Although the US FDA recently banned the sale of kits used to correct a common pelvic floor problem in women called uterovaginal prolapse, a recent novel study called “SUPeR” sponsored by the Pelvic Floor Disorder Network, in partnership with RTI International, and led by a number of prominent clinical investigational sites, reveals that results from the procedure are, on the whole, positive. The study indicates that mesh hysteropexy, the banned procedure, could provide an alternative for women suffering from uterovaginal prolapse—a condition where the pelvic floor muscles and ligaments stretch and weaken and can no longer hold up the uterus and vagina. 13% of U.S. women have some form of pelvic organ prolapse surgery by age 80.
What is uterovaginal prolapse?
According to the Mayo Clinic, uterovaginal prolapse occurs when pelvic floor muscles and ligaments stretch and weaken and no longer offer enough support for the uterus. Consequently, the uterus slips down into or protrudes out of the vagina. This condition may occur at any age but often affects postmenopausal women who’ve had one or more vaginal deliveries. Typically, mild conditions don’t require treatment. However, if uterine prolapse starts creating major discomfort, then treatment becomes an option. In severe cases, the uterus is removed in a hysterectomy.
According to Eunice Kennedy Shriver National Institute of Child Health and Human Development (an institute within the NIH), a pelvic floor disorder (PFD) occurs when the muscles or connective tissues of the pelvic area weaken or are injured.
What is the Situation?
Traditionally, surgeons treat vaginal prolapse by removing the uterus, thereby providing access to deep pelvic ligaments, such as the uterosacral ligaments. The top of the vagina can then be attached to those ligaments in a procedure known as uterosacral ligament suspension. Other procedures, such as mesh hysteropexy, do not require removal of the uterus and instead use mesh to suspend the uterus and pelvic organs so they no longer fall out of place. However, the U.S. Food and Drug Administration (FDA) banned the sale of mesh kits for vaginal prolapse repair back on April 16, 2019 for safety concerns, after the current study was completed. The FDA noted in April 2019 that manufacturers (Boston Scientific and Coloplast) had “not demonstrated reasonable assurance of safety and effectiveness for these devices, which is the premarket standard that now applies to them since the agency reclassified them into class III (high risk) in 2016.”
The Clinical Trial: SUPeR
Known as “Study of Uterine Prolapse Procedures—Randomized Trial” or “SUPeR” the primary purpose of this randomized clinical trial was to compare the effectiveness and safety of two transvaginal apical suspension strategies for uterovaginal prolapse: a mesh augmented hysteropexy versus vaginal hysterectomy and uterosacral suspension (USLS). 183 postmenopausal women participated at nine clinical investigational sites across the United States. 93 women were randomized to mesh hysteropexy and 90 were randomized to hysterectomy with uterosacral ligament suspension.
The primary aim of the sponsors (NICHD’s Pelvic Floor Disorders Network) was to determine whether treatment success in women who undergo the different procedures differ at time points through 3 years. Additionally, a supplemental study investigates anterior vaginal wall movement resulting from descent or rotation of the vaginal apex and/or anterior vaginal elongation, in women in both of the study arms of SUPeR. The study was funded by the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and Office of Research on Women’s Health and included a commercial interest (Boston Scientific Corp). The study results were published in the Journal of the American Medical Association.
To date, this study offers the longest-term comparison of the procedures and researchers will continue to follow the patients for a total of five years.
As reported in the NICHD press release summarizing the findings, research team compiled a failure rate of each procedure using a standard examination called the Pelvic Organ Prolapse Quantification System and whether women reported new symptoms of prolapse or needed retreatment for prolapse (i.e., another surgery or use of a supportive device called a pessary). The team found that after three years, mesh hysteropexy had a 26% failure rate, while hysterectomy had a 38% failure rate. The difference in the two rates was not statistically significant, according to the authors.
No differences were found in patient-reported outcomes on surgical pain, pelvic pain, and body image. Similar proportions in each group reported “much better” or “very much better” improvements in their symptoms (90% of respondents for mesh hysteropexy, 89% for hysterectomy) when queried at three years. Both groups also reported improvements in sexual function and lower incidence of painful sex (dyspareunia).
The study team also found no significant differences in adverse events, such as urinary tract infections and incontinence, between the two groups. The mesh hysteropexy group had an 8% mesh exposure rate, meaning the mesh became visible through the vaginal wall. For some women, this causes no symptoms, but for others, it may cause pain, bleeding or other problems. None of the women in this study required surgery for their mesh-related complications. The study team also did not observe any significant problems with uterine tissue in the mesh group during the three years of follow-up. Surgery for mesh hysteropexy was shorter than hysterectomy by about 45 minutes (average of 111.5 minutes compared to 156.7 minutes).
Clinical Investigator Comments: No Absolute Conclusions
Charles W. Nager, lead author and chair of the Department of Obstetrics, Gynecology and Reproductive Sciences at UC San Diego Health, commented: “More long-term research is needed to determine if one procedure is better than the other.” Dr. Nager emphasized, “After the five-year follow-up period, we’ll reanalyze the results.”
Donna Mazloomdoost, MD and study author and program director with the study sponsor’s NICHD Pelvic Floor Disorders Network noted “These findings provide important information for women who have had these procedures and for the physicians entrusted with their care.”
Study Sponsor: Pelvic Floor Disorders Network (PFDN)
The sponsor is the NICHD’s Pelvic Floor Disorder Network, which was created by ICHD in 2001 to encourage collaborative research on pelvic floor disorders (PFDs) and improve patient care. It was founded based on the statistic that as many as one in five women will have surgery for a PFD at some time in her life.
PFDN includes eight clinical centers and a data coordinating center (DCC) located at U.S. universities and medical centers. Leadership at each clinical center is provided by a Principal Investigator (PI), who is a practicing physician with substantial experience in treating PFDs. A research coordinator oversees the progress of PFDN’s clinical trials under the supervision of the PI and a multidisciplinary team. PFDN is funded through a Cooperative Clinical Research award mechanism (U10 and U01). A steering committee guides the development and conduct of research protocols and the preparation of PFDN publications. The steering committee is composed of the PIs from each clinical center, the DCC, a steering committee chair, and NICHD staff. A full listing of sites and investigators is available here. Investigative sites include: Duke, UCSD, Kaiser Permanente (Downey), UT Southwestern, University of Pittsburgh (Magee), University of Pennsylvania and Women & Infants Hospital (Brown University).
Charles W. Nager, lead author and chair of the Department of Obstetrics, Gynecology and Reproductive Sciences at UC San Diego Health
Donna Mazloomdoost, MD and study author and program director with the study sponsor’s NICHD Pelvic Floor Disorders Network
Call to Action: Do you or a loved one have a Pelvic Floor Disorder? Familiarize yourself with the issues—why the FDA banned the procedure (and associated meshes) and why the study appears to be coming up with an alternative conclusion. See one of the clinical investigators in your area—the list is included in the Pelvic Floor Disorder Network link. If you want to track this moving forward, sign up for the TrialSite Newsletter.