Study of Uterine Prolapse Procedures - Randomized Trial

The study population will be adult women (>21 years of age) with symptomatic uterovaginal
prolapse at or beyond the hymen who desire vaginal surgical management. This study is
intended to be done only on women who have completed child-bearing and have an inactive
uterus, defined as amenorrhea for 1 year. Therefore women will be postmenopausal or will have
amenorrhea from an endometrial ablation. Amenorrhea caused from exogenous steroids, or
hypothalamic disorders will not allow inclusion.

Participants will be obtained from the clinic population of each of the eight Pelvic Floor
Disorders Network (PFDN) sites. Participants will be randomly assigned to have either vaginal
hysterectomy and USLS or mesh hysteropexy suspension for treatment of their uterovaginal
prolapse. The surgical assignment will be revealed in the operating room, after the
participant is under anesthesia.

Participants will be followed for at least 36-months (3-years) post surgery and up to a
maximum of 60-months (5-years). Follow-up data will be obtained during in-person clinic
visits, and study staff who are masked to the surgical assignment will be the primary person
who obtain follow-up data. Although the primary study outcome does not depend on masked
participants and blinded evaluators, several important participant reported secondary aims
are subject to reporting bias if the participant is aware of her study assignment. Therefore,
study participants, coordinators, and nurses will be masked to the study assignment. Study
surgeons and anatomic evaluators will be unmasked. Evaluators conducting the POPQ exam will
be a co-investigator, fellow or other qualified nurse who did not perform the study surgery.

Surgical failure rates will be compared using survival analysis approaches appropriate for
interval censored data (classic log-rank tests and survival models using a generalized linear
model approach with a complementary log-log link) and secondary outcomes will be reported as
rates in each group or as group means and evaluated with the appropriate parametric or
nonparametric statistical tests.

Throughout the study, the PFDN Data Safety and Monitoring Committee (DSMB) will review study
data and decide if the study can or cannot continue. Additionally, this study will adhere to
the CONSORT guidelines for performing and reporting randomized controlled trials (Begg et al
1996). Women who are eligible but decline enrollment will be characterized in a manner
consistent with CONSORT requirements.

Inclusion Criteria:

1. Women aged 21 or older who have completed child -bearing

2. Prolapse beyond the hymen (defined as Ba, Bp, or C > 0 cm)

3. Uterine descent into at least the lower half of the vagina (defined as point C>
-TVL/2) )

4. Bothersome bulge symptoms as indicated on question 3 of the PFDI-20 form relating to
'sensation of bulging' or 'something falling out'

5. Desires vaginal surgical treatment for uterovaginal prolapse

6. Available for up to 60 month follow-up

7. Amenorrhea for the past 12 months from either menopause or endometrial ablation

8. Not pregnant, not at risk for pregnancy or agree to contraception if at risk for
pregnancy (only applicable to the rare endometrial ablation patient)

9. Eligible for no cervical cancer screening for at least 3 years

Exclusion Criteria:

1. Previous synthetic material (placed vaginally or abdominally) to augment POP repair

2. Known previous uterosacral or sacrospinous uterine suspension

3. Known adverse reaction to synthetic mesh or biological grafts; these complications
include but are not limited to erosion, fistula, or abscess

4. Chronic pelvic pain

5. Pelvic radiation

6. Cervical elongation- defined as an expectation that the C point would be Stage 2 or
greater postoperatively if a hysteropexy was performed. (Note: cervical shortening or
trachelectomy is not an allowed intraoperative procedure within the hysteropexy
treatment group).

7. Women at increased risk of cervical dysplasia requiring cervical cancer screening more
often than every 3 years (e.g. HIV+ status, immunosuppression because of transplant
related medications, Diethylstilbestrol (DES) exposure in utero, or previous treatment
for cervical intraepithelial neoplasia (CIN)2, CIN3, or cancer)

8. Uterine abnormalities (symptomatic uterine fibroids, polyps, endometrial hyperplasia,
endometrial cancer, or any uterine disease that precluded prolapse repair with uterine
preservation in the opinion of the surgeon

9. Indication for ovarian removal (adnexal mass, BRCA 1/2 positivity, family history of
ovarian cancer)

10. Current condition of amenorrhea caused by exogenous sex steroids or hypothalamic
conditions.