The Microcirculation of Vaginal Tissue in Women with Obstetric Vesicovaginal Fistula and Short-Term Effects of Surgical Repair on Microvascular Parameters.

OBJECTIVES: The objective of the study was to better understand the extent of the ischemic trauma and the effects of surgical repair on the vaginal microcirculation in patients with obstetric vesicovaginal fistula (VVF). DESIGN: In this observational study, we evaluated the vaginal microvasculature surrounding VVF using handheld vital microscopy (HVM) before, during, and 2 weeks after surgical VVF repair. PARTICIPANTS: Seventeen women undergoing VVF repair were included in this study. SETTING: The study was conducted in the Fistula Care Centre in Lilongwe, Malawi. METHODS: We used HVM with incident dark-field imaging to non-invasively visualize the microvasculature of the vaginal tissue surrounding fistulas. The primary outcome was the presence of microvascular flow. Secondary outcomes included angioarchitecture, fistula closure (postoperative dye test), and urinary continence (pad weight test). RESULTS: Microvascular flow was present before, during, and after surgical repair in, respectively, 83.8%, 83.9%, and 93.4% of obtained image sequences. The angioarchitecture was normal in 75.8% of the image sequences before surgery, 69.4% at fistula closure, and 89.1% two weeks after VVF repair. Fourteen (82.4%) patients had a closed fistula after surgical repair. LIMITATIONS: The study was limited by the lack of a control group and the relatively small sample size. CONCLUSION: Although the vaginal microcirculation in women with VVF is compromised, extensive ischemic damage is not observed in the tissue surrounding fistulas. This suggests significant regenerative capacity of the vaginal vasculature in young women, or less extensive ischemic damage than presumed. Following surgical repair, we observed improvement of microcirculatory flow and angioarchitecture, suggesting that surgery is a good option for patients with obstetric VVF.

The effect of CO2 laser therapy on vaginal microcirculatory parameters in an animal model for genitourinary syndrome of menopause.

BACKGROUND: Vaginal laser therapy for the treatment of genitourinary syndrome of menopause (GSM) has been introduced to the market with limited (pre)clinical and experimental evidence supporting its efficacy. It is suggested that vaginal laser therapy increases epithelial thickness and improves vascularization, but the underlying biological working mechanism has not been substantiated yet. OBJECTIVE: To evaluate the effects of CO2 laser therapy on vaginal atrophy using noninvasive incident dark field (IDF) imaging in a large animal model for GSM. DESIGN, SETTING, AND PARTICIPANTS: An animal study was conducted between 2018 and 2019 and included 25 Dohne Merino ewes, of which 20 underwent bilateral ovariectomy (OVX) to induce iatrogenic menopause, and 5 did not. The total study duration was 10 months. INTERVENTIONS: Five months after OVX, ovariectomized ewes received monthly applications of CO2 laser (n = 7), vaginal estrogen (n = 7), or no treatment (n = 6) for 3 months. IDF imaging was performed monthly in all animals. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the proportion of image sequences containing capillary loops (angioarchitecture). Secondary outcomes included focal depth (epithelial thickness), and quantitative measures of vessel density and perfusion. Treatment effects were evaluated using ANCOVA and binary logistic regression. RESULTS AND LIMITATIONS: Compared to OVX-only, ewes treated with estrogen demonstrated a higher capillary loops proportion (4% vs. 75%, p < 0.01), and higher focal depth (60 (IQR 60-80) vs. 80 (IQR 80-80) p < 0.05). CO2 laser therapy did not change microcirculatory parameters. As the ewes' vaginal epithelium is thinner than that of humans, it may demand different laser settings. CONCLUSIONS: In a large animal model for GSM, CO2 laser therapy does not affect microcirculatory outcomes related to GSM, whereas vaginal estrogen treatment does. Until more homogeneous and objective evidence about its efficacy is available, CO2 laser therapy should not be adopted into widespread practice for treating GSM.

Non-invasive biomechanical assessment of the prolapsed vaginal wall: an explorative pilot study on cutometry and indentometry.

The clinical assessment of pelvic organ prolapse (POP) and associated treatment strategies is currently limited to anatomical and subjective outcome measures, which have limited reproducibility and do not include functional properties of vaginal tissue. The objective of our study was to evaluate the feasibility of using cutometry and indentometry for non-invasive biomechanical assessment of the vaginal wall in women with POP. Both techniques were applied on the vaginal wall of 20 women indicated for surgical correction of POP stage two or higher. The primary outcome was the measurement success rate. Measurements were considered successful if biomechanical parameters were generated after a maximum of three attempts. Secondary outcomes included acquisition time, number of attempts to obtain a successful measurement, and biomechanical parameters. Measurements were successfully performed on the anterior vaginal wall of 12 women with cystocele and the posterior vaginal wall of eight women with rectocele. The success rate was 100% for both techniques and acquisition time was under 1 minute for all 20 measurements. Tissue fast elasticity of the posterior vaginal wall (rectocele) was significantly higher than that of the anterior vaginal wall (cystocele) and negatively correlated with age (r = - 0.57, P < 0.05). In women with POP, measuring the biomechanical properties of the vaginal wall using cutometry and indentometry is technically feasible. Objective evaluation of biomechanical properties may help to understand the pathophysiology behind surgical outcomes, providing an opportunity for the identification of patients at risk for (recurrent) prolapse, and individualized treatment decisions.

Laser versus sham for genitourinary syndrome of menopause: A randomised controlled trial.

OBJECTIVE: To assess whether CO2 laser treatment is more effective than sham application in relieving the most bothersome symptom (MBS) in women with genitourinary syndrome of menopause (GSM). DESIGN: Single-centre, sham-controlled, double-blind, randomised trial. SETTING: A tertiary centre in Belgium. POPULATION: Sixty women with moderate to severe GSM symptoms. METHODS: All participants eventually received three consecutive laser and three consecutive sham applications, either first laser followed by sham, or conversely. MAIN OUTCOME MEASURES: The primary outcome was the participant-reported change in severity of the MBS at 12 weeks. Secondary outcomes included subjective (patient satisfaction, sexual function, urinary function) and objective (pH, Vaginal Health Index Score, in vivo microscopy) measurements assessing the short-term effect and the longevity of treatment effects at 18 months after start of the therapy. Adverse events were reported at every visit. RESULTS: The MBS severity score decreased from 2.86 ± 0.35 to 2.17 ± 0.93 (-23.60%; 95% CI -36.10% to -11.10%) in women treated with laser compared with 2.90 ± 0.31 to 2.52 ± 0.78 (-13.20%; 95% CI -22.70% to -3.73%) in those receiving sham applications (p = 0.13). There were no serious adverse events reported up to 18 months. CONCLUSIONS: In women with GSM, the treatment response 12 weeks after laser application was comparable to that of sham applications. There were no obvious differences for secondary outcomes and no serious adverse events were reported.

Sexual Function Following Treatment for Stress Urinary Incontinence With Bulk Injection Therapy and Mid-Urethral Sling Surgery.

BACKGROUND: Peri-urethral bulking injections (PBI) gain popularity for the treatment of stress urinary incontinence (SUI), but - in contrast to mid-urethral sling (MUS) surgery - little is known about its impact on sexual function. METHODS: This was a secondary analysis of a prospective cohort study that included patients with moderate to severe SUI undergoing either MUS surgery or PBI with polydimethylsiloxane Urolastic (PDMS-U). The validated Dutch and English version of the 'Pelvic Organ Prolapse and/or Urinary Incontinence Sexual Function Questionnaire - IUGA Revised' (PISQ-IR) was used to assess sexual function at baseline, at 6 and 12 months of follow-up. For between-group analysis, differences in baseline characteristics were corrected using multivariate analysis of covariance. OUTCOMES: The primary outcome was the PISQ-IR single summary score of sexually active (SA) women following both procedures, calculated by mean calculation. Secondary outcomes were the PISQ-IR subscale scores of SA and non-sexually active (NSA) women, the proportions of sexual activity and subjective improvement ('Patient Global Impression of Improvement' (PGI-I)). RESULTS: A total of 259 women (MUS: n = 146, PBI: n = 113) were included in this study. The PISQ-IR single summary score of SA women improved following both interventions (in the MUS group from 3.2 to 3.4 and in the PBI group from 3.0 to 3.3 after 12 months). After correcting for differences in baseline characteristics, the PISQ-IR summary score at 6 and 12 months was similar for both treatment groups. For SA women, condition-specific and condition-impact subscale scores significantly improved following both procedures. CLINICAL IMPLICATIONS: In treating SUI, PBI is inferior to MUS surgery. However, there is a need for less invasive strategies, especially for women who are unfit for surgery or have contraindications. Sexual function improves after PBI using PDMS-U, which is relevant for the counselling of women with SUI about available treatment options. STRENGTHS & LIMITATIONS: Strength: until this study, there was a lack of knowledge about the effects of PBI on sexual function. LIMITATION: there may be indication bias as we did not perform a randomized controlled trial. CONCLUSION: PBI using PMDS-U and MUS surgery for the treatment of SUI improve sexual function equally in SA women, mainly by decreasing the condition's impact on sexual activity and quality. Latul YP, Casteleijn FM, Zwolsman SE, et al. Sexual Function Following Treatment for Stress Urinary Incontinence With Bulk Injection Therapy and Mid-Urethral Sling Surgery. J Sex Med 2022;19:1116-1123.

Noninvasive, in vivo assessment of the cervical microcirculation using incident dark field imaging.

AIM: This study evaluates the feasibility of handheld vital microscopy for noninvasive, objective assessment of the microcirculation of the human uterine cervix. We qualitatively and quantitatively describe the microcirculation in healthy subjects in order to provide a basis for its application in cervical pathology. METHODS: Incident dark field imaging was used to image the microcirculation in four quadrants of the uterine ectocervix in ten healthy participants. If the squamocolumnar junction was visible, measurements were repeated on the endocervical columnar epithelium as well. Image acquisition time was recorded and participants scored the experienced level of discomfort. Angioarchitecture was classified according to Weber's classification. Quantitative parameters included capillary density (CD), total and perfused vessel density (TVD, PVD), proportion of perfused vessels (PPV) and microvascular flow index (MFI). RESULTS: Image acquisition was easy, fast and well tolerated. Angioarchitecture was characterized by two distinctive and organized patterns; capillary loops underneath the squamous epithelium of the ectocervix and vascular networks underneath the columnar epithelium. In the image sequences containing capillary loops, mean CD was 33.2 cpll/mm2 (95% CI 28.2-38.2 cpll/mm2). In the image sequences with vascular networks, mean TVD was 12.5 mm/mm2 (95% CI 11.2-13.77 mm/mm2), mean PVD was 12.2 (95% CI 11.0-13.5 mm/mm2), MFI was 3 and PPV was 100%. CONCLUSIONS: Incident dark field imaging allows for noninvasive, real time visualization and objective evaluation and quantification of the microcirculation of the uterine cervix. The organized vascular patterns and optimal perfusion observed in healthy subjects allow for comparison with cervical pathology, for example in patients with cervical dysplasia or cervical cancer.

Angiogenesis in gynecological cancers and the options for anti-angiogenesis therapy.

Angiogenesis is required in cancer, including gynecological cancers, for the growth of primary tumors and secondary metastases. Development of anti-angiogenesis therapy in gynecological cancers and improvement of its efficacy have been a major focus of fundamental and clinical research. However, survival benefits of current anti-angiogenic agents, such as bevacizumab, in patients with gynecological cancer, are modest. Therefore, a better understanding of angiogenesis and the tumor microenvironment in gynecological cancers is urgently needed to develop more effective anti-angiogenic therapies, either or not in combination with other therapeutic approaches. We describe the molecular aspects of (tumor) blood vessel formation and the tumor microenvironment and provide an extensive clinical overview of current anti-angiogenic therapies for gynecological cancers. We discuss the different phenotypes of angiogenic endothelial cells as potential therapeutic targets, strategies aimed at intervention in their metabolism, and approaches targeting their (inflammatory) tumor microenvironment.