24-month assessment. Adverse events were collected. Eighty-three of 115 patients completed the 24-month follow-up assessment. At 24 months, 62.7% of patients were considered responders and experienced a ≥ 50% reduction in the total number of FI episodes. The median number of FI episodes declined by 68.8% (P < 0.001). Episodes of both solid and liquid stool incontinence decreased. The mean number of incontinence-free days increased from 14.6 at baseline to 21.7 at 24 months (P < 0.001). Incontinence scores and FI quality of life scores also showed significant improvements. The most common adverse events (AEs) were proctalgia (13.3%) and pyrexia (9.6%). The majority of AEs were mild to moderate, self-limited and resolved within 1 month of the injection. The authors concluded that NASHA/Dx is safe, effective and durable over a 24-month period with a majority of patients experiencing significant improvement in multiple symptoms associated with FI. The study was limited by lack of blinding, non-comparative nature of study, a considerable attrition rate and lack of long-term follow-up. The study was funded by Q- Med AB, the manufacturer of NASHA Dx.

In 2015, the American College of Obstetricians and Gynecologists (ACOG) published an update on the practice bulletin on urinary incontinence in Women, which was reaffirmed in 2022. These conclusions and recommendations are based on limited or inconsistent scientific evidence (Level B). They state that Urethral bulking injections are a relatively noninvasive treatment for stress urinary incontinence that may be appropriate if surgery has failed to achieve adequate symptom reduction, if symptoms recur after surgery, in women with symptoms who do not have urethral mobility, or in older women with comorbidities who cannot tolerate anesthesia or more invasive surgery.

The 2023 updates to surgical treatment of female stress urinary incontinence (SUI): AUA/SUFU guideline published by the American Urological Association and Society of Urodynamics state that, “because re-treatment is common for urethral bulking injection, outcomes assessment is challenging. Inadequate data exist to support recommendation of 1 injectable agent over another. Still, bulking agents may have a role in patients who wish to avoid more invasive surgical management, lengthier recovery time after surgery, or who experience insufficient improvement following an anti-incontinence procedure. Patients should be counseled on the expected need for repeat injections. There are limited long-term data on bulking agents. Calcium hydroxyapatite, polydimethylsiloxane, and polyacrylamide hydrogel (PAHG) have longer-term data that show persistence of effect at 73.2, 83, and 96 months, respectively. In an index SUI patient group studied in a recent RCT, PAHG demonstrated a lower satisfaction rate compared with TVT; however, the majority of women treated with PAHG were considered cured or improved at 3-year follow-up.20,21 Some interpret this finding to suggest that patients may choose the less invasive urethral bulking injection over sling surgery despite lower success. While re-injection may be required with all bulking agents, erosions were not noted in PAHG patients as with other bulking agents in multiple studies.”

In 2019, the National Institute for Health and Care Excellence published updated guidelines on urinary incontinence and pelvic organ prolapse in women. The guidance asks to consider intramural bulking agents to manage stress urinary incontinence if alternative surgical procedures are not suitable for or acceptable to the woman. Explain to the patient that these are permanent injectable materials, repeat injections may be needed to achieve effectiveness, limited evidence suggests that they are less effective than the surgical, procedures listed in recommendation 1.5.2 and the effects wear off over time, and there is limited evidence on long-term effectiveness and adverse events. It also states that If an intramural bulking agent is injected, give the woman written information about the bulking agent, including its name, manufacturer, date of injection, and the injecting surgeon's name and contact details.

In 2019, the American College of Obstetricians and Gynecologists (ACOG) published the Practice bulletin on Fecal Incontinence, which was reconfirmed in 2023. These recommendations are based on limited or inconsistent scientific evidence (Level B).They state that anal sphincter bulking agents may be effective in decreasing fecal incontinence episodes up to 6 months and can be considered as a short-term treatment option for fecal incontinence in women who have failed more conservative treatments.

In 2017, the American Gastroenterological Association (AGA) published the guidance on Surgical Interventions and the Use of Device-Aided Therapy for the Treatment of Fecal Incontinence and Defecatory Disorders. They state that “Perianal bulking agents such as intra-anal injection of dextranomer may be considered when conservative measures and biofeedback therapy fail”.

In 2007, the National Institute for Health and Care Excellence (NICE) published a guidance on Injectable bulking agents for fecal incontinence. The NICE states that current evidence on the safety and efficacy of injectable bulking agents for fecal incontinence does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research, which should take place in the context of a clinical trial or formal audit protocol that includes information on well-defined patient groups. Clinicians wishing to inject bulking agents for the treatment of fecal incontinence should inform the clinical governance leads in their trusts, ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. In addition, use of NICE's information for the public is recommended. They also recommend audit and review of clinical outcomes of all patients receiving injectable bulking agents for fecal incontinence. The procedure should only be performed in units specializing in the assessment and treatment of fecal incontinence. NICE may review the procedure upon publication of further evidence.

In 2023, the American Society of Colon and Rectal Surgeons published the Clinical Practice Guidelines for the Management of Fecal Incontinence. They state that “Injection of Biocompatible Bulking Agents Into the anal canal Is not routinely recommended for the treatment of FI. Given the limited improvement over placebo, diminishing long-term results, and cost, injectable bulking agents are not considered first-line treatment for FI.”

Reference List

1. Siddiqui ZA, Abboudi H, Crawford R, Shah S. Intraurethral bulking agents for the management of female stress urinary incontinence: a systematic review. Int Urogynecol J. 2017;28(9):1275-1284. doi:10.1007/s00192-017-3278-7
2. Hoe V, Haller B, Yao HH, O'Connell HE. Urethral bulking agents for the treatment of stress urinary incontinence in women: A systematic review. Neurourol Urodyn. 2021;40(6):1349-1388. doi:10.1002/nau.24696
3. Braga A, Caccia G, Papadia A, et al. Urethral bulking agents for the treatment of recurrent stress urinary incontinence: A systematic review and meta-analysis. Maturitas. 2022;163:28-37. doi:10.1016/j.maturitas.2022.05.007
4. Itkonen Freitas AM, Mentula M, Rahkola-Soisalo P, Tulokas S, Mikkola TS. Tension-Free Vaginal Tape Surgery versus Polyacrylamide Hydrogel Injection for Primary Stress Urinary Incontinence: A Randomized Clinical Trial. J Urol. 2020;203(2):372-378. doi:10.1097/JU.0000000000000517
5. Itkonen Freitas AM, Isaksson C, Rahkola-Soisalo P, Tulokas S, Mentula M, Mikkola TS. Tension-Free Vaginal Tape and Polyacrylamide Hydrogel Injection for Primary Stress Urinary Incontinence: 3-Year Followup from a Randomized Clinical Trial. J Urol. 2022;208(3):658-667. doi:10.1097/JU.000000000000272
6. Clark L, Fitzgerald B, Noble S, et al. Proper understanding of recurrent stress urinary incontinence treatment in women (PURSUIT): a randomised controlled trial of endoscopic and surgical treatment. Trials. 2022;23(1):628. Published 2022 Aug 3. doi:10.1186/s13063-022-06546-9
7. Simillis C, Lal N, Pellino G, et al. A systematic review and network meta-analysis comparing treatments for faecal incontinence. Int J Surg. 2019;66:37-47. doi:10.1016/j.ijsu.2019.04.007
8. Forte ML, Andrade KE, Butler M, et al. Treatments for Fecal Incontinence (Comparative Effectiveness Review No. 165). Rockville, MD: Agency for Healthcare Research and Quality; 2016.
9. Graf W, Mellgren A, Matzel KE, et al. Efficacy of dextranomer in stabilised hyaluronic acid for treatment of faecal incontinence: a randomised, sham-controlled trial. Lancet. 2011;377(9770):997-1003. doi:10.1016/S0140-6736(10)62297-0
10. Mellgren A, Matzel KE, Pollack J, et al. Long-term efficacy of NASHA Dx injection therapy for treatment of fecal incontinence. Neurogastroenterol Motil. 2014;26(8):1087-1094. doi:10.1111/nmo.12360
11. Dehli T, Stordahl A, Vatten LJ, et al. Sphincter training or anal injections of dextranomer for treatment of anal incontinence: a randomized trial. Scand J Gastroenterol. 2013;48(3):302-310. doi:10.3109/00365521.2012.758770
12. Dodi G, Jongen J, de la Portilla F, Raval M, Altomare DF, Lehur PA. An Open-Label, Noncomparative, Multicenter Study to Evaluate Efficacy and Safety of NASHA/Dx Gel as a Bulking Agent for the Treatment of Fecal Incontinence. Gastroenterol Res Pract. 2010;2010:467136. doi: 10.1155/2010/467136. Epub 2010 Dec 27. PMID: 21234379; PMCID: PMC3017894.
13. La Torre F, de la Portilla F. Long-term efficacy of dextranomer in stabilized hyaluronic acid (NASHA/Dx) for treatment of faecal incontinence. Colorectal Dis. 2013;15(5):569-574. doi:10.1111/codi.12155
14. Food and Drug Administration: Durasphere Injectable bulking agent. https://www.accessdata.fda.gov/cdrh_docs/pdf/P980053B.pdf
15. Food and Drug Administration: Coaptite®. https://www.accessdata.fda.gov/cdrh_docs/pdf4/p040047b.pdf
16. Food and Drug Administration: Macroplastique implants. https://www.accessdata.fda.gov/cdrh_docs/pdf4/P040050B.pdf
17. Food and Drug Administration: Solesta injectable gel. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P100014
18. ACOG Practice Bulletin No. 155: Urinary Incontinence in Women. Obstet Gynecol. 2015;126(5):e66-e81. doi:10.1097/AOG.0000000000001148
19. Kobashi KC, Albo ME, Dmochowski RR, et al. Surgical Treatment of Female Stress Urinary Incontinence: AUA/SUFU Guideline. J Urol. 2017;198(4):875-883. doi:10.1016/j.juro.2017.06.061
20. Kobashi KC, Vasavada S, Bloschichak A, et al. Updates to Surgical Treatment of Female Stress Urinary Incontinence (SUI): AUA/SUFU Guideline (2023). J Urol. 2023;209(6):1091-1098. doi:10.1097/JU.0000000000003435
21. National Institute for Health and Care Excellence (NICE). Urinary incontinence and pelvic organ prolapse in women: management [NG123]. 2019; https://www.nice.org.uk/guidance/ng123.
22. ACOG Practice Bulletin No. 210: Fecal Incontinence [published correction appears in Obstet Gynecol. 2019 Nov;134(5):1121. doi: 10.1097/AOG.0000000000003572]. Obstet Gynecol. 2019;133(4):e260-e273. doi:10.1097/AOG.0000000000003187
23. National Institute for Health and Care Excellence (NICE). Injectable bulking agents for faecal incontinence [IPG210]. 2007; https://www.nice.org.uk/guidance/ipg210/chapter/1-guidance. Accessed September 4, 2023.
24. Bordeianou, Liliana G. M.D., M.P.H.1; Thorsen, Amy J. M.D.2; Keller, Deborah S. M.S., M.D.3; Hawkins, Alexander T. M.D., M.P.H.4; Messick, Craig M.D.5; Oliveira, Lucia M.D., Ph.D.6; Feingold, Daniel L. M.D.7; Lightner, Amy L. M.D.8; Paquette, Ian M. M.D.9. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Fecal Incontinence. Diseases of the Colon & Rectum 66(5):p 647-661, May 2023. | DOI: 10.1097/DCR.0000000000002776