Amy Rothman Schonfeld

PROVIDENCE, R.I. – A short course of the urinary antibiotic nitrofurantoin after midurethral sling placement for stress incontinence reduced the incidence of postprocedure urinary tract infection by nearly 50%, according to Dr. Daniel Jackson.

"In the last 10 years, the literature has shown that the incidence of UTIs after sling placement ranges from 8.9% to 34%," said Dr. Jackson of the University of Missouri–Columbia. "We asked whether the incidence of postoperative bladder infection related to midurethral sling placement could be significantly reduced by a short course of a common, inexpensive urinary antibiotic."

In this prospective, double-blind study, 159 women from two academic medical centers scheduled to undergo outpatient vaginal surgery for stress incontinence were randomized to receive either nitrofurantoin (100 mg twice daily) or placebo for 3 days after surgery. Data were analyzed from 74 women who received an antibiotic and 75 women who received placebo. All patients received preoperative treatment with a third-generation cephalosporin. At the 6-week visit, a positive diagnosis depended on a positive review of systems for dysuria and frequency and a negative review of systems for vaginal discharge or irritation, as well as a positive urine dip and urine culture.

Almost one-quarter of women who underwent midurethral sling placement (n = 37/149, 24.8%) were diagnosed with a UTI during the study period. Treatment with an antibiotic significantly reduced the incidence of UTIs, from 32% in the placebo group to 17.6% in the nitrofurantoin group, he reported at the annual meeting of the American Urogynecologic Society.

Multivariate analysis indicated that two variables, antibiotic use and no postoperative catheter use, were independently associated with a reduced risk of UTI development.

No adverse events were reported. One woman developed a peripheral neuropathy and discontinued her study medication, but after the study was unblinded, it was discovered she was in the placebo group.

In response to a question from the audience, Dr. Jackson said that the choice of antibiotic, nitrofurantoin, was based on its cost and his institution’s preferences, but he said he had no definitive evidence regarding whether other urinary antibiotics would produce comparable or better results.

Dr. Jackson said he had no relevant financial disclosures.

PROVIDENCE, R.I. – A short course of the urinary antibiotic nitrofurantoin after midurethral sling placement for stress incontinence reduced the incidence of postprocedure urinary tract infection by nearly 50%, according to Dr. Daniel Jackson.

"In the last 10 years, the literature has shown that the incidence of UTIs after sling placement ranges from 8.9% to 34%," said Dr. Jackson of the University of Missouri–Columbia. "We asked whether the incidence of postoperative bladder infection related to midurethral sling placement could be significantly reduced by a short course of a common, inexpensive urinary antibiotic."

In this prospective, double-blind study, 159 women from two academic medical centers scheduled to undergo outpatient vaginal surgery for stress incontinence were randomized to receive either nitrofurantoin (100 mg twice daily) or placebo for 3 days after surgery. Data were analyzed from 74 women who received an antibiotic and 75 women who received placebo. All patients received preoperative treatment with a third-generation cephalosporin. At the 6-week visit, a positive diagnosis depended on a positive review of systems for dysuria and frequency and a negative review of systems for vaginal discharge or irritation, as well as a positive urine dip and urine culture.

Almost one-quarter of women who underwent midurethral sling placement (n = 37/149, 24.8%) were diagnosed with a UTI during the study period. Treatment with an antibiotic significantly reduced the incidence of UTIs, from 32% in the placebo group to 17.6% in the nitrofurantoin group, he reported at the annual meeting of the American Urogynecologic Society.

Multivariate analysis indicated that two variables, antibiotic use and no postoperative catheter use, were independently associated with a reduced risk of UTI development.

No adverse events were reported. One woman developed a peripheral neuropathy and discontinued her study medication, but after the study was unblinded, it was discovered she was in the placebo group.

In response to a question from the audience, Dr. Jackson said that the choice of antibiotic, nitrofurantoin, was based on its cost and his institution’s preferences, but he said he had no definitive evidence regarding whether other urinary antibiotics would produce comparable or better results.

Dr. Jackson said he had no relevant financial disclosures.

PROVIDENCE, R.I. – A short course of the urinary antibiotic nitrofurantoin after midurethral sling placement for stress incontinence reduced the incidence of postprocedure urinary tract infection by nearly 50%, according to Dr. Daniel Jackson.

"In the last 10 years, the literature has shown that the incidence of UTIs after sling placement ranges from 8.9% to 34%," said Dr. Jackson of the University of Missouri–Columbia. "We asked whether the incidence of postoperative bladder infection related to midurethral sling placement could be significantly reduced by a short course of a common, inexpensive urinary antibiotic."

In this prospective, double-blind study, 159 women from two academic medical centers scheduled to undergo outpatient vaginal surgery for stress incontinence were randomized to receive either nitrofurantoin (100 mg twice daily) or placebo for 3 days after surgery. Data were analyzed from 74 women who received an antibiotic and 75 women who received placebo. All patients received preoperative treatment with a third-generation cephalosporin. At the 6-week visit, a positive diagnosis depended on a positive review of systems for dysuria and frequency and a negative review of systems for vaginal discharge or irritation, as well as a positive urine dip and urine culture.

Almost one-quarter of women who underwent midurethral sling placement (n = 37/149, 24.8%) were diagnosed with a UTI during the study period. Treatment with an antibiotic significantly reduced the incidence of UTIs, from 32% in the placebo group to 17.6% in the nitrofurantoin group, he reported at the annual meeting of the American Urogynecologic Society.

Multivariate analysis indicated that two variables, antibiotic use and no postoperative catheter use, were independently associated with a reduced risk of UTI development.

No adverse events were reported. One woman developed a peripheral neuropathy and discontinued her study medication, but after the study was unblinded, it was discovered she was in the placebo group.

In response to a question from the audience, Dr. Jackson said that the choice of antibiotic, nitrofurantoin, was based on its cost and his institution’s preferences, but he said he had no definitive evidence regarding whether other urinary antibiotics would produce comparable or better results.

Dr. Jackson said he had no relevant financial disclosures.

PROVIDENCE, R.I. – Vitamin D levels were significantly lower in women diagnosed with a pelvic floor disorder than in a comparison group of gynecology patients without pelvic floor disorders, based on a retrospective chart review of patients seen at a urogynecology care clinic between 2008 and 2010.

In the study, 550 patients had both a clinic visit and an assessment of vitamin D levels, but 156 were excluded from consideration because of missing clinical data (n = 137), stage III or greater kidney disease (n = 17), or other medical conditions (n = 2).

Of the 394 remaining patients, 268 had at least one pelvic floor disorder (PFD). The most common diagnoses were pelvic organ prolapse (49%) and mixed urinary incontinence (30%). In the "benign gynecologic" group used for comparison, 126 women were seen for routine gynecologic exams but were not diagnosed with any PFD.

The women with PFDs were older (64.3 years vs. 60.2 years, P = .005), and included a greater percentage of blacks (40% vs. 20%, P = .05), reported Dr. Candace Y. Parker-Autry, who presented the findings as a poster at the annual meeting of the American Urogynecologic Society.

Dr. Parker-Autry reported that total mean 25(OH)D levels were 29.3 ng/mL (± 11.5) in women with PFDs and 35.0 ng/mL (± 14.1 ng/mL) in women without PFDs. The difference was statistically significant (P = .001).

Vitamin D insufficiency was defined as levels between 15 ng/mL and 29 ng/mL; levels below 15 ng/mL were deemed deficient.

Among women with PFDs, 51.5% had insufficient or deficient vitamin D levels with mean 25(OH)D levels of 18.6 ng/mL and 48.5% were found to be vitamin D-sufficient with mean 25(OH)D levels of 38.4 ng/mL (P = .001). Women who had PFDs and were vitamin D sufficient were significantly more likely to have taken vitamin D and calcium supplements.

Some racial disparity was noted. Vitamin D insufficiency/deficiency was noted in 50% of non-Hispanic whites and in 68% of black women with PFDs.

Approximately 73% of U.S. adults and 80% of reproductive aged women have insufficient vitamin D levels, according to Dr. Parker-Autry, who is affiliated with the division of urogynecology and pelvic reconstructive surgery at the University of Alabama at Birmingham. The question remains whether vitamin D insufficiency contributes to pelvic muscle weakness and PFDs.

At their baseline evaluations, women in the PFD group were asked to complete three validated questionnaires, assessing the impact of their symptoms on quality of life, including the Pelvic Floor Distress Inventory and its three subscales (Pelvic Organ Prolapse Distress Severity (POPDI-6), the Colorectal-Anal Distress Inventory (CRDAI-8), and the Urogenital Distress Inventory for Incontinence (UDI-6); the Medical, Epidemiologic, and Social Aspects of Aging (MESA) questionnaire, and the Incontinence Impact Questionnaire (IIQ-7). After controlling for confounding variables, vitamin D insufficiency was associated with a greater negative impact from urinary incontinence symptoms (P = .001 on the IIQ-7) but there were no other significant differences regarding other pelvic or colorectal symptoms.

Dr. Parker-Autry had no disclosures.

PROVIDENCE, R.I. – Vitamin D levels were significantly lower in women diagnosed with a pelvic floor disorder than in a comparison group of gynecology patients without pelvic floor disorders, based on a retrospective chart review of patients seen at a urogynecology care clinic between 2008 and 2010.

In the study, 550 patients had both a clinic visit and an assessment of vitamin D levels, but 156 were excluded from consideration because of missing clinical data (n = 137), stage III or greater kidney disease (n = 17), or other medical conditions (n = 2).

Of the 394 remaining patients, 268 had at least one pelvic floor disorder (PFD). The most common diagnoses were pelvic organ prolapse (49%) and mixed urinary incontinence (30%). In the "benign gynecologic" group used for comparison, 126 women were seen for routine gynecologic exams but were not diagnosed with any PFD.

The women with PFDs were older (64.3 years vs. 60.2 years, P = .005), and included a greater percentage of blacks (40% vs. 20%, P = .05), reported Dr. Candace Y. Parker-Autry, who presented the findings as a poster at the annual meeting of the American Urogynecologic Society.

Dr. Parker-Autry reported that total mean 25(OH)D levels were 29.3 ng/mL (± 11.5) in women with PFDs and 35.0 ng/mL (± 14.1 ng/mL) in women without PFDs. The difference was statistically significant (P = .001).

Vitamin D insufficiency was defined as levels between 15 ng/mL and 29 ng/mL; levels below 15 ng/mL were deemed deficient.

Among women with PFDs, 51.5% had insufficient or deficient vitamin D levels with mean 25(OH)D levels of 18.6 ng/mL and 48.5% were found to be vitamin D-sufficient with mean 25(OH)D levels of 38.4 ng/mL (P = .001). Women who had PFDs and were vitamin D sufficient were significantly more likely to have taken vitamin D and calcium supplements.

Some racial disparity was noted. Vitamin D insufficiency/deficiency was noted in 50% of non-Hispanic whites and in 68% of black women with PFDs.

Approximately 73% of U.S. adults and 80% of reproductive aged women have insufficient vitamin D levels, according to Dr. Parker-Autry, who is affiliated with the division of urogynecology and pelvic reconstructive surgery at the University of Alabama at Birmingham. The question remains whether vitamin D insufficiency contributes to pelvic muscle weakness and PFDs.

At their baseline evaluations, women in the PFD group were asked to complete three validated questionnaires, assessing the impact of their symptoms on quality of life, including the Pelvic Floor Distress Inventory and its three subscales (Pelvic Organ Prolapse Distress Severity (POPDI-6), the Colorectal-Anal Distress Inventory (CRDAI-8), and the Urogenital Distress Inventory for Incontinence (UDI-6); the Medical, Epidemiologic, and Social Aspects of Aging (MESA) questionnaire, and the Incontinence Impact Questionnaire (IIQ-7). After controlling for confounding variables, vitamin D insufficiency was associated with a greater negative impact from urinary incontinence symptoms (P = .001 on the IIQ-7) but there were no other significant differences regarding other pelvic or colorectal symptoms.

Dr. Parker-Autry had no disclosures.

PROVIDENCE, R.I. – Vitamin D levels were significantly lower in women diagnosed with a pelvic floor disorder than in a comparison group of gynecology patients without pelvic floor disorders, based on a retrospective chart review of patients seen at a urogynecology care clinic between 2008 and 2010.

In the study, 550 patients had both a clinic visit and an assessment of vitamin D levels, but 156 were excluded from consideration because of missing clinical data (n = 137), stage III or greater kidney disease (n = 17), or other medical conditions (n = 2).

Of the 394 remaining patients, 268 had at least one pelvic floor disorder (PFD). The most common diagnoses were pelvic organ prolapse (49%) and mixed urinary incontinence (30%). In the "benign gynecologic" group used for comparison, 126 women were seen for routine gynecologic exams but were not diagnosed with any PFD.

The women with PFDs were older (64.3 years vs. 60.2 years, P = .005), and included a greater percentage of blacks (40% vs. 20%, P = .05), reported Dr. Candace Y. Parker-Autry, who presented the findings as a poster at the annual meeting of the American Urogynecologic Society.

Dr. Parker-Autry reported that total mean 25(OH)D levels were 29.3 ng/mL (± 11.5) in women with PFDs and 35.0 ng/mL (± 14.1 ng/mL) in women without PFDs. The difference was statistically significant (P = .001).

Vitamin D insufficiency was defined as levels between 15 ng/mL and 29 ng/mL; levels below 15 ng/mL were deemed deficient.

Among women with PFDs, 51.5% had insufficient or deficient vitamin D levels with mean 25(OH)D levels of 18.6 ng/mL and 48.5% were found to be vitamin D-sufficient with mean 25(OH)D levels of 38.4 ng/mL (P = .001). Women who had PFDs and were vitamin D sufficient were significantly more likely to have taken vitamin D and calcium supplements.

Some racial disparity was noted. Vitamin D insufficiency/deficiency was noted in 50% of non-Hispanic whites and in 68% of black women with PFDs.

Approximately 73% of U.S. adults and 80% of reproductive aged women have insufficient vitamin D levels, according to Dr. Parker-Autry, who is affiliated with the division of urogynecology and pelvic reconstructive surgery at the University of Alabama at Birmingham. The question remains whether vitamin D insufficiency contributes to pelvic muscle weakness and PFDs.

At their baseline evaluations, women in the PFD group were asked to complete three validated questionnaires, assessing the impact of their symptoms on quality of life, including the Pelvic Floor Distress Inventory and its three subscales (Pelvic Organ Prolapse Distress Severity (POPDI-6), the Colorectal-Anal Distress Inventory (CRDAI-8), and the Urogenital Distress Inventory for Incontinence (UDI-6); the Medical, Epidemiologic, and Social Aspects of Aging (MESA) questionnaire, and the Incontinence Impact Questionnaire (IIQ-7). After controlling for confounding variables, vitamin D insufficiency was associated with a greater negative impact from urinary incontinence symptoms (P = .001 on the IIQ-7) but there were no other significant differences regarding other pelvic or colorectal symptoms.

Dr. Parker-Autry had no disclosures.

PROVIDENCE, R.I. – Compared with cesarean birth without labor, undergoing vaginal birth increased the risk of stress incontinence and prolapse in women who were examined 5–10 years after childbirth, Dr. Victoria L. Handa reported.

The risk of all pelvic disorders, including prolapse, was elevated even further in women who had undergone operative vaginal delivery, she said.

“The results suggest no measurable differences in the relative odds of any pelvic floor disorder for women delivering by cesarean section, including those who labored into the second stage. For vaginal birth, the picture is very different,” said Dr. Handa, director of the advanced training program in female pelvic medicine and reconstructive surgery at Johns Hopkins University, Baltimore.

In this longitudinal cohort study based on hospital obstetric records, 8,285 women who had their first child 5–10 years previously were recruited for the study and 1,011 were enrolled. Women were selected if their obstetric history met one of five categories: cesarean without labor (considered the reference group; n = 192), cesarean during active labor (n = 228), cesarean after complete cervical dilation (n = 140), spontaneous vaginal birth (n = 325), and operative vaginal birth (n = 126). Groups were matched for age at first delivery and interval from first delivery, and were similar with respect to parity and smoking status. At enrollment, a validated questionnaire (Epidemiology of Prolapse and Incontinence Questionnaire) was used to assess pelvic floor symptoms, and the women were examined for pelvic organ support using the Pelvic Organ Prolapse Quantification (POP-Q) System.

“One of the strengths of our study is that [obstetric] exposures were verified by chart review with validated outcomes, and there was [anatomical] evidence of prolapse,” Dr. Handa said.

Overall, 11% of the 1,011 women had stress urinary incontinence, 8% had overactive bladder, and 11% had anal incontinence; 3% reported prolapse symptoms, and 7% had prolapse upon examination (Obstet. Gynecol. 2011;118:777–84).

Compared with women who had a cesarean birth before active labor, women who had a vaginal birth (but no operative vaginal births) had almost a threefold increased risk of stress incontinence and symptomatic prolapse. The odds ratio for prolapse was increased more than fivefold.

Women who had undergone operative vaginal birth fared even worse. The adjusted odds of stress incontinence and overactive bladder were more than quadrupled. There was almost an eightfold increased risk of prolapse upon exam.

In her report, Dr. Handa noted that in addition to demonstrating the dramatic increase in pelvic floor disorders in women with a history of at least one operative vaginal birth, the results showed an increase in urinary incontinence after operative delivery – a finding that had not been definitively documented before. For those who had undergone cesarean delivery, the results showed no association between active labor and pelvic floor disorders.

The study was also the first to demonstrate an association between operative vaginal birth and prolapse, even in asymptomatic women. By continuing to monitor these women, Dr. Handa hopes to be able to document the natural history of prolapse over time, especially in those women who were unaware of their condition.

Dr. Handa did not report any relevant financial disclosures.

PROVIDENCE, R.I. – Compared with cesarean birth without labor, undergoing vaginal birth increased the risk of stress incontinence and prolapse in women who were examined 5–10 years after childbirth, Dr. Victoria L. Handa reported.

The risk of all pelvic disorders, including prolapse, was elevated even further in women who had undergone operative vaginal delivery, she said.

“The results suggest no measurable differences in the relative odds of any pelvic floor disorder for women delivering by cesarean section, including those who labored into the second stage. For vaginal birth, the picture is very different,” said Dr. Handa, director of the advanced training program in female pelvic medicine and reconstructive surgery at Johns Hopkins University, Baltimore.

In this longitudinal cohort study based on hospital obstetric records, 8,285 women who had their first child 5–10 years previously were recruited for the study and 1,011 were enrolled. Women were selected if their obstetric history met one of five categories: cesarean without labor (considered the reference group; n = 192), cesarean during active labor (n = 228), cesarean after complete cervical dilation (n = 140), spontaneous vaginal birth (n = 325), and operative vaginal birth (n = 126). Groups were matched for age at first delivery and interval from first delivery, and were similar with respect to parity and smoking status. At enrollment, a validated questionnaire (Epidemiology of Prolapse and Incontinence Questionnaire) was used to assess pelvic floor symptoms, and the women were examined for pelvic organ support using the Pelvic Organ Prolapse Quantification (POP-Q) System.

“One of the strengths of our study is that [obstetric] exposures were verified by chart review with validated outcomes, and there was [anatomical] evidence of prolapse,” Dr. Handa said.

Overall, 11% of the 1,011 women had stress urinary incontinence, 8% had overactive bladder, and 11% had anal incontinence; 3% reported prolapse symptoms, and 7% had prolapse upon examination (Obstet. Gynecol. 2011;118:777–84).

Compared with women who had a cesarean birth before active labor, women who had a vaginal birth (but no operative vaginal births) had almost a threefold increased risk of stress incontinence and symptomatic prolapse. The odds ratio for prolapse was increased more than fivefold.

Women who had undergone operative vaginal birth fared even worse. The adjusted odds of stress incontinence and overactive bladder were more than quadrupled. There was almost an eightfold increased risk of prolapse upon exam.

In her report, Dr. Handa noted that in addition to demonstrating the dramatic increase in pelvic floor disorders in women with a history of at least one operative vaginal birth, the results showed an increase in urinary incontinence after operative delivery – a finding that had not been definitively documented before. For those who had undergone cesarean delivery, the results showed no association between active labor and pelvic floor disorders.

The study was also the first to demonstrate an association between operative vaginal birth and prolapse, even in asymptomatic women. By continuing to monitor these women, Dr. Handa hopes to be able to document the natural history of prolapse over time, especially in those women who were unaware of their condition.

Dr. Handa did not report any relevant financial disclosures.

PROVIDENCE, R.I. – Compared with cesarean birth without labor, undergoing vaginal birth increased the risk of stress incontinence and prolapse in women who were examined 5–10 years after childbirth, Dr. Victoria L. Handa reported.

The risk of all pelvic disorders, including prolapse, was elevated even further in women who had undergone operative vaginal delivery, she said.

“The results suggest no measurable differences in the relative odds of any pelvic floor disorder for women delivering by cesarean section, including those who labored into the second stage. For vaginal birth, the picture is very different,” said Dr. Handa, director of the advanced training program in female pelvic medicine and reconstructive surgery at Johns Hopkins University, Baltimore.

In this longitudinal cohort study based on hospital obstetric records, 8,285 women who had their first child 5–10 years previously were recruited for the study and 1,011 were enrolled. Women were selected if their obstetric history met one of five categories: cesarean without labor (considered the reference group; n = 192), cesarean during active labor (n = 228), cesarean after complete cervical dilation (n = 140), spontaneous vaginal birth (n = 325), and operative vaginal birth (n = 126). Groups were matched for age at first delivery and interval from first delivery, and were similar with respect to parity and smoking status. At enrollment, a validated questionnaire (Epidemiology of Prolapse and Incontinence Questionnaire) was used to assess pelvic floor symptoms, and the women were examined for pelvic organ support using the Pelvic Organ Prolapse Quantification (POP-Q) System.

“One of the strengths of our study is that [obstetric] exposures were verified by chart review with validated outcomes, and there was [anatomical] evidence of prolapse,” Dr. Handa said.

Overall, 11% of the 1,011 women had stress urinary incontinence, 8% had overactive bladder, and 11% had anal incontinence; 3% reported prolapse symptoms, and 7% had prolapse upon examination (Obstet. Gynecol. 2011;118:777–84).

Compared with women who had a cesarean birth before active labor, women who had a vaginal birth (but no operative vaginal births) had almost a threefold increased risk of stress incontinence and symptomatic prolapse. The odds ratio for prolapse was increased more than fivefold.

Women who had undergone operative vaginal birth fared even worse. The adjusted odds of stress incontinence and overactive bladder were more than quadrupled. There was almost an eightfold increased risk of prolapse upon exam.

In her report, Dr. Handa noted that in addition to demonstrating the dramatic increase in pelvic floor disorders in women with a history of at least one operative vaginal birth, the results showed an increase in urinary incontinence after operative delivery – a finding that had not been definitively documented before. For those who had undergone cesarean delivery, the results showed no association between active labor and pelvic floor disorders.

The study was also the first to demonstrate an association between operative vaginal birth and prolapse, even in asymptomatic women. By continuing to monitor these women, Dr. Handa hopes to be able to document the natural history of prolapse over time, especially in those women who were unaware of their condition.

Dr. Handa did not report any relevant financial disclosures.

PROVIDENCE, R.I. – Use of a prophylactic mid-urethral sling during the course of transvaginal prolapse repair significantly reduced the risk of urinary incontinence symptoms at 3 and 12 months post surgery, according to Dr. John T. Wei.

“The basis for this trial is a common dilemma we face: When a woman with significant vaginal prolapse but no stress-related urinary incontinence undergoes transvaginal prolapse repair, should a sling be placed in all women or should treatment be delayed until she develops symptomatic urinary incontinence? Level 1 evidence does not exist to address that question, and that is why the Pelvic Floor Disorders Network [PFDN] commissioned the OPUS [Outcomes Following Vaginal Prolapse Repair and Midurethral Sling] trial,” said Dr. Wei, professor of urology at the University of Michigan, Ann Arbor. Dr. Wei's presentation earned the “Best Overall Paper” award at the meeting.

The PFDN was created by the National Institute of Child Health and Human Development's contraception and reproductive health branch. It consists of eight clinical sites and one data-coordinating center. This is the first protocol conducted by the PFDN.

In the OPUS trial, 337 women with symptomatic greater than or equal to stage 2 anterior prolapse who did not report symptoms of stress urinary incontinence (SUI) were randomized to undergo either insertion of retropubic tension-free vaginal tape (TVT) (n=165) or sham incisions (n=172) during prolapse surgery. The primary end point was urinary incontinence (UI) failure, defined as having at least one of the following: a positive cough stress test, bothersome UI symptoms, or treatment for UI (pharmacologic or surgical).

Three months after surgery, the rate of UI failure in those who received a prophylactic sling was less than half of that seen in the sham-operated group (23.6% vs. 49.4%, P less than .0001). Similar results were noted at 12 months (27.3% vs. 43.0%, P = .0024), even after allowing for additional UI postoperative treatment. Significant differences favoring the sling also were found for quality of life measures. However, no significant differences between groups were found for measures of other pelvic floor conditions such as prolapse, pain, or decreased sexual function or general health (as measured by the short form SF-36 questionnaire).

Although there were no significant differences between groups in serious and unexpected adverse events, those in the TVT group had higher rates of bladder perforations (6.7% vs. 0%), urinary tract infections (31% vs. 17.2%), major bleeding/vascular complications (3% vs. 0%) or incomplete bladder emptying at 6 weeks (3.7% vs. 0%).

In a companion presentation by Dr. Wei, the question was raised as to whether a preoperative prolapse reduction stress test (PRST) was of value for predicting which women would benefit most from prophylactic sling insertion. To answer this question, the group did a post hoc analysis, comparing outcomes according to whether the PRST was positive or negative.

The preoperative PRST was performed by retrograde fill (300 mL), removing the catheter and performing Valsalva and cough testing in lithotomy position without prolapse reduction, in lithotomy with prolapse reduced with Procto Swabs, and standing with prolapse reduced. A positive stress test was defined as urine leakage in either position, with or without reduction. The PRST results were masked to the surgeons, so the results had no influence on treatment assignment. Almost all women enrolled in the trial (98%) had undergone PRST.

Dr. Wei found that, at 3 months, insertion of the sling had a beneficial effect, whether or not the PRST was positive or negative, but the magnitude of effect of the sling was greater if the patient had a positive PRST. Treatment failure at 3 months in the positive PRST group was 29.6% in the sling group vs. 71.9% in the sham group; in the negative PRST group the rates were 20.6% in the sling group vs. 38.1% in the sham group (interaction P = .06). Similar trends were seen at 12 months but the differences were not significant.

“Women with a positive PRST who do not receive a TVT are at highest risk of having at UI at 3 months after vaginal prolapse surgery,” he said.

Another group included in the study was a “patient preference cohort” (PPC) which included a group of women who were eligible for inclusion in the randomized controlled trial but elected not to participate because of randomization. According to Dr. Wei, the goal was to measure the level of nonparticipation bias to improve the validity of the generalizability of the trial. “Both in magnitude and statistics, those in the PPC looked remarkably like those in the clinical trial.”

“The low bias in the PPC group, the high rate of participation, and the high rate of follow-up all makes this an exceptional trial,” he said.

PROVIDENCE, R.I. – Use of a prophylactic mid-urethral sling during the course of transvaginal prolapse repair significantly reduced the risk of urinary incontinence symptoms at 3 and 12 months post surgery, according to Dr. John T. Wei.

“The basis for this trial is a common dilemma we face: When a woman with significant vaginal prolapse but no stress-related urinary incontinence undergoes transvaginal prolapse repair, should a sling be placed in all women or should treatment be delayed until she develops symptomatic urinary incontinence? Level 1 evidence does not exist to address that question, and that is why the Pelvic Floor Disorders Network [PFDN] commissioned the OPUS [Outcomes Following Vaginal Prolapse Repair and Midurethral Sling] trial,” said Dr. Wei, professor of urology at the University of Michigan, Ann Arbor. Dr. Wei's presentation earned the “Best Overall Paper” award at the meeting.

The PFDN was created by the National Institute of Child Health and Human Development's contraception and reproductive health branch. It consists of eight clinical sites and one data-coordinating center. This is the first protocol conducted by the PFDN.

In the OPUS trial, 337 women with symptomatic greater than or equal to stage 2 anterior prolapse who did not report symptoms of stress urinary incontinence (SUI) were randomized to undergo either insertion of retropubic tension-free vaginal tape (TVT) (n=165) or sham incisions (n=172) during prolapse surgery. The primary end point was urinary incontinence (UI) failure, defined as having at least one of the following: a positive cough stress test, bothersome UI symptoms, or treatment for UI (pharmacologic or surgical).

Three months after surgery, the rate of UI failure in those who received a prophylactic sling was less than half of that seen in the sham-operated group (23.6% vs. 49.4%, P less than .0001). Similar results were noted at 12 months (27.3% vs. 43.0%, P = .0024), even after allowing for additional UI postoperative treatment. Significant differences favoring the sling also were found for quality of life measures. However, no significant differences between groups were found for measures of other pelvic floor conditions such as prolapse, pain, or decreased sexual function or general health (as measured by the short form SF-36 questionnaire).

Although there were no significant differences between groups in serious and unexpected adverse events, those in the TVT group had higher rates of bladder perforations (6.7% vs. 0%), urinary tract infections (31% vs. 17.2%), major bleeding/vascular complications (3% vs. 0%) or incomplete bladder emptying at 6 weeks (3.7% vs. 0%).

In a companion presentation by Dr. Wei, the question was raised as to whether a preoperative prolapse reduction stress test (PRST) was of value for predicting which women would benefit most from prophylactic sling insertion. To answer this question, the group did a post hoc analysis, comparing outcomes according to whether the PRST was positive or negative.

The preoperative PRST was performed by retrograde fill (300 mL), removing the catheter and performing Valsalva and cough testing in lithotomy position without prolapse reduction, in lithotomy with prolapse reduced with Procto Swabs, and standing with prolapse reduced. A positive stress test was defined as urine leakage in either position, with or without reduction. The PRST results were masked to the surgeons, so the results had no influence on treatment assignment. Almost all women enrolled in the trial (98%) had undergone PRST.

Dr. Wei found that, at 3 months, insertion of the sling had a beneficial effect, whether or not the PRST was positive or negative, but the magnitude of effect of the sling was greater if the patient had a positive PRST. Treatment failure at 3 months in the positive PRST group was 29.6% in the sling group vs. 71.9% in the sham group; in the negative PRST group the rates were 20.6% in the sling group vs. 38.1% in the sham group (interaction P = .06). Similar trends were seen at 12 months but the differences were not significant.

“Women with a positive PRST who do not receive a TVT are at highest risk of having at UI at 3 months after vaginal prolapse surgery,” he said.

Another group included in the study was a “patient preference cohort” (PPC) which included a group of women who were eligible for inclusion in the randomized controlled trial but elected not to participate because of randomization. According to Dr. Wei, the goal was to measure the level of nonparticipation bias to improve the validity of the generalizability of the trial. “Both in magnitude and statistics, those in the PPC looked remarkably like those in the clinical trial.”

“The low bias in the PPC group, the high rate of participation, and the high rate of follow-up all makes this an exceptional trial,” he said.

PROVIDENCE, R.I. – Use of a prophylactic mid-urethral sling during the course of transvaginal prolapse repair significantly reduced the risk of urinary incontinence symptoms at 3 and 12 months post surgery, according to Dr. John T. Wei.

“The basis for this trial is a common dilemma we face: When a woman with significant vaginal prolapse but no stress-related urinary incontinence undergoes transvaginal prolapse repair, should a sling be placed in all women or should treatment be delayed until she develops symptomatic urinary incontinence? Level 1 evidence does not exist to address that question, and that is why the Pelvic Floor Disorders Network [PFDN] commissioned the OPUS [Outcomes Following Vaginal Prolapse Repair and Midurethral Sling] trial,” said Dr. Wei, professor of urology at the University of Michigan, Ann Arbor. Dr. Wei's presentation earned the “Best Overall Paper” award at the meeting.

The PFDN was created by the National Institute of Child Health and Human Development's contraception and reproductive health branch. It consists of eight clinical sites and one data-coordinating center. This is the first protocol conducted by the PFDN.

In the OPUS trial, 337 women with symptomatic greater than or equal to stage 2 anterior prolapse who did not report symptoms of stress urinary incontinence (SUI) were randomized to undergo either insertion of retropubic tension-free vaginal tape (TVT) (n=165) or sham incisions (n=172) during prolapse surgery. The primary end point was urinary incontinence (UI) failure, defined as having at least one of the following: a positive cough stress test, bothersome UI symptoms, or treatment for UI (pharmacologic or surgical).

Three months after surgery, the rate of UI failure in those who received a prophylactic sling was less than half of that seen in the sham-operated group (23.6% vs. 49.4%, P less than .0001). Similar results were noted at 12 months (27.3% vs. 43.0%, P = .0024), even after allowing for additional UI postoperative treatment. Significant differences favoring the sling also were found for quality of life measures. However, no significant differences between groups were found for measures of other pelvic floor conditions such as prolapse, pain, or decreased sexual function or general health (as measured by the short form SF-36 questionnaire).

Although there were no significant differences between groups in serious and unexpected adverse events, those in the TVT group had higher rates of bladder perforations (6.7% vs. 0%), urinary tract infections (31% vs. 17.2%), major bleeding/vascular complications (3% vs. 0%) or incomplete bladder emptying at 6 weeks (3.7% vs. 0%).

In a companion presentation by Dr. Wei, the question was raised as to whether a preoperative prolapse reduction stress test (PRST) was of value for predicting which women would benefit most from prophylactic sling insertion. To answer this question, the group did a post hoc analysis, comparing outcomes according to whether the PRST was positive or negative.

The preoperative PRST was performed by retrograde fill (300 mL), removing the catheter and performing Valsalva and cough testing in lithotomy position without prolapse reduction, in lithotomy with prolapse reduced with Procto Swabs, and standing with prolapse reduced. A positive stress test was defined as urine leakage in either position, with or without reduction. The PRST results were masked to the surgeons, so the results had no influence on treatment assignment. Almost all women enrolled in the trial (98%) had undergone PRST.

Dr. Wei found that, at 3 months, insertion of the sling had a beneficial effect, whether or not the PRST was positive or negative, but the magnitude of effect of the sling was greater if the patient had a positive PRST. Treatment failure at 3 months in the positive PRST group was 29.6% in the sling group vs. 71.9% in the sham group; in the negative PRST group the rates were 20.6% in the sling group vs. 38.1% in the sham group (interaction P = .06). Similar trends were seen at 12 months but the differences were not significant.

“Women with a positive PRST who do not receive a TVT are at highest risk of having at UI at 3 months after vaginal prolapse surgery,” he said.

Another group included in the study was a “patient preference cohort” (PPC) which included a group of women who were eligible for inclusion in the randomized controlled trial but elected not to participate because of randomization. According to Dr. Wei, the goal was to measure the level of nonparticipation bias to improve the validity of the generalizability of the trial. “Both in magnitude and statistics, those in the PPC looked remarkably like those in the clinical trial.”

“The low bias in the PPC group, the high rate of participation, and the high rate of follow-up all makes this an exceptional trial,” he said.

PROVIDENCE, R.I. – After the Food and Drug Administration issued an updated safety communication concerning the surgical placement of transvaginal mesh to repair pelvic organ prolapse on July 13, leaders of the American Urogynecologic Society sprang into action.

The American Urogynecologic Society (AUGS) leadership alerted its members, participated in a stakeholders' conference call the following day with the FDA, polled its members, created a blog on its website, released its own recommendations, and testified before an FDA investigatory panel Sept. 8–9 regarding the safe and effective use of transvaginal mesh for both pelvic organ prolapse (POP) and stress urinary incontinence (SUI).

The FDA's Safety Communication

It is beyond the scope of this report to review all the recommendations made by the FDA concerning transvaginal placement of surgical mesh for POP; for more detailed information, see

www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm262435.htm

After a systematic review of the literature from 1996 to 2011, the FDA concluded that transvaginal POP repair with mesh may have an anatomic benefit that may not necessarily improve symptoms or quality of life over traditional nonmesh repair. They stated that in most cases, POP can be treated successfully without mesh, and mesh surgery should be chosen only after weighing associated risks and benefits.

 The FDA Panel Hearing

On Sept. 8–9, the FDA convened an Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee to consider the use of transvaginal mesh for POP and SUI. The 19-person panel, chaired by Dr. Tommaso Falcone of the Cleveland Clinic, included 12 physicians, 2 statisticians, and representatives of patients, consumers, and industry. Five were members of AUGS, including Dr. Cheryl B. Iglesia, director of the Section of Female Pelvic Medicine and Reconstructive Surgery at Washington (D.C.) Hospital Center, who spoke about her experiences at the AUGS annual meeting.

The AUGS' Stand and the Panel's Recs

On Sept. 15, at the AUGS annual meeting, an update was held to inform members about new developments regarding vaginal placement of mesh. President Deborah Myers presented the AUGS leadership stance, which was also outlined in an executive summary (available on the organization's website,

www.augs.org

The AUGS statement described some of the complexities regarding the use of transvaginal mesh for pelvic reconstruction. The society indicated that it supports the FDA Safety Communication Update recommendations: that often POP can be treated successfully without mesh. However, while AUGS does not support the routine use of vaginal mesh for POP repair, it recognizes “that there may be particular circumstances when the placement of transvaginal mesh is beneficial and appropriate.”

After discussion of a number of serious adverse events associated with the use of vaginal mesh for POP repair, the panel's consensus was that the safety of such mesh is not well established. Depending on the compartment, vaginal placement of mesh for POP repair may not be more effective than traditional “native-tissue” repair without mesh, and the consensus was that the risk/benefit of vaginal placement of mesh for POP repair is not well established.

The AUGS statement indicated that there is insufficient data available to guide treatment decisions for individual patients, noting that such decisions should be made collaboratively by physicians and patients. Although outcomes reflect both surgical training and skill, many members of AUGS report excellent outcomes and low complication rates with transvaginal mesh. With this in mind, “AUGS does not support a 'blanket' withdrawal of currently available transvaginal mesh products from the market.” Instead, AUGS supports the judicious use of transvaginal mesh for POP repair performed only by surgeons with appropriate training on patients who have been fully informed of the risks and benefits of all available treatment options.

AUGS' stance on informed consent is “in sync” with the FDA. It supports a consent process that informs patients of nonsurgical options, alternative native tissue surgical repairs, and abdominal repairs, as well as possible adverse outcomes associated with mesh. The organization is planning to offer an online informed consent checklist.

Within the next 12 months, AUGS plans to develop educational and training recommendations to guide hospitals in privileging those who may conduct POP surgery using transvaginal mesh. Until those recommendations are issued, AUGS suggests “that continued placement of transvaginal mesh for POP be performed only by providers who have extensive training in pelvic surgery, maintain a high volume of surgical procedures for prolapse, have specific training in the device and method used, and are able to track both objective and subjective short-term and long-term outcomes.”

Currently, postmarketing surveillance is voluntary and not inclusive of all vaginal meshes. AUGS recommends that the FDA invoke its power under section 522 of the Food and Drug Administration Modernization Act of 1997 to require postmarketing surveillance by means of a postmarket registry and/or national database of all users of vaginally placed mesh, to track both positive and negative anatomic and subjective outcomes. Until the registry is created, AUGS recommends all surgeons track their own outcomes.

The most contentious issue concerns the type of clinical evidence needed to support continued use of mesh already in the marketplace and future technology. Currently available mesh were generally approved as class II devices under the 510(k) process, often with another legally marketed, predicate device as control. “Many things we deal with are class II, requiring general or special controls,” said Dr. Matthew Barber of the Cleveland Clinic, president-elect of AUGS. Class III devices require a premarket approval application (PMA), and such devices are often considered high risk, life sustaining, life supporting or of substantial health importance, or present unreasonable risk or injury. Like drugs, class III devices require independent assessment of safety and effectiveness prior to marketing.

AUGS stated that it supports mandatory clinical trials for transvaginal mesh for POP and is in favor of a requirement that premarket notifications or PMAs include clinical trials that use patient-centered outcomes and long-term patient follow-up. The studies should be prospective, and can be cohort studies, registries or randomized, controlled trials, but randomized controlled trials are not required. Clinical trials should have a minimum of 1 year of follow-up with an additional 2–4 years of patient follow-up, and FDA reporting for new prolapse mesh devices or for significant modifications of existing devices. AUGS supports keeping transvaginal mesh devices as class II devices, and would assist the FDA in developing special controls if required by the FDA.

“The bottom line is, we want them to leave slings alone and place them into a registry,” remarked Dr. Myers of Brown University, Providence, R.I.

The panel called for stricter standards than currently exist or requested by AUGS, recommending that premarket evaluation of vaginal mesh for POP was needed, and that the control arm for such studies be women undergoing surgical repair of POP without the use of mesh. Therefore, class II special controls would not be sufficient, and the panel's consensus was that vaginal mesh for POP repair be reclassified from class II to class III. The panel felt that there were enough data available to support the use of mesh for abdominal sacral colpopexy. There was no need for clinical performance data for new mesh products similar to products already on the market, and postmarketing surveillance was not needed.

AUGS also clearly makes the distinction between the use of mesh for prolapse and use for SUI. It “strongly opposes withdrawal of synthetic mesh devices for surgical treatment of SUI and does not feel any change in the current regulatory status of synthetic mesh for this use is warranted.” Noting the considerable evidence supporting its use, AUGS asserts that midurethral slings, placed either by a retropubic or transobturator approach, is the current standard of care for the surgical treatment of SUI. AUGS supports establishing a postmarket registry for mesh used for SUI, and appropriate premarket clinical trials for devices significantly different from those that are currently available.

The situation is still in flux. Recommendations made by the advisory panel are not mandatory, noted Dr. Iglesia. “If the recommendations are adopted by the FDA, it will take several years to take effect, and existing products will stay on the market.

No financial disclosures were listed for Dr. Myers, Dr. Barber, or Dr. Iglesia.

PROVIDENCE, R.I. – After the Food and Drug Administration issued an updated safety communication concerning the surgical placement of transvaginal mesh to repair pelvic organ prolapse on July 13, leaders of the American Urogynecologic Society sprang into action.

The American Urogynecologic Society (AUGS) leadership alerted its members, participated in a stakeholders' conference call the following day with the FDA, polled its members, created a blog on its website, released its own recommendations, and testified before an FDA investigatory panel Sept. 8–9 regarding the safe and effective use of transvaginal mesh for both pelvic organ prolapse (POP) and stress urinary incontinence (SUI).

The FDA's Safety Communication

It is beyond the scope of this report to review all the recommendations made by the FDA concerning transvaginal placement of surgical mesh for POP; for more detailed information, see

www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm262435.htm

After a systematic review of the literature from 1996 to 2011, the FDA concluded that transvaginal POP repair with mesh may have an anatomic benefit that may not necessarily improve symptoms or quality of life over traditional nonmesh repair. They stated that in most cases, POP can be treated successfully without mesh, and mesh surgery should be chosen only after weighing associated risks and benefits.

 The FDA Panel Hearing

On Sept. 8–9, the FDA convened an Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee to consider the use of transvaginal mesh for POP and SUI. The 19-person panel, chaired by Dr. Tommaso Falcone of the Cleveland Clinic, included 12 physicians, 2 statisticians, and representatives of patients, consumers, and industry. Five were members of AUGS, including Dr. Cheryl B. Iglesia, director of the Section of Female Pelvic Medicine and Reconstructive Surgery at Washington (D.C.) Hospital Center, who spoke about her experiences at the AUGS annual meeting.

The AUGS' Stand and the Panel's Recs

On Sept. 15, at the AUGS annual meeting, an update was held to inform members about new developments regarding vaginal placement of mesh. President Deborah Myers presented the AUGS leadership stance, which was also outlined in an executive summary (available on the organization's website,

www.augs.org

The AUGS statement described some of the complexities regarding the use of transvaginal mesh for pelvic reconstruction. The society indicated that it supports the FDA Safety Communication Update recommendations: that often POP can be treated successfully without mesh. However, while AUGS does not support the routine use of vaginal mesh for POP repair, it recognizes “that there may be particular circumstances when the placement of transvaginal mesh is beneficial and appropriate.”

After discussion of a number of serious adverse events associated with the use of vaginal mesh for POP repair, the panel's consensus was that the safety of such mesh is not well established. Depending on the compartment, vaginal placement of mesh for POP repair may not be more effective than traditional “native-tissue” repair without mesh, and the consensus was that the risk/benefit of vaginal placement of mesh for POP repair is not well established.

The AUGS statement indicated that there is insufficient data available to guide treatment decisions for individual patients, noting that such decisions should be made collaboratively by physicians and patients. Although outcomes reflect both surgical training and skill, many members of AUGS report excellent outcomes and low complication rates with transvaginal mesh. With this in mind, “AUGS does not support a 'blanket' withdrawal of currently available transvaginal mesh products from the market.” Instead, AUGS supports the judicious use of transvaginal mesh for POP repair performed only by surgeons with appropriate training on patients who have been fully informed of the risks and benefits of all available treatment options.

AUGS' stance on informed consent is “in sync” with the FDA. It supports a consent process that informs patients of nonsurgical options, alternative native tissue surgical repairs, and abdominal repairs, as well as possible adverse outcomes associated with mesh. The organization is planning to offer an online informed consent checklist.

Within the next 12 months, AUGS plans to develop educational and training recommendations to guide hospitals in privileging those who may conduct POP surgery using transvaginal mesh. Until those recommendations are issued, AUGS suggests “that continued placement of transvaginal mesh for POP be performed only by providers who have extensive training in pelvic surgery, maintain a high volume of surgical procedures for prolapse, have specific training in the device and method used, and are able to track both objective and subjective short-term and long-term outcomes.”

Currently, postmarketing surveillance is voluntary and not inclusive of all vaginal meshes. AUGS recommends that the FDA invoke its power under section 522 of the Food and Drug Administration Modernization Act of 1997 to require postmarketing surveillance by means of a postmarket registry and/or national database of all users of vaginally placed mesh, to track both positive and negative anatomic and subjective outcomes. Until the registry is created, AUGS recommends all surgeons track their own outcomes.

The most contentious issue concerns the type of clinical evidence needed to support continued use of mesh already in the marketplace and future technology. Currently available mesh were generally approved as class II devices under the 510(k) process, often with another legally marketed, predicate device as control. “Many things we deal with are class II, requiring general or special controls,” said Dr. Matthew Barber of the Cleveland Clinic, president-elect of AUGS. Class III devices require a premarket approval application (PMA), and such devices are often considered high risk, life sustaining, life supporting or of substantial health importance, or present unreasonable risk or injury. Like drugs, class III devices require independent assessment of safety and effectiveness prior to marketing.

AUGS stated that it supports mandatory clinical trials for transvaginal mesh for POP and is in favor of a requirement that premarket notifications or PMAs include clinical trials that use patient-centered outcomes and long-term patient follow-up. The studies should be prospective, and can be cohort studies, registries or randomized, controlled trials, but randomized controlled trials are not required. Clinical trials should have a minimum of 1 year of follow-up with an additional 2–4 years of patient follow-up, and FDA reporting for new prolapse mesh devices or for significant modifications of existing devices. AUGS supports keeping transvaginal mesh devices as class II devices, and would assist the FDA in developing special controls if required by the FDA.

“The bottom line is, we want them to leave slings alone and place them into a registry,” remarked Dr. Myers of Brown University, Providence, R.I.

The panel called for stricter standards than currently exist or requested by AUGS, recommending that premarket evaluation of vaginal mesh for POP was needed, and that the control arm for such studies be women undergoing surgical repair of POP without the use of mesh. Therefore, class II special controls would not be sufficient, and the panel's consensus was that vaginal mesh for POP repair be reclassified from class II to class III. The panel felt that there were enough data available to support the use of mesh for abdominal sacral colpopexy. There was no need for clinical performance data for new mesh products similar to products already on the market, and postmarketing surveillance was not needed.

AUGS also clearly makes the distinction between the use of mesh for prolapse and use for SUI. It “strongly opposes withdrawal of synthetic mesh devices for surgical treatment of SUI and does not feel any change in the current regulatory status of synthetic mesh for this use is warranted.” Noting the considerable evidence supporting its use, AUGS asserts that midurethral slings, placed either by a retropubic or transobturator approach, is the current standard of care for the surgical treatment of SUI. AUGS supports establishing a postmarket registry for mesh used for SUI, and appropriate premarket clinical trials for devices significantly different from those that are currently available.

The situation is still in flux. Recommendations made by the advisory panel are not mandatory, noted Dr. Iglesia. “If the recommendations are adopted by the FDA, it will take several years to take effect, and existing products will stay on the market.

No financial disclosures were listed for Dr. Myers, Dr. Barber, or Dr. Iglesia.

PROVIDENCE, R.I. – After the Food and Drug Administration issued an updated safety communication concerning the surgical placement of transvaginal mesh to repair pelvic organ prolapse on July 13, leaders of the American Urogynecologic Society sprang into action.

The American Urogynecologic Society (AUGS) leadership alerted its members, participated in a stakeholders' conference call the following day with the FDA, polled its members, created a blog on its website, released its own recommendations, and testified before an FDA investigatory panel Sept. 8–9 regarding the safe and effective use of transvaginal mesh for both pelvic organ prolapse (POP) and stress urinary incontinence (SUI).

The FDA's Safety Communication

It is beyond the scope of this report to review all the recommendations made by the FDA concerning transvaginal placement of surgical mesh for POP; for more detailed information, see

www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm262435.htm

After a systematic review of the literature from 1996 to 2011, the FDA concluded that transvaginal POP repair with mesh may have an anatomic benefit that may not necessarily improve symptoms or quality of life over traditional nonmesh repair. They stated that in most cases, POP can be treated successfully without mesh, and mesh surgery should be chosen only after weighing associated risks and benefits.

 The FDA Panel Hearing

On Sept. 8–9, the FDA convened an Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee to consider the use of transvaginal mesh for POP and SUI. The 19-person panel, chaired by Dr. Tommaso Falcone of the Cleveland Clinic, included 12 physicians, 2 statisticians, and representatives of patients, consumers, and industry. Five were members of AUGS, including Dr. Cheryl B. Iglesia, director of the Section of Female Pelvic Medicine and Reconstructive Surgery at Washington (D.C.) Hospital Center, who spoke about her experiences at the AUGS annual meeting.

The AUGS' Stand and the Panel's Recs

On Sept. 15, at the AUGS annual meeting, an update was held to inform members about new developments regarding vaginal placement of mesh. President Deborah Myers presented the AUGS leadership stance, which was also outlined in an executive summary (available on the organization's website,

www.augs.org

The AUGS statement described some of the complexities regarding the use of transvaginal mesh for pelvic reconstruction. The society indicated that it supports the FDA Safety Communication Update recommendations: that often POP can be treated successfully without mesh. However, while AUGS does not support the routine use of vaginal mesh for POP repair, it recognizes “that there may be particular circumstances when the placement of transvaginal mesh is beneficial and appropriate.”

After discussion of a number of serious adverse events associated with the use of vaginal mesh for POP repair, the panel's consensus was that the safety of such mesh is not well established. Depending on the compartment, vaginal placement of mesh for POP repair may not be more effective than traditional “native-tissue” repair without mesh, and the consensus was that the risk/benefit of vaginal placement of mesh for POP repair is not well established.

The AUGS statement indicated that there is insufficient data available to guide treatment decisions for individual patients, noting that such decisions should be made collaboratively by physicians and patients. Although outcomes reflect both surgical training and skill, many members of AUGS report excellent outcomes and low complication rates with transvaginal mesh. With this in mind, “AUGS does not support a 'blanket' withdrawal of currently available transvaginal mesh products from the market.” Instead, AUGS supports the judicious use of transvaginal mesh for POP repair performed only by surgeons with appropriate training on patients who have been fully informed of the risks and benefits of all available treatment options.

AUGS' stance on informed consent is “in sync” with the FDA. It supports a consent process that informs patients of nonsurgical options, alternative native tissue surgical repairs, and abdominal repairs, as well as possible adverse outcomes associated with mesh. The organization is planning to offer an online informed consent checklist.

Within the next 12 months, AUGS plans to develop educational and training recommendations to guide hospitals in privileging those who may conduct POP surgery using transvaginal mesh. Until those recommendations are issued, AUGS suggests “that continued placement of transvaginal mesh for POP be performed only by providers who have extensive training in pelvic surgery, maintain a high volume of surgical procedures for prolapse, have specific training in the device and method used, and are able to track both objective and subjective short-term and long-term outcomes.”

Currently, postmarketing surveillance is voluntary and not inclusive of all vaginal meshes. AUGS recommends that the FDA invoke its power under section 522 of the Food and Drug Administration Modernization Act of 1997 to require postmarketing surveillance by means of a postmarket registry and/or national database of all users of vaginally placed mesh, to track both positive and negative anatomic and subjective outcomes. Until the registry is created, AUGS recommends all surgeons track their own outcomes.

The most contentious issue concerns the type of clinical evidence needed to support continued use of mesh already in the marketplace and future technology. Currently available mesh were generally approved as class II devices under the 510(k) process, often with another legally marketed, predicate device as control. “Many things we deal with are class II, requiring general or special controls,” said Dr. Matthew Barber of the Cleveland Clinic, president-elect of AUGS. Class III devices require a premarket approval application (PMA), and such devices are often considered high risk, life sustaining, life supporting or of substantial health importance, or present unreasonable risk or injury. Like drugs, class III devices require independent assessment of safety and effectiveness prior to marketing.

AUGS stated that it supports mandatory clinical trials for transvaginal mesh for POP and is in favor of a requirement that premarket notifications or PMAs include clinical trials that use patient-centered outcomes and long-term patient follow-up. The studies should be prospective, and can be cohort studies, registries or randomized, controlled trials, but randomized controlled trials are not required. Clinical trials should have a minimum of 1 year of follow-up with an additional 2–4 years of patient follow-up, and FDA reporting for new prolapse mesh devices or for significant modifications of existing devices. AUGS supports keeping transvaginal mesh devices as class II devices, and would assist the FDA in developing special controls if required by the FDA.

“The bottom line is, we want them to leave slings alone and place them into a registry,” remarked Dr. Myers of Brown University, Providence, R.I.

The panel called for stricter standards than currently exist or requested by AUGS, recommending that premarket evaluation of vaginal mesh for POP was needed, and that the control arm for such studies be women undergoing surgical repair of POP without the use of mesh. Therefore, class II special controls would not be sufficient, and the panel's consensus was that vaginal mesh for POP repair be reclassified from class II to class III. The panel felt that there were enough data available to support the use of mesh for abdominal sacral colpopexy. There was no need for clinical performance data for new mesh products similar to products already on the market, and postmarketing surveillance was not needed.

AUGS also clearly makes the distinction between the use of mesh for prolapse and use for SUI. It “strongly opposes withdrawal of synthetic mesh devices for surgical treatment of SUI and does not feel any change in the current regulatory status of synthetic mesh for this use is warranted.” Noting the considerable evidence supporting its use, AUGS asserts that midurethral slings, placed either by a retropubic or transobturator approach, is the current standard of care for the surgical treatment of SUI. AUGS supports establishing a postmarket registry for mesh used for SUI, and appropriate premarket clinical trials for devices significantly different from those that are currently available.

The situation is still in flux. Recommendations made by the advisory panel are not mandatory, noted Dr. Iglesia. “If the recommendations are adopted by the FDA, it will take several years to take effect, and existing products will stay on the market.

No financial disclosures were listed for Dr. Myers, Dr. Barber, or Dr. Iglesia.

PROVIDENCE, R.I. – Compared with cesarean birth without labor, undergoing vaginal birth increased the risk of stress incontinence and prolapse in women who were examined 5–10 years after childbirth, Dr. Victoria L. Handa reported.

The risk of all pelvic disorders, including prolapse, was elevated even further in women who had undergone operative vaginal delivery, she said.

“The results suggest no measurable differences in the relative odds of any pelvic floor disorder for women delivering by cesarean section, including those who labored into the second stage. For vaginal birth, the picture is very different,” said Dr. Handa, director of the advanced training program in female pelvic medicine and reconstructive surgery at Johns Hopkins University, Baltimore.

In this longitudinal cohort study based on hospital obstetric records, 8,285 women who had their first child 5–10 years previously were recruited for the study and 1,011 were enrolled. Women were selected if their obstetric history met one of five categories: cesarean without labor (considered the reference group; n = 192), cesarean during active labor (n = 228), cesarean after complete cervical dilation (n = 140), spontaneous vaginal birth (n = 325), and operative vaginal birth (n = 126). Groups were matched for age at first delivery and interval from first delivery, and were similar with respect to parity and smoking status. At enrollment, a validated questionnaire (Epidemiology of Prolapse and Incontinence Questionnaire) was used to assess pelvic floor symptoms, and the women were examined for pelvic organ support using the Pelvic Organ Prolapse Quantification (POP-Q) System.

“One of the strengths of our study is that [obstetric] exposures were verified by chart review with validated outcomes, and there was [anatomical] evidence of prolapse,” Dr. Handa said.

Overall, 11% of the 1,011 women had stress urinary incontinence, 8% had overactive bladder, and 11% had anal incontinence; 3% reported prolapse symptoms, and 7% had prolapse upon examination (Obstet. Gynecol. 2011;118:777–84).

Compared with women who had a cesarean birth before active labor, women who had a vaginal birth (but no operative vaginal births) had almost a threefold increased risk of stress incontinence and symptomatic prolapse. The odds ratio for prolapse was increased more than fivefold.

Women who had undergone operative vaginal birth fared even worse. The adjusted odds of stress incontinence and overactive bladder were more than quadrupled. There was almost an eightfold increased risk of prolapse upon exam.

In her report, Dr. Handa noted that in addition to demonstrating the dramatic increase in pelvic floor disorders in women with a history of at least one operative vaginal birth, the results showed an increase in urinary incontinence after operative delivery – a finding that had not been definitively documented before. For those who had undergone cesarean delivery, the results showed no association between active labor and pelvic floor disorders.

The study was also the first to demonstrate an association between operative vaginal birth and prolapse, even in asymptomatic women. By continuing to monitor these women, Dr. Handa hopes to be able to document the natural history of prolapse over time, especially in those women who were unaware of their condition.

Dr. Handa did not report any relevant financial disclosures.

PROVIDENCE, R.I. – Compared with cesarean birth without labor, undergoing vaginal birth increased the risk of stress incontinence and prolapse in women who were examined 5–10 years after childbirth, Dr. Victoria L. Handa reported.

The risk of all pelvic disorders, including prolapse, was elevated even further in women who had undergone operative vaginal delivery, she said.

“The results suggest no measurable differences in the relative odds of any pelvic floor disorder for women delivering by cesarean section, including those who labored into the second stage. For vaginal birth, the picture is very different,” said Dr. Handa, director of the advanced training program in female pelvic medicine and reconstructive surgery at Johns Hopkins University, Baltimore.

In this longitudinal cohort study based on hospital obstetric records, 8,285 women who had their first child 5–10 years previously were recruited for the study and 1,011 were enrolled. Women were selected if their obstetric history met one of five categories: cesarean without labor (considered the reference group; n = 192), cesarean during active labor (n = 228), cesarean after complete cervical dilation (n = 140), spontaneous vaginal birth (n = 325), and operative vaginal birth (n = 126). Groups were matched for age at first delivery and interval from first delivery, and were similar with respect to parity and smoking status. At enrollment, a validated questionnaire (Epidemiology of Prolapse and Incontinence Questionnaire) was used to assess pelvic floor symptoms, and the women were examined for pelvic organ support using the Pelvic Organ Prolapse Quantification (POP-Q) System.

“One of the strengths of our study is that [obstetric] exposures were verified by chart review with validated outcomes, and there was [anatomical] evidence of prolapse,” Dr. Handa said.

Overall, 11% of the 1,011 women had stress urinary incontinence, 8% had overactive bladder, and 11% had anal incontinence; 3% reported prolapse symptoms, and 7% had prolapse upon examination (Obstet. Gynecol. 2011;118:777–84).

Compared with women who had a cesarean birth before active labor, women who had a vaginal birth (but no operative vaginal births) had almost a threefold increased risk of stress incontinence and symptomatic prolapse. The odds ratio for prolapse was increased more than fivefold.

Women who had undergone operative vaginal birth fared even worse. The adjusted odds of stress incontinence and overactive bladder were more than quadrupled. There was almost an eightfold increased risk of prolapse upon exam.

In her report, Dr. Handa noted that in addition to demonstrating the dramatic increase in pelvic floor disorders in women with a history of at least one operative vaginal birth, the results showed an increase in urinary incontinence after operative delivery – a finding that had not been definitively documented before. For those who had undergone cesarean delivery, the results showed no association between active labor and pelvic floor disorders.

The study was also the first to demonstrate an association between operative vaginal birth and prolapse, even in asymptomatic women. By continuing to monitor these women, Dr. Handa hopes to be able to document the natural history of prolapse over time, especially in those women who were unaware of their condition.

Dr. Handa did not report any relevant financial disclosures.

PROVIDENCE, R.I. – Compared with cesarean birth without labor, undergoing vaginal birth increased the risk of stress incontinence and prolapse in women who were examined 5–10 years after childbirth, Dr. Victoria L. Handa reported.

The risk of all pelvic disorders, including prolapse, was elevated even further in women who had undergone operative vaginal delivery, she said.

“The results suggest no measurable differences in the relative odds of any pelvic floor disorder for women delivering by cesarean section, including those who labored into the second stage. For vaginal birth, the picture is very different,” said Dr. Handa, director of the advanced training program in female pelvic medicine and reconstructive surgery at Johns Hopkins University, Baltimore.

In this longitudinal cohort study based on hospital obstetric records, 8,285 women who had their first child 5–10 years previously were recruited for the study and 1,011 were enrolled. Women were selected if their obstetric history met one of five categories: cesarean without labor (considered the reference group; n = 192), cesarean during active labor (n = 228), cesarean after complete cervical dilation (n = 140), spontaneous vaginal birth (n = 325), and operative vaginal birth (n = 126). Groups were matched for age at first delivery and interval from first delivery, and were similar with respect to parity and smoking status. At enrollment, a validated questionnaire (Epidemiology of Prolapse and Incontinence Questionnaire) was used to assess pelvic floor symptoms, and the women were examined for pelvic organ support using the Pelvic Organ Prolapse Quantification (POP-Q) System.

“One of the strengths of our study is that [obstetric] exposures were verified by chart review with validated outcomes, and there was [anatomical] evidence of prolapse,” Dr. Handa said.

Overall, 11% of the 1,011 women had stress urinary incontinence, 8% had overactive bladder, and 11% had anal incontinence; 3% reported prolapse symptoms, and 7% had prolapse upon examination (Obstet. Gynecol. 2011;118:777–84).

Compared with women who had a cesarean birth before active labor, women who had a vaginal birth (but no operative vaginal births) had almost a threefold increased risk of stress incontinence and symptomatic prolapse. The odds ratio for prolapse was increased more than fivefold.

Women who had undergone operative vaginal birth fared even worse. The adjusted odds of stress incontinence and overactive bladder were more than quadrupled. There was almost an eightfold increased risk of prolapse upon exam.

In her report, Dr. Handa noted that in addition to demonstrating the dramatic increase in pelvic floor disorders in women with a history of at least one operative vaginal birth, the results showed an increase in urinary incontinence after operative delivery – a finding that had not been definitively documented before. For those who had undergone cesarean delivery, the results showed no association between active labor and pelvic floor disorders.

The study was also the first to demonstrate an association between operative vaginal birth and prolapse, even in asymptomatic women. By continuing to monitor these women, Dr. Handa hopes to be able to document the natural history of prolapse over time, especially in those women who were unaware of their condition.

Dr. Handa did not report any relevant financial disclosures.

Major Finding: Childhood-onset SLE may be difficult to diagnose because its symptoms differ from that of adult-onset SLE. But cSLE is a predictor of mortality, and steps should be taken to control morbidities such as infection, premature atherosclerosis, and nephropathy. Prednisone remains a cornerstone of pharmacotherapy but has serious side effects, including osteoporosis and impaired growth. Additional nontargeted and targeted options are available.

Data Source: A clinical update presentation based on published reports and clinical experience.

Disclosures: Dr. Kahn reports no relevant disclosures.

NEW YORK – The good news in the management of childhood-onset systemic lupus erythematosus is that children who are diagnosed with the disease have a better prognosis and are living longer.

The bad news is that over the course of a lifetime, affected children develop more morbidities and experience more medication-induced toxicities, which create additional management challenges, according to Dr. Phillip Kahn, who spoke at the meeting.

About 15%-20% of lupus cases present in childhood. Children younger than age 5 years rarely have the disease, but up to 40% of patients with childhood-onset SLE (cSLE) present prior to puberty, said Dr. Kahn of New York University.

The incidence of cSLE is estimated to be 10-20 cases per 100,000 individuals, but the incidence is higher in blacks, at 200 cases per 100,000 individuals (Lupus 2007;16:546-9; 2005;14:83-8).

Often the diagnosis is delayed in children, as their clinical features do not fall within those defined by the 1997 American College of Rheumatology's SLE criteria, which have not been validated in children.

For example, Dr. Kahn described the case of a 13-year-old girl who presented with “constitutional symptoms” such as diffuse lymphadenopathy, malaise, weight loss, and fever – none of which are included in the 1997 criteria.

Mucocutaneous lesions are common in children, with up to 70% presenting with malar rash, 30% with alopecia, 66% with oral ulcers, and 10% with nasal ulcers.

“Although nasal ulcers are less common in children than adults, they still may result in perforation of the septum,” he said. Other common manifestations include painful polyarthritis, hepatosplenomegaly, headache, photosensitivity, and Raynaud's phenomenon.

Up to 40% of cSLE patients have neuropsychiatric symptoms, significantly more than do adults (Lupus 2008;17:314-22).

An important diagnostic tool for cSLE is a positive ANA (antinuclear antibody) finding, which is present in essentially all children with cSLE. In contrast, up to 10% of adults with SLE do not have a positive ANA, said Dr. Kahn.

Childhood-onset lupus may predict mortality in adults (Arthritis Care Res. [Hoboken] 2010;62:1152-9) and thus physicians must be vigilant about detecting, preventing, and aggressively treating some of its more dangerous manifestations.

To prevent recurrent infection, Dr. Kahn recommends keeping a child up to date with immunizations, treating infections promptly when they occur, and considering PCP (pneumocystis carinii pneumonia) prophylaxis in the appropriate patient. Children with cSLE are also at increased risk for premature atherosclerosis, with dyslipidemia seen in 60%-85% of affected children (Nat. Clin. Pract. Rheumatol. 2008;4:258-65). Statin therapy may be appropriate in these children, especially to prevent long-term adverse events such as early MI. For example, adults – especially women – who had cSLE have increased incidence of MI when they reach their 30s (Arthritis Rheum. 2009;61:13-20). The ongoing APPLE (Atherosclerosis Prevention in Pediatric Lupus Erythematosus) trial is investigating, in greater detail, cardiovascular risk and the use of statins in cSLE (Lupus 2010;19:1315-25).

Because nephropathy is the main cause of mortality and morbidity in cSLE, it is important to monitor urinary markers of renal function. Nephropathy may take a greater toll on a pediatric patient, compared with adults; data show that children are more likely to have renal involvement, need hemodialysis and kidney transplantation, and require hospitalization and emergency department visits (Lupus 2008;17:314-22; Arthritis Rheum. 2009;61:13-20).

To avoid end-stage renal disease, Dr. Kahn urges tight blood pressure control, as well as antihypertensive medication as necessary.

“We know that 90% of the patients who ultimately develop renal disease will do so within the first 2 years of disease, so if you follow a patient for [more than 2] years and they do not develop the disease, the good news is they are much less likely to develop nephropathy,” said Dr. Kahn.

In the 1950s, the 5-year survival rate for SLE in adults and children ranged from 18% to 70%; 30 years later, 5-year survival rose to 60%-93%, in large part because of the introduction of prednisone.

Currently, prednisone is almost universally given to those with cSLE, and the proportion of children who are treated with prednisone is significantly higher than the proportion of adults with SLE (97% vs. 70%; P less than .0001) (Arthritis Rheum. 2008;58:556-62). The result is greater risk of osteoporosis, diabetes, and growth failure.

In fact, up to 40% of cSLE patients have growth failure or short stature, in part because of chronic steroids.

That is why Dr. Kahn posed the question, “Can we move beyond steroids?”

Until recently, the only Food and Drug Administration–approved medications for SLE were prednisone, hydroxychloroquine, and aspirin.

Steroid-sparing immunomodulatory therapy is sometimes used off label when major organ (such as brain or kidney) involvement develops, but most evidence regarding the efficacy of these medications pertains to renal proliferative disease in adults.

Cyclophosphamide is often used for induction of nephritis, but 30% of patients may still develop end-stage renal disease despite treatment, said Dr. Kahn. Mycophenolate mofetil has been shown to have equal efficacy to cyclophosphamide in induction of remission of nephritis, but sufficient pediatric data are lacking. Azathioprine is effective for maintenance therapy of nephritis after the induction phase.

Other options that are sometimes used include intravenous immunoglobulin, methotrexate, calcineurin inhibitors (such as tacrolimus), plasmapheresis, and autologous stem cell transplantation/immunoablative therapy.

More recently, the focus has been on target-specific therapy for SLE with potentially fewer side effects.

Rituximab, which targets B cells that have the CD20 surface antigen, is sometimes used to treat resistant patients, but there is no strong clinical evidence to demonstrate its effectiveness in cSLE (Arthritis Rheum. 2009;61:482-7; Clin. J. Am. Soc. Nephrol. 2009;4:579-87).

Abatacept, which targets T cells by binding to B7 peripheral membrane protein, has shown some clinical benefit in a phase IIB randomized clinical trial, and is undergoing clinical testing as an add-on induction therapy with cyclophosphamide (Arthritis Rheum. 2010;62:3077-87).

Belimumab, a monoclonal antibody that targets BLyS (B-lymphocyte stimulator)/BAFF (B-cell activating factor), is the first FDA-approved medication for SLE in more than 50 years, based on recent clinical trials that demonstrate increased efficacy and fewer flares of disease, compared with placebo (Arthritis Rheum. 2009;61:1168-78; Lancet 2011;377:721-31).

Although recent data regarding belimumab provide some hope, it “may be naive to think that a target-specific therapy exists in this complex, polygenic, heterogeneous disease,” commented Dr. Kahn.

In concluding his talk, Dr. Kahn spoke about some barriers to the effective treatment of cSLE.

These include physicians' failure to detect the subtle changes of early disease, a lack of awareness regarding the neuropsychiatric manifestations of the disease, and physicians' fear of being overly aggressive with treatment.

He also warned about overt or covert adolescent noncompliance, and the danger of adolescents' dropping out of the health care system once they need to transition to adult care.

Major Finding: Childhood-onset SLE may be difficult to diagnose because its symptoms differ from that of adult-onset SLE. But cSLE is a predictor of mortality, and steps should be taken to control morbidities such as infection, premature atherosclerosis, and nephropathy. Prednisone remains a cornerstone of pharmacotherapy but has serious side effects, including osteoporosis and impaired growth. Additional nontargeted and targeted options are available.

Data Source: A clinical update presentation based on published reports and clinical experience.

Disclosures: Dr. Kahn reports no relevant disclosures.

NEW YORK – The good news in the management of childhood-onset systemic lupus erythematosus is that children who are diagnosed with the disease have a better prognosis and are living longer.

The bad news is that over the course of a lifetime, affected children develop more morbidities and experience more medication-induced toxicities, which create additional management challenges, according to Dr. Phillip Kahn, who spoke at the meeting.

About 15%-20% of lupus cases present in childhood. Children younger than age 5 years rarely have the disease, but up to 40% of patients with childhood-onset SLE (cSLE) present prior to puberty, said Dr. Kahn of New York University.

The incidence of cSLE is estimated to be 10-20 cases per 100,000 individuals, but the incidence is higher in blacks, at 200 cases per 100,000 individuals (Lupus 2007;16:546-9; 2005;14:83-8).

Often the diagnosis is delayed in children, as their clinical features do not fall within those defined by the 1997 American College of Rheumatology's SLE criteria, which have not been validated in children.

For example, Dr. Kahn described the case of a 13-year-old girl who presented with “constitutional symptoms” such as diffuse lymphadenopathy, malaise, weight loss, and fever – none of which are included in the 1997 criteria.

Mucocutaneous lesions are common in children, with up to 70% presenting with malar rash, 30% with alopecia, 66% with oral ulcers, and 10% with nasal ulcers.

“Although nasal ulcers are less common in children than adults, they still may result in perforation of the septum,” he said. Other common manifestations include painful polyarthritis, hepatosplenomegaly, headache, photosensitivity, and Raynaud's phenomenon.

Up to 40% of cSLE patients have neuropsychiatric symptoms, significantly more than do adults (Lupus 2008;17:314-22).

An important diagnostic tool for cSLE is a positive ANA (antinuclear antibody) finding, which is present in essentially all children with cSLE. In contrast, up to 10% of adults with SLE do not have a positive ANA, said Dr. Kahn.

Childhood-onset lupus may predict mortality in adults (Arthritis Care Res. [Hoboken] 2010;62:1152-9) and thus physicians must be vigilant about detecting, preventing, and aggressively treating some of its more dangerous manifestations.

To prevent recurrent infection, Dr. Kahn recommends keeping a child up to date with immunizations, treating infections promptly when they occur, and considering PCP (pneumocystis carinii pneumonia) prophylaxis in the appropriate patient. Children with cSLE are also at increased risk for premature atherosclerosis, with dyslipidemia seen in 60%-85% of affected children (Nat. Clin. Pract. Rheumatol. 2008;4:258-65). Statin therapy may be appropriate in these children, especially to prevent long-term adverse events such as early MI. For example, adults – especially women – who had cSLE have increased incidence of MI when they reach their 30s (Arthritis Rheum. 2009;61:13-20). The ongoing APPLE (Atherosclerosis Prevention in Pediatric Lupus Erythematosus) trial is investigating, in greater detail, cardiovascular risk and the use of statins in cSLE (Lupus 2010;19:1315-25).

Because nephropathy is the main cause of mortality and morbidity in cSLE, it is important to monitor urinary markers of renal function. Nephropathy may take a greater toll on a pediatric patient, compared with adults; data show that children are more likely to have renal involvement, need hemodialysis and kidney transplantation, and require hospitalization and emergency department visits (Lupus 2008;17:314-22; Arthritis Rheum. 2009;61:13-20).

To avoid end-stage renal disease, Dr. Kahn urges tight blood pressure control, as well as antihypertensive medication as necessary.

“We know that 90% of the patients who ultimately develop renal disease will do so within the first 2 years of disease, so if you follow a patient for [more than 2] years and they do not develop the disease, the good news is they are much less likely to develop nephropathy,” said Dr. Kahn.

In the 1950s, the 5-year survival rate for SLE in adults and children ranged from 18% to 70%; 30 years later, 5-year survival rose to 60%-93%, in large part because of the introduction of prednisone.

Currently, prednisone is almost universally given to those with cSLE, and the proportion of children who are treated with prednisone is significantly higher than the proportion of adults with SLE (97% vs. 70%; P less than .0001) (Arthritis Rheum. 2008;58:556-62). The result is greater risk of osteoporosis, diabetes, and growth failure.

In fact, up to 40% of cSLE patients have growth failure or short stature, in part because of chronic steroids.

That is why Dr. Kahn posed the question, “Can we move beyond steroids?”

Until recently, the only Food and Drug Administration–approved medications for SLE were prednisone, hydroxychloroquine, and aspirin.

Steroid-sparing immunomodulatory therapy is sometimes used off label when major organ (such as brain or kidney) involvement develops, but most evidence regarding the efficacy of these medications pertains to renal proliferative disease in adults.

Cyclophosphamide is often used for induction of nephritis, but 30% of patients may still develop end-stage renal disease despite treatment, said Dr. Kahn. Mycophenolate mofetil has been shown to have equal efficacy to cyclophosphamide in induction of remission of nephritis, but sufficient pediatric data are lacking. Azathioprine is effective for maintenance therapy of nephritis after the induction phase.

Other options that are sometimes used include intravenous immunoglobulin, methotrexate, calcineurin inhibitors (such as tacrolimus), plasmapheresis, and autologous stem cell transplantation/immunoablative therapy.

More recently, the focus has been on target-specific therapy for SLE with potentially fewer side effects.

Rituximab, which targets B cells that have the CD20 surface antigen, is sometimes used to treat resistant patients, but there is no strong clinical evidence to demonstrate its effectiveness in cSLE (Arthritis Rheum. 2009;61:482-7; Clin. J. Am. Soc. Nephrol. 2009;4:579-87).

Abatacept, which targets T cells by binding to B7 peripheral membrane protein, has shown some clinical benefit in a phase IIB randomized clinical trial, and is undergoing clinical testing as an add-on induction therapy with cyclophosphamide (Arthritis Rheum. 2010;62:3077-87).

Belimumab, a monoclonal antibody that targets BLyS (B-lymphocyte stimulator)/BAFF (B-cell activating factor), is the first FDA-approved medication for SLE in more than 50 years, based on recent clinical trials that demonstrate increased efficacy and fewer flares of disease, compared with placebo (Arthritis Rheum. 2009;61:1168-78; Lancet 2011;377:721-31).

Although recent data regarding belimumab provide some hope, it “may be naive to think that a target-specific therapy exists in this complex, polygenic, heterogeneous disease,” commented Dr. Kahn.

In concluding his talk, Dr. Kahn spoke about some barriers to the effective treatment of cSLE.

These include physicians' failure to detect the subtle changes of early disease, a lack of awareness regarding the neuropsychiatric manifestations of the disease, and physicians' fear of being overly aggressive with treatment.

He also warned about overt or covert adolescent noncompliance, and the danger of adolescents' dropping out of the health care system once they need to transition to adult care.

Major Finding: Childhood-onset SLE may be difficult to diagnose because its symptoms differ from that of adult-onset SLE. But cSLE is a predictor of mortality, and steps should be taken to control morbidities such as infection, premature atherosclerosis, and nephropathy. Prednisone remains a cornerstone of pharmacotherapy but has serious side effects, including osteoporosis and impaired growth. Additional nontargeted and targeted options are available.

Data Source: A clinical update presentation based on published reports and clinical experience.

Disclosures: Dr. Kahn reports no relevant disclosures.

NEW YORK – The good news in the management of childhood-onset systemic lupus erythematosus is that children who are diagnosed with the disease have a better prognosis and are living longer.

The bad news is that over the course of a lifetime, affected children develop more morbidities and experience more medication-induced toxicities, which create additional management challenges, according to Dr. Phillip Kahn, who spoke at the meeting.

About 15%-20% of lupus cases present in childhood. Children younger than age 5 years rarely have the disease, but up to 40% of patients with childhood-onset SLE (cSLE) present prior to puberty, said Dr. Kahn of New York University.

The incidence of cSLE is estimated to be 10-20 cases per 100,000 individuals, but the incidence is higher in blacks, at 200 cases per 100,000 individuals (Lupus 2007;16:546-9; 2005;14:83-8).

Often the diagnosis is delayed in children, as their clinical features do not fall within those defined by the 1997 American College of Rheumatology's SLE criteria, which have not been validated in children.

For example, Dr. Kahn described the case of a 13-year-old girl who presented with “constitutional symptoms” such as diffuse lymphadenopathy, malaise, weight loss, and fever – none of which are included in the 1997 criteria.

Mucocutaneous lesions are common in children, with up to 70% presenting with malar rash, 30% with alopecia, 66% with oral ulcers, and 10% with nasal ulcers.

“Although nasal ulcers are less common in children than adults, they still may result in perforation of the septum,” he said. Other common manifestations include painful polyarthritis, hepatosplenomegaly, headache, photosensitivity, and Raynaud's phenomenon.

Up to 40% of cSLE patients have neuropsychiatric symptoms, significantly more than do adults (Lupus 2008;17:314-22).

An important diagnostic tool for cSLE is a positive ANA (antinuclear antibody) finding, which is present in essentially all children with cSLE. In contrast, up to 10% of adults with SLE do not have a positive ANA, said Dr. Kahn.

Childhood-onset lupus may predict mortality in adults (Arthritis Care Res. [Hoboken] 2010;62:1152-9) and thus physicians must be vigilant about detecting, preventing, and aggressively treating some of its more dangerous manifestations.

To prevent recurrent infection, Dr. Kahn recommends keeping a child up to date with immunizations, treating infections promptly when they occur, and considering PCP (pneumocystis carinii pneumonia) prophylaxis in the appropriate patient. Children with cSLE are also at increased risk for premature atherosclerosis, with dyslipidemia seen in 60%-85% of affected children (Nat. Clin. Pract. Rheumatol. 2008;4:258-65). Statin therapy may be appropriate in these children, especially to prevent long-term adverse events such as early MI. For example, adults – especially women – who had cSLE have increased incidence of MI when they reach their 30s (Arthritis Rheum. 2009;61:13-20). The ongoing APPLE (Atherosclerosis Prevention in Pediatric Lupus Erythematosus) trial is investigating, in greater detail, cardiovascular risk and the use of statins in cSLE (Lupus 2010;19:1315-25).

Because nephropathy is the main cause of mortality and morbidity in cSLE, it is important to monitor urinary markers of renal function. Nephropathy may take a greater toll on a pediatric patient, compared with adults; data show that children are more likely to have renal involvement, need hemodialysis and kidney transplantation, and require hospitalization and emergency department visits (Lupus 2008;17:314-22; Arthritis Rheum. 2009;61:13-20).

To avoid end-stage renal disease, Dr. Kahn urges tight blood pressure control, as well as antihypertensive medication as necessary.

“We know that 90% of the patients who ultimately develop renal disease will do so within the first 2 years of disease, so if you follow a patient for [more than 2] years and they do not develop the disease, the good news is they are much less likely to develop nephropathy,” said Dr. Kahn.

In the 1950s, the 5-year survival rate for SLE in adults and children ranged from 18% to 70%; 30 years later, 5-year survival rose to 60%-93%, in large part because of the introduction of prednisone.

Currently, prednisone is almost universally given to those with cSLE, and the proportion of children who are treated with prednisone is significantly higher than the proportion of adults with SLE (97% vs. 70%; P less than .0001) (Arthritis Rheum. 2008;58:556-62). The result is greater risk of osteoporosis, diabetes, and growth failure.

In fact, up to 40% of cSLE patients have growth failure or short stature, in part because of chronic steroids.

That is why Dr. Kahn posed the question, “Can we move beyond steroids?”

Until recently, the only Food and Drug Administration–approved medications for SLE were prednisone, hydroxychloroquine, and aspirin.

Steroid-sparing immunomodulatory therapy is sometimes used off label when major organ (such as brain or kidney) involvement develops, but most evidence regarding the efficacy of these medications pertains to renal proliferative disease in adults.

Cyclophosphamide is often used for induction of nephritis, but 30% of patients may still develop end-stage renal disease despite treatment, said Dr. Kahn. Mycophenolate mofetil has been shown to have equal efficacy to cyclophosphamide in induction of remission of nephritis, but sufficient pediatric data are lacking. Azathioprine is effective for maintenance therapy of nephritis after the induction phase.

Other options that are sometimes used include intravenous immunoglobulin, methotrexate, calcineurin inhibitors (such as tacrolimus), plasmapheresis, and autologous stem cell transplantation/immunoablative therapy.

More recently, the focus has been on target-specific therapy for SLE with potentially fewer side effects.

Rituximab, which targets B cells that have the CD20 surface antigen, is sometimes used to treat resistant patients, but there is no strong clinical evidence to demonstrate its effectiveness in cSLE (Arthritis Rheum. 2009;61:482-7; Clin. J. Am. Soc. Nephrol. 2009;4:579-87).

Abatacept, which targets T cells by binding to B7 peripheral membrane protein, has shown some clinical benefit in a phase IIB randomized clinical trial, and is undergoing clinical testing as an add-on induction therapy with cyclophosphamide (Arthritis Rheum. 2010;62:3077-87).

Belimumab, a monoclonal antibody that targets BLyS (B-lymphocyte stimulator)/BAFF (B-cell activating factor), is the first FDA-approved medication for SLE in more than 50 years, based on recent clinical trials that demonstrate increased efficacy and fewer flares of disease, compared with placebo (Arthritis Rheum. 2009;61:1168-78; Lancet 2011;377:721-31).

Although recent data regarding belimumab provide some hope, it “may be naive to think that a target-specific therapy exists in this complex, polygenic, heterogeneous disease,” commented Dr. Kahn.

In concluding his talk, Dr. Kahn spoke about some barriers to the effective treatment of cSLE.

These include physicians' failure to detect the subtle changes of early disease, a lack of awareness regarding the neuropsychiatric manifestations of the disease, and physicians' fear of being overly aggressive with treatment.

He also warned about overt or covert adolescent noncompliance, and the danger of adolescents' dropping out of the health care system once they need to transition to adult care.

PROVIDENCE, R.I. – After the Food and Drug Administration issued an updated safety communication concerning the surgical placement of transvaginal mesh to repair pelvic organ prolapse on July 13, 2011, leaders of the American Urogynecologic Society sprang into action.

The American Urogynecologic Society (AUGS) leadership alerted its members, participated in a stakeholders’ conference call the following day with the FDA, polled its members, created a blog on its website, released its own recommendations, and testified before an FDA investigatory panel Sept. 8-9 regarding the safe and effective use of transvaginal mesh for both pelvic organ prolapse (POP) and stress urinary incontinence (SUI).

The FDA’s Safety Communication of 7/13/2011

The FDA’s safety communication concerning transvaginal placement of surgical mesh for POP was actually the second one issued by the agency regarding transvaginal placement of surgical mesh. The first one was issued in 2008 after more than 1,000 adverse events were reported to the FDA for surgical mesh used in the repair of POP and SUI. From Jan. 1, 2008, through Dec. 31, 2010, the FDA received 2,874 additional reports of adverse events, with 1,503 linked to POP repairs and 1,371 linked to surgery for SUI.

After a systematic review of the literature from 1996 to 2011, the FDA concluded that transvaginal POP repair with mesh may have an anatomic benefit that may not necessarily improve symptoms or quality of life over traditional nonmesh repair. They stated that in most cases, POP can be treated successfully without mesh, and mesh surgery should be chosen only after weighing associated risks and benefits.

The FDA Panel Hearing

It was clear that AUGS members have a variety of opinions regarding intravaginal mesh for POP.

On Sept. 8-9, 2011, the FDA convened an Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee to consider the use of transvaginal mesh for POP and SUI. The 19-person panel, chaired by Dr. Tommaso Falcone of the Cleveland Clinic, included 12 physicians, 2 statisticians, and representatives of patients, consumers, and industry. Five were members of AUGS, including Dr. Cheryl B. Iglesia, director of the Section of Female Pelvic Medicine and Reconstructive Surgery at Washington (D.C.) Hospital Center, who spoke about her experiences at the AUGS annual meeting.

The AUGS’ Stand and the Panel’s Recommendations

On Sept. 15, 2011, at the AUGS annual meeting, an update was held to inform members about new developments regarding vaginal placement of mesh. President Deborah Myers presented the AUGS leadership stance, which was also outlined in an executive summary (available on the organization’s website, www.augs.org). Dr. Iglesia presented a summary of the recommendations made by the panel to the FDA.

The AUGS statement described some of the complexities regarding the use of transvaginal mesh for pelvic reconstruction. The society indicated that it supports the FDA Safety Communication Update recommendations: that often POP can be treated successfully without mesh. However, while AUGS does not support the routine use of vaginal mesh for POP repair, it recognizes "that there may be particular circumstances when the placement of transvaginal mesh is beneficial and appropriate."

After discussion of a number of serious adverse events associated with the use of vaginal mesh for POP repair, the panel’s consensus was that the safety of such mesh is not well established. Depending on the compartment, vaginal placement of mesh for POP repair may not be more effective than traditional "native-tissue" repair without mesh, and the consensus was that the risk/benefit of vaginal placement of mesh for POP repair is not well established.

The AUGS statement indicated that there is insufficient data available to guide treatment decisions for individual patients, noting that such decisions should be made collaboratively by physicians and patients. Although outcomes reflect both surgical training and skill, many members of AUGS report excellent outcomes and low complication rates with transvaginal mesh.

With this in mind, "AUGS does not support a 'blanket' withdrawal of currently available transvaginal mesh products from the market." Instead, AUGS supports the judicious use of transvaginal mesh for POP repair performed only by surgeons with appropriate training on patients who have been fully informed of the risks and benefits of all available treatment options.

AUGS’ stance on informed consent is "in sync" with the FDA. It supports a consent process that informs patients of nonsurgical options, alternative native tissue surgical repairs, and abdominal repairs, as well as possible adverse outcomes associated with mesh. The organization is planning to offer an online informed consent checklist.

Strategies for Mesh in POP Surgery

Within the next 12 months, AUGS plans to develop educational and training recommendations to guide hospitals in privileging those who may conduct POP surgery using transvaginal mesh. Until those recommendations are issued, AUGS suggests "that continued placement of transvaginal mesh for POP be performed only by providers who have extensive training in pelvic surgery, maintain a high volume of surgical procedures for prolapse, have specific training in the device and method used, and are able to track both objective and subjective short-term and long-term outcomes."

Currently, postmarketing surveillance is voluntary and not inclusive of all vaginal meshes. AUGS recommends that the FDA invoke its power under section 522 of the Food and Drug Administration Modernization Act of 1997 to require postmarketing surveillance by means of a postmarket registry and/or national database of all users of vaginally placed mesh, to track both positive and negative anatomic and subjective outcomes. Until the registry is created, AUGS recommends all surgeons track their own outcomes.

The most contentious issue concerns the type of clinical evidence needed to support continued use of mesh already in the marketplace and future technology. Currently available mesh were generally approved as class II devices under the 510(k) process, often with another legally marketed, predicate device as control.

"Many things we deal with are class II, requiring general or special controls," said Dr. Matthew Barber of the Cleveland Clinic, president-elect of AUGS. Class III devices require a premarket approval application (PMA), and such devices are often considered high risk, life sustaining, life supporting or of substantial health importance, or present unreasonable risk or injury. Like drugs, class III devices require independent assessment of safety and effectiveness prior to marketing.

"There may be particular circumstances when the placement of transvaginal mesh is beneficial and appropriate."

AUGS stated that it supports mandatory clinical trials for transvaginal mesh for POP and is in favor of a requirement that premarket notifications or PMAs include clinical trials that use patient-centered outcomes and long-term patient follow-up. The studies should be prospective, and can be cohort studies, registries or randomized, controlled trials, but randomized controlled trials are not required. Clinical trials should have a minimum of 1-year of follow-up with an additional 2-4 years of patient follow-up, and FDA reporting for new prolapse mesh devices or for significant modifications of existing devices. AUGS supports keeping transvaginal mesh devices as class II devices, and would assist the FDA in developing special controls if required by the FDA.

"The bottom line is, we want them to leave slings alone and place them into a registry," remarked Dr. Myers of Brown Medical School, Providence, R.I..

Setting Standards and Evaluating Vaginal Mesh

The panel called for stricter standards than currently exist or requested by AUGS, recommending that premarket evaluation of vaginal mesh for POP was needed, and that the control arm for such studies be women undergoing surgical repair of POP without the use of mesh. Therefore, class II special controls would not be sufficient, and the panel’s consensus was that vaginal mesh for POP repair be reclassified from class II to class III. The panel felt that there were enough data available to support the use of mesh for abdominal sacral colpopexy. There was no need for clinical performance data for new mesh products similar to products already on the market, and postmarketing surveillance was not needed.

AUGS also clearly makes the distinction between the use of mesh for prolapse and use for SUI. It "strongly opposes withdrawal of synthetic mesh devices for surgical treatment of SUI and does not feel any change in the current regulatory status of synthetic mesh for this use is warranted." Noting the considerable evidence supporting its use, AUGS asserts that midurethral slings, placed either by a retropubic or transobturator approach, is the current standard of care for the surgical treatment of SUI. AUGS supports establishing a postmarket registry for mesh used for SUI, and appropriate premarket clinical trials for devices significantly different from those that are currently available.

The situation is still in flux. Recommendations made by the advisory panel are not mandatory, noted Dr. Iglesia. "If the recommendations are adopted by the FDA, it will take several years to take effect, and existing products will stay on the market."

During the question-and-answer session following the AUGS update, it was clear that AUGS members have a variety of opinions regarding intravaginal mesh for POP, with some extolling their use and others overwhelmed by the need to repair mesh-related complications, especially mesh implanted by inadequately trained practitioners.

No financial disclosures were listed for Dr. Myers, Dr. Barber, or Dr. Iglesia.

PROVIDENCE, R.I. – After the Food and Drug Administration issued an updated safety communication concerning the surgical placement of transvaginal mesh to repair pelvic organ prolapse on July 13, 2011, leaders of the American Urogynecologic Society sprang into action.

The American Urogynecologic Society (AUGS) leadership alerted its members, participated in a stakeholders’ conference call the following day with the FDA, polled its members, created a blog on its website, released its own recommendations, and testified before an FDA investigatory panel Sept. 8-9 regarding the safe and effective use of transvaginal mesh for both pelvic organ prolapse (POP) and stress urinary incontinence (SUI).

The FDA’s Safety Communication of 7/13/2011

The FDA’s safety communication concerning transvaginal placement of surgical mesh for POP was actually the second one issued by the agency regarding transvaginal placement of surgical mesh. The first one was issued in 2008 after more than 1,000 adverse events were reported to the FDA for surgical mesh used in the repair of POP and SUI. From Jan. 1, 2008, through Dec. 31, 2010, the FDA received 2,874 additional reports of adverse events, with 1,503 linked to POP repairs and 1,371 linked to surgery for SUI.

After a systematic review of the literature from 1996 to 2011, the FDA concluded that transvaginal POP repair with mesh may have an anatomic benefit that may not necessarily improve symptoms or quality of life over traditional nonmesh repair. They stated that in most cases, POP can be treated successfully without mesh, and mesh surgery should be chosen only after weighing associated risks and benefits.

The FDA Panel Hearing

It was clear that AUGS members have a variety of opinions regarding intravaginal mesh for POP.

On Sept. 8-9, 2011, the FDA convened an Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee to consider the use of transvaginal mesh for POP and SUI. The 19-person panel, chaired by Dr. Tommaso Falcone of the Cleveland Clinic, included 12 physicians, 2 statisticians, and representatives of patients, consumers, and industry. Five were members of AUGS, including Dr. Cheryl B. Iglesia, director of the Section of Female Pelvic Medicine and Reconstructive Surgery at Washington (D.C.) Hospital Center, who spoke about her experiences at the AUGS annual meeting.

The AUGS’ Stand and the Panel’s Recommendations

On Sept. 15, 2011, at the AUGS annual meeting, an update was held to inform members about new developments regarding vaginal placement of mesh. President Deborah Myers presented the AUGS leadership stance, which was also outlined in an executive summary (available on the organization’s website, www.augs.org). Dr. Iglesia presented a summary of the recommendations made by the panel to the FDA.

The AUGS statement described some of the complexities regarding the use of transvaginal mesh for pelvic reconstruction. The society indicated that it supports the FDA Safety Communication Update recommendations: that often POP can be treated successfully without mesh. However, while AUGS does not support the routine use of vaginal mesh for POP repair, it recognizes "that there may be particular circumstances when the placement of transvaginal mesh is beneficial and appropriate."

After discussion of a number of serious adverse events associated with the use of vaginal mesh for POP repair, the panel’s consensus was that the safety of such mesh is not well established. Depending on the compartment, vaginal placement of mesh for POP repair may not be more effective than traditional "native-tissue" repair without mesh, and the consensus was that the risk/benefit of vaginal placement of mesh for POP repair is not well established.

The AUGS statement indicated that there is insufficient data available to guide treatment decisions for individual patients, noting that such decisions should be made collaboratively by physicians and patients. Although outcomes reflect both surgical training and skill, many members of AUGS report excellent outcomes and low complication rates with transvaginal mesh.

With this in mind, "AUGS does not support a 'blanket' withdrawal of currently available transvaginal mesh products from the market." Instead, AUGS supports the judicious use of transvaginal mesh for POP repair performed only by surgeons with appropriate training on patients who have been fully informed of the risks and benefits of all available treatment options.

AUGS’ stance on informed consent is "in sync" with the FDA. It supports a consent process that informs patients of nonsurgical options, alternative native tissue surgical repairs, and abdominal repairs, as well as possible adverse outcomes associated with mesh. The organization is planning to offer an online informed consent checklist.

Strategies for Mesh in POP Surgery

Within the next 12 months, AUGS plans to develop educational and training recommendations to guide hospitals in privileging those who may conduct POP surgery using transvaginal mesh. Until those recommendations are issued, AUGS suggests "that continued placement of transvaginal mesh for POP be performed only by providers who have extensive training in pelvic surgery, maintain a high volume of surgical procedures for prolapse, have specific training in the device and method used, and are able to track both objective and subjective short-term and long-term outcomes."

Currently, postmarketing surveillance is voluntary and not inclusive of all vaginal meshes. AUGS recommends that the FDA invoke its power under section 522 of the Food and Drug Administration Modernization Act of 1997 to require postmarketing surveillance by means of a postmarket registry and/or national database of all users of vaginally placed mesh, to track both positive and negative anatomic and subjective outcomes. Until the registry is created, AUGS recommends all surgeons track their own outcomes.

The most contentious issue concerns the type of clinical evidence needed to support continued use of mesh already in the marketplace and future technology. Currently available mesh were generally approved as class II devices under the 510(k) process, often with another legally marketed, predicate device as control.

"Many things we deal with are class II, requiring general or special controls," said Dr. Matthew Barber of the Cleveland Clinic, president-elect of AUGS. Class III devices require a premarket approval application (PMA), and such devices are often considered high risk, life sustaining, life supporting or of substantial health importance, or present unreasonable risk or injury. Like drugs, class III devices require independent assessment of safety and effectiveness prior to marketing.

"There may be particular circumstances when the placement of transvaginal mesh is beneficial and appropriate."

AUGS stated that it supports mandatory clinical trials for transvaginal mesh for POP and is in favor of a requirement that premarket notifications or PMAs include clinical trials that use patient-centered outcomes and long-term patient follow-up. The studies should be prospective, and can be cohort studies, registries or randomized, controlled trials, but randomized controlled trials are not required. Clinical trials should have a minimum of 1-year of follow-up with an additional 2-4 years of patient follow-up, and FDA reporting for new prolapse mesh devices or for significant modifications of existing devices. AUGS supports keeping transvaginal mesh devices as class II devices, and would assist the FDA in developing special controls if required by the FDA.

"The bottom line is, we want them to leave slings alone and place them into a registry," remarked Dr. Myers of Brown Medical School, Providence, R.I..

Setting Standards and Evaluating Vaginal Mesh

The panel called for stricter standards than currently exist or requested by AUGS, recommending that premarket evaluation of vaginal mesh for POP was needed, and that the control arm for such studies be women undergoing surgical repair of POP without the use of mesh. Therefore, class II special controls would not be sufficient, and the panel’s consensus was that vaginal mesh for POP repair be reclassified from class II to class III. The panel felt that there were enough data available to support the use of mesh for abdominal sacral colpopexy. There was no need for clinical performance data for new mesh products similar to products already on the market, and postmarketing surveillance was not needed.

AUGS also clearly makes the distinction between the use of mesh for prolapse and use for SUI. It "strongly opposes withdrawal of synthetic mesh devices for surgical treatment of SUI and does not feel any change in the current regulatory status of synthetic mesh for this use is warranted." Noting the considerable evidence supporting its use, AUGS asserts that midurethral slings, placed either by a retropubic or transobturator approach, is the current standard of care for the surgical treatment of SUI. AUGS supports establishing a postmarket registry for mesh used for SUI, and appropriate premarket clinical trials for devices significantly different from those that are currently available.

The situation is still in flux. Recommendations made by the advisory panel are not mandatory, noted Dr. Iglesia. "If the recommendations are adopted by the FDA, it will take several years to take effect, and existing products will stay on the market."

During the question-and-answer session following the AUGS update, it was clear that AUGS members have a variety of opinions regarding intravaginal mesh for POP, with some extolling their use and others overwhelmed by the need to repair mesh-related complications, especially mesh implanted by inadequately trained practitioners.

No financial disclosures were listed for Dr. Myers, Dr. Barber, or Dr. Iglesia.

PROVIDENCE, R.I. – After the Food and Drug Administration issued an updated safety communication concerning the surgical placement of transvaginal mesh to repair pelvic organ prolapse on July 13, 2011, leaders of the American Urogynecologic Society sprang into action.

The American Urogynecologic Society (AUGS) leadership alerted its members, participated in a stakeholders’ conference call the following day with the FDA, polled its members, created a blog on its website, released its own recommendations, and testified before an FDA investigatory panel Sept. 8-9 regarding the safe and effective use of transvaginal mesh for both pelvic organ prolapse (POP) and stress urinary incontinence (SUI).

The FDA’s Safety Communication of 7/13/2011

The FDA’s safety communication concerning transvaginal placement of surgical mesh for POP was actually the second one issued by the agency regarding transvaginal placement of surgical mesh. The first one was issued in 2008 after more than 1,000 adverse events were reported to the FDA for surgical mesh used in the repair of POP and SUI. From Jan. 1, 2008, through Dec. 31, 2010, the FDA received 2,874 additional reports of adverse events, with 1,503 linked to POP repairs and 1,371 linked to surgery for SUI.

After a systematic review of the literature from 1996 to 2011, the FDA concluded that transvaginal POP repair with mesh may have an anatomic benefit that may not necessarily improve symptoms or quality of life over traditional nonmesh repair. They stated that in most cases, POP can be treated successfully without mesh, and mesh surgery should be chosen only after weighing associated risks and benefits.

The FDA Panel Hearing

It was clear that AUGS members have a variety of opinions regarding intravaginal mesh for POP.

On Sept. 8-9, 2011, the FDA convened an Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee to consider the use of transvaginal mesh for POP and SUI. The 19-person panel, chaired by Dr. Tommaso Falcone of the Cleveland Clinic, included 12 physicians, 2 statisticians, and representatives of patients, consumers, and industry. Five were members of AUGS, including Dr. Cheryl B. Iglesia, director of the Section of Female Pelvic Medicine and Reconstructive Surgery at Washington (D.C.) Hospital Center, who spoke about her experiences at the AUGS annual meeting.

The AUGS’ Stand and the Panel’s Recommendations

On Sept. 15, 2011, at the AUGS annual meeting, an update was held to inform members about new developments regarding vaginal placement of mesh. President Deborah Myers presented the AUGS leadership stance, which was also outlined in an executive summary (available on the organization’s website, www.augs.org). Dr. Iglesia presented a summary of the recommendations made by the panel to the FDA.

The AUGS statement described some of the complexities regarding the use of transvaginal mesh for pelvic reconstruction. The society indicated that it supports the FDA Safety Communication Update recommendations: that often POP can be treated successfully without mesh. However, while AUGS does not support the routine use of vaginal mesh for POP repair, it recognizes "that there may be particular circumstances when the placement of transvaginal mesh is beneficial and appropriate."

After discussion of a number of serious adverse events associated with the use of vaginal mesh for POP repair, the panel’s consensus was that the safety of such mesh is not well established. Depending on the compartment, vaginal placement of mesh for POP repair may not be more effective than traditional "native-tissue" repair without mesh, and the consensus was that the risk/benefit of vaginal placement of mesh for POP repair is not well established.

The AUGS statement indicated that there is insufficient data available to guide treatment decisions for individual patients, noting that such decisions should be made collaboratively by physicians and patients. Although outcomes reflect both surgical training and skill, many members of AUGS report excellent outcomes and low complication rates with transvaginal mesh.

With this in mind, "AUGS does not support a 'blanket' withdrawal of currently available transvaginal mesh products from the market." Instead, AUGS supports the judicious use of transvaginal mesh for POP repair performed only by surgeons with appropriate training on patients who have been fully informed of the risks and benefits of all available treatment options.

AUGS’ stance on informed consent is "in sync" with the FDA. It supports a consent process that informs patients of nonsurgical options, alternative native tissue surgical repairs, and abdominal repairs, as well as possible adverse outcomes associated with mesh. The organization is planning to offer an online informed consent checklist.

Strategies for Mesh in POP Surgery

Within the next 12 months, AUGS plans to develop educational and training recommendations to guide hospitals in privileging those who may conduct POP surgery using transvaginal mesh. Until those recommendations are issued, AUGS suggests "that continued placement of transvaginal mesh for POP be performed only by providers who have extensive training in pelvic surgery, maintain a high volume of surgical procedures for prolapse, have specific training in the device and method used, and are able to track both objective and subjective short-term and long-term outcomes."

Currently, postmarketing surveillance is voluntary and not inclusive of all vaginal meshes. AUGS recommends that the FDA invoke its power under section 522 of the Food and Drug Administration Modernization Act of 1997 to require postmarketing surveillance by means of a postmarket registry and/or national database of all users of vaginally placed mesh, to track both positive and negative anatomic and subjective outcomes. Until the registry is created, AUGS recommends all surgeons track their own outcomes.

The most contentious issue concerns the type of clinical evidence needed to support continued use of mesh already in the marketplace and future technology. Currently available mesh were generally approved as class II devices under the 510(k) process, often with another legally marketed, predicate device as control.

"Many things we deal with are class II, requiring general or special controls," said Dr. Matthew Barber of the Cleveland Clinic, president-elect of AUGS. Class III devices require a premarket approval application (PMA), and such devices are often considered high risk, life sustaining, life supporting or of substantial health importance, or present unreasonable risk or injury. Like drugs, class III devices require independent assessment of safety and effectiveness prior to marketing.

"There may be particular circumstances when the placement of transvaginal mesh is beneficial and appropriate."

AUGS stated that it supports mandatory clinical trials for transvaginal mesh for POP and is in favor of a requirement that premarket notifications or PMAs include clinical trials that use patient-centered outcomes and long-term patient follow-up. The studies should be prospective, and can be cohort studies, registries or randomized, controlled trials, but randomized controlled trials are not required. Clinical trials should have a minimum of 1-year of follow-up with an additional 2-4 years of patient follow-up, and FDA reporting for new prolapse mesh devices or for significant modifications of existing devices. AUGS supports keeping transvaginal mesh devices as class II devices, and would assist the FDA in developing special controls if required by the FDA.

"The bottom line is, we want them to leave slings alone and place them into a registry," remarked Dr. Myers of Brown Medical School, Providence, R.I..

Setting Standards and Evaluating Vaginal Mesh

The panel called for stricter standards than currently exist or requested by AUGS, recommending that premarket evaluation of vaginal mesh for POP was needed, and that the control arm for such studies be women undergoing surgical repair of POP without the use of mesh. Therefore, class II special controls would not be sufficient, and the panel’s consensus was that vaginal mesh for POP repair be reclassified from class II to class III. The panel felt that there were enough data available to support the use of mesh for abdominal sacral colpopexy. There was no need for clinical performance data for new mesh products similar to products already on the market, and postmarketing surveillance was not needed.

AUGS also clearly makes the distinction between the use of mesh for prolapse and use for SUI. It "strongly opposes withdrawal of synthetic mesh devices for surgical treatment of SUI and does not feel any change in the current regulatory status of synthetic mesh for this use is warranted." Noting the considerable evidence supporting its use, AUGS asserts that midurethral slings, placed either by a retropubic or transobturator approach, is the current standard of care for the surgical treatment of SUI. AUGS supports establishing a postmarket registry for mesh used for SUI, and appropriate premarket clinical trials for devices significantly different from those that are currently available.

The situation is still in flux. Recommendations made by the advisory panel are not mandatory, noted Dr. Iglesia. "If the recommendations are adopted by the FDA, it will take several years to take effect, and existing products will stay on the market."

During the question-and-answer session following the AUGS update, it was clear that AUGS members have a variety of opinions regarding intravaginal mesh for POP, with some extolling their use and others overwhelmed by the need to repair mesh-related complications, especially mesh implanted by inadequately trained practitioners.

No financial disclosures were listed for Dr. Myers, Dr. Barber, or Dr. Iglesia.

PROVIDENCE, R.I. – Use of a prophylactic mid-urethral sling during the course of transvaginal prolapse repair significantly reduced the risk of urinary incontinence symptoms at 3 and 12 months post surgery, according to Dr. John T. Wei, who presented the results at the annual meeting of the American Urogynecologic Society.

"The basis for this trial is a common dilemma we face: When a woman with significant vaginal prolapse but no stress-related urinary incontinence undergoes transvaginal prolapse repair, should a sling be placed in all women or should treatment be delayed until she develops symptomatic urinary incontinence? Level 1 evidence does not exist to address that question, and that is why the Pelvic Floor Disorders Network [PFDN] commissioned the OPUS [Outcomes Following Vaginal Prolapse Repair and Midurethral Sling] trial," said Dr. Wei, professor of urology at the University of Michigan, Ann Arbor. Dr. Wei’s presentation earned the "Best Overall Paper" award at the meeting.

The PFDN was created by the National Institute of Child Health and Human Development’s contraception and reproductive health branch. It consists of eight clinical sites and one data-coordinating center. This is the first protocol conducted by the PFDN.

In the OPUS trial, 337 women with symptomatic greater than or equal to stage-2 anterior prolapse who did not report symptoms of stress urinary incontinence (SUI) were randomized to undergo either insertion of retropubic tension-free vaginal tape (TVT) (n=165) or sham incisions (n=172) during prolapse surgery. The primary endpoint was urinary incontinence (UI) failure, defined as having at least one of the following: a positive cough stress test, bothersome UI symptoms, or treatment for UI (pharmacologic or surgical).

Three months after surgery, the rate of UI failure in those who received a prophylactic sling was less than half of that seen in the sham-operated group (23.6% vs. 49.4%, P less than .0001). Similar results were noted at 12 months (27.3% vs. 43.0%, P = .0024), even after allowing for additional UI postoperative treatment. Significant differences favoring the sling also were found for quality of life measures. However, no significant differences between groups were found for measures of other pelvic floor conditions such as prolapse, pain, or decreased sexual function or general health (as measured by the short form SF-36 questionnaire).

Although there were no significant differences between groups in serious and unexpected adverse events, those in the TVT group had higher rates of bladder perforations (6.7% vs. 0%), urinary tract infections (31% vs. 17.2%), major bleeding/vascular complications (3% vs. 0%) or incomplete bladder emptying at 6 weeks (3.7% vs. 0%).

In a companion presentation by Dr. Wei, the question was raised as to whether a preoperative prolapse reduction stress test (PRST) was of value for predicting which women would benefit most from prophylactic sling insertion. To answer this question, the group did a post hoc analysis, comparing outcomes according to whether the PRST was positive or negative.

The preoperative PRST was performed by retrograde fill (300 mL), removing the catheter and performing Valsalva and cough testing in lithotomy position without prolapse reduction, in lithotomy with prolapse reduced with Procto Swabs, and standing with prolapse reduced. A positive stress test was defined as urine leakage in either position, with or without reduction. The PRST results were masked to the surgeons, so the results had no influence on treatment assignment. Almost all women enrolled in the trial (98%) had undergone PRST.

Dr. Wei found that, at 3 months, insertion of the sling had a beneficial effect, whether or not the PRST was positive or negative, but the magnitude of effect of the sling was greater if the patient had a positive PRST. Treatment failure at 3 months in the positive PRST group was 29.6% in the sling group vs. 71.9% in the sham group; in the negative PRST group the rates were 20.6% in the sling group vs. 38.1% in the sham group (interaction P = .06). Similar trends were seen at 12 months but the differences were not significant.

"Women with a positive PRST who do not receive a TVT are at highest risk of having at UI at 3 months after vaginal prolapse surgery," he said.

Another group included in the study was a "patient preference cohort" (PPC) which included a group of women who were eligible for inclusion in the randomized controlled trial but elected not to participate because of randomization. According to Dr. Wei, the goal was to measure the level of nonparticipation bias to improve the validity of the generalizability of the trial. "Both in magnitude and statistics, those in the PPC looked remarkably like those in the clinical trial."

"The low bias in the PPC group, the high rate of participation, and the high rate of follow-up all makes this an exceptional trial," he said.

Dr. Wei disclosed that he does contracted research for Sanofi-Aventis.

PROVIDENCE, R.I. – Use of a prophylactic mid-urethral sling during the course of transvaginal prolapse repair significantly reduced the risk of urinary incontinence symptoms at 3 and 12 months post surgery, according to Dr. John T. Wei, who presented the results at the annual meeting of the American Urogynecologic Society.

"The basis for this trial is a common dilemma we face: When a woman with significant vaginal prolapse but no stress-related urinary incontinence undergoes transvaginal prolapse repair, should a sling be placed in all women or should treatment be delayed until she develops symptomatic urinary incontinence? Level 1 evidence does not exist to address that question, and that is why the Pelvic Floor Disorders Network [PFDN] commissioned the OPUS [Outcomes Following Vaginal Prolapse Repair and Midurethral Sling] trial," said Dr. Wei, professor of urology at the University of Michigan, Ann Arbor. Dr. Wei’s presentation earned the "Best Overall Paper" award at the meeting.

The PFDN was created by the National Institute of Child Health and Human Development’s contraception and reproductive health branch. It consists of eight clinical sites and one data-coordinating center. This is the first protocol conducted by the PFDN.

In the OPUS trial, 337 women with symptomatic greater than or equal to stage-2 anterior prolapse who did not report symptoms of stress urinary incontinence (SUI) were randomized to undergo either insertion of retropubic tension-free vaginal tape (TVT) (n=165) or sham incisions (n=172) during prolapse surgery. The primary endpoint was urinary incontinence (UI) failure, defined as having at least one of the following: a positive cough stress test, bothersome UI symptoms, or treatment for UI (pharmacologic or surgical).

Three months after surgery, the rate of UI failure in those who received a prophylactic sling was less than half of that seen in the sham-operated group (23.6% vs. 49.4%, P less than .0001). Similar results were noted at 12 months (27.3% vs. 43.0%, P = .0024), even after allowing for additional UI postoperative treatment. Significant differences favoring the sling also were found for quality of life measures. However, no significant differences between groups were found for measures of other pelvic floor conditions such as prolapse, pain, or decreased sexual function or general health (as measured by the short form SF-36 questionnaire).

Although there were no significant differences between groups in serious and unexpected adverse events, those in the TVT group had higher rates of bladder perforations (6.7% vs. 0%), urinary tract infections (31% vs. 17.2%), major bleeding/vascular complications (3% vs. 0%) or incomplete bladder emptying at 6 weeks (3.7% vs. 0%).

In a companion presentation by Dr. Wei, the question was raised as to whether a preoperative prolapse reduction stress test (PRST) was of value for predicting which women would benefit most from prophylactic sling insertion. To answer this question, the group did a post hoc analysis, comparing outcomes according to whether the PRST was positive or negative.

The preoperative PRST was performed by retrograde fill (300 mL), removing the catheter and performing Valsalva and cough testing in lithotomy position without prolapse reduction, in lithotomy with prolapse reduced with Procto Swabs, and standing with prolapse reduced. A positive stress test was defined as urine leakage in either position, with or without reduction. The PRST results were masked to the surgeons, so the results had no influence on treatment assignment. Almost all women enrolled in the trial (98%) had undergone PRST.

Dr. Wei found that, at 3 months, insertion of the sling had a beneficial effect, whether or not the PRST was positive or negative, but the magnitude of effect of the sling was greater if the patient had a positive PRST. Treatment failure at 3 months in the positive PRST group was 29.6% in the sling group vs. 71.9% in the sham group; in the negative PRST group the rates were 20.6% in the sling group vs. 38.1% in the sham group (interaction P = .06). Similar trends were seen at 12 months but the differences were not significant.

"Women with a positive PRST who do not receive a TVT are at highest risk of having at UI at 3 months after vaginal prolapse surgery," he said.

Another group included in the study was a "patient preference cohort" (PPC) which included a group of women who were eligible for inclusion in the randomized controlled trial but elected not to participate because of randomization. According to Dr. Wei, the goal was to measure the level of nonparticipation bias to improve the validity of the generalizability of the trial. "Both in magnitude and statistics, those in the PPC looked remarkably like those in the clinical trial."

"The low bias in the PPC group, the high rate of participation, and the high rate of follow-up all makes this an exceptional trial," he said.

Dr. Wei disclosed that he does contracted research for Sanofi-Aventis.

PROVIDENCE, R.I. – Use of a prophylactic mid-urethral sling during the course of transvaginal prolapse repair significantly reduced the risk of urinary incontinence symptoms at 3 and 12 months post surgery, according to Dr. John T. Wei, who presented the results at the annual meeting of the American Urogynecologic Society.

"The basis for this trial is a common dilemma we face: When a woman with significant vaginal prolapse but no stress-related urinary incontinence undergoes transvaginal prolapse repair, should a sling be placed in all women or should treatment be delayed until she develops symptomatic urinary incontinence? Level 1 evidence does not exist to address that question, and that is why the Pelvic Floor Disorders Network [PFDN] commissioned the OPUS [Outcomes Following Vaginal Prolapse Repair and Midurethral Sling] trial," said Dr. Wei, professor of urology at the University of Michigan, Ann Arbor. Dr. Wei’s presentation earned the "Best Overall Paper" award at the meeting.

The PFDN was created by the National Institute of Child Health and Human Development’s contraception and reproductive health branch. It consists of eight clinical sites and one data-coordinating center. This is the first protocol conducted by the PFDN.

In the OPUS trial, 337 women with symptomatic greater than or equal to stage-2 anterior prolapse who did not report symptoms of stress urinary incontinence (SUI) were randomized to undergo either insertion of retropubic tension-free vaginal tape (TVT) (n=165) or sham incisions (n=172) during prolapse surgery. The primary endpoint was urinary incontinence (UI) failure, defined as having at least one of the following: a positive cough stress test, bothersome UI symptoms, or treatment for UI (pharmacologic or surgical).

Three months after surgery, the rate of UI failure in those who received a prophylactic sling was less than half of that seen in the sham-operated group (23.6% vs. 49.4%, P less than .0001). Similar results were noted at 12 months (27.3% vs. 43.0%, P = .0024), even after allowing for additional UI postoperative treatment. Significant differences favoring the sling also were found for quality of life measures. However, no significant differences between groups were found for measures of other pelvic floor conditions such as prolapse, pain, or decreased sexual function or general health (as measured by the short form SF-36 questionnaire).

Although there were no significant differences between groups in serious and unexpected adverse events, those in the TVT group had higher rates of bladder perforations (6.7% vs. 0%), urinary tract infections (31% vs. 17.2%), major bleeding/vascular complications (3% vs. 0%) or incomplete bladder emptying at 6 weeks (3.7% vs. 0%).

In a companion presentation by Dr. Wei, the question was raised as to whether a preoperative prolapse reduction stress test (PRST) was of value for predicting which women would benefit most from prophylactic sling insertion. To answer this question, the group did a post hoc analysis, comparing outcomes according to whether the PRST was positive or negative.

The preoperative PRST was performed by retrograde fill (300 mL), removing the catheter and performing Valsalva and cough testing in lithotomy position without prolapse reduction, in lithotomy with prolapse reduced with Procto Swabs, and standing with prolapse reduced. A positive stress test was defined as urine leakage in either position, with or without reduction. The PRST results were masked to the surgeons, so the results had no influence on treatment assignment. Almost all women enrolled in the trial (98%) had undergone PRST.

Dr. Wei found that, at 3 months, insertion of the sling had a beneficial effect, whether or not the PRST was positive or negative, but the magnitude of effect of the sling was greater if the patient had a positive PRST. Treatment failure at 3 months in the positive PRST group was 29.6% in the sling group vs. 71.9% in the sham group; in the negative PRST group the rates were 20.6% in the sling group vs. 38.1% in the sham group (interaction P = .06). Similar trends were seen at 12 months but the differences were not significant.

"Women with a positive PRST who do not receive a TVT are at highest risk of having at UI at 3 months after vaginal prolapse surgery," he said.

Another group included in the study was a "patient preference cohort" (PPC) which included a group of women who were eligible for inclusion in the randomized controlled trial but elected not to participate because of randomization. According to Dr. Wei, the goal was to measure the level of nonparticipation bias to improve the validity of the generalizability of the trial. "Both in magnitude and statistics, those in the PPC looked remarkably like those in the clinical trial."

"The low bias in the PPC group, the high rate of participation, and the high rate of follow-up all makes this an exceptional trial," he said.

Dr. Wei disclosed that he does contracted research for Sanofi-Aventis.

PROVIDENCE, R.I. – Compared with cesarean birth without labor, undergoing vaginal birth increased the risk of stress incontinence and prolapse in women who were examined 5-10 years after childbirth, Dr. Victoria L. Handa reported at the annual meeting of the American Urogynecologic Society.

The risk of all pelvic disorders, including prolapse, was elevated even further in women who had undergone operative vaginal delivery, she said.

"The results suggest no measurable differences in the relative odds of any pelvic floor disorder for women delivering by cesarean section, including those who labored into the second stage. For vaginal birth, the picture is very different," said Dr. Handa, director of the advanced training program in female pelvic medicine and reconstructive surgery at Johns Hopkins University, Baltimore.

In this longitudinal cohort study based on hospital obstetric records, 8,285 women who had their first child 5-10 years previously were recruited for the study and 1,011 were enrolled. Women were selected if their obstetric history met one of five categories: cesarean without labor (considered the reference group; n = 192), cesarean during active labor (n = 228), cesarean after complete cervical dilation (n = 140), spontaneous vaginal birth (n = 325), and operative vaginal birth (n = 126). Groups were matched for age at first delivery and interval from first delivery, and were similar with respect to parity and smoking status. At enrollment, a validated questionnaire (Epidemiology of Prolapse and Incontinence Questionnaire) was used to assess pelvic floor symptoms, and the women were examined for pelvic organ support using the Pelvic Organ Prolapse Quantification (POP-Q) System.

"One of the strengths of our study is that [obstetric] exposures were verified by chart review with validated outcomes, and there was [anatomical] evidence of prolapse," Dr. Handa said.

Overall, 11% of the 1,011 women had stress urinary incontinence, 8% had overactive bladder, and 11% had anal incontinence; 3% reported prolapse symptoms, and 7% had prolapse upon examination (Obstet. Gynecol. 2011;118:777-84).

When the group was analyzed according to obstetric history, the impact of vaginal birth emerged. Compared with women who had a cesarean birth before active labor, women who had a vaginal birth (but no operative vaginal births) had almost a threefold increased risk of stress incontinence and symptomatic prolapse. The odds ratio for prolapse to or beyond the hymen was increased more than fivefold.

Women who had undergone operative vaginal birth fared even worse. The adjusted odds of stress incontinence and overactive bladder were more than quadrupled and the odds of anal incontinence were doubled. There was almost an eightfold increased risk of prolapse to or beyond the hymen upon examination.

In her report, Dr. Handa noted that in addition to demonstrating the dramatic increase in pelvic floor disorders in women with a history of at least one operative vaginal birth, the results showed an increase in urinary incontinence after operative delivery – a finding that had not been definitively documented before. For those who had undergone cesarean delivery, the results showed no association between active labor and pelvic floor disorders.

The study was also the first to demonstrate an association between operative vaginal birth and prolapse, even in asymptomatic women. By continuing to monitor these women, Dr. Handa hopes to be able to document the natural history of prolapse over time, especially in those women who were unaware of their condition.

Dr. Handa did not report any relevant financial disclosures.

PROVIDENCE, R.I. – Compared with cesarean birth without labor, undergoing vaginal birth increased the risk of stress incontinence and prolapse in women who were examined 5-10 years after childbirth, Dr. Victoria L. Handa reported at the annual meeting of the American Urogynecologic Society.

The risk of all pelvic disorders, including prolapse, was elevated even further in women who had undergone operative vaginal delivery, she said.

"The results suggest no measurable differences in the relative odds of any pelvic floor disorder for women delivering by cesarean section, including those who labored into the second stage. For vaginal birth, the picture is very different," said Dr. Handa, director of the advanced training program in female pelvic medicine and reconstructive surgery at Johns Hopkins University, Baltimore.

In this longitudinal cohort study based on hospital obstetric records, 8,285 women who had their first child 5-10 years previously were recruited for the study and 1,011 were enrolled. Women were selected if their obstetric history met one of five categories: cesarean without labor (considered the reference group; n = 192), cesarean during active labor (n = 228), cesarean after complete cervical dilation (n = 140), spontaneous vaginal birth (n = 325), and operative vaginal birth (n = 126). Groups were matched for age at first delivery and interval from first delivery, and were similar with respect to parity and smoking status. At enrollment, a validated questionnaire (Epidemiology of Prolapse and Incontinence Questionnaire) was used to assess pelvic floor symptoms, and the women were examined for pelvic organ support using the Pelvic Organ Prolapse Quantification (POP-Q) System.

"One of the strengths of our study is that [obstetric] exposures were verified by chart review with validated outcomes, and there was [anatomical] evidence of prolapse," Dr. Handa said.

Overall, 11% of the 1,011 women had stress urinary incontinence, 8% had overactive bladder, and 11% had anal incontinence; 3% reported prolapse symptoms, and 7% had prolapse upon examination (Obstet. Gynecol. 2011;118:777-84).

When the group was analyzed according to obstetric history, the impact of vaginal birth emerged. Compared with women who had a cesarean birth before active labor, women who had a vaginal birth (but no operative vaginal births) had almost a threefold increased risk of stress incontinence and symptomatic prolapse. The odds ratio for prolapse to or beyond the hymen was increased more than fivefold.

Women who had undergone operative vaginal birth fared even worse. The adjusted odds of stress incontinence and overactive bladder were more than quadrupled and the odds of anal incontinence were doubled. There was almost an eightfold increased risk of prolapse to or beyond the hymen upon examination.

In her report, Dr. Handa noted that in addition to demonstrating the dramatic increase in pelvic floor disorders in women with a history of at least one operative vaginal birth, the results showed an increase in urinary incontinence after operative delivery – a finding that had not been definitively documented before. For those who had undergone cesarean delivery, the results showed no association between active labor and pelvic floor disorders.

The study was also the first to demonstrate an association between operative vaginal birth and prolapse, even in asymptomatic women. By continuing to monitor these women, Dr. Handa hopes to be able to document the natural history of prolapse over time, especially in those women who were unaware of their condition.

Dr. Handa did not report any relevant financial disclosures.

PROVIDENCE, R.I. – Compared with cesarean birth without labor, undergoing vaginal birth increased the risk of stress incontinence and prolapse in women who were examined 5-10 years after childbirth, Dr. Victoria L. Handa reported at the annual meeting of the American Urogynecologic Society.

The risk of all pelvic disorders, including prolapse, was elevated even further in women who had undergone operative vaginal delivery, she said.

"The results suggest no measurable differences in the relative odds of any pelvic floor disorder for women delivering by cesarean section, including those who labored into the second stage. For vaginal birth, the picture is very different," said Dr. Handa, director of the advanced training program in female pelvic medicine and reconstructive surgery at Johns Hopkins University, Baltimore.

In this longitudinal cohort study based on hospital obstetric records, 8,285 women who had their first child 5-10 years previously were recruited for the study and 1,011 were enrolled. Women were selected if their obstetric history met one of five categories: cesarean without labor (considered the reference group; n = 192), cesarean during active labor (n = 228), cesarean after complete cervical dilation (n = 140), spontaneous vaginal birth (n = 325), and operative vaginal birth (n = 126). Groups were matched for age at first delivery and interval from first delivery, and were similar with respect to parity and smoking status. At enrollment, a validated questionnaire (Epidemiology of Prolapse and Incontinence Questionnaire) was used to assess pelvic floor symptoms, and the women were examined for pelvic organ support using the Pelvic Organ Prolapse Quantification (POP-Q) System.

"One of the strengths of our study is that [obstetric] exposures were verified by chart review with validated outcomes, and there was [anatomical] evidence of prolapse," Dr. Handa said.

Overall, 11% of the 1,011 women had stress urinary incontinence, 8% had overactive bladder, and 11% had anal incontinence; 3% reported prolapse symptoms, and 7% had prolapse upon examination (Obstet. Gynecol. 2011;118:777-84).

When the group was analyzed according to obstetric history, the impact of vaginal birth emerged. Compared with women who had a cesarean birth before active labor, women who had a vaginal birth (but no operative vaginal births) had almost a threefold increased risk of stress incontinence and symptomatic prolapse. The odds ratio for prolapse to or beyond the hymen was increased more than fivefold.

Women who had undergone operative vaginal birth fared even worse. The adjusted odds of stress incontinence and overactive bladder were more than quadrupled and the odds of anal incontinence were doubled. There was almost an eightfold increased risk of prolapse to or beyond the hymen upon examination.

In her report, Dr. Handa noted that in addition to demonstrating the dramatic increase in pelvic floor disorders in women with a history of at least one operative vaginal birth, the results showed an increase in urinary incontinence after operative delivery – a finding that had not been definitively documented before. For those who had undergone cesarean delivery, the results showed no association between active labor and pelvic floor disorders.

The study was also the first to demonstrate an association between operative vaginal birth and prolapse, even in asymptomatic women. By continuing to monitor these women, Dr. Handa hopes to be able to document the natural history of prolapse over time, especially in those women who were unaware of their condition.

Dr. Handa did not report any relevant financial disclosures.