Neighborhood disadvantage is associated with decreased ovarian reserve in women with overweight and obesity.

OBJECTIVE(S): To evaluate the association between neighborhood disadvantage and ovarian reserve stratified by body mass index (BMI). DESIGN: Cross-sectional cohort study. SETTING: Single academic medical center. PATIENT(S): A total of 193 healthy reproductive-age women with regular menstrual cycles in the St. Louis, Missouri metropolitan area. INTERVENTION(S): Residence in a disadvantaged neighborhood. MAIN OUTCOME MEASURE(S): Ovarian reserve as assessed by ovarian antral follicle count (AFC) and serum anti-Müllerian hormone (AMH) concentration. RESULT(S): Women (n = 193) ranged from 20 to 44 years. The majority had overweight or obesity (59%, n = 117) with mean BMI of 28±7 kg/m2. Forty-eight women lived in the most disadvantaged neighborhood quartile, of which 75% had overweight or obesity, compared with 54% of the 145 women living in the 3 less disadvantaged neighborhood quartiles. When controlling for age, race, and smoking status, women with overweight or obesity living in the most disadvantaged neighborhoods had significantly lower AMH compared with those living in the less disadvantaged neighborhoods. Antral follicle count did not differ among women with overweight or obesity by neighborhood of residence. Neighborhood disadvantage was not associated with ovarian reserve by AFC or AMH in women with normal weight or underweight status. CONCLUSION(S): Living in a socioeconomically deprived area is associated with lower markers of ovarian reserve among women with an elevated BMI.

Successful oocyte cryopreservation using letrozole as an adjunct to stimulation in a transgender adolescent after GnRH agonist suppression.

OBJECTIVE: To report a successful case of ovarian hyperstimulation and oocyte cryopreservation in a transgender male adolescent after suppression with a gonadotropin-releasing hormone (GnRH) agonist while using the aromatase inhibitor letrozole to maintain low serum estradiol. DESIGN: Case report. SETTING: Division of Reproductive Endocrinology and Infertility, Washington University in St. Louis School of Medicine, St Louis, Missouri. PATIENT(S): A 15-year-old Tanner II transgender male adolescent with a GnRH agonist implant. INTERVENTION(S): The GnRH agonist implant was removed. The patient was given letrozole (5 mg daily) while undergoing ovarian stimulation with an antagonist protocol. After oocyte retrieval, the patient began taking testosterone. MAIN OUTCOME MEASURE(S): Successful oocyte cryopreservation with minimal changes in breast budding. RESULT(S): The patient's peak serum estradiol concentration was 510 pg/mL. Twenty-two mature oocytes were cryopreserved. Small increases in breast budding occurred between baseline and the time of oocyte retrieval. CONCLUSION(S): We successfully used letrozole to maintain low serum estradiol in a transgender male adolescent during ovarian stimulation. Maintaining low estradiol to minimize pubertal development and possibly prevent gender dysphoria symptoms may make oocyte cryopreservation more desirable for transgender male adolescents.

Ovarian stimulation for fertility preservation in women with cancer: A systematic review and meta-analysis comparing random and conventional starts.

OBJECTIVE: In female cancer patients anticipating chemotherapy or radiation, oocyte retrieval for fertility should be performed as efficiently as possible to avoid postponing cancer treatments. Our objective was to compare clinical outcomes among female cancer patients who underwent a conventional early follicular phase-start ovarian stimulation cycle and those who underwent a random-start ovarian stimulation cycle. EVIDENCE REVIEW: A systematic review of the literature was performed in accordance with PRISMA guidelines. Medline, Embase.com, Scopus, Cochrane Library, and Clinicaltrials.gov databases were searched to identify all original research published in English through July 2020 on the topic of female cancer patients undergoing ovarian stimulation with a random or conventional start. Studies lacking a comparison group or including women who had already undergone chemotherapy at the time of ovarian stimulation were excluded. The primary author assessed all identified article titles and abstracts, and two independent reviewers assessed full-text articles and extracted data. A meta-analysis with a random-effects model was used to calculate weighted mean differences (WMDs) for outcomes of interest. The primary outcome was the number of mature (meiosis II) oocytes retrieved. Secondary outcomes included duration of stimulation, total dose of gonadotropins, total number of oocytes retrieved, fertilization rate, and number of embryos or zygotes cryopreserved. RESULTS: A total of 446 articles were screened, and 9 full-text articles (all retrospective cohort or prospective observational) were included for review. Additionally, pooled primary retrospective data from two institutions were included. In total, data from 10 studies including 1653 women were reviewed. Five studies reported the number of embryos cryopreserved, and four reported fertilization rates. Random-start cycles were slightly longer (WMD 0.57 days, 95 % confidence interval [CI] 0.0-1.14 days) and used more total gonadotropins (WMD 248.8 international units, 95 % CI 57.24-440.40) than conventional-start cycles. However, there were no differences in number of mature oocytes retrieved (WMD 0.41 oocytes, 95 % CI -0.84-1.66), number of total oocytes retrieved (WMD 0.90 oocytes, 95 % CI -0.21-2.02), fertilization rates (WMD -0.12, 95 % CI -1.22-0.98), or number of embryos cryopreserved (WMD 0.12 embryos, 95 %CI -0.98-1.22) between random-start and conventional-start cycles. All outcomes except for the parameter "total oocytes retrieved" yielded an I2 of over 50 %, indicating substantial heterogeneity between studies. CONCLUSION(S): Although random-start cycles may entail a longer duration of stimulation and use more total gonadotropins than conventional-start cycles, the absolute differences are small and likely do not significantly affect treatment costs. The similar numbers of mature oocytes retrieved, fertilization rates, and number of embryos cryopreserved in the two start-types suggest that they do not differ in any clinically important ways. Given that random-start cycles can be initiated quickly, they may help facilitate fertility preservation for cancer patients.

Sex-specific risk profiles for substance use among college students.

INTRODUCTION: Growing evidence indicates sex and gender differences exist in substance use. Framed by a lifecourse perspective, we explored prospectively by sex the effects of distal and proximal factors on the initiation of drug use in college. METHODS: College students without prior drug use (n = 5,120 females; n = 2,951 males) were followed longitudinally across 4 years. Analyses were estimated as a multigroup survival analysis separately by sex within a latent variable SEM framework with illicit drug use (6 or more times in past year) as the latent factor. RESULTS: More males initiated drug use (8.5%) than females (6.4%, χ2 (1) = 10.351, p = .001), but less so for Black males (AOR 0.33, 95% CI [0.18, 0.60]) and females (0.35 [0.23, 0.54]). Students initiating drug use more likely included students smoking cigarettes at baseline (males 1.40 [1.23, 1.59]; females 1.43 [1.24, 1.64]), using alcohol (males 1.04 [1.02, 1.06]; females 1.04 [1.02, 1.06]), or having cannabis using peers (males 1.79 [1.52, 2.11]; females 1.70 [1.49, 1.93]). Impulsivity domain associations differed by sex [negative urgency: females (1.23 [1.02, 1.49) and sensation seeking: males (1.33 [1.01, 1.75])]. History of unwanted/uncomfortable sexual experience predicted drug use for males (1.60 [1.09, 2.35]) and females (1.95 [1.45, 2.62]) but physical assault only for females (1.45 [1.08, 1.94]). Mood symptoms predicted drug use only for males [depression (0.73 [0.56, 0.95]); anxiety (1.40 [1.04, 1.89])]. CONCLUSIONS: Risk factors for initiating drug use during college differ by sex. As substance use during early age predisposes one for addiction, sex- and gender-informed interventions for young adults are needed.

Buprenorphine management: a conundrum for the anesthesiologist and beyond - a one-act play.

We have witnessed a worldwide upsurge of streamlined enhanced recovery after surgery (ERAS) pathways advocating for consistency and compliance within their guidelines. At a recent national conference, two experts defended their institutional policies on perioperative management of buprenorphine, one defending its continuation, while the other suggesting its discontinuation. The moderator diplomatically proclaimed the need to have guidance at the institutional level and following it for favorable patient outcomes. Unfortunately, perioperative management of buprenorphine remains an understudied topic with a lack of national guidelines leading to variations at a local level despite its increased use nationally in the current opioid crisis. Although the moderator made a valid statement, we demonstrate via our one-act play the importance of recognizing a subset of the population within an ERAS pathway that necessitates multidisciplinary discussion, communication, and patient-centric care to formulate a perioperative plan coordinating a patient's care. More robust research is needed to minimize variability in current practices and to further develop comprehensive evidence-based guidelines that encompass risk factors and anticipated postsurgical and peripartum pain for patients on buprenorphine.

Co-occurring substance use disorder: The impact on treatment adherence in women with locally advanced cervical cancer.

The purpose of this study was to identify the prevalence of substance use disorder and its association with adherence to treatment and survival in locally advanced cervical cancer patients treated with primary radiation therapy. This is a retrospective case series of locally advanced cervical cancer patients with substance use disorder in a single academic institution treated with radiation therapy between 2005 and 2016. Substance use disorder was identified through chart review. Those with substance use disorder were compared to those without in regards to demographics, Charlson comorbidity index, treatment details and outcomes. Of the 129 patients with locally advanced cervical cancer, 16 (12.4%) were identified as having substance use disorder. Patients with substance use disorder were younger (42.1 years vs 51.5 years, p = .013) and more likely to be smokers (81.3% vs 42.5%, p = .004). The majority of patients with substance use disorder received concurrent chemotherapy (93.8%) and brachytherapy in addition to external beam radiation therapy (81.3%). There was no significant difference in days to completion of radiation therapy between patients with and without substance use disorder. Radiation dose received, toxicities and survival were similar between groups. Among cervical cancer patients receiving treatment with radiation therapy, substance use disorder was not associated with poorer adherence, longer radiation treatment times or a difference in total dose of radiation received. Our experience demonstrates that patients with substance use disorder are able to adhere to complex, multimodal treatment plans resulting in similar cancer specific outcomes compared to patients without substance use disorder.

Recent trends in treatment admissions for marijuana use during pregnancy.

OBJECTIVES: The objective of this study was to investigate recent trends in substance abuse treatment admissions for marijuana use during pregnancy in the United States. METHODS: Data were obtained from the Treatment Episodes Data Set from 1992 to 2012 and analyzed for trends over time using χ, Cochran-Armitage, and Moran's I tests. RESULTS: The proportion of treatment admissions for women who were pregnant remained stable at 4%; however, admissions of pregnant women reporting any marijuana use increased substantially from 29% to 43% (P < 0.01). The West North Central census division (20%) experienced the greatest increase followed by the Middle Atlantic (18%) and Pacific (14%) divisions. The demographic characteristics of pregnant marijuana admissions changed over time, with white non-Hispanic women, criminal justice referrals, and those with a psychiatric comorbidity becoming more common whereas polysubstance users decreased (P < 0.01). CONCLUSIONS: Even though more women using marijuana are seeking and receiving substance abuse treatment during pregnancy, targeting certain risk groups while improving screening and treatment referral systems by health care providers, such as prenatal caregivers, should be emphasized.

Endocannabinoid regulation in human endometrium across the menstrual cycle.

Humans produce endogenous cannabinoids (endocannabinoids), a group of molecules that activate the same receptors as tetrahydrocannabinol. Endocannabinoids play important roles in reproduction in multiple species, but data in human endometrium are limited. Because endocannabinoids such as anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) often act within tissues as paracrine factors, their effects can be modulated by changes in expression of locally produced synthetic and degradative/oxidative enzymes. The objective of this study was to localize and quantify expression of these key synthetic and degradative/oxidative enzymes for AEA and 2-AG in human endometrium throughout the menstrual cycle. Key synthetic enzymes include N-arachidonyl-phosphatidylethanolamine phospholipase-D (NAPE-PLD), diacylglycerol-lipase a (DAGL-α, and DAGL-ß. Key degradative enzymes include fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL); cyclooxygenase 2 (COX2) is an oxidative enzyme. Endometrial samples were collected in 49 regularly cycling, normal women. Protein localization and expression were achieved by immunohistochemistry and messenger RNA (mRNA) expression by real-time reverse transcriptase polymerase chain reaction. No significant cycle-dependent mRNA expression was observed except that of COX2 (P = .002), which demonstrated maximum expression in the proliferative phase. During the secretory phase, NAPE-PLD protein had increased expression in luminal (P = .001), stromal (P = .007), and glandular (P = .04) epithelia, while FAAH had increased glandular (P = .009) and luminal (P = .01) expression. Increased expression in glandular epithelia was identified for MAGL (P = .03). The COX2 had increased luminal expression during the early secretory phase (P < .0001). In conclusion, maximal expression of degradatory/oxidative enzymes in the secretory phase may foster decreased endocannabinoid tone during implantation.

Evaluation of a single-visit approach to cervical cancer screening and treatment in Guyana: feasibility, effectiveness and lessons learned.

AIM: To evaluate a cervical cancer prevention project in Guyana utilizing visual inspection with acetic acid (VIA) and immediate cryotherapy in a single-visit approach; and to identify lessons learned to inform the improvement of cervical cancer prevention programs in Guyana and other low-resource settings. METHODS: Service records from January 2009 to June 2012 were analyzed for 18 cervical cancer prevention sites across Guyana. Records included women's HIV status, data on visual inspection with acetic acid screening and treatment status for women's initial and 1-year follow-up screenings, provider training and retention. A process evaluation was conducted in 2011 to identify programmatic strengths and interventions for integration, scale-up and sustainability. RESULTS: During the 42-month interval, 21,597 new screenings were performed, reaching 95% of HIV(+) women enrolled in care and 17% of women aged 25-49 years in Guyana. The VIA(+) rate was 13% (n = 2806); 85% of women eligible for cryotherapy received immediate treatment. Half of VIA(+) women treated with cryotherapy or loop electrosurgical excision procedure returned for a 1-year follow-up screening (n = 1027); 95% were VIA(-) at the second screening. Non-physician providers were more likely to continue offering services than physicians. Most programmatic challenges were related to systemic rather than technical/clinical issues. CONCLUSION: The single-visit approach-based program is feasible, effective, and when scaled up, likely to have an impact on overall incidence of cervical cancer. Services can be shifted to non-physicians for scale-up of high-quality cervical cancer prevention services nationally. To ensure sustainability and expansion, support structures should be prioritized.

Biopsychosocial correlates of persistent postsurgical pain in women with endometriosis.

OBJECTIVE: To examine pain and biopsychosocial correlates over time for women with persistent postsurgical pain after surgery for endometriosis. METHODS: Cross-sectional study of women who underwent any endometriosis surgery between 2003 and 2006. Following surgery, patients completed validated questionnaires (Short-Form McGill Pain Questionnaire, 12-item Short-Form Health Survey, Beck Depression Inventory, Coping Strategies Questionnaire catastrophizing subscale). The primary outcome was pelvic pain intensity, measured by the McGill total pain score. Bivariate comparisons between each potential predictor and pain intensity were performed using the χ(2) and t tests, 1-way analysis of variance, and simple linear regression. RESULTS: In total, 79 completed the questionnaires and were included in the present analysis. The McGill affective pain score was negatively correlated with age (ß-coefficient -0.12, P=0.002) and positively correlated with catastrophization (ß-coefficient 0.66, P=0.01). Women with a history of dyspareunia scored significantly higher on the McGill total pain score (P<0.001); there was no association between pain intensity and endometriosis severity. CONCLUSION: Younger age and catastrophization are correlated with persistent pain following surgery for endometriosis. The severity of endometriosis does not predict persistent pain. Further evaluation of psychosocial factors may identify patients who are least likely to benefit from surgeries for endometriosis-associated pelvic pain.