Biopsychosocial factors intersecting with weekly sleep difficulties in the menopause transition.

OBJECTIVES: Sleep difficulties are common in the menopause transition and increase risk for a variety of physical and psychological problems. The current study investigated potential interactions between psychosocial variables and within-person changes in ovarian hormones in predicting perimenopausal sleep problems as well as the potential interactions between poor sleep and psychosocial factors in predicting worsened mood, affect, and attention. STUDY DESIGN: The sample included 101 perimenopausal individuals. Participants completed 12 weekly assessments of self-reported sleep outcomes, depressive mood and affect, and attention function, and of estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) levels (urinary metabolites of estradiol and progesterone, respectively); they also had 24-h tracking of vasomotor symptoms. Other psychosocial variables such as trauma history and stressful life events were assessed at baseline. RESULTS: A history of depression, baseline depressive symptoms, trait anxiety, and more severe and bothersome vasomotor symptoms predicted worsened sleep outcomes. Recent stressful life events, trauma history, and person-centred E1G and PdG changes did not predict sleep outcomes. However, there was an interaction whereby person-centred E1G decreases predicted lower sleep efficiency in those with higher baseline depressive symptoms. Higher baseline depression and trauma history also amplified the effect of vasomotor symptoms on sleep outcomes. In evaluating the effect of poor sleep on psychological and cognitive outcomes, stressful life events emerged as a moderating factor. Finally, trauma history and poor sleep interacted to predict worsened attention function. CONCLUSIONS: The current study suggests that certain individuals may be at greater risk of perimenopausal sleep problems and the resulting negative effects on mood and cognition.

Pilot trial of a new self-directed psychological intervention for infertility-related distress.

BACKGROUND: Now affecting one in six couples in Canada, infertility is defined as a lack of conception after 12 or more months of regular, unprotected heterosexual intercourse. Infertility is associated with immense psychological burden, particularly for individuals assigned female at birth. Yet existing psychological interventions are not specialized to this population and have been shown to be only marginally effective at relieving distress related to infertility. Thus, a new online self-directed psychological intervention was co-created with a panel of women experiencing infertility, and ultimately consisted of six 10-min video modules addressing the cognitive, emotional, and interpersonal aspects of infertility-related distress. METHODS: In the current study, 21 women experiencing reduced quality of life related to infertility were recruited to participate in a one-arm pre-post pilot testing the feasibility, acceptability, and preliminary efficacy of the program. Participant adherence and retention were monitored, and participants rated the credibility of the program and the helpfulness of each module as well as provided feedback on the content and format of the program. Pre-to-post changes in fertility quality of life, anxious symptoms, depressive symptoms, and relationship satisfaction were examined. RESULTS: The program modules were highly rated by participants, with average helpfulness ratings ranging from 7.5 to 8.2/10. Two participants became pregnant and therefore stopped prematurely, 79% of the remaining participants completed all six modules, and participants reported completing 52.8 (SD = 82.0) min of homework per week. Participants perceived the intervention as highly credible and generally approved of the format, length, and speed; however, 68% of participants had recommendations for additional content to be included in the intervention. While relationship satisfaction did not change significantly over time, large pre-to-post improvements in fertility quality of life, depression, and anxiety were observed (p < .001; Cohen's ds = 0.9-1.3). CONCLUSIONS: This self-directed intervention was well received and has the potential to be highly effective in reducing infertility-related distress, informing future development and optimization. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05103982.

Testing the efficacy of a narrative short film in educating the public about providing emotional support to individuals with fertility problems.

BACKGROUND: To educate the public on how best to support people with fertility problems, a narrative short film "Ten Things Not to Say to Someone Struggling with Infertility" was created, depicting the impact that helpful versus unhelpful dialogue has on someone with fertility problems. METHODS: Before and after watching the video, 419 participants from the public were presented with a hypothetical vignette describing a woman experiencing fertility problems and asked about the likelihood that they would endorse a series of helpful and unhelpful statements when communicating with the protagonist. Pre and post endorsement of helpful versus unhelpful statements were compared, as were self-perceived knowledge about the mental health aspects of fertility problems, confidence in providing emotional support to someone with fertility problems, and empathy for the protagonist. RESULTS: Participants endorsed fewer unhelpful statements after the video relative to before (M(SD) = 2.2(2.3) vs. 1.3(2.3), p < .001) and fewer participants endorsed at least one unhelpful statement (72% to 47%, p < .001). Self-perceived knowledge of fertility problems, confidence in providing support, and empathy increased at post-test (ps < .001; Cohen's d = .56-.83) indicating medium-large effects. CONCLUSIONS: A narrative short film appears to be an effective dissemination strategy for sensitizing the public to the emotional struggles of individuals experiencing fertility problems.

A novel method for quantifying affective sensitivity to endogenous ovarian hormones.

Increased sensitivity to ovarian hormone changes is implicated in the etiology of reproductive mood disorders across the female lifespan, including menstrually-related mood disorders, perinatal mood disorders, and perimenopausal depression. Developing a method to accurately quantify sensitivity to endogenous hormone fluctuations may therefore facilitate the prediction and prevention of these mental health conditions. Here, we propose one such method applying a synchrony analysis to compute time-lagged cross-correlations between repeated assessments of endogenous hormone levels and self-reported affect. We apply this method to a dataset containing frequent repeated assessments of affective symptoms and the urinary metabolites of estradiol (E2) and progesterone (P4) in 94 perimenopausal females. These preliminary findings suggest that, with further refinement and validation, the proposed method holds promise as a diagnostic tool to be used in clinical practice and to advance research investigating the etiology of reproductive mood disorders.

Acceptance and commitment therapy adapted for women with infertility: a pilot study of the Infertility ACTion program.

BACKGROUND: Approximately one in six couples are currently infertile, defined as unable to achieve pregnancy despite 12 or more months of active attempts to conceive. Experiencing infertility has been disproportionately associated with an array of psychological difficulties, particularly in women. However, currently available psychological interventions have had minimal benefits for distress, anxiety, or depression related to infertility. METHODS: A one-arm pilot study was conducted to test the acceptability of a newly created acceptance and commitment therapy-based self-guided program-Infertility ACTion. Twenty women, located in Canada, completed the program and completed measures assessing expectancy of improvement, treatment credibility, participant satisfaction, treatment completion and retention, psychological flexibility, fertility quality of life, depression, and anxiety. Participants were also asked to provide feedback on how the researchers could improve the intervention. Paired sample t-tests were conducted to compare pre- and post-intervention outcomes. RESULTS: Sixteen out of 20 participants completed the entire intervention. Reported treatment expectancy, credibility and satisfaction were favorable. Eighty-one percent of participants reported that they would recommend the program to a friend and 88% thought the program was worth their time. Medium increases in psychological flexibility and fertility quality of life were observed. Improvements in anxious and depressive symptoms were in the small to medium range but were not significant. Participants had several recommendations for program improvement. CONCLUSIONS: This acceptance and commitment therapy-based self-guided program proved to be an acceptable treatment for infertility-related distress. Participant feedback will be used to adjust the current intervention in preparation for a more rigorous randomized-controlled trial testing this program.

Understanding Adolescents' Experiences With Menstrual Pain to Inform the User-Centered Design of a Mindfulness-Based App: Mixed Methods Investigation Study.

BACKGROUND: Digital interventions are increasingly popular for the provision of nonpharmacological pain interventions, but few exist for adolescents with menstrual pain. User-centered design involves incorporating users across phases of digital health intervention design, development, and implementation and leads to improved user engagement and outcomes. A needs assessment is the first step of this approach. OBJECTIVE: The goal of this study was to conduct a needs assessment to understand menstrual pain management needs and preferences and mindfulness experiences, preferences, and knowledge of adolescents with menstrual pain to inform the future development of an app for managing menstrual pain. METHODS: We used an explanatory sequential mixed method design that included a survey followed by focus groups. Adolescents aged 13-17 years completed a survey (n=111) and participated in focus groups (n=16). Data were analyzed using descriptive statistics and thematic content analysis and synthesized to provide specific recommendations based on adolescent responses. RESULTS: Adolescents (n=111) who completed the survey reported a moderate understanding of mindfulness and menstrual pain. Over three-quarters (n=87, 78%) of participants practiced some form of mindfulness and 87% (n=97) of survey participants used nonpharmacological pain management strategies. Teens had a moderate perception that mindfulness could help their menstrual pain (mean 4.51/10, SD 2.45, with higher scores suggesting more interest). Themes were generated related to mindfulness experiences, menstrual pain knowledge and experiences, and app functionality. These themes underscored adolescents' need for continued support and flexible access to mindfulness activities; their awareness of multiple influences to pain, with potential for further education in this area; and the need for menstrual pain-specific content, along with content relevant to typical day-to-day experiences of adolescents. CONCLUSIONS: Adolescents with menstrual pain have an interest in using a mindfulness app for pain but have unique needs that need to be addressed to ensure app engagement and relevance for this population. Concrete recommendations for future app development are provided.

Promoting good mental health over the menopause transition.

The potential risk for mental health conditions over the menopause transition shapes women's expectations and informs putative physiological mechanisms regulating women's mental health. We review evidence from prospective studies reporting on associations between mental health conditions and the menopause transition. Major depressive disorder and the more prevalent subthreshold depressive symptoms are the most common conditions studied. We reviewed 12 prospective studies reporting depressive symptoms, major depressive disorder, or both over the menopause transition and found no compelling evidence for a universal increased risk for either condition. However, specific subgroups of participants, primarily defined by menopause-related risk factors (ie, vasomotor symptoms that are severe or disturb sleep, a long duration of the transition, or reproductive hormone dynamics) and psychosocial risk factors (eg, stressful life events), were vulnerable to depressive symptoms. The increased risk of major depressive disorder over the menopause transition appears predominantly in individuals with previous major depressive disorder. Greater focus on recognising risk factors in primary care is warranted. On the basis of scarce data, we found no compelling evidence that risk of anxiety, bipolar disorder, or psychosis is universally elevated over the menopause transition. Potential misattribution of psychological distress and psychiatric disorders to menopause could harm women by delaying accurate diagnosis and the initiation of effective psychotropic treatments, and by creating negative expectations for people approaching menopause. A paradigm shift is needed. We conclude with recommendations for the detection and treatment of depressive symptoms or major depressive disorder and strategies to promote good mental health over the menopause transition, while responsibly preparing and supporting those at risk.

Testing an Evidence-Based Self-Help Program for Infertility-Related Distress: Protocol for a Randomized Controlled Trial.

BACKGROUND: Infertility-the inability to achieve pregnancy despite ≥12 months of focused attempts to conceive-is experienced by 1 in 6 couples. Women typically carry a disproportionate share of the psychological burden associated with infertility, experiencing poor quality of life, and 30%-40% experiencing depressive mood or anxiety. Unfortunately, currently available psychological interventions targeting infertility-related distress are associated with modest effects. OBJECTIVE: Our team, in collaboration with patient advisors, has designed a self-help intervention for infertility-related distress involving 7 weekly 10-minute videos addressing the cognitive, behavioral, and interpersonal challenges associated with infertility, delivered through a mobile app. A feasibility study suggests that it is well accepted and highly effective in reducing symptoms of anxiety and depressed mood among distressed individuals dealing with infertility. This study represents the next step in this line of research: a fully powered randomized controlled trial comparing the intervention to a waitlist control group. METHODS: We will recruit 170 individuals struggling to become pregnant in Canada or the United States to be randomized to our 7-week self-help program or a treatment-as-usual condition. The primary outcome will be fertility quality of life, while secondary outcomes will include depressive symptoms, anxious symptoms, and relationship quality, assessed before and after the program as well as biweekly for 16 weeks following completion of the program. Self-reported health care use and the presence of diagnosed mood and anxiety disorders, assessed through a structured psychiatric interview, will also be assessed immediately following the intervention and at the 16-week follow-up assessment. Treatment adherence and retention will also be recorded throughout the intervention. Multilevel modeling will compare the intervention arm to the treatment-as-usual condition in terms of all continuous outcomes across the 9 measurement points. Logistic regression will be used to assess the occurrence of mood and anxiety disorders in the 2 treatment arms at the posttreatment assessment as well as at the 16-week follow-up. Sensitivity analyses will examine potential treatment moderators: membership in the LGBTQIA+ (lesbian, gay, bisexual, transgender, queer, intersex, and asexual) communities, baseline fertility quality of life, cultural background, disability status, and pursuit of conception through medical intervention. RESULTS: We expect our intervention to be more effective than treatment-as-usual in improving all mental health parameters assessed and decreasing health care use related to both mental and reproductive health. Effects are expected to be larger with decreasing baseline quality of life and equally effective regardless of membership in the LGBTQIA+ communities, cultural background, or disability status. CONCLUSIONS: If our intervention is successful, this would suggest that it should be scaled up and made publicly available. The availability of this program would fill an important gap in light of the high rates of psychopathology among those experiencing infertility and considering the current lack of effective psychotherapy approaches for infertility. TRIAL REGISTRATION: Clinicaltrials.gov NCT06006936; https://classic.clinicaltrials.gov/ct2/show/NCT06006936. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52662.

Within-person changes in reproductive hormones and cognition in the menopause transition.

OBJECTIVES: Most women complain of cognitive deficits in the menopause transition, though the cause is unclear. The current study investigated the role that within-person changes in reproductive hormones, particularly estradiol, may play in triggering such perimenopausal cognitive difficulties. STUDY DESIGN: Participants were 43 women aged 45-55 years and currently in the menopause transition. Once a week for 12 weeks, participants provided a urine sample for the measurement of estrone glucuronide (E1G), a urinary metabolite of estradiol. Every three weeks across the 12-week period, participants also underwent cognitive testing, including assessments of immediate and delayed memory, attention, and executive function, and completed questionnaires assessing subjective cognitive performance. Potential confounding variables including sleep quality, vasomotor symptoms, and depressive symptoms were also assessed. RESULTS: Within-person E1G was positively associated with objective measures of attention, particularly the ability to passively register auditory information on the first pass, as well as subjective measures of memory, specifically relating to a lower frequency of forgetting things in everyday life. Perimenopausal women with lower estimated levels of intellectual functioning furthermore exhibited a stronger relationship between E1G changes and objective cognitive performance. While depressive mood, poor sleep, and vasomotor symptoms were all negatively associated with at least one aspect of cognitive function, the E1G-cognition relationship was not explained by these factors. CONCLUSIONS: This study provides evidence that validates perimenopausal women's cognitive complaints but also suggests that cognitive deficits are generally mild and transient.

Menstrual cycle influences on cue-induced smoking cravings and heart rate variability.

Women experience greater difficulties in quitting smoking than men, though the hormonal factors contributing to this sex difference remain to be clarified. The current study aimed to examine menstrual cycle effects on smoking cue-induced cravings as well as examine dynamic reproductive hormone change as a potential mediator underlying any cycle effects observed. Twenty-one women who smoke underwent two laboratory sessions - one in the mid-follicular phase and the other in the late luteal phase - involving an in-vivo smoking cue task, administered before and after exposure to a psychosocial laboratory stressor. Heart rate variability (HRV) and subjective smoking cravings were assessed in response to the cue task. The degree of change in the urinary metabolites of estradiol and progesterone from 2 days before to the day of each laboratory session was measured. Results revealed that both before and following exposure to psychosocial stress, highly nicotine-dependent women exhibited smaller cue-induced increases in HRV relative to the follicular phase. In contrast, less nicotine-dependent women exhibit an increase in HRV in both menstrual cycle phases. Results furthermore suggest that menstrual cycle effects seen in highly nicotine-dependent women are driven by the decline in estradiol and progesterone occurring in the late luteal phase. Though limited by a small sample size, this study suggests that withdrawal from reproductive hormones in the late luteal phase may alter highly nicotine-dependent women's physiological response to smoking cues, which may reflect greater difficulty resisting temptation. These findings may provide some insight regarding women's greater difficulty in maintaining abstinence after quitting smoking.

The effect of physical activity on fertility: a mini-review.

Although lifestyle factors such as diet, cigarette smoking, and alcohol consumption are increasingly recognized as important contributors to the risk of subfertility, the role of exercise in fertility remains less clear. As such, it is challenging for healthcare providers to deliver clear, evidence-based recommendations to patients regarding the optimal frequency and intensity with which they should exercise to maximize their chances of conception. Therefore, this review provides a critical overview of the available research for various patient populations.

A research and development (R&D) roadmap for broadly protective coronavirus vaccines: A pandemic preparedness strategy.

Broadly protective coronavirus vaccines are an important tool for protecting against future SARS-CoV-2 variants and could play a critical role in mitigating the impact of future outbreaks or pandemics caused by novel coronaviruses. The Coronavirus Vaccines Research and Development (R&D) Roadmap (CVR) is aimed at promoting the development of such vaccines. The CVR, funded by the Bill & Melinda Gates Foundation and The Rockefeller Foundation, was generated through a collaborative and iterative process, which was led by the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota and involved 50 international subject matter experts and recognized leaders in the field. This report summarizes the major issues and areas of research outlined in the CVR and identifies high-priority milestones. The CVR covers a 6-year timeframe and is organized into five topic areas: virology, immunology, vaccinology, animal and human infection models, and policy and finance. Included in each topic area are key barriers, gaps, strategic goals, milestones, and additional R&D priorities. The roadmap includes 20 goals and 86 R&D milestones, 26 of which are ranked as high priority. By identifying key issues, and milestones for addressing them, the CVR provides a framework to guide funding and research campaigns that promote the development of broadly protective coronavirus vaccines.

Efficacy of psychological interventions for mental health and pregnancy rates among individuals with infertility: a systematic review and meta-analysis.

BACKGROUND: Depression and anxiety are highly prevalent among individuals struggling with infertility. Thus, numerous psychological interventions have been adapted to infertility, with the aim of relieving distress as well as increasing pregnancy rates. OBJECTIVE AND RATIONALE: This systematic review and meta-analysis aimed to identify all randomized controlled trials (RCTs) evaluating the effect of psychological interventions on infertility-related distress and pregnancy rates among individuals and/or couples with infertility and to analyse their overall effect. It also sought to examine potential treatment moderators, including intervention length, format and therapeutic approach. SEARCH METHODS: An electronic search of 11 databases, including MEDLINE, EMBASE, PsycINFO and Cochrane Central Register of Controlled Trials, was performed for studies published until January 2022. The inclusion criteria were RCTs conducted on humans and published in English. Psychological outcomes of interest included anxiety, depression, infertility-related distress, wellbeing and marital satisfaction. The Cochrane Risk of Bias tool was used to assess study quality, and the Grading of Recommendations Assessment, Development and Evaluation was used to assess the overall quality of the research evidence. OUTCOMES: There were 58 RCTs in total, including 54 which included psychological outcomes and 21 which assessed pregnancy rates. Studies originated from all regions of the world, but nearly half of the studies were from the Middle East. Although a beneficial effect on combined psychological outcomes was found (Hedge's g = 0.82, P < 0.0001), it was moderated by region (P < 0.00001) such that studies from the Middle East exhibited large effects (g = 1.40, P < 0.0001), while the effects were small among studies conducted elsewhere (g = 0.23, P < 0.0001). Statistically adjusting for study region in a meta-regression, neither intervention length, therapeutic approach, therapy format, nor participant gender (P > 0.05) moderated the effect of treatment. A beneficial treatment effect on pregnancy (RR (95% CI) = 1.25 (1.07-1.47), P = 0.005) was not moderated by region, treatment length, approach or format (P > 0.05). Largely due to the lack of high quality RCTs, the quality of the available evidence was rated as low to moderate. WIDER IMPLICATIONS: This is the first meta-analysis of RCTs testing the effect of psychological interventions on infertility-related distress and pregnancy rates. These findings suggest that in most regions of the world, psychological interventions are associated with small reductions in distress and modest effects on conception, suggesting the need for more effective interventions. These findings must be considered in light of the fact that the majority of the included RCTs were deemed to be at high risk of bias. Rigorously conducted trials are needed.

A Neuropsychological Approach to Mild Cognitive Impairment.

OBJECTIVE: A neuropsychological approach to the detection and classification of mild cognitive impairment (MCI) using "gold standard" clinical ratings (CRs) was examined in a sample of independently functioning community dwelling seniors. The relationship between CRs and life satisfaction, concurrent validity of cognitive screening measures, and agreement between CRs and existing criteria for MCI were also determined. METHOD: One hundred and forty-two participants, aged 75 years and older, were administered a comprehensive battery of neuropsychological tests, along with self-report measures of psychological and psychosocial functioning, and functional independence. CRs were based on demographically corrected neuropsychological variables. RESULTS: The prevalence of MCI identified using CRs in this sample was 26.1%. Single and multiple domain subtypes of MCI were readily identified with subtypes reflecting Amnestic and Executive Function impairment predominating. Executive Function was a significant predictor of Life Satisfaction. The MoCA and MMSE both showed weak performance in detecting MCI based on CRs. There was substantial agreement between CRs and the classification criteria for MCI defined by Petersen/Winblad and Jak/Bondi. A global deficit score had near perfect performance as a proxy for CRs in detecting MCI in this sample. CONCLUSIONS: The results provide strong support for the utility of neuropsychological CRs as a "gold standard" operational definition in the detection and classification of MCI in older adults.

Fertility Knowledge Among Women Struggling to Conceive Without Medical Intervention: A Brief Report.

INTRODUCTION: Approximately 1 in 6 women experience infertility. Though medical treatments for infertility exist, they are very costly and highly burdensome for women. It is therefore desirable to optimize women's chances of conception without medical intervention by ensuring that they have adequate knowledge of the female menstrual cycle and the timing of the fertile window. The current study therefore aimed to assess the degree to which women struggling to conceive without medical intervention are knowledgeable about these topics. METHODS: One hundred and two women of reproductive age (18-45 years old) in Canada and the United States who had been struggling to conceive without medical intervention for ≥12 months completed an online survey including a questionnaire assessing knowledge related to reproduction and fertility. RESULTS: Mean accuracy score on the Fertility Knowledge Questionnaire was 67%. Seventy-two women were not aware that the week before ovulation was associated with the highest chances of conception. Women using cervical mucus tracking to increase chances of conception were more knowledgeable (p = 0.02), as were women with more formal education (p = 0.01). Conversely, women who had been attempting to conceive for longer had lower fertility knowledge (p = 0.03). Age, number of children, and family income were unrelated to fertility knowledge (p > 0.05). DISCUSSION: Our findings suggest that women who are struggling to conceive would benefit from education related to the timing and identification of the fertile window. Reproductive and primary healthcare providers can play an important role in assessing fertility knowledge and addressing knowledge gaps to improve chances of successful conception.

Infertility-related distress and clinical targets for psychotherapy: a qualitative study.

OBJECTIVES: An estimated 30%-40% of women attending infertility tertiary care facilities experience clinically significant depression and anxiety. However, current psychological interventions for infertility are only modestly effective in this population. In this study, we aimed to identify the specific psychological components of infertility-related distress to assist in the development of a more targeted and effective therapeutic intervention. To our knowledge, this study is the first of its kind to include the views and opinions of mental health professionals who specialise in the field of infertility and the first to explore therapies currently used by mental health professionals. DESIGN: A qualitative approach using semistructured individual interviews and focus group interviews with women who have experience with infertility and also mental health professionals specialising in the field of infertility. Thematic analysis was used to identify patterns and themes emerging from the data. PARTICIPANTS: Twenty-one women (aged 25-41 years) struggling to conceive for ≥12 months and 14 mental health professionals participated in semistructured interviews about the psychological challenges related to infertility. RESULTS: Five themes, each divided into subthemes, emerged from the data and these were developed into a model of infertility-related distress. These five themes are: (1) anxiety, (2) mood disturbance, (3) threat to self-esteem, identity and purpose, (4) deterioration of the couple and (5) weakened support network. In addition, therapeutic techniques used by mental health professionals were identified. CONCLUSIONS: The results of this study suggest specific clinical targets that future interventions treating infertility-related distress should address.