Evaluation of progestogen supplementation for luteal phase support in fresh in vitro fertilization cycles

© 2019 American Society for Reproductive Medicine Objective: To evaluate the effectiveness of progestogen supplementation in improving clinical pregnancy rates in women undergoing fresh IVF cycles and to compare different routes, start times, durations, and estrogen coadministration regimen. Design: Comprehensive systematic review and meta-analysis. Setting: University. Patient(s): Women undergoing fresh IVF cycles who did and did not receive progestogen supplementation. Intervention(s): Summary odds ratios (ORs) were calculated by binomial logistic regression. Main Outcome Measure(s): Clinical pregnancy rates. Result(s): Eighty-two articles (26,726 women) were included. Clinical pregnancy rates were increased by IM (OR = 4.57), vaginal (OR = 3.34), SC (OR = 3.36), or oral (OR = 2.57) progestogen supplementation versus no treatment. The greatest benefit was observed when progestogens were supplemented IM versus vaginally (OR = 1.37). The optimal time to commence administration was between oocyte retrieval and ET (OR = 1.31), with oocyte retrieval +1 day being most beneficial. Coadministration of estrogen had no benefit (OR = 1.33), whether progestogens were coadministered vaginally or IM. Clinical pregnancy rates were equivalent when progestogen supplementation was ceased after ≤3 weeks or continued for up to 12 weeks (OR = 1.06). Conclusion(s): This broad-ranging meta-analysis highlights the need to reevaluate current clinical practice. The use of progestogens in fresh IVF cycles is substantially beneficial to clinical pregnancy. Critically, the use of IM progestogens should not be dismissed, as it yielded the greatest clinical pregnancy rates. Pregnancy success was impacted by initiation of therapy, with 1 day after oocyte retrieval being optimal. There is little evidence to support coadministration of estrogen or prolonging progestogen treatment beyond 3 weeks

Willingness to Vaccinate against COVID-19 Declines in Australia, Except in Lockdown Areas

This study investigates changes in willingness to vaccinate against COVID-19 and the effect of the extended restrictions in metropolitan Victoria on this change. Longitudinal and repeated cross-sectional data were collected from online surveys distributed in April, between July and August, and December 2020. Australian adults who were ≥18 years old were recruited through email lists, social media networks, and paid Facebook advertisement. Willingness to vaccinate against COVID-19 was self-reported. The results showed that participants were more willing to vaccinate if the vaccine was safe at survey 1 (longitudinal: adjusted OR (aOR) = 1.88, 95%CI = 1.38, 2.56; cross-sectional: aOR = 3.73, 95%CI = 2.55, 5.45) and survey 2 (longitudinal: aOR = 1.54, 95%CI = 1.19, 2.00; cross-sectional: aOR = 2.48, 1.67, 3.67), compared to survey 3. The change in willingness to vaccinate if the vaccine was safe and effective was not significant for those in Metropolitan Victoria; but was for those living in other Australian locations at survey 1 (OR = 2.13, 95%CI = 1.64, 2.76) and survey 2 (OR = 1.62, 95%CI = 1.30, 2.01), compared to survey 3. Willingness to vaccinate even if a vaccine had not been proven safe decreased at survey 3 (OR = 2.02, 95%CI = 1.14, 3.57) for those living in Metropolitan Victoria. In conclusion willingness to vaccinate against COVID-19 decreased over time among Australians, except for those living in metropolitan Victoria, where an additional strict and prolonged lockdown was implemented around the time of survey 2. Either the experience of the lockdown, or the presence of the COVID-19 virus itself had a positive influence on participants’ willingness to vaccinate, even if such a vaccine was not yet proven to be safe and effective

Depression, anxiety and stress during covid-19: associations with changes in physical activity, sleep, tobacco and alcohol use in Australian adults.

The novel coronavirus (COVID-19) has enforced dramatic changes to daily living including economic and health impacts. Evidence for the impact of these changes on our physical and mental health and health behaviors is limited. We examined the associations between psychological distress and changes in selected health behaviors since the onset of COVID-19 in Australia. An online survey was distributed in April 2020 and included measures of depression, anxiety, stress, physical activity, sleep, alcohol intake and cigarette smoking. The survey was completed by 1491 adults (mean age 50.5 ± 14.9 years, 67% female). Negative change was reported for physical activity (48.9%), sleep (40.7%), alcohol (26.6%) and smoking (6.9%) since the onset of the COVID-19 pandemic. Significantly higher scores in one or more psychological distress states were found for females, and those not in a relationship, in the lowest income category, aged 18-45 years, or with a chronic illness. Negative changes in physical activity, sleep, smoking and alcohol intake were associated with higher depression, anxiety and stress symptoms. Health-promotion strategies directed at adopting or maintaining positive health-related behaviors should be utilized to address increases in psychological distress during the pandemic. Ongoing evaluation of the impact of lifestyle changes associated with the pandemic is needed

Depression, anxiety and stress during COVID-19: Associations with changes in physical activity, sleep, tobacco and alcohol use in Australian adults

Alley, SJ ORCiD: 0000-0001-9666-5071; Khalesi, S ORCiD: 0000-0002-8208-2518; Stanton, R ORCiD: 0000-0002-6684-5087; To, GQ ORCiD: 0000-0002-3355-6326; Vandelanotte, CL ORCiD: 0000-0002-4445-8094; Williams, SL ORCiD: 0000-0003-4289-9248The novel coronavirus (COVID-19) has enforced dramatic changes to daily living including economic and health impacts. Evidence for the impact of these changes on our physical and mental health and health behaviors is limited. We examined the associations between psychological distress and changes in selected health behaviors since the onset of COVID-19 in Australia. An online survey was distributed in April 2020 and included measures of depression, anxiety, stress, physical activity, sleep, alcohol intake and cigarette smoking. The survey was completed by 1491 adults (mean age 50.5 ± 14.9 years, 67% female). Negative change was reported for physical activity (48.9%), sleep (40.7%), alcohol (26.6%) and smoking (6.9%) since the onset of the COVID-19 pandemic. Significantly higher scores in one or more psychological distress states were found for females, and those not in a relationship, in the lowest income category, aged 18–45 years, or with a chronic illness. Negative changes in physical activity, sleep, smoking and alcohol intake were associated with higher depression, anxiety and stress symptoms. Health-promotion strategies directed at adopting or maintaining positive health-related behaviors should be utilized to address increases in psychological distress during the pandemic. Ongoing evaluation of the impact of lifestyle changes associated with the pandemic is needed. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

STRADα deficiency results in aberrant mTORC1 signaling during corticogenesis in humans and mice

Polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE) is a rare human autosomalrecessive disorder characterized by abnormal brain development, cognitive disability, and intractable epilepsy. It is caused by homozygous deletions of STE20-related kinase adaptor α (STRADA). The underlying pathogenic mechanisms of PMSE and the role of STRADA in cortical development remain unknown. Here, we found that a human PMSE brain exhibits cytomegaly, neuronal heterotopia, and aberrant activation of mammalian target of rapamycin complex 1 (mTORC1) signaling. STRADα normally binds and exports the protein kinase LKB1 out of the nucleus, leading to suppression of the mTORC1 pathway. We found that neurons in human PMSE cortex exhibited abnormal nuclear localization of LKB1. To investigate this further, we modeled PMSE in mouse neural progenitor cells (mNPCs) in vitro and in developing mouse cortex in vivo by knocking down STRADα expression. STRADα-deficient mNPCs were cytomegalic and showed aberrant rapamycin-dependent activation of mTORC1 in association with abnormal nuclear localization of LKB1. Consistent with the observations in human PMSE brain, knockdown of STRADα in vivo resulted in cortical malformation, enhanced mTORC1 activation, and abnormal nuclear localization of LKB1. Thus, we suggest that the aberrant nuclear accumulation of LKB1 caused by STRADα deficiency contributes to hyperactivation of mTORC1 signaling and disruption of neuronal lamination during corticogenesis, and thereby the neurological features associated with PMSE

STRADα deficiency results in aberrant mTORC1 signaling during corticogenesis in humans and mice

Polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE) is a rare human autosomal-recessive disorder characterized by abnormal brain development, cognitive disability, and intractable epilepsy. It is caused by homozygous deletions of STE20-related kinase adaptor α (STRADA). The underlying pathogenic mechanisms of PMSE and the role of STRADA in cortical development remain unknown. Here, we found that a human PMSE brain exhibits cytomegaly, neuronal heterotopia, and aberrant activation of mammalian target of rapamycin complex 1 (mTORC1) signaling. STRADα normally binds and exports the protein kinase LKB1 out of the nucleus, leading to suppression of the mTORC1 pathway. We found that neurons in human PMSE cortex exhibited abnormal nuclear localization of LKB1. To investigate this further, we modeled PMSE in mouse neural progenitor cells (mNPCs) in vitro and in developing mouse cortex in vivo by knocking down STRADα expression. STRADα-deficient mNPCs were cytomegalic and showed aberrant rapamycin-dependent activation of mTORC1 in association with abnormal nuclear localization of LKB1. Consistent with the observations in human PMSE brain, knockdown of STRADα in vivo resulted in cortical malformation, enhanced mTORC1 activation, and abnormal nuclear localization of LKB1. Thus, we suggest that the aberrant nuclear accumulation of LKB1 caused by STRADα deficiency contributes to hyperactivation of mTORC1 signaling and disruption of neuronal lamination during corticogenesis, and thereby the neurological features associated with PMSE