This study aimed to compare the accuracy of IFN-τ stimulated gene abundance (ISGs) in peripheral blood mononuclear cells (PBMCs), CL blood perfusion by Doppler ultrasound (Doppler-US), plasma ...concentration of P4 on Day 21 and pregnancy-associated glycoproteins (PAGs) test on Day 25 after timed-artificial insemination (TAI) for early pregnancy diagnosis in dairy cows and heifers. Holstein cows (n = 140) and heifers (n = 32) were subjected to a hormonal synchronization protocol and TAI on Day 0. On Day 21 post-TAI, blood samples were collected for PBMC isolation and plasma concentration of P4. The CL blood perfusion was evaluated by Doppler-US. Plasma samples collected on Day 25 were assayed for PAGs. The abundance of ISGs (ISG15 and RSAD2) in PBMCs was determined by RT-qPCR. Pregnancy was confirmed on Days 32 and 60 post-TAI by B-mode ultrasonography. Statistical analyses were performed by ANOVA using the MIXED procedure and GLIMMIX in SAS software. The pregnancy biomarkers were used to categorize the females as having undergone late luteolysis (LL); early embryonic mortality (EEM); late embryonic mortality (LEM); or late pregnancy loss (LPL). The abundance of ISGs, CL blood perfusion by Doppler-US, and concentrations of P4 on Day 21, and PAGs test on Day 25 were significant (P < 0.05) predictors of early pregnancy in dairy cows and heifers. Dairy cows had a greater (P = 0.01) occurrence of LL than heifers, but there was no difference (P > 0.1) for EEM, LEM, and LPL in heifers compared to cows. Cows with postpartum reproductive issues had a greater (P = 0.008) rate of LEM and a lesser (P = 0.01) rate of LPL compared to cows without reproductive issues. In summary, the CL blood perfusion by Doppler-US had the highest accuracy and the least number of false negatives, suggesting it is the best predictor of pregnancy on Day 21 post-TAI. The PAGs test was the most reliable indicator of pregnancy status on Day 25 post-TAI in dairy heifers and cows. The application of machine learning, specifically the MARS algorithm, shows promise in enhancing the accuracy of predicting early pregnancies in cows.
•Combination of pregnancy biomarkers improves sensitivity and reduces false negatives for early pregnancy detection.•PAGs test on day 25 post-TAI has high accuracy for predicting pregnancy in dairy cows and heifers.•Late luteolysis occurred more frequently in dairy cows than heifers and is unrelated to the interferon-tau stimulus.•Machine learning models achieved 72 % accuracy for predicting pregnancy status in early gestation.
Mammalian pregnancy creates unique challenges for immune systems highly evolved to detect and eliminate invading pathogens. Recognition of the challenges created by gestating a semi-allogeneic fetus ...evolved from the discipline of transplantation biology and were informed by studies on the unique natural parabiosis that occurs when female calves are gestated with twin male fetuses. These pregnancies typically result in an intersex female termed a freemartin, which revealed insights into development of the male and female reproductive tracts. However, they also uncovered important clues on immune tolerance with wide-ranging implications to reproductive biology, transplantation biology and autoimmune disease. Many studies focused on identifying mechanisms through which the fetus evades maternal immune detection and elimination. These included studies characterizing immune interactions between the fetus and mother at the nourishing interface of the placenta and uterine endometrium. This immunological forbearance only occurs under high concentrations of circulating progesterone. Beyond the requirement for progesterone, there has been considerable progress towards understanding the effects of conceptus signals on maternal immune function. One common theme is that pregnancy induces a T helper 2 immune bias as shown in several mammalian species, including domestic ruminants. However, a growing body of evidence shows that the fetus not only evades, but also provokes immune responses locally in the uterus and in peripheral tissues. This is perhaps most dramatically illustrated by domestic ruminants where the conceptus secretes a unique interferon in the opening salvo of hormonal communication with the maternal immune system. The role of interferon tau in regulating expression of genes of the innate immune system in the uterus has been extensively studied. More recently, it was determined that these same genes are also induced in peripheral immune cells and other tissues throughout the body. In addition to interferon tau and progesterone, pregnancy associate glycoproteins and chaperonin 10 (aka Early Pregnancy Factor) are implicated in altering immune function both locally and systemically during pregnancy. While it is tempting to speculate that this activation of innate immunity is designed to counteract selective immunosuppression, knowledge of the importance of local and systemic immune activation to the success of pregnancy remains incomplete. This area remains fertile ground for developing better approaches to diagnose and treat infertility in domestic farm species and humans alike.
•Pregnancy presents an immunological challenge to the mother.•Pregnancy involves immune evasion, suppression, reprogramming and activation.•Progesterone is an essential component of immune regulation during pregnancy.•Conceptus proteins affect immune function in the uterus and systemically.•The importance of systemic immune modulation in pregnancy remains unclear.
Internationally there are no defined standards for expressing the performance of home-based pregnancy tests, nor any pre-defined accuracy standard requirements. The aim of this study was to evaluate ...the accuracy of a selection of home-based pregnancy tests relative to their packaging/product insert claims.
Eight home-based pregnancy tests were evaluated using human chorionic gonadotrophin (hCG) urine standards (0, 15, 25 mlU/mL). Testing was performed by a technician and results were read by a technician and a panel of consumer volunteers (each blinded to the expected result) and compared with the expected result based on the manufacturer's claimed accuracy. Volunteers also completed questionnaires relating to various device attributes.
The overall agreement between the technician reading and expected reading from the hCG concentration was >90% for the Clearblue® DIGITAL, Clearblue® PLUS, Confirme® Plus, David® and Haus™ tests, and approximately 80% for Predictor® Early; agreement was <50% for Femitest® Jet Ultra and Cyclotest® Early tests. RESULTS were available from 72 volunteers (aged 18-45 years). Overall the percentage agreement between volunteer result and expected result was >95% for Clearblue DIGITAL and Clearblue PLUS tests; agreement for all other tests was <75% (lowest were Cyclotest Early and Femitest Jet Ultra, 33.0% and 39.4%, respectively). The Clearblue DIGITAL test was scored most highly by volunteers in the questionnaires.
Many home-based pregnancy tests commonly used by women are not as accurate as their packaging information claims. International test standards which define appropriate performance characteristics for home pregnancy tests are urgently required.
Respect for patient autonomy is a pillar of medical ethics, manifested predominantly through informed consent. Mandatory (routine) nonconsented preoperative urine pregnancy testing does not ...adequately respect patient autonomy, is potentially coercive, and has the potential to cause harm medically, psychologically, socially, and financially. Inaccuracies in pregnancy testing can result in false-positive and false-negative results, especially in early pregnancy. There is substantial scientific evidence that anesthesia is not harmful to the fetus, raising the question of whether pregnancy testing provides substantial benefit to the patient. Not performing a preanesthesia pregnancy test has not been associated with significant medicolegal consequences. We review the ethical implications of mandatory preanesthesia pregnancy testing in light of these facts.
To assess whether planning high-sensitivity urine pregnancy tests (HSPT) rather than facility-based tests for medication abortion follow-up may increase risk of unplanned clinical visits or ...procedural completion of the abortion.
We used data from the TelAbortion Project, a 5-year study assessing the safety and feasibility of providing mifepristone and misoprostol by telemedicine and mail in the United States. We categorized participants by whether the pretreatment follow-up plan included HSPT at home 3–5 weeks after treatment or facility-based tests (ultrasound or serum human chorionic gonadotropin) within 2 weeks after treatment. We used multivariable logistic regression to compare likelihood of post-treatment unplanned, abortion-related clinical visits and procedural intervention in these groups.
Of 1324 patients who planned HSPT follow-up and 576 who planned facility-based tests, 85% and 83%, respectively, provided outcome information. Post-treatment clinical visits were less frequent in the HSPT group (19%) than in the facility-based test group (79%); most of the latter were to obtain the planned test. However, unplanned, abortion-related visits were significantly more common in the HSPT group (adjusted risk difference: 6.5%; p < 0.01). The likelihood of procedural completion did not differ by group. Planned follow-up test was not associated with delay in procedural completion or detection of ongoing pregnancy.
Follow-up of medication abortion with home HSPT was associated with fewer post-treatment clinical visits, modestly more unplanned, abortion-related clinical visits, and no increase in the risk of procedural interventions or delayed identification or management of treatment failures. This option is an appropriate follow-up approach after medication abortion.
Use of home high-sensitivity pregnancy tests rather than facility-based tests for outcome assessment after medication abortion is associated with a modest increase in unplanned clinical visits but does not lead to an increase in procedural interventions or delays identification and management of treatment failure.
A growing array of biomedical goods and services has become central to the North American experience of navigating illness and pursuing good health. Yet despite the utility of consumption as an ...analytical framework within the social sciences, the selection, purchase, and use of biomedical goods and services has been understudied. By using the home pregnancy test as a case study, we suggest new approaches to thinking about the consumption of these goods and services. We chose the home pregnancy test because it is the best-known example of a mass-produced diagnostic tool used by consumers. We draw on two sources of data for this qualitative analysis: a set of stories submitted between 2003 and 2005 by women and men to an online exhibit mounted by the National Institutes of Health called “A Thin Blue Line: The History of the Pregnancy Test Kit,” which we analysed between 2006 and 2007; and web sampling conducted in 2009 and 2010 of personal web and video logs of women and men who have posted stories and opinions about their experiences with contemporary home pregnancy testing products. We adapt the term “domestication” from Science and Technology Studies scholarship to describe the movement of diagnostic devices into homes for use by consumers. Specifically, we propose that the consumption of domesticated biomedical devices, goods, and services should be theorized as work performed by consumers, in two senses: as a form of tool use that allows non-experts to produce diagnostic knowledge about their own bodies and health; and as the ongoing biopolitical work that is expected of citizens to produce healthy bodies. Our paper draws attention to these understudied phenomena, while suggesting new approaches to theorizing the social and cultural elements of goods and services for health.
► Biomedical goods and services for consumers have proliferated in North America. ► Domestication describes the movement of biomedical goods and services into homes. ► The home pregnancy test is a domesticated health tool. ► Consumption of domesticated goods and services can be theorized as work. ► Domestication refers to a set of user practices, not just a place.
We aimed to evaluate the accuracy of Interferon-tau stimulated genes (ISG) abundance in peripheral blood polymorphonuclear cells (PMNs) on D20 after fixed-time artificial insemination (FTAI; D0) as a ...pregnancy diagnosis method against CL evaluation by Doppler ultrasonography and progesterone (P4) concentrations on D20, as well as Pregnancy Associated Glycoproteins (PAG) concentrations on D25. Additionally, we evaluated the potential of ISG abundance in PMNs as pregnancy loss predictors. Nelore heifers (n = 103) and cows (n = 144) underwent estrous synchronization and were artificially inseminated on D0. Pregnancy was diagnosed by B-mode ultrasonography on D30 and D70, and after the final diagnosis, females were classified in four groups: Pregnant; Non-pregnant; Functional CL on D20 but non-pregnant (CL-NP) and Pregnancy loss between D30 and D70 (PL). After determining cutoff values, the Sensitivity (SE), Specificity (SP), Positive Predictive Value (PPV), Negative Predictive Value (NPV) and Accuracy (ACC) were determined for each method. All methods were classified as significant (P < 0.05) predictors of pregnancy. Both ISG expression and PAG concentrations were greater (P < 0.05) in pregnant females than in non-pregnant and CL-NP females but did not differ (P > 0.05) from the PL group. ISG15 expression was greater (P < 0.05) in heifers than in cows, but this difference was not found in OAS1 expression and PAG concentrations. All the methods evaluated were proven to be adequate predictors of pregnancy, but greater accuracies were obtained through PAG concentrations and Doppler-US, due to the decreased number of false positive and false negative results.
•The expression of ISG15 in PMN is more pronounced in beef heifers than in cows.•Luteal fuction determined by Doppler ultrassonography or P4 are the methods with highest accuracies to detect non-pregnant females at day 20 after TAI.•Neither ISG expression nor PAG concentrations were able to predict pregnancy losses after 30 days of pregnancy.•About one third of the non-pregnant females with a functional CL on day 20 after TAI experienced embryonic losses until day 30.
Our objectives were to assess (1) the economic value of decreasing the interval between timed artificial insemination (TAI) services when using a pregnancy test that allows earlier identification of ...nonpregnant cows; and (2) the effect of pregnancy loss and inaccuracy of a chemical test (CT) on the economic value of a pregnancy test for dairy farms. Simulation experiments were performed using a spreadsheet-based decision support tool. In experiment 1, we assessed the effect of changing the interbreeding interval (IBI) for cows receiving TAI on the value of reproductive programs by simulating a 1,000-cow dairy herd using a combination of detection of estrus (30 to 80% of cows detected in estrus) and TAI. The IBI was incremented by 7d from 28 to 56d to reflect intervals either observed (35 to 56d) or potentially observed (28d) in dairy operations. In experiment 2, we evaluated the effect of accuracy of the CT and additional pregnancy loss due to earlier testing on the value of reproductive programs. The first scenario compared the use of a CT 31±3d after a previous AI with rectal palpation (RP) 39±3d after AI. The second scenario used a CT 24±3d after AI or transrectal ultrasound (TU) 32d after AI. Parameters evaluated included sensitivity (Se), specificity (Sp), questionable diagnosis (Qd), cost of the CT, and expected pregnancy loss. Sensitivity analysis was performed for all possible combinations of parameter values to determine their relative importance on the value of the CT. In experiment 1, programs with a shorter IBI had greater economic net returns at all levels of detection of estrus, and use of chemical tests available on the market today might be beneficial compared with RP. In experiment 2, the economic value of programs using a CT could be either greater or less than that of RP and TU, depending on the value for each of the parameters related to the CT evaluated. The value of the program using the CT was affected (in order) by (1) Se, (2) Sp, (3) pregnancy loss, (4) proportion of Qd, (5) percentage of cows AI in estrus, and (6) cost of CT. A change of 1% in the Se of the CT was 1.8 times more important than a similar change in Sp or pregnancy loss, and 13.7, 55.0, and 305.8 times more important than similar changes in Qd, cows inseminated in estrus, and cost of CT. We conclude that the major effect of using a CT is the potential of decreasing the IBI. Moreover, inaccuracy of the CT and additional pregnancy loss due to earlier testing resulted in smaller economic differences than when using RP or TU 8d later.
Understanding the timing of pregnancy suspicion and confirmation, including the role of home pregnancy tests, can facilitate earlier entry into pregnancy-related care and identify individuals likely ...to be impacted by gestation-based abortion restrictions.
We use data from 259 pregnant individuals participating in a cross-sectional survey at 8 primary and reproductive health care clinics in 6 U.S. states (2016-2017). We use regression models to identify differences in utilization of HPTs, barriers to use, and to compare gestational duration at pregnancy confirmation.
Three-quarters (74%) of respondents took a home pregnancy test as the first step in confirming pregnancy; this figure was lower among adolescents versus young adults (65 vs 81%, p = 0.01). Two-thirds (64%) reported delays in home testing, higher among adolescents (85%). People taking a test at home confirmed pregnancy 10 days earlier than those first testing at a clinic (41.3 vs 51.8 days gestation, p = 0.02). Those that did not test at home cited concerns about test accuracy (42%) and difficulties accessing one (26%). While overall 21% confirmed pregnancy at ≥7 weeks gestation, and 35% at ≥6 weeks, confirmation at ≥7 weeks was higher among adolescents versus young adults (47 vs 13%, p = 0.001), Latina versus white women (28 vs 11%, p = 0.02), food insecure versus secure women (28 vs 17%, p = 0.06), and people with unplanned versus planned/mistimed pregnancies (25 vs 13%, p = 0.07).
Home pregnancy testing is common and associated with earlier pregnancy confirmation. Still, barriers to at-home testing are evident, particularly among adolescents. Efforts to expand access to home pregnancy tests and increase knowledge about their accuracy may be impactful in increasing utilization.
While at home pregnancy testing is common and facilitates earlier confirmation of pregnancy, one in 5 confirm pregnancy at 7 weeks gestation or later (and one in 3 do so at 6 weeks or later). Gestational bans in the first trimester will disproportionately prevent young people, people of color, and those living with food insecurity from being able to access abortion.
Two experiments were conducted to evaluate a pregnancy-detection assay based on the measurement of pregnancy-associated glycoproteins (PAG) in milk samples. In experiment 1, milk samples were ...collected on the day of first pregnancy check (33–52 d postinsemination; n=119) or second check (60–74 d postinsemination; n=60). The accuracy in identification of pregnant and nonpregnant cows was 99% at first check. Only 6% of samples were found to be within an intermediate range of PAG concentrations and classified as requiring recheck by the assay. At second check, the accuracy of the assay was 98%. Fifteen percent of these samples were classified as requiring recheck. In experiments 2a (n=17 cows) and 2b (n=16 cows), milk and plasma samples were collected from cows at weekly intervals beginning 2 (experiment 2a) or 4 d (experiment 2b) after insemination. The earliest time point at which pregnant cows were accurately classified as pregnant by the assay was on d 30 postinsemination. A transient decline in PAG levels into the intermediate range was observed on d 46 to 72 postinsemination. This coincides with the time of recheck in experiment 1. Results obtained with the plasma samples were essentially the same. The accuracy of pregnancy identification based on milk samples from nonpregnant and pregnant cows was 99%. Levels of PAG in milk were useful in identifying 6 incidences of embryonic mortality. No consistent relationship was noted between the timing of the decline in PAG levels and the timing of luteal regression in this small number of cows.
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