Discussion of the Use of Biological Mesh for Pelvic Organ Prolapse Repair

An article in Current Urology Reports Journal published in June of 2012 detailed the use of biological grafts in the repair of pelvic organ prolapse. Specific information is presented in this article regarding the complications associated with the different prolapse compartments (posterior, middle and anterior). When the pelvic floor weakens—generally due to childbirth, surgery, menopause or aging—organs can drop from their normal position causing significant discomfort, pain and a variety of other symptoms. There may also be a genetic predisposition which contributes to the development of pelvic organ prolapse. The authors state that by the age of 80, at least 11% of all women will require POP surgery.

Unfortunately, there is also a 30% chance of recurrence which will require subsequent surgical procedures. There are other patient characteristics which can increase the risk of pelvic organ prolapse as well as surgical failure including obesity, the number of children, a history of smoking, constipation or a chronic cough and the overall state of the immune system. To improve the overall results of POP surgery both biologic and synthetic meshes are used, however synthetic meshes—while improving anatomic results—can bring complications such as mesh extrusion or erosion. Biological grafts can offer similarity to recipient tissue, decreasing the recurrence rate. 

Biologic grafts are either harvested from the patient’s own body from the vaginal lining, the rectum or the thighs, and while there is no risk of rejection or transmission of disease, operating times are extended and there can be complications at the site of the graft. Allografts are grafts which are extracted from cadaver tissue, and while an overall good choice there is some risk of disease transmission. Xenografts come primarily from cows and pigs. With both allografts and xenografts, disease screening is performed and the techniques for harvesting are fairly standard. The processing techniques can vary, however, with no clear consensus regarding the best method.

Anterior compartment prolapse tends to be the most common form of pelvic organ prolapse. Anterior prolapse occurs when the bladder and/or urethra are protruding; the use of biological tissue in the repair of this type of prolapse has shown inconclusive results. Middle compartment prolapse can involve the uterus, bowel, rectum, bladder or vaginal vault. Comparing biologic grafts to synthetic grafts in the transvaginal and abdominal repair of middle compartment prolapse has shown biologic grafts to be inferior to synthetic. Posterior compartment prolapse involves the herniation of the anterior rectal into the vagina leading to sexual dysfunction and chronic constipation. While traditional repair of posterior prolapse has shown high rates of success, painful sexual intercourse can be a typical side effect.

Regarding biological grafts in pelvic organ prolapse repairs, the most common complications included graft erosions which were less serious than the synthetic mesh erosions. The FDA issued an updated warning in 2011 regarding the use of transvaginal surgical mesh stating there was insufficient evidence to show any benefits of mesh over more traditional methods and that mesh complications were “not rare.” Better patient monitoring following surgery is recommended by the FDA as well as alterations in the pre-market application approval process.

Synthetic Mesh Materials used for Pelvic Organ Prolapse Repair

This article will summarize findings by a review article published in the June, 2012 issue of Current Urology Reports Journal which assesses outcomes and complications when synthetic mesh is used in the surgical treatment of pelvic organ prolapse as well as FDA findings on the subject. Pelvic organ prolapse occurs when the muscles and tissues which hold such organs as the bladder, uretha, uterus and vagina in place break down, allowing the organs to move downward. The location of the defect determines its classification, including anterior (cystocele), posterior (rectocele) and apical (enterocele).

Traditional pelvic organ prolapse repair known as a colporrhaphy, either folds the native tissue or anchors them to surrounding structures. 17% of the repairs which use these techniques will require further surgical procedures. Grafts are used to strengthen weak tissues, decreasing the likelihood of recurrence. Graft use also allows surgeons to repair multiple sites in the same operation. Biologic grafts can consist of autografts (tissue from the same individual) allografts (tissue from another human) or xenografts (non-human organism tissue). Limitations to biologic grafts include cost, limited availability and the risk of disease transmission. Because of these limitations, synthetic mesh used in the repair of POP was approved by the FDA in 2001.

Synthetic grafts are classified according to filament number and pore size with variations in weight and flexibility. Type 1 mesh is macroporous, monofilament polypropylene, marketed under such brand names as Marlex™, Atrium™, Prolene™, Gynemesh™ and Pelvitex™. Type 1 mesh appears to have the highest rate of success due to its larger pore size which leads to better tissue grown and lower rates of infection. Despite this success rate, these vaginal mesh kits can provoke the body’s defense cell responses, causing the formation of granulomas.

The specific surgical technique used also has bearing on the rate of success in POP repair. Whether anterior, posterior or apical, the traditional colporrhaphy procedure may be implemented or the augmented procedure can be used. Regarding anterior repairs, mesh augmentation decreased recurrence rates however showed higher rates of complications. Apical compartment repairs also showed better results when mesh augmentation was used however no significant differences were noted between colporrhaphy and mesh augmented procedures when repairing the posterior compartment.

Complications associated with synthetic mesh kits are classified by the affected area, subdivided by time of occurrence such as an immediate physician-caused injury, short-term erosion and bleeding or long-term mesh extrusion, pain or painful sexual intercourse. According to the data in this particular article, incidence of erosion and extrusion range from 5-19%. Stress incontinence as a side effect of surgery occurred less often in colporrhaphy procedures than those which used surgical mesh. Painful sexual intercourse occurred equally in both groups, with the exception of a higher rate in posterior compartment colporrhaphy repairs. One study presented in the article noted that polypropylene meshes can retract up to 66% following surgery, leading to vaginal shortening and narrowing.

The French Health Authorities stated in 2006 that more research is required regarding the use of synthetic mesh in POP repair. The FDA followed in 2008 by issuing a public health notification regarding the use of synthetic mesh in POP repair. Suggestions offered included specialized physician training as well as using mesh only after weighing other alternatives. Physicians were advised to inform patients of potential complications as well as to ensure they understand that the mesh is considered permanent. An update to the 2008 notification was issued by the FDA in 2011 which stated that complications from the use of mesh in POP repair were “not rare” and that it was unclear whether the use of mesh showed any benefit over traditional repairs. Literature in this article, however, concluded that the FDA’s view was biased and that further research was necessary to compare colporrhaphy to repair using synthetic mesh kits.

The Use of Synthetic Mesh in Central and Apical Compartment Repair

A review article published in the Current Urology Reports Journal in June, 2012, describes the various methods used in the repair of central and apical compartment pelvic organ prolapse using synthetic mesh. This article details the FDA’s recommendations and concerns regarding the use of synthetic mesh in these particular procedures. Pelvic organ prolapse is a relatively common condition which affects women, particularly those who have gone through childbirth, menopause or surgery. When the muscles and tissue of the pelvic floor weaken the organs begin to drop down, causing discomfort and pain. Age increases the risk of developing pelvic organ prolapse, and because the muscle and tissue are already weakened, there is a high recurrence rate of POP after surgery.

This high recurrence rate when using traditional surgical procedures led to the use of synthetic meshes which have been used successfully in the repair of abdominal wall hernias for decades. Synthetic meshes are classified according to type, pore size and filament type and are believed to be less invasive with a more standardized approach to placement. The typical placement techniques include surgeon-fashioned patches and tension-free vaginal kits which can be trocar, anchor or suture-based. The first kits designed specifically for the treatment of apical compartment repair in POP cases used trocars—sharp-edged instruments inside a cylinder—which passed through the membrane which closes the “hole” in the pelvis. Such kits are marketed under such brand names as Gynecare, Anterior Prolift, Perigree and Avaulta.

Single-incision kits using needle drivers or self-fixating tips include brand names such as Pinnacle, Uphold and Elevate. Finally, the Procima kit is a single-incision, non-fixation system which is held in place for three weeks by a vaginal support device which is sewn into place during the surgical procedure. Mesh patches are typically used in single or multi-compartment repairs with the approach depending on the individual case and the surgeon.

Apical vaginal compartment repair is usually accomplished through abdominal sacrocolpopexy (ASC) although highly skilled surgeons have developed their own technique to address defects in the anterior and posterior compartments during ASC. ASC, typically performed on younger, sexually active patients, may be performed in three ways: open, laparoscopic or robotic surgery. Aside from the variation in approach, the ASC surgical procedure has remained largely unchanged. A permanent mesh graft is secured to the sacral promontory and vaginal cuff. Enteroceles are reduced using culdoplasty which reduces the chance of recurrence. The laparoscopic procedure is suitable for elderly patients as it results in decreased loss of blood and a shorter hospital stay.

ASC can lead to both intraoperative and postoperative complications; a study of 1,500 patients concluded that subsequent operations following mesh procedures occur more frequently following transvaginal mesh placement into the anterior compartment.  Smoking, sexual activity, mesh placement and age contribute to the risks associated with mesh surgery. A report released in 2008 by the FDA discussed potential complications associated with pelvic organ prolapse surgery using transvaginal mesh. This report was updated in 2011 at which time the FDA stated it was unclear whether there were any advantages in using mesh over more traditional methods and that complications from transvaginal mesh were not as rare as previously reported.

Further clinical studies were proposed, and mesh kits which had previously been classified as Class II were moved up to a Class III which required that manufacturers submit study design demonstrating mesh procedures were not inferior to native tissue repairs. Mesh used in ASC was specifically excluded as their safety and efficacy have been well-established. Supporters of the use of surgical mesh believe it is difficult to make comparisons as data comparing mesh and non-mesh procedures are not entered into a device database. Further, they attribute mesh complications to technical deficiencies and the lack of skilled surgeons, leading the authors to emphasize the fact that training for mesh placement should be increased.

Synthetic or Native Tissue--Which is Better in the Repair of Posterior Vaginal Wall Prolapse Repair?

Women who have undergone menopause, childbirth or surgery are at particular risk for developing pelvic organ prolapse. As women age, their risk increases with approximately 11% of women requiring pelvic organ prolapse surgery by the age of 80. A history of smoking, being overweight or a compromised immune system can all increase the risk of pelvic organ prolapse as well as the risk of recurrence following surgery. A Current Urology Reports Journal article published in June, 2012 assesses the risks and benefits of using synthetic mesh when repairing posterior vaginal wall prolapse.

As many as 30% of women who undergo this surgery will experience a recurrence of POP. In an effort to lower this number, the procedures for using grafts to expand native tissue have been updated and in the past ten years the use of synthetic mesh has become more common. Surgical mesh kits designed specifically to repair anterior, posterior and vaginal vault pelvic organ prolapse have been FDA approved, although there is not enough post-market manufacturer’s data to thoroughly evaluate results. The data reviewed in the article listed above comes from publicly available research.

The posterior compartment is traditionally repaired using a sort of “folding” and suturing of the connective tissues to restore normal anatomy which is compromised when those tissues lose their elasticity and the organs drop from their normal positions. This “traditional” type of surgery typically has few complications and recurrence rates are low. Anatomic surgery is generally reserved for women with stage 0-1 of prolapse severity although approximately 35% have stage II. When failure is defined as prolapse beyond the hymen, presence of symptoms or recurrence, posterior pelvic organ prolapse repair cure rates are at least 90%, with recurrence following traditional methods at 3%. When synthetic mesh is used, complication rates are almost 17% and recurrence rates range from 4.1-16.9%.

Patients presenting symptoms of pelvic organ prolapse may need multiple-compartment repair requiring either a total vaginal mesh or combination of anterior-posterior mesh. Most complications noted occurred following anterior compartment or total vaginal repair using synthetic mesh. The complications occurred during the surgery, from the operating room to recovery unit or post-op. Complications ranged from puncture to bleeding and infection during or immediately following surgery. Delayed complications included mesh extrusion, retraction, chronic pain and sexual dysfunction.

In 2008 the FDA issued a safety communication which they later updated in 2011 regarding complication related to transvaginal mesh. Additional information was collected using the FDA database known as MAUDE or Manufacturer and User Facility Device Experience. Voluntary reports of adverse events involving medical devices such as surgical mesh are entered into this database although the data is not sufficient to compare rates across devices. The updated communication in 2011 was based on an analysis of 3,000 complication reports submitted between 2008 and 2011 and concluded that complications from transvaginal mesh were “not rare.” Further, the FDA stated there was little evidence to support the use of synthetic mesh over more traditional methods in the repair of pelvic organ prolapse. Since that 2011 FDA communication, lawsuits against manufacturers of synthetic mesh are on the rise with close to 700 cases being filed.

The authors of the Current Urology Reports Journal article state that the post-market studies requested by the FDA will result in a higher level of safety and efficacy data being made available which will in turn allow a thorough assessment of the use of synthetic mesh in posterior POP repair. Based on current data, however, traditional methods involving native tissue appear to have similar outcomes to synthetic mesh used in the repair of posterior pelvic organ prolapse however synthetic mesh has a higher risk of complications. The standard treatment for posterior compartment POP will remain traditional, using native tissue for a positive outcome and few complications.

Update on Synthetic Mesh Used in the Repair of Anterior Pelvic Organ Prolapse

It is believed pelvic organ prolapse affects millions of women, however many women do not seek medical intervention due to the nature of the problem. Pelvic organ prolapse occurs when an organ within the pelvic region drops from its normal spot, pushing against the vaginal walls. Approximately 200,000 women will undergo a surgical procedure for pelvic organ prolapse annually. Of the women who undergo the procedure, at least 30 percent will require an additional prolapse repair procedure. Most women with pelvic organ prolapse experience discomfort and pain on a daily basis. Many will also be unable to exercise or engage in sexual relations.

Pelvic organ prolapse primarily occurs when the muscles holding the pelvic organs in place are weakened from childbirth or surgery. Women going through menopause and elderly women are also more likely to suffer from pelvic organ prolapse. When the pelvic muscles and connective tissues—which are largely comprised of collagen and elastin— are subject to repeated or severe strain, they will no longer hold the pelvic organs in place. Candidates for surgical repair of pelvic organ prolapse are generally women for whom conservative management has not offered significant relief. The type of surgical procedure will depend on the site of the prolapse, whether urinary incontinence is present, the overall health of the patient and the specific patient preferences.

An article published last June in the Current Urology Reports Journal reviews the use of synthetic mesh in the treatment of pelvic organ prolapse. Significant data supports mesh use for POP surgeries although the authors of the Journal article also note the risks involved in the use of transvaginalmesh. Fibroblasts—cells which are involved in the synthesis of the connective tissues—are responsible for a decrease in elastin and an increase in the enzyme which breaks down elastin. It is likely that the increased levels of this enzyme, elastase, probably plays a role in the high failure rates of pelvic organ prolapse surgeries which is estimated to be as high as 29%.

While native tissue was widely used prior to the introduction of synthetic mesh—and continues to be used in many cases—the use of native tissue can further break down connective tissues. Biological grafts also have the tendency to break down when placed in an environment known to break down those proteins. Because of this, the use of mesh seems to have a definite advantage over native tissue or biological grafts as they are—in theory at least—resistant to these protein breakdowns.

The authors consider the ideal graft, whether biological or synthetic, to be “sterile, inert, non-carcinogenic, durable, non-inflammatory, inexpensive, readily available and easy to use.” Mesh implants with larger pore sizes are believed to encourage tissue growth and prevent infections when compared with smaller pore mesh. The most common type of mesh used is made from polypropylene and classified as Type 1, macroporous. Type II mesh, Gore-Tex, is microporous which allows limited tissue growth. In turn, that limited tissue growth may lead to higher erosion and infection rates.

The FDA issued a warning regarding synthetic mesh in 2011; the authors of this study present data from four trials as well as summaries from an additional three trials which compare the repair of the anterior vaginal wall through colporrhaphy vs. the use of mesh. Colporrhaphy is a surgical procedure in which narrowing of the vagina is accomplished through the use of sutures. While the mesh procedures resulted in lower rates of anatomic failures, from 3.2-19% of those patients required treatment for vaginal extrusion. Mesh extrusion can result in painful intercourse, vaginal discharge, odor, pelvic pain and bleeding.

Although most extrusions can be treated in a doctor’s office, others require surgical intervention. The article concludes that while there is insufficient data to support the FDAwarning regarding pelvic pain and mesh contraction, the following improvements suggested by the FDA should be implemented: improved regulations, the careful selection of mesh patients, improvement in patient education, open discussions with patients regarding the risks and benefits of mesh treatment, deeper incisions to allow adequate vaginal tissue coverage and the appropriate training of physicians.

$3.35 Million Dollar Award Considered a Victory for all Upcoming Mesh Cases

Linda Gross, a 47-year old hospice nurse from South Dakota was awarded $3.35 million dollars as a result of her lawsuit against Ethicon and Johnson & Johnson—the manufacturers of the Prolift vaginal mesh implant. This is the first trial of over 4,000—nearly half of which will take place in the same New Jersey court. In addition to the compensatory award, a second phase of the trial will allow jurors to consider punitive damages. Under New Jersey law, punitive damages of up to five times the compensatory damages are permitted. This first trial, Gross v. Ethicon, took over six weeks with five days of jury deliberation following closing arguments by both sides. Claims of defective design were rejected by the jury however the jury did find sufficient evidence of failure to warn physicians and patients of the potential harm as well as fraudulent representation.

Serious Harm Suffered as a Result of Ethicon’s Prolift Mesh Device

Of the $3.5 million award, $185,000 was awarded to Gross’s husband for loss of consortium with $680,000 as compensation for past and future wages due to Gross’s inability to work following the mesh implantation. The remainder of the jury award addressed household-help expenses, medical expenses, disability, impairment and pain and mental anguish. Following her implantation of the Prolift in 2005 as a treatment for pelvic organ prolapse, Gross claimed she suffered debilitating injuries.

Gross underwent 18 surgical procedures to correct complications from the Prolift, had over 400 doctor visits and currently takes over 20 daily medications to address the chronic pain she suffers. The mesh device hardened in Gross’s body leading her to characterize her life as a “living hell” when she testified. Gross stated she had suffered scar tissue formation, mesh erosion, chronic inflammation and neurologic compromise which had rendered her unable to engage in sex with her husband, unable to sit for even twenty minutes without experiencing excruciating pain, and unable to return to work.

How Ethicon Circumvented the FDA

The Prolift surgical mesh somehow evaded FDA approval prior to its being marketed in March, 2005. That evasion exposed thousands of women to serious complications after being implanted with Prolift. Ethicon withdrew the Prolift from the market in 2012, claiming the mesh implants lacked commercial practicality—with no mention of safety concerns. As opposed to the prior generation mesh, the Gynemesh PS, the Prolift comes pre-cut in a kit, however was comprised of a larger volume of mesh which had the potential to lead to greater inflammatory reactions. Further, the “arms” of the Prolift were put in locations which would be both difficult and dangerous to access should complications arise.

Because there was technically no “substantially similar” product on the market at the time the Prolift became available, the FDA’s 510(k) process was not deemed the appropriate process. Medical devices which are significantly different than their predecessors require classification by the FDA as well as time-consuming and expensive pre-market application. These rules are meant to assure the safety and performance of a medical device, evaluating all potential risks to patients. A representative of Ethicon claimed the changes made to the Prolift were not significant enough to warrant 510(k) approval.

FDA Approval—Three Years after Prolift Marketing Began

When the FDA realized the approval omission—nearly three years after the device had been marketed and implanted in thousands of women—they granted approval to Ethicon. The instructions for use, patient brochure and website for the Prolift all failed to warn of potential complications of the mesh product. Further, nothing warned that surgeons implanting the device could need special training.

A Victory for Other Plaintiffs

Lawyers and their clients who have currently filed suit against Ethicon and Johnson & Johnson believe this verdict to be a victory for their own upcoming cases. Thousands of women suffered serious complications and harm from the Prolift because of Ethicon’s rush to get Prolift to market and increase company revenues.