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.

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.

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.

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.

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.

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.

How Ohio's proposed abortion bans would impact travel distance to access abortion care.

CONTEXT: Since March 2021, the Ohio legislature has been actively considering laws that would ban abortion if the United States Supreme Court overturns the Roe v. Wade decision that legalized abortion nationally in 1973. METHODS: We used a national database of publicly advertised abortion facilities to calculate driving distances for Ohioans before and after the activation of proposed abortion bans. Using a legal analysis of abortion laws following the overturn of Roe, we determined which states surrounding Ohio would continue providing abortion care. We calculated distances from each Ohio county centroid to the nearest open abortion facility in three scenarios: (1) as of February 2022, (2) the best-case post-Roe scenario (two of the five surrounding states continue to offer abortion care), and (3) worst-case post-Roe scenario (no surrounding states continue to offer abortion care). We calculated population-weighted distances using county-level data about women aged 15-44 years from the 2019 American Community Survey. RESULTS: In February 2022, all Ohio county centroids were at most 99 miles from an abortion facility (median = 50 miles). The best-case post-Roe scenario shows 62 of Ohio's 88 counties to be 115-279 miles away from the nearest facility (median = 146). The worst-case shows 85 counties to be 191-339 miles away from the nearest facility (median = 264). The current average population-weighted driving distance from county centroid to the nearest facility is 26 miles; the post-Roe scenarios would increase this to 157 miles (best-case) or 269 miles (worst-case). CONCLUSIONS: Ohio's proposed abortion bans would substantially increase travel distances to abortion care, impacting over 2.2 million reproductive-aged Ohioans.

Alobar holoprosencephaly: Exploring mothers' perspectives on prenatal decision-making and prognostication.

OBJECTIVES: Parents receiving a prenatal diagnosis of alobar holoprosencephaly (HPE) often experience uncertainty regarding the pregnancy prognosis. There is little known about how best to counsel and support families receiving the diagnosis. This study explored parental experiences and wishes after receiving a prenatal diagnosis of alobar HPE. METHODS: This was a retrospective qualitative study. Semi-structured interviews were conducted to determine factors impacting parents' decision-making process, experiences with healthcare providers, and expectations for their child's length and quality of life. Interviews were analyzed using qualitative content analysis. RESULTS: Eight mothers who received a prenatal diagnosis of alobar HPE between 2013 and 2019 participated in the study. Parental expectations were based on information conveyed during prenatal counseling. Religious and personal beliefs, perceived suffering, and provider prognostication contributed to parent decisions and goals of care. Participants reported pressure to terminate the pregnancy. Parents were not prepared for the possibility of survival beyond the perinatal period. Most parents reported no regret in their choices. CONCLUSION: Patients receiving a prenatal diagnosis of alobar HPE desire access to balanced prenatal counseling about prognosis, morbidity, and mortality. Providers should explore values and beliefs that contribute to parents' goals of care and offer appropriate information and referrals.

Experiences of adolescents and their parents after receiving adolescents' genomic screening results.

There has been considerable debate over whether adolescents should have the opportunity to learn genetic information about adult-onset disease risk and carrier status without a clinical indication. Adolescents face increasing opportunities to learn more about such genetic risks through the return of secondary findings from clinical genomic testing, direct-to-consumer genetic testing, and research opportunities. However, little is known about the perspectives of adolescents who have received genomic screening results. We conducted separate qualitative interviews with 15 adolescents and their parents who enrolled in a research protocol where they decided which genomic screening results to receive for the adolescent for up to 32 conditions informed by 84 genes. The goal of these interviews was to explore the impact of adolescents learning genomic results without a clinical indication for screening. Of the participating dyads, four received positive results for a pathogenic/likely pathogenic (P/LP) variant for an autosomal dominant (AD) condition, five received carrier results for a heterozygous P/LP variant for an autosomal recessive (AR) condition, and six received negative results. An interpretive descriptive qualitative approach was used. Interview transcripts were coded using a guide developed by the study team based on themes that emerged from the interviews. Degree of recall and description of results, actionability, and emotional responses differed according to the types of results received. However, all participants were satisfied with their decision to learn results, and most did not report any lasting psychological harms. Participants adapted to genomic information about themselves, even after learning about unexpected increased risk for future health problems. Our findings support the position that, whenever possible, perspectives and wishes of adolescents should be strongly considered and respected in the decision-making process regarding genetic testing.

Experiences of reproductive genetic counselors with abortion regulations in Ohio.

Since 2010, Ohio legislators have passed more than 15 legislative changes related to abortion and abortion providers, and nine procedural abortion clinics have closed. We investigated reproductive genetic counselors' perceptions, attitudes and self-reported practices regarding Ohio's current and proposed abortion regulations. We conducted five focus groups and two telephone interviews in 2019-2020, with a total of 19 reproductive genetic counselors. Participants discussed difficulties keeping current on abortion legislation and clinics' and hospitals' policies, resulting in anticipatory anxiety and leading to additional work to discuss the laws with patients. Participants articulated that practices of reproductive genetic counseling-and patient advocacy-are impeded by the legislation. Genetic counselors perceive negative impacts on patients' autonomy, particularly reflective of healthcare disparities of marginalized groups, which may contribute to frustration and anger. Ultimately, the mental and emotional burden on genetic counselors created by abortion legislation contributes to compassion fatigue and burnout. Our findings show that Ohio's abortion regulations negatively impact reproductive genetic counselors and their relationships with their patients. Repealing existing abortion regulations and preventing future restrictive legislation may ameliorate the negative effects of regulations on reproductive genetic counselors and their patients. In the event that these laws remain, innovative communication tools and proactive professional society advocacy are potential means to mitigate the negative impact on reproductive genetic counselors.

Federal, state, and institutional barriers to the expansion of medication and telemedicine abortion services in Ohio, Kentucky, and West Virginia during the COVID-19 pandemic.

OBJECTIVES: We aimed to characterize the combined impact of federal, state, and institutional policies on barriers to expanding medication and telemedicine abortion care delivery during the COVID-19 pandemic in the abortion-restrictive states of Ohio, Kentucky, and West Virginia. STUDY DESIGN: We analyzed 4 state policies, 2 COVID-related state executive orders, and clinic-level survey data on medication abortion provision from fourteen abortion facilities in Ohio, Kentucky, and West Virginia from December 2019 to December 2020. We calculated the percent of medication abortions provided at these facilities during the study period by state, to assess changes in medication abortion use during the pandemic. RESULTS: We ascertained that COVID-19-executive orders in Ohio and West Virginia that limited procedural abortion in Spring 2020 coincided with an increase in the overall number and proportion of medication abortions in this region, peaking at 1613 medication abortions (70%) in April 2020. Ohio and West Virginia, which had executive orders limiting procedural abortion, saw relatively greater increases in April compared to Kentucky. Despite temporary lifting of the mifepristone REMS, prepandemic regulations banning telemedicine abortion in Kentucky and West Virginia and requiring in-person clinic visits for medication abortion distribution in Ohio limited clinics' ability to adapt to offer medication abortion by mail. CONCLUSIONS: Our findings illustrate how restrictive medication and telemedicine abortion policies in Ohio, Kentucky, and West Virginia created additional obstacles for patients seeking medication abortion during the pandemic. Permanently lifting federal regulations on in-clinic distribution of mifepristone would only advantage abortion seekers in states without restrictive telehealth and medication abortion policies. State policies that limit access to comprehensive abortion services should be central in larger efforts toward dismantling barriers that impinge upon reproductive autonomy. IMPLICATION STATEMENT: We find that abolishing the REMS on mifepristone would not be enough to expand access to patients in abortion-restrictive states with telemedicine and medication abortion laws. While the REMS is a barrier, it represents one of several hindrances to the expansion of telemedicine abortion distribution across the United States.