Multiomic analysis of uterine leiomyomas in self-described Black and White women: molecular insights into health disparities.

BACKGROUND: Black women are at an increased risk of developing uterine leiomyomas and experiencing worse disease prognosis than White women. Epidemiologic and molecular factors have been identified as underlying these disparities, but there remains a paucity of deep, multiomic analysis investigating molecular differences in uterine leiomyomas from Black and White patients. OBJECTIVE: To identify molecular alterations within uterine leiomyoma tissues correlating with patient race by multiomic analyses of uterine leiomyomas collected from cohorts of Black and White women. STUDY DESIGN: We performed multiomic analysis of uterine leiomyomas from Black (42) and White (47) women undergoing hysterectomy for symptomatic uterine leiomyomata. In addition, our analysis included the application of orthogonal methods to evaluate fibroid biomechanical properties, such as second harmonic generation microscopy, uniaxial compression testing, and shear-wave ultrasonography analyses. RESULTS: We found a greater proportion of MED12 mutant uterine leiomyomas from Black women (>35% increase; Mann-Whitney U, P<.001). MED12 mutant tumors exhibited an elevated abundance of extracellular matrix proteins, including several collagen isoforms, involved in the regulation of the core matrisome. Histologic analysis of tissue fibrosis using trichrome staining and secondary harmonic generation microscopy confirmed that MED12 mutant tumors are more fibrotic than MED12 wild-type tumors. Using shear-wave ultrasonography in a prospectively collected cohort, Black patients had fibroids that were firmer than White patients, even when similar in size. In addition, these analyses uncovered ancestry-linked expression quantitative trait loci with altered allele frequencies in African and European populations correlating with differential abundance of several proteins in uterine leiomyomas independently of MED12 mutation status, including tetracoidpeptide repeat protein 38. CONCLUSION: Our study shows that Black women have a higher prevalence of uterine leiomyomas harboring mutations in MED12 and that this mutational status correlates with increased tissue fibrosis compared with wild-type uterine leiomyomas. Our study provides insights into molecular alterations correlating with racial disparities in uterine leiomyomas and improves our understanding of the molecular etiology underlying uterine leiomyoma development within these populations.

The Correlation Between the Sonographic Course of Transobturator Slings and Sling-Related Pain.

OBJECTIVES: To determine whether transobturator slings follow a consistent path and whether there is an association between ultrasonographically visualized sling pattern or position with sling-related pain. METHODS: This was a cross-sectional retrospective pilot study. We evaluated women who were presented to our clinic for pain or other urogynecologic symptoms following transobturator sling placement between 2009 and 2014. Patients had undergone a 3-dimensional endovaginal pelvic floor ultrasound, assessing minimal levator hiatus, antero-posterior diameter, left-right diameter, and the hiatal shape. The mesh patterns were categorized as seagull patterns (normal), lopsided, flat, and convoluted. RESULTS: A total of 68 cases were reviewed. Fifty patients reported pain, and 18 did not. There were wide variations in the course of the slings. The sling center- minimal levator hiatus position ranged 14.8 mm below and 17.9 mm above the minimal levator hiatus. The lateral arm insertion points ranged between 17.1 mm below and 16.6 mm above the minimal levator hiatus. The right arm insertion points ranged between 9.6 mm below and 18.8 mm above the minimal levator hiatus. Thirty-five of 68 (70%) patients with pain and 13 of 18 (72.2%) without had abnormal sling patterns. The abnormal sling shape was not correlated with pain (P = 1). The levator shape trended toward a statistical significant correlation with sling shape abnormality (P = .084). CONCLUSIONS: This population of women with transobturator sling complications demonstrated wide variations in anatomic paths. Neither the abnormal sling shape nor the distance of the center of the tape from the minimal levator hiatus level were correlated with pain.

Levator ani muscle volume and architecture in normal vs. muscle damage patients using 3D endovaginal ultrasound: a pilot study.

INTRODUCTION AND HYPOTHESIS: This study aimed to compare the difference in levator ani muscle (LAM) volumes between 'normal' and those with sonographically visualized LAM defects. We hypothesized that the 'muscle damage' group would have a significantly lower muscle volume. METHODS: The study included patients who had undergone a 3D endovaginal ultrasound. The normal (NM) and damage (DM) muscle groups' architectural changes were evaluated based on anterior-posterior (AP), left-right (LR) diameter, and minimal levator hiatus (MLH) area. The puboanalis-puboperinealis (PA), puborectalis (PR), and pubococcygeus-iliococcygeus (PC) were manually segmented using 2.5 vs. 1.0 mm to find the optimal sequence and to compare the volumes between NM and DM groups. POPQs were compared between the NM and DM groups. RESULTS: The 1.0-mm segmentation volumes created superior volume analysis. Comparing NM to the DM group showed no significant difference in LAM volume. Respectively, the mean total LAM volumes were 17.27 cm3 (SD = 3.97) and 17.04 cm3 (SD = 4.32), p = 0.79. The mean MLH measurements for both groups respectively were 10.06 cm2 (SD = 2.93) and 12.18 cm2 (SD = 2.93), indicating a significant difference (p = 0.01). POPQ analysis demonstrated statistically significant differences at Ba and Bp parameters suggesting that the DM group had worse prolapse (p = 0.05, 0.01, respectively). CONCLUSIONS: While LAM volumes are similar, there is a significant difference in the physical architecture of the LAM and the POPQ parameters in muscle-damaged patients compared to the normal group.

Clinical Consensus Statement: Vaginal Energy-Based Devices.

ABSTRACT: This clinical consensus statement on vaginal energy-based devices (EBDs) reflects an update by content experts from the American Urogynecologic Society's EBD writing group. In 2019, the American Urogynecologic Society's EBD writing group used a modified Delphi process to assess statements that were evaluated for consensus after a structured literature search. A total of 40 statements were assessed and divided into 5 categories: (1) patient criteria, (2) health care provider criteria, (3) efficacy, (4) safety, and (5) treatment considerations. Of the 40 statements that were assessed, 28 reached consensus and the remaining 12 did not. Lack of evidence was among the main reasons that vulvovaginal EBD treatment statements did not reach consensus. In March 2022, these statements were reassessed using the interim literature.

Automatic Plane of Minimal Hiatal Dimensions Extraction From 3D Female Pelvic Floor Ultrasound.

There is an increasing interest in the applications of 3D ultrasound imaging of the pelvic floor to improve the diagnosis, treatment, and surgical planning of female pelvic floor dysfunction (PFD). Pelvic floor biometrics are obtained on an oblique image plane known as the plane of minimal hiatal dimensions (PMHD). Identifying this plane requires the detection of two anatomical landmarks, the pubic symphysis and anorectal angle. The manual detection of the anatomical landmarks and the PMHD in 3D pelvic ultrasound requires expert knowledge of the pelvic floor anatomy, and is challenging, time-consuming, and subject to human error. These challenges have hindered the adoption of such quantitative analysis in the clinic. This work presents an automatic approach to identify the anatomical landmarks and extract the PMHD from 3D pelvic ultrasound volumes. To demonstrate clinical utility and a complete automated clinical task, an automatic segmentation of the levator-ani muscle on the extracted PMHD images was also performed. Experiments using 73 test images of patients during a pelvic muscle resting state showed that this algorithm has the capability to accurately identify the PMHD with an average Dice of 0.89 and an average mean boundary distance of 2.25mm. Further evaluation of the PMHD detection algorithm using 35 images of patients performing pelvic muscle contraction resulted in an average Dice of 0.88 and an average mean boundary distance of 2.75mm. This work had the potential to pave the way towards the adoption of ultrasound in the clinic and development of personalized treatment for PFD.

Effects of Pueraria mirifica on vaginal artery vascularization in postmenopausal women with genitourinary syndrome of menopause.

OBJECTIVE: To compare the effects of 6% Pueraria mirifica vaginal gel with those of placebo gel on vaginal blood flow, vaginal maturation index (VMI), vaginal health index (VHI), endometrial thickness and genitourinary symptoms in postmenopausal women. STUDY DESIGN: In a randomized, double-blinded, placebo-controlled study (TCTR20200624007), 72 postmenopausal women were randomized into the P. mirifica or the placebo gel group. Both groups were followed up at week 4 and week 12. MAIN OUTCOME MEASURE: Doppler ultrasonography pulsatility index (PI) and resistance index (RI), VMI, VHI, endometrial thickness and genitourinary symptoms were evaluated at baseline, at week 4 and week 12 of treatment. RESULTS: Sixty-three participants completed the study. After 4 and 12 weeks of treatment, PI and RI had significantly decreased in the P. mirifica group compared with the placebo group. At week 12, PI in the P. mirifica group and in the placebo group were 3.03 + 1.09 and 6.88 + 2.16, respectively (p = 0.002). Similar changes were also demonstrated in the resistance indices. The P. mirifica group demonstrated a markedly higher mean VMI at week 12 compared with the placebo group, 55.19 ± 18.53 and 20.29 ± 28.46 (p = 0.012). In addition, all parameters of VHI based on the vaginal physical findings at week 12 in the P. mirifica group were significantly higher than in the placebo group (p < 0.001). CONCLUSION: In this study, 6% P. mirifica vaginal gel for 12 weeks in postmenopausal women with GSM appeared to increase vaginal artery circulation and restore atrophic vaginal tissue. CLINICAL TRIAL REGISTRATION NUMBER: TCTR20200624007.

Correlation between pelvic floor ultrasound parameters and vaginal pressures in nulliparous women: a subanalysis of the SUM-AN study.

INTRODUCTION AND HYPOTHESIS: Pelvic floor ultrasound is used as a validated technique for measuring levator ani dimensions. Vaginal manometry has been used in the past as a method to assess levator ani muscle (LAM) strength. Whether the combination of both methods can contribute to our understanding of pelvic floor pathophysiology has not yet been described. We hypothesized that as female pelvic floor muscular hiatus increases, the vaginal pressure and strength decrease. METHODS: We recruited 20 asymptomatic nulliparous women ages 18-85 years. Minimal levator hiatus (MLH) area, anteroposterior/left-right (AP/LR) diameter ratio, the distance between levator plate and the pubic symphysis (LP-PS) while at rest and squeeze were measured using endovaginal ultrasound (US). Vaginal pressure at rest, squeeze (Kegel) and Valsalva were measured using 3D manometry. Logistic and linear regression analysis was performed to assess correlations. RESULTS: MLH area was negatively correlated with the sum of all the squeeze pressures produced on the four walls of the vagina (p = 0.049, R2 = 0.197). There was also a borderline negative correlation between MLH and the sum of rest pressures (p = 0.09, R2 = 0.15). AP/LR ratio was negatively correlated with the sum of squeeze pressures (p = 0.056, R2 = 0.197). LP-PS distances, both while at rest and during squeeze, were negatively correlated with the vaginal squeeze pressure (p = 0.046, R2 = 0.21; p = 0.011, R2 = 0.31, respectively). LP-V distance, both at rest and during squeeze, was negatively correlated with the sum of squeeze pressures on four vaginal walls (p = 0.02, R2 = 0.25; p = 0.005, R2 = 0.36, respectively). CONCLUSIONS: Stronger levator ani muscles, smaller MLH area and a more oval shape of pelvic floor hiatus as assessed by pelvic floor ultrasound are associated with higher squeeze vaginal pressures as assessed by 3D manometry.

Biomechanical integrity score of the female pelvic floor.

INTRODUCTION AND HYPOTHESIS: The aim of this study is to develop and validate a new integral parameter, the Biomechanical Integrity score (BI-score), for the characterization of the female pelvic floor. METHODS: A total of 253 subjects with normal and pelvic organ prolapse (POP) conditions were included in the multi-site observational, case-control study; 125 subjects had normal pelvic floor conditions, and 128 subjects had POP stage II or higher. A Vaginal Tactile Imager (VTI) was used to acquire and automatically calculate 52 biomechanical parameters for eight VTI test procedures (probe insertion, elevation, rotation, Valsalva maneuver, voluntary muscle contractions in two planes, relaxation, and reflex contraction). Statistical methods were applied (t-test, correlation) to identify the VTI parameters sensitive to the pelvic conditions. RESULTS: Twenty-six parameters were identified as statistically sensitive to POP development. They were subdivided into five groups to characterize (1) tissue elasticity, (2) pelvic support, (3) pelvic muscle contraction, (4) involuntary muscle relaxation, and (5) pelvic muscle mobility. Every parameter was transformed to its standard deviation units against the patient age similar to T-score for bone density. Linear combinations with specified weights led to the composition of five component parameters for groups (1)-(5) and the BI-score in standard deviation units. The p-value for the BI-score has p = 4.3 × 10-31 for POP versus normal conditions. A reference BI-score curve against age for normal pelvic floor conditions was defined. CONCLUSIONS: Quantitative transformations of the pelvic tissues, support structures, and functions under diseased conditions may be studied with the BI-score in future research and practical applications.

Does aging affect the elastic properties of the bladder and the urethra in nulliparous women: An ultrasound shear-wave elastography study.

OBJECTIVE: To investigate how aging and menopausal status in absence of pregnancy and childbirth affect the elasticity of the bladder and urethra. STUDY DESIGN: A single-center prospective observational study including nulliparous 10 pre- and 12 postmenopausal women. Data collection included baseline characteristics, physical examination data, questionnaire scores, PDFI and the Pelvic Floor Impact Questionnaire, and pelvic floor sonographic measurements as well as elastography measurements. The shear wave elastography (SWE) of tissue was measured using Kilopascal (kPa). The elastography measurements were taken over the rhabdosphincter, the suburethra smooth muscle, and the trigonal areas. RESULTS: A total of 22 nulliparous subjects were enrolled in the study. The cohort's mean age was 43.5 years, the mean body mass index (BMI) was 26.8, and 86% were of Caucasian ethnicity. The postmenopausal group was older and with higher BMI (p < 0.001 and p = 0.05). They also had higher scores in all the questionnaires (p < 0.05 for all) and did not demonstrate prolapse in any compartments. The SWE results for the whole group were 35.2 kPa in the rhabdosphincter measuring point, 40.2 kPa in the sub-urethra point, and 20.6 kPa in the trigone point. Comparing the premenopause and postmenopause groups, we found lower measurements in the rhabdosphincter area and equivocal measurements for the suburethral zone. No statistically significant differences were found between the groups CONCLUSIONS: The elastic properties of the different bladder components and the urethra change with age and menopause. Using elastic properties of the tissues, we can further explore both stress urinary incontinence and overactive bladder.

Clinical and Patient Reported Outcomes of Pre- and Postsurgical Treatment of Symptomatic Uterine Leiomyomas: A 12-Month Follow-up Review of TRUST, a Surgical Randomized Clinical Trial Comparing Laparoscopic Radiofrequency Ablation and Myomectomy.

STUDY OBJECTIVE: The objective of this study was to determine the efficacy, safety, and healthcare resource use of laparoscopic radiofrequency ablation (LAP-RFA) compared with myomectomy in patients with symptomatic uterine leiomyomas (ULs). DESIGN: This was a secondary analysis of the original postmarket randomized, multicenter, longitudinal, comparative TRUST (Treatment Results of Uterine Sparing Technologies) United States trial in patients with symptomatic ULs. After the procedure, subjects were followed over a 12-month period. SETTING: Multicenter trial, including hospitals with or without an academic affiliation, surgery centers, and fertility centers performing outpatient procedures for uterine myomas. PARTICIPANTS: A total of 57 patients were randomized to either LAP-RFA (n = 30) or myomectomy (n = 27). INTERVENTIONS: LAP-RFA or myomectomy (laparoscopic or abdominal). MEASUREMENTS AND MAIN RESULTS: The main outcome measures of this study were part of the secondary outcomes of the original TRUST trial. The primary outcome of this study was the reduction of UL symptoms and the improvement in patient-reported outcomes scores over time. Secondary outcomes included postprocedure hospitalization, length of stay, complications, reinterventions, and recovery time. There was a significant improvement in UL symptoms at 3 and 12 months after the procedure within each treatment group, and these improvements were similar between treatment groups. There was a significant reduction in UL symptoms per month between baseline and 12-months after the procedure for both LAP-RFA and myomectomy of 72% and 85%, respectively. A significant improvement was seen in all patient-reported outcomes scores over time for both groups. At 3 and 12 months after the procedure, the percentages of patients who were hospitalized in the LAP-RFA group were 74% and 49% lower than those of patients in the laparoscopic myomectomy group, respectively, with the 3-month difference being statistically significant. The length of hospital stay was significantly shorter in the LAP-RFA group compared with the myomectomy group (8.0 ± 5.7 hours vs 18.8 ± 14.6 hours; p < .05). Doctors recommended taking significantly less time off before returning to work for the patients in the LAP-RFA group compared with those in the myomectomy group (10.3 ± 5.1 days vs 14.5 ± 5.4 days; p < .05). The total number of days until back to normal activity was significantly lower in the LAP-RFA group compared with the myomectomy group (16.3 ± 15.2 days vs 26.5 ± 15.9 days; p < .05). CONCLUSION: The results from this 12-month follow-up study suggest that LAP-RFA is a safe, effective, uterine-sparing alternative to laparoscopic myomectomy in the treatment of ULs. These data points build on previously published studies showing that LAP-RFA has lower healthcare resource use overall, including lower postprocedure hospitalization rate and shorter length of stay. In clinical practice, LAP-RFA is a promising treatment approach to ULs for women.

Vaginal ultrasound-guided Pouch of Douglas robotic entry in a live ovine model and human female cadaveric specimens.

We aimed to determine whether intraoperative ultrasound is a feasible tool for visualization of the pouch of Douglas (POD) to facilitate a safe vaginal entry for direct robotic vaginal trocar insertion for pelvic floor surgery. Endovaginal ultrasound-guided needle insertion of a trocar into the POD was performed in six fresh frozen female cadavers and a live sheep animal model. Using an endovaginal probe the POD was identified as a fluid-filled space clear of bowel or adhesions, then a Veress needle was also used to confirm POD localization. Access to the POD was achieved using a robotic trocar designed for this purpose. The animal study was approved by the Ethics Committee of Asaf-Harofe hospital. Direct visualization during laparoscopy in cadavers and open cadaveric dissections confirmed safe POD entry and accurate trocar placement. This method was found feasible in the development of a safe vaginal entry in both the animal and cadaveric model, possibly negating the need for laparoscopic umbilical observation.

Evaluation of the American College of Surgeons National Surgical Quality Improvement Program Risk Calculator to predict outcomes after hysterectomies.

OBJECTIVE: To evaluate the American College of Surgeons (ACS) surgical risk calculator's reliability in predicting outcomes in hysterectomies. METHODS: This is a prospective cohort study at a large community-based hospital. Twenty-one preoperative and postoperative criteria were abstracted from the electronic medical record and entered into the online ACS calculator to determine a risk score. Logistical regression was used to determine the association between risk score and actual outcome. The prediction capability was analyzed with c-statistic, Hosmer-Lemeshow, and Brier score. RESULTS: A total of 634 hysterectomies were performed during the study period from January to April 2019. Patients were predominantly 55 years old, white (53%) and overweight (body mass index 30). Predicted perioperative adverse events were significantly higher than actual adverse events across all domains. In all, 54/634 (8.5%) patients experienced postoperative urinary tract infection. C-statistics for return to operating room, renal failure, and readmission were 0.607 (95% C Statistic index [CI] 0.370-0.845), 0.882 (95% CI 0.802-0.962), 0.637 (95% CI 0.524-0.750), respectively. Brier scores approached one in all categorical domains. CONCLUSION: The ACS surgical risk calculator holds the promise of predicting postoperative complications or length of stay for patients undergoing hysterectomy. Further adjustment to this tool is required before it can be advocated for use in the clinical setting.

Consensus Definitions and Interpretation Templates for Magnetic Resonance Imaging of Defecatory Pelvic Floor Disorders: Proceedings of the Consensus Meeting of the Pelvic Floor Disorders Consortium of the American Society of Colon and Rectal Surgeons, the Society of Abdominal Radiology, the International Continence Society, the American Urogynecologic Society, the International Urogynecological Association, and the Society of Gynecologic Surgeons.

The Pelvic Floor Disorders Consortium (PFDC) is a multidisciplinary organization of colorectal surgeons, urogynecologists, urologists, gynecologists, gastroenterologists, radiologists, physiotherapists, and other advanced care practitioners. Specialists from these fields are all dedicated to the diagnosis and management of patients with pelvic floor conditions, but they approach, evaluate, and treat such patients with their own unique perspectives given the differences in their respective training. The PFDC was formed to bridge gaps and enable collaboration between these specialties. The goal of the PFDC is to develop and evaluate educational programs, create clinical guidelines and algorithms, and promote high quality of care in this unique patient population. The recommendations included in this article represent the work of the PFDC Working Group on Magnetic Resonance Imaging of Pelvic Floor Disorders (members listed alphabetically in Table 1). The objective was to generate inclusive, rather than prescriptive, guidance for all practitioners, irrespective of discipline, involved in the evaluation and treatment of patients with pelvic floor disorders.

The Fresh Frozen Cadaveric Study of Direct Pouch of Douglas Laparoscopic and Robotic Trocar Insertion for Vaginal Natural Orifice Transluminal Endoscopic Surgery.

STUDY OBJECTIVE: To determine the distances and angles that assure a safe entry into the pouch of Douglas (POD) during blind laparoscopic and robotic trocar entry. DESIGN: Trocars were inserted into the POD of 4 intact fresh frozen female pelves. Cadaveric dissection was performed, and the distance from the POD to the sacrum at rest and with maximal pressure to POD with the trocar was measured. In addition, the optimal angle for trocar insertion and entry was evaluated. SETTING: Inova Advanced Simulation and Technology Evaluation Center. PATIENTS: Fresh frozen cadavers with intact reproductive organs. INTERVENTIONS: Vaginal POD trocar insertion. MEASUREMENTS AND MAIN RESULTS: Measurements were recorded from the sacrum to the POD at rest and from the sacrum to the hymen with trocar pressure. The dissection demonstrated correct trocar placement in the POD of human cadaveric specimens. The mean distances from the sacrum to the hymen, the sacrum to the POD, and the sacrum to the POD with pressure were 18.75 cm, 9.75 cm, and 7.25 cm, respectively. After the deployment of the trocar, the tip was observed to be 2 cm below the cervix in the POD. The mean trocar angle to clear the sacral promontory and the neurovascular structures without injury to the uterus was 25° to 40° from the horizontal plane and 15° to 30° from the coronal plane. CONCLUSION: A direct trocar entry into the POD has been found to be feasible in fresh frozen cadaveric specimens. This study provided valuable information for the angle of entry into the POD to facilitate vaginal and robotic trocar entry for minimally invasive gynecologic procedures.