Prenatal exposure to environmental toxins and comprehensive dental findings in a population cohort of children.

Environmental toxins are known to have many impacts on growth and development in humans, starting in utero. Alterations in amelogenesis, caused by chemical and physical trauma that occur during the antenatal, perinatal and postnatal time periods, may result in developmental defects in deciduous and permanent tooth enamel, as demonstrated in animal studies. These defects can be clinically visible and result in a variety of morphological and functional problems in the dentition. Since enamel does not remodel after formation, it may serve as a permanent record of insults during organ development.Our primary purpose was to investigate any possible relationship between intrauterine exposure to endocrine disrupting chemicals (phenols and phthalates) and developmental defects in enamel in children, while also accounting for fluoride exposure. Our secondary purpose was to report descriptively on findings from comprehensive dental examinations performed on 356 children that were drawn from the general paediatric population. A cohort of children from the Utah Children's Project (N = 356) that had full medical exams, comprehensive medical and family histories and available biospecimens were given extraoral and intraoral examinations. They also completed an oral health questionnaire. Standardized intraoral photographs were taken of the teeth and viewed by standardised examiners and the dental observations were recorded for a full inventory of findings, including: tooth morphology, caries, restorations, colorations, attrition, erosion, fractures and hypomineralization. Perinatal maternal urine samples were assessed for the concentration of fluoride, phenols and phthalates, including bisphenol A (BPA).Pairwise statistical analyses were done to correlate the dental findings with one another and with the presence of environment chemicals found in the urine samples. Hypomineralization was the most common finding (96% of children; 37% of deciduous teeth, 42% of permanent teeth), consistent with molar incisor hypomineralization (MIH) described in other human populations. No consistent correlations were seen between dental findings and the presence of phenols and phthalates in prenatal urine, but the number of samples available for the assessment was limited (n = 35).In conclusion, we found a high proportion of dental hypomineralization in a population based paediatric cohort, but did not find an association with prenatal exposure to phenols and phthalates.

Cardiovascular disease risk in long-term breast cancer survivors: A population-based cohort study.

BACKGROUND: Breast cancer survival is increasing, making late effects such as cardiovascular disease (CVD) more relevant. The purpose of this study was to evaluate incident CVD following breast cancer diagnosis among long-term survivors and to investigate possible risk factors for CVD. METHODS: A population-based cohort of 6641 breast cancer survivors diagnosed between 1997 and 2009 who survived at least 10 years was identified within the Utah Cancer Registry. In addition, 36,612 cancer-free women from the general population, matched by birth year and state, were identified within the Utah Population Database. Cox proportional hazards models were used to calculate CVD hazard ratios (HRs) for >10 to 15 and >15 years. RESULTS: Long-term breast cancer survivors had an increased risk of newly diagnosed diseases of the circulatory system (HR, 1.32; 99% confidence interval [CI], 1.00-1.75) from 10 to 15 years following cancer diagnosis compared with the general population. No increased CVD risks were observed after 15 years. Breast cancer survivors with Charlson Comorbidity Index score ≥2 had a significantly higher risk of diseases of the circulatory system (HR, 2.64; 95% CI, 1.08-6.45) beyond 10 years following breast cancer diagnosis. Similarly, older age, obesity, lower education, and family history of CVD and breast cancer were risk factors for heart and circulatory system diseases among long-term breast cancer survivors. CONCLUSION: Risk of CVD compared to the general population was moderate among this cohort of long-term breast cancer survivors between 10 to 15 years since cancer diagnosis. Awareness of CVD risks is important for breast cancer survivors.

Does a short luteal phase correlate with an increased risk of miscarriage? A cohort study.

BACKGROUND: Miscarriage is defined as spontaneous loss of pregnancy prior to 20 weeks gestation. With an estimated risk of 15% of clinically confirmed pregnancies ending in miscarriage, it is the most common adverse event in pregnancy. Woman's age is the primary risk factor for miscarriage, while medical conditions, including hormonal abnormalities, are also associated. Progesterone is essential for maintaining pregnancy. A short luteal phase may reflect inadequate levels of progesterone production, but it is unclear whether a short luteal phase correlates with an increase in the risk of miscarriage. METHODS: Using a cohort study design, we conducted a secondary data analysis from four cohorts of couples who used a standardized protocol to track biomarkers of the female cycles. A short luteal phase was defined as less than 10 days, with < 11, < 9, and < 8 days as alternate definitions in sensitivity analyses. We included women who experienced a pregnancy with a known outcome, identified the length of the luteal phase in up to 3 cycles prior to conception and assessed the relationship with miscarriage using a modified Poisson regression analysis, adjusting for demographic characteristics, smoking, alcohol use and previous pregnancy history. RESULTS: In our sample of 252 women; the overall miscarriage rate was 18.7%. The adjusted incident risk ratio of miscarriage in women who had at least one short luteal phase < 10 days, compared to those who had none, was 1.01 (95% CI: 0.57, 1.80) Similar null risk was found when assessing alternative lengths of short luteal phase. Women who had short luteal phases < 10 days in all 3 cycles prior to the conception cycle had an incident risk ratio of 2.14 (95% CI: 0.7, 6.55). CONCLUSIONS: Our study found that a short luteal phase in the three cycles prior to conception was not associated with higher rates of miscarriage in an international cohort of women tracking their cycles, but our sample size was limited. Further research to determine if short luteal phases or luteal phase deficiency is associated with early pregnancy losses among preconception cohorts with daily tracking of cycle parameters, in addition to progesterone and human chorionic gonadotropin levels, is warranted. Additionally, future studies should include women with recurrent short luteal phases as a more likely risk factor than isolated short luteal phases.

This study looks at whether women have a higher risk of miscarriage if the second half of their menstrual or reproductive cycle is shorter than normal. The second half of the cycle, referred to as the luteal phase, is normally 11 to 16 days long. If the luteal phase is too short this may suggest a woman does not have enough progesterone, the hormone essential for maintaining pregnancy.This study included 252 pregnant women for whom we had data on the length of at least one luteal phase prior to pregnancy and for whom we knew the outcome of the pregnancy. Almost one-fifth of the women in our study had a miscarriage. However, we found there was no difference in the risk for miscarriage if women had a short or a normal luteal phase.

Fertility treatments and the risk of preterm birth among women with subfertility: a linked-data retrospective cohort study.

BACKGROUND: In vitro fertilization (IVF) births contribute to a considerable proportion of preterm birth (PTB) each year. However, there is no formal surveillance of adverse perinatal outcomes for less invasive fertility treatments. The study objective was to describe associations between fertility treatment (in vitro fertilization, intrauterine insemination, usually with ovulation drugs (IUI), or ovulation drugs alone) and preterm birth, compared to no treatment in subfertile women. METHODS: The Fertility Experiences Study (FES) is a retrospective cohort study conducted at the University of Utah between April 2010 and September 2012. Women with a history of primary subfertility self-reported treatment data via survey and interviews. Participant data were linked to birth certificates and fetal death records to asses for perinatal outcomes, particularly preterm birth. RESULTS: A total 487 birth certificates and 3 fetal death records were linked as first births for study participants who completed questionnaires. Among linked births, 19% had a PTB. After adjustment for maternal age, paternal age, maternal education, annual income, religious affiliation, female or male fertility diagnosis, and duration of subfertility, the odds ratios and 95% confidence intervals (CI) for PTB were 2.17 (CI 0.99, 4.75) for births conceived using ovulation drugs, 3.17 (CI 1.4, 7.19) for neonates conceived using IUI and 4.24 (CI 2.05, 8.77) for neonates conceived by IVF, compared to women with subfertility who used no treatment during the month of conception. A reported diagnosis of female factor infertility increased the adjusted odds of having a PTB 2.99 (CI 1.5, 5.97). Duration of pregnancy attempt was not independently associated with PTB. In restricting analyses to singleton gestation, odds ratios were not significant for any type of treatment. CONCLUSION: IVF, IUI, and ovulation drugs were all associated with a higher incidence of preterm birth and low birth weight, predominantly related to multiple gestation births.

Infertility treatments such as in vitro fertilization are associated with preterm birth, but less is known about how other less invasive treatments contribute to preterm birth. This study compares different types of fertility treatments and rates of preterm birth with women who are also struggling with infertility but did not use fertility treatments at the time of their pregnancy. 490 women were recruited at the University of Utah between 2010 and 2012. Participants were asked to complete a survey and were linked to birth certificate and fetal death certificate data. Women who used in vitro fertilization were 4.24 times more likely to have a preterm birth than those who used no treatment. Use of intrauterine insemination were 3.17 times more likely to have a preterm birth than those who used no treatment at time of conception. Ovulation stimulating drugs were 2.17 times more likely to have a preterm birth. Having female factor infertility was also associated with higher odds of having preterm birth. For those who are having trouble conceiving, trying less invasive treatments to achieve pregnancy might reduce their risk of preterm birth.

Cervical mucus patterns and the fertile window in women without known subfertility: a pooled analysis of three cohorts.

STUDY QUESTION: What is the normal range of cervical mucus patterns and number of days with high or moderate day-specific probability of pregnancy (if intercourse occurs on a specific day) based on cervical mucus secretion, in women without known subfertility, and how are these patterns related to parity and age? SUMMARY ANSWER: The mean days of peak type (estrogenic) mucus per cycle was 6.4, the mean number of potentially fertile days was 12.1; parous versus nulliparous, and younger nulliparous (<30 years) versus older nulliparous women had more days of peak type mucus, and more potentially fertile days in each cycle. WHAT IS KNOWN ALREADY: The rise in estrogen prior to ovulation supports the secretion of increasing quantity and estrogenic quality of cervical mucus, and the subsequent rise in progesterone after ovulation causes an abrupt decrease in mucus secretion. Cervical mucus secretion on each day correlates highly with the probability of pregnancy if intercourse occurs on that day, and overall cervical mucus quality for the cycle correlates with cycle fecundability. No prior studies have described parity and age jointly in relation to cervical mucus patterns. STUDY DESIGN, SIZE, DURATION: This study is a secondary data analysis, combining data from three cohorts of women: 'Creighton Model MultiCenter Fecundability Study' (CMFS: retrospective cohort, 1990-1996), 'Time to Pregnancy in Normal Fertility' (TTP: randomized trial, 2003-2006), and 'Creighton Model Effectiveness, Intentions, and Behaviors Assessment' (CEIBA: prospective cohort, 2009-2013). We evaluated cervical mucus patterns and estimated fertile window in 2488 ovulatory cycles of 528 women, followed for up to 1 year. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were US or Canadian women age 18-40 years, not pregnant, and without any known subfertility. Women were trained to use a standardized protocol (the Creighton Model) for daily vulvar observation, description, and recording of cervical mucus. The mucus peak day (the last day of estrogenic quality mucus) was used as the estimated day of ovulation. We conducted dichotomous stratified analyses for cervical mucus patterns by age, parity, race, recent oral contraceptive use (within 60 days), partial breast feeding, alcohol, and smoking. Focusing on the clinical characteristics most correlated to cervical mucus patterns, linear mixed models were used to assess continuous cervical mucus parameters and generalized linear models using Poisson regression with robust variance were used to assess dichotomous outcomes, stratifying by women's parity and age, while adjusting for recent oral contraceptive use and breast feeding. MAIN RESULTS AND THE ROLE OF CHANCE: The majority of women were <30 years of age (75.4%) (median 27; IQR 24-29), non-Hispanic white (88.1%), with high socioeconomic indicators, and nulliparous (70.8%). The mean (SD) days of estrogenic (peak type) mucus per cycle (a conservative indicator of the fertile window) was 6.4 (4.2) days (median 6; IQR 4-8). The mean (SD) number of any potentially fertile days (a broader clinical indicator of the fertile window) was 12.1 (5.4) days (median 11; IQR 9-14). Taking into account recent oral contraceptive use and breastfeeding, nulliparous women age ≥30 years compared to nulliparous women age <30 years had fewer mean days of peak type mucus per cycle (5.3 versus 6.4 days, P = 0.02), and fewer potentially fertile days (11.8 versus 13.9 days, P < 0.01). Compared to nulliparous women age <30 years, the likelihood of cycles with peak type mucus ≤2 days, potentially fertile days ≤9, and cervical mucus cycle score (for estrogenic quality of mucus) ≤5.0 were significantly higher among nulliparous women age ≥30 years, 1.90 (95% confidence interval (CI) 1.18, 3.06); 1.46 (95% CI 1.12, 1.91); and 1.45 (95% CI 1.03, 2.05), respectively. Between parous women, there was little difference in mucus parameters by age. Thresholds set a priori for within-woman variability of cervical mucus parameters by cycle were examined as follows: most minus fewest days of peak type mucus >3 days (exceeded by 72% of women), most minus fewest days of non-peak type mucus >4 days (exceeded by 54% of women), greatest minus least cervical mucus cycle score >4.0 (exceeded by 73% of women), and most minus fewest potentially fertile days >8 days (found in 50% of women). Race did not have any association with cervical mucus parameters. Recent oral contraceptive use was associated with reduced cervical mucus cycle score and partial breast feeding was associated with a higher number of days of mucus (both peak type and non-peak type), consistent with prior research. Among the women for whom data were available (CEIBA and TTP), alcohol and tobacco use had minimal impact on cervical mucus parameters. LIMITATIONS, REASONS FOR CAUTION: We did not have data on some factors that may impact ovulation, hormone levels, and mucus secretion, such as physical activity and body mass index. We cannot exclude the possibility that some women had unknown subfertility or undiagnosed gynecologic disorders. Only 27 women were age 35 or older. Our study participants were geographically dispersed but relatively homogeneous with regard to race, ethnicity, income, and educational level, which may limit the generalizability of the findings. WIDER IMPLICATIONS OF THE FINDINGS: Patterns of cervical mucus secretion observed by women are an indicator of fecundity and the fertile window that are consistent with the known associations of age and parity with fecundity. The number of potentially fertile days (12 days) is likely greater than commonly assumed, while the number of days of highly estrogenic mucus (and higher probability of pregnancy) correlates with prior identifications of the fertile window (6 days). There may be substantial variability in fecundability between cycles for the same woman. Future work can use cervical mucus secretion as an indicator of fecundity and should investigate the distribution of similar cycle parameters in women with various reproductive or gynecologic pathologies. STUDY FUNDING/COMPETING INTEREST(S): Funding for the three cohorts analyzed was provided by the Robert Wood Johnson Foundation (CMFS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (TTP), and the Office of Family Planning, Office of Population Affairs, Health and Human Services (CEIBA). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Differential impacts of particulate air pollution exposure on early and late stages of spermatogenesis.

BACKGROUND: Despite increasing evidence that particulate air pollution has adverse effects on human semen quality, few studies examine the impact of air pollution on clinically relevant thresholds used to diagnose male fertility problems. Furthermore, exposure is often assessed using average air pollution levels in a geographic area rather than individualized estimates. Finally, physiologically-informed exposure windows are inconsistent. OBJECTIVES: We sought to test the hypothesis that airborne particulate exposures during early-phase spermatogenesis will have a differential impact on spermatogenic formation compared to late-phase exposures, using an individualized model of exposure to particulate matter ≤ 2.5 µm and ≤ 10 µm (PM2.5 and PM10, respectively). METHODS: From an original cohort of 183 couples, we conducted a retrospective analysis of 130 healthy males seeking to become parents, using spermatogenesis-relevant exposure windows of 77-34 days and 37-0 days prior to semen collection to encompass sperm development stages of mitosis/meiosis and spermiogenesis, respectively. Individualized residential exposure to PM2.5 and PM10 was estimated by selecting multiple air pollution sensors within the same geographic air basin as participants and employing inverse distance weighting to calculate mean daily exposure levels. We used multiple logistic regression to assess the association between pollution, temperature, and dichotomized World Health Organization semen parameters. RESULTS: During the early phase of spermatogenesis, air pollution exposure is associated with 1.52 (95% CI: 1.04-2.32) times greater odds of < 30% normal heads per 1-unit increase in IQR for PM2.5. In the late phase of spermatogenesis, air pollution exposure is associated with 0.35 (95% CI: 0.10-0.74) times greater odds of semen concentration < 15 million/mL per 1-unit increase in IQR for PM2.5, and 0.28 (95% CI: 0.07-0.72) for PM10. CONCLUSION: Particulate exposure has a differential and more deleterious impact on sperm during early-phase spermatogenesis than late-phase.

Genitourinary disease risks among ovarian cancer survivors in a population-based cohort study.

OBJECTIVE: While genitourinary complications during treatment for ovarian cancer are well-known, long-term adverse outcomes have not been well characterized. The number of ovarian cancer survivors has been increasing. The aim of this study was to investigate long-term adverse genitourinary outcomes in a population-based cohort. METHODS: We identified a cohort of 1270 ovarian cancer survivors diagnosed between 1996 and 2012 from the Utah Cancer Registry, and 5286 cancer-free women were matched on birth year and state from the Utah Population Database. Genitourinary disease diagnoses were identified through ICD-9 codes from electronic medical records and statewide healthcare facilities data. Cox proportional hazards models were used to estimate hazard ratios (HR) for genitourinary outcomes at 1 to <5 years and 5+ years after ovarian cancer diagnosis. RESULTS: Ovarian cancer survivors had increased risks for urinary system disorders (HR: 2.53, 95% CI: 2.12-3.01) and genital organ disorders (HR: 1.88, 95% CI: 1.57-2.27) between 1 and <5 years after cancer diagnosis compared to the general population cohort. Increased risks were observed for acute renal failure, chronic kidney disease, calculus of kidney, hydronephrosis, pelvic peritoneal adhesions, and pelvic organ inflammatory conditions. Increased risks of several of these diseases were observed 5+ years after cancer diagnosis. CONCLUSIONS: Ovarian cancer survivors experience increased risks of various genitourinary diseases compared to women in the general population in the long-term. Understanding the multimorbidity trajectory among ovarian cancer survivors is important to improve clinical care after cancer treatment is completed.

Long-term diabetes risk among endometrial cancer survivors in a population-based cohort study.

OBJECTIVE: The majority of endometrial cancer patients are overweight or obese at cancer diagnosis. Obesity is a shared risk factor for both endometrial cancer and diabetes, but it is unknown whether endometrial cancer patients have increased diabetes risks. The aim of our study was to investigate diabetes risk among endometrial cancer patients. METHODS: Endometrial cancer patients diagnosed between 1997 and 2012 in Utah (n = 2,314) were identified. Women from the general population (n = 8,583) were matched to the cancer patients on birth year and birth state. Diabetes diagnoses were identified from electronic medical records and statewide healthcare facility databases. Cox proportional hazards models were used to estimate hazard ratios for diabetes after cancer diagnosis. RESULTS: Endometrial cancer survivors had a significantly higher risk of type II diabetes when compared to women from the general population in the first year after cancer diagnosis (HR = 5.22, 95% CI = 4.05, 6.71), >1-5 years after cancer diagnosis (HR = 1.67, 95% CI = 1.31, 2.12), and >5 years after cancer diagnosis (HR = 1.65, 95% CI = 1.29, 2.11). Endometrial cancer patients who were obese at cancer diagnosis had a three-fold increase in type II diabetes risk (HR = 2.99, 95%CI = 2.59, 3.45). Although endometrial cancer patients diagnosed at distant stage had a higher risk of diabetes, cancer treatment did not appear to contribute to any diabetes risks. CONCLUSIONS: In conclusion, endometrial cancer survivors had a higher risk of diabetes than women in the general population. These results suggest that long term monitoring for diabetes is indicated for endometrial cancer survivors.

Opioid Misuse and Dependence Screening Practices Prior to Surgery.

BACKGROUND: A majority of surgical patients are prescribed opioids for pain management. Many patients have pre-existing chronic pain managed with opioids and/or opioid use disorders (OUDs), which can complicate perioperative management. Patients who use opioids prior to surgery are at increased risk of developing OUD after surgery. To date, no studies have examined the prevalence of opioid screening and electronic medical record (EMR) documentation prior to surgery. MATERIALS AND METHODS: A 40-item survey was administered to 268 patients at their first postoperative care visit at a single tertiary academic center from October 2017 to July 2018. A chart review of a random sample of 100 patients was performed to determine provider opioid screening prevalence in the presurgical setting. Log-binomial models were used to calculate prevalence ratios (PRs) to determine the provider role (surgeon, advanced practice clinicians [APC], surgical trainee) association with opioid screening documentation. Exploratory qualitative interviews were conducted with surgical providers to identify barriers to screening and screening documentation. RESULTS: Only 7% of patients were screened preoperatively for opioid use. A total of 38% of patients self-reported that they had used opioids in the past year. Of that group, only 3% had screening by a surgical provider prior to surgery documented in their EMR. Provider role was not associated with likelihood of opioid screening (surgeon versus trainee, PR = 1.2, 95% CI 0.2-8.5) (surgeons versus APCs, PR = 1.05, 95% CI 0.17-8.53). EMRs were discordant with patient survey results for patients with no ICD-10 codes for opioid use. The most common perceived barriers to preoperative screening were insufficient clinic time; logistics of who should screen/not required as part of their clinical workflow; not perceiving screening as a priority; and lack of expertise in the area of chronic opioid use and OUD. CONCLUSIONS: Preoperative screening for opioid use is uncommon, and EMRs are often discordant with patient self-reported use. Efforts to increase preoperative screening will need to address barriers screening practices and increasing health system support by incorporating screening into the clinical workflow and adding it to documentation templates.

Comparison of woman-picked, expert-picked, and computer-picked Peak Day of cervical mucus with blinded urine luteinising hormone surge for concurrent identification of ovulation.

BACKGROUND: Previous research has demonstrated that women instructed in fertility awareness methods can identify the Peak Day of cervical mucus discharge for each menstrual cycle, and the Peak Day has high agreement with other indicators of the day of ovulation. However, previous studies enrolled experienced users of fertility awareness methods or were not fully blinded. OBJECTIVE: To assess the agreement between cervical mucus Peak Day identified by fertile women without prior experience on assessing cervical mucus discharge with the estimated day of ovulation (1 day after urine luteinising hormone surge). METHODS: This study is a secondary analysis of data from a randomised trial of the Creighton Model FertilityCareTM System (CrM), conducted 2003-2006, for women trying to conceive. Women who had no prior experience tracking cervical mucus recorded vulvar observations daily using a standardised assessment of mucus characteristics for up to seven menstrual cycles. Four approaches were used to identify the Peak Day. The referent day was defined as one day after the first identified day of luteinising hormone (LH) surge in the urine, assessed blindly. The percentage of agreement between the Peak Day and the referent day of ovulation was calculated. RESULTS: Fifty-seven women with 187 complete cycles were included. A Peak Day was identified in 117 (63%) cycles by women, 185 (99%) cycles by experts, and 187 (100%) by computer algorithm. The woman-picked Peak Day was the same as the referent day in 25% of 117 cycles, within ±1 day in 58% of cycles, ±2 days in 84%, ±3 days in 87%, and ±4 days in 92%. The ±1 day and ± 4 days' agreement was 50% and 90% for the expert-picked and 47% and 87% for the computer-picked Peak Day, respectively. CONCLUSIONS: Women's daily tracking of cervical mucus is a low-cost alternative for identifying the estimated day of ovulation.

Menstrual bleeding, cycle length, and follicular and luteal phase lengths in women without known subfertility: A pooled analysis of three cohorts.

BACKGROUND: There is variability between women for days of menstrual bleeding, cycle lengths, follicular phase lengths, and luteal phase lengths, related to age and parity. OBJECTIVE: To describe total cycle length; anovulatory cycles; follicular and luteal phase lengths; and days and intensity of menstrual and non-menstrual bleeding in women without known subfertility over the course of 1 year. METHODS: 581 women (3,324 cycles) with no known subfertility (18-40 years of age) were followed for up to 1 year. Women recorded vaginal bleeding and mucus discharge daily. We used the peak day of cervical mucus as the estimated day of ovulation and the last day of the follicular phase. We used generalised linear mixed models stratified by age and parity to describe menstrual cycle parameters. RESULTS: The majority of women were <30 years of age (74.5%), non-Hispanic White (88.6%), and nulliparous (70.4%). The mean menses length was 6.2 (1.5) days, median 6; cycle length 30.3 (6.7) days, median 29; follicular phase length 18.5 (6.5) days, median 17; and luteal phase length 11.7 (2.8) days, median 12. Nulliparous women aged ≥30 years vs nulliparous women aged <30 had shorter cycles (29.2 days, 95% confidence interval (CI) 27.8, 30.7 vs 31.5 days, 95% CI 30.8, 32.2) and shorter follicular phases (17.6 days, 95% CI 16.2, 18.9 vs 19.6 days, 95% CI 18.9, 20.2). Among all women, within-woman differences between the longest and shortest menses length >3 days, total cycle length >7 days, follicular phase >7 days, and luteal phase >3 days were found in 11.6%, 43.0%, 41.7%, and 58.8% of women, respectively. CONCLUSIONS: Our findings confirm variability between women of menstrual cycle parameters related to age and parity, and also highlight within-woman variability in the follicular and luteal phases.

Association between peri-conceptional bisphenol A exposure in women and men and time to pregnancy-The HOPE study.

BACKGROUND: Bisphenol A (BPA) is a non-persistent endocrine-disrupting chemical with nearly ubiquitous, involuntary exposure. Previous studies have shown that BPA causes reproductive dysfunction in animal models, but there are limited data regarding the effects of BPA exposure on time to pregnancy (TTP) in humans. OBJECTIVE: To evaluate whether peri-conceptional BPA exposure of women and men is associated with couples' TTP. METHODS: A total of 164 heterosexual couples (164 women; 163 men) who have available BPA information as well as time to pregnancy from the Home Observation of Peri-conceptional Exposures (HOPE) Study were included and were followed up to 12 months. Women collected first-morning urine samples starting at the beginning of the fertile window and continued until the onset of menses or 18 days after the estimated day of ovulation (EDO+18 days). The time to pregnancy (TTP) after the enrolment was self-reported and used for the analysis. Discrete-time Cox proportional hazards models were performed to generate fecundability odds ratio (FOR) between BPA and TTP after adjusting for education and age, accounting for right censoring and prior number of cycles trying to conceive. RESULTS: Among 164 couples, 125 couples became pregnant during the study. There was no association between TTP and peri-conceptional BPA exposure for both men (FOR 1.02, 95% CI 0.72, 1.47) and women (FOR 1.07, 95% CI 0.75, 1.53) after adjusting for education and age. CONCLUSIONS: No association was found between peri-conceptional BPA exposure and fecundability in this preconception cohort of relatively young, healthy pregnancy planners.

The Preconception Period analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium.

BACKGROUND: Preconception health may have intergenerational influences. We have formed the PrePARED (Preconception Period Analysis of Risks and Exposures influencing health and Development) research consortium to address methodological, conceptual, and generalisability gaps in the literature. OBJECTIVES: The consortium will investigate the effects of preconception exposures on four sets of outcomes: (1) fertility and miscarriage; (2) pregnancy-related conditions; (3) perinatal and child health; and (4) adult health outcomes. POPULATION: A study is eligible if it has data measured for at least one preconception time point, has a minimum of selected core data, and is open to collaboration and data harmonisation. DESIGN: The included studies are a mix of studies following women or couples intending to conceive, general-health cohorts that cover the reproductive years, and pregnancy/child cohort studies that have been linked with preconception data. The majority of the participating studies are prospective cohorts, but a few are clinical trials or record linkages. METHODS: Data analysis will begin with harmonisation of data collected across cohorts. Initial areas of interest include nutrition and obesity; tobacco, marijuana, and other substance use; and cardiovascular risk factors. PRELIMINARY RESULTS: Twenty-three cohorts with data on almost 200 000 women have combined to form this consortium, begun in 2018. Twelve studies are of women or couples actively planning pregnancy, and six are general-population cohorts that cover the reproductive years; the remainder have some other design. The primary focus for four was cardiovascular health, eight was fertility, one was environmental exposures, three was child health, and the remainder general women's health. Among other cohorts assessed for inclusion, the most common reason for ineligibility was lack of prospectively collected preconception data. CONCLUSIONS: The consortium will serve as a resource for research in many subject areas related to preconception health, with implications for science, practice, and policy.

The Home Observation of Periconceptional Exposures (HOPE) study, a prospective cohort: aims, design, recruitment and compliance.

BACKGROUND: To examine transient environmental exposures and their relationship with human fecundity, exposure assessment should occur optimally at the time of conception in both members of the couple. We performed an observational, prospective cohort study with biomonitoring in both members of a heterosexual couple trying to conceive. Couples collected urine, saliva, and semen specimens for up to two menstrual cycles on days corresponding to the time windows of fertilization, implantation, and early pregnancy, identified based on the woman's observations of her cervical fluid. RESULTS: Three hundred nine eligible couples were screened between 2011 and 2015, of which 183 enrolled. Eleven couples (6.0 %) withdrew or were lost to follow up. The most successful and cost effective recruiting strategies were word of mouth (40 % of participating couples), posters and flyers (37 %), and targeted Facebook advertising (13 %) with an overall investment of $37.35 spent on recruitment per couple. Both men and women collected ≥97.2 % of requested saliva samples, and men collected ≥89.9 % of requested semen samples. Within the periovulatory days (±3 days), there was at least one urine specimen collected by women in 97.1 % of cycles, and at least one by men in 91.7 % of cycles. Daily compliance with periovulatory urine specimens ranged from 66.5 to 92.4 % for women and from 55.7 to 75.0 % for men. Compliance was ≥88 % for questionnaire completion at specified time points. CONCLUSIONS: Couples planning to conceive can be recruited successfully for periconceptional monitoring, and will comply with intensive study protocols involving home collection of biospecimens and questionnaire data.

Predictors of patient adherence to follow-up recommendations after an ED visit.

BACKGROUND: It is unclear whether factors identified during the emergency department (ED) visit predict noncompliance with ED recommendations. STUDY OBJECTIVE: We sought to determine predictors of adherence to medical recommendations after an ED visit. METHODS: We conducted a prospective, observational study at a single urban medical center. Eligible ED patients provided baseline demographic data as well as information regarding insurance status, whether they had a primary care physician (PCP), and the impact of cost of care on their ability to follow medical recommendations. Patients were contacted at least 1 week after the ED visit and answered questions regarding adherence to medical recommendations. RESULTS: Four hundred twenty-two patients agreed to participate in the study. At follow-up, 89.7% of patients reported that they had complied with recommendations made during the ED visit. Patients who were adherent to follow-up recommendations were more likely to have a primary care provider (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.1-6.1), have an annual income of greater than $35000 (OR, 2.9; 95% CI, 1.2-7.2), and report a non-Hispanic ethnicity or race (OR, 2.8; 95% CI, 1.1-7.1). Individuals who reported that cost "sometimes" or "always" impacts their ability to follow their physician's recommendations were significantly less likely to comply with ED recommendations (OR, 2.7; 95% CI, 1.3-5.6). CONCLUSION: Individuals who reported that cost affects their ability to follow their physician's recommendations and those who did not have a PCP were less likely to follow ED recommendations. Identification of predictors of noncompliance during the ED visit may aid in ensuring compliance with ED recommendations.

Development and initial validation of a fertility experiences questionnaire.

BACKGROUND: Many women throughout the world have history of subfertility (resolved or unresolved), but much remains unknown about services and treatments chosen. METHODS: We developed a mixed-mode fertility experiences questionnaire (FEQ) in 2009 through literature review and iterative pilot work to optimize question format and mode of administration. The focus of the FEQ is to collect data retrospectively on time at risk for pregnancy, fertility treatments received and declined, pregnancy, time to pregnancy and pregnancy outcomes. We conducted a validation of key elements of the FEQ with comparison to medical records in 2009 and 2010. The validation sample was selected from women initially seen at a specialized fertility treatment center in Utah in 2004. RESULTS: The FEQ was optimized with two components: 1) written (paper or web-based), self-administered, followed by 2) telephone- administered questions. In 63 patients analyzed, high levels of correlation were identified between patient self-report and medical records for the use of intrauterine insemination and assisted reproductive technology, pregnancy and live birth histories, time at risk for pregnancy and time to pregnancy. There was low correlation between medical records and self-report for the use of oral ovulation drugs and injectable ovulation drugs. Compared to the medical record, the FEQ was over 90% sensitive for all elements, except injectable ovulation drugs (70% sensitivity). CONCLUSIONS: The FEQ accurately captured elements of fertility treatment history at 5-6 years after the first visit to a specialty clinic.

Specialty of prescribers associated with prescription opioid fatalities in Utah, 2002-2010.

UNLABELLED: Opioid adverse events are widespread, and deaths have been directly attributed to opioids prescribed by medical professionals. Little information exists on the amount of opioids various medical specialties prescribe and the opioid fatality rate that would be expected if prescription opioid-related deaths were independent of medical specialty. OBJECTIVE: To compute the incidence of prescription opioid fatalities by medical specialty in Utah and to calculate the attributable risk (AR) of opioid fatality by medical specialty. DESIGN: Prevalence database study design linking the Utah Controlled Substance Database (CSD) for prescribing data with the Utah Medical Examiner data to identify prescription opioid fatalities. AR were calculated for each medical specialty and year. RESULTS: Opioid prescriptions are common with 23,302,892 recorded in the CSD for 2002-2010, 0.64% of which were associated with a fatality. We attached specialty to 90.2% of opioid prescriptions. Family medicine and internal medicine physicians wrote the largest proportion of prescriptions (24.1% and 10.8%) and were associated with the greatest number of prescription opioid fatalities. The number of active prescriptions at time of death decreased each year. The AR of fatality by provider specialty varied each year with some specialties, such as pain medicine and anesthesiology, consistently associated with more fatalities per 1,000 opioid prescriptions than internal medicine physicians the same year. CONCLUSIONS: Primary care providers were the most frequent prescribers and the most often associated with opioid fatalities and should be targeted for education about safe prescribing along with specialties that prescribe less frequently but are associated with a positive AR for opioid fatality.

Pilot test and validation of the peak day method of prospective determination of ovulation against a handheld urine hormone monitor.

BACKGROUND: Transient exposures may influence fertility and early embryonic development. To assess the time of conception in vivo and conduct concurrent biomonitoring, ovulation must be identified prospectively. We report on the development and validation of a simple, prospective method, the Peak Day method, to determine likely day of ovulation based upon daily observations of cervical fluid. METHODS: We recruited 98 women to learn the Peak Day method from a brochure, 26 of whom concurrently used the method with blinded daily urine hormone monitoring (estrone glucuronide and luteinizing hormone). All women were instructed to complete an exposure questionnaire immediately upon identifying ovulation. Briefly, the exposure questionnaire captured time-varying and transient exposures such as medication use, water consumption, and amount of sleep. We assessed timely completion of the exposure questionnaire, agreement of women's estimated day of ovulation (EDO) and the EDO by expert review, and agreement between the EDO by expert review and by blinded urine monitoring. RESULTS: Of 147 cycles evaluated, women selected an EDO in 130 (88%) and subsequently completed the periovulatory exposure questionnaire in 122 (94%) cycles. Of the 26 cycles evaluated with blinded hormonal monitoring, the Peak Day "best quality" algorithm, based upon cervical fluid, identified ovulation ± 3 days of the urine monitor in 24 cycles (92%). CONCLUSIONS: With simple written instructions, women can identify an estimated day of ovulation and perform periovulatory exposure assessment. The Peak Day method is highly cost-effective and could be applied by researchers to target periconceptional or very early developmental stage exposure assessment.

Emergency physician knowledge of reimbursement rates associated with emergency medical care.

STUDY OBJECTIVE: We investigated emergency physician knowledge of the Centers for Medicare & Medicaid Services (CMS) reimbursement for common tests ordered and procedures performed in the emergency department (ED), determined the relative accuracy of their estimation, and reported the impact of perceived costs on physicians' ordering and prescribing behavior. METHODS: We distributed an online survey to 189 emergency physicians in 11 EDs across multiple institutions. The survey asked respondents to estimate reimbursement rates for a limited set of medical tests and procedures, rate their level of current cost knowledge, and determine the effect of health expenditures on their medical decision making. We calculated relative accuracy of cost knowledge as a percent difference of participant estimation of cost from the CMS reimbursement rate. RESULTS: Ninety-seven physicians participated in the study. Most respondents (65%) perceived their knowledge of costs as inadequate, and 39.3% indicated that beliefs about cost impacted their ordering behavior. Eighty percent of physicians surveyed were unable to estimate 25% of the costs within ±25%, and no physicians estimated at least 50% of costs within 25% of the CMS reimbursement and only 17.3% of medical services were estimated correctly within ±25% by 1 or more physicians. CONCLUSION: Most emergency physicians indicated they should consider cost in their decision making but have a limited knowledge of cost estimates used by CMS to calculate reimbursement rates. Interventions that are easily accessible and applicable in the ED setting are needed to educate physicians about costs, reimbursement, and charges associated with the care they deliver.

Use of fertility treatments in relation to the duration of pregnancy attempt among women who were trying to become pregnant and experienced a live birth.

The purpose of this study was to compare the utilization of medical help for fertility among women who reported up to a year versus more than a year of trying to become pregnant and to describe the characteristics of those women seeking early treatment. Data from the 2004-2008 Pregnancy Risk Assessment Monitoring System (PRAMS) survey were used to assess attempt duration and use of fertility treatments in a sample of 9,517 women who had a recent live birth in Utah. PRAMS respondents who were trying to become pregnant at the time of conception were asked questions about fertility treatments (sampling n = 5,238; representative n = 153,036). Univariate and bivariate analyses were used to describe and compare characteristics of women who sought treatment after attempting pregnancy for a year or less and women who waited at least a year to seek treatment. Among women who were trying to become pregnant, 9.5 % reported using some medical assistance to conceive. Among the women trying to become pregnant, 89.3 % had been trying for ≤12 months and 10.7 % reported having tried >12 months. 5.2 % of those trying to become pregnant for up to a year reported use of fertility treatment, compared with 45.8 % of those trying for a year or more. Women who had previous live births were significantly more likely to use early treatment than nulliparous women (aOR = 2.4, 95 % CI = 1.5, 3.9). The use of fertility drugs and other treatments were more common than ART among recipients of early treatment (aOR = 3.7, 95 % CI = 1.7, 7.9). Some women may be receiving fertility treatment before it is clinically indicated. Instead of invasive treatment, these women may benefit from preconception counseling on folic acid, healthy prepregnancy weight and use of ovulation monitoring to time intercourse.