Inflammatory Cells in Control and Prolapsed Uterosacral Ligament Tissue.

Pelvic organ prolapse (POP), a downward descent of the vagina and/or uterus through the vaginal canal, is a prevalent condition affecting up to 40% of women. Several risk factors of POP have been identified, including childbirth, connective tissue defects, and chronic intra-abdominal pressure; however, the underlying etiologies of POP development are not fully understood, leading to a high burden on patients and the healthcare systems. The uterosacral ligaments are key support structures of the uterus and upper vagina. Our previous work describes observed histopathological changes in uterosacral ligament (USL) tissue and demonstrates the presence of neutrophils in a subgroup of POP individuals. This presence of neutrophils prompted an examination for the presence of a broader spectrum of inflammatory cell types in the USL. Immunohistochemical staining was performed to identify neutrophils, lymphocytes, macrophages, and mast cells outside of the vasculature. All 4 inflammatory cell types were increased in the POP-HQ system-defined POP-Inflammatory (POP-I) phenotype USL tissue relative to the USL tissues of control or other POP-HQ phenotypes. Focal T-lymphocyte and macrophage co-accumulations were observed in the arterial walls from some patients of the POP-vascular (POP-V) phenotype suggesting previous arterial injury. In addition, 1 control and 2 POP-V subjects' USLs contained arterial wall foamy macrophages, evidence of atherosclerosis. These findings further support a complex etiology for POP and indicate that personalized approaches to preventing and treating the condition may be warranted.

Estrogen and Androgen Receptor Status in Uterosacral Ligaments of Women with Pelvic Organ Prolapse Stratified by the Pelvic Organ Prolapse Histology Quantification System.

Menopause is a significant risk factor for pelvic organ prolapse (POP), suggesting that ovarian sex steroids play a major role in the etiology of the condition. POP results from failure of the uterine-cervix-vagina support structures, including the uterosacral ligament (USL). We previously identified consistent degenerative USL phenotypes that occur in POP and used their characteristics to develop a standardized POP Histologic Quantification System (POP-HQ). In this study, POP and matched control USL tissue was first segregated into the unique POP-HQ phenotypes, and specimens were then compared for estrogen receptor (ER) alpha (ERα), ERbeta (ERß), the G-protein estrogen receptor (GPER), and androgen receptor (AR) content via immunohistochemical staining. ER and AR expression levels in the control USL tissues were indistinguishable from those observed in the POP-A phenotype, and partially overlapped with those of the POP-I phenotype. However, control-USL steroid receptor expression was statistically distinct from the POP-V phenotype. This difference was driven mainly by the increased expression of GPER and AR in smooth muscle, connective tissue, and endothelial cells, and increased expression of ERα in connective tissue. These findings support a multifactorial etiology for POP involving steroid signaling that contributes to altered smooth muscle, vasculature, and connective tissue content in the USL. Furthermore, these data support the concept that there are consistent and distinct degenerative processes that lead to POP and suggest that personalized approaches are needed that target specific cell and tissues in the pelvic floor to treat or prevent this complex condition.

Clinical applications of pelvic floor imaging: opinion statement endorsed by the society of abdominal radiology (SAR), American Urological Association (AUA), and American Urogynecologic Society (AUGS).

Pelvic floor dysfunction is prevalent, with multifactorial causes and variable clinical presentations. Accurate diagnosis and assessment of the involved structures commonly requires a multidisciplinary approach. Imaging is often complementary to clinical assessment, and the most commonly used modalities for pelvic floor imaging include fluoroscopic defecography, magnetic resonance defecography, and pelvic floor ultrasound. This collaboration opinion paper was developed by representatives from multiple specialties involved in care of patients with pelvic floor dysfunction (radiologists, urogynecologists, urologists, and colorectal surgeons). Here, we discuss the utility of imaging techniques in various clinical scenarios, highlighting the perspectives of referring physicians. The final draft was endorsed by the Society of Abdominal Radiology (SAR), American Urogynecologic Society (AUGS), and the American Urological Association (AUA).

Using the novel pelvic organ prolapse histologic quantification system to identify phenotypes in uterosacral ligaments in women with pelvic organ prolapse.

BACKGROUND: Pelvic organ prolapse is common, but the underlying etiologies are poorly understood, which limits our current prevention and treatment options. OBJECTIVE: Our primary objective was to compare the uterosacral ligament histologic features in women with and without prolapse using the novel pelvic organ prolapse histologic quantification system. Our secondary aim was to determine whether composite histologic findings in uterosacral ligaments are associated with prolapse risk factors. STUDY DESIGN: This was a prospective cohort study in which paracervical uterosacral ligament biopsies were performed at the time of hysterectomy for primary prolapse or other benign gynecologic indications and processed for histologic evaluation. The pelvic organ prolapse quantification system was used to determine the prolapse stage. In this study, 9 prominent histologic features were semiquantitatively scored using the pelvic organ prolapse histologic quantification system in a blinded fashion and compared between prolapse and control groups. Unbiased principal component analysis of these scores was independently performed to identify potential relationships between histologic measures and prolapse risk factors. RESULTS: The histologic scores of 81 prolapse and 33 control ligaments were analyzed. Compared with the control group, women in the prolapse group were significantly older and more likely to be in the menopausal phase. There was no difference in the number of vaginal deliveries, body mass index, hormone use, or smoking status between the groups. To control for baseline differences, patients were also stratified by age over 40 years and menopausal status. Compared with the control group, the prolapse ligaments in the premenopausal group had significantly more loss of smooth muscle fibers within the fascicles (P<.001), increased inflammatory infiltrates of neutrophils within the tissue and perineural inflammatory cells (P<.01 and P=.04, respectively), and reduced neointimal hyperplasia (P=.02). Prolapse ligaments in the postmenopausal group exhibited elevated adipose content compared with that of the control group (P=.05). Amount of fibrillar collagen, total nonvascular smooth muscle, and muscle fiber vesicles of prolapse ligaments did not differ in either the premenopausal or postmenopausal group compared with that of the control group. Unbiased principal component analysis of the histologic scores separated the prolapse ligaments into 3 phenotypes: (1) increased adipose accumulation, (2) increased inflammation, and (3) abnormal vasculature, with variable overlap with controls. Posthoc analysis of these subgroups demonstrated a positive correlation between increasing number of vaginal deliveries and body mass index with increasing adipose content in the adipocyte accumulation and inflammatory phenotype and increasing neointimal hyperplasia in the vascular phenotype. However, only the relationship between vaginal delivery and adipocytes was significant in the adipose phenotype (R2=0.13; P=.04). CONCLUSION: Histologic phenotypes exist in pelvic support ligaments that can be distinguished using the pelvic organ prolapse histologic quantification system and principle component analysis. Vaginal delivery is associated with aberrant adipose accumulation in uterosacral ligaments. Our findings support a multifactorial etiology for pelvic organ prolapse contributing to altered smooth muscle, vasculature, and connective tissue content in crucial pelvic support structures. To confirm these associations and evaluate the biomechanical properties of histologic phenotypes of prolapse, larger studies are warranted. Closing this gap in knowledge will help optimize personalized medicine and help identify targets for prevention and treatment of this complex condition.

The complex relationship between urinary and defecatory disorders in young and adolescent girls.

PURPOSE OF REVIEW: Scientific advancements have led to enhanced clarity about the interrelationship between urinary tract pathology and functional bowel disturbances. The present article will review the current literature regarding the cause, pathophysiology, diagnosis, and treatment of lower urinary tract dysfunction and abnormal bowel habits in young and adolescent girls. RECENT FINDINGS: Complex neurological, physiological mechanisms and functional behaviors exist that contribute to the development of coexisting urinary symptoms and defecatory disorders in young and adolescent girls. Bladder bowel dysfunction (BBD) in childhood and adolescence is carried into adulthood creating a lifetime health burden. SUMMARY: Practitioners should be aware and actively screen for conditions mimicking BBD with time-efficient and effective history-taking and physical exams that reduce anxiety and fear. The present review provides guide to comprehensive treatment strategies for managing complex pelvic floor disorders including urinary incontinence, defecatory disorders, pelvic and perineal pain, and constipation. More research is needed to elucidate pathophysiology and optimal treatment strategies of the BBD.

Knowledge of Pelvic Floor Disorders in Obstetrics.

OBJECTIVES: The aim of this study was to investigate knowledge and demographic factors associated with a lack of knowledge proficiency about urinary incontinence (UI) and pelvic organ prolapse (POP) among pregnant and postpartum women. METHODS: This was a cross-sectional survey of women receiving antepartum and postpartum care at 9 Connecticut sites. Knowledge was assessed using the validated Prolapse and Incontinence Knowledge Questionnaire. Lack of knowledge proficiency was defined as less than 80% and less than 50% correct responses on the Prolapse and Incontinence Knowledge Questionnaire UI and POP subscales. Logistic regression was used to evaluate unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs). P < 0.05 was considered statistically significant. RESULTS: Surveys from 399 diverse pregnant and postpartum women were analyzed. Three quarters showed a lack of knowledge proficiency about UI and POP (74.2%, 70.6%). After adjustment, increased odds of lacking UI knowledge proficiency were associated with primiparity versus nulliparity (OR, 4.73; 95% CI, 2.24-9.98), Hispanic versus white race (OR, 2.72; 95% CI, 1.18-6.01), and having a high school diploma/General Education Development/less (OR, 3.17; 95% CI, 1.34-7.48) or some college (OR, 2.55; 95% CI, 1.08-6.01) versus bachelor's degree; greater lack of POP knowledge proficiency was associated with having a high school diploma/General Education Development versus bachelor's degree (OR, 2.11; 95% CI, 1.05-4.26) and never seeing a urologist/urogynecologist versus those who had (OR, 0.30; 95% CI, 0.12-0.77). Women working in a medical field versus those who did not demonstrated decreased odds of lacking UI and POP knowledge proficiency (ORs, 0.26 [95% CI, 0.13-0.52] and 0.38 [95% CI, 0.21-0.70]). CONCLUSIONS: Pregnant and postpartum women lack knowledge about UI and POP. Preconceptional counseling provides an opportunity for educational intervention.

The Effects of a Genital Vibratory Stimulation Device on Sexual Function and Genital Sensation.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of a genital vibratory stimulation device in improving sexual function in women with arousal and orgasm disorders. METHODS: In this single-arm, prospective study, baseline and 1- and 3-month assessments were performed to evaluate women with sexual arousal and/or orgasmic disorders, who received therapy using a genital vibratory stimulation device. Sexual function, satisfaction, and distress were evaluated using the Female Sexual Function Index (FSFI), the Female Sexual Distress Scale, and the Female Intervention Efficacy Index questionnaires. Genital sensation was evaluated using quantitative sensory testing. RESULTS: Seventy women, aged 19 to 64 years, were evaluated from October 2009 to August 2013. Forty-seven (67.1%) and 37 (52.9%) women completed 1- and 3-month follow-ups, respectively. The FSFI arousal and orgasm domain scores and total FSFI scores improved at 1 and 3 months (P < 0.001 for all outcomes). Mean (SD) total FSFI scores increased from 20.04 (4.65) (baseline) to 25.03 (5.21) (1 month) to 26.66 (5.42) (3 months; both Ps < 0.0001). Female Sexual Distress Scale scores reflected significantly decreased distress at 1 (P = 0.0006) and 3 (P < 0.0001) months compared with baseline and at 3 months compared with 1 month (P = 0.03). Neurological sensation was increased at all genital sites at 1 and 3 months (P < 0.0001 for all). After adjustment for age, there was a significant interaction between arousal domain scores and clitoral and right labial sensation. At 3 months, perceptions of increased vaginal lubrication, orgasm, and genital sensation were reported by 67.5%, 65.0%, and 82.5% of the participants. No major adverse events were noted. CONCLUSIONS: Genital vibratory stimulation device use resulted in uniform improvements in sexual function, satisfaction, sexually related distress and genital sensation.

Comparative histology of mouse, rat, and human pelvic ligaments.

INTRODUCTION AND HYPOTHESIS: The uterosacral (USL) and cardinal ligaments (CL) provide support to the uterus and pelvic organs, and the round ligaments (RL) maintain their position in the pelvis. In women with pelvic organ prolapse (POP), the connective tissue, smooth muscle, vasculature, and innervation of the pelvic support structures are altered. Rodents are commonly used animal models for POP research. However, the pelvic ligaments have not been defined in these animals. In this study, we hypothesized that the gross anatomy and histological composition of pelvic ligaments in rodents and humans are similar. METHODS: We performed an extensive literature search for anatomical and histological descriptions of the pelvic support ligaments in rodents. We also performed anatomical dissections of the pelvis to define anatomical landmarks in relation to the ligaments. In addition, we identified the histological components of the pelvic ligaments and performed quantitative analysis of the smooth muscle bundles and connective tissue of the USL and RL. RESULTS: The anatomy of the USL, CL, and RL and their anatomical landmarks are similar in mice, rats, and humans. All species contain the same cellular components and have similar histological architecture. However, the cervical portion of the mouse USL and RL contain more smooth muscle and less connective tissue compared with rat and human ligaments. CONCLUSION: The pelvic support structures of rats and mice are anatomically and histologically similar to those of humans. We propose that both mice and rats are appropriate, cost-effective models for directed studies in POP research.

The Effect of Body Mass Index on Pelvic Floor Support 1 Year Postpartum.

Elevated body mass index (BMI) is associated with the incidence, prevalence, and progression of pelvic organ prolapse (POP). This study investigated the effect of peripartum BMI on pelvic floor support 1 year postpartum (PP1y). One hundred eight nulliparous women had their BMI recorded and underwent POP assessments using the Pelvic Organ Prolapse Quantification System at baseline, third trimester (36th to 38th week of pregnancy [G36-38w]), and PP1y. Pelvic organ prolapse was defined as ≥stage II. Women gained on average 1.9 kg between baseline and PP1y. After adjustment, increasing BMI PP1y was associated with increasing anterior wall descent (P < .0001) and higher odds of having POP PP1y (odds ratio: 1.41, 95% confidence interval: 1.01-1.97, P = .045). Trial of labor compared to unlabored cesarean delivery, POP G36-38w, and decreased fetal weight were independently associated with anterior vaginal wall laxity PP1y. Our finding suggests that postpartum BMI influences pelvic floor laxity 1 year after delivery. Postpartum weight reduction may serve as a strategy for POP prevention in some women.

Les†lanternes†rouges: the race for information about cycling-related female sexual dysfunction.

INTRODUCTION: Cycling is growing in popularity among women. As in men, it is associated with genital neuropathies and decreased sensation in female riders. However, there is a gap in research and information addressing the relationship between cycling and female sexual dysfunction (FSD) in women. AIMS: To review the literature investigating pelvic floor injuries and sexual dysfunction in female cyclists. METHODS: Searches in several electronic databases were conducted, and relevant articles that met the inclusion criteria were identified for critical review. MAIN OUTCOME MEASURES: The main outcome measure to be determined was the strength of the current body of evidence in published literature of a correlation between cycling-related pelvic floor injuries and FSD. RESULTS: Data on FSD from cycling-related injuries in women are limited. Research indicates that bicycle setup and riding equipment may be contributing factors. Women's ergonomics and physiology interact differently with the bicycle than men's. Current evidence offers insufficient foundation to recommend various effect-mitigating equipment and products. CONCLUSIONS: While gender-specific cycling products offer a promising direction for protecting women riders, studies addressing FSD and pelvic floor injuries in women cyclists are inadequate to indicate clear etiology or provide treatment recommendations. Current evidence is also insufficient to recommend effect-mitigating equipment and products.

Clitoral epidermoid cyst presenting as pseudoclitoromegaly of pregnancy.

Objective Acquired clitoromegaly is rare and may result from hormonal and nonhormonal causes, and evaluation of the pregnant patient with clitoromegaly invokes a specific set of differential diagnoses. Methods Case report. Results We describe the case of a young woman with pregnancy-associated clitoral enlargement whose hormonal evaluation proved negative. Further investigation concluded that an epidermoid cyst was the culprit of her pseudoclitoromegaly. The patient underwent successful surgical resection and has had no recurrence at her subsequent pregnancy. Conclusion We review the differential diagnosis of clitoromegaly, including hormonal and nonhormonal causes, with focus on the evaluation of pregnancy-associated clitoromegaly.

Impact of the 2011 FDA transvaginal mesh safety update on AUGS members' use of synthetic mesh and biologic grafts in pelvic reconstructive surgery.

OBJECTIVE: To describe the frequency of use and recent change in use of synthetic mesh and biologic grafts in pelvic organ prolapse (POP) and stress urinary incontinence surgery by American Urogynecology Society (AUGS) members. METHODS: An electronic survey of AUGS members was conducted between December 2011 and January 2012. Frequency of graft use in POP (overall and by transvaginal and transabdominal approaches) and stress urinary incontinence surgery was queried relative to the timing of the 2011 Food and Drug Administration (FDA) safety update. Rates of materials' use before and after the statement were compared using Wilcoxon signed rank test. RESULTS: Fifty-three percent (507/962) of AUGS members responded and were included in analysis; 79% were urogynecologists. Before the FDA warning, in POP surgery, most (90%) used synthetic mesh and fewer (34%) used biologic grafts; 99% used synthetic mesh slings. After the FDA statement, respondents reported an overall decrease in the percent of POP cases in which they used synthetic mesh (P < 0.001) but no change in biologic graft use for POP (P = 0.37) or synthetic mesh sling use (P = 0.10). Specifically, transvaginal mesh use decreased: 40% reported decreased use and 12% stopped use. However, transvaginal mesh was still used by 61% of respondents in at least some cases. No change (62%) or increased use (12%) of mesh was reported for transabdominal POP procedures. CONCLUSIONS: Synthetic mesh use in transvaginal POP surgery decreased after the 2011 FDA safety update, but synthetic mesh use for transabdominal POP repair and sling procedures and overall biologic graft use in POP surgery did not decrease.

Cost-effectiveness of endometrial evaluation prior to morcellation in surgical procedures for prolapse.

OBJECTIVE: The objective of the study was to compare the cost-effectiveness of 3 screening options for endometrial cancer in asymptomatic, postmenopausal women prior to undergoing morcellation in minimally invasive supracervical hysterectomy and minimally invasive sacral colpopexy for the treatment of pelvic organ prolapse. STUDY DESIGN: A decision tree model was constructed to compare no screening, endometrial biopsy, and transvaginal ultrasound for asymptomatic, postmenopausal women prior to surgery. Effectiveness was measured by life-years. The incremental cost-effectiveness ratio, defined as the difference in cost between 2 screening options divided by the difference in life-years between the 2 options, was calculated in 2012 US dollars for endometrial biopsy and transvaginal ultrasound, in comparison with no screening. RESULTS: Using an endometrial cancer prevalence of 0.6% and a 40% risk of upstaging after morcellation, the expected per-patient cost was $8800, $9023, and $9112 over 5 years for no screening, endometrial biopsy, and transvaginal ultrasound, respectively. The expected life-years saved compared with no screening were 0.00108 for endometrial biopsy and 0.00105 for transvaginal ultrasound, ie, 0.39 and 0.38 days, respectively. The estimated incremental cost-effectiveness ratio was $207,348 for endometrial biopsy and $298,038 for transvaginal ultrasound compared with no screening. A sensitivity analysis showed that the prevalence of endometrial cancer and the risk of endometrial cancer upstaging after morcellation had the greatest impact on the cost-effectiveness of screening. CONCLUSION: For asymptomatic, postmenopausal women, preoperative endometrial evaluation via endometrial biopsy or transvaginal ultrasound helps improve the preoperative detection of endometrial cancer, but universal screening is not cost effective.

Sexual function in older women after oophorectomy.

OBJECTIVE: To compare the sexual function of older women who had bilateral oophorectomy with that of older women who had retained their ovaries. METHODS: This cross-sectional study involved analysis of 1,352 women aged 57 to 85 years from the National Social Life, Health, and Aging Project. Women with previous bilateral oophorectomy were compared with women who retained their ovaries. The primary outcome of interest was self-report of sexual ideation, chosen because having thoughts about sexual experiences is not prohibited by either a partner or a woman's own physical limitations. RESULTS: Three hundred fifty-six (25.8%) women reported previous bilateral oophorectomy. Our analysis achieved 90% power to detect a difference of 10% in sexual ideation. No significant difference in the report of sexual ideation was found between women with previous bilateral oophorectomy and women who retained their ovaries (54.5% and 95% confidence interval [CI] 48.1-61.0 compared with 49.9% and 95% CI 45.3-54.5, P=.230), even after adjusting for current hormone therapy, age, education, and race (adjusted odds ratio 1.32, 95% CI 0.96-1.80). CONCLUSION: Bilateral oophorectomy may not play a pivotal role in sexual ideation and function among older women. LEVEL OF EVIDENCE: II.

The bar sinister: does handlebar level damage the pelvic floor in female cyclists?

INTRODUCTION: Cycling is associated with genital neuropathies and erectile dysfunction in males. Women riders also have decreased genital sensation; however, sparse information exists addressing the effects of modifiable risks on neurological injuries in females. AIM: This study assesses the effects of bicycle setup and cyclists' attributes on GS and saddle pressures among female cyclists. METHODS: Previously, we compared genital sensation in competitive female cyclists (N = 48) to that of female runners (N = 22). The current study is a subanalysis of the 48 cyclists from the original study group. Nonpregnant, premenopausal women who rode at least 10 miles per week, 4 weeks per month were eligible for participation. MAIN OUTCOME MEASURES: Genital sensation was measured in microns using biosthesiometry measures of vibratory thresholds (VTs). Perineal and total saddle pressures were determined using a specialized pressure map and recorded in kilopascals (kPA). RESULTS: Handlebars positioned lower than the saddle correlated with increased perineum saddle pressures and decreased anterior vaginal and left labial genital sensation (P < 0.05, P < 0.02, P < 0.03, respectively). Low handlebars were not associated with total saddle pressures or altered genital sensation in other areas. After adjusting for age and saddle type, low handlebars were associated with a 3.47-kPA increase in mean perineum saddle pressures (P < 0.04) and a 0.86-micron increase in anterior vagina VT (P < 0.01). CONCLUSION: Handlebars positioned lower than the saddle were significantly associated with increased perineum saddle pressures and decreased genital sensation in female cyclists. Modifying bicycle setup may help alleviate neuropathies in females. Additional research is warranted to further assess the extent of the associations.

Women's bike seats: a pressing matter for competitive female cyclists.

INTRODUCTION: There are numerous genital complaints in women cyclists, including pain, numbness, and edema of pelvic floor structures. Debate ensues about the best saddle design for protection of the pelvic floor. AIM: To investigate the relationships between saddle design, seat pressures, and genital nerve function in female, competitive cyclists. METHODS: We previously compared genital sensation in healthy, premenopausal, competitive women bicyclists and runners. The 48 cyclists from our original study comprise the study group in this subanalysis. MAIN OUTCOME MEASURES: Main outcome measures were: (i) genital vibratory thresholds (VTs) determined using the Medoc Vibratory Sensation Analyzer 3000 and (ii) saddle pressures as determined using a specially designed map sensor. RESULTS: More than half of the participants (54.8%) used traditional saddles, and the remainder (45.2%) rode with cut-out saddles. On bivariate analysis, use of traditional saddles was associated with lower mean perineal saddle pressures (MPSP) than riding on cut-out saddles. Peak perineal saddle pressures (PPSP) were also lower; however, the difference did not reach statistical significance. Saddle design did not affect mean or peak total saddle pressures (MTSP, PTSP). Saddle width was significantly associated with PPSP, MTSP, and PTSP but not with MPSP. Women riding cut-out saddles had, on average, a 4 and 11 kPa increase in MPSP and PPSP, respectively, compared with women using traditional saddles (P = 0.008 and P = 0.010), after adjustment for other variables. Use of wider saddles was associated with lower PPSP and MTSP after adjustment. Although an inverse correlation was seen between saddle pressures and VTs on bivariate analysis, these differences were not significant after adjusting for age. CONCLUSION: Cut-out and narrower saddles negatively affect saddle pressures in female cyclists. Effects of saddle design on pudendal nerve sensory function were not apparent in this cross-sectional analysis. Longitudinal studies evaluating the long-term effects of saddle pressure on the integrity of the pudendal nerve, pelvic floor, and sexual function are warranted.

Cesarean scar ectopic pregnancy: case series and review of the literature.

Cesarean scar ectopic pregnancy is becoming increasingly common at tertiary care hospitals around the world. It is a condition in which the embryo implants within the myometrium at the site of a previous cesarean hysterotomy, and it can occur in women with only one prior cesarean delivery. We present four cases of cesarean scar ectopic pregnancy diagnosed within a 6-month period between 2007 and 2008. Their initial presentations and management are discussed, followed by a review of the published literature summarizing both diagnostic and management recommendations.