Project description:BackgroundApproximately 1 in 7 couples experience subfertility, many of whom have lifestyles that negatively affect fertility, such as poor nutrition, low physical activity, obesity, smoking, or alcohol consumption. Reducing lifestyle risk factors prior to pregnancy or assisted reproductive technology treatment contributes to the improvement of reproductive health, but cost-implications are unknown.ObjectiveThe goal of this study was to evaluate reproductive, maternal pregnancy, and birth outcomes, as well as the costs of pre-conception lifestyle intervention programs in subfertile couples and obese women undergoing assisted reproductive technology.MethodsUsing a hypothetical model based on quantitative parameters from published literature and expert opinion, we evaluated the following lifestyle intervention programs: (1) Smarter Pregnancy, an online tool; (2) LIFEstyle, which provides outpatient support for obese women; (3) concurrent use of both Smarter Pregnancy and LIFEstyle for obese women; (4) smoking cessation in men; and (5) a mindfulness mental health support program using group therapy sessions. The model population was based on data from the Netherlands.ResultsAll model-based analyses of the lifestyle interventions showed a reduction in the number of in vitro fertilization, intracytoplasmic sperm injection, or intrauterine insemination treatments required to achieve pregnancy and successful birth for couples in the Netherlands. Smarter Pregnancy was modeled to have the largest increase in spontaneous pregnancy rate (13.0%) and the largest absolute reduction in potential assisted reproductive technology treatments. Among obese subfertile women, LIFEstyle was modeled to show a reduction in the occurrence of gestational diabetes, maternal hypertensive pregnancy complications, and preterm births by 4.4%, 3.8%, and 3.0%, respectively, per couple. Modeled cost savings per couple per year were €41 (US $48.66), €360 (US $427.23), €513 (US $608.80), €586 (US $695.43), and €1163 (US $1380.18) for smoking cessation, mindfulness, Smarter Pregnancy, combined Smarter Pregnancy AND LIFEstyle, and LIFEstyle interventions, respectively.ConclusionsAlthough we modeled the potential impact on reproductive outcomes and costs of fertility treatment rather than collecting real-world data, our model suggests that of the lifestyle interventions for encouraging healthier behaviors, all are likely to be cost effective and appear to have positive effects on reproductive, maternal pregnancy, and birth outcomes. Further real-world data are required to determine the cost-effectiveness of pre-conception lifestyle interventions, including mobile apps and web-based tools that help improve lifestyle, and their effects on reproductive health. We believe that further implementation of the lifestyle app Smarter Pregnancy designed for subfertile couples seeking assistance to become pregnant is likely to be cost-effective and would allow reproductive health outcomes to be collected.
Project description:We determined the length of time within which frozen-thawed semen delivered a high conception rate in present-day lactating dairy cows. The cows utilized were a total 100 milking Holstein-Friesian cows kept in tie-stall style farms. We carried out artificial insemination (AI) during the periovulatory period at a predicted time based on ovulation, and checked ovulation at 6-h intervals after AI. The period from AI to ovulation ranged from 48 h (i.e., 48 h before ovulation) to -12 h (i.e., 12 h after ovulation). High conception rates averaging 63.0% were obtained by carrying out AI > 6-30 h before ovulation, significantly higher than the conception rates of 30.0% (P < 0.05) and 26.9% (P < 0.01) from AI carried out earlier than 30 h before ovulation and later than 6 h before ovulation, respectively. It was concluded that frozen-thawed semen delivers a conception rate of ? 60% for > 24-30 h after AI, and that a conception rate of ? 60% can be achieved by carrying out AI 6-30 h before ovulation using frozen-thawed semen.
Project description:More extreme cold weather and larger weather variations have raised concerns regarding their effects on public health. Although prior studies assessed the effects of cold air temperature on health, especially mortality, limited studies evaluated wind chill temperatures on morbidity, and health effects under the current cold warning threshold. This study identified the thresholds, lag periods, and best indicators of extreme cold on cardiovascular disease (CVD) by comparing effects of wind chill temperatures and cold air temperatures on CVD emergency department (ED) visits in winter and winter transition months. Information was collected on 662,625 CVD ED visits from statewide hospital discharge dataset in New York State. Meteorological factors, including air temperature, wind speed, and barometric pressure were collected from National Oceanic and Atmospheric Administration. A case-crossover approach was used to assess the extreme cold-CVD relationship in winter (December-February) and transition months (November and March) after controlling for PM2.5. Conditional logistic regression models were employed to analyze the association between cold weather factors and CVD ED visits. We observed CVD effects occurred when wind chill temperatures were as high as -3.8?°C (25?°F), warmer than current wind chill warning standard (?-28.8?°C or ?-20?°F). Wind chill temperature was a more sensitive indicator of CVD ED visits during winter with temperatures???-3.8?°C (25?°F) with delay effect (lag 6); however, air temperature was better during transition months for temperatures???7.2?°C (45?°F) at earlier lag days (1-3). Among all CVD subtypes, hypertension ED visit had the strongest negative association with both wind chill temperature and air temperature. This study recommends modifying the current cold warning temperature threshold given larger proportions of CVD cases are occurring at considerably higher temperatures than the current criteria. We also recommend issuing cold warnings in winter transitional months.
Project description:Background and purposeWhen mapping the ischemic core and penumbra in patients with acute ischemic stroke using perfusion imaging, the core is currently delineated by applying the same threshold value for relative CBF at all time points from onset to imaging. We investigated whether the degree of perfusion abnormality and optimal perfusion parameter thresholds for defining ischemic core vary with time from onset to imaging.Materials and methodsIn a prospectively maintained registry, consecutive patients were analyzed who had ICA or M1 occlusion, baseline perfusion and diffusion MR imaging, treatment with IV tPA and/or endovascular thrombectomy, and a witnessed, well-documented time of onset. Ten superficial and deep MCA ROIs were analyzed in ADC and perfusion-weighted images.ResultsAmong the 66 patients meeting entry criteria, onset-to-imaging time was 162 minutes (range, 94-326 minutes). Of the 660 ROIs analyzed, 164 (24.8%) showed severely or moderately reduced ADC (ADC ≤ 620, ischemic core), and 496 (75.2%), mildly reduced or normal ADC (ADC > 620). In ischemic core ADC regions, longer onset-to-imaging times were associated with more highly abnormal perfusion parameters-relative CBF: Spearman correlation, r = -0.22, P = .005; relative CBV: r = -0.41, P < .001; MTT: - r = -0.29, P < .001; and time-to-maximum: r = 0.35, P < .001. As onset-to-imaging times increased, the best cutoff values for relative CBF and relative CBV to discriminate core from noncore tissue became progressively lower and overall accuracy of the core tissue definition increased.ConclusionsPerfusion abnormalities in ischemic core regions become progressively more abnormal with longer intervals from onset to imaging. Perfusion parameter value thresholds that best delineate ischemic core are more severely abnormal and have higher accuracy with longer onset-to-imaging times.
Project description:Improvements in bull reproductive performance are necessary to optimize the efficiency of cattle production. Female fertility has been enhanced through assisted reproductive technologies as well as genetic selection; however, improving beef bull fertility has been largely ignored. Phenotypes routinely collected at bull semen collection facilities are believed to affect fertility and provide the phenotypes necessary for a genetic evaluation. The first objective of this study was to determine the significant fixed effects for modeling beef bull fertility using data from bull semen collection facilities. The second objective was to estimate variance components, heritabilities, repeatabilities, and correlations between beef bull semen attributes. Beef bull fertility phenotypes including volume (VOL), concentration (CONC), number of spermatozoa (NSP), initial motility (IMot), post-thaw motility (PTMot), 3-h post-thaw motility (3HRPTMot), percentage of normal spermatozoa (%NORM), primary abnormalities (PRIM), and secondary abnormalities (SEC) were obtained from two bull semen collection facilities. A total of 1,819 Angus bulls with 50,624 collection records were analyzed. Of the fixed class and covariate effects tested, the significant class effects were collection location and collection day within year and the significant covariate effects included age at collection, days since previous collection, and cumulative comprehensive climate index (CCI). For this study, the CCI was calculated for a 75-d period including the 61-d spermatogenesis cycle and 14-d epididymal transit time. The 75 d prior to collection accounted for the environmental stress a bull may have experienced over the course of development of the spermatozoa, which was more significant than the CCI calculated for collection day or spermatogenesis start date. Pre-thaw beef bull semen traits had low heritability estimates of 0.11 ± 0.02 (VOL), 0.09 ± 0.02 (CONC), 0.08 ± 0.02 (NSP), and 0.12 ± 0.03 (IMot). Heritabilities of post-thaw beef bull semen attributes were more variable at 0.10 ± 0.02 (PTMot), 0.05 ± 0.04 (3HRPTMot), 0.10 ± 0.04 (%NORM), 0.03 ± 0.03 (PRIM), and 0.18 ± 0.04 (SEC). Correlations of breeding values for these traits with scrotal circumference (SC) expected progeny difference (EPD) are low. The low to moderate heritability estimates indicate that genetic improvement can be made in beef bull semen quality traits if new tools are developed to augment the scrotal circumference EPD that are currently available within the industry.
Project description:Sperm count, morphology, and motility have been reported to be predictive of pregnancy, although with equivocal basis prompting some authors to question the prognostic value of semen analysis. To assess the utility of including semen quality data in predicting conception delay or requiring >6 cycles to become pregnant (referred to as conception delay), we utilized novel data-driven analytic techniques in a pre-conception cohort of couples prospectively followed up for time-to-pregnancy. The study cohort comprised 402 (80%) male partners who provided semen samples and had time-to-pregnancy information. Female partners used home pregnancy tests and recorded results in daily journals. Odds ratios (OR), false discovery rates, and 95% confidence intervals (CIs) for conception delay (time-to-pregnancy > 6 cycles) were estimated for 40 semen quality phenotypes comprising 35 semen quality endpoints and 5 closely related fecundity determinants (body mass index, time of contraception, lipids, cotinine and seminal white blood cells). Both traditional and strict sperm phenotype measures were associated with lower odds of conception delay. Specifically, for an increase in percent morphologically normal spermatozoa using traditional methods, we observed a 40% decrease in conception delay (OR = 0.6, 95% CI = 0.50, 0.81; p = 0.0003). Similarly, for an increase in strict criteria, we observed a 30% decrease in odds for conception delay (OR = 0.7, 95% CI = 0.52, 0.83; p = 0.001). On the other hand, an increase in percent coiled tail spermatozoa was associated with a 40% increase in the odds for conception delay (OR = 1.4, 95% CI = 1.12, 1.75; p = 0.003). However, our findings suggest that semen phenotypes have little predictive value of conception delay (area under the curve of 73%). In a multivariate model containing significant semen factors and traditional risk factors (i.e. age, body mass index, cotinine and ever having fathered a pregnancy), there was a modest improvement in prediction of conception delay (16% increase in area under the curve, p < 0.0002).
Project description:BACKGROUND:Prenatal phthalate exposure has been inconsistently associated with fetal growth and infant birth weight. However, the effect of exposure during the paternal and maternal preconception period remains understudied. OBJECTIVES:To investigate associations of paternal and maternal preconception and maternal prenatal urinary phthalate metabolite concentrations with birth weight. METHODS:The study comprised 364 singletons born to 364 mothers and 195 fathers (195 couples) from the EARTH Study, a prospective cohort of couples from Boston, MA. Births were categorized by mode of conception: in-vitro fertilization based (IVF) (n=208) or non-IVF based (n=156, intrauterine insemination or non-medically assisted/natural conception). We measured urinary concentrations of eleven phthalate metabolites in maternal (n=1425) and paternal (n=489) preconception and maternal prenatal (n=781) samples. Birth weight was abstracted from delivery records. Covariate-adjusted associations between loge-phthalate metabolite concentrations and birth weight were evaluated separately by mode of conception using multivariable linear regression. RESULTS:Each loge-unit increase in paternal urinary concentration of the sum of di(2-ethylhexyl) phthalate (?DEHP) metabolites was associated with a 90 gram (95% CI: -165, -15) decrease in birth weight among IVF singletons, but not among non-IVF singletons (18g; 95% CI: -76, 113). Additional adjustment for maternal prenatal ?DEHP concentrations modestly strengthened findings among IVF singletons. While few associations were found with maternal preconception phthalate metabolites, we observed an inverse relationship between several maternal prenatal urinary phthalate metabolite concentrations and birth weight among IVF singletons in covariate-adjusted models. However, with further adjustment for specific paternal phthalate metabolite concentrations, these associations were attenuated and no longer significant. CONCLUSIONS:Paternal preconception urinary concentration of ?DEHP metabolites was associated with a decrease in birth weight among IVF-conceived singletons. These results, if replicated, highlight the importance of preconception health, especially among subfertile couples.
Project description:BACKGROUND:Subfertility among couples affected by HIV has an impact on the well-being of couples who desire to have children and may prolong HIV exposure. Subfertility in the antiretroviral therapy era and its determinants have not yet been well characterized. OBJECTIVE:The objective of the study was to investigate the burden and determinants of subfertility among HIV-affected couples seeking safer conception services in South Africa. STUDY DESIGN:Nonpregnant women and male partners in HIV seroconcordant or HIV discordant relationships desiring a child were enrolled in the Sakh'umndeni safer conception cohort at Witkoppen Clinic in Johannesburg between July 2013 and April 2017. Clients were followed up prospectively through pregnancy (if they conceived) or until 6 months of attempted conception, after which they were referred for infertility services. Subfertility was defined as not having conceived within 6 months of attempted conception. Robust Poisson regression was used to assess the association between baseline characteristics and subfertility outcomes; inverse probability weighting was used to account for missing data from women lost to safer conception care before 6 months of attempted conception. RESULTS:Among 334 couples enrolled, 65% experienced subfertility (inverse probability weighting weighted, 95% confidence interval, 0.59-0.73), of which 33% were primary subfertility and 67% secondary subfertility. Compared with HIV-negative women, HIV-positive women not on antiretroviral therapy had a 2-fold increased risk of subfertility (weighted and adjusted risk ratio, 2.00; 95% confidence interval, 1.19-3.34). Infertility risk was attenuated in women on antiretroviral therapy but remained elevated, even after ?2 years on antiretroviral therapy (weighted and adjusted risk ratio, 1.63; 95% confidence interval, 0.98-2.69). Other factors associated with subfertility were female age (weighted and adjusted risk ratio, 1.03, 95% confidence interval, 1.01-1.05 per year), male HIV-positive status (weighted and adjusted risk ratio, 1.31; 95% confidence interval, 1.02-1.68), male smoking (weighted and adjusted risk ratio, 1.29; 95% confidence interval, 1.05-1.60), and trying to conceive for ?1 year (weighted and adjusted risk ratio, 1.38; 95% confidence interval, 1.13-1.68). CONCLUSION:Two in 3 HIV-affected couples experienced subfertility. HIV-positive women were at increased risk of subfertility, even when on antiretroviral therapy. Both male and female HIV status were associated with subfertility. Subfertility is an underrecognized reproductive health problem in resource-limited settings and may contribute to prolonged HIV exposure and transmission within couples. Low-cost approaches for screening and treating subfertility in this population are needed.
Project description:The smallest detectable interaural time difference (ITD) for sine tones was measured for four human listeners to determine the dependence on tone frequency. At low frequencies, 250-700 Hz, threshold ITDs were approximately inversely proportional to tone frequency. At mid-frequencies, 700-1000 Hz, threshold ITDs were smallest. At high frequencies, above 1000 Hz, thresholds increased faster than exponentially with increasing frequency becoming unmeasurably high just above 1400 Hz. A model for ITD detection began with a biophysically based computational model for a medial superior olive (MSO) neuron that produced robust ITD responses up to 1000 Hz, and demonstrated a dramatic reduction in ITD-dependence from 1000 to 1500 Hz. Rate-ITD functions from the MSO model became inputs to binaural display models-both place based and rate-difference based. A place-based, centroid model with a rigid internal threshold reproduced almost all features of the human data. A signal-detection version of this model reproduced the high-frequency divergence but badly underestimated low-frequency thresholds. A rate-difference model incorporating fast contralateral inhibition reproduced the major features of the human threshold data except for the divergence. A combined, hybrid model could reproduce all the threshold data.
Project description:BACKGROUND:Women with irregular menstruation should be considered to benefit from the ovarian stimulation. However, most literature did not separate ovulatory disorders from normal menstrual cycles. Our purpose was to assess the superiority of ovarian mild stimulation compared with the natural cycle in IUI for subfertile couples when the women with regular menstruation. METHODS:A retrospective study in a single medical center in which 2413 couples with 3573 IUI cycles were studied from 2013 to 2018. The results of IUI in natural cycles versus low-dose HMG induced cycles were analyzed. RESULTS:For young women (age?<?35?years) with normal menstrual cycle, HMG induced ovulation combined with IUI can improve clinical pregnancy outcome (13.55% in two follicular induced cycles vs. 7.23% in natural cycles, p?<?0.01); even if only one follicle was induced, the clinical pregnancy rate was increased to 10.32% (p?<?0.01). When two growth follicles were induced in HMG cycles, a remarkable improvement of the live birthrate (10.28% vs. 5.91% in natural cycles, p?<?0.05) was noted. Simultaneously, twin pregnancy rates were increased to 20.69% (p?<?0.01). Twin pregnancies showed significantly increased risk of both ectopic pregnancy and preterm birth (p?=?0.00 for both). For advanced women (age???35?years) with regular menstrual cycle, ovulation induction didn't improve clinical pregnancy and live birthrates, while age was the only relevant factor. CONCLUSIONS:Combining HMG induced ovulation and IUI can improve pregnancy outcome in young women with normal menstrual cycles. 1-2 follicles with diameter???14?mm served as the purpose of ovulation induction. Further, both twin and ectopic pregnancy rate in HMG cycles with two growth follicles were significantly higher than those in natural cycles were. Therefore, doctors must evaluate the risk before making choices and inform the patients to achieve the best results. For advanced women with normal menstrual cycles, natural IUI cycles were optional.