State of the Science and Ethical Considerations for Preimplantation Genetic Testing for Monogenic Cystic Kidney Diseases and Ciliopathies.

There is a broad phenotypic spectrum of monogenic polycystic kidney diseases (PKDs). These disorders often involve cilia-related genes and lead to the development of fluid-filled cysts and eventual kidney function decline and failure. Preimplantation genetic testing for monogenic (PGT-M) disorders has moved into the clinical realm. It allows prospective parents to avoid passing on heritable diseases to their children, including monogenic PKD. The PGT-M process involves embryo generation through in vitro fertilization, with subsequent testing of embryos and selective transfer of those that do not harbor the specific disease-causing variant(s). There is a growing body of literature supporting the success of PGT-M for autosomal-dominant and autosomal-recessive PKD, although with important technical limitations in some cases. This technology can be applied to many other types of monogenic PKD and ciliopathies despite the lack of existing reports in the literature. PGT-M for monogenic PKD, like other forms of assisted reproductive technology, raises important ethical questions. When considering PGT-M for kidney diseases, as well as the potential to avoid disease in future generations, there are regulatory and ethical considerations. These include limited government regulation and unstandardized consent processes, potential technical errors, high cost and equity concerns, risks associated with pregnancy for mothers with kidney disease, and the impact on all involved in the process, including the children who were made possible with this technology.

Ethical and Legal Obligations for Research Involving Pregnant Persons in a Post-Dobbs Context.

In light of a history of categorical exclusion, it is critical that pregnant people are included in research to help improve the knowledge base and interventions needed to address public health. Yet the volatile legal landscape around reproductive rights in the United States threatens to undue recent progress made toward the greater inclusion of pregnant people in research. We offer ethical and practical guidance for researchers, sponsors, and institutional review boards to take specific steps to minimize legal risks and ensure the ethical conduct of research with pregnant people in an evolving legal environment.

Sexual and Reproductive Health Concerns in Adults With Cloacal Anomalies: A Qualitative Study.

STUDY OBJECTIVE: Long-term gynecologic data are lacking to inform the care of patients with cloacal malformations. We seek to examine perceived sexual and reproductive health challenges of patients born with cloacal anomalies and characterize the experiences of patients as adults. DESIGN AND SETTING: Virtual semi-structured focus groups and single-participant interviews were conducted using an online video platform. Retrospective chart review was performed to abstract available demographics and surgical history. PARTICIPANTS: Adult patients were contacted from a database of 143 patients born with cloaca who had been seen at or referred to a tertiary care pediatric colorectal center. Participants were recruited until data collection reached thematic saturation. Twenty patients aged 18-53 years participated in 5 focus groups and 3 single-participant interviews. The hospital IRB determined the research activities to be exempt from IRB review and oversight. INTERVENTIONS AND MAIN OUTCOME MEASURES: Interviews and focus groups were transcribed and analyzed using the constant comparative method to identify themes regarding sexual and reproductive health and compared with medical and surgical history abstracted from chart review. RESULTS: Participants reported many perceived barriers to intercourse and intimacy including bowel and bladder continence management. All participants reported discussion of pregnancy and fertility with healthcare providers as important. Other common themes included concerns about independence and transitioning from pediatric to adult providers. CONCLUSION: Anorectal malformations are associated with sexual and reproductive health concerns. Patients seek guidance on family building, intimacy, and transition to adult care. Future quantitative study of these topics is needed to develop best practices for counseling and clinical management of these patients. LEVEL OF EVIDENCE: Level VI. TYPE OF STUDY: Prognosis Study.

Young adults' reasoning for involving a parent in a genomic decision-making research study.

Young adults have increasing genomic testing opportunities; however, little is known about how equipped they feel about making decisions to learn personal genomic information. We conducted qualitative interviews with 19 young adults, ages 18-21 years old, enrolled in a research study where they made decisions about learning personal genomic risk for developing preventable, treatable, and adult-onset conditions and carrier status for autosomal recessive conditions. Participants had the option to include a parent in their study visit and the decision-making process. The goal of this project was to explore young adults' reasons for involving or not involving a parent in the study and to assess young adults' perspectives about parental roles in their healthcare. Nine participants included a parent in the study and ten did not include a parent. Eleven participants received genomic test results before the interview, while eight participants had not yet received their results at the time of the interview. The study team developed a coding guide and coded interview transcripts inductively and deductively using an interpretive descriptive-analytic approach. Logistical issues dominated solo participants' reasons for not involving a parent in the study, whereas those who involved a parent often cited a close relationship with the parent and the parent's previous involvement in the participant's healthcare as reasons for involving them. Both groups of participants described gradually transitioning to independent healthcare decision-making with age and felt their comfort in medical decision-making depends on the severity of and their familiarity with the situation. Participants recommended that future genomic researchers or clinicians give young adults the option to involve a parent or friend as a support person in research or clinical visits. Although young adults may have different journeys toward independent healthcare decision-making, some may benefit from continued parental or peer involvement after reaching the age of legal adulthood.

COVID-19 and abortion in the Ohio River Valley: A case study of Kentucky, Ohio, and West Virginia.

INTRODUCTION: During early stages of COVID-19 in the United States, government representatives in Kentucky, Ohio, and West Virginia restricted or threatened to restrict abortion care under elective surgery bans. We examined how abortion utilization changed in these states. METHODOLOGY: We examined COVID-19 abortion-related state policies implemented in March and April 2020 using publicly available sources. We analyzed data on abortions by method and gestation and experiences of facility staff, using a survey of 14 facilities. We assessed abortions that took place in February-June 2020 and February-June 2021. RESULTS: In February-June 2020 the monthly average abortion count was 1916; 863 (45%) were medication abortions and 229 (12%) were ≥14 weeks gestation. Of 1959 abortions performed across all three states in April 2020, 1319 (67%) were medication abortions and 231 (12%) were ≥14 weeks gestation. The shift toward medication abortion that took place in April 2020 was not observed in April 2021. Although the total abortion count in the three-state region remained steady, West Virginia had the greatest decline in total abortions, Ohio experienced a shift from instrumentation to medication abortions, and Kentucky saw little change. Staff reported increased stress from concerns over health and safety and increased scrutiny by the state and anti-abortion protesters. DISCUSSION: Although abortion provision continued in this region, policy changes restricting abortion in Ohio and West Virginia resulted in a decrease in first trimester instrumentation abortions, an overall shift toward medication abortion care, and an increase in stress among facility staff during the early phase of COVID-19.

Adolescents' and Parents' Perspectives on a Novel Decision-Making Process for Return of Results in Genomic Research.

To understand whether they found a two-step decision process helpful and why, adolescent-parent dyads participating in a study investigating return of genomic testing results were asked about their decision-making experience. Responses were qualitatively coded and analyzed using thematic analysis. Adolescents and parents found both joint and independent decision-making stages helpful. Regarding independent decision-making, adolescents appreciated exercising independence, while parents valued both adolescent and parental independence. Joint decision-making allowed each to hear the other's viewpoints. Some found joint decision-making irrelevant but recognized it might help others. Overall, adolescents and parents had similar reasons for finding the two-step decision-making process helpful. Our findings support using such a process for engaging parents and adolescents in challenging research and clinical decisions.

State of Confusion: Ohio's Restrictive Abortion Landscape and the Production of Uncertainty in Reproductive Health Care.

This study examines an underexplored source of medical uncertainty: the political context of care. Since 2011, Ohio has passed over 16 abortion-restrictive laws. We know little about how this legislation affects reproductive health care outside of abortion clinics. Drawing on focus groups and interviews with genetic counselors and obstetrician-gynecologists, we examine how abortion legislation impacts their work. We find that interpretation and implementation of legislation is not straightforward and varies by institution and region of the state. An ever-changing legislative landscape combined with uneven implementation of restrictions into policy produces uncertainty in reproductive health care. We also found uncertainty about the legal consequences of abortion in restrictive contexts, with obstetrician-gynecologists reporting greater concerns given their proximity to care provision. We argue that uncertainty can result in stricter interpretations of regulations than necessitated by the law, thereby amplifying the impacts of an already restrictive context for abortion care.

Studying the impact of translational genomic research: Lessons from eMERGE.

Two major goals of the Electronic Medical Record and Genomics (eMERGE) Network are to learn how best to return research results to patient/participants and the clinicians who care for them and also to assess the impact of placing these results in clinical care. Yet since its inception, the Network has confronted a host of challenges in achieving these goals, many of which had ethical, legal, or social implications (ELSIs) that required consideration. Here, we share impediments we encountered in recruiting participants, returning results, and assessing their impact, all of which affected our ability to achieve the goals of eMERGE, as well as the steps we took to attempt to address these obstacles. We divide the domains in which we experienced challenges into four broad categories: (1) study design, including recruitment of more diverse groups; (2) consent; (3) returning results to participants and their health care providers (HCPs); and (4) assessment of follow-up care of participants and measuring the impact of research on participants and their families. Since most phases of eMERGE have included children as well as adults, we also address the particular ELSI posed by including pediatric populations in this research. We make specific suggestions for improving translational genomic research to ensure that future projects can effectively return results and assess their impact on patient/participants and providers if the goals of genomic-informed medicine are to be achieved.

Engaging Adolescents and Young Adults in Decisions About Return of Genomic Research Results: a mixed-methods longitudinal clinical trial protocol.

Background: To protect minors' future autonomy, professional organizations have historically discouraged returning predictive adult-onset genetic test results and carrier status to children. Recent clinical guidance diverges from this norm, suggesting that when minors have genomic sequencing performed for clinical purposes, parents and children should have the opportunity to learn secondary findings, including for some adult-onset conditions. While parents can currently opt in or out of receiving their child's secondary findings, the American Society of Human Genetics Workgroup on Pediatric Genetic and Genomic Testing suggests including adolescents in the decision-making process. However, it is not clear what factors young people consider when given the opportunity to learn genetic findings for themselves. We are examining adolescents', young adults', and parents' (if applicable) decisions about learning genomic information for the adolescent. Methods: We are enrolling assenting (ages 13-17) adolescents and consenting (ages 18-21) young adults in a prospective genomic screening study to assess the choices they make about receiving individual genomic results. Participants use an online tool to indicate whether they want to learn their personal genetic risk for specific preventable, treatable, and adult-onset conditions, as well as carrier status for autosomal recessive conditions. We are examining 1) how choices differ between adolescent and young adult cohorts (as well as between adolescents/young adults and parents) and 2) decisional conflict and stability across study timepoints. Results are returned based on participants' choices. Qualitative interviews with a subset of participants explore decisional stability, adolescent/young adult engagement with parents in decision-making, and the impact of learning pathogenic/likely pathogenic and carrier results. Discussion: This study explores decision making and decision stability between adolescents and parents (where applicable), as well as the ethical implications and impact of return of clinical-grade genetic research results to adolescents and young adults. The results of this study will contribute empirical evidence to support best practices and guidance on engaging young people in genetic research studies and clinical care that offer return of results.

Kentucky's abortion landscape, 2010 to 2019: an analysis of pre-Dobbs abortion disparities in a rural, restrictive state.

Background: Since 2010, many US states have passed laws restricting abortion providers' ability to provide care. Such legislation has no demonstrated health benefits and creates inequitable barriers for patients. Methods: To examine how Kentucky's abortion policies coincided with facility closures and abortion utilisation, we conducted a review of state abortion policies from 2010 to 2019 using newspapers and websites. We calculated abortion rates (abortions per 1000 women ages 15-44) by state of residence and provision for Kentucky, the South, and the US using data from the CDC and Kentucky Department of Health. We calculated percentages leaving and from out-of-state, and analysed abortions by race, pregnancy duration, and method. Findings: Of 17 policies passed between 2010 and 2019, ten were enacted, including 20-week and telemedicine bans. One of Kentucky's two abortion facilities closed in 2017. The pooled average abortion rate in Kentucky (4.1) and for Kentuckians (5.8) was lower than national averages (11.8 and 11.1). An average of 38% of Kentuckians left their state for care, compared to 7% nationally. In 2019, the abortion rate in Kentucky was 5.8 times higher for Black patients than White patients (compared to 4.8 times nationally). The majority (62%) of abortions in Kentucky took place at 7-13 weeks' gestation. Interpretation: Abortions in Kentucky were less frequent than in the South and US. The larger Black-White abortion rate gap reflects race- and class-based structural inequities in healthcare. Without federal protections, abortion access in Kentucky will continue waning. Funding: This study was supported by a philanthropic foundation that makes grants anonymously.

Unlimited Discretion: How Unchecked Bureaucratic Discretion Can Threaten Abortion Availability.

Previous research has assessed the impact of state regulations on abortion clinics and patients, but how bureaucrats implement them is less understood and is increasingly important as states arbitrate abortion regulation. The authors conducted a case study of how bureaucrats use discretion to implement state regulations on abortion, focusing on two abortion facilities in southwest Ohio from 2010 to 2022. Ohio abortion facilities are required to obtain a written transfer agreement, despite it offering no demonstrable health or safety benefits. The authors find that state requirements for obtaining variances-a process that allows abortion facilities to operate without a written transfer agreement-have become exceedingly difficult to comply with. The authors show how state statutes and administrative law have enabled bureaucrats to wield unlimited discretion and enforce arbitrary requirements. This unlimited bureaucratic discretion and accompanying administrative burden exacerbated clinic instability and threatened abortion availability in southwest Ohio for almost a decade. As implementation and interpretation of abortion policy is increasingly left to state bureaucrats and civil servants following the Supreme Court's Dobbs decision, how bureaucrats use discretion will influence clinic stability and abortion availability. The authors posit that unlimited bureaucratic discretion may exert greater influence on abortion availability across the nation as states scramble to clarify and implement policies after Dobbs.

Seeking abortion care in Ohio and Texas during the COVID-19 pandemic.

OBJECTIVES: Political and public health responses to the COVID-19 pandemic changed provision of abortion care and exacerbated existing barriers. We aimed to explore experiences of individuals seeking abortion care in 2 abortion-restrictive states in the United States where state policies and practice changes disrupted abortion provision during the pandemic. STUDY DESIGN: We conducted 22 semistructured interviews in Texas (n = 10) and Ohio (n = 12) to assess how state executive orders limiting abortion, along with other public health guidance and pandemic-related service delivery changes, affected individuals seeking abortion care. We included individuals 18 years and older who contacted a facility for abortion care between March and November 2020. We coded and analyzed interview transcripts using both inductive and deductive approaches. RESULTS: Participants reported obstacles to obtaining their preferred timing and method of abortion. These obstacles placed greater demands on those seeking abortion and resulted in delays in obtaining care for as long as 11 weeks, as well as some being unable to obtain an abortion at all. CONCLUSIONS: Political and public health responses to the COVID-19 pandemic - exacerbated pre-pandemic barriers and existing restrictions and constrained options for people seeking abortion in Ohio and Texas. Delays were consequential for all participants, regardless of their ultimate ability to obtain an abortion. IMPLICATIONS: During the COVID-19 pandemic, state executive orders and clinic practices exacerbated already constrained access to care. Findings highlight the importance of protecting timely care and the full range of abortion methods. Findings also preview barriers individuals seeking abortion may encounter in states that restrict or ban abortion.

The double-edged sword of abortion regulations: Decreasing training opportunities while increasing knowledge requirements.

PURPOSE: The authors explore how abortion regulations in Ohio, an abortion-restrictive state in the USA, impact obstetrician-gynecologists' (OB/GYNs) training in reproductive healthcare and describe what OB/GYNs believe to be the broader impact of Ohio's regulations on skill-building, skills maintenance, and professional retention of reproductive healthcare providers in the state. Authors discuss how their findings foreshadow abortion training limitations in Ohio and other abortion-restrictive states now that abortion regulations have returned to the states. METHODS: The authors conducted four semi-structured focus groups and five in-depth interviews between April 2019 and March 2020. Participants included OB/GYNs practicing obstetrics and gynecology in Ohio between 2010 and 2020. Thematic analysis was conducted using Atlas.ti. RESULTS: Twenty attending physicians and 15 fellows and residents participated in the study. Participants discussed the impact of Ohio's written transfer agreement, gestational-limit, and abortion method and facility bans on training and skill-building opportunities. Participants felt that Ohio's strict abortion regulations 1) limit opportunities to observe and perform abortion procedures during training; 2) require learning the ever-changing legality of abortion provision; 3) limit the number of abortions OB/GYNs can provide, leading to the atrophy of their skills over time; and 4) may prevent prospective medical students and residents from choosing to study in Ohio and may lead to physician attrition from the state. CONCLUSION: Prior to the reversal of federal protections for abortion in 2022, OB/GYNs in Ohio and other abortion-hostile states experienced barriers to training in abortion care. In returning abortion regulation to the states, access to training is likely to be increasingly restricted. This research demonstrates how abortion-restrictions hamper physicians' skills needed to care for patients, particularly in emergent situations. This puts patients at risk and places physicians in precarious ethical positions. Expanding protections and reducing restrictions on abortion will ensure OB/GYNs and trainees have the skills necessary to care for patients presenting for reproductive healthcare.

A Mixed Methods Analysis of Requests for Religious Exemptions to a COVID-19 Vaccine Requirement.

Background: While employers are increasingly considering and implementing COVID-19 vaccination requirements, little is known about the reasons offered by employees seeking religious exemptions.Methods: We conducted a mixed methods analysis of all the requests for religious exemptions submitted during the initial implementation of a COVID-19 vaccination requirement at a single academic medical center in the United States.Results: Five hundred sixty-five (3.4%) employees requested religious exemptions. At least 305 (54.0%) requesters had job titles suggesting that they had direct patient contact. Four hundred ninety-nine (88.3%) of requesters self-identified as Christian, of whom 120 (21.2%) identified as Roman Catholic. Requesters offered 0 to 8 (mean 2.7) categories of reasons for their request. The most frequently stated reasons pertained to the use of fetal cell lines in vaccine development and manufacturing (382, 67.6%), interest in maintaining purity (221, 39.1%), or belief in divine healing (172, 30.4%). Some requesters also volunteered evidence of the sincerity of their beliefs including examples of their religious practices (116, 20.5%), other practices (66, 11.7%), and emotional states (32, 5.7%). One hundred fifty-two applications (26.9%) contained text copied without attribution, primarily from sample religious exemption request letters available on the Internet.Conclusions: Most requesters focused on the use of fetal cell lines in the development or manufacturing of the vaccines as the justification for their request. The development of vaccines that are not reliant on fetal cell lines may increase vaccination rates. Understanding reasons for religious exemption requests may inform vaccine education and vaccination policies.

Developing video education materials for the return of genomic test results to parents and adolescents.

Objective: To describe the development, implementation, and revision of a video to provide information about genomic testing and the return of genomic research results to adolescents and parents. Methods: Formative, community-engaged research was conducted in three stages: development, implementation, and revision. Existing research participant advisory groups were used for focus groups and convenience sampling was used for interviews. Participants included parents, young adults without children, and adolescents. Transcripts of recorded sessions were used for formative analysis. Results: Video was the preferred format for delivering genomic testing information to adolescents during the development stage. During implementation, adolescents identified video length as an impediment to recall. During the revision stage, participants preferred the video in separate short segments, supported plan to require only one short video and leaving other short videos optional. Participants were divided on whether the required short video provided enough information, but all participants reported that watching additional videos would not have changed their decisions about receiving test results. Conclusion: Genomic education videos should be brief (<4 mins) to improve the odds that participants will view the entirety of any required video. Innovation: The development of participant materials should incorporate plans for monitoring implementation and plans for revising materials.

Outcomes of Returning Medically Actionable Genomic Results in Pediatric Research.

PURPOSE: The electronic Medical Records and Genomics (eMERGE) Phase III study was undertaken to assess clinical utility of returning medically actionable genomic screening results. We assessed pediatric clinical outcomes following return of pathogenic/likely pathogenic (P/LP) variants in autosomal dominant conditions with available effective interventions. METHODS: The two eMERGE III pediatric sites collected outcome data and assessed changes in medical management at 6 and 12 months. RESULTS: We returned P/LP results to 29 participants with outcome data. For 23 of the 29 participants, the P/LP results were previously unknown. Five of the 23 participants were already followed for conditions related to the P/LP variant. Of those receiving novel results and not being followed for the condition related to the P/LP result (n = 18), 14 (77.8%) had a change in healthcare after return of results (RoR). Following RoR, cascade testing of family members occurred for 10 of 23 (43.5%). CONCLUSIONS: The most common outcomes post-RoR included imaging/laboratory testing and health behavior recommendations. A change in healthcare was documented in 77.8% of those receiving results by 6 months. Our findings demonstrate how return of genomic screening results impacts healthcare in pediatric populations.

Ohio Abortion Regulations and Ethical Dilemmas for Obstetrician-Gynecologists.

OBJECTIVE: To analyze obstetrician-gynecologists' (ob-gyns') experiences with, and perspectives on, how Ohio's abortion-restrictive regulatory landscape affects their health care practices. METHODS: Between 2019 and 2020, we conducted qualitative interviews and focus groups with ob-gyns (N=35) who had practiced in Ohio for at least 6 months between 2010 and 2020. Discussions were recorded, transcribed, coded, and analyzed thematically using ATLAS.ti software. RESULTS: Participants perceived Ohio abortion regulations affecting their practice in three key ways: abortion regulations framed abortion and physicians who provide abortion as separate and distinct from other medical practices and physicians; many institutional interpretations of abortion regulations undermined physician expertise and professional autonomy; and the constellation of abortion regulations, institutional interpretations, physicians' trepidation, and their perceived inability to exercise clinical judgment worked together to limit abortion access and increase risks to patients' lives and health. The combined factors left participants feeling distraught that they were unable to practice medicine in an ethical and compassionate manner. CONCLUSION: Ohio abortion regulations limit ob-gyns' ability to provide comprehensive reproductive health care, creating ethical dilemmas for these physicians as they attempt to care for their patients. As Ohio's abortion laws increase in number and restrictiveness, they further undermine obstetric and gynecologic ethical practice guidelines. However, medical institutions play a key role in determining abortion provision in Ohio; through their interpretation of the law, institutions can demonstrate support or further limit ob-gyns' ability to exercise clinical judgment and provide ethical, compassionate care to their patients. Considerable work remains to bring Ohio's abortion regulations, institutional interpretations, and physician practices into alignment with professional clinical practice and ethics guidelines.