Evaluation of Menstrual Cycle Tracking Behaviors in the Ovulation and Menstruation Health Pilot Study: Cross-Sectional Study.

BACKGROUND: Menstrual cycle tracking apps (MCTAs) have potential in epidemiological studies of women's health, facilitating real-time tracking of bleeding days and menstrual-associated signs and symptoms. However, information regarding the characteristics of MCTA users versus cycle nontrackers is limited, which may inform generalizability. OBJECTIVE: We compared characteristics among individuals using MCTAs (app users), individuals who do not track their cycles (nontrackers), and those who used other forms of menstrual tracking (other trackers). METHODS: The Ovulation and Menstruation Health Pilot Study tested the feasibility of a digitally enabled evaluation of menstrual health. Recruitment occurred between September 2017 and March 2018. Menstrual cycle tracking behavior, demographic, and general and reproductive health history data were collected from eligible individuals (females aged 18-45 years, comfortable communicating in English). Menstrual cycle tracking behavior was categorized in 3 ways: menstrual cycle tracking via app usage, that via other methods, and nontracking. Demographic factors, health conditions, and menstrual cycle characteristics were compared across the menstrual tracking method (app users vs nontrackers, app users vs other trackers, and other trackers vs nontrackers) were assessed using chi-square or Fisher exact tests. RESULTS: In total, 263 participants met the eligibility criteria and completed the digital survey. Most of the cohort (n=191, 72.6%) was 18-29 years old, predominantly White (n=170, 64.6%), had attained 4 years of college education or higher (n= 209, 79.5%), and had a household income below US $50,000 (n=123, 46.8%). Among all participants, 103 (39%) were MCTA users (app users), 97 (37%) did not engage in any tracking (nontrackers), and 63 (24%) used other forms of tracking (other trackers). Across all groups, no meaningful differences existed in race and ethnicity, household income, and education level. The proportion of ever-use of hormonal contraceptives was lower (n=74, 71.8% vs n=87, 90%, P=.001), lifetime smoking status was lower (n=6, 6% vs n=15, 17%, P=.04), and diagnosis rate of gastrointestinal reflux disease (GERD) was higher (n=25, 24.3% vs n=12, 12.4%, P=.04) in app users than in nontrackers. The proportions of hormonal contraceptives ever used and lifetime smoking status were both lower (n=74, 71.8% vs n=56, 88.9%, P=.01; n=6, 6% vs n=11, 17.5%, P=.02) in app users than in other trackers. Other trackers had lower proportions of ever-use of hormonal contraceptives (n=130, 78.3% vs n=87, 89.7%, P=.02) and higher diagnostic rates of heartburn or GERD (n=39, 23.5% vs n=12, 12.4%, P.03) and anxiety or panic disorder (n=64, 38.6% vs n=25, 25.8%, P=.04) than nontrackers. Menstrual cycle characteristics did not differ across all groups. CONCLUSIONS: Our results suggest that app users, other trackers, and nontrackers are largely comparable in demographic and menstrual cycle characteristics. Future studies should determine reasons for tracking and tracking-related behaviors to further understand whether individuals who use MCTAs are comparable to nontrackers.

Sex-specific impact of maternal obesity on fetal placental macrophages and cord blood triglycerides.

INTRODUCTION: Maternal obesity is associated with increased risk of offspring obesity and cardiometabolic disease. Altered fetoplacental immune programming is a potential candidate mechanism. Differences in fetal placental macrophages, or Hofbauer cells (HBCs), have been observed in maternal obesity, and lipid metabolism is a key function of resident macrophages that may be deranged in inflammation/immune activation. We sought to test the following hypotheses: 1) maternal obesity is associated with altered HBC density and phenotype in the term placenta and 2) obesity-associated HBC changes are associated with altered placental lipid transport to the fetus. The impact of fetal sex was evaluated in all experiments. METHODS: We quantified the density and morphology of CD163-and CD68-positive HBCs in placental villi in 34 full-term pregnancies undergoing cesarean delivery (N = 15, maternal BMI ≥30 kg/m2; N = 19, BMI <30 kg/m2). Antibody-positive cells in terminal villi were detected and cell size and circularity analyzed using a semi-automated method for thresholding of bright-field microscopy images (ImageJ). Placental expression of lipid transporter genes was quantified using RTqPCR, and cord plasma triglycerides (TGs) were profiled using modified Wahlefeld method. The impact of maternal obesity and fetal sex on HBC features, lipid transporters, and cord TGs were evaluated by two-way ANOVA. Spearman correlations of cord TGs, HBC metrics and gene expression levels were calculated. RESULTS: Maternal obesity was associated with significantly increased density of HBCs, with male placentas most affected (fetal sex by maternal obesity interaction p = 0.04). CD163+ HBCs were larger and rounder in obesity-exposed male placentas. Sexually dimorphic expression of placental FATP4, FATP6, FABPPM, AMPKB1 and AMPKG and cord TGs was noted in maternal obesity, such that levels were higher in males and lower in females relative to sex-matched controls. Cord TGs were positively correlated with HBC density and FATP1 expression. DISCUSSION: Maternal obesity is associated with sex-specific alterations in HBC density and placental lipid transporter expression, which may impact umbilical cord blood TG levels and offspring cardiometabolic programming.

Patterns of spread and genetic alterations of primary endometrioid carcinomas of the ovary.

OBJECTIVE: The primary objective was to characterize the rate of lymph node involvement in a cohort of patients with primary ovarian endometrioid adenocarcinoma. Additionally, we sought to quantify the recurrence rate, genetic alterations, and impact of lymphadenectomy on survival in this group of patients. METHODS: Patients diagnosed with primary endometrioid adenocarcinoma of the ovary without synchronous carcinomas of the female genital tract between 2012 and 2021 were identified. Demographic and disease-related data were collected from pathology reports and clinical records. Kaplan-Meier survival analysis using log rank test and Cox regression was performed. RESULTS: Sixty-three patients met inclusion criteria. Median age was 60 (range 22-90) years. Histologic grade was 1 in 20 (32%), 2 in 27 (43%), and 3 in 16 (25%) tumors. International Federation of Gynecology and Obstetrics (FIGO) stage after surgery included IA/B (n=20, 32%), IC (n=23, 37%), II (n=16, 25%), and III (n=4, 6%). Forty-one (65%) patients had pelvic and 33 (52%) had both pelvic and para-aortic lymphadenectomy. All assessed lymph nodes were negative for metastatic carcinoma. No patients with clinically pelvis-confined disease had tumors upstaged by either lymphadenectomy or omentectomy. Twenty-eight patients (44%) had germline mutational status documented; two had a germline BRCA mutation, confirmed to be pathogenic by molecular studies. Complete staging did not significantly impact progression free or overall survival, after adjusting for age and histologic grade in a Cox proportional hazards model. The recurrence rate was 15% for patients with grade 1 endometrioid carcinoma, 7% for grade 2, and 31% for grade 3, respectively. CONCLUSION: There were no lymph node metastases in patients with comprehensively staged primary endometrioid ovarian carcinoma. Staging did not impact survival and may be omitted, regardless of grade. Germline BRCA mutations are rare in ovarian endometrioid carcinoma compared with reported rates in high-grade serous carcinomas.

Incidence of de novo stress urinary incontinence following minimally invasive sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the incidence and risk factors of postoperative de novo stress urinary incontinence (SUI) in stress-continent women following minimally invasive sacrocolpopexy without an anti-incontinence procedure. METHODS: We completed a multicenter, retrospective cohort study of women undergoing laparoscopic sacrocolpopexy without concurrent anti-incontinence procedures from October 2006 through January 2021. RESULTS: Of the 169 women who underwent minimally invasive sacrocolpopexy, 17.1% (n=30) developed de novo SUI, and 7.1% eventually underwent a midurethral sling placement. On logistic regression, BMI, preoperative urinary urgency, and history of transvaginal mesh repair were found to be significantly associated with and predictive of de novo SUI. When the concordance index (C-index) was calculated with the model published by Jelovsek et al. for women who developed de novo SUI within 12 months of the prolapse surgery, the current de novo SUI calculator was able to discriminate de novo SUI outcome (C-index = 0.71). CONCLUSIONS: The incidence of de novo SUI after minimally invasive sacrocolpopexy without anti-incontinence procedure correlates directly with higher BMI, preoperative urinary urgency, and transvaginal mesh history for POP. Preoperative counseling for minimally invasive sacrocolpopexy should include discussing the risk of de novo SUI and preoperative factors that may increase this risk.

Digital Global Recruitment for Women's Health Research: Cross-sectional Study.

BACKGROUND: With the increased popularity of mobile menstrual tracking apps and boosted Facebook posts, there is a unique opportunity to recruit research study participants from across the globe via these modalities to evaluate women's health. However, no studies to date have assessed the feasibility of using these recruitment sources for epidemiological research on ovulation and menstruation. OBJECTIVE: The objective of this study was to assess the feasibility of recruiting a diverse sample of women to an epidemiological study of ovulation and menstruation (OM) health (OM Global Health Study) using digital recruitment sources. The feasibility and diversity were assessed via click and participation rates, geographic location, BMI, smoking status, and other demographic information. METHODS: Participants were actively recruited via in-app messages using the menstrual tracking app Clue (BioWink GmbH) and a boosted Facebook post by DivaCup (Diva International Inc.). Other passive recruitment methods also took place throughout the recruitment period (eg, email communications, blogs, other social media). The proportion of participants who visited the study website after viewing and clicking the hypertext link (click rates) in the in-app messages and boosted Facebook post and the proportion of participants who completed the surveys per the number of completed consent and eligibility screeners (participation rates) were used to quantify the success of recruiting participants to the study website and study survey completion, respectively. Survey completion was defined as finishing the pregnancy and birth history section of the OM Global Health Study questionnaire. RESULTS: The recruitment period was from February 27, 2018, through January 24, 2020. In-app messages and the boosted Facebook post were seen by 104,000 and 21,400 people, respectively. Overall, 215 participants started the OM Global Health Study survey, of which 140 (65.1%), 39 (18.1%), and 36 (16.8%) participants were recruited via the app, the boosted Facebook post, and other passive recruitment methods, respectively. The click rate via the app was 18.9% (19,700 clicks/104,000 ad views) and 1.6% via the boosted Facebook post (340 clicks/21,400 ad views.) The overall participation rate was 44.6% (198/444), and the average participant age was 21.8 (SD 6.1) years. In terms of geographic and racial/ethnic diversity, 91 (44.2%) of the participants resided outside the United States and 147 (70.7%) identified as non-Hispanic White. In-app recruitment produced the most geographically diverse stream, with 44 (32.8%) of the 134 participants in Europe, 77 (57.5%) in North America, and 13 (9.8%) in other parts of the world. Both human error and nonhuman procedural breakdowns occurred during the recruitment process, including a computer programming error related to age eligibility and a hacking attempt by an internet bot. CONCLUSIONS: In-app messages using the menstrual tracking app Clue were the most successful method for recruiting participants from many geographic regions and producing the greatest numbers of started and completed surveys. This study demonstrates the utility of digital recruitment to enroll participants from diverse geographic locations and provides some lessons to avoid technical recruitment errors in future digital recruitment strategies for epidemiological research.

Urinary symptoms in women with faecal incontinence.

AIM: Faecal incontinence (FI) is estimated to affect 8.9% of women in the United States, with a significant impact on quality of life. Our aim was to compare urinary symptoms in patients with and without FI with different degrees of severity. METHODS: This prospective cohort of women presented for care at a pelvic floor disorder centre between May 2007 and January 2019. We excluded women with a history of bowel resection, prior history of pelvic organ prolapse surgery or existing prolapse symptoms reported by the patient during intake. The primary outcome was the presence of urinary symptoms in women with and without FI by validated questionnaires. A logistic regression model for association of urinary symptoms with FI was performed, adjusting for age, smoking, diabetes, prior hysterectomy and irritable bowel syndrome. RESULTS: A total of 2932 met inclusion criteria, and of these 1404 (47.89%) reported FI. In the univariate analysis, patients with FI were more likely to have urgency urinary incontinence (P = 0.01) or mixed urinary incontinence (P < 0.001), report nocturnal enuresis (P < 0.001) or have leakage of urine during sex (P < 0.001). In an adjusted model, FI was associated with concurrent stress (adjusted OR 1.28, P = 0.034), urgency (adjusted OR 1.52, P < 0.001) and mixed incontinence (adjusted OR 1.94, P < 0.001). CONCLUSION: In women with pelvic floor disorders, the presence of FI is associated with a higher prevalence of urinary incontinence. Pelvic floor specialists should assess urinary incontinence symptoms along with the presence and severity of FI to provide comprehensive care and guide appropriate therapy.

Response to ovulation induction treatments in women with polycystic ovary syndrome as a function of serum anti-Müllerian hormone levels.

PURPOSE: To assess whether anti-Müllerian hormone (AMH) can predict response to ovulation induction (OI) with clomiphene citrate (CC), letrozole (LET), or follicle-stimulating hormone (FSH) in women with polycystic ovary syndrome (PCOS) undergoing OI/intrauterine inseminations (IUI). METHODS: A total of 738 OI/IUI cycles from 242 patients at an academic center were stratified in three groups by medication: CC (n = 295), LET (n = 180), and FSH (n = 263), in a retrospective fashion. Ovarian response to treatment (RT, development of at least one dominant follicle) was assessed using mixed effects logistic regression models. RESULTS: Overall, RT cycles had lower AMH levels compared to no-RT cycles (p < 0.001). This finding persisted when analysis was limited to oral agents but attenuated in FSH cycles. For CC and LET cycles, the predicted probability (PProb) for RT decreased as AMH levels increased (PProb (95%CI): 97% (93-100), 79% (70-88), and 75% (61-89); 85% (78-93), 75% (67-83), and 73% (63-86) for AMH pct.: ≤ 25th, ≥ 50th, and ≥ 75th, for CC and LET, respectively)). However, RT was noted in 98.5% of FSH/IUI cycles regardless of AMH. For CC cycles, those with AMH ≥ 75th pct. had lower odds for RT over cycles with AMH < 75th pct. (OR 0.2, 95%CI 0.04-0.8, p = 0.02). Similarly, lower odds for RT were observed in LET cycles with AMH ≥ 75th pct. (0.6, 0.3-1.4, p = 0.25). CONCLUSION: In PCOS, increasing serum AMH levels are associated with lower probability of RT to oral agents. Our findings constitute a valuable tool for the clinician when counseling PCOS patients and designing a personalized ovulation induction treatment strategy.

Association Between Hemoglobin A1c and Midurethral Sling Complications in Diabetic Women: A Cohort Study.

OBJECTIVE: We aimed to evaluate the association between hemoglobin A1c (HbA1c) levels and midurethral sling (MUS) complications. METHODS: This was a multihospital, retrospective cohort study from 2010 to 2020. We included all women with diabetes mellitus who underwent a synthetic mesh MUS procedure and had a preoperative HbA1c within 3 months of surgery. The primary outcome was a composite of complications, including MUS mesh exposure, surgical site granulation tissue or infection, urinary tract infection, surgical site pain beyond 6 weeks postoperatively, and MUS failure. A sensitivity analysis analyzing MUS failure alone was performed. RESULTS: During the study period, 109 women met the inclusion criteria. Most were White (52.2%) and had a median body mass index of 31.2 kg/m2, and 84.9% were postmenopausal. Median HbA1c was 7.2% (interquartile range, 6.3%-7.7%). Urinary tract infection was the most common complication in 12 (11.0%) women. Mesh exposure was diagnosed in 7 (6.4%) women. Seventeen (15.6%) had MUS failure. On univariate regression analysis, a higher HbA1c was associated with increased odds of composite complications (odds ratio, 1.67; 95% confidence interval, 1.20-2.32; P = 0.002) and MUS failure (odds ratio, 1.81, 95% confidence interval, 1.26-2.60; P = 0.001). On multivariate analysis, higher HbA1c levels were associated with a composite of complications and failure (P < 0.05). Based on the receiver operating characteristic curve, HbA1c greater than 8% demonstrated a specificity of 85.7% and a sensitivity of 50% for MUS failure. CONCLUSIONS: In diabetic patients, a higher HbA1c was associated with a higher risk of MUS complications and failure. Obtaining an HbA1c within 3 months of surgery may help with risk stratification.

A patient-specific model combining antimüllerian hormone and body mass index as a predictor of polycystic ovary syndrome and other oligo-anovulation disorders.

OBJECTIVE: To determine whether a patient-specific predictive model combining antimüllerian hormone (AMH) levels and body mass index (BMI) can aid in the diagnosis of polycystic ovary syndrome (PCOS) and other ovulatory dysfunction disorders (OVDYS) among infertile women. DESIGN: Retrospective cohort study. SETTING: Academic fertility center. PATIENT(S): One thousand and ten infertile women undergoing 3,160 intrauterine insemination (IUI) cycles, stratified by diagnosis in three groups: PCOS, OVDYS, and other etiologies. INTERVENTION(S): Ovulation induction followed by IUI or ultrasound-monitored natural cycles. MAIN OUTCOME MEASURE(S): The probability of either PCOS or OVDYS diagnosis based on AMH levels alone and a patient-specific predictive model that combines serum AMH and patient's BMI. RESULT(S): Median and interquartile range (IQR) for the serum AMH levels (ng/mL) were the highest in women with PCOS, and lowest in those with other infertility causes. Overall, for every 1 ng/mL increase in AMH, the odds of PCOS and OVDYS versus other causes increased by 55% and 24%, respectively. Postestimation from multivariate logistic regression models showed that PCOS diagnosis can be predicted with lower AMH values in women with a higher BMI compared with the AMH values predicting PCOS in normal-weight or underweight patients. The receiver operating characteristic curves reinforced these findings, and the best cutoffs for PCOS diagnosis were 7.5, 4.4, and 4.1 ng/mL for women belonging to the BMI groups 18.5-24.9, 25.0-29.9, and ≥30.0 kg/m2, respectively. CONCLUSION(S): Taking into account AMH and BMI, we developed a model that predicts the probability of an oligo-anovulation diagnosis, thus facilitating patient-specific counseling in the infertility setting.

Palliative care referral patterns and measures of aggressive care at the end of life in patients with cervical cancer.

INTRODUCTION: Fifteen per cent of women with cervical cancer are diagnosed with advanced disease and carry a 5 year survival rate of only 17%. Cervical cancer may lead to particularly severe symptoms that interfere with quality of life, yet few studies have examined the rate of palliative care referral in this population. This study aims to examine the impact of palliative care referral on women who have died from cervical cancer in two tertiary care centers. METHODS: We conducted a retrospective review of cervical cancer decedents at two tertiary institutions from January 2000 to February 2017. We examined how aggressive measures of care at the end of life, metrics defined by the National Quality Forum, interacted with clinical variables to understand if end-of-life care was affected. Univariate and multivariate parametric and non-parametric testing was used, and linear regression models were generated to determine unadjusted and adjusted associations between aggressive measures of care at the end of life with receipt of palliative care as the main exposure. RESULTS: Of 153 cervical cancer decedents, 73 (47%) received a palliative care referral and the majority (57%) of referrals occurred during an inpatient admission. The median time from palliative care consultation to death was 2.3 months and 34% were referred to palliative care in the last 30 days of life. Palliative care referral was associated with fewer emergency department visits (OR 0.18, 95% CI 0.05 to 0.56), inpatient stays (OR 0.21, 95% CI 0.07 to 0.61), and intensive care unit admissions (OR 0.24, 95% CI 0.06 to 0.93) in the last 30 days of life. Palliative care did not affect chemotherapy or radiation administration within 14 days of death (p=0.36). Women evaluated by palliative care providers were less likely to die in the acute care setting (OR 0.19, 95% CI 0.07 to 0.51). DISCUSSION: In two tertiary care centers, less than half of cervical cancer decedents received palliative care consultations, and those referred to palliative care were often evaluated late in their disease course. Palliative care utilization was also associated with a lower incidence of poor-quality end-of-life care.

Professional Burnout Survey for Practicing Female Pelvic Medicine and Reconstructive Surgeons: A Cross-sectional Study.

OBJECTIVES: The objective of this study was to determine the prevalence of burnout among active practicing members of the American Urogynecologic Society (AUGS). METHODS: This was an anonymous electronic survey of AUGS nontrainee physician members. Basic demographic, personal, and professional characteristics were collected. Levels of emotional exhaustion, depersonalization and personal accomplishment, as defined by the Maslach Burnout Inventory-Human Services Survey, were utilized to categorize participants into burnout profiles and to determine 2 alternative burnout definitions. Descriptive statistics and models were used to summarize provider characteristics and to explore differences among the burnout profiles. RESULTS: Of the 1039 active members of AUGS, 280 (26.9%) responded to the survey. Burnout profiles were delineated using the Maslach Burnout Inventory-Human Services Survey. Forty-three percent fit the Engaged profile, whereas 13% fit the Burnout profile. Significant differences were seen in the distribution of the burnout profiles for physicians who take call (P=0.015), have a current mentor (P=0.016), screen positive for major depression (P < 0.001), experience suicidal ideation (P=0.018), have a feeling of control regarding their schedule (P < 0.001) and those who would become a physician again (P < 0.001). The overall rate of burnout in female pelvic medicine and reconstructive surgery providers was significantly different depending on the definition utilized (P < 0.01) and ranged from as low as 6.5% to as high as 51.9%. CONCLUSIONS: There were some differences in respondent characteristics seen among the burnout profiles. The chosen definition of burnout significantly affected the purported rate of burnout, complicating comparisons among provider populations.

Mid-trimester cervical length not associated with HIV status among pregnant women in Botswana.

OBJECTIVE: HIV-infected women on antiretroviral therapy have a higher risk of preterm birth than HIV-uninfected women in Botswana. To better understand the mechanism for preterm birth among HIV-infected women, we evaluated whether mid-trimester cervical length differed by HIV status as cervical shortening is associated with an increased risk for preterm birth. METHODS: We conducted a prospective cohort study among pregnant women receiving care at the Scottish Livingstone Hospital in Molepolole, Botswana. Consecutive women referred for routine obstetrical ultrasound were consented and enrolled if between 22w0d and 24w6d by ultrasound biometry. Blinded to maternal HIV status, an obstetrician measured transvaginal cervical length using standardized criteria. Cervical length, as well as the proportion of women with a short cervix (<25mm), were compared among HIV-infected and HIV-uninfected women. The acceptability of transvaginal ultrasound was also evaluated. RESULTS: Between April 2016 and April 2017, 853 women presenting for obstetric ultrasound were screened, 187 (22%) met eligibility criteria, and 179 (96%) were enrolled. Of those enrolled, 50 (28%) were HIV-infected (86% on antiretroviral therapy), 127 (71%) were HIV-uninfected, and 2 (1%) had unknown HIV status. There was no significant difference in mean cervical length between HIV-infected and HIV-uninfected women (32mm vs 31mm, p = 0.21), or in the proportion with a short cervix (10% vs 14%, p = 0.44). Acceptability data was available for 115 women who underwent a transvaginal ultrasound exam. Of these, 112 of 115 (97%) women deemed the transvaginal scan acceptable. CONCLUSIONS: The increased risk of preterm birth observed among HIV-infected women receiving antiretroviral therapy in Botswana is unlikely associated with mid-trimester cervical shortening. Further research is needed to understand the underlying mechanism for preterm birth among HIV-infected women.

The effect of follicular phase length on cycle outcomes and endometrial development in gonadotrophin ovarian stimulation/intrauterine insemination cycles.

RESEARCH QUESTION: Does a shorter follicular phase length (FPL) affect cycle outcomes and endometrial development among women undergoing gonadotrophin ovarian stimulation/intrauterine insemination (OS/IUI)? DESIGN: Retrospective cohort study of 4773 OS/IUI cycles among 2054 patients. FPL was analysed first continuously, then dichotomously using an arbitrary cut-off at the 15th percentile (8 days) to divide cycles into shorter and longer FPL groups. Receiver operating characteristic (ROC) curves were constructed to further analyse the impact of FPL on all outcomes. Primary outcomes included clinical pregnancy, spontaneous abortion, multiple pregnancy and non-viable (ectopic/biochemical) pregnancy rates (CPR, SABR, MPR and NVPR, respectively). Secondary outcomes included endometrial thickness. All analyses controlled for age, day 3 FSH and body mass index. RESULTS: When analysing FPL continuously, CPR increased by 6.0% (adjusted odds ratio [aOR] 1.06, 95% CI 1.03-1.09, P < 0.001) with each additional follicular phase day. Similarly, in the dichotomous analysis, cycles with a longer FPL resulted in higher CPR with 45% higher odds of clinical pregnancy (aOR 1.45, 95% CI 1.07-1.97, P = 0.018). No effect of FPL was noted on NVPR, SABR or MPR. Endometrial thickness increased by 0.09 mm (95% CI 0.06-0.12, P < 0.001) with each additional FPL day and was increased in the longer compared with the shorter FPL group (adjusted mean difference 1.08 mm, 95% CI 0.81-1.34, P < 0.001). CONCLUSIONS: The data suggest that in gonadotrophin OS/IUI cycles, FPL might impact both chance of clinical pregnancy and endometrial thickness, independent of maternal age and ovarian reserve.

Presacral Anatomy in Women With a Horseshoe Kidney.

OBJECTIVE: Horseshoe kidney (HSK) is the most common renal fusion defect that can alter vascular and upper urinary tract anatomy. Anatomic variations in the presacral space can make surgical dissection very challenging. The aim of this study was to characterize presacral anatomy in women with HSK. METHODS: Large academic centers' database was queried to identify imaging studies in adult women with HSK. Available multiplanar computed tomography and magnetic resonance imaging images were reviewed, and relevant vascular and upper urinary tract anatomy was measured and compared with published normal values. Study population was compared with the normal controls using Student t test, χ test, or Fisher exact test as appropriate. RESULTS: One hundred seventy-eight women were identified initially, and 20 confirmed to have HSK on imaging. The mean ± SD age was 54.5 ± 16.9 years, and body mass index was 27.3 ± 7.5 kg/m. Women with HSK had a narrower angle of aortic bifurcation (39.1 ± 18.7 degrees vs 55.6 ± 4.5 degrees, P = 0.014); the right ureter was closer to midline (22.9 ± 8.8 mm vs 32.3 ± 1.2 mm, P < 0.001) when compared with normal controls anatomy. In 40% of women with HSK, the bifurcation of the vena cava was below the level of L5 in contrast to the 8% in the normal population (P < 0.001). In 60% of women with HSK, the inferior pole of the kidney was at or below L5. CONCLUSIONS: Ureteral, renal, and vascular anatomic alterations in women with HSK may make presacral surgical anatomy challenging by obscuring the anterior longitudinal ligament anchoring point. Preoperative imaging is warranted to determine the feasibility of female pelvic reconstructive surgery in HSK patients.

Association Between Vulvovaginal Discomfort and Activity of Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) affect 200-400 people per 100,000 in the United States, about half of whom are women. We aimed to define the prevalence of vulvovaginal symptoms and association with IBD activity in a large cohort of women. METHODS: Women more than 18 years old with IBD (1250) completed an online survey querying the presence and severity of vulvar or vaginal itch, burn, or irritation, vaginal discharge or dryness, and vulvovaginal pain. The survey collected information on demographic features and IBD activity (categorized using the Manitoba index). Women with and without symptoms were compared using bivariate analyses. Logistic regression evaluated associations between IBD severity and vulvovaginal symptoms, adjusted for diagnosis, menopause, smoking, depression, and use of medications to treat IBD. RESULTS: A total of 512 (41%) women reported at least 1 moderate-severe vulvovaginal symptom. All vulvovaginal symptoms except vaginal dryness were more common in women with active IBD. In a multivariate model controlled for menopause, smoking, t-score from the PROMIS depression instrument, and use of IBD medications, women with constant or frequent active IBD, based on Manitoba index scores, had increased odds for moderate-severe vulvovaginal symptoms (odds ratio, 1.68; 95% CI, 1.22-2.32) compared to women in remission. Vulvovaginal discomfort frequently or always decreased interest in sex (n=336; 28%) or ability to have sex (n=207; 16%). CONCLUSIONS: In an online survey of 1250 women, we found that women with more active IBD have increased prevalence of vulvovaginal discomfort, compared to women in remission. These symptoms affect sexual health.

Predictors of reproductive outcomes following myomectomy for intramural fibroids.

RESEARCH QUESTION: Which factors are associated with reproductive outcomes among infertile women undergoing myomectomy for intramural fibroids? DESIGN: This was a historical cohort study including 127 infertile women who underwent myomectomy due to intramural fibroids as part of fertility enhancement treatment at a single academic tertiary-care medical centre between the years 2011 and 2015. Demographic characteristics, pre-operative evaluation, surgical factors and post-surgical factors were compared between women who successfully conceived and those who did not following myomectomy. RESULTS: The overall clinical pregnancy rate following myomectomy was 58.3% (n = 74). Women with successful conception were significantly younger (35.4 ± 4.5 years versus 37.2 ± 4.0 years; P = 0.022), and mostly white (63.5% versus 24.3% African-American; P = 0.008). In addition, patients who conceived had larger fibroids demonstrated in pre-operative imaging and during surgery (7.3 versus 6.1 cm and 7.8 versus 6.6 cm; P = 0.003 and 0.022, respectively), with fewer cases of cavity entry determined during surgery (9.5% versus 28.3%; P = 0.005). Multivariable modified Poisson regression models identified the patient's age (risk ratio [RR] 0.96, 95% confidence interval [CI] 0.93-0.99; P =0.014) and race (RR for African-American women versus white women 0.58, 95% CI 0.38-0.88; P = 0.011) as factors significantly associated with the probability of conceiving following myomectomy. CONCLUSION(S): Age and race play a significant role in the reproductive outcomes of infertile women undergoing intramural fibroid myomectomy as part of fertility enhancement treatment. Further large prospective studies are needed to identify specific factors associated with achieving pregnancy, which will help to determine the clinical management of infertile women with intramural fibroids.

Women's health providers' perspectives on preimplantation genetic testing.

RESEARCH QUESTION: What are the perspectives of women's health providers on the use of preimplantation genetic testing (PGT) for common medical disorders? DESIGN: A cross-sectional 15-question online anonymous survey was conducted of women's health providers specializing in general obstetrics/gynaecology, gynaecologic oncology and infertility at a tertiary care academic institution in Massachusetts, USA. Respondents could answer 'yes', 'no' or 'unsure' to each thematic question. RESULTS: The survey was sent to 1060 providers and 240 providers responded (response rate 22.6%). Overall, 93% of respondents supported the use of PGT for the identification of genetic mutations which lead to childhood-onset disease, 83% supported the use of PGT for chromosomal aneuploidy screening, and 76% supported the use of PGT for cancer-related genetic disorders. Only 1.7% of respondents supported the use of PGT for non-disease-related indications, including sex selection and physical traits. Compared with general obstetrics/gynaecology providers, infertility specialists were more supportive of PGT. In total, 22.5% of respondents reported no prior knowledge of PGT. CONCLUSIONS: In a sample of women's health providers across multiple different obstetrics/gynaecology specialties, there was overall support for the use of PGT for a variety of common indications. Infertility specialists were the most supportive, which may reflect the familiarity that these providers have with this procedure. There was an overwhelmingly non-supportive response for the use of PGT for non-disease-related indications. The percentage of medical professionals working in women's health without prior knowledge of PGT (22.5%) was higher than expected, identifying the need for more education regarding the availability and potential indications for this procedure.

Unexpected term NICU admissions: a marker of obstetrical care quality?

BACKGROUND: Unexpected admissions of term neonates to the neonatal intensive care unit and unexpected postnatal complications have been proposed as neonatal-focused quality metrics for intrapartum care. Previous studies have noted significant variation in overall hospital neonatal intensive care unit admission rates; however, little is known about the influence of obstetric practices on these rates or whether variation among unanticipated admissions in low-risk, term neonates can be attributed to systemic hospital practices. OBJECTIVE: The objective of the study was to examine the relative effects of patient characteristics and intrapartum events on unexpected neonatal intensive care unit admissions and to quantify the between-hospital variation in neonatal intensive care unit admission rates among this group of neonates. STUDY DESIGN: We performed a retrospective cross-sectional study using data collected as part of the Consortium for Safe Labor study. Women who delivered term (≥37 weeks), singleton, nonanomalous, liveborn infants without an a priori risk for neonatal intensive care unit admission were included. The primary outcome was neonatal intensive care unit admission among this population. Multilevel mixed-effect models were used to calculate adjusted odds ratios for demographics (age, race, insurer), pregnancy characteristics (parity, gestational age, tobacco use, birthweight), maternal comorbidities (chronic and pregnancy-induced hypertension), hospital characteristics (delivery volume, hospital and neonatal intensive care unit level, academic affiliation), and intrapartum events (prolonged second stage, induction of labor, trial of labor after cesarean delivery, chorioamnionitis, meconium-stained amniotic fluid, and abruption). Intraclass correlation coefficients were used to estimate the between-hospital variance in a series of hierarchical models. RESULTS: Of the 143,951 infants meeting all patient and hospital inclusion criteria, 7995 (5.6%) were admitted to the neonatal intensive care unit after birth. In the fully adjusted model, the factors associated with the highest odds for neonatal intensive care unit admission included: nulliparity (adjusted odds ratio, 1.62 [95% confidence interval, 1.53-1.71]), large for gestational age (adjusted odds ratio, 1.59 [95% confidence interval, 1.47-1.71]), and small for gestational age (adjusted odds ratio, 1.60 [95% confidence interval, 1.47-1.73]). Induction of labor (adjusted odds ratio, 0.95 [95% confidence interval, 0.89-1.01]) was not associated with increased odds of neonatal intensive care unit admission compared with women who labored spontaneously. The events associated with higher odds of neonatal intensive care unit admission included: prolonged second stage (adjusted odds ratio, 1.66 [95% confidence interval, 1.51-1.83]); chorioamnionitis (adjusted odds ratio, 3.89 [95% confidence interval, 3.42-4.44]), meconium-stained amniotic fluid (adjusted odds ratio, 1.96 [95% confidence interval, 1.82-2.10]), and abruption (adjusted odds ratio, 2.64 [95% confidence interval, 2.16-.21]). Compared with women who did not labor, the odds of neonatal intensive care unit admission were lower for women who labored: adjusted odds ratio, 0.48 (95% confidence interval, 0.45-0.52) for women with no uterine scar and adjusted odds ratio, 0.83 (95% confidence interval, 0.73-0.94) for women with a uterine scar. There was significant variation in neonatal intensive care unit admission rates by hospital, ranging from 2.9% to 11.2%. After accounting for case mix and hospital characteristics, the between-hospital variance was 1.9%, suggesting that little of the variation was explained by the effect of the hospital. CONCLUSION: This study contributes to the currently limited understanding of term, neonatal intensive care unit admission rates as a marker of obstetrical care quality. We demonstrated that significant variation exists in hospital unexpected neonatal intensive care unit admission rates and that certain intrapartum events are associated with an increased risk for neonatal intensive care unit admission after delivery. However, the between-hospital variation was low. Unmeasured confounders and extrinsic factors, such as neonatal intensive care unit bed availability, may limit the ability of unexpected term neonatal intensive care unit admissions to meaningfully reflect obstetrical care quality.

Postoperative Opioid Consumption After Scheduled Compared With Unscheduled Cesarean Delivery.

OBJECTIVE: To identify characteristics associated with high inpatient daily opioid consumption after cesarean delivery. METHODS: This is a retrospective cohort study of all cesarean deliveries performed under neuraxial anesthesia with neuraxial morphine, at a single institution from January 1, 2015, to December 31, 2015. Women with preoperative opioid use disorder or chronic opioid use were excluded. Sociodemographic data, medical comorbidities, use of anxiolytics or antidepressants, smoking history, nonopioid substance use, intrapartum and cesarean delivery characteristics, and opioid consumption data (converted to morphine milligram equivalents) were abstracted. We defined high opioid use as a mean daily opioid consumption, standardized to the postoperative length of stay (excluding the first 24 postoperative hours to account for neuraxial morphine), greater than the 75th percentile of all opioid consumption. We used multivariable Poisson regression, stratified by whether or not cesarean delivery was scheduled, to identify characteristics associated with high opioid consumption. RESULTS: Among 949 women who underwent cesarean delivery, the mean (SD) and median (interquartile range) daily opioid consumption was 48.6 (22.8) and 44.6 (36.6-66.6) morphine milligram equivalents, respectively. Among those women with high opioid consumption, the mean (SD) and median (interquartile range) daily opioid consumption was 78.8 (8.5) and 78.3 (72.9-83.5) morphine milligram equivalents, respectively. Daily opioid consumption among those with high consumption was similar among women with scheduled compared with unscheduled cesarean delivery. Sociodemographic characteristics were similar among women with and without high opioid consumption. No sociodemographic, antepartum, or intrapartum characteristics were associated with high opioid consumption for either women having unscheduled or scheduled cesarean deliveries. CONCLUSION: For a quarter of women undergoing cesarean delivery, daily consumption of opioids is equivalent to 10 tablets of oxycodone 5 mg daily. No characteristics were associated with high opioid use for women having a scheduled or unscheduled cesarean delivery. Understanding opioid consumption after cesarean delivery is critical to managing women's postoperative pain while decreasing opioid exposure and risks of long-term opioid use disorder.

PARP Inhibition Induces Enrichment of DNA Repair-Proficient CD133 and CD117 Positive Ovarian Cancer Stem Cells.

PARP inhibitors (PARPi) are FDA-approved monotherapy agents for the treatment of recurrent ovarian cancer in patients with and without a BRCA mutation. Despite promising response rates, not all patients derive benefit, and the majority develop resistance. PARPi treatment in vitro and in vivo induced an enrichment of CD133+ and CD117+ ovarian cancer stem cells (CSC). This effect was not affected by BRCA mutation status. In the CSC fractions, PARPi induced cell-cycle arrest in G2-M with a consequent accumulation of γH2AX, RAD51, and uniquely DMC1 foci. DNA damage and repair monitoring assays demonstrated that CSCs display more efficient DNA repair due, in part, to activation of embryonic repair mechanisms which involved the RAD51 homologue, DMC1 recombinase. Preserved and induced homologous repair (HR) could be a mechanism of an inherent resistance of CSCs to the synthetic lethality of PARPi that likely promotes disease recurrence. IMPLICATIONS: Treatment with PARPi fails to significantly affect ovarian cancer CSC populations, likely contributing to recurrent disease. Ovarian cancer CSCs stabilize genomic integrity after PARPi treatment, due to a more efficient inherent DNA repair capacity. PARPi-induced DMC1 recombinase and HR proficiency provide CSCs the opportunity to repair DNA damage more efficiently.Visual Overview: http://mcr.aacrjournals.org/content/molcanres/17/2/431/F1.large.jpg.