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Pelvic organ prolapse is a very prevalent condition, affecting up to half of all women over 50 years old. Biological grafts may be useful in certain patients but long-term trials are needed to guide their proper use.
Pelvic organ prolapse (POP) is a very prevalent condition, affecting up to half of all women over 50 years old.1 Results from the Women’s Health Initiative suggest that up to 33% of parous women have a clinically significant cystocele; 18% have rectoceles; and 14% have either uterine or post-hysterectomy vaginal vault prolapse.2 Although many patients with POP are asymptomatic and may not require treatment, a recent study by Wu et al. demonstrated that the lifetime risk of surgery for POP among women in the United States is 12.6%.3
Pelvic reconstructive surgeons frustrated with high recurrence rates with traditional (or so-called “native tissue”) repairs took the lead from general surgeons who reported improved success rates in inguinal hernia repairs by using synthetic mesh to augment their repairs.4 Starting in the early 2000’s, many reports in the literature suggested that synthetic mesh used for POP decreased failure rates.5-7 On the other hand, reports began to surface that the use of synthetic mesh was associated with complications, such as mesh exposure, pelvic pain, and dyspareunia. In 2008, the US Food and Drug Administration (FDA) came out with a Public Health Notification (PHN) stating that the use of synthetic mesh for prolapse was associated with these and other potential complications.8 The FDA made several recommendations to pelvic surgeons, including specialized training, improving the informed consent process, and providing labeling information to patients. In 2011, the FDA published a Safety Update, which essentially stated the same information contained in the PHN, but went further by stating the incidence of such complications was “not rare.”9
It is important to note that the FDA did not withdraw any of the commercially available mesh kits on the market. Rather, the FDA took action to demand that medical device companies that wanted to keep their prolapse products on the market perform post-market surveillance studies. Although the FDA also recognized that full-length midurethral slings (both retropubic and transobturator) were well-studied and did not require any additional studies, they did mandate that companies that were marketing single incision slings also needed to conduct post-market surveillance studies (“522 studies”) to evaluate the success and potential complications of such devices. The FDA also decided to include manufacturers of xenografts (animal-derived grafts) that were marketing their products for POP to conduct these studies. Interestingly, the FDA did not require manufactures of allografts (human cadaveric tissue) to run these studies.
One can clearly see why interest in use of biologic grafts has been increasing since the FDA notifications regarding transvaginal mesh. Surgeons performing surgery for POP may be reluctant to use synthetic mesh, but are still looking for ways to decrease failure rates when they have patients who are at risk of failure with native tissue repairs. Patients who may have an increased risk of recurrence include those with advance stages of prolapse, those who have failed previous native tissue repairs, and women with chronically increased intra abdominal pressure, such as those with obesity, chronic constipation, and occupations or hobbies that require heavy lifting.
It is easy to assume that if 1 biologic graft demonstrates success (or failure, for that matter) in treating prolapse, then this should apply to all biologic grafts. One cannot, however, make this assumption, since there are several important differences between these grafts. Grafts differ in their origin (autograft, allograft, xenograft), source (eg, dermis, fascia, pericardium, small intestinal submucosa), life stage (fetal, adult), proprietary processing (eg, washes, enzymes, chemicals, lyophilization), cross-linking (eg, gluteraldehyde) and sterilization (eg, ethylene oxide, gamma irradiation). Each of these variables may influence the behavior of the graft post-implantation, including degredation, long-term success rate, and complications.
The process of cross-linking biologic grafts changes the absorption profile of the graft, so that biologic grafts act more like synthetic materials that do not resorb or even remodel with host tissue. One of the cross-linked grafts that was previously available was PelvicolTM (Bard, Covington, Georgia) which was marketed for pelvic floor repair. The body’s response to PelvicolTM was to encapsulate the material, and there are reports of seroma formation and wound separations after vaginal repairs with PelvicolTM that required removal of the graft.10-12
A growing number of reconstructive surgeons advocate for biologic grafts in which the host tissue repopulates the graft with blood vessels, fibroblast infiltration, and subsequent collagen deposition, creating a new tissue layer that lasts after the graft resorbs.13 There are 3 potential outcomes of a biologic graft after surgical implantation: absorption, encapsulation, and remodeling. The first potential outcome is simple absorption of the material. This may occur if the host tissue does not recognize the graft as remodelable and simply forms scar tissue in response to insertion of the graft. This response is similar to what might happen if an absorbable synthetic mesh material, such as polyglycolic acid (eg, Vicryl) was implanted.
As mentioned earlier, another potential response to a biologic material, especially one that has been cross-linked with some chemical, such as gluteraldehyde, is encapsulation. The body will attempt to wall off the material by forming a fibrous capsule around the material.
The most desirable outcome, however, is remodeling, whereby the host tissue sees the graft as a material in which it may re-populate with blood vessels, blood cells, collagen, and growth factors. The anticipated result is that after the biologic graft reabsorbs, the patient is left with a stronger layer of “fascia” beneath the vaginal epithelium.
There are currently 5 clinically available biological grafts on the market for pelvic floor reconstructive surgery (see Table). The 2 commercially available xenografts are XenformTM (Boston Scientific Corporation, Marlborough, Massachusetts) and MatriStemTM (ACell, Columbia, Maryland). XenformTM is noncross-linked fetal porcine dermis. During the manufacturing process the matrix undergoes chemical viral inactivation as well as sterilization with ethylene oxide gas. ACell MatriStemTM is a 6-layer acellular and noncross-linked matrix derived from porcine urinary bladder.
The 3 available allografts are: RepliformTM (Boston Scientific Corporation), AxisTM (Coloplast, Minneapolis, Minnesota) and SuspendTM (Coloplast). RepliformTM is an acellular cadaveric, noncross-linked dermal matrix, which is sterilized to ensure clinical safety. AxisTM is a human cadaveric dermal graft (harvested from the back and dorsum of upper leg) and SuspendTM is human fascia lata. The AxisTM and SuspendTM grafts are both noncross-linked and sterilized using a proprietary process (Tutoplast) to prevent the transmission of pathogens. All biological grafts come in a variety of sizes and can be trimmed to the appropriate size for the patient.
The anterior vaginal wall is the most common site of POP and has the highest recurrence rate of up to 70%.14 Given this, several types of graft material have been used to support the anterior vaginal wall with varying ranges of success. A Cochrane review on the surgical management of prolapse by Maher et al. concluded that the anatomical failure rate was higher in those women who underwent a traditional anterior colporrhaphy (28%) compared with the cohort who had biological graft augmentation (18%).15 There are many reports in the literature of various biomaterials that have been used to augment prolapse surgery. The outcomes of these studies appear to be dependent not only on the types of graft material used, but also on the surgical approach and the points of graft attachment. Meshcia utilized cross-linked porcine dermis (PelvicolTM) at time of anterior colporrhaphy and found that the objective recurrence rate was significantly higher in the anterior colporrhaphy (20/103) group compared to the porcine dermis group (7/98) at 1 year.16 Guerette et al. randomized women to either a traditional anterior colporrhaphy or an anterior repair with bovine pericardium collagen matrix graft reinforcement.17 At 2 years, they found no difference in objective recurrence rates (Ba ≥ -1) and there were no infections or erosions reported in the graft cohort.17 Feldner and colleagues compared traditional anterior colporrhaphy with augmentation with porcine small intestine submucosa (SIS) graft (Fortagen, Organogenesis, Inc., Canton, Massachusetts) and demonstrated an 86.2% anatomic cure rate in the SIS group compared with a 59.3% success rate in the traditional anterior repair group (P = 0.03).18 There was no difference in quality of life measures or rate of dyspareunia between the two groups. Gandhi et al., in a prospective study comparing anterior colporrhaphy alone to anterior repair with cadaveric fascia lata (Tutoplast®, Bard) noted no difference in success rates between the two procedures (71% compared to 82%, P = 0.07 respectively).19
Data are limited evaluating the role of graft augmentation in the posterior compartment. Two trials investigated a traditional posterior colporrhaphy compared with SIS augmentation and surprisingly found that the objective recurrence rate was lower in the traditional colporrhaphy group compared to the SIS graft cohort.20,21 In a prospective cohort study by Altman and colleagues, posterior augmentation with porcine dermis (PelvicolTM) in 23 women resulted in a recurrence rate of 41% at 3 years postoperatively.22 Grimes et al. performed a retrospective review of all posterior repairs performed at a single institution.23 One hundred and twenty-four women underwent a traditional posterior colporrhaphy and 39 women underwent posterior repair with 1 of 3 different biological grafts: non-cross-linked cadaveric dermis (RepliformTM), cross-linked porcine dermis (PelvicolTM), and non-crosslinked porcine dermis (XenformTM).23 They found no improvement in anatomical or functional outcomes with the addition of a graft.23 In a case series, Kohli and Miklos reported a 7% failure rate at 1 year in 30 women who underwent a posterior colporrhaphy with cadaveric dermal graft.24
Sung and colleague in 2008 performed a systematic review of the literature available on this topic and concluded that the literature does not allow for ample assessment of the use of a biological graft for pelvic organ prolapse repair.25 There are limited randomized control trials comparing biological grafts to native tissue repair. Furthermore, the literature is restricted to grafts that are no longer on the market and the current biological grafts that are clinically available have not been studied in randomized control trials. However, a prospective, non-randomized, multicenter study evaluating XenformTM versus native tissue repair for treatment of women with anterior/apical prolapse has finished recruitment and results of this trial should be available in 2019. In addition, ACell is recruiting participants in a non-randomized 3-year clinical trial comparing the safety and effectiveness of MatriStemTM to native tissue repairs for POP. Larger prospective randomized trials need to be undertaken to evaluate if a colporrhaphy with a biological graft is superior to a traditional colporrhaphy for any compartment. Furthermore, quality of life measures need to be addressed to allow for more meaningful conclusions and expand upon the currently incomplete data available.
The other difficulty with comparing the efficacy and safety of biologic grafts for POP is the lack of consensus as to how the graft augmentation should be performed technically. Whereas some surgeons simply place an “on lay” graft over a native tissue repair, others will attach the graft to the endopelvic fascia, while others will attach the graft to specific supporting structures in the pelvis, such as the sacrospinous ligament (SSL) or arcus tendineus fascia pelvis.
The surgeon may elect to perform a native tissue repair before placement of the biologic graft. Although it is unclear whether this improves the ultimate success of the repair, for large cystoceles and rectoceles this step may facilitate graft placement by reducing the prolapse and keeping it out of harm’s way.
The SSL is a consistently substantial ligament that has been frequently used for direct attachment of the vaginal vault as well as for indirect attachment of the vagina to the ligament with the graft material bridging the gap. Many reconstructive pelvic surgeons use this ligament with biologic grafts as well for either uterine or vaginal vault prolapse. The SSL can be approached through either an anterior or posterior vaginal dissection, depending on which compartment has the more significant prolapse. With either approach, once the initial lateral sharp dissection is accomplished, blunt dissection along the levator ani fascia can usually be performed until the ischial spine is reached. Any overlying tissue should be dissected off the sacrospinous ligament and a suture is placed in the mid-portion of the sacrospinous ligament, at least 3 cm medial to the ischial spine to avoid injury to the pudendal nerve and vessels. The surgeon should also avoid placing sutures above the superior margin of the ligament, to protect the sciatic nerve, which lies over (ventral to) the soft piriformis muscle. We use an automatic suturing device (Capio™ Slim, Boston Scientific Corporation) that throws and captures the suture, although several other instruments can be used for this purpose. Whether the approach is anterior or posterior, a trapezoidal shape of graft is used to cover the defect. The proximal portion of the graft is sutured in the midline with delayed-absorbable or permanent suture to the cervix or vaginal vault. The base of the trapezoid is usually approximately 8 cm, so it can span the distance between the mid-portions of the SSL, and the length of the graft is customized to the patient, with an anterior graft extending to the bladder neck and a posterior graft usually brought down distally to the perineal body. The graft can be attached laterally to the pelvic sidewall at the level of the fascial white line. We use a pulley stitch when attaching the SSL suture to the proximal corner of the graft, which can be used to lift the graft into position, effectively reducing the prolapse. If the vaginal vault is foreshortened and does not reach the level of the SSL, the graft is tailored so that undue tension is not placed on the vaginal apex.
Once the graft has been placed, the vaginal epithelium can be closed with a running or interrupted delayed-absorbable suture. We prefer to trim redundant vaginal epithelium and close the dead space between the vaginal wall and the graft to avoid hematoma formation by including the graft in several of the vaginal wall repair stitches.
In addition to vaginal prolapse repair, biologic grafts have been used with variable results in other applications, including sacrocolpopexy. In 1 trial, women with vaginal vault prolapse were randomized to either synthetic mesh versus cadaveric fascia lata during robotic sacrocolpopexy. After 1 year, the objective success rate (defined as Stage 0-1 prolapse) was 91% in the synthetic mesh group, compared with only 68% in the fascia lata group.26 In another study, women were randomized to either synthetic mesh or a cross-linked porcine dermis (PelviSoft, Bard).27 There was no significant difference in success rate between these 2 grafts, which is not surprising given the fact that the cross-linking of the biologic graft makes the graft resistant to degredation. It is unclear what advantage there would be to using a biologic graft that does not degrade, since there is abundant literature to support the efficacy and safety of polypropylene mesh in sacrocolpopexy.
As shown by the conflicting findings in the scientific literature, it appears that not all biological grafts are created equal, nor can one extrapolate results from different anatomical compartments. Biological grafts may be useful as an alternative to synthetic mesh in patients with POP who are at risk for failure with native tissue repairs. More robust long-term trials need to be undertaken to help guide the proper use of specific biological grafts in pelvic reconstructive surgery.
1. Samuelsson EC, Arne Victor FT, Tibblin G, Svardsudd KF. Signs of genital prolapse in a Swedish population of women 20 to 59 years of age and possible related factors. Am J Obstet Gynecol. 1999;180:299–305.
2. Hendrix SL, Clark A, Nygaard I, Aragaki A, Barnebei V, McTiernan A. Pelvic organ prolapse in the Women’s Health Initiative: gravity and gravidity. Am J Obstet Gynecol. 2002; 186 (6):1160–6.
3. Wu J, Matthews C, Conover M, Pata V, Funk M. Lifetime risk of stress urinary incontinence or pelvic organ prolapse surgery. Am J Obstet Gynecol. 2014;123(6):1201-06.
4. Luijendij R., A Comparison of Suture Repair with Mesh Repair for Incisional Hernia. N Engl J Med. 2000;343:392-8.
5. Sand PK, Koduri S, Lobel RW, et al Prospective randomized trial of polyglactin 910 mesh to prevent recurrence of cystoceles and rectoceles. Am J Obstet Gynecol.2001;184:1357-62.
6. Julian TM. The efficacy of Marlex mesh in the repair of severe, recurrent vaginal prolapse of the anterior midvaginal wall. Am J Obstet Gynecol. 1996;175:1472-5.
7. Lim YN, Rane A, Muller R. An ambispective observational study in the safety and efficacy of posterior colporrhaphy with composite Vicryl Prolene mesh. Int Urogynecol J Pelvic Floor Dysfunc. 2005, 16:126-31.
8. http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/ucm061976.htm. Accessed on November 12, 2014.
9. FDA Safety Communication: UPDATE on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm262435.htm. Accessed on August 08, 2011.
10. Mukati MS, Shobeiri SA. Erosion of Pelvicol used in sacrocolpopexy. Female Pelvic Med Reconstr Surg. 2013; Sep-Oct;19(5):301-2.
11. Gomelsky A, Haverkorn RM, Simoneaux WJ, Bilello S, Kubricht WS. Incidence and management of vaginal extrusion of acellular porcine dermis after incontinence and prolapse surgery. Int Urogynecol J. 2007:18:1337-41.
12. Rudnicki M. Biomesh (Pelvicol) erosion following repair of anterior vaginal wall prolapse. Int Urogynecol J Pelvic Floor Dysfunct. 2007;18(6):693-5.
13. Cornwell KG, Landsman A, James KS. Extracellular Matrix Biomaterials for Soft Tissue Repair. Clin Podiatr Med Surg. 2009; 26:507-523.
14. Weber AM, Walters M, Piedmonte MR, Ballard LA. Anterior colporrhaphy: a randomized trial of three surgical techniques. Am J Obstet Gynecol. 2001;185:1299-1306.
15. Maher C, Feiner B, Baessler K, Schmid C. Surgical management of pelvic organ prolapse. Cochrane Database of Systemic Review. 2013. Issue 4.
16. Meschia M, Pifarotti P, Nernasconi F, Magatti F, Riva D, Kocjancic E. Porcine skin collagen implants to prevent anterior vaginal wall prolapse recurrence: a multicenter, randomized study. J Urol. 2007;177:192-195.
17. Guerette N, Peterson TV, Aguirre OA, VanDrie DM, Biller DH, Davila GW. Anterior repair with or without collagen matrix reinforcement. Obstet Gynecol. 2009;114:59-65.
18. Feldner P, Castro R, Cipolotti L, Delroy C, Sartori F, Girao M. Anterior vaginal wall prolapse: a randomized controlled trial of SIS graft versus traditional colporrhaphy. Int Urogynecol J. 2010;21:1057-1063.
19. Gandhi S, Goldberg R, Kwon C, et al. A prospective randomized trial using solvent dehydrated fascia lata for the prevention of recurrent anterior vaginal wall prolapse. Am J Obstet Gynecol. 2005;192:1649-54.
20. Paraiso M, Barber M, Muir T, Walters M. Rectocele Repair: a randomized trial of three surgical techniques including graft augmentation. Am J Obstet Gynecol. 2006;195:1762-71.
21. Sung V, Rardin CR, Raker CA, Lasala CA, Myers DL. Porcine subintestinal submucosal graft augmentation for rectocele repair: a randomized controlled trial. Obstet Gynecol. 2012;119(1):125-33.
22. Altman D, Zetterstrom J, Mellgren A, Gustafsson C, Anzen B, Lopez A. A three year prospective assessment of rectocele repair using porcine xenograft. Obstet Gynecol. 2006;107:59-65.
23. Grimes C, Tan-Kim J, Whitcomb E, Lukacz E, Menefee S. Long-term outcomes after native tissue vs. biological graft-augmented repair in the posterior compartment. Int Urogynecol J. 2012;23:597-604.
24. Kohli N, Miklos J. Dermal graft-augmented rectocele repair. Int Urogynecol J. 2003;14:146-149.
25. Sung V, Rogers R, Schaffer J, et al. Graft use in transvaginal pelvic organ prolapse repair. Obstet Gynecol. 2008:112(5):1131-42.
26. Culligan P, Blackwall L, Goldsmith L, Graham C, Roger A, Heit M. A randomized controlled trial comparing fascia lata and synthetic mesh for sacral colpopexy. Obstet Gynecol. 2005;106:29-37.
27. Culligan PJ, Salamon C, Priestley JL, Shariati A. Porcine dermis compared with polypropylene mesh for laparoscopic sacrocolpopexy: a randomized controlled trial. Obstet Gynecol. 2013;121(1):143-51.