Trial Outcomes & Findings for Radiofrequency and Hybrid Fractional Laser for Vaginal Rejuvenation (NCT NCT03316950)

Last Updated: 2023-01-04

Results Overview

VSQ is a 21-item validated survey designed to assess postmenopausal quality-of-life parameters, namely vulvovaginal symptoms, emotions, life and sexual impact. Min: 0; Max: 21 Higher score would indicate greater number of symptoms.

Recruitment status

COMPLETED

Study phase

Target enrollment

52 participants

Primary outcome timeframe

Baseline, 3 Month Post- treatments and 6 Month Post Treatments

Results posted on

2023-01-04

Participant Flow

Subjects were recruited via flyers placed on the UT Southwestern Campus until recruitment concluded in 2020. The first participant was enrolled on June 15, 2018.

Of the 52 patients enrolled, 5 were screen failures. Hence, total 47 participants were assigned to the interventions. The Placebo Arms (DiVa Sham and IntraGen Sham) are combined here into one Placebo arm since this is how the data was assessed. The Dual Group includes all the Placebo arm participants who initially received 3 placebo treatments and then received 3 dual treatments (DIVA/IntraGen). All subjects assigned to each of the interventions didn't receive treatment between 3-6 months.

Participant milestones

Participant milestones
Measure	Hybrid Fractional Laser (HFL) Group Patients randomized into the DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.	Radiofrequency (RF) Group Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.	Placebo Arm Participants from the DiVa Sham Group and Intragen Sham Group combined DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue.	Dual (HFL & RF) Group Patients previously randomized into the DiVA Sham and IntraGen Sham groups will be placed in the Dual Treatment group. Patients will have a total of 3 dual treatments, spaced 1 month apart. Each treatment will last approximately 20 minutes. Prior to dual treatments, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken at follow up visits. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.
Initial Intervention (1 to 3 Months) STARTED	12	12	23	0
Initial Intervention (1 to 3 Months) COMPLETED	9	8	14	0
Initial Intervention (1 to 3 Months) NOT COMPLETED	3	4	9	0
Dual Intervention (6 to 8 Months) STARTED	0	0	0	14
Dual Intervention (6 to 8 Months) COMPLETED	0	0	0	14
Dual Intervention (6 to 8 Months) NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Hybrid Fractional Laser (HFL) Group Patients randomized into the DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.	Radiofrequency (RF) Group Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.	Placebo Arm Participants from the DiVa Sham Group and Intragen Sham Group combined DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue.
Initial Intervention (1 to 3 Months) Withdrawal by Subject	1	2	3
Initial Intervention (1 to 3 Months) Physician Decision	2	0	1
Initial Intervention (1 to 3 Months) Lost to Follow-up	0	2	5

Baseline Characteristics

During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Hybrid Fractional Laser (HFL) Group n=12 Participants Patients randomized into this DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment.	Radiofrequency (RF) Group n=12 Participants Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment.	Placebo Group n=23 Participants Participants from the DiVa Sham Group and Intragen Sham Group combined DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue.	Dual (HFL & RF) Group n=14 Participants Patients previously randomized into the DiVA Sham and IntraGen Sham groups will be placed in the Dual Treatment group. Patients will have a total of 3 dual treatments, spaced 1 month apart. Each treatment will last approximately 20 minutes. Prior to dual treatments, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken at follow up visits.	Total n=61 Participants Total of all reporting groups
Age, Categorical Initial Intervention · <=18 years	0 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=23 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=47 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Age, Categorical Initial Intervention · Between 18 and 65 years	12 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	12 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	23 Participants n=23 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	47 Participants n=47 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Age, Categorical Initial Intervention · >=65 years	0 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=23 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=47 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Age, Categorical Dual Intervention · <=18 years	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Age, Categorical Dual Intervention · Between 18 and 65 years	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	14 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	14 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Age, Categorical Dual Intervention · >=65 years	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Sex: Female, Male Initial Intervention · Female	12 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	12 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	23 Participants n=23 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	47 Participants n=47 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Sex: Female, Male Initial Intervention · Male	0 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=23 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=47 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Sex: Female, Male Dual Intervention · Female	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	14 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	14 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Sex: Female, Male Dual Intervention · Male	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Race/Ethnicity, Customized Initial Intervention · Caucasian	5 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	9 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	15 Participants n=23 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	29 Participants n=47 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Race/Ethnicity, Customized Initial Intervention · Hispanic	1 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	1 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	2 Participants n=23 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	4 Participants n=47 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Race/Ethnicity, Customized Initial Intervention · Black or African American	6 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	2 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	5 Participants n=23 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	13 Participants n=47 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Race/Ethnicity, Customized Initial Intervention · Caucasian / Hispanic	0 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants n=12 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	1 Participants n=23 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	1 Participants n=47 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Race/Ethnicity, Customized Dual Intervention · Caucasian	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	8 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	8 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Race/Ethnicity, Customized Dual Intervention · Hispanic	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	1 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	1 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Race/Ethnicity, Customized Dual Intervention · Black or African American	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	4 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	4 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.
Race/Ethnicity, Customized Dual Intervention · Caucasian / Hispanic	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	0 Participants During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	1 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.	1 Participants n=14 Participants • During Initial intervention period there were 0 participants in the dual group. During the dual intervention period there were 14 participants included that were all from the placebo arm who underwent dual intervention and thus were analyzed.

PRIMARY outcome

Timeframe: Baseline, 3 Month Post- treatments and 6 Month Post Treatments

Population: Subjects originally in DIVA sham and IntraGen Sham arms were combined to create the dual treatment group- these subjects initially received 3 placebo treatments and then received 3 dual treatments (DIVA/IntraGen). Our data was not collected at the 6 Month time point for the placebo arm.

Outcome measures

Outcome measures
Measure	Hybrid Fractional Laser (HFL) Group n=9 Participants Patients randomized into the DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.	Radiofrequency (RF) Group n=8 Participants Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.	Placebo Arm n=14 Participants Participants from the DiVa Sham Group and Intragen Sham Group combined DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue.	Dual (HFL & RF) Group n=14 Participants Patients previously randomized into the DiVA Sham and IntraGen Sham groups will be placed in the Dual Treatment group. Patients will have a total of 3 dual treatments, spaced 1 month apart. Each treatment will last approximately 20 minutes. Prior to dual treatments, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken at follow up visits. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.
Vulvovaginal Symptoms Questionnaire Baseline	8 score on a scale Standard Deviation 5.5	7.88 score on a scale Standard Deviation 5.49	5.93 score on a scale Standard Deviation 4.67	5.93 score on a scale Standard Deviation 4.67
Vulvovaginal Symptoms Questionnaire 3 Month Post Treatment	3.22 score on a scale Standard Deviation 2.77	5 score on a scale Standard Deviation 6.12	3 score on a scale Standard Deviation 3.46	1.86 score on a scale Standard Deviation 2.51
Vulvovaginal Symptoms Questionnaire 6 Month Post Treatment	3.43 score on a scale Standard Deviation 3.87	2.33 score on a scale Standard Deviation 4.41	—	1.7 score on a scale Standard Deviation 2.36

PRIMARY outcome

Timeframe: Baseline, 3 Months Post Treatments and 6 Months Post Treatments

The VLQ is a Likert scale with seven responses regarding self-reported vaginal laxity; answer option range from "Very Loose" to "Very Tight". Min: 1; Max: 7 A higher score would indicate "Very Tight" response provided by the subject.

Outcome measures

Outcome measures
Measure	Hybrid Fractional Laser (HFL) Group n=9 Participants Patients randomized into the DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.	Radiofrequency (RF) Group n=8 Participants Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.	Placebo Arm n=14 Participants Participants from the DiVa Sham Group and Intragen Sham Group combined DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue.	Dual (HFL & RF) Group n=14 Participants Patients previously randomized into the DiVA Sham and IntraGen Sham groups will be placed in the Dual Treatment group. Patients will have a total of 3 dual treatments, spaced 1 month apart. Each treatment will last approximately 20 minutes. Prior to dual treatments, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken at follow up visits. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.
Vaginal Laxity Questionnaire Baseline	3.57 score on a scale Standard Deviation 2.51	3.67 score on a scale Standard Deviation 2.25	2.79 score on a scale Standard Deviation 1.93	2.79 score on a scale Standard Deviation 1.93
Vaginal Laxity Questionnaire 3 Months Post Treatment	4.44 score on a scale Standard Deviation 1.74	3.75 score on a scale Standard Deviation 2.19	3.5 score on a scale Standard Deviation 1.74	3.93 score on a scale Standard Deviation 1.82
Vaginal Laxity Questionnaire 6 Months Post Treatment	3.83 score on a scale Standard Deviation 1.72	4.5 score on a scale Standard Deviation 1.38	—	4.2 score on a scale Standard Deviation 1.4

SECONDARY outcome

Timeframe: Baseline and 3 Months Post Treatment

Population: Subjects originally in DIVA sham and IntraGen Sham arms were combined to create the dual treatment group- these subjects initially received 3 placebo treatments and then received 3 dual treatments (DIVA/IntraGen). We were unable to collect data for some of the participants who were assigned to each of these arms due to an equipment malfunction and hence these subjects were not included in this analysis.

Perceived changes in vaginal laxity is measured by Zimmern probe which measures vaginal wall elasticity.

Outcome measures

Outcome measures
Measure	Hybrid Fractional Laser (HFL) Group n=1 Participants Patients randomized into the DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.	Radiofrequency (RF) Group n=5 Participants Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.	Placebo Arm n=8 Participants Participants from the DiVa Sham Group and Intragen Sham Group combined DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue.	Dual (HFL & RF) Group n=6 Participants Patients previously randomized into the DiVA Sham and IntraGen Sham groups will be placed in the Dual Treatment group. Patients will have a total of 3 dual treatments, spaced 1 month apart. Each treatment will last approximately 20 minutes. Prior to dual treatments, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken at follow up visits. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.
Perceived Changes in Vaginal Laxity as Measured by Zimmern Probe at 3 Months Post Treatment	0.44 mmHg Standard Deviation NA Only 1 participant was analyzed	0.78 mmHg Standard Deviation 1.3	0.7 mmHg Standard Deviation 2.47	0.36 mmHg Standard Deviation 1.33

SECONDARY outcome

Timeframe: Baseline and 6 Months Post Treatment

Population: Collected data were not considered valid due to an equipment malfunction.

Perceived changes in vaginal laxity is measured by Zimmern probe which measures vaginal wall elasticity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 3 Months Post Treatments and 6 Months Post Treatments

UDI-6 measures multiple domains to assess for presence and severity of physical symptoms such as frequency in urination, urine leakage and pain/discomfort. Min: 0; Max: 100 Higher score would indicate a higher disability

Outcome measures

Outcome measures
Measure	Hybrid Fractional Laser (HFL) Group n=9 Participants Patients randomized into the DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.	Radiofrequency (RF) Group n=8 Participants Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.	Placebo Arm n=14 Participants Participants from the DiVa Sham Group and Intragen Sham Group combined DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue.	Dual (HFL & RF) Group n=14 Participants Patients previously randomized into the DiVA Sham and IntraGen Sham groups will be placed in the Dual Treatment group. Patients will have a total of 3 dual treatments, spaced 1 month apart. Each treatment will last approximately 20 minutes. Prior to dual treatments, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken at follow up visits. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.
Urogenital Distress Short Form (UDI-6) Baseline	36.11 score on a scale Standard Deviation 17.92	34.38 score on a scale Standard Deviation 24.37	28.15 score on a scale Standard Deviation 23.23	28.15 score on a scale Standard Deviation 23.23
Urogenital Distress Short Form (UDI-6) 3 Month Post Treatment	25.65 score on a scale Standard Deviation 18.93	41.15 score on a scale Standard Deviation 31.61	27.14 score on a scale Standard Deviation 23.11	21.13 score on a scale Standard Deviation 23.2
Urogenital Distress Short Form (UDI-6) 6 Month Post Treatment	25.69 score on a scale Standard Deviation 21.8	23.61 score on a scale Standard Deviation 20.18	—	24.63 score on a scale Standard Deviation 19.16

SECONDARY outcome

Timeframe: Baseline, 3 Months Post Treatments and 6 Months Post Treatments

The Incontinence Impact Questionnaire assesses the impact and extent of incontinence on patients' everyday lives. Min: 0; Max: 100 Higher scores corresponds to greater degree of disability.

Outcome measures

Outcome measures
Measure	Hybrid Fractional Laser (HFL) Group n=9 Participants Patients randomized into the DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.	Radiofrequency (RF) Group n=8 Participants Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.	Placebo Arm n=14 Participants Participants from the DiVa Sham Group and Intragen Sham Group combined DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue.	Dual (HFL & RF) Group n=14 Participants Patients previously randomized into the DiVA Sham and IntraGen Sham groups will be placed in the Dual Treatment group. Patients will have a total of 3 dual treatments, spaced 1 month apart. Each treatment will last approximately 20 minutes. Prior to dual treatments, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken at follow up visits. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.
Incontinence Impact Questionnaire Short Form (IIQ-7) Baseline	22.75 score on a scale Standard Deviation 18.1	22.02 score on a scale Standard Deviation 29.01	10.2 score on a scale Standard Deviation 17	10.2 score on a scale Standard Deviation 17
Incontinence Impact Questionnaire Short Form (IIQ-7) 3 Month Post Treatment	7.41 score on a scale Standard Deviation 12.62	11.31 score on a scale Standard Deviation 13.21	15.98 score on a scale Standard Deviation 32.33	8.16 score on a scale Standard Deviation 20.24
Incontinence Impact Questionnaire Short Form (IIQ-7) 6 Month Post Treatment	11.9 score on a scale Standard Deviation 14.04	10.32 score on a scale Standard Deviation 18.42	—	10.48 score on a scale Standard Deviation 31.49

SECONDARY outcome

Timeframe: Baseline, 3 Months Post Treatments and 6 Months Post Treatments

The FSFI is a 19-item validated questionnaire that assesses several domains of sexual function including, desire, arousal, lubrication, orgasm, satisfaction and pain. Min: 2; Max: 36 Higher scores indicate fewer symptoms and greater sexual satisfaction.

Outcome measures

Outcome measures
Measure	Hybrid Fractional Laser (HFL) Group n=9 Participants Patients randomized into the DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.	Radiofrequency (RF) Group n=8 Participants Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.	Placebo Arm n=14 Participants Participants from the DiVa Sham Group and Intragen Sham Group combined DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue.	Dual (HFL & RF) Group n=14 Participants Patients previously randomized into the DiVA Sham and IntraGen Sham groups will be placed in the Dual Treatment group. Patients will have a total of 3 dual treatments, spaced 1 month apart. Each treatment will last approximately 20 minutes. Prior to dual treatments, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken at follow up visits. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.
Female Sexual Function Index (FSFI) Baseline	14.96 score on a scale Standard Deviation 9.23	15.69 score on a scale Standard Deviation 10.34	15.98 score on a scale Standard Deviation 10.04	16.09 score on a scale Standard Deviation 9.62
Female Sexual Function Index (FSFI) 3 Months Post Treatments	21.38 score on a scale Standard Deviation 11.62	18.73 score on a scale Standard Deviation 12.72	17.28 score on a scale Standard Deviation 10.98	20.67 score on a scale Standard Deviation 10.88
Female Sexual Function Index (FSFI) 6 Months Post Treatments	18.2 score on a scale Standard Deviation 12.33	21.7 score on a scale Standard Deviation 14.01	—	24.19 score on a scale Standard Deviation 11.06

SECONDARY outcome

Timeframe: Baseline and 3 Months Post Treatments

Population: Study staff was unable to collect a biopsy sample during all visits. Subjects originally in DIVA sham and IntraGen Sham arms were combined to create the dual treatment group- these subjects initially received 3 placebo treatments and then received 3 dual treatments (DIVA/IntraGen).

Biopsies taken of the anterior vaginal wall will be analyzed for gene expression Fold change= sample/average of the baseline

Outcome measures

Outcome measures
Measure	Hybrid Fractional Laser (HFL) Group n=9 Participants Patients randomized into the DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.	Radiofrequency (RF) Group n=8 Participants Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.	Placebo Arm n=23 Participants Participants from the DiVa Sham Group and Intragen Sham Group combined DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue.	Dual (HFL & RF) Group n=14 Participants Patients previously randomized into the DiVA Sham and IntraGen Sham groups will be placed in the Dual Treatment group. Patients will have a total of 3 dual treatments, spaced 1 month apart. Each treatment will last approximately 20 minutes. Prior to dual treatments, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken at follow up visits. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.
Gene Expression- Col1A1 as Measured by Fold Change	0.67 fold change Standard Error 0.32	0.48 fold change Standard Error 0.24	1 fold change Standard Error 0.25	0.95 fold change Standard Error 0.26

SECONDARY outcome

Timeframe: Baseline and 3 Months Post Treatments

Biopsies taken of the anterior vaginal wall will be analyzed for gene expression Fold change= sample/average of the baseline

Outcome measures

Outcome measures
Measure	Hybrid Fractional Laser (HFL) Group n=9 Participants Patients randomized into the DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.	Radiofrequency (RF) Group n=8 Participants Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.	Placebo Arm n=23 Participants Participants from the DiVa Sham Group and Intragen Sham Group combined DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue.	Dual (HFL & RF) Group n=14 Participants Patients previously randomized into the DiVA Sham and IntraGen Sham groups will be placed in the Dual Treatment group. Patients will have a total of 3 dual treatments, spaced 1 month apart. Each treatment will last approximately 20 minutes. Prior to dual treatments, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken at follow up visits. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.
Gene Expression- Col3A1 as Measured by Fold Change	0.95 fold change Standard Error 0.41	0.82 fold change Standard Error 0.55	1 fold change Standard Error 0.35	1.23 fold change Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline and 3 Months Post Treatments

Biopsies taken of the anterior vaginal wall will be analyzed for gene expression Fold change= sample/average of the baseline

Outcome measures

Outcome measures
Measure	Hybrid Fractional Laser (HFL) Group n=9 Participants Patients randomized into the DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.	Radiofrequency (RF) Group n=8 Participants Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.	Placebo Arm n=23 Participants Participants from the DiVa Sham Group and Intragen Sham Group combined DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue.	Dual (HFL & RF) Group n=14 Participants Patients previously randomized into the DiVA Sham and IntraGen Sham groups will be placed in the Dual Treatment group. Patients will have a total of 3 dual treatments, spaced 1 month apart. Each treatment will last approximately 20 minutes. Prior to dual treatments, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken at follow up visits. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.
Gene Expression- ELN as Measured by Fold Change	0.40 fold change Standard Error 0.18	0.33 fold change Standard Error 0.20	1 fold change Standard Error 0.16	0.79 fold change Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline and 3 Months Post Treatments

Biopsies taken of the anterior vaginal wall will be analyzed for gene expression Fold change= sample/average of the baseline

Outcome measures

Outcome measures
Measure	Hybrid Fractional Laser (HFL) Group n=9 Participants Patients randomized into the DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.	Radiofrequency (RF) Group n=8 Participants Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.	Placebo Arm n=23 Participants Participants from the DiVa Sham Group and Intragen Sham Group combined DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue.	Dual (HFL & RF) Group n=14 Participants Patients previously randomized into the DiVA Sham and IntraGen Sham groups will be placed in the Dual Treatment group. Patients will have a total of 3 dual treatments, spaced 1 month apart. Each treatment will last approximately 20 minutes. Prior to dual treatments, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken at follow up visits. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.
Gene Expression- LOX as Measured by Fold Change	2.72 fold change Standard Deviation 1.71	0.75 fold change Standard Deviation .28	1 fold change Standard Deviation 0.16	0.95 fold change Standard Deviation 0.17

Adverse Events

Hybrid Fractional Laser (HFL) Group

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Radiofrequency (RF) Group

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo Arm

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Dual (HFL & RF) Group

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Hybrid Fractional Laser (HFL) Group n=12 participants at risk Patients randomized into the DiVA treatment group will receive treatment per DiVA protocol. Patients will have a total of 3 treatments, space 1 month apart. Each treatment will last approximately 10 minutes. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner.	Radiofrequency (RF) Group n=12 participants at risk Patients will undergo treatment with radiofrequency device, using the device's standard protocol. Patients will have 3 treatments space one month apart. Each treatment will be a total of 20 minutes for internal treatment only. Prior to treatment, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken 3 months after final treatment. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.	Placebo Arm n=23 participants at risk Participants from the DiVa Sham Group and Intragen Sham Group combined DiVa Placebo: patients will undergo a three-part placebo treatment, spaced 1 month apart (+/- 10 days) of the vulvovaginal area. The vaginal HFL handpiece will be inserted into the vaginal canal but sub-therapeutic energy will not be delivered to the tissue. IntraGen Placebo: patients will undergo a three-part placebo treatment, space 1 month apart (+/- 10 days) of the vulvovaginal area. This will be achieved through application of the probe, but with applying sub-therapeutic energy to the tissue.	Dual (HFL & RF) Group n=14 participants at risk Patients previously randomized into the DiVA Sham and IntraGen Sham groups will be placed in the Dual Treatment group. Patients will have a total of 3 dual treatments, spaced 1 month apart. Each treatment will last approximately 20 minutes. Prior to dual treatments, the Zimmern probe will be used to measure vaginal wall elasticity and a 0.33mm biopsy will be taken. At each visit, the Zimmern probe will be used. Biopsies will be taken at follow up visits. DiVA: DiVA device utilizes a hybrid fractional laser technology in a wand hand piece. The hand piece is covered by a single use strengthened quartz dilator that allows the hand piece to rotate and provide treatment in a uniform manner. IntraGen RF: IntraGen is a radiofrequency vaginal rejuvenation device FDA approved for use in dermatological and general surgical procedures for electrocoagulation and hemostasis. The hand piece is a disposable monopolar applicator that is used to apply energy internally and externally.
Reproductive system and breast disorders Vaginal Odor/Itching/Spotting	8.3% 1/12 • 15 months	0.00% 0/12 • 15 months	4.3% 1/23 • 15 months	35.7% 5/14 • 15 months
Reproductive system and breast disorders UTI/Yeast Infection	0.00% 0/12 • 15 months	16.7% 2/12 • 15 months	8.7% 2/23 • 15 months	0.00% 0/14 • 15 months
Reproductive system and breast disorders Urine Leakage	0.00% 0/12 • 15 months	0.00% 0/12 • 15 months	4.3% 1/23 • 15 months	0.00% 0/14 • 15 months
Reproductive system and breast disorders Abdominal Discomfort	0.00% 0/12 • 15 months	0.00% 0/12 • 15 months	4.3% 1/23 • 15 months	7.1% 1/14 • 15 months
Reproductive system and breast disorders Vaginal perspiration	0.00% 0/12 • 15 months	0.00% 0/12 • 15 months	0.00% 0/23 • 15 months	7.1% 1/14 • 15 months
Reproductive system and breast disorders Other	58.3% 7/12 • 15 months	33.3% 4/12 • 15 months	21.7% 5/23 • 15 months	7.1% 1/14 • 15 months

Additional Information

Research Coordinator

UT Southwestern

Phone: 214-645-8907

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place