Permanent Versus Absorbable Colpopexy Trial

Symptomatic pelvic organ prolapse is common and 13%1 to 19%2,3 of women undergo surgical
repair. Reconstructive pelvic surgery is broadly divided into procedures that rely on
existing native tissue versus the use of graft augmentation, either with synthetic or
biologic materials. Native tissue vaginal repair, while associated with the lowest rate of
surgical complications,4 has a high rate of recurrent prolapse. A recent randomized trial of
uterosacral versus sacrospinous ligament fixation for POP demonstrated a 30% recurrence rate
at 2 years.3

Abdominal sacrocolpopexy (SCP) is considered to be the most durable operation for advanced
pelvic organ prolapse with reoperation rates of less than 5%.5-7 Minimally-invasive
techniques of SCP, such as robotic-assistance, are associated with improved recovery times
and less cost than abdominal SCP without a demonstrable difference in efficacy.8,9 While
traditionally reserved for women with vaginal vault prolapse, SCP is increasingly considered
as a primary surgical option for women who present with uterovaginal prolapse in an attempt
to improve longer-term surgical outcomes. The optimal management of the uterus and cervix in
these cases is unclear.

Rationale for total versus supracervical hysterectomy with concomitant SCP

While supracervical hysterectomy and concomitant SCP are associated with lower rates of mesh
exposure,10-12 potential negative consequences of a supracervical hysterectomy include
morcellation of unanticipated uterine malignancy,13 cervical stump prolapse/elongation,
cyclic vaginal bleeding, and reduced anterior vaginal support (Myers EM, Matthews et al., in
press). When conducting a supracervical hysterectomy, power morcellators are the most common
method used to extract the amputated uterine corpus. The potential risks of power
morcellation were recently highlighted by the FDA safety notification which focused on the
potential to disseminate fragments of an undiagnosed uterine leiomyosarcoma throughout the
abdomen, which negatively impacts prognosis
(http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm393576.htm). With these recent
developments the focus has shifted towards performing total hysterectomy for delivery of an
intact specimen through the vagina.

Vaginal mesh exposure has been a problematic complication with both abdominal SCP and
minimally invasive SCP. Widely disparate rates of mesh exposure ranging from 0%14 to 27%15
have been reported. A systematic review of ASCP outcomes in 2004 reported an overall rate of
3.4%,6 and a recent meta-analysis of robotic-assisted SCP reported an overall rate of 2%.16
Some consistent risk factors for mesh exposure are non-Type 1 polypropylene mesh (knitted,
small-pore mesh materials) and smoking.17,18 Some studies have identified total hysterectomy
as a significant risk factor. In an evaluation of patients enrolled in the CARE trial, 6% had
evidence of mesh exposure at 2 years, with concomitant hysterectomy presenting almost a
5-fold increased risk.18 The rate at 6 years rose to 10.5%. 5 More than 50% of subjects in
this trial, however, had a non-Type 1 polypropylene mesh. Akyol et al. demonstrated a 2-fold
increased risk (12%)19 and Bensinger et al. a 7-fold increased risk (8.2%)20 of concomitant
total hysterectomy. In contrast, 4 retrospective studies in which Type1 polypropylene mesh
was used revealed no increased risk of mesh erosion with concomitant total
hysterectomy.14,21-23 These widely discrepant rates of mesh exposure may be related to
surgical technique, graft material and/or suture materials used for mesh attachment.

Rationale for need to study suture material for mesh attachment during SCP

The effect of suture on mesh exposure may be as significant as concomitant hysterectomy or
mesh type. At UNC, we reported on mesh exposure using a permanent suture for mesh attachment
during SCP with and without concomitant total hysterectomy, with rates of 8% at 1 year.24
There is some evidence that a delayed absorbable suture may reduce the risk of mesh or suture
erosion. In a retrospective review comparing braided permanent suture to delayed absorbable
monofilament suture for SCP mesh attachment, rates of mesh exposure were reduced in the
absorbable suture group (3.7% vs 0%), with no associated POP recurrence.25 Similarly, in
another retrospective review, when delayed absorbable monofilament suture was used for SCP
mesh attachment in 67 women undergoing total abdominal hysterectomy and SCP, no mesh
exposures were noted at a median follow up of 27 months.26 The use of permanent sutures for
vaginal mesh attachment has historically been advocated as a means to reduce POP recurrence
risk; yet, no prospective study has definitively answered this question. The tradeoff of
using a permanent suture may be an increased risk of mesh or suture exposure, as a permanent
suture that has breached the vaginal epithelium may serve as a nidus for bacterial seeding,
theoretically increasing the risk of mesh exposure. As SCP appears to be a more durable
procedure for women with advanced uterovaginal prolapse, there is an urgent need to identify
the ideal method of vaginal mesh attachment that minimizes the risk of mesh-related
complications while maintaining effectiveness of the POP repair.

Choice of mesh material

Upsylon™ (Boston Scientific, Natick, MA) is a pre-formed Y-mesh that is light-weight (25
g/m2), composed of Type I polypropylene material, with a pore size of 2.8 mm2 and surface
area ration of 1.11. It was FDA approved in 2012. The mesh is blue in color that may aide in
the ability to detect even small areas of mesh exposure and erosion. No data currently exist
regarding the performance of this particular mesh product in SCP. It is lighter in mesh
weight than the IntePro™ y-mesh (American Medical Systems, Minneapolis, MN), which we
previously used in the comparative trial of robotic to abdominal SCP in which our mesh
exposure rates were 8%.

The primary aim of this randomized trial, therefore, is to test the hypothesis that use of
the Upsylon™ mesh with a delayed absorbable suture for mesh attachment at the time of
robotic-assisted total laparoscopic hysterectomy and SCP will reduce the risk of vaginal mesh
and/or suture exposure compared to a permanent monofilament suture. Secondary aims will
include an evaluation of the effect of this light-weight mesh and absorbable suture on
prolapse and quality of life outcomes and surgical complications at 1 year after surgery.

Inclusion Criteria:

- Age ≥18

- Subject must have apical with anterior or posterior vaginal prolapse with leading edge
of prolapse to or beyond the hymen. This is defined as stage 2-4 pelvic organ prolapse
( C > - (TVL / 2) AND Ba or Bp ≥ 0 by the POP)

- Subject reports a bothersome bulge they can see or feel per PFDI-20, question 3,
response of 2 or higher (i.e., responses of "somewhat", "moderately", or "quite a
bit")

- Eligible for robotic or laparoscopic sacral colpopexy

- Desires surgical treatment for primary, symptomatic uterovaginal prolapse

- English speaking

- Willing to undergo hysterectomy

Exclusion Criteria:

- Patients who had prior hysterectomy

- Patients who are not surgical candidates due to medical comorbidities

- Current foreign body complications (including but not limited to erosion, fistula,
abscess). This covers foreign bodies of any type (e.g. synthetic and biologic
including allograft, xenograft).

- Desires uterine conservation

- Inability to give informed consent or to complete the testing or data collection

- Anticipated circumstances resulting in an inability to follow up (geographic
relocation, etc).

- Pregnant or intends to become pregnant

- Active/chronic systemic infection including any gynecologic infection, untreated UTI
or tissue necrosis

- History of pelvic organ cancer (e.g. uterine, ovarian, bladder, or cervical)

- Prior or currently undergoing radiation, laser therapy, or chemotherapy in the pelvic
area

- Subject has taken systemic steroids (within the last month), or immunosuppressive or
immunomodulatory treatment (within the last 3 months)

- Systemic connective tissue disease (e.g. scleroderma, Marfan's syndrome, Ehlers
Danhlos, collagenosis, polymyositis or polymyalgia rheumatica)

- Chronic systemic pain that includes the pelvic area or chronic focal pain that
involves the pelvis

- Poorly controlled diabetes mellitus (DM), as indicated by Hemoglobin A1c > 9

- Those requiring concomitant rectopexy

- Subject is not able to conform to steep trendelenburg position

- Known sensitivity to polypropylene