The FDA in the Crosshairs-Science, Politics, and Abortion.

In this Viewpoint, the Supreme Court case FDA v AHM is used to illustrate the tension the FDA faces between science and politics, and state authority over abortion vs federal authority over which drugs may be marketed nationwide.

Explaining the Fifth Circuit Court of Appeals Ruling on Mifepristone Access.

This Viewpoint summarizes the Fifth Circuit Court of Appeals ruling on access to mifepristone, the first of 2 pills used in medication abortion.

Requests for Self-managed Medication Abortion Provided Using Online Telemedicine in 30 US States Before and After the Dobbs v Jackson Women's Health Organization Decision.

This study assesses changes in online telemedicine requests to self-manage abortions with medications before vs after the Dobbs v Jackson Women's Health Organization Supreme Court decision overturning Roe v Wade.

Clinical Update on Uses for Mifepristone in Obstetrics and Gynecology.

Importance: Mifepristone (RU-486) is a selective progesterone receptor modulator that has antagonist properties on the uterus and cervix. Mifepristone is an effective abortifacient, prompting limitations on its use in many countries. Mifepristone has many uses outside of induced abortion, but these are less well known and underutilized by clinicians because of challenges in accessing and prescribing this medication. Objectives: To provide clinicians with a history of the development of mifepristone and mechanism of action and safety profile, as well as detail current research on uses of mifepristone in both obstetrics and gynecology. Evidence Acquisition: A PubMed search of mifepristone and gynecologic and obstetric conditions was conducted between January 2018 and December 2021. Other resources were also searched, including guidelines from the American College of Obstetricians and Gynecologists and the Society of Family Planning. Results: Mifepristone is approved by the Food and Drug Administration for first-trimester medication abortion but has other off-label uses in both obstetrics and gynecology. Obstetric uses that have been investigated include management of early pregnancy loss, intrauterine fetal demise, treatment of ectopic pregnancy, and labor induction. Gynecologic uses that have been investigated include contraception, treatment of abnormal uterine bleeding, and as an adjunct in treatment of gynecologic cancers. Conclusions and Relevance: Mifepristone is a safe and effective medication both for its approved use in first-trimester medication abortion and other off-label uses. Because of its primary use as an abortifacient, mifepristone is underutilized by clinicians. Providers should consider mifepristone for other indications as clinically appropriate.

Medication Abortion.

This JAMA Patient Page describes medication abortion and its risks and effectiveness.

Termination of pregnancy in the second trimester - the course of different therapy regimens.

OBJECTIVES: To compare two prostaglandin analogs and two application intervals between mifepristone and the prostaglandin analog administration on the time to abortion in second trimester termination of pregnancy. Other endpoints were live birth rate and fetal lifetime after expulsion. METHODS: Retrospective data of 373 abortions performed were evaluated. Four medical induction subgroups and two feticide subgroups were considered. The definition criteria of the subgroups were the choice of administered prostaglandin analog (misoprostol vs. sulprostone) and the time interval between mifepristone and prostaglandin analog administration (48 vs. 24 h). The outcome parameters were the time to complete uterine evacuation (TCUE), the live birth rate and duration of fetal life. RESULTS: In the misoprostol subgroups, the median TCUE was 1.6 h longer in the 24-h group than in the 48-h group (p=0.950). In the sulprostone subgroups, the median TCUE was 1.9 h shorter in the 24-h group than in the 48-h group (p=0.950). The median TCUE was shorter for sulprostone than for misoprostol in all six subgroups (p<0.001). The rate of fetal live births ranged between 13.6 and 15.9% within the medical induction subgroups (p=0.969). The median fetal lifetime was slightly shorter in the sulprostone groups than in the misoprostol groups (p=0.563). CONCLUSIONS: Both application intervals and prostaglandin analogs are similarly effective. The therapy regime should be adapted to the personal preferences of the woman, the situational and clinical conditions.

Glucocorticoid receptor blockers.

Mifepristone is the only glucocorticoid receptor antagonist currently approved for the treatment of Cushing's syndrome. Although originally developed as an abortifacient due to its blockade of the progesterone receptor, a number of case reports documented its efficacy as a glucocorticoid receptor blocker going back to 1985. The SEISMIC trial, published in 2012, provided sufficient data on efficacy and adverse effects for regulatory approval. Mifepristone provides clear benefits on glycemia, blood pressure, muscle weakness, body weight and the other myriad clinical manifestations of Cushing's syndrome. However, because it blocks the glucocorticoid receptor, blood cortisol and ACTH levels actually rise, rather than fall; this complicates patient management. Doses are adjusted based on clinical manifestations rather than hormone levels. Adverse effects include adrenal insufficiency due to overdosage, hypokalemia, and menorrhagia. Treatment of severe adrenal insufficiency requires high doses of dexamethasone. Other glucocorticoid receptor blockers without effects on the progesterone receptor are being developed. Because mifepristone inhibits CYP3A and CYP2C8/2C9, drug-drug interactions can occur. These potential adverse effects can largely be avoided with careful attention to detail. My opinion is that its current place in therapy is in patients with severe disease and in those not responding to other treatments.

Similarities and differences between embryonic implantation and CTC invasion: Exploring the roles of abortifacients in cancer metastasis chemoprevention.

Mifepristone (RU486) is a chemical contraceptive marketed in more than 55 countries and used by hundreds of millions of women worldwide. Current studies reported its uses by both genders for a safe and long-term psychotic depression and particularly for traditional cancer chemotherapy. Here, we investigated the multidisciplinary data from recent large epidemiological chemoprevention studies for long-term use of oral contraceptives to reduce cancer risk, and from the unsuccessful clinical trials of mifepristone used as a post-metastatic anticancer drug, and elucidated the similarities and differences in cellular and molecular processes between embryonic implantation to endometrium and adhesion/invasion of circulating tumor cells (CTCs) to vascular endothelium. The deep analyses provide a stronger scientific basis for repurposing abortifacients for safe and effective cancer metastatic chemoprevention. Initiation of such cancer drug development strategy represents a paradigm shift from traditional post-metastasis treatments to novel pre-metastasis chemoprevention.

Management of 14 patients with cornual heterotopic pregnancy following embryo transfer: experience from the past decade.

OBJECTIVE: There are two major management approach for cornual heterotopic pregnancy, transvaginal cornual embryo reduction with ultrasound guidance, or laparoscopic cornual resection. This no consensus on the optimal management for cornual heterotopic pregnancy. Here, we are trying to determine the optimal management approach for patients with viable cornual heterotopic pregnancy following embryo transfer. METHODS: This is a retrospective cohort study conducted at the locally largest reproductive center of a tertiary hospital. A total of 14 women diagnosed as viable cornual heterotopic pregnancy following embryo transfer. Six patients were treated with cornual pregnancy reduction under transvaginal ultrasound guidance without the use of feticide drug (treatment 1), and eight patients were treated with laparoscopic cornual pregnancy resection (treatment 2). RESULTS: All 14 patients of cornual heterotopic pregnancy following embryo transfer due to fallopian tubal factor, among which, 12 patients had cornual pregnancy occurred in the ipsilateral uterine horn of tubal pathological conditions. Nine (64.29%) showed a history of ectopic pregnancy. Thirteen (92.86%) patients were transferred with two embryos and only one patient had single embryo transferred. Six patients received treatment 1, and 2 (33.33%) had uterine horn rupture and massive bleeding which required emergency laparoscopic surgery for homostasis. No cornual rupture occurred among patients received treatment 2. Each treatment group had one case of spontaneous miscarriage. The remaining 5 cases in treatment 1 group and the remaining 7 cases in treatment 2 group delivered healthy live offspring. CONCLUSION: Patients with tubal factors attempting for embryo transfer, especially those aiming for multiple embryos transfer, should be informed with risk of cornual heterotopic pregnancy and the subsequent cornual rupture. Compared with cornual pregnancy reduction under transvaginal ultrasound guidance, laparoscopic cornual resection might be a favorable approach for patients with viable cornual heterotopic pregnancy.

"It was close enough, but it wasn't close enough": A qualitative exploration of the impact of direct-to-patient telemedicine abortion on access to abortion care.

OBJECTIVE: To understand how obtaining a medication abortion by mail with telemedicine counseling versus traditional in-clinic care impacted participants' access to care. STUDY DESIGN: We conducted a qualitative study with semi-structured telephone interviews with individuals who completed a medication abortion by mail through the TelAbortion study. We asked participants how they learned about telemedicine abortion, reasons for choosing it, what their alternative would have been, and about their experience. We transcribed, coded, and performed qualitative content analysis of the interviews and are presenting a subset of themes related to access to care when the restrictions on clinic dispensing of mifepristone are removed. RESULTS: We interviewed 45 people from January to July 2020. Direct-to-patient telemedicine abortion was more convenient and accessible than in-clinic abortion care when considering the burdens of travel, clinic availability, logistics, and cost that were associated with in-clinic abortion. Stigma led to a prioritization of privacy, and by going to a clinic, participants feared a loss of privacy whereas obtaining a medication abortion by mail made it easier to maintain confidentiality. Faced with these barriers, 13% of participants stated they would have continued their pregnancy if TelAbortion had not been an option. Participants found direct-to-patient telemedicine abortion to be acceptable and recommended it to others. Benefits of telemedicine were amplified during the COVID-19 pandemic due to concerns around infection exposure with in-clinic care. CONCLUSION: Going to a clinic was a burden for participants, to the point where some would not have otherwise been able to get an abortion. Medication abortion by mail with telemedicine counseling was a highly acceptable alternative. IMPLICATIONS: Medication abortion by mail can increase access to abortion with the added benefits of increased perceived privacy and decreased logistical burdens. Removing the in-person dispensing requirement for mifepristone would allow direct-to-patient telemedicine abortion to be implemented outside of a research setting without compromising the patient experience.

Greasing the wheels: The impact of COVID-19 on US physician attitudes and practices regarding medication abortion.

OBJECTIVE: To explore US provider perspectives about self-sourced medication abortion and how their attitudes and clinic practices changed in the context of the COVID-19 pandemic. STUDY DESIGN: We conducted a multi-method study of survey and interview data. We performed 40 baseline interviews and surveys in spring 2019 and 36 follow-up surveys and ten interviews one year later. We compared pre- and post-Likert scale responses of provider views on the importance of different aspects of standard medication abortion assessment and evaluation (e.g., related to ultrasounds and blood-typing). We performed content analysis of the follow-up interviews using deductive-inductive analysis. RESULTS: Survey results revealed that clinics substantially changed their medication abortion protocols in response to COVID-19, with more than half increasing their gestational age limits and introducing telemedicine for follow-up of a medication abortion. Interview analysis suggested that physicians were more supportive of self-sourced medication abortion in response to changing clinic protocols that decreased in-clinic assessment and evaluation for medication abortion, and as a result of physicians' altered assessments of risk in the context of COVID-19. Having evidence already in place that supported these practice changes made the implementation of new protocols more efficient, while working in a state with restrictive abortion policies thwarted the flexibility of clinics to adapt to changes in standards of care. CONCLUSION: This exploratory study reveals that the COVID-19 pandemic has altered clinical assessment of risk and has shifted practice towards a less medicalized model. Further work to facilitate person-centered abortion information and care can build on initial modifications in response to the pandemic. IMPLICATIONS: COVID-19 has shifted clinician perception of risk and has catalyzed a change in clinical protocols for medication abortion. However, state laws and policies that regulate medication abortion limit physician ability to respond to changes in risk assessment.

Factors associated with successful implementation of telehealth abortion in 4 United States clinical practice settings.

OBJECTIVE: To overcome obstacles to delivering medication abortion services during the COVID-19 pandemic, clinics and providers implemented new medication abortion service models not requiring in-person care. This study identifies organizational factors that promoted successful implementation of telehealth and adoption of "no test" medication abortion protocols. STUDY DESIGN: We conducted 21 semi-structured, in-depth interviews with health care providers and clinic administrators implementing clinician-supported telehealth abortion during the COVID pandemic. We selected 15 clinical sites to represent 4 different practice settings: independent primary care practices, online medical services, specialty family planning clinics, and primary care clinics within multispecialty health systems. The Consolidated Framework for Implementation Research guided our thematic analysis. RESULTS: Successful implementation of telehealth abortion included access to formal and informal inter-organizational networks, including professional organizations and informal mentorship relationships with innovators in the field; organizational readiness for implementation, such as having clinic resources available for telehealth services like functional electronic health records and options for easy-to-use virtual patient-provider interactions; and motivated and effective clinic champions. CONCLUSIONS: In response to the need to offer remote clinical services, 4 different practice settings types leveraged key operational factors to facilitate successful implementation of telehealth abortion. Information from this study can inform implementation strategies to support the dissemination and adoption of this model. IMPLICATIONS: Examples of successfully implemented telehealth medication abortion services provide a framework that can be used to inform and implement similar patient-centered telehealth models in diverse practice settings.

Family medicine provision of online medication abortion in three US states during COVID-19.

OBJECTIVE: To examine provision of direct-to-patient medication abortion during COVID-19 by United States family physicians through a clinician-supported, asynchronous online service, Aid Access. STUDY DESIGN: We analyzed data from United States residents in New Jersey, New York, and Washington who requested medication abortion from 3 family physicians using the online service from Aid Access between April and November 2020. This study seeks to examine individual characteristics, motivations, and geographic locations of patients receiving abortion care through the Aid Access platform. RESULTS: Over 7 months, three family physicians using the Aid Access platform provided medication abortion care to 534 residents of New Jersey, New York, and Washington. There were no demographic differences between patients seeking care in these states. A high percentage (85%) were less than 7 weeks gestation at the time of their request for care. The reasons patients chose Aid Access for abortion services were similar regardless of state residence. The majority (71%) of Aid Access users lived in urban areas. Each family physician provided care to most counties in their respective states. Among those who received services in the three states, almost one-quarter (24%) lived in high Social Vulnerability Index (SVI) counties, with roughly one-third living in medium-high SVI counties (33%), followed by another quarter (26%) living in medium-low SVI counties. CONCLUSIONS: Family physicians successfully provided medication abortion in three states using asynchronous online consultations and medications mailed directly to patients. IMPLICATIONS: Primary care patients are requesting direct-to-patient first trimester abortion services online. By providing abortion care online, a single provider can serve the entire state, thus greatly increasing geographic access to medication abortion.

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.

Medical management of induced and incomplete first-trimester abortion by non-physicians in low- and middle-income countries: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Unsafe abortion is the cause of a substantial number of maternal mortalities and morbidities globally, but specifically in low- and middle-income countries. Medical abortion methods provided by non-physicians may be a way to reduce the burden of unsafe abortions. Currently, only one systematic review comparing non-physicians with physicians for medical abortion exists. However, the review does not have any setting restrictions and newer evidence has since been published. Therefore, this review aims to evaluate the effectiveness, acceptability, and safety of first-trimester abortion managed by non-physicians compared with physicians in low- and middle-income countries. MATERIAL AND METHODS: The databases PubMed, Cochrane Library, Global Health Library, and EMBASE were searched using a structured search strategy. Further, the trial registries clinicaltrials.gov and The International Clinical Trial Registry Platform were searched for published and unpublished trials. Randomized controlled trials comparing provision of medical abortion by non-physicians with that by physicians in low- or middle-income countries were included. Risk of bias was assessed using the Cochrane Risk of Bias tool. Trials that reported effect estimates on the effectiveness of medical methods on complete abortion were included in the meta-analysis. The protocol was prospectively registered in the PROSPERO database, ID: CRD42020176811. RESULTS: Six papers from four different randomized controlled trials with a total of 4021 participants were included. Two of the four included trials were assessed to have overall low risk of bias. Four papers had outcome data on complete abortion and were included in the meta-analyses. Medical management of first-trimester abortion and medical treatment of incomplete abortion were found to be equally effective when provided by a non-physician as when provided by a physician (risk ratio 1.00; 95% CI 0.99-1.01). Further, the treatment was equally safe, and women were equally satisfied when a non-physician provided the treatment compared with a physician. CONCLUSIONS: Provision of medical abortion or medical treatment for incomplete abortion in the first trimester is equally effective, safe, and acceptable when provided by non-physicians compared with physicians in low- and middle-income countries. We recommend that the task of providing medical abortion and medical treatment for incomplete abortion in low- and middle-income countries should be shared with non-physicians.

Glancing at the past and course-setting for the future: lessons from the last decade of research on medication abortion in high-income countries.

OBJECTIVE: Although medication abortion has become more common in high-income countries, the procedure has not yet met early expectations for widening access to abortion. High-quality evidence can serve as a catalyst for changes in policy and practice. To direct research priorities, it is important to understand where quality evidence is concentrated and where gaps remain. High-income countries have developed a body of evidence that may have implications for the future of medication abortion. This literature review assesses the characteristics and quality of published studies on medication abortion conducted in the last 10 years in high-income countries and indicates future areas for research to advance policy and practice, and broaden access. STUDY DESIGN: A structured search for literature resulted in 207 included studies. A framework based upon the World Health Organization definition of sub-tasks for medication abortion was developed to categorize research by recognized stages of the medication abortion process. Using an iterative and inductive approach, additional sub-themes were created under each of these categories. Established quality assessment frameworks were drawn upon to gauge the internal and external validity of the included research. RESULTS: Studies in the US and the UK have dominated research on MA in high-income countries. The political and social contexts of these countries will have shaped of this body of research. The past decade of research has focused largely on clinical aspects of medication abortion. CONCLUSION: Researchers should consider refocusing energies toward testing service delivery approaches demonstrating promise and prioritizing research that has broader generalizability and relevance outside of narrow clinical contexts. Although medication abortion is more commonly available worldwide, it is not being used as often as people thought it would be, particularly in high income countries. In order to encourage changes in policy and practice that would allow greater use, we need good quality evidence. If we can understand where we do not have enough research and where we have good amounts of research, we can determine where to invest energies in further studies. Many high-income countries have produced research on medication abortion that could influence policy and practice in similarly resourced contexts. I conducted a literature review to be able to understand the type and quality of research on medication abortion conducted in high-income countries in the past 10 years. I conducted the review in an organized way to make sure that the papers reviewed discussed studies that I thought would be important for answering this question. The literature review found 207 papers. Each of these papers were reviewed and organized them by theme. I also used existing methods to determinine the quality of each study. Most of the research came from the US and the UK. Furthermore, most of the research conducted in the past 10 years was focused on clinical studies of medication abortion. In future studies, researchers should focus more on new ways of providing medication abortion to women that offers greater access. Also, the studies should be designed so that the results have meaning for a broader group of people or situations beyond where the study was done.