Successful anterior vaginal wall repair continues to be challenging. Traditional anterior colporrhaphy has reported failure rates of up to 70%.1 As a consequence, numerous prosthetic materials have been used to reinforce anterior vaginal repairs.2,3 The reported success rates of permanent synthetic reinforcement are high at 75–100%. However, high rates of mesh erosion (1.4–13%) and postoperative dyspareunia are reported (Hardiman P, Oyawoye S, Browning J. Cystocele repair using polypropylene mesh [abstract]. Br J Obstet Gynaecol 2000;107:825. Salvatore S, Soligo M, Meschia M, Luppino G, Piffarotti P, Arcari V. Prosthetic surgery for genital prolapse: functional outcome [abstract]. Neurourol Urodynam 2002;21:296–7).2,4–10 Reinforcement with delayed absorbable synthetic materials such as polyglactin 910 have low rates of complications but have demonstrated variable benefit over plication alone.1,11
The use of biologic materials has potential advantages compared with synthetic mesh, but there is a paucity of data from randomized controlled trials. Gandhi et al,12 in a prospective analysis, noted no improvement in outcomes with cadaveric fascia lata. Recently, good results using porcine implants for preventing recurrent anterior vaginal wall prolapse have been reported.13,14
The bovine pericardium collagen matrix implant (Veritas, Synovis Life Technologies, St. Paul, MN) is a non–cross-linked biologic graft and is approved by the Food and Drug Administration for use as a prosthesis for urinary incontinence and reconstruction of the female pelvic floor. It is intended to be gradually infiltrated by the host's endogenous collagen and undergo neovascularization such that the graft becomes fully incorporated into the host tissue.15 The objective of this study was to compare prospectively the outcomes of anterior colporrhaphy alone to anterior colporrhaphy reinforced with overlap of a xenograft (Veritas—bovine pericardium) implanted in a standardized fashion at multiple centers.
MATERIALS AND METHODS
From January 2004 to June 2005, women were enrolled at three centers. The institutional review board at all three centers approved this research protocol before patient enrollment.
Inclusion criteria included age 18 years or older, female gender, stage II cystocele or greater (Pelvic Organ Prolapse Quantification [POP-Q] System point Ba more than –1 cm), and desire for surgical correction. Exclusion criteria included the presence of a vaginal epithelial ulceration or infection, previous pelvic organ prolapse surgery using an implant, known allergy to bovine material, severe vaginal atrophy (defined by dryness, pallor, and loss of rugation), previously shortened vaginal length (total vaginal length less than 6 cm), future desire for pregnancy, and an isolated paravaginal defect.
Initial evaluation included a comprehensive urogynecologic history and examination, including use of the POP-Q system, multichannel urodynamics, and, if indicated, cystoscopy. Specific factors recorded for the study included age, height, weight, race, POP-Q examination, menopausal status, urogenital atrophy, pelvic floor muscle strength, urinalysis, comorbidities, relevant pelvic surgical history, and urodynamics results.
Urogenital atrophy was assessed based on physical examination (vaginal secretions, vaginal epithelial integrity, vaginal epithelial surface thickness, and vaginal color). All patients displaying a degree of vaginal atrophy were treated with local estrogen cream for at least 4 weeks preoperatively. Pelvic floor muscle strength was determined by duration and intensity of muscle contraction assessed subjectively by digital examination. All enrollees also completed two validated quality-of-life questionnaires, the Urogenital Distress Inventory-6 (UDI-6) and Pelvic Organ Prolapse–Urinary Incontinence Sexual Function Questionnaire-12 (PISQ-12) before surgery.16,17
To ensure consistency in surgical technique, all centers used a surgical protocol determined before the initiation of the study. Randomization was performed using group assignment in a sealed envelope that was brought into the operating room but remained sealed until surgery was under way. The surgeons were blinded to the contents of the envelope.
All patients received prophylactic antibiotics, were positioned in a high lithotomy position with a Foley catheter in place, and were prepared in a standard manner. The anterior vagina was infiltrated with 1% lidocaine with epinephrine (1:100,000). The vaginal epithelium was incised vertically and dissected off the underlying endopelvic fascia (fibromuscular layer) to the level of the lateral vaginal sulcus and urogenital diaphragm. This layer was then plicated in the midline with interrupted 2–0 polyglactin 910 suture (Vicryl, Ethicon, Somerville, NJ) from the level of the bladder neck to the vaginal apex. The apical-most plication was incorporated onto the apical support tissue.
Once the anterior colporrhaphy was completed, the randomization envelope was opened. If the patient was assigned to receive graft reinforcement, the graft was applied in a standard manner. The graft was cut to extend from the bladder neck to the vaginal apex and from vaginal sulcus to vaginal sulcus without tension. It was bilaterally anchored to the obturator internus fascia at the lateral-most aspect of the dissection distally and proximally as well as to the bladder neck and vaginal apex in the midline using 2–0 polyglactin suture. The vaginal epithelium was appropriately trimmed and closed with a nonlocking continuous 2–0 polyglactin suture. Most concomitant procedures were performed vaginally as indicated. All patients received postoperative vaginal packing for 24 hours. Perioperative data included estimated blood loss, length of surgical procedure, length of hospitalization, and any intraoperative or perioperative complications.
Follow-up data were recorded at 3 months, 6 months, 12 months, and 24 months postoperatively. Follow-up data included POP-Q assessment, presence of any healing abnormalities (granulation tissue or erosion) or infection, assessment of urogenital atrophy, and complications. The patients also completed the UDI-6 and PISQ-12 at the follow-up time intervals. The same team of physicians performing the surgeries performed the follow-up examinations.
Sample size was calculated by estimating a recurrence rate of 35% with anterior colporrhaphy and 10% with graft reinforcement. Assuming a two-tailed hypothesis test with 5% type I error and 80% power, 80 patients would be required. We enrolled 94 patients assuming a dropout rate of 15%. Randomization was computer generated. Wilcoxon rank sum test was used to compare treatment groups with regard to ordinal and continuous variables. Wilcoxon matched pairs signed rank test was used to compare baseline and follow-up quality-of-life data. Pearson χ2 was used to test for differences in treatment groups regarding race. The Kaplan-Meier approach was used to examine time between surgery and recurrence of prolapse. A χ2 test with Yates correction, Fisher exact test, or McNemar χ2 test were used, as appropriate, to compare categorical relationships, with P<.05 considered statistically significant. All data were managed by the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL).
A total of 94 women were enrolled in the study. Forty-seven participants were assigned to the graft-reinforced group and 47 to anterior colporrhaphy alone. More than 3 month follow-up comprised the evaluated cohort. Baseline characteristics were similar for the groups (Table 1). There were no differences in the rate of prior hysterectomy, prior prolapse surgery, or antiincontinence surgery between the anterior colporrhaphy alone and bovine pericardium graft groups (Table 2). Additionally, there were no differences in the severity and type of pelvic organ prolapse (as measured by POP-Q scores) between the anterior colporrhaphy alone and bovine pericardium graft groups (Table 3).
Quality-of-life assessment did not differ between the bovine pericardium graft and anterior colporrhaphy–alone groups at baseline. The bovine pericardium graft group had a mean UDI-6 score of 45.7 compared with 41.8 in the anterior colporrhaphy–alone group (P=.314). Pelvic Organ Prolapse–Urinary Incontinence Sexual Function Questionnaire-12 scores at baseline were also the same, with a mean score of 16.0 in the bovine pericardium graft group and 13.9 in the anterior colporrhaphy–alone group (P=.118).
There were no statistically significant differences in the type and number of concomitant procedures performed in the anterior colporrhaphy alone and bovine pericardium graft groups (Table 4). No significant intraoperative or perioperative complications were reported in either group. Median (range) operative blood loss was 150.0 (75–300) mL for the bovine pericardium graft group and was 150.0 (50–500) mL for the anterior colporrhaphy–alone group (P=.379). Median (range) total operating time was 120.0 (90–236) minutes in the bovine pericardium graft group and 130.0 (30–247) minutes in the anterior colporrhaphy–alone group (P=.749). The bovine pericardium graft group's median (range) hospitalization was 2.0 (1–4) days and the anterior colporrhaphy–alone group had a median hospitalization of 2.0 (1–5) days (P=.447).
Postoperative complications primarily consisted of urinary tract infections. A total number of 10 complications were recorded for the bovine pericardium graft group and 16 for the anterior colporrhaphy–alone group over the 24-month follow-up period (P=.249). Nine vaginal epithelial healing abnormalities, primarily mild granulation tissue at suture sites along the epithelial closure line, were recorded in the bovine pericardium graft group at 3 months postoperatively compared with 10 in the anterior colporrhaphy–alone group (P=.794). The bovine pericardium graft group had no abnormalities recorded at 6 months postoperatively compared with three in the anterior colporrhaphy–alone group (P=.100). At 12 months postoperatively, the bovine pericardium graft group again had no epithelial abnormalities noted, and the anterior colporrhaphy–alone group had one (P=1.00). At 24 months neither of the groups had healing abnormalities. All epithelial abnormalities in both groups consisted of minor granulation tissue at suture sites that were treated in the office. There were no graft erosions, exposures, or infections noted in any participant at follow-up.
Follow-up of anatomic data were available beyond 3 months in 75 participants (80%); 38 patients in bovine pericardium graft group and 37 in the anterior colporrhaphy–alone group. Reasons for lack of follow-up beyond 3 months included difficulty in coming in for examinations due to geographic distance (10 patients), no longer living in area (two patients), change in health insurance (three patients), personal reasons (three patients), and death from pulmonary embolus (one patient).
The cohort of 72 (77%) patients provided follow-up up to 12 months. Of those who did not provide objective follow-up after 3 months, contact by telephone at 1 year revealed none had symptomatic recurrence or had undergone reoperation.
A cohort of 59 patients (63%) offered 2-year follow-up, although POP-Q was performed in 44 patients—27 in anterior colporrhaphy–alone group and 17 in bovine pericardium graft group (Fig. 1). Nine patients from the bovine pericardium graft group and six from the anterior colporrhaphy–alone group refused pelvic examination, and for those, we collected only subjective data. In the bovine pericardium graft group, eight patients considered themselves cured, with no prolapse, and one patient reported prolapse that was not palpable and did not interfere with her activities. In the anterior colporrhaphy–alone group, five patients stated they were cured and one patient had a nonpalpable prolapse. Objective data on these patients were not used for statistical analysis.
One year after surgery, successful anterior vaginal support (defined as Ba more than –1) was obtained in 30 of 35 (85.7%) patients in the bovine pericardium graft group and 29 of 37 (78.4%) patients in the anterior colporrhaphy–alone group (P=.544). Two years postoperatively, the bovine pericardium graft group and the anterior colporrhaphy–alone group had 13 of 17 (76.5%) and 17 of 27 (63%) successes, respectively (P=.509).
Recurrences included five (14.3%) in bovine pericardium graft group (two to the introitus) and eight (21.6%) recurrences in the anterior colporrhaphy–alone group (five to or beyond the introitus) at 12 months (P=.347). At 24 months, the anterior colporrhaphy–alone group had 10 (37%) recurrences (three beyond the introitus), and the bovine pericardium graft group had four (23.5%) recurrences (two to the introitus). All POP-Q data points are represented in Table 5. Analysis was performed on overall POP-Q stage and points Aa, Ba, and C.
We analyzed factors that could possibly be related to the success or failure of the procedures in the groups. There were no differences in age, prior anterior colporrhaphy, performance of mid urethral sling procedure, and urogenital atrophy when comparing patients with Ba more than –1 and Ba –1 or less in anterior colporrhaphy alone and bovine pericardium graft groups.
To control for the possibility of recurrent vault prolapse, the POP-Q analysis was repeated for each group, separating participants into good vault support (total vaginal length—C 1 or less) and potentially significant vault support weakness (total vaginal length—C 1 or more). This yielded evidence of a significantly higher overall POP-Q stage at 6 months in the anterior colporrhaphy–alone group compared with the bovine pericardium graft group (P=.027), with the difference being limited to apical support and not anterior points. Based on Kaplan-Meier analysis, time-to-event analysis revealed that the percentage of patients who could be expected to remain free of prolapse recurrence at 2 years was 72% for the bovine pericardium graft group and 70% for the control group (P>.774).
Preoperatively, 50 of 94 (53%) patients were sexually active. Dyspareunia was reported preoperatively by 37% patients (18 in bovine the pericardium graft group and 17 in the anterior colporrhaphy–alone group). At 1 year follow-up, 58% women in the anterior colporrhaphy–alone group and 42% in the bovine pericardium graft group were sexually active, and dyspareunia rates decreased similarly in both groups (P=.01). Dyspareunia was reported in 3 of 20 (15%) patients from the bovine pericardium graft group and 3 of 16 (20%) from anterior colporrhaphy–alone group. Only one patient from anterior colporrhaphy–alone group reported de novo dyspareunia 1 year after surgery.
Both groups showed significant declines in UDI-6 scores compared with baseline at each follow-up period (P<.001), and neither group demonstrated an advantage over the other. Similarly, PISQ-12 scores decreased significantly from baseline to all follow-up periods within both groups. There were no statistically significant differences between the groups. However, the rate of questionnaire invalidation due to incompleteness was high in both groups.
Developing an enduring repair for prolapse of the anterior vaginal wall continues to be one of the most challenging aspects of female pelvic surgery. When a woman is upright, the normal physiologic position of the upper two thirds of the vagina is nearly horizontal. Therefore, the anterior vaginal wall is likely subject to markedly higher forces than either the apical or posterior compartment. Some vaginal vault suspension techniques, such as sacrospinous fixation, further exaggerate the displacement of abdominal forces by deviation of the vaginal axis more posteriorly.
Given the amount of force applied to the anterior vagina with routine physical activities, it is not surprising that techniques that use suture plication of already compromised native tissues have a high failure rate. Subsequently, numerous materials and techniques have been described to reinforce or replace inadequate anterior vaginal tissue. Considering the number of procedures described, there are surprisingly few studies of high scientific quality evaluating outcomes. There are few randomized prospective studies available that have proved significant benefit with the use of reinforcement material over anterior colporrhaphy alone.
Weber et al1 showed no benefit with the addition of polyglactin 910 mesh compared with anterior colporrhaphy. They reported optimal results in 30% of patients with colporrhaphy alone compared with 42% with colporrhaphy plus 910 polyglactin mesh, with a median follow-up of 23.3 months. Nguyen and Burchette18 demonstrated 55% satisfactory anterior vaginal support in patients who underwent colporrhaphy alone compared with 87% with polypropylene mesh reinforcement. This study, however, reported an erosion rate of 5%.
Biologic grafts may have potential benefits, but there is lack of data in long-term follow-up. Gandhi et al12 noted 21% recurrence after colporrhaphy reinforced with fascia lata compared with 29% with colporrhaphy alone, with a median follow-up of 13 months. Meschia et al14 described 7% vaginal anterior recurrence using porcine dermis collagen implant with a 1-year follow-up. There are a variety of biologic graft types available for transvaginal surgery. It is not clear whether permanent synthetic (ie, polypropylene), degradable synthetic (polyglactin), or biologic grafts are associated with improved outcomes. Cross-linked materials are chemically treated to prevent degradation after implantation. The graft is not integrated into host tissue and may encapsulate, harden and alter normal anatomy. Non–cross-linked materials are incorporated into host tissue by neovascularization and collagen ingrowth.
The graft used in this study is a non–cross-linked biologic graft. It is not treated chemically to avoid degradation by the patient's endogenous enzymes. Some participants may break down the implant more rapidly, reducing its effectiveness and resulting in prolapse recurrence.
Application of the bovine pericardium graft does not significantly increase the length of time of the procedure, the potential for bleeding, or perioperative morbidity. Postoperatively, the graft was well-tolerated and not associated with increased healing difficulties. No infections or erosions were reported in this study. Complications in both groups were minor, mostly consisting of urinary tract infections. Pelvic organ prolapse quantification analysis did not show statistically significant differences between the groups. Continence and sexual function were significantly improved in both groups postoperatively, as measured by the UDI-6 and PISQ-12. The UDI-6 scores were fairly robust because there were few invalidated questionnaires, noting marked improvement in continence and voiding function in both the bovine pericardium graft and anterior colporrhaphy–alone groups at all follow-up periods. We emphasize, however that some patients had concomitant antiincontinence procedures, which may affect the quality of life.
The PISQ-12 results indicated significant improvement in sexual function after surgery compared with baseline in both groups at all time periods. These values need to be interpreted with some caution, however, because a large number of questionnaires were invalidated due to more than two missing answers.
There were several limitations to the study. The study was initially intended for 1-year follow-up. We completed 24 months of follow-up; however, the sample that comprised this cohort was small. The difference in cystocele recurrence rate between the groups was less than we estimated at all follow-up periods. Thus, the power calculation was suboptimal. It is possible the sample size was inadequate to detect small differences in the groups. The technique for anterior colporrhaphy and graft reinforcement was agreed upon before initiating the study, but because there were numerous surgeons at three centers, it is possible that variations in technique could have influenced outcomes. This, however, more closely represents realistic surgical practice. Although information identifying the participant's group was not available during follow-up exams, the same surgeons who operated performed the postoperative evaluations, which could be a potential source of bias. A high rate of PISQ-12 questionnaire invalidation weakened the ability to interpret postoperative sexual function.
We conclude that bovine pericardium collagen matrix graft material is not associated with increased perioperative or postoperative problems. Continence, voiding, and sexual function seem to improve significantly with the above-described procedures, with and without graft usage. Reinforcement with a bovine pericardium graft did not reveal a statistically significant improvement over midline plication at 1 and 2 years. In selected patients, such as those with very poor endopelvic fascia not amenable to midline plication, reinforcement with a biologic graft may prove beneficial. Further quality studies are required to further clarify whether biologic implant grafted anterior vaginal wall repair techniques offer a distinct advantage over plain anterior colporrhaphy.
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