Emergency department utilization for ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a rare, but serious, risk of assisted reproductive technologies. In severe cases, patients may present to the emergency department (ED) for assessment, treatment of related complications, and even in-patient admission. Significant effort has been made to reduce the incidence and complications of OHSS; however, it is unknown if these strategies have decreased patient presentation for treatment in the ED. PURPOSE: To assess ED utilization for OHSS over time and to examine admission rates, patient demographics, and charges. METHODS: Retrospective longitudinal study utilizing data from the Nationwide Emergency Department Sample Database and the National ART Surveillance System. All ED visits between 2006 and 2016 with an ICD-9 or -10 diagnosis of OHSS were included. Demographics including age, geographic location, and income quartile and alternative diagnoses, admission rates, overall charges, and number of stimulation cycles annually were assessed. RESULTS: The number of ovarian stimulation cycles steadily increased from 2006 (n = 110,183) to 2016 (n = 157,721), while the number of OHSS-related ED visits remained relatively stable (APC 2.08, p = 0.14). Admission rates for OHSS decreased from 52.7% in 2006 to 33.1% in 2016 (APC -4.43%, p < 0.01). The average charge for OHSS-related ED visits almost doubled from 2006 to 2016 (APC 8.53, p < 0.01) and was significantly higher than charges for non-OHSS-related visits for age-matched controls (p < 0.01). CONCLUSION: Despite an increase in total stimulation cycles, there was no significant change in the estimated number of patients presenting to the ED; however, admission rates significantly declined. These observations suggest a possible shift in the severity and/or management of OHSS during the study period.

Pre-conception blood pressure and evidence of placental malperfusion.

BACKGROUND: Evidence of placental maternal vascular malperfusion is associated with significant perinatal outcomes such as preeclampsia, intrauterine growth restriction and preterm birth. Elevations in pre-pregnancy blood pressure increase the risk for poor perinatal outcomes; however, the evidence linking pre-pregnancy blood pressure and placental malperfusion is sparse. MATERIALS AND METHODS: We conducted a retrospective case-control study of women with singleton gestations with placental evaluations who delivered at Magee-Womens Hospital in 2012. Charts from 100 deliveries with placental malperfusion lesions (vasculopathy, advanced villous maturation, infarct, or fibrin deposition) and 102 deliveries without placental malperfusion were randomly selected for screening. Blood pressure, demographic, and clinical data were abstracted from pre-pregnancy electronic medical records and compared between women with and without subsequent placental malperfusion lesions. RESULTS: Overall, 48% of women had pre-pregnancy records, and these were similarly available for women with and without placental malperfusion. Women with placental malperfusion demonstrated a reduction in their pre- to early pregnancy decrease in diastolic blood pressure (DBP). Adjusted for race, pre-pregnancy BMI, age, pre-conception interval, and gestational age at the first prenatal visit, the difference in pre- to early pregnancy DBP was significantly less in women with placental malperfusion compared to those without this pathologic finding (- 1.35 mmHg drop vs - 5.6mmg, p < 0.05). CONCLUSION: A blunted early gestation drop in DBP may be a risk factor for placental malperfusion, perhaps related to early pregnancy vascular maladaptation. The ability of the electronic medical record to provide pre-pregnancy data serves as an underutilized approach to study pre-pregnancy health.

Fertility Preservation Outcomes in Adolescent and Young Adult Feminizing Transgender Patients.

BACKGROUND: Fertility preservation enables patients undergoing gonadotoxic therapies to retain the potential for biological children and now has broader implications in the care of transgender individuals. Multiple medical societies recommend counseling on fertility preservation before initiating therapy for gender dysphoria; however, outcome data pre- and posttreatment are limited in feminizing transgender adolescents and young adults. METHODS: The University of Pittsburgh Institutional Research Board approved this study. Data were collected retrospectively on transgender patients seeking fertility preservation between 2015 and 2018, including age at initial consultation and semen analysis parameters. RESULTS: Eleven feminizing transgender patients accepted a referral for fertility preservation during this time; consultation occurred at median age 19 (range 16-24 years). Ten patients attempted and completed at least 1 semen collection. Eight patients cryopreserved semen before initiating treatment. Of those patients, all exhibited low morphology with otherwise normal median semen analysis parameters. In 1 patient who discontinued leuprolide acetate to attempt fertility preservation, transient azoospermia of 5 months' duration was demonstrated with subsequent recovery of spermatogenesis. In a patient who had previously been treated with spironolactone and estradiol, semen analysis revealed persistent azoospermia for the 4 months leading up to orchiectomy after discontinuation of both medications. CONCLUSIONS: Semen cryopreservation is a viable method of fertility preservation in adolescent and young adult transgender individuals and can be considered in patients who have already initiated therapy for gender dysphoria. Further research is needed to determine the optimal length of time these therapies should be discontinued to facilitate successful semen cryopreservation.

Conception rates and contraceptive use after bariatric surgery among women with infertility: Evidence from a prospective multicenter cohort study.

BACKGROUND: Lack of prospective trials have resulted in a dearth of information regarding postbariatric surgery conception rates in women with a preoperative history of infertility. OBJECTIVE: To examine associations between preoperative history of infertility and postbariatric surgery conception. SETTING: A multicenter cohort study at 10 United States hospitals (2006-2009). METHODS: Participants completed a preoperative reproductive health questionnaire, with annual postoperative assessments for up to 7 years until January 2015. This report was restricted to women 18- to 44-years old with no history of menopause, hysterectomy, or hormone replacement therapy. The primary outcomes were postoperative (0 to <90 mo) conception rate, early conception rate (0 < 18 mo), and postoperative unprotected intercourse with a male partner while not trying to conceive. RESULTS: Of 740 eligible women, 650 (87.8%) provided required responses. Median interquartile range (IQR) preoperative age was 34 (30-39) years and follow-up was 6.5 (5.9-7.0) years. Nulliparous women with a preoperative history of infertility represented 8.0% (52/650) of the total cohort, 63.5% (33/52) of whom had never conceived. Compared with women without this history, these women had a higher postoperative conception rate (121.2 [95% confidence interval (CI), 102.3-143.5]/1000 versus 47.0 [95%CI, 34.2-62.9]/1000 woman-yr; P < .001), early conception rate (115.4 [95%CI, 96.1-138.5]/1000 versus 33.9 [95%CI, 23.6-47.1]/1,000 woman-yr; P < .01), and a higher risk of unprotected intercourse (ARR 1.48 [95% CI, 1.14-1.90], P = 0.003). CONCLUSION: After bariatric surgery, preoperative history of infertility and nulliparity was associated higher conception rates and unprotected intercourse.

Selective Serotonin Reuptake Inhibitors and Fertility: Considerations for Couples Trying to Conceive.

BACKGROUND: Depression and anxiety are prevalent disorders and are often treated with selective serotonin reuptake inhibitors (SSRIs). Infertility is also common among couples, and rates of depression and anxiety are elevated in this population, but the impact of SSRIs on fertility has received modest attention. This review explores the literature available on SSRIs, fertility, and infertility-treatment outcomes to assist clinicians in better counseling their patients. METHODS: A literature search was performed using the search terms infertility, fertility, antidepressants, and SSRIs to identify studies that investigated the relationship between SSRI use and fertility or infertility-treatment outcomes. RESULTS: Twenty relevant articles were identified, 16 of which were original research studies. The studies varied in design, quality, and outcome measures, limiting meta-analysis. The prevalence of antidepressant use ranged from 3.5%-10% in reproductive-age women, with infertile populations reporting less use. The two studies examining the impact of SSRIs in fertile women had conflicting results. Six of the seven studies in infertility patients found no significant association between SSRIs and treatment outcomes; three observed a trend, however, toward reduced fecundability or negatively influenced fertility biomarkers. One study found treatment increased pregnancy rates. In males, most studies were of relatively poor quality, though six of the seven studies found SSRIs to have an adverse effect on semen parameters. CONCLUSIONS: There is insufficient evidence at present to propose that SSRIs reduce fertility or influence infertility-treatment outcomes. SSRIs may have an adverse impact on sperm quality, but further research is warranted.

Contraception and Conception After Bariatric Surgery.

OBJECTIVE: To examine contraceptive practices and conception rates after bariatric surgery. METHODS: The Longitudinal Assessment of Bariatric Surgery-2 is a multicenter, prospective cohort study of adults undergoing first-time bariatric surgery as part of routine clinical care at 10 U.S. hospitals. Recruitment occurred between 2005 and 2009. Participants completed preoperative and annual postsurgical assessments for up to 7 years until January 2015. This report was restricted to women 18-44 years old with no history of menopause, hysterectomy, or estrogen and progesterone therapy. Primary outcomes were self-reported contraceptive practices, overall conception rate, and early (less than 18 months) postsurgical conception. Contraceptive practice (no intercourse, protected intercourse, unprotected intercourse, or tried to conceive) was classified based on the preceding year. Conception rates were determined from self-reported pregnancies. RESULTS: Of 740 eligible women, 710 (95.9%) completed follow-up assessment(s). Median (interquartile range) preoperative age was 34 (30-39) years. In the first postsurgical year, 12.7% (95% CI 9.4-16.0) of women had no intercourse, 40.5% (95% CI 35.6-45.4) had protected intercourse only, 41.5% (95% CI 36.4-46.6) had unprotected intercourse while not trying to conceive, and 4.3% (95% CI 2.4-6.3) tried to conceive. The prevalence of the first three groups did not significantly differ across the 7 years of follow-up (P for all >.05); however, more women tried to conceive in the second year (13.1%, 95% CI 9.3-17.0; P<.001). The conception rate was 53.8 (95% CI 40.0-71.1) per 1,000 woman-years across follow-up (median [interquartile range] 6.5 [5.9-7.0] years); 42.3 (95% CI 30.2-57.6) per 1,000 woman-years in the 18 months after surgery. Age (adjusted relative risk 0.41 [95% CI 0.19-0.89] per 10 years, P=.03), being married or living as married (adjusted relative risk 4.76 [95% CI 2.02-11.21], P<.001), and rating future pregnancy as important preoperatively (adjusted relative risk 8.50 [95% CI 2.92-24.75], P<.001) were associated with early conception. CONCLUSIONS: Postsurgical contraceptive use and conception rates do not reflect recommendations for an 18-month delay in conception after bariatric surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00465829.

Geographic access to assisted reproductive technology health care in the United States: a population-based cross-sectional study.

OBJECTIVE: To evaluate the geographic distribution of assisted reproductive technology (ART) clinics and the number of ART clinics within U.S. Census metropolitan areas and to estimate the number of reproductive-age women who have geographic access to ART services in the United States. DESIGN: A population-based cross-sectional study. SETTING: Not applicable. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of U.S. reproductive-age women living in areas with no ART clinic, a single ART clinic, or more than one ART clinic. RESULT(S): There were 510 ART clinics in the United States in 2009-2013. Multiple ART clinics were present in 76 metropolitan areas (median population of 1.45 million people), where a total of 442 clinics were located. A single ART clinic was present in 68 metropolitan areas (median population of 454,000 people). Among U.S. reproductive-age women in 2010, 38.1 million (60.4% of the U.S. population) lived in an area with multiple ART clinics, 6.8 million (10.8% of the U.S. population) lived in an area with a single clinic, and 18.2 million (28.8% of the U.S. population) lived in an area (metropolitan and nonmetropolitan) with no ART clinics. CONCLUSION(S): Nearby geographic access to ART services is limited or absent for more than 25 million reproductive-age women (39.6% of the U.S. population) in the United States. This population estimate should spur continued policy and technological progress to increase access to ART services.

Impact of Reduced ATGL-Mediated Adipocyte Lipolysis on Obesity-Associated Insulin Resistance and Inflammation in Male Mice.

Emerging evidence suggests that impaired regulation of adipocyte lipolysis contributes to the proinflammatory immune cell infiltration of metabolic tissues in obesity, a process that is proposed to contribute to the development and exacerbation of insulin resistance. To test this hypothesis in vivo, we generated mice with adipocyte-specific deletion of adipose triglyceride lipase (ATGL), the rate-limiting enzyme catalyzing triacylglycerol hydrolysis. In contrast to previous models, adiponectin-driven Cre expression was used for targeted ATGL deletion. The resulting adipocyte-specific ATGL knockout (AAKO) mice were then characterized for metabolic and immune phenotypes. Lean and diet-induced obese AAKO mice had reduced adipocyte lipolysis, serum lipids, systemic lipid oxidation, and expression of peroxisome proliferator-activated receptor alpha target genes in adipose tissue (AT) and liver. These changes did not increase overall body weight or fat mass in AAKO mice by 24 weeks of age, in part due to reduced expression of genes involved in lipid uptake, synthesis, and adipogenesis. Systemic glucose and insulin tolerance were improved in AAKO mice, primarily due to enhanced hepatic insulin signaling, which was accompanied by marked reduction in diet-induced hepatic steatosis as well as hepatic immune cell infiltration and activation. In contrast, although adipocyte ATGL deletion reduced AT immune cell infiltration in response to an acute lipolytic stimulus, it was not sufficient to ameliorate, and may even exacerbate, chronic inflammatory changes that occur in AT in response to diet-induced obesity.

A retrospective analysis of the utility of an artificial neural network to predict ED volume.

OBJECTIVE: The objectives of this study are to design an artificial neural network (ANN) and to test it retrospectively to determine if it may be used to predict emergency department (ED) volume. METHODS: We conducted a retrospective review of patient registry data from February 4, 2007, to December 31, 2009, from an inner city, tertiary care hospital. We harvested data regarding weather, days of week, air quality, and special events to train the ANN. The ANN belongs to a class of neural networks called multilayer perceptrons. We designed an ANN composed of 37 input neurons, 22 hidden neurons, and 1 output neuron designed to predict the daily number of ED visits. The training method is a supervised backpropagation algorithm that uses mean squared error to minimize the average squared error between the ANN's output and the number of ED visits over all the example pairs. RESULTS: A linear regression between the predicted and actual ED visits demonstrated an R2 of 0.957 with a slope of 0.997. Ninety-five percent of the time, the ANN was within 20 visits. CONCLUSION: The results of this study show that a properly designed ANN is an effective tool that may be used to predict ED volume. The scatterplot demonstrates that the ANN is least predictive at the extreme ends of the spectrum suggesting that the ANN may be missing important variables. A properly calibrated ANN may have the potential to allow ED administrators to staff their units more appropriately in an effort to reduce patient wait times, decrease ED physician burnout rates, and increase the ability of caregivers to provide quality patient care. A prospective is needed to validate the utility of the ANN.

Aromatase inhibition causes increased amplitude, but not frequency, of hypothalamic-pituitary output in normal women.

OBJECTIVE: To better understand the site and mode of action of aromatase inhibitors. DESIGN: Prospective study. SETTING: Academic research environment. PATIENT(S): Five eumenorrheic (without polycystic ovary syndrome), early follicular phase women with a normal body mass index (mean: 20.47±0.68 kg/m2), and 12 normal weight, midreproductive aged, early follicular phase women with a normal body mass index (mean: 20.8±1.7 kg/m2) as historical controls. INTERVENTION(S): 2.5 mg letrozole daily for 7 days, with daily urine collection (first morning void), thrice weekly blood sampling, and 4 hours of blood sampling every 10 minutes. MAIN OUTCOME MEASURE(S): Serum luteinizing hormone (LH) measured by a well-characterized immunofluorometric assay with LH pulse characteristics compared between treated and control groups using t tests. RESULT(S): Mean LH and LH pulse amplitude more than doubled in the women who had taken letrozole compared with the controls, but the LH pulse frequency did not differ between the women taking letrozole and the controls. CONCLUSION(S): These results indicate that the release of negative feedback inhibition of estradiol on the hypothalamic-pituitary axis in normal women by aromatase inhibitors creates an amplitude-related increase in endogenous hypothalamic-pituitary drive. The finding that the mean LH and LH pulse amplitude, but not the frequency, increased after letrozole suggests a possible pituitary site of action.

Biologic therapeutics and molecular profiling to optimize wound healing.

Non-healing wounds represent a significant cause of morbidity and mortality for a large portion of the adult population. Wounds that fail to heal are entrapped in a self-sustaining cycle of chronic inflammation leading to the destruction of the extracellular matrix. Among cancer patients, malnutrition, radiation, physical dehabilitation, chemotherapy, and the malignancy itself increase the likelihood of chronic wound formation, and these co-morbidity factors inhibit the normal wound healing process. Current wound treatments are aimed at some, but not all, of the underlying causes responsible for delayed healing of wounds. These impediments block the normal processes that allow normal progression through the specific stages of wound healing. This review summarizes the current information regarding the management and treatment of complex wounds that fail to heal normally and offers some insights into novel future therapies [Menke N, Ward KR, Diegelmann R. Non-healing wounds. Emerg Med Rep 2007; 28(4).,Menke NB, Ward KR, Witten TM, Bonchev DG, Diegelmann RF. Impaired wound healing. Clin Dermatol 2007;25:19-25].

Genetic approaches to polycystic ovarian syndrome.

PURPOSE OF REVIEW: This review clarifies the challenges facing investigators in the search for polycystic ovarian syndrome candidate genes. RECENT FINDINGS: Evidence for fibillin 3 has emerged as a polycystic ovarian syndrome candidate gene. The sex hormone binding gene also shows promise, as does evidence for fetal programming and X-chromosome inactivation. SUMMARY: As with many complex disorders, the heritability of polycystic ovarian syndrome has eluded investigators. Although familial aggregation studies have demonstrated clearly a genetic component to the syndrome, simple Mendelian models do not characterize its mode of inheritance. Instead, multiple loci and epigenetic modification may play a role in the phenotype. The candidate gene approach relies upon improved statistical and technological methods to analyze potential genes based on biologic plausibility. Pathways that affect steroidogenesis, insulin resistance, gonadotropin function, and obesity provide potential genes for investigation. Obstacles such as phenotypic variability, lack of a male phenotype, multiple attempts at analysis, and small sample sizes hamper these efforts. Nevertheless, great care must be taken to apply rigorous standards as we proceed with genetic studies. In addition to increasing our knowledge of common disorders, potential benefits include personalized medicine, with pharmacogenetics allowing therapies tailored to the individual.

Genetics of polycystic ovarian syndrome.

Polycystic ovarian syndrome is a complex disorder with multiple factors affecting its etiology. Elucidation of specific genes and mode of inheritance remains a significant challenge. Linkage and association studies have resulted in over 50 candidate genes as a source of heritable predisposition; however, small sample sizes and failure to reproduce results have hindered efforts. In addition, low fecundity, lack of a male phenotype, and variation of diagnostic criteria represent unique challenges to discovery of polycystic ovarian syndrome genes. A concerted effort will be necessary to conclusively rule in or rule out candidate genes.