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:Study questionWhat are the experiences and the support and sexual advice needs of subfertile couples continuing to attempt natural conception after the diagnostic fertility work-up?Summary answerExploration of the experiences of couples showed that couples would have appreciated fertility clinic staff embedding expectant management into the fertility clinic trajectory, supportive staff with female and male patient interactions and advice on common experiences of peers and on managing their lifestyle, distress and subfertility-related sexual challenges.What is known alreadyDutch and British professional guidelines advise newly diagnosed subfertile couples with a 'good prognosis' to continue to attempt natural conception and do not require fertility clinic staff to interact with patients. Fertility clinic staff and subfertile couples struggle to follow these guidelines as they feel an urgent need for action. Subfertile couples might benefit from sexual advice, as subfertility is negatively associated with sexual functioning, which is important for natural conception.Study design size durationTwelve one-time in-depth interviews (2015-2017) were conducted with 10 heterosexual couples and 2 women whose partners did not participate, then the interviews were subjected to inductive content analysis, reaching inductive thematic saturation.Participants/materials setting methodsThe 22 interviewees had experienced 3-18 months of expectant management after their diagnostic fertility work-up in a Belgian or a Dutch tertiary fertility clinic. The face-to-face in-depth interviews explored positive and negative experiences and unmet needs. The transcribed interviews were subjected to inductive content analysis, by two researchers discussing initial disagreements.Main results and the role of chanceCouples would appreciate fertility clinic staff embedding expectant management in the fertility clinic trajectory, by starting off with reassuring couples that their very thorough diagnostic fertility work-up demonstrated their good chance of natural conception, and by involving couples in deciding on the duration of expectant management and by planning the follow-up appointment after expectant management up front. Couples had encountered sexual challenges during expectant management and had an interest in sexual advice, focused on increasing pleasure and partner bonding and preventing the rise of dysfunctions. The couples agreed that a (secured) website with evidence-based, non-patronizing text and mixed media would be an appropriate format for a novel support programme. Couples were keen for interactions with fertility clinic staff which addressed both partners of subfertile couples. Couples also valued advice on managing their lifestyle and distress and would have liked information on the experiences of their peers.Limitations reasons for cautionRecall bias is plausible given the retrospective nature of this study. This explorative interview study was not designed for examining country or gender differences in experiences and needs but it did generate new findings on inter-country differences.Wider implications of the findingsRather than simply advising expectant management, fertility clinics are encouraged to offer couples who continue to attempt natural conception after their diagnostic fertility work-up, supportive patient-staff interactions with advice on common experiences of peers and on managing their lifestyle, distress and sexual challenges related to subfertility.Study funding/competing interestsFunded by Flanders Research Foundation and the University of Amsterdam. There are no competing interests.Trial registration numberN/A.
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:PurposeTo examine trends of population-level semen quality over a 20-year period.Materials and methodsWe performed a retrospective review of data from the andrology lab of a high volume tertiary hospital. All men with semen samples between 2000 and 2019 were included and men with azoospermia were excluded. Semen parameters were reported using the World Health Organization (WHO) 4th edition. The primary outcome of interest was changes in semen parameters over time. Generalized least squares (GLS) with restricted cubic splines were used to estimate average-monthly measurements, adjusting for age and abstinence period. Contrasts of the estimated averages based on GLS between the first and last months of collection were calculated.ResultsA total of 8,990 semen samples from subfertile non-azoospermic men were included in our study. Semen volume decreased over time and estimate average at the beginning and end were statistically different (p<0.001). Similarly sperm morphology decreased over time, with a statistically significant difference between estimated averages from start to finish (p<0.001). Semen pH appeared to be increasing over time, but this difference was not significant over time (p=0.060). Sperm concentration and count displayed an increase around 2003 to 2005, but otherwise remained fairly constant over time (p=0.100 and p=0.054, respectively). Sperm motility appeared to decrease over time (p<0.001).ConclusionsIn a large sample of patients presenting to a single institution for fertility assessment, some aspects of semen quality declined across more than two decades. An understanding of the etiologies and driving forces of changing semen parameters over time is warranted.
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:BackgroundPrenatal 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.ObjectivesTo investigate associations of paternal and maternal preconception and maternal prenatal urinary phthalate metabolite concentrations with birth weight.MethodsThe 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.ResultsEach loge-unit increase in paternal urinary concentration of the sum of di(2-ethylhexyl) phthalate (ΣDEHP) 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 ΣDEHP 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.ConclusionsPaternal preconception urinary concentration of ΣDEHP 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: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.