A survey study evaluating donor gamete utilization rates, patient satisfaction and fertility treatment outcomes according to desired race and ethnicity.

OBJECTIVE: To evaluate donor gamete utilization, patient satisfaction, and fertility treatment outcomes of patients pursuing treatment with donor gametes stratified by the desired race and ethnicity of the gamete donor. DESIGN: Survey study SUBJECTS: Patients planning to undergo treatment using donor sperm and/or donor oocytes at a single academic fertility clinic in the Southeastern United States between 2015 and 2020. INTERVENTION OR EXPOSURE: None MAIN OUTCOME MEASURES: Utilization rates of donor gametes, satisfaction with donor gamete selection and fertility treatment outcomes stratified by race and ethnicity of patient, as well as that of their gamete donor. RESULTS: Four hundred fifty patients were eligible for inclusion and 170 (38%) responded to the survey. Amongst the respondents, 59% desired a non-Hispanic White gamete donor and 20% desired a non-Hispanic Black gamete donor. Patients seeking a non-Hispanic Black gamete donor had lower odds of utilizing donor gametes (OR = 0.13, 95% CI 0.04 - 0.40) compared to individuals seeking a non-Hispanic White gamete donor. When evaluating satisfaction with donor gamete selection, patients seeking a non-Hispanic Black gamete donor reported lower satisfaction compared to individuals seeking a non-Hispanic White gamete donor (OR 0.19, 95% CI [0.09-0.43]). When evaluating fertility outcomes, Non-Hispanic Black patients and those utilizing non-Hispaninc Black gamete donors were found to have a lower odds of successful conception compared to non-Hispanic White patients (OR=0.18, 95% CI 0.07-0.46) and individuals seeking non-Hispanic White gamete donors (OR=0.26, 95% CI 0.09-0.75), respectively. CONCLUSION: Patients seeking non-Hispanic Black donor gametes have lower utilization rates, less satisfaction with gamete donor selection, and lower odds of conception when compared to those seeking non-Hispanic White gamete donors. These findings highlight the need for more racial diversity within donor gamete banks, as well as within the donor pools available through agencies and fertility clinics.

MyTrack+: Human-centered design of an mHealth app to support long-term weight loss maintenance.

A growing body of research has focused on the utility of adaptive intervention models for promoting long-term weight loss maintenance; however, evaluation of these interventions often requires customized smartphone applications. Building such an app from scratch can be resource-intensive. To support a novel clinical trial of an adaptive intervention for weight loss maintenance, we developed a companion app, MyTrack+, to pair with a main commercial app, FatSecret (FS), leveraging a user-centered design process for rapid prototyping and reducing software engineering efforts. MyTrack+ seamlessly integrates data from FS and the BodyTrace smart scale, enabling participants to log and self-monitor their health data, while also incorporating customized questionnaires and timestamps to enhance data collection for the trial. We iteratively refined the app by first developing initial mockups and incorporating feedback from a usability study with 17 university students. We further improved the app based on an in-the-wild pilot study with 33 participants in the target population, emphasizing acceptance, simplicity, customization options, and dual app usage. Our work highlights the potential of using an iterative human-centered design process to build a companion app that complements a commercial app for rapid prototyping, reducing costs, and enabling efficient research progress.

Adoption as an Alternative Family-Building Strategy: Perceptions of Female, Young Adult Cancer Survivors Receiving Gonadotoxic Treatments.

Female survivors of young adult (YA) cancers are at risk of fertility impacts following cancer treatment. For these women, fertility-related distress is both prevalent and persistent. Yet there is little research regarding survivors' perspectives on alternative family-building options, particularly adoption. This exploratory secondary data analysis analyzed semistructured interviews and explored survivors' views of adoption. Overall, female YA survivors reported openness to adoption as a possible substitute for biological conception and an alternative to fertility preservation. It is imperative that this population receives support in decision-making around and consideration of the unique barriers to adoption for cancer survivors.

Integrated Behavioral Health Care in Reproductive Medicine: How and Why to Include Mental Health Professionals in Infertility Care Teams.

Despite fertility patients' reports of significant distress, few have access to integrated mental health care services. We elucidate the benefits and challenges of mental health integration in infertility practices from the perspective of both patients and providers. We outline specific models of integration, financial viability, and the first steps fertility clinics could take to improve their patients' access to these critical supports.

Survey assessing policies regarding patient age and provision of fertility treatment in the United States.

PURPOSE: To determine what policies exist regarding age and provision of fertility treatment in United States fertility clinics. METHODS: Medical directors of the Society for Assisted Reproductive Technology (SART) member clinics were surveyed regarding clinic demographics and current policies pertaining to age and provision of fertility treatment. Univariate comparisons were performed using Chi-square and Fisher exact tests as appropriate, with significance set at P ≤ 0.05. RESULTS: Of the 366 clinics surveyed, 18.9% (69/366) responded. A majority of clinics who responded 88.4% (61/69) reported having a policy regarding patient age and provision of fertility treatment. Responding clinics with an age policy did not differ from those without a policy on the basis of geographical location, (p = 0.5), insurance mandate status (p = 0.9), practice type (p = 0.4), or annual number of ART cycles (p = 0.7). Of all clinics who responded, 73.9% (51/69) had a maximum maternal age for autologous IVF, with a median of 45 years (range 42-54). Similarly, 79.7% (55/69) of responding clinics had a maximum maternal age for donor oocyte IVF, with a median of 52 years (range 48-56). Slightly under half, 43.4% (30/69) of responding clinics had a maximum maternal age for fertility treatment other than IVF (including ovulation induction or ovarian stimulation with or without IUI) with a median of 46 years (range 42-55). Of note, only 4.3% (3/69) of responding clinics had a policy with respect to maximum paternal age, with a median of 55 years (range 55-70). The most commonly cited reasons for having an age-limit policy were maternal risks of pregnancy, lower ART success rates, fetal/neonatal risks, and concerns about patients' ability to parent at an older age. More than half 56.5% (39/69) of responding clinics reported making exceptions to these policies, most commonly for patients who have pre-existing embryos. The majority of medical directors who responded to the survey believed there should be an ASRM guideline regarding maximum maternal age for autologous IVF 71% (49/69), donor oocyte IVF 78% (54/69) and other fertility treatments 62% (43/69). CONCLUSIONS: Most fertility clinics who responded to this national survey reported having a policy regarding maternal age (but not paternal age) and provision of fertility treatment. Policies were based on risk of maternal/fetal complications, lower success rates at older age, and concerns about patients' ability to parent at an older age. The majority of medical directors of responding clinics believed there should be an ASRM guideline regarding age and provision of fertility treatment.

Identifying modifiable factors associated with psychological health in women experiencing infertility.

This study assessed the relationship between modifiable psychological variables and depression, anxiety, and posttraumatic growth in women experiencing infertility. U.S. women (N = 457) who identified as experiencing infertility completed standardized self-report measures of mindfulness, self-compassion, positive affect, intolerance of uncertainty, relationship satisfaction, experiential avoidance, depression, anxiety, and posttraumatic growth. Clinical and demographic characteristics (age, duration trying to conceive, miscarriage, and childlessness) did not predict depression or anxiety. Lower positive affect and higher experiential avoidance were associated with depression and anxiety. Lower self-compassion was associated with depression; higher intolerance of uncertainty was associated with anxiety. There were indirect effects of mindfulness on anxiety and depression via these variables. Future research should explore whether intervening on these factors reduces depressive and anxiety symptoms. Promoting mindfulness may have beneficial effects on symptoms via its downstream effects on multiple coping variables. Counterintuitively, posttraumatic growth was associated with higher intolerance of uncertainty and experiential avoidance.

Analytic Review of Using Augmented Reality for Situational Awareness.

Situational awareness is the perception and understanding of the surrounding environment. Maintaining situational awareness is vital for performance and error prevention in safety critical domains. Prior work has examined applying augmented reality (AR) to the context of improving situational awareness, but has mainly focused on the applicability of using AR rather than on information design. Hence, there is a need to investigate how to design the presentation of information, especially in AR headsets, to increase users' situational awareness. We conducted a Systematic Literature Review to research how information is currently presented in AR, especially in systems that are being utilized for situational awareness. Comparing current presentations of information to existing design recommendations aided in identifying future areas of design. In addition, this survey further discusses opportunities and challenges in applying AR to increasing users' situational awareness.

The risky business of advanced paternal age: neurodevelopmental and psychosocial implications for children of older fathers.

The last several decades are notable for an increase in the percentage of births attributable to men in their 40s and 50s. There is general recognition of offspring health risks related to advanced maternal age, however, fewer patients and providers are informed about the impacts of advanced paternal age (APA). This review examined the literature investigating the association between APA and offspring outcomes, specifically, neurodevelopmental, psychiatric, academic, and behavioral impairment, the impact of paternal health decline and death, and the influence of age on parenting behaviors. This analysis revealed that children, and even grandchildren, of older fathers face significantly increased incidence rates of psychiatric disease and behavioral impairment. The data do not show evidence of superior parenting behaviors among men with APA. Finally, children of men with APA are significantly more likely to experience early bereavement, which is associated with psychological and developmental consequences. An understanding of the degree to which APA can negatively impact the offspring is imperative for patient counseling and development of practice guidelines.

The Routines-Based Model Internationally Implemented.

Professionals from 10 countries are implementing practices from the Routines-Based Model, which has three main components: needs assessment and intervention planning, a consultative approach, and a method for running classrooms. Its hallmark practices are the Routines-Based Interview, support-based visits with families, and a focus on child engagement. Implementers were interested in actual practices for putting philosophy and theory into action in their systems and cultures. We describe implementation challenges and successes and conclude that (a) models have to be adaptable, (b) some principles and practices are indeed universal, (c) we can shape excellent practices for international use, and (d) leadership is vital.

Surrogacy Laws in the United States: What Obstetrician-Gynecologists Need to Know.

The first child carried by a surrogate after in vitro fertilization in the United States was born in 1985. Since then, the number of such births has steadily grown. According to the Centers for Disease Control and Prevention, the number of gestational carrier cycles increased from 727 in 1999 to 3,432 in 2013, encompassing more than 18,000 children born over this period. Surrogacy offers an alternative to adoption. However, it also disrupts traditional notions of parentage and gestation and complicates the role of obstetrician-gynecologists (ob-gyns) in helping their patients navigate difficult ethical issues. Surrogacy legislation falls under the jurisdiction of each individual state, which results in a variety of approaches. In this article, we review the legal aspects of surrogacy important for specialist ob-gyns, including select landmark court cases, states' approaches to surrogacy legislation, and unique components of informed consent. We also provide clinical recommendations specific to the United States for working with gestational surrogates and intended parents, spanning preconception, prenatal care, and delivery.

Is it time to establish age restrictions in ART?

Providers specializing in reproductive medicine are treating increasing numbers of women pursuing parenthood in their 40s, 50s, and beyond. The rise in later-life parenting can be linked to factors ranging from the advent of assisted reproductive technologies and donor oocytes to the highly publicized pregnancies of older celebrities. We explore the medical and psychosocial implications of this trend for both older parents and their children. We also discuss ethical arguments regarding older parents' access to fertility care, existing professional guidelines, and both public and provider opinions about setting age limits for fertility treatment. Finally, we share preliminary considerations of whether age policies should be established, applied to men as well as women, and standardized or considered on a case-by-case basis.

MUC5B variant is associated with visually and quantitatively detected preclinical pulmonary fibrosis.

BACKGROUND: Relatives of patients with familial interstitial pneumonia (FIP) are at increased risk for pulmonary fibrosis. We assessed the prevalence and risk factors for preclinical pulmonary fibrosis (PrePF) in first-degree relatives of patients with FIP and determined the utility of deep learning in detecting PrePF on CT. METHODS: First-degree relatives of patients with FIP over 40 years of age who believed themselves to be unaffected by pulmonary fibrosis underwent CT scans of the chest. Images were visually reviewed, and a deep learning algorithm was used to quantify lung fibrosis. Genotyping for common idiopathic pulmonary fibrosis risk variants in MUC5B and TERT was performed. FINDINGS: In 494 relatives of patients with FIP from 263 families of patients with FIP, the prevalence of PrePF on visual CT evaluation was 15.6% (95% CI 12.6 to 19.0). Compared with visual CT evaluation, deep learning quantitative CT analysis had 84% sensitivity (95% CI 0.72 to 0.89) and 86% sensitivity (95% CI 0.83 to 0.89) for discriminating subjects with visual PrePF diagnosis. Subjects with PrePF were older (65.9, SD 10.1 years) than subjects without fibrosis (55.8 SD 8.7 years), more likely to be male (49% vs 37%), more likely to have smoked (44% vs 27%) and more likely to have the MUC5B promoter variant rs35705950 (minor allele frequency 0.29 vs 0.21). MUC5B variant carriers had higher quantitative CT fibrosis scores (mean difference of 0.36%), a difference that remains significant when controlling for age and sex. INTERPRETATION: PrePF is common in relatives of patients with FIP. Its prevalence increases with age and the presence of a common MUC5B promoter variant. Quantitative CT analysis can detect these imaging abnormalities.

Third-party reproduction in the Internet Age: the new, patient-centered landscape.

The rise of the Internet Age has brought a host of sweeping changes to the landscape of third-party reproduction. What began as a dyadic relationship between doctor and patient has evolved into a more complex system in which patients are able to access information online from a variety of external sources. Patients often seek to play a more active role in their third-party reproductive care, and the Internet allows them to do so. Further, demand for both medical and psychosocial information about donors and donor-conceived siblings, available online through patient forums and genetic registries, has altered the perception of gamete donation from a one-time event to an ongoing relationship. The advantages and disadvantages for patients and providers of this freer flow of information between third-party participants are examined. Search motivations of recipients and offspring, as well as types of information sought, are detailed. Recommendations are made regarding strategies fertility programs can use to optimally support their patients and navigate this new landscape.

Dyadic goal appraisal during treatment for infertility: how do different perspectives relate to partners' adjustment?

BACKGROUND: Infertility often is a dyadic stressor that constitutes blockage of a major life goal. PURPOSE: This study's primary aims were to examine heterosexual partners' goal appraisals during treatment for infertility and to test whether the direct effects of and interactions between partners' goal-related perceptions were associated with each partner's adjustment. METHOD: Women (n = 37) receiving fertility treatment and their male partners (n = 37) completed measures of goal appraisal and psychological adjustment. RESULTS: Partners did not differ on ratings of the importance of the goal of parenthood, but women indicated lower perceived chance of becoming pregnant and higher perceived goal blockage than their partners. Goal appraisals were moderately correlated between partners and uncorrelated with the number of treatment procedures undergone by the couple. Women reported greater depressive symptoms, more infertility-specific thought intrusion, and lower positive states of mind than their partners. Women's appraisal of greater likelihood of becoming pregnant was psychologically protective, but greater perceived likelihood of becoming pregnant reported by their partners was associated with women's negative psychological adjustment. CONCLUSION: Examining the associations between couples' goal appraisals and psychological adjustment may aid in developing targeted interventions to promote psychological adjustment to infertility. The small sample may have prevented identifying interactions between partners' goal assessment measures.

Moving forward during major goal blockage: situational goal adjustment in women facing infertility.

Individuals confronting chronic medical conditions often face profound challenges to cherished life goals. The primary aim of this study was to examine the associations of goal adjustment with psychological adjustment in the context of infertility. At study entry (T1; n = 97) and 6 months later (T2; n = 47), women in fertility treatment completed measures of goal blockage, goal adjustment ability, and psychological adjustment. At T1, greater perceived and actual goal blockage were related to negative psychological adjustment. Ability to disengage from the goal of biological parenthood was associated with less infertility-specific thought intrusion, whereas engagement with other goals was related to fewer depressive symptoms and greater positive states of mind. Greater general goal engagement was protective against the negative relationships between low goal disengagement and the dependent variables. Promoting letting go of the unattainable and investing in the possible may be a useful intervention to foster well-being among individuals experiencing profound goal blockage.

Regulation of haematopoietic progenitor cell proliferation and survival: The involvement of the osteoblast.

Haematopoietic progenitor cells (HPC) traffic between the circulation and the bone marrow. Through contact with osteoblasts in the bone marrow niche, their survival, maintenance and proliferation is regulated. This review summarizes recent observations regarding the interaction between osteoblasts and HPCs, and the resulting downstream effects on signaling and niche maintenance. Using live imaging, amongst other techniques, HPCs were found to make prolonged contact with the osteoblast, via a specialized region of their membrane with high expression of prominin 1, CD63 and rhodamine PE. Following contact, portions of the HPC membrane expressing these molecules were phagocytosed by the osteoblast into SARA-positive signaling-endosomes. In response, Smad signaling was downregulated in the osteoblasts, leading to increased production of SDF-1; a chemokine involved in progenitor cell homing to the bone marrow, and thus regulating progenitor cell trafficking. The study summarised here presents important findings regarding progenitor cell trafficking, maintenance, proliferation and survival in the bone marrow and potentially other niche microenvironments, following signaling events initiated and propagated through single cell interactions.

Anticancer mechanisms of doxorubicin and zoledronic acid in breast cancer tumor growth in bone.

Patients with advanced breast cancer frequently develop bone metastases, and at this stage, the disease is considered incurable. Here, we show that a 6-week course of weekly administration of doxorubicin (2 mg/kg), followed 24 hours later by the bisphosphonate zoledronic acid (100microg/kg), causes substantial inhibition of MDA-MB-436 breast tumor burden in bone of immunocompromised mice, compared with administration of the single agents. Molecular analysis of tumors from animals treated sequentially with doxorubicin followed by zoledronic acid showed reduced numbers of proliferating tumor cells and decreased expression of cyclins E1, B, D1, and D3 as well as cdk2 and cdk4. Tumors from the sequential treatment group also displayed increased levels of apoptosis, increased expression of bcl2-associated X protein, decreased expression of B-cell chronic lymphocytic leukemia/lymphoma 2, and activation of caspase 3, 8, and 9. Zoledronic acid caused a small reduction in tumor volume, reduced tumor cell proliferation, and decreased expression of cyclins D1 and D3, compared with tumors from animals treated with saline or doxorubicin. Doxorubicin had no effect on tumor growth, cell cycle, or apoptosis in vivo, but did cause increased accumulation of a bisphosphonate in MDA-MB-436 cells in vitro, suggesting that doxorubicin may affect subsequent uptake of zoledronic acid. In support of this, accumulation of unprenylated Rap1A, a surrogate marker of zoledronic acid, was only detected in tumors following sequential treatment, and not following treatment with zoledronic acid alone. Our data are the first to show the specific molecular pathways by which sequential treatment with doxorubicin and zoledronic acid induce tumor cell apoptosis and inhibit proliferation in an in vivo model of breast tumor growth in bone.

Crossing the endothelium: E-selectin regulates tumor cell migration under flow conditions.

Diapedesis is a vital part of tumor metastasis, whereby tumor cells attach to and cross the endothelium to enter the circulation. Specific adhesion molecules, expressed by both the tumor and endothelial cells, mediate this process. This review summarizes recent findings regarding the mechanisms by which colon cancer cells migrate through the endothelium under flow conditions mediated by E-selectin. Using a laminar flow chamber and a tissue engineered human blood vessel, E-selectin was found to regulate initial attachment and rolling of colon cancer cells and also the subsequent diapedesis through the endothelium. Three different mechanisms of diapedesis were reported to be regulated by E-selectin; the formation of a mosaic chimeric layer of tissue, paracellular diapedesis between endothelial cells and transcellular diapedesis, in which tumor cells were transported via large vacuoles within the endothelial cells. Moreover activation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase by E-selectin was further required for paracellular diapedesis. This study is the first to report these observations under dynamic and shear stress conditions.