Vaginal and rectal microbiome contribute to genital inflammation in chronic pelvic pain.

BACKGROUND: Chronic pelvic pain (CPP) is a multifactorial syndrome that can substantially affect a patient's quality of life. Endometriosis is one cause of CPP, and alterations of the immune and microbiome profiles have been observed in patients with endometriosis. The objective of this pilot study was to investigate differences in the vaginal and gastrointestinal microbiomes and cervicovaginal immune microenvironment in patients with CPP and endometriosis diagnosis compared to those with CPP without endometriosis and no CPP. METHODS: Vaginal swabs, rectal swabs, and cervicovaginal lavages (CVL) were collected among individuals undergoing gynecologic laparoscopy. Participants were grouped based on patients seeking care for chronic pain and/or pathology results: CPP and endometriosis (CPP-Endo) (n = 35), CPP without endometriosis (n = 23), or patients without CPP or endometriosis (controls) (n = 15). Sensitivity analyses were performed on CPP with endometriosis location, stage, and co-occurring gynecologic conditions (abnormal uterine bleeding, fibroids). 16S rRNA sequencing was performed to profile the microbiome, and a panel of soluble immune mediators was quantified using a multiplex assay. Statistical analysis was conducted with SAS, R, MicrobiomeAnalyst, MetaboAnalyst, and QIIME 2. RESULTS: Significant differences were observed between participants with CPP alone, CPP-Endo, and surgical controls for body mass index, ethnicity, diagnosis of ovarian cysts, and diagnosis of fibroids. In rectal microbiome analysis, both CPP alone and CPP-Endo exhibited lower alpha diversity than controls, and both CPP groups revealed enrichment of irritable bowel syndrome-associated bacteria. CPP-Endo exhibited an increased abundance of vaginal Streptococcus anginosus and rectal Ruminococcus. Patients with CPP and endometrioma (s) demonstrated increased vaginal Streptococcus, Lactobacillus, and Prevotella compared to other endometriosis sites. Further, abnormal uterine bleeding was associated with an increased abundance of bacterial vaginosis-associated bacteria. Immunoproteomic profiles were distinctly clustered by CPP alone and CPP-Endo compared to controls. CPP-Endo was enriched in TNF⍺, MDC, and IL-1⍺. CONCLUSIONS: Vaginal and rectal microbiomes were observed to differ between patients with CPP alone and CPP with endometriosis, which may be useful in personalized treatment for individuals with CPP and endometriosis from those with other causes of CPP. Further investigation is warranted in patients with additional co-occurring conditions, such as AUB/fibroids, which add additional complexity to these conditions and reveal the enrichment of distinct pathogenic bacteria in both mucosal sites. This study provides foundational microbiome-immunoproteomic knowledge related to chronic pelvic pain, endometriosis, and co-occurring gynecologic conditions that can help improve the treatment of patients seeking care for pain.

The Effect of Patient Positioning on Ureteral Efflux During Intraoperative Cystoscopy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To identify the relationship between patient position during surgery and time to confirmation of ureteral patency on cystoscopy. DESIGN: Randomized controlled trial. SETTING: Academic tertiary care medical center. PATIENTS OR PARTICIPANTS: A total of 91 adult women undergoing laparoscopic (either conventional or robotic) hysterectomy between February 2021 and February 2022 were randomized to intervention (n = 45) or control (n = 46). Exclusion criteria included known kidney disease or urinary tract anomaly, current ureteral stent, pregnancy, malignancy, and recognized intraoperative urinary tract injury. INTERVENTIONS: Subjects in the control group were placed in a 0° supine position during cystoscopy. Subjects in the intervention group were placed in a 20° angle in reverse Trendelenburg (RT) position during cystoscopy. MEASUREMENTS AND MAIN RESULTS: The primary outcome, time to confirmation of bilateral ureteral patency, was measured at the time the second ureteral jet was viewed during intraoperative cystoscopy. There was no significant difference in mean time to confirmation (66.5 seconds in supine vs 67 seconds in RT, p = .2) nor in total cystoscopy time (111 seconds in supine vs 104.5 seconds in RT, p = .39). There were no significant differences in need for alternative modalities to aid in ureteral efflux visualization, delayed diagnosis of ureteric injury, and operative time. RT position seemed to have reduced the time to confirmation for the small group of patients with longer confirmation time (>120 seconds). CONCLUSION: RT position does not change time to confirmation of bilateral ureteral patency compared with supine position. However, there may be a benefit in position change if time to confirmation is >120 seconds.

The surgical gender gap: the impact of surgeon gender in medicine and gynecologic surgery.

PURPOSE OF REVIEW: The purpose of this review is to summarize the current literature evaluating the effect of surgeon gender on patient outcomes and satisfaction, and the impact of gender bias on female surgeons. RECENT FINDINGS: The proportion of female physicians has increased in recent years, especially in Obstetrics and Gynecology. Recent literature assessing this impact supports equivalent or superior medical and surgical outcomes for women surgeons and physicians. It also reveals superior counseling and communication styles as perceived by patients. However, women in medicine receive lower patient ratings in competence, medical knowledge, and technical skills despite the existing evidence. Additionally, female physicians experience pay inequality, limited advancement opportunities, higher prevalence of microaggressions, and higher rates of burnout. SUMMARY: Recognition of gender bias is essential to correcting this issue and improving the negative impact it has on female physicians, our patients, and the field of women's health.

Impact of Retained Cystoscopy Fluid after Laparoscopic Hysterectomy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To investigate the impact of retained cystoscopy fluid after laparoscopic hysterectomy on time to spontaneous void, time to discharge, urinary retention, bladder discomfort, and patient satisfaction. DESIGN: Single-blind randomized controlled trial. SETTING: An academic medical center. PATIENTS: One hundred and twenty patients who underwent laparoscopic hysterectomy with universal cystoscopy for benign indications, excluding pelvic organ prolapse and urinary incontinence indications. INTERVENTIONS: From October 10, 2018, to October 17, 2019, we compared 200 mL retained cystoscopy fluid and complete bladder emptying after laparoscopic hysterectomy with universal cystoscopy. MEASUREMENTS AND MAIN RESULTS: A total of 120 patients were enrolled and randomized (59 in the retained cystoscopy fluid group and 61 in the emptied fluid group). The primary outcome was time to first spontaneous void. The secondary outcomes were time to discharge, urinary retention rates, bladder discomfort, and patient satisfaction. A sample size of 120 was calculated to detect a 57-minute difference in time to spontaneous void. There were minimal differences in baseline demographics and surgical characteristics between the groups. There was an apparent, although not significant, difference in time to void of 25 minutes (143 minutes vs 168 minutes, p = .20). Time to discharge and urinary retention rates did not differ (199 minutes vs 214 minutes, p = .40, and 13.6% vs 8.2%, p = .51, respectively). There was no difference in postoperative bladder discomfort and patient satisfaction. CONCLUSION: Retained cystoscopy fluid after laparoscopic hysterectomy did not significantly affect time to first spontaneous void, time to discharge, urinary retention, bladder discomfort, or patient satisfaction.

Perioperative pain management in minimally invasive gynecologic surgery.

PURPOSE OF REVIEW: The purpose of this review is to summarize the most recent evidence-based interventions for perioperative pain management in minimally invasive gynecologic surgery. RECENT FINDINGS: With particular emphasis on preemptive interventions in recent studies, we found preoperative counseling, nutrition, exercise, psychological interventions, and a combination of acetaminophen, celecoxib, and gabapentin are highly important and effective measures to reduce postoperative pain and opioid demand. Intraoperative local anesthetics may help at incision sites, as a paracervical block, and a transversus abdominus plane block. Postoperatively, an effort should be made to utilize non-narcotic interventions such as abdominal binders, ice packs, simethicone, bowel regimens, gabapentin, and scheduled NSAIDs and acetaminophen. When prescribing narcotics, providers should be aware of recommended amounts of opioids required per procedure so as to avoid overprescribing. SUMMARY: Our findings emphasize the evolving importance of preemptive interventions, including prehabilitation and pharmacologic agents, to improve postoperative pain after minimally invasive gynecologic surgery. Additionally, a multimodal approach to nonnarcotic intraoperative and postoperative interventions decreases narcotic requirement and improves opioid stewardship.

Smooth Muscle Cells in Pelvic Washings at Time of Benign Hysterectomy.

STUDY OBJECTIVE: To evaluate if smooth muscle cells can be detected in pelvic washings at the time of intact hysterectomy. DESIGN: A multicentered pilot cohort study (Canadian Task Force classification II-2). SETTING: Two academically affiliated tertiary referral centers. PATIENTS: Patients undergoing total hysterectomy for benign indications without morcellation by minimally invasive gynecologic surgeons were enrolled from January 2018 to July 2018. INTERVENTIONS: Pelvic washings were collected at 2 times during surgery: after abdominal entry and after vaginal cuff closure. Cell blocks were generated, and slides were stained using hematoxylin and eosin, smooth muscle actin, and desmin and interpreted by 1 expert pathologist at each institution. MEASUREMENTS AND MAIN RESULTS: Thirty-eight subjects were recruited; 3 subjects were excluded because of unplanned morcellation. Smooth muscle uterine cells were detected in 1 prewash specimen and 2 postwash specimens. The group with positive washings was noted to have longer procedure times (136 vs 114 minutes), lower blood loss (25 vs 86 mL), and higher uterine weight (242 vs 234 g) compared with negative washings group. CONCLUSION: Tissue dissemination of uterine cells may be possible at the time of hysterectomy. Larger prospective studies are needed to better describe the incidence of and risk factors for tissue dissemination.

Practice patterns and postoperative complications before and after US Food and Drug Administration safety communication on power morcellation.

BACKGROUND: In April 2014, the US Food and Drug Administration (FDA) published its first safety communication discouraging "the use of laparoscopic power morcellation during hysterectomy or myomectomy for the treatment of women with uterine fibroids." Due to the concern of worsening outcomes for patients with occult uterine malignancy, specifically uterine leiomyosarcoma, the FDA recommended a significant change to existing surgical planning, patient consent, and surgical technique in the United States. OBJECTIVE: We sought to report temporal trends in surgical approach to hysterectomy and postoperative complications before and after the April 17, 2014, FDA safety communication concerning the use of power morcellation during myomectomy or hysterectomy. STUDY DESIGN: A retrospective cohort study was performed with patients undergoing hysterectomy for benign indications in the Michigan Surgical Quality Collaborative from Jan. 1, 2013, through Dec. 31, 2014. The rates of abdominal, laparoscopic, and vaginal hysterectomy, as well as the rates of major postoperative complications and 30-day hospital readmissions and reoperations, were compared before and after April 17, 2014, the date of the original FDA safety communication. Major postoperative complications included blood transfusions, vaginal cuff infection, vaginal cuff dehiscence, ureteral obstruction, vesicovaginal fistula, deep and organ space surgical site infection, acute renal failure, respiratory failure, sepsis, pulmonary embolism, deep vein thrombosis requiring therapy, cerebral vascular accident, cardiac arrest, and death. We calculated the median episode cost related to hysterectomy readmissions using Michigan Value Collaborative data. Analyses were performed using robust multivariable multinomial and logistic regression models. RESULTS: There were 18,299 hysterectomies available for analysis during the study period. In all, 2753 cases were excluded due to an indication for cancer, cervical dysplasia, or endometrial hyperplasia, and 174 cases were excluded due to missing covariate data. Compared to the 15 months preceding the FDA safety communication, in the 8 months afterward, utilization of laparoscopic hysterectomies decreased by 4.1% (P = .005) and both abdominal and vaginal hysterectomies increased (1.7%, P = .112 and 2.4%, P = .012, respectively). Major surgical complications not including blood transfusions significantly increased after the date of the FDA safety communication, from 2.2-2.8% (P = .015), and the rate of hospital readmission within 30 days also increased from 3.4-4.2% (P = .025). The rate of all major surgical complications or hospital reoperations did not change significantly after the date of the FDA communication (P = .177 and P = .593, respectively). The median risk-adjusted total episode cost for readmissions was $5847 (interquartile range $5478-10,389). CONCLUSION: Following the April 2014 FDA safety communication regarding power morcellation, utilization of minimally invasive hysterectomy decreased, and major surgical, nontransfusion complications and 30-day hospital readmissions increased.

A Favorability Score for Vaginal Hysterectomy in a Statewide Collaborative.

STUDY OBJECTIVE: Because it is associated with fewer complications and more rapid recovery, the vaginal approach is preferred for benign hysterectomy. Patient characteristics that traditionally favor a vaginal approach include adequate vaginal access, small uterine size, and low suspicion for extrauterine disease. However, the low proportion of hysterectomies performed vaginally in the United States suggests that these data are not routinely applied in clinical practice. We sought to analyze the association of parity, prior pelvic surgery, and uterine weight with the use of the vaginal, laparoscopic, robotic, and abdominal approaches to hysterectomy. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: The Michigan Surgical Quality Collaborative is a statewide organization of 52 academic and community hospitals in Michigan funded by Blue Cross and Blue Shield of Michigan/Blue Care Network, including patients from all insurance payers. PATIENTS: Five thousand six hundred eight women undergoing hysterectomy for benign gynecologic conditions from January 1, 2013, through December 8, 2013, and included in the Michigan Surgical Quality Collaborative. INTERVENTIONS: To assess potential for vaginal hysterectomy, a favorability score of 0, 1, 2, or 3 was calculated by summing 1 point each for parity ≥1, no prior pelvic surgery, and uterine weight <250 g. Frequencies of surgical approaches to hysterectomy were compared using chi-square tests across favorability scores. MEASUREMENTS AND MAIN RESULTS: The use of robotic hysterectomy was most frequent (41.9%, n = 2349/5608) followed by abdominal (19.7%, n = 1103/5608), laparoscopic (14.4%, n = 809/5608), vaginal (13.5%, n = 758/5608), and laparoscopic-assisted vaginal (10.5%, n = 589/5608) hysterectomy. With favorability scores of 0, 1, 2, and 3, vaginal hysterectomy was performed in 0.6% (n = 1/167), 5% (n = 66/1324), 13.7% (n = 415/3036), and 25.5% (n = 276/1081) of cases and abdominal hysterectomy in 41.9% (n = 70/167), 30.8% (n = 408/1324), 17.5% (n = 531/3036), and 8.7% (n = 94/1081), respectively. There was little variation in the rates of laparoscopic hysterectomy (13.3%-16.8%, p = .429) and robotic hysterectomy (39.5%-42.4%, p = .518) across favorability scores. CONCLUSION: In a population of women undergoing hysterectomy in the state of Michigan, the use of vaginal and abdominal hysterectomy varied with respect to parity, prior pelvic surgery, and uterine weight, but there was little variation in the use of laparoscopic and robotic approaches. The favorability score could potentially be used as a quality improvement tool to evaluate practice patterns with respect to the use of various surgical approaches to hysterectomy.

Cervicovaginal Metabolome and Tumor Characteristics for Endometrial Cancer Detection and Risk Stratification.

PURPOSE: Endometrial cancer is highly prevalent and lacking noninvasive diagnostic techniques. Diagnosis depends on histological investigation of biopsy samples. Serum biomarkers for endometrial cancer have lacked sensitivity and specificity. The objective of this study was to investigate the cervicovaginal environment to improve the understanding of metabolic reprogramming related to endometrial cancer and identify potential biomarker candidates for noninvasive diagnostic and prognostic tests. EXPERIMENTAL DESIGN: Cervicovaginal lavages were collected from 192 participants with endometrial cancer (n = 66) and non-malignant conditions (n = 108), and global untargeted metabolomics was performed. Using the metabolite data (n = 920), we completed a multivariate biomarker discovery analysis. RESULTS: We analyzed grade 1/2 endometrioid carcinoma (n = 53) and other endometrial cancer subtypes (n = 13) to identify shared and unique metabolic signatures between the subtypes. When compared to non-malignant conditions, downregulation of proline (P < 0.0001), tryptophan (P < 0.0001), and glutamate (P < 0.0001) was found among both endometrial cancer groups, relating to key hallmarks of cancer including immune suppression and redox balance. Upregulation (q < 0.05) of sphingolipids, fatty acids, and glycerophospholipids was observed in endometrial cancer in a type-specific manner. Furthermore, cervicovaginal metabolites related to tumor characteristics, including tumor size and myometrial invasion. CONCLUSIONS: Our findings provide insights into understanding the endometrial cancer metabolic landscape and improvement in diagnosis. The metabolic dysregulation described in this article linked specific metabolites and pathophysiological mechanisms including cellular proliferation, energy supply, and invasion of neighboring tissues. Furthermore, cervicovaginal metabolite levels related to tumor characteristics, which are used for risk stratification. Overall, development of noninvasive diagnostics can improve both the acceptability and accessibility of diagnosis.

Impact of pneumoperitoneum pressure during laparoscopic hysterectomy: A randomized controlled trial.

OBJECTIVE: Minimally invasive hysterectomy is a commonly performed gynecologic procedure with associated postoperative pain managed with opioid medications. Uncontrolled postoperative pain leads to increased opioid use/abuse, longer hospital stays, increase in healthcare visits, and may negatively affect patient satisfaction. Current data suggests that reduced pneumoperitoneum insufflation pressure during laparoscopic surgery may impact postoperative pain. Given the current opioid epidemic, surgeons are proactively finding ways to reduce postoperative pain. It is unclear how reduced pneumoperitoneum pressure impacts the surgeon. We investigated the impact of reduced pneumoperitoneum insufflation pressure on surgeon satisfaction. STUDY DESIGN: This was a pilot, double-blinded, randomized controlled trial from March 2020 to July 2021 comparing pneumoperitoneum pressure of 15 mmHg to reduced pressures of 12 mmHg and 10 mmHg during laparoscopic hysterectomy. RESULTS: A total of 40 patients were randomized (13 - 15 mmHg, 13 - 12 mmHg, and 14 - 10 mmHg). The primary outcome was surgeon satisfaction. Secondary outcomes included patient satisfaction, operative time, blood loss, postoperative pain, opioid usage, and discharge timing. There were no differences in baseline demographics or perioperative characteristics. Surgeon satisfaction was negatively impacted with lower pneumoperitoneum pressures greatest with 10 mmHg, including overall satisfaction (p =.01), overall effect of the pneumoperitoneum (p =.04), and quality of visualization (p =.01). There was an apparent although not statistically significant difference in operative time (p =.06) and blood loss (p =.054). There was no difference in patient satisfaction, postoperative pain scores, opioid usage, or time to discharge. CONCLUSION(S): Reduced pneumoperitoneum insufflation pressure during laparoscopic hysterectomy negatively impacted surgeon satisfaction with a trend towards longer operative times and greater blood loss, and did not positively impact patient satisfaction, postoperative pain, opioid demand, or discharge timing.

Virtual reality for the treatment of postoperative pain after laparoscopic hysterectomy for benign Indications: A randomized controlled trial.

OBJECTIVE: The primary objective of this study was to determine if immediate post-operative use of virtual reality impacts pain scores or opioid consumption following hysterectomy. STUDY DESIGN: A randomized controlled trial was performed at a university associated tertiary referral hospital in the United States among patients undergoing laparoscopic hysterectomy for benign indications. Prior to surgery, participants were randomized to use a VR program versus routine care postoperatively in the post anesthesia care unit. Postoperative pain was measured using visual analogue scale, and morphine milligram equivalent to quantify narcotic usage. Patient satisfaction was assessed with a survey. A total of 15 patients were randomized to the virtual reality intervention and 15 to the standard care group. The test statistic was a one-sided T-test, with a significance level targeted of 0.05. Categorical variables were analyzed using chi-square analysis and t-test for continuous variables. Pain score differences between the virtual reality and standard care groups at each time assessment were compared using the Wilcoxon Rank Sum test. RESULTS: The use of virtual reality did not significantly affect pain scores or postoperative narcotics required; however, it did have a positive impact on the subject's perception of their postoperative course. No adverse events were reported. CONCLUSION: Although virtual reality use following hysterectomy did not improve pain scores or decrease narcotic usage, it was well received by patients.

COVID-19 vaccination and changes in the menstrual cycle among vaccinated persons.

OBJECTIVE: To describe the characteristics of people who experience changes to their menstrual cycle after COVID-19 vaccination. DESIGN: Longitudinal study. PATIENT(S): We recruited a volunteer sample with and without a history of SARS-CoV-2 infection who enrolled in the Arizona COVID-19 Cohort (CoVHORT) study and participated in a reproductive sub-cohort who were pre-menopausal, not pregnant, and had received a COVID-19 vaccine in 2021 (n = 545). EXPOSURE(S): Demographic and reproductive characteristics were collected via self-reports. MAIN OUTCOME MEASURE(S): Information on self-reported changes in the menstrual cycle after COVID-19 vaccination was collected from May 2021 to December 2021. We looked at demographic and reproductive characteristics as predictors of menstrual cycle change. RESULT(S): The majority of our vaccinated sample received the Pfizer-BioNTech vaccine (58%), and were 26-35 years old (51%), non-Hispanic (84%), and White (88%). Approximately 25% of vaccinated participants reported a change in their menstrual cycle after vaccination; the majority reported changes after their second dose (56%) as compared with their first (18%) and third (14%) doses. The most commonly reported changes were irregular menstruation (43%), increased premenstrual symptoms (34%), increased menstrual pain or cramps (30%), and abnormally heavy or prolonged bleeding (31%). High self-reported perceived stress levels compared with low perceived stress (OR, 2.22; 95% CI 1.12-4.37) and greater body mass index (OR, 1.04; 95% CI 1.00-1.07) were associated with greater odds of experiencing the menstrual cycle changes after the vaccination. Participants having a history of SARS-CoV-2 infection were less likely to report changes in their menstrual cycle after vaccination compared with the participants with no history of SARS-CoV-2 infection (OR, 0.58; 95% CI 0.32-1.04). CONCLUSION(S): Among vaccinated participants, approximately 25% of them reported predominantly temporary changes in the menstrual cycle, however, we are unable to determine whether these changes are due to normal cycle variability. The COVID-19 vaccines are safe and effective for everyone, including pregnant people and people trying to conceive; hence, these findings should not discourage vaccination.

The Effect of an Automated Order on Postpartum Opioid Use After Uncomplicated Vaginal Deliveries.

Background: To address the opioid epidemic, physicians are encouraged to identify means of reducing patient opioid exposure. Electronic medical records (EMRs) often include default order sets with automated orders for opioid medications, which may influence how much opioids physicians prescribe. We sought to evaluate the impact of de-selecting an automated order for oxycodone-acetaminophen from an EMR order set for postpartum vaginal deliveries on inpatient opioid exposure by comparing the proportion of patients who received an opioid after an uncomplicated vaginal delivery before and after the EMR change. As secondary outcomes, the impact on average total morphine milligram equivalents (MMEs) and discharge opioid prescriptions was investigated. Materials and Methods: A quality improvement study was conducted through retrospective chart review of uncomplicated vaginal deliveries for the four quarters before and after the EMR order set change occurred. The total proportion of patients who received an opioid in the postpartum period was then determined for the preexposure and postexposure groups. The total average MME consumed for patients who received an opioid in each group was determined and the total proportion of patients who received an opioid prescription at discharge was compared. Results: A total of 5826 records of uncomplicated vaginal deliveries met the criteria for analysis. In the preintervention group, 32.9% of patients received an opioid postpartum, compared to 12.5% of patients in the postintervention group, representing a decrease of 62.0% (p < 0.001). Of those who received opioids, the preintervention mean total opioid consumption was 28.4 MME (±27.6) compared to 33.6 MME (±46.4) postintervention, and there was no significant difference in median total opioid consumption: 22.5 MME (interquartile range [IQR]: 7.5-47.5) preintervention compared with 20.8 MME (IQR: 7.5-45.0) postintervention (p = 0.902). No significant difference was found with discharge opioid prescriptions between the two groups. Conclusion: Order sets within EMR systems appear to have a significant influence on physician prescribing behaviors and removing these automated orders for opioids should be considered.

Immunometabolic profiling of cervicovaginal lavages identifies key signatures associated with adenomyosis.

Adenomyosis is a burdensome gynecologic condition that is associated with pelvic pain, dysmenorrhea, and abnormal uterine bleeding, leading to a negative impact on quality of life; and yet is often left undiagnosed. We recruited 108 women undergoing hysterectomy for benign gynecologic conditions and collected non-invasive cervicovaginal lavage samples for immunometabolic profiling. Patients were grouped according to adenomyosis status. We investigated the levels of 72 soluble immune proteins and >900 metabolites using multiplex immunoassays and an untargeted global metabolomics platform. There were statistically significant alterations in the levels of several immune proteins and a large quantity of metabolites, particularly cytokines related to type II immunity and amino acids, respectively. Enrichment analysis revealed that pyrimidine metabolism, carnitine synthesis, and histidine/histamine metabolism were significantly upregulated pathways in adenomyosis. This study demonstrates utility of non-invasive sampling combined with immunometabolic profiling for adenomyosis detection and a greater pathophysiological understanding of this enigmatic condition.

Protein biomarkers in cervicovaginal lavages for detection of endometrial cancer.

BACKGROUND: Rates of endometrial cancer (EC) are increasing. For a definitive diagnosis, women undergo various time-consuming and painful medical procedures, such as endometrial biopsy with or without hysteroscopy, and dilation and curettage, which may create a barrier to early detection and treatment, particularly for women with inadequate healthcare access. Thus, there is a need to develop robust EC diagnostics based on non- or minimally-invasive sampling. The objective of this study was to quantify a broad range of immuno-oncology proteins in cervicovaginal lavage (CVL) samples and investigate these proteins as predictive diagnostic biomarkers for EC. METHODS: One hundred ninety-two women undergoing hysterectomy for benign or malignant indications were enrolled in this cross-sectional study. Classification of women to four disease groups: benign conditions (n = 108), endometrial hyperplasia (n = 18), low-grade endometrioid carcinoma (n = 53) and other EC subtypes (n = 13) was based on histopathology of biopsy samples collected after the surgery. CVL samples were collected in the operating room during the standard-of-care hysterectomy procedure. Concentrations of 72 proteins in CVL samples were evaluated using multiplex immunoassays. Global protein profiles were assessed using principal component and hierarchical clustering analyses. The relationships between protein levels and disease groups and disease severity were determined using Spearman correlation, univariate and multivariate receiver operating characteristics, and logistic regression analyses. RESULTS: Women with EC and benign conditions exhibited distinctive cervicovaginal protein profiles. Several proteins in CVL samples (e.g., an immune checkpoint protein, TIM-3, growth factors, VEGF, TGF-α, and an anti-inflammatory cytokine, IL-10) discriminated EC from benign conditions, particularly, when tested in combinations with CA19-9, CA125, eotaxin, G-CSF, IL-6, MCP-1, MDC, MCP-3 and TRAIL (sensitivity of 86.1% and specificity of 87.9%). Furthermore, specific biomarkers (e.g., TIM-3, VEGF, TGF-α, TRAIL, MCP-3, IL-15, PD-L2, SCF) associated with histopathological tumor characteristics, including histological type and grade, tumor size, presence and depth of myometrial invasion or mismatch repair protein status, implying their potential utility for disease prognosis or monitoring therapies. CONCLUSIONS: This proof-of-principle study demonstrated that cervicovaginal sampling coupled with multiplex immunoassay technology can offer a minimally to non-invasive method for EC detection.

Mindfulness Effects in Obstetric and Gynecology Patients During the Coronavirus Disease 2019 (COVID-19) Pandemic: A Randomized Controlled Trial.

OBJECTIVE: To assess the effect of a consumer-based mobile meditation application (app) on wellness in outpatient obstetric and gynecology patients during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted a randomized controlled trial at a university outpatient clinic of obstetric and gynecology patients during the COVID-19 pandemic. Women were randomly assigned to the intervention group, who was prescribed a mobile meditation app for 30 days, or the control group, which received standard care. The primary outcome was self-reported perceived stress. Secondary outcomes included self-reported depression, anxiety, sleep disturbance, and satisfaction with the meditation app. A sample size of 80 participants (40 per group) was calculated to achieve 84% power to detect a 3-point difference in the primary outcome. RESULTS: From April to May 2020, 101 women were randomized in the study-50 in the meditation app group and 51 in the control group. Analysis was by intention-to-treat. Most characteristics were similar between groups. Perceived stress was significantly less in the intervention group at days 14 and 30 (mean difference 4.27, 95% CI 1.30-7.24, P=.005, d=0.69 and mean difference 4.28, 95% CI 1.68-6.88, P=.002, d=0.69, respectively). Self-reported depression and anxiety were significantly less in the intervention group at days 14 and 30 (depression: P=.002 and P=.04; anxiety: P=.01, and P=.04, respectively). Sleep disturbance was significantly less in the intervention group at days 14 and 30 (P=.001 and P=.02, respectively). More than 80% of those in the intervention group reported high satisfaction with the meditation app, and 93% reported that mindfulness meditation improved their stress. CONCLUSION: Outpatient obstetric and gynecology patients who used the prescribed consumer-based mobile meditation app during the COVID-19 pandemic had significant reductions in perceived stress, depression, anxiety, and sleep disturbance compared with standard care. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04329533.

The role of gut and genital microbiota and the estrobolome in endometriosis, infertility and chronic pelvic pain.

BACKGROUND: Endometriosis is a chronic, burdensome condition that is historically understudied. Consequently, there is a lack of understanding of the etiology of the disease and its associated symptoms, including infertility and chronic pelvic pain (CPP). Endometriosis development is influenced by estrogen metabolism and inflammation, which are modulated by several factors including the microbiome and the estrobolome (the collection of genes encoding estrogen-metabolizing enzymes in the gut microbiome). Therefore, there is increasing interest in understanding the role of microbiota in endometriosis etiology. OBJECTIVE AND RATIONALE: To date, there is no cure for endometriosis and treatment options often are ineffective. This manuscript will review the potential relationship between the microbiome and endometriosis, infertility and CPP and highlight the available data on the microbiome in relation to endometriosis and its related symptoms. The overarching goal of this manuscript is to inform future microbiome research that will lead to a deeper understanding of the etiology of the disease and possible diagnostic modalities and treatments. The potential impact of the microbiome on estrogen regulation modulated by the estrobolome, as well as inflammation and other endometriosis-promoting mechanisms within the genital tract, will be reviewed. The methodological limitations of microbiome-related studies will be critically assessed to provide improved guidelines for future microbiome and clinical studies. SEARCH METHODS: PubMed databases were searched using the following keywords: endometriosis AND microbiome, infertility AND microbiome, pelvic pain AND microbiome, IVF (in-vitro fertilization) AND microbiome, endometriosis AND infertility. Clinical and preclinical animal trials that were eligible for review, and related to microbiome and endometriosis, infertility or CPP were included. All available manuscripts were published in 2002-2021. OUTCOMES: In total, 28 clinical and 6 animal studies were included in the review. In both human and animal studies, bacteria were enriched in endometriosis groups, although there was no clear consensus on specific microbiota compositions that were associated with endometriosis, and no studies included infertility or CPP with endometriosis. However, bacterial vaginosis-associated bacteria and Lactobacillus depletion in the cervicovaginal microbiome were associated with endometriosis and infertility in the majority (23/28) of studies. Interpretation of endometrial studies is limited owing to a variety of methodological factors, discussed in this review. In addition, metadata outlining antibiotic usage, age, race/ethnicity, menopausal status and timing of sample collection in relation to diagnosis of endometriosis was not consistently reported. Animal studies (6/6) support a bidirectional relationship between the gut microbiota and endometriosis onset and progression. WIDER IMPLICATIONS: There is evidence that a dysbiotic gut or genital microbiota is associated with multiple gynecologic conditions, with mounting data supporting an association between the microbiome and endometriosis and infertility. These microbiomes likely play a role in the gut-brain axis, which further supports a putative association with the spectrum of symptoms associated with endometriosis, including infertility and CPP. Collectively, this review highlights the demand for more rigorous and transparent methodology and controls, consistency across the field, and inclusion of key demographic and clinical characteristics of disease and comparison participants. Rigorous study designs will allow for a better understanding of the potential role of the microbiome in endometriosis etiology and the relationship to other disorders of the female reproductive tract.

Prospective randomized controlled trial comparing cephalad migration in robotic gynecologic surgery using egg-crate foam versus the Pink Pad®.

The objectives of the study were to compare the cephalad migration of two patient positioning pads used in robotic gynecologic surgery and to determine if any correlation exists between cephalad movement and time in Trendelenburg position or body mass index. This was a prospective randomized controlled open-label trial (Canadian Task Force classification I). Sixty women undergoing robotic-assisted laparoscopic gynecologic surgery were randomized to the Pink Pad® system or egg-crate foam pre-operatively. Patients were placed under general anesthesia and then positioned in dorsal lithotomy. The locations of the iliac crest, acromion process, and buttock were marked on the table before and after surgery to calculate cephalad migration during surgery. The primary outcome was centimeters of cephalad migration at the three anatomic landmarks. Comparing the Pink Pad® (n = 24) to the egg-crate group (n = 26) revealed similar mean cephalad migration at the iliac crest (4.8 cm vs 4.3 cm, p = 0.56) and the shoulder (4.6 cm vs 3.9 cm, p = 0.39), and less cephalad migration at the buttock (median 3.0 cm vs 2.0 cm, p = 0.041). The total time in Trendelenburg was not correlated with cephalad migration at any anatomic landmark. Body mass index was positively correlated with cephalad migration only at the iliac crest (p = 0.032) regardless of pad type. The egg-crate foam resulted in less cephalad migration at all anatomic sites and significantly less migration at the buttocks compared to the Pink Pad®. This suggests that the less-costly egg-crate foam is noninferior to the Pink Pad® system and trends at superiority.

Surgical Equipment Price Awareness Amongst Obstetrician-Gynecologists.

BACKGROUND AND OBJECTIVES: Physicians typically have little information of surgical device pricing, although this trend has not been studied in the field of obstetrics and gynecology. We therefore aimed to determine how accurately obstetrician-gynecologists estimate surgical device prices, and to identify factors associated with accuracy. METHODS: An anonymous survey was emailed to all obstetrician-gynecologist attendings, fellows, and residents at 3 teaching hospitals in a single healthcare system in Arizona. We obtained demographic data, perceptions of price transparency and self-rated price knowledge, and price estimates for 31 surgical devices. RESULTS: After participants provided consent and demographics, they then estimated the purchasing price of 31 devices. We defined price accuracy as being within ±10% of the hospital's purchasing price. Fifty-six of the 170 (32.9%) invitees completed the survey and 48 (28.2%) provided price estimates. On average, participants identified 1.9 items correctly (6.1%; range, 0-7 items) out of 31 with no difference in accuracy based on seniority, surgical volume, physician reimbursement structure, nor subspecialty practice-focus. All (100%) respondents felt pricing should be transparent, and only 1.8% felt it is at least somewhat transparent. CONCLUSION: We found that price-estimate accuracy was very low and had no association with any of the demographics. Also notable was the perception that pricing is not transparent despite a unanimous desire for transparency. Although physicians reported a preference for using less-expensive surgical devices, we conclude that physicians are unequipped to make cost-conscious decisions highlighting a large potential for education.

The incidence of neonatal herpes infection.

OBJECTIVE: The incidence of perinatal transmission of neonatal herpes infection has recently been reported at 1 in 3200 births. The main objective of this study was to determine a population-based incidence of neonatal herpes simplex virus infection. STUDY DESIGN: This was a retrospective chart review of newborn infants presenting with herpes infection established by cerebrospinal fluid polymerase chain reaction or lesion culture between 1999 and 2003. Only infants delivered at our institution were considered to establish a population-based incidence. RESULTS: Four cases of neonatal herpes infection were identified based on polymerase chain reaction and culture diagnosis. During the study period 78,115 infants were delivered at our institution yielding an incidence of 1 in 20,000 live births. CONCLUSION: The incidence of neonatal herpes infection at our institution is lower than reported elsewhere. A national surveillance program of neonatal herpes is needed to measure the burden of disease across the United States.