Maternal urinary vascular endothelial growth factor (VEGF) versus N.T. pro brain natriuretic peptide (NT-pro BNP) as novel biomarkers for placental accreta spectrum (PAS): A case-control study.

This study planned to compare the predictive ability of maternal urinary vascular endothelial growth factor (VEGF) versus N-terminal pro B-type natriuretic peptide (NT-pro BNP) for prediction of placenta accreta spectrum (PAS). This was a prospective case-control study carried out in a tertiary university hospital. It included pregnant women between 37-39 weeks. The study included 50 pregnant women classified in two groups. Group (Ι, n=25) were pregnant women with PAS, and group (II, n=25) women with uncomplicated pregnancies, as controls. Urine samples were collected, and quantitative analyses of VEGF and NT-pro BNP were performed by ELISA. VEGF was assessed with a cut point of 215.6 pg/ml and NT-pro BNP with a cut point of 182.2 pg/ml to predict the condition of PAS. Both biomarkers were good predictors of PAS with the area under the ROC curve (AUC) equal to (0.871 and 0.904), respectively. However, maternal urinary VEGF levels could predict PAS better than NT-pro BNP (OR=9.967, 95%CI 2.032-48.879, p=0.005) versus (OR=8.066, 95% CI 1.520 - 42.811, p=0.014) in NT-pro BNP. In conclusion, third trimester urinary levels of both VEGF and NT-pro BNP appear to be s crucially good predictors for PAS. However, VEGF is superior to NT-pro BNP in predicting women with PAS. These biomarkers present promising candidates as they can help to detect patients at high probability of PAS. They can be assessed by non-invasive, simple, and low-cost procedures.

The use of ultrasound sliding sign for prediction of adhesions in women undergoing repeated caesarean section.

We carried out this study to validate the use of ultrasound sliding sign to predict intraperitoneal adhesions in women undergoing repeated caesarean section (CS). A cross-section study was performed in women with at least one CS scheduled for an elective CS. We used the sliding sign of the uterus against the anterior abdominal wall to assess intraperitoneal adhesions, positive sliding sign if uterus moved freely and a negative sliding sign if limited mobility. The obstetrician was blind to the ultrasound results, asked to report if adhesions were absent or present during CS to validate accuracy of the sliding sign. We examined 120 women, negative sliding was reported in 54 patients, positive sliding in 66 women. The presence of intra-abdominal adhesions was confirmed in 44/54 cases assigned to the high-risk group, while the prediction of low risk for adhesions confirmed in 66/66 patients with a sensitivity of 100%, specificity of 86.84%. Sliding sign is an effective method to detect intra-abdominal adhesions in women with a history of repeated caesarean delivery.Impact statementWhat is already known on this subject? There has been a dramatic increase in the caesarean section (CS) rate worldwide; repeated CSs may be associated with intraperitoneal adhesions that result in difficulty during the procedure and may be related to bowel or bladder injuries and neonatal morbidities.What do the results of this study add? The sliding sign by ultrasound has a sensitivity of 100%, specificity of 86.84%, a positive predictive value of 81.5, a negative predictive value of 100, and accuracy of 91.67, considering it rapid, easy and reliable method for prediction of intraperitoneal adhesions.What are the implications of these findings for clinical practice and/or future research? The use of sliding sign by ultrasound in cases with repeated CSs offers a good predictor tool for presence of intraperitoneal adhesions and subsequently avoid severe sequels during surgery and good preparation.

Medical Management of Uterine Arteriovenous Malformation: A Case Series.

BACKGROUND: There has been increasing interest in medical management of uterine Arteriovenous Malformations (AVMs) in hemodynamically stable patients as a means of decreasing the need for invasive treatment that may impact fertility. CASES: Amongst six cases of sonographically diagnosed uterine AVM managed medically with combined oral contraceptive pills or medroxyprogesterone acetate, three experienced complete resolution and three experienced partial resolution. Amongst those with complete resolution, all had a subsequent pregnancy that had no complication attributable to previous AVM or medical therapy. Amongst those with partial resolution, one is currently pregnant, one remains on therapy, and one has discontinued treatment with resumption of normal menses. CONCLUSION: Medical management is effective in completely or partially resolving uterine AVMs. Subsequent pregnancies in this population are feasible and are not at higher risk for perinatal complications.

A new grading system for female sexual dysfunction based on the female sexual function index in Egyptian women: a cross-sectional study.

OBJECTIVE: To provide a grading system that accurately reflects the grades of female sexual dysfunction (FSD) severity. PATIENTS AND METHODS: A cross-sectional study was conducted in Assiut University Hospital. It included 500 women who answered the Arabic version of the Female Sexual Function Index (FSFI) after getting their consent. A gradient of FSD severity was created, classifying FSD into five grades: severe, moderate, mild to moderate, mild, and no FSD. RESULTS: According to our grading system, FSD was detected in 339 women (67.8 %); Mild FSD in 20.4%, mild to moderate in 41.6%, moderate in 15.3%, and severe in 22.7%. Mean scores of desire show a linear trend of reduction from 3.8 in mild to 3.36 in mild to moderate to 2.25 in moderate and markedly reduced to 2.1 in severe grade. This difference was highly statistically significant (p= 0.002). The same was reported in arousal, orgasm, and satisfaction domains, while in lubrication and pain domains, the difference was not statistically significant. CONCLUSION: In this study, our grading system was complementary to the FSFI. Moreover, it seems to be more practical and useful in grading the severity of FSD.

Lidocaine-prilocaine cream versus local infiltration anesthesia in pain relief during repair of perineal trauma after vaginal delivery: a systematic review and meta-analysis.

Background: Perineal trauma is a common problem that may affect women during vaginal delivery; this trauma can be either spontaneous (tear) or intentional (episiotomy). When repair of perineal trauma is required, adequate analgesics must be obtained. Topical products as lidocaine-prilocaine (EMLA) cream is one of the suggested methods, but still there is lack of evidence with regard to its efficacy and safety.Objective: The aim of this review is to assess the evidence of utilizing EMLA cream in comparison to local perineal infiltration anesthesia for pain control during perineal repair after vaginal delivery.Data sources: Medline, Embase, Dynamed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov and the Cochrane Library were searched electronically from January 2006 to May 2018 for studies investigating the effect of lidocaine-prilocaine cream in relieving pain during repair of perineal trauma.Methods of study selection: All randomized controlled trials assessing effect of lidocaine-prilocaine cream versus local infiltration anesthesia in relieving pain during repair of perineal trauma were considered for this meta-analysis. Fifteen studies were identified of which four studies deemed eligible for this review. Quality and risk of bias assessment was performed for all studies.Data extraction: Two researchers independently extracted the data from the individual articles and entered into RevMan software. The weighted mean difference (WMD) and 95% confidence interval (CI) was calculated. Statistical heterogeneity between studies was assessed by the Higgins chi-square and (I2) statistics. When heterogeneity was significant, a random-effects model was used for meta-analysis. Otherwise, the fixed effect meta-analysis was used when there was no significant heterogeneity.Results: Pooled analysis of result in "pain score" was insignificant between the two groups (WMD -1.11; 95% CI (-2.55 to 0.33); p = .13). Furthermore, the use of additional analgesia showed no statistically significant difference between the two groups (WMD 1.34; 95% CI (0.66-2.71), p = .42). Regarding patient satisfaction, an overall analysis of three studies showed significant results favoring EMLA cream group users (WMD 4.65; 95% CI (1.96-11.03), p = .0005). The pooled analysis of the outcome "duration of repair" showed the significantly shorter duration of repair in EMLA cream users (n = 92) than local infiltration anesthesia (n = 95) (1.72 min; 95% CI (-2.76 to -0.67), p = .001).Conclusions: This meta-analysis suggests that topical lidocaine-prilocaine cream gives comparable results in reducing pain during perineal repair after vaginal delivery.

Effect of topical glyceryl trinitrate cream on pain perception during intrauterine device insertion in multiparous women: A randomized double-blinded placebo-controlled study.

OBJECTIVE: Intrauterine contraceptive device (IUD) insertion-related pain presents a push beyond the decline of women to use IUD for family planning. We aimed to investigate the analgesic effect of glyceryl trinitrate cream (GTN) in reducing pain during IUD insertion. MATERIALS AND METHODS: We conducted a randomized double-blinded placebo-controlled study (NCT02708251, clinicaltrials.gov) in a tertiary University hospital. Reproductive-aged women requesting Copper IUD for contraception were considered. Eligible women for IUD insertion were randomized (1:1) to glyceryl trinitrate cream (GTN arm) or Placebo. Three minutes before IUD insertion, 1 ml of GTN cream or placebo was applied to the cervical lip at the planned tenaculum site, followed by 1 ml placed in the cervical canal up to the level of the internal os using a Q-tip applicator. Our outcomes were the participant's self-rated pain perception utilizing a 10-cm Visual Analogue Scale (VAS) during cervical tenaculum placement, uterine sound and IUD insertion, then 15 min post-procedure. RESULTS: 100 women were enrolled and randomized to GTN arm (n = 50) or placebo (n = 50). Women in the GTN arm reported lower VAS scores during tenaculum placement, sound and IUD insertion (median: 2 vs. 4, p < 0.0001; 2.5 vs. 4.5, p < 0.001;3 vs. 5.5, p < 0.0001, respectively). Higher ease of insertion score was also determined among GTN arm (mean ± SD: 6.9 ± 1.15 vs. 4.7 ± 1.38, p < 0.0001). Additionally, women in the GTN arm were more satisfied by the end of the insertion (92% vs. 74%, p = 0.003). CONCLUSION: Application of cervical GTN cream before IUD insertion seems to reduce the induced pain with subsequent easy insertion.

Repeated recovery of immature oocytes in a woman with a previous history of empty follicle syndrome.

The empty follicle syndrome (EFS) is defined as a failure to aspirate any oocyte (s) from the follicles after ovarian hyperstimulation in preparation for IVF/ICSI. It is a frustrating and vague syndrome; and a controversial one concerning its existence, causes and possible treatment. Recurrent EFS or the recovery of immature oocytes thereafter is a more challenging problem. Delayed injection after leaving the immature oocytes for in vitro-maturation (IVM) has been suggested to be a possible option if immature oocytes are retrieved. Here, we present a case of repeated retrieval of a few immature oocytes after a first incidence of EFS. IVM was tried twice for those immature oocytes. Unfortunately, in this case IVM was unsuccessful and the oocytes failed to mature in vitro. Assistance is required for future management of these unfortunate couples.

Prospective Cohort of Deep Dyspareunia in an Interdisciplinary Setting.

INTRODUCTION: Deep dyspareunia is a common symptom in women, including in half of women with endometriosis, but little is known about its response to treatment and predictors of persistent deep dyspareunia over time. AIM: To follow up deep dyspareunia severity over a 1-year prospective cohort at an interdisciplinary center, and to identify baseline predictors of more persistent deep dyspareunia at 1 year. METHODS: Prospective 1-year cohort study at a tertiary referral center for pelvic pain and endometriosis, where a range of interdisciplinary treatments are provided at a single center (surgical, hormonal, physical, and psychological therapies). Exclusion criteria were menopause, age >50 years, and never previously sexually active. Primary outcome (deep dyspareunia severity) and secondary outcome (sexual quality of life) were followed up over 1 year. Ordinal logistic regression was performed, controlling for baseline severity of deep dyspareunia, to identify baseline predictors of deep dyspareunia severity at 1 year. MAIN OUTCOME MEASURE: Primary outcome was severity of deep dyspareunia on an 11-point numeric rating scale (0-10), categorized into absent-mild (0-3), moderate (4-6), and severe (7-10); secondary outcome was sexual quality of life measured by the Endometriosis Health Profile-30. RESULTS: 1-year follow-up was obtained for 278 subjects (56% response rate at 1 year; 278/497). Severity of deep dyspareunia improved over the 1 year (McNemar test, P < .0001): the proportion of patients in the severe category decreased from 55.0% to 30.4%, the moderate category remained similar from 17.7% to 25.0%, and the absent-mild category increased from 27.3% to 44.6%. Sexual quality of life also improved (56% to 43% on the sex subscale of the Endometriosis Health Profile-30) (Welch t test, P < .001). On ordinal regression, severity of deep dyspareunia at 1 year was independently associated with younger age (OR = 0.94, 95% CI = 0.91-0.97, P = .008), and with a higher baseline depression score on the Patient Health Questionnaire-9 (OR = 1.07, 95% CI = 1.03-1.11, P = .01). CLINICAL IMPLICATIONS: Clinicians should consider employing an interdisciplinary approach for deep dyspareunia, and screening for and treating depression symptoms in these women. STRENGTH & LIMITATIONS: Strengths of the study include its prospective nature, and assessment of deep dyspareunia specifically (as opposed to superficial dyspareunia). Limitations include non-randomized design, and the patients lost to follow-up over the 1 year. CONCLUSION: Over 1 year in an interdisciplinary setting, improvements were observed in deep dyspareunia and sexual quality of life, but younger women and those with more severe depression at baseline had more persistent deep dyspareunia at 1 year. Yong PJ, Williams C, Bodmer-Roy S, et al. Prospective Cohort of Deep Dyspareunia in an Interdisciplinary Setting. J Sex Med 2018;15:1765-1775.

Chronic pelvic pain in an interdisciplinary setting: 1-year prospective cohort.

BACKGROUND: Chronic pelvic pain affects ∼15% of women, and presents a challenging problem for gynecologists due to its complex etiology involving multiple comorbidities. Thus, an interdisciplinary approach has been proposed for chronic pelvic pain, where these multifactorial comorbidities can be addressed by different interventions at a single integrated center. Moreover, while cross-sectional studies can provide some insight into the association between these comorbidities and chronic pelvic pain severity, prospective longitudinal cohorts can identify comorbidities associated with changes in chronic pelvic pain severity over time. OBJECTIVE: We sought to describe trends and factors associated with chronic pelvic pain severity over a 1-year prospective cohort at an interdisciplinary center, with a focus on the role of comorbidities and controlling for baseline pain, demographic factors, and treatment effects. STUDY DESIGN: This was a prospective 1-year cohort study at an interdisciplinary tertiary referral center for pelvic pain and endometriosis, which provides minimally invasive surgery, medical management, pain education, physiotherapy, and psychological therapies. Exclusion criteria included menopause or age >50 years. Sample size was 296 (57% response rate at 1 year; 296/525). Primary outcome was chronic pelvic pain severity at 1 year on an 11-point numeric rating scale (0-10), which was categorized for ordinal regression (none-mild 0-3, moderate 4-6, severe 7-10). Secondary outcomes included functional quality of life and health utilization. Baseline comorbidities were endometriosis, irritable bowel syndrome, painful bladder syndrome, abdominal wall pain, pelvic floor myalgia, and validated questionnaires for depression, anxiety, and catastrophizing. Multivariable ordinal regression was used to identify baseline comorbidities associated with the primary outcome at 1 year. RESULTS: Chronic pelvic pain severity decreased by a median 2 points from baseline to 1 year (6/10-4/10, P < .001). There was also an improvement in functional quality of life (42-29% on the pain subscale of the Endometriosis Health Profile-30, P < .001), and a reduction in subjects requiring a physician visit (73-36%, P < .001) or emergency visit (24-11%, P < .001) in the last 3 months. On multivariable ordinal regression for the primary outcome, chronic pelvic pain severity at 1 year was independently associated with a higher score on the Pain Catastrophizing Scale at baseline (odds ratio, 1.10; 95% confidence interval, 1.00-1.21, P = .04), controlling for baseline pain, treatment effects (surgery), age, and referral status. CONCLUSION: Improvements in chronic pelvic pain severity, quality of life, and health care utilization were observed in a 1-year cohort in an interdisciplinary setting. Higher pain catastrophizing at baseline was associated with greater chronic pelvic pain severity at 1 year. Consideration should be given to stratifying pelvic pain patients by catastrophizing level (rumination, magnification, helplessness) in research studies and in clinical practice.

The effect of low-dose aspirin on fetal weight of idiopathic asymmetrically intrauterine growth restricted fetuses with abnormal umbilical artery Doppler indices: a randomized clinical trial.

OBJECTIVE: To investigate the effect of aspirin on fetal weight in fetuses with idiopathic asymmetrical intrauterine growth restriction (IUGR) complicated by abnormal umbilical artery Doppler indices. MATERIALS AND METHODS: The study was a randomized controlled trial conducted at Woman's Health Hospital, Assiut, Egypt, between June 2016 and the January 2017 included 60 pregnant women (28-30 weeks) with idiopathic asymmetrical IUGR associated with abnormal umbilical artery Doppler indices. Women were randomly assigned to group I (aspirin 75 mg) daily for four weeks or group II (no intervention). The primary outcome was the fetal weight after four weeks. Secondary outcomes included Doppler blood flow changes in the umbilical artery plus delivery and neonatal outcomes. RESULTS: The estimated fetal weight and umbilical artery blood flow increased significantly in aspirin group (p = .00) when compared with no intervention group. As regard neonatal outcomes; aspirin group showed better results and encouraging outcomes (p < .05). CONCLUSIONS: Aspirin improves fetal weight and umbilical artery blood flow in idiopathic asymmetrical IUGR fetuses complicated by abnormal umbilical artery Doppler blood flow.

Anatomic Sites and Associated Clinical Factors for Deep Dyspareunia.

INTRODUCTION: Deep dyspareunia negatively affects women's sexual function. There is a known association between deep dyspareunia and endometriosis of the cul-de-sac or uterosacral ligaments in reproductive-age women; however, other factors are less clear in this population. AIM: To identify anatomic sites and associated clinical factors for deep dyspareunia in reproductive-age women at a referral center. METHODS: This study involved the analysis of cross-sectional baseline data from a prospective database of 548 women (87% consent rate) recruited from December 2013 through April 2015 at a tertiary referral center for endometriosis and/or pelvic pain. Exclusion criteria included menopausal status, age at least 50 years, previous hysterectomy or oophorectomy, and not sexually active. We performed a standardized endovaginal ultrasound-assisted pelvic examination to palpate anatomic structures for tenderness and reproduce deep dyspareunia. Multivariable regression was used to determine which tender anatomic structures were independently associated with deep dyspareunia severity and to identify clinical factors independently associated with each tender anatomic site. MAIN OUTCOME MEASURE: Severity of deep dyspareunia on a numeric pain rating scale of 0 to 10. RESULTS: Severity of deep dyspareunia (scale = 0-10) was independently associated with tenderness of the bladder (b = 0.88, P = .018), pelvic floor (levator ani) (b = 0.66, P = .038), cervix and uterus (b = 0.88, P = .008), and cul-de-sac or uterosacral ligaments (b = 1.39, P < .001), but not with the adnexa (b = -0.16, P = 0.87). The number of tender anatomic sites was significantly correlated with more severe deep dyspareunia (Spearman r = 0.34, P < .001). For associated clinical factors, greater depression symptom severity was specifically associated with tenderness of the bladder (b = 1.05, P = .008) and pelvic floor (b = 1.07, P < .001). A history of miscarriage was specifically associated with tenderness of the cervix and uterus (b = 2.24, P = .001). Endometriosis was specifically associated with tenderness of the cul-de-sac or uterosacral ligaments (b = 3.54, P < .001). CONCLUSIONS: In reproductive-age women at a tertiary referral center, deep dyspareunia was independently associated not only with tenderness of the cul-de-sac and uterosacral ligaments but also with tenderness of the bladder, pelvic floor, and cervix and uterus. Yong PJ, Williams C, Yosef A, et al. Anatomic Sites and Associated Clinical Factors for Deep Dyspareunia. Sex Med 2017;5:e184-e195.

Ovarian reserve after salpingectomy: a systematic review and meta-analysis.

INTRODUCTION: Although there has been a growing concern over the possible damaging effect of salpingectomy on ovarian reserve, this issue remains uncertain. The purpose of this meta-analysis was to test the hypothesis that salpingectomy may compromise ovarian reserve. MATERIAL AND METHODS: A detailed search was conducted using MEDLINE, Embase, Dynamed Plus, ScienceDirect, TRIP database and the Cochrane Library from January 2000 to November 2016. All cohort, cross-sectional and randomized controlled studies investigating changes in circulating anti-Müllerian hormone (AMH) after salpingectomy were considered. Thirty-seven studies were identified, of which eight were eligible. Data were extracted and entered into RevMan software for calculation of the weighted mean difference (WMD) and 95% CI. Two groups of studies were analyzed separately: group 1 (six studies, n = 464) comparing data before and after salpingectomy and group 2 (two studies) comparing data in women who have undergone salpingectomy (n = 169) vs. healthy controls (n = 154). RESULTS: Pooled results of group 1 studies showed no statistically significant change in serum AMH concentration after salpingectomy (WMD, -0.10 ng/mL; 95% CI -0.19 to 0.00, I2 = 0%). Similarly, meta-analysis of group 2 showed no statistically significant difference in serum AMH concentration between salpingectomy group and controls (WMD, -0.11 ng/mL; 95% CI -0.37 to 0.14, I2 = 77%). Subgroup analyses based on laterality of surgery, type of AMH kit and participants' age (<40 years) still showed no statistically significant changes in circulating AMH. CONCLUSION: Salpingectomy does not seem to compromise ovarian reserve in the short-term. However, the long-term effect of salpingectomy on ovarian reserve remains uncertain.

The impact of laparoscopic ovarian drilling on AMH and ovarian reserve: a meta-analysis.

Laparoscopic ovarian drilling (LOD) has been widely used as an effective treatment of anovulatory women with polycystic ovarian syndrome (PCOS). However, there has been a growing concern over a possible damaging effect of this procedure on ovarian reserve. The objective of this study was to investigate the hypothesis that LOD compromises ovarian reserve as measured by post-operative changes in circulating anti-Müllerian hormone (AMH). This meta-analysis included all cohort studies as well as randomised controlled trials (RCTs) investigating serum AMH concentrations and other ovarian reserve markers in women with PCOS undergoing LOD. Various databases were searched including MEDLINE, EMBASE, Dynamed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov and Cochrane Library from January 2000 to December 2016. Sixty studies were identified, of which seven were deemed eligible for this review. AMH data were extracted from each study and entered into the RevMan software to calculate the weighted mean difference (WMD) between pre- and post-operative values. Pooled analysis of all studies (n = 442) revealed a statistically significant decline in serum AMH concentration after LOD (WMD -2.13 ng/mL; 95% confidence interval (CI) -2.97 to -1.30). Subgroup analysis based on duration of follow-up, AMH kit, laterality of surgery and amount of energy applied during LOD consistently showed a statistically significant fall in serum AMH concentration. In conclusion, although LOD seems to markedly reduce circulating AMH, it remains uncertain whether this reflects a real damage to ovarian reserve or normalisation of the high pre-operative serum AMH levels. Further long-term studies on ovarian reserve after LOD are required to address this uncertainty.

Multifactorial contributors to the severity of chronic pelvic pain in women.

BACKGROUND: Chronic pelvic pain affects ∼15% of women, and is associated with significant societal cost and impact on women's health. Identifying factors involved in chronic pelvic pain is challenging due to its multifactorial nature and confounding between potential factors. For example, while some women with endometriosis have chronic pelvic pain, there may be comorbid conditions that are implicated in the chronic pelvic pain rather than the endometriosis itself. OBJECTIVE: We sought to explore multifactorial variables independently associated with the severity of chronic pelvic pain in women. STUDY DESIGN: We used baseline cross-sectional data from an ongoing prospective cohort, collected from patient online questionnaires, physical examination, and physician review of medical records. Participants were recruited from a tertiary referral center for endometriosis and chronic pelvic pain in Vancouver, British Columbia, Canada, from December 2013 through April 2015. Exclusion criteria included menopausal status or age >50 years. Primary outcome was self-reported severity of chronic pelvic pain in the last 3 months (0-10 numeric rating scale). Potential associated factors ranged from known pain conditions assessed by standard diagnostic criteria, validated psychological questionnaires, musculoskeletal physical exam findings, as well as pain-related, reproductive, medical/surgical, familial, demographic, and behavioral characteristics. Mann-Whitney, Kruskal-Wallis, or Spearman test were used to identify variables with an association with the primary outcome (P < .05), followed by multivariable linear regression to control for confounding and to identify independent associations with the primary outcome (P < .05). RESULTS: Overall, 656 women were included (87% consent rate), of whom 55% were diagnosed with endometriosis. The following factors were independently associated with higher severity of chronic pelvic pain: abdominal wall pain (P = .005), pelvic floor tenderness (P = .004), painful bladder syndrome (P = .019), higher score on Pain Catastrophizing Scale (P < .001), adult sexual assault (P = .043), higher body mass index (P = .023), current smoking (P = .049), and family history of chronic pain (P = .038). Severity of chronic pelvic pain was similar between women with and without endometriosis. CONCLUSION: Multifactorial variables independently associated with severity of chronic pelvic pain were identified, ranging from myofascial/musculoskeletal, urological, family history, and psycho-social factors. Continued research is required to validate these factors and to determine whether any are potentially modifiable for the management of chronic pelvic pain.

Nerve Bundles and Deep Dyspareunia in Endometriosis.

The etiology of deep dyspareunia in endometriosis is unclear. Our objective was to determine whether nerve bundle density in the cul-de-sac/uterosacrals (zone II) is associated with deep dyspareunia in women with endometriosis. We conducted a blinded retrospective immunohistochemistry study (n = 58) at a tertiary referral center (2011-2013). Patients were stringently phenotyped into a study group and 2 control groups. The study group (tender endometriosis, n = 29) consisted of patients with deep dyspareunia, a tender zone II on examination, and an endometriosis lesion in zone II excised at surgery. Control group 1 (nontender endometriosis, n = 17) consisted of patients without deep dyspareunia, a nontender zone II on examination, and an endometriosis lesion in zone II excised at surgery. Control group 2 (tender nonendometriosis, n = 12) consisted of patients with deep dyspareunia, a tender zone II on examination, and a nonendometriosis lesion (eg, normal histology) in zone II excised at surgery. Protein gene product 9.5 (PGP9.5) immunohistochemistry was performed to identify nerve bundles (nerve fibers surrounded by perineurium) in the excised zone II lesion. PGP9.5 nerve bundle density (bundles/high powered field [HPF]) was then scored by a pathologist blinded to the group. We found a significant difference in PGP9.5 nerve bundle density between the 3 groups (analysis of variance, F2,55 = 6.39, P = .003). Mean PGP9.5 nerve bundle density was significantly higher in the study group (1.16 ± 0.56 bundles/HPF [±standard deviation]) compared to control group 1 (0.65 ± 0.36, Tukey test, P = .005) and control group 2 (0.72 ± 0.56, Tukey test, P = .044). This study provides evidence that neurogenesis in the cul-de-sac/uterosacrals may be an etiological factor for deep dyspareunia in endometriosis.