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Objective: To evaluate safety, feasibility, and acceptability of a telemedicine medical abortion service without pre‐treatment in‐person tests in Ukraine, Uzbekistan, and Azerbaijan. Methods: We conducted an open‐label, prospective, observational clinical study at five clinics in the three countries. Interested and eligible participants scheduled a telemedicine consultation with a study provider by phone or video. Medical abortion pills could be obtained by mail or courier or picked up at the study clinic or a pharmacy. Study providers contacted participants 1 week after mifepristone ingestion to assess abortion outcomes based on symptoms, and 3 weeks later to review the result of an at‐home, high‐sensitivity, urine pregnancy test. Participants were referred to in‐person visit based on symptoms, urine pregnancy test results, or initiative by the participant. Results: In all, 300 women participated in the study. Almost all participants received medical abortion medications the same day as their first contact with the study clinic, and the majority (n = 297, 99.0%) did not experience any problems receiving them. All except two women (0.67%) followed provider instructions on administration of medications. The majority of participants had a complete abortion without a procedure (Ukraine: n = 115, 95.8%; Uzbekistan: n = 127, 97.7%; Azerbaijan: n = 49, 98.0%), few had in‐person visits (Ukraine: n = 30, 25.0%; Uzbekistan: n = 3, 2.3%; Azerbaijan: n = 4, 8.0%), and most were very satisfied or satisfied with the service (Ukraine: n = 116, 96%; Uzbekistan: n = 128, 98%; Azerbaijan: n = 45, 90%). No serious adverse events occurred. Conclusion: Telemedicine medical abortion using the no‐test protocol is safe, feasible and acceptable for women in Ukraine, Uzbekistan, and Azerbaijan. Synopsis: Telemedicine medical abortion using a no‐test protocol is safe, feasible, and highly acceptable to women in Ukraine, Uzbekistan, and Azerbaijan. [ABSTRACT FROM AUTHOR]

This analysis explores the basis for the US Food and Drug Administration (FDA) requiring a Risk Evaluation and Mitigation Strategy (REMS) for mifepristone for the termination of intrauterine pregnancy. Controversies surround mifepristone and its REMS. The safety and efficacy of mifepristone are briefly reviewed with respect to FDA's actions. It is difficult to justify the continued requirement for a REMS for mifepristone by applying the regulatory framework and considering mifepristone's safety record. Drugs with higher risks are on the US market without an FDA‐mandated REMS. Canada removed all restrictions on the use of mifepristone for abortion, which has not resulted in patient safety concerns. All pharmacists should be permitted to dispense mifepristone. The continued requirement for a mifepristone REMS in the US appears to be based more on politics rather than evidence. [ABSTRACT FROM AUTHOR]

Mifepristone is an anti‐progestational drug that is the first component of the standard medical abortion regimen. For women who take mifepristone and then do not take misoprostol, which is the second component of the medical abortion regimen, it is possible that their pregnancy may continue to live birth. Since mifepristone is commonly used for medical abortion up to 9–10 weeks gestation, any adverse or teratogenic effects on the developing embryo/fetus must be considered, given exposure during the critical time of its development and organogenesis. Toxicology and teratology reports have cited studies demonstrating teratogenic effect of mifepristone in some animals. Current clinical guidelines for women exposed to mifepristone in the first trimester of pregnancy state that it is not known to be teratogenic based on limited published evidence from humans. The aim of this narrative systematic review was to investigate embryonic/fetal exposure to mifepristone and any association with congenital or fetal anomalies. This study was conducted by systematic searches of health databases from inception to February 2024. The references of relevant citations were manually searched to retrieve any additional citations not captured in database searching. Congenital anomalies and adverse outcomes were encountered at various doses of mifepristone exposure. A number of the congenital anomalies encountered in this review were explained by circumstances other than exposure to mifepristone. The present systematic review did not find data to support mifepristone being implicated as a teratogen. [ABSTRACT FROM AUTHOR]

Background Objectives Search Strategy Selection Criteria Data Collection and Analysis Main Results Conclusion Misoprostol is largely used in labor induction in cases of intrauterine fetal death. However, recent randomized clinical trials (RCTs) showed that the combination of mifepristone and misoprostol might have better effects than the use of misoprostol alone.To compare mifepristone and misoprostol lines of treatment.Pubmed, Embase, Cochrane and Web of Science databases were systematically searched until April 9, 2024.The eligibility criteria were (1) RCT, (2) comparing misoprostol alone versus the combined treatment, (3) patients undergoing labor induction due to intrauterine fetal death and (4) reporting at least one relevant outcome.Data were examined using the Mantel–Haenszel method and 95% CIs. Heterogeneity was assessed using I2 statics. R, version 4.2.3 was used for statistical analysis. The analyzed outcomes were delivery time interval, adverse effects (fever, vomiting, diarrhea and nausea) and the preinduction Bishop score. Other important outcomes, such as uterus rupture, could not be included due to lack of data from the included studies.A total of seven RCTs comprising 599 patients with intrauterine fetal death were randomized to misoprostol or combined treatment to induce labor. Compared to the misoprostol only group, combined treatment presented lower delivery time interval (MD –6.86 h; 95% CI: −10.32 to −3.4; P = 0.0001; I2 = 87%). However, in terms of adverse effects, the combined treatment group presented lower occurrence of fever (2.25% vs 12.12%; RR 0.26; 95% CI: 0.09–0.74; P = 0.01; I2 = 0%) and vomiting (7.64% vs 14.45%; RR 0.54; 95% CI: 0.29–1.01; P = 0.05; I2 = 0%). No statistically significant differences were observed when comparing the preinduction Bishop score of the two groups (MD –0.09; 95% CI: −0.28–0.10; P = 0.35; I2 = 0%). Additionally, the mean of the preinduction Bishop score of the combined treatment was 2 versus 2.1 of the control group.In this updated meta‐analysis, consistent results suggest that the combined treatment is associated with more beneficial outcomes than the misoprostol alone treatment in patients undergoing labor induction in intrauterine fetal death. [ABSTRACT FROM AUTHOR]

Many studies show that supranational governance structures (SGS)—understood as international organizations or international treaties—contribute to the global diffusion of public policies. However, we still have a limited understanding of which properties of SGS hasten the number of policy adoptions. To advance this literature, we argue that SGS making legally binding and univocal claims are more likely to act as diffusion accelerators. We demonstrate the suitability of this argument through a case study of the global diffusion of mifepristone approvals, a single‐purpose medicine to terminate pregnancies that has revolutionized abortion services. The analysis supports our expectation. Links to the EU and the Maputo Protocol—the only two considered SGS that make binding claims with clear implications for this policy field—hasten mifepristone approvals. By contrast, ratification of four other treaties—that do not make binding and univocal claims—and exposure to World Health Organization guidelines on medical abortion does not hasten these approvals. [ABSTRACT FROM AUTHOR]

Introduction: The 2022 Massachusetts Shield Law protects telemedicine providers who care for abortion seekers in other states from criminal, civil, and licensure penalties. In this article we explore the characteristics of patients of The Massachusetts Medication Abortion Access Project (The MAP). Methods: The MAP is an asynchronous telemedicine service that offers mifepristone/misoprostol to abortion seekers in all 50 states who are at or under 11 weeks pregnancy gestation on initial intake. The MAP charges USD250 using a pay‐what‐you‐can model. We analyzed medical questionnaires and payments submitted by patients who received care from The MAP during its first 6 months of operations using descriptive statistics and for content and themes. Results: From October 1, 2023–March 31, 2024, 1994 patients accessed care through The MAP. Almost all (n = 1973, 99%) identified as women/girls and about half (n = 984, 49%) were aged 20–29. The MAP cared for patients in 45 states; 84% (n = 1672) of these patients received pills in abortion ban or restricted southern states. Patients paid USD134.50 on average; 29% (n = 577) paid USD25 or less. Nearly two‐thirds (n = 1293, 65%) received subsidized care; financial hardship featured prominently in patient comments. Discussion: Considerable demand exists for medication abortion care from Shield Law providers. The MAP demonstrates that providers can trust women and other pregnancy capable people to decide for themselves whether to obtain medication abortion pills by mail and to pay what they can afford without being required to justify their need. Identifying ways to support Shield Law provision and further subsidize abortion care are needed. [ABSTRACT FROM AUTHOR]

Research Summary Policy Implications The U.S. Supreme Court's Dobbs decision overturning Roe v. Wade has profound implications for the 58,000 incarcerated women who are pregnant. Especially in states that now ban abortion, women in prisons and jails who prefer to terminate their pregnancy will be denied that choice by the government and will be forced to give birth. Based on a July 2023 YouGov survey (N = 800) employing three experiments and measuring attitudes toward inmate abortion and parental aid, the current study examines public opinion on coerced motherhood, focusing on states prohibiting reproductive choice. The results reveal that a majority of the American public favors providing incarcerated women in these states with access to abortion through surgical procedures or medication (pills). Among respondents residing in states banning abortion, more endorse than oppose reproductive rights. Support for abortion is particularly high when the pregnancy is due to rape or poses a risk to a woman's health. Respondents also approve incarcerated mothers receiving parental aid (e.g., baby food, baby clothing, nursery care). Notably, conservative Republicans are most in favor of coercing motherhood and least in favor of providing parental aid.Coerced motherhood behind bars is a human rights violation. Our study shows that it is also opposed by the American public. Thus, ideological space exists for reforms aimed at providing incarcerated women with access to reproductive services. Every correctional facility should be given a written protocol (Model Reproductive Services Code) that mandates pregnancy screenings, counseling, and assistance in scheduling services, as well as transportation for surgery and/or access to pills for a medical abortion. Above all, transparency is needed to raise consciousness about coerced motherhood behind bars and to shed light on how corrections professionals handle inmate pregnancies. [ABSTRACT FROM AUTHOR]

After the legalization of abortion in 2018, Ireland needed clinicians to become abortion providers and make this political win a medical reality. Yet Irish doctors had next‐to‐no training in abortion care, and barriers ranging from stigma to economic pressures in the healthcare system impacted doctors' desire to volunteer. How did hundreds of Irish doctors make the shift from family doctor to abortion provider? Drawing on ethnographic research conducted between 2017 and 2020, this article explores the process by which Irish general practitioners became abortion providers, attending to the material impact of medical technologies on that journey. Drawing from medical anthropologists who have examined similar themes of agency, pharmaceuticals, and medico‐legal frameworks within the topic of assisted dying, I build on Anita Hannig's idea of "agentive displacement" to frame the productive impact of abortion pills on this transition. [ABSTRACT FROM AUTHOR]

Background: Glucocorticoid (GR) and mineralocorticoid (MR) receptors are highly expressed in cardiac tissue, and both can be activated by corticosteroids. MR activation, in acute myocardial infarction (AMI), worsens cardiac function, and increase NHE activity contributing to the deleterious process. In contrast, effects of GR activation are not fully understood, probably because of the controversial scenario generated by using different doses or potencies of corticosteroids. Aims: We tested the hypothesis that an acute dose of hydrocortisone (HC), a low‐potency glucocorticoid, in a murine model of AMI could be cardioprotective by regulating NHE1 activity, leading to a decrease in oxidative stress. Materials and Methods: Isolated hearts from Wistar rats were subjected to regional ischemic protocol. HC (10 nmol/L) was added to the perfusate during early reperfusion. Infarct size and oxidative stress were determined. Isolated papillary muscles from non‐infarcted hearts were used to evaluate HC effect on sodium‐proton exchanger 1 (NHE1) by analysing intracellular pH recovery from acute transient acidosis. Results: HC treatment decreased infarct size, improved cardiac mechanics, reduced oxidative stress after AMI, while restoring the decreased level of the pro‐fusion mitochondrial protein MFN‐2. Co‐treatment with the GR‐blocker Mifepristone avoided these effects. HC reduced NHE1 activity by increasing the NHE1 pro‐inhibiting Ser648 phosphorylation site and its upstream kinase AKT. HC restored the decreased AKT phosphorylation and anti‐apoptotic BCL‐2 protein expression detected after AMI. Conclusions: Our results provide the first evidence that acute HC treatment during early reperfusion induces cardioprotection against AMI, associated with a non‐genomic HC‐triggered NHE1 inhibition by AKT and antioxidant action that might involves mitochondrial dynamics improvement. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have demonstrated quality concerns with misoprostol. Mifepristone, however, has not been extensively assessed for quality. Between 2020 and 2021, Concept Foundation and the International Planned Parenthood Federation conducted a study to determine the quality of these medical abortion drugs in low‐ and middle‐income countries (LMIC). Methods: The collection of batch samples of misoprostol and mifepristone was carried out by trained sampling agents in selected LMIC. Single drug packs and combipacks were sampled. A World Health Organization prequalified laboratory conducted testing method verifications and subsequent sample analysis. Tests included identification, assay, related substances, and content uniformity for misoprostol, and identification, assay, related substances, and dissolution for mifepristone. Results: Samples were collected from Burkina Faso, Cambodia, Democratic Republic of Congo, India, Kyrgyzstan, Moldova, Nepal, Nigeria, Pakistan, Uganda and Vietnam. Sixty‐four pooled batch samples were tested, consisting of 31 combipacks, 26 misoprostol‐only and seven mifepristone‐only products. Overall, 54.7% of samples were non‐compliant with one or more of the specifications, representing 51.6% of combipack products, 57.1% of misoprostol tablets analyzed and 23.7% of mifepristone tablets. One falsified misoprostol‐only product was found. Conclusion: The present study confirms that a significant problem still exists in relation to the quality of medical abortion drugs in LMIC. For misoprostol, our findings suggest that historical concerns around primary packaging may have been largely resolved but that manufacturing processes for both finished product and active pharmaceutical ingredient need to be improved. The present study also provides evidence of mifepristone quality issues. Synopsis: Over half of mifepristone, misoprostol, and combipack samples collected and tested did not meet one or more requirements. One product was falsified. [ABSTRACT FROM AUTHOR]

This article explores the potential of simvastatin (SIM) and mifepristone (MIF) as a combined treatment for uterine fibroids. The study investigates the effects of SIM on the progesterone receptor (PR) pathway and fibroid cell proliferation using human tissue samples, cell cultures, and a xenograft mouse model. The results show that SIM inhibits fibroid growth by suppressing PR expression and downstream signaling pathways. Additionally, the combination of SIM and MIF demonstrates a synergistic effect in inhibiting fibroid cell proliferation and affecting extracellular matrix dynamics. The findings suggest that SIM and MIF may have potential as a multi-pronged treatment for uterine fibroids. [Extracted from the article]

A rising percentage of patients are electing medication abortion over procedural abortion for increased safety and privacy. Access to medication abortion is essential healthcare, but many Americans face unsurmountable barriers when pursuing this option. This has been in large part due to unnecessary restrictions imposed by the United States Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy (REMS) for mifepristone, used in combination with misoprostol for medication abortion. Moreover, many states have imposed additional restrictions on abortion, further impeding access to care. Since its original approval in 2000, mifepristone can only be prescribed by certified prescribers. Until recently, mifepristone could only be dispensed by certified prescribers, whereby more accessible community and mail‐order pharmacies were prohibited from dispensing mifepristone. During the Coronavirus disease 2019 public health emergency, there was a temporary allowance for certified prescribers to utilize mail or mail‐order pharmacies to deliver medications to patients. In January 2023, the FDA approved modifications to the mifepristone REMS to allow certified pharmacies to dispense the medication. Given the established safety and effectiveness of mifepristone, the evidence supports its distribution via pharmacies and leveraging pharmacists to expand medication abortion access. Pharmacists are one of the most widely accessible healthcare providers and their responsibility centers on patient and medication safety and improving health outcomes. This article, an opinion of the American College of Clinical Pharmacy Women's Health Practice and Research Network, adds the voice of members of the pharmacy profession to the collective efforts to ensure access to medication abortion, including pharmacist dispensing of mifepristone. We encourage pharmacists to embrace this fresh opportunity to provide medication abortion care in their communities. [ABSTRACT FROM AUTHOR]

Novel gonadotrophin releasing hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add‐back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix and linzagolix have assessed treatment efficacy for fibroid‐related heavy menstrual blood loss in comparison to placebo. Marketing authorization has been granted by several agencies including those in Europe, the United Kingdom and the United States. While the registration trials report a robust effect on the reduction of heavy menstrual blood loss and improvement in quality of life scores, reticence is advised before widespread prescription. In this review, we demonstrate limitations in the trial data, namely a lack of generalizability due to the restricted study population, the lack of transparency in the distribution of disease‐level characteristics limiting the predictability of treatment success in the real‐world diverse population, and the absence of any comparison to current alternative treatment methods. Importantly, no clinically meaningful volume reductions were found with GnRH antagonist combination preparations, and long‐term safety data, particularly concerning modest but stable bone mineral density decline, need further addressing. Symptoms related to uterine fibroids adversely affect many women's quality of life and effective medical treatments are lacking. However, despite the urgent need for conservative treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness and cost‐effectiveness in a representative population and are compared with alternative treatment methods before introduction into mainstream clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether letrozole pre‐treatment is non‐inferior to mifepristone pre‐treatment, followed by misoprostol, for complete evacuation in the medical treatment of first‐trimester missed miscarriage. Design: Prospective open‐label non‐inferiority randomised controlled trial. Setting: A university‐affiliated hospital. Population: We recruited 294 women diagnosed with first‐trimester missed miscarriage who opted for medical treatment. Methods: Participants were randomly assigned to: (i) the mifepristone group, who received 200 mg mifepristone orally followed 24–48 h later by 800 μg misoprostol vaginally; or (ii) the letrozole group, who received 10 mg letrozole orally once‐a‐day for 3 days, followed by 800 μg misoprostol vaginally on the third (i.e. last) day of letrozole administration. Main outcome measures: The primary outcome was the rate of complete evacuation without surgical intervention at 42 days post‐treatment. Secondary outcomes included induction‐to‐expulsion interval, adverse effects, women's satisfaction, number of doses of misoprostol required, duration of vaginal bleeding, pain score on the day of misoprostol administration and other adverse events. Results: The complete evacuation rates were 97.8% (95% CI 95.1%–100%) and 97.2% (95% CI 94.4%–99.9%) in the letrozole and mifepristone groups, respectively (p ≤ 0.001 for non‐inferiority). The mean induction‐to‐tissue expulsion interval in the letrozole group was longer compared with the mifepristone group (15.4 vs 9.0 h) (p = 0.03). The letrozole group had less heavy post‐treatment bleeding and an earlier return of menses. There were no statistically significant differences in the number of doses of misoprostol required, the duration of vaginal bleeding, the pain score on the day of misoprostol administration and the rate of other adverse events between the two groups. The majority of the women (91.2% and 93.9% in the letrozole and mifepristone groups, respectively) were satisfied with their treatment option. Conclusions: Letrozole is non‐inferior to mifepristone as a pre‐treatment, followed by misoprostol, for the medical treatment of first‐trimester missed miscarriage. [ABSTRACT FROM AUTHOR]

Aim: This pilot study aimed to assess the utility of an oral progesterone treatment protocol for women who commenced medical abortion and then changed their mind and wished instead to maintain their pregnancy. Methods: The Progesterone‐After‐Mifepristone—pilot for efficacy and reproducibility (PAMper) trial was designed as a prospective single‐arm pilot clinical trial, conducted via telehealth. Women aged 18 to 45 years in Australia who reported ingesting mifepristone within the last 72 h to initiate medical abortion and had not taken misoprostol were included. Initial contact was by a web‐based form. Following informed consent, participants were prescribed oral progesterone to be taken 400 mg twice per day for 3 days then 400 mg at night until completion of a 19 day course. Pregnancy viability was assessed by ultrasound scan after 14 days of progesterone treatment. Results: Between October 2020 and June 2021, nine women contacted the PAMper trial, of whom six enrolled and commenced progesterone treatment. These women reported ingesting mifepristone at 40–70 days of gestation, with progesterone being commenced within 5.7–72 h of mifepristone ingestion. Five participants had ongoing, live pregnancies at the primary endpoint (ultrasound at >2 weeks). One participant had a miscarriage after 9 days of progesterone treatment. There were no clinically significant adverse events. Conclusion: This small study demonstrated a clinically sound protocol for researching the use of progesterone‐after‐mifepristone for women in this circumstance. Results of this pilot study support the need for further larger scale trials in this field. [ABSTRACT FROM AUTHOR]

The UK is usually viewed as having liberal abortion regulations, providing good access to abortion care within a publicly funded health service. However, the underlying laws are authoritarian, dating from an era when public executions drew large crowds and 67 years before women were able to vote. Abortion is only legal when two doctors certify it meets the permitted grounds, and the penalty for self‐managed abortion is up to life imprisonment for both the woman and any accomplice. These laws had prevented the use of mifepristone and misoprostol at home. Changes to the regulations for misoprostol in 2018 and mifepristone in 2020 permitted home use, but the government announced they were rescinding the approval for mifepristone in 2022. This article discusses how, despite the opposition of government, significant progressive changes to the abortion laws were achieved. Early medical abortion at home is now protected in law, and safe access zones protect patients and staff from harassment and intimidation from protesters. Despite this progress, increasing numbers of women are facing criminal investigation and face long prison sentences if convicted. The need for decriminalization and for abortion care to be regulated like all other health care is the next pressing issue. Synopsis: How the most progressive changes to abortion laws in 50 years in the UK were won, and why decriminalization is now an urgent priority. [ABSTRACT FROM AUTHOR]

Randomized controlled trial comparing efficacy of a combination regime containing two cervical sensitizers (mifepristone + Foley's catheter) versus single agent mifepristone or Foley's catheter for labor induction in women attempting TOLAC at late third trimester with a dead fetus in utero. Aim: To compare efficacy and safety of a new combination regime comprising of two cervical sensitizers used simultaneously with single agents, for labor induction in women attempting TOLAC at ≥34 weeks' gestation with a dead fetus. Method: This was a multiarm randomized controlled trial (RCT) where participants received one of the three regimes—single agent oral Mifepristone 200 mg, intracervical Foley's catheter (16 Fr size, filled with 40 mL normal saline after intracervical instillation), and combination regime consisting of both used simultaneously. Number of women undergoing vaginal birth within 48 h of induction (VB48) was the primary outcome compared between groups. Results: VB48 was higher in participants on combination regime in comparison to participants on Foley's catheter (54 vs. 42). Total vaginal births were higher in participants on combination regime compared to both single agents (58 vs. 48 and 44). Duration and dose of oxytocin augmentation was lower in participants on combination regime compared to both single agents. Induction birth interval was short in participants on combination regime compared to those on Foley's catheter. Maternal complications between groups were similar. Conclusion: Combination of cervical sensitizers for labor induction in late third trimester among women with dead fetus attempting TOLAC resulted in higher proportion of vaginal births and might reduce risk of scar dehiscence due to requirement of a lower dose of oxytocin for augmentation. [ABSTRACT FROM AUTHOR]

Context: Early pregnancy loss (EPL) affects 1 million patients in the United States (US) annually, but integration of mifepristone into EPL care may be complicated by regulatory barriers, practice‐related factors, and abortion stigma. Methods: We conducted qualitative, semi‐structured interviews among obstetrician‐gynecologists in independent practice in Massachusetts, US on mifepristone use for EPL. We recruited participants via professional networks and purposively sampled for mifepristone use, practice type, time in practice, and geographic location within Massachusetts until we reached thematic saturation. We analyzed interviews using inductive and deductive coding under a thematic analysis framework to identify facilitators of and barriers to mifepristone use. Results: We interviewed 19 obstetrician‐gynecologists; 12 had used mifepristone for EPL and 7 had not. Participants were in private practice (n = 12), academic practice (n = 6), or worked at a federally qualified health center (n = 1). Seven had fellowship training, including four in complex family planning. The most common facilitators of mifepristone use for EPL were access to the expertise or protocols of local‐regional experts, leadership from a "champion," prior experience with abortion care, and hospital capacity constraints during the COVID‐19 pandemic. The most common barriers were related to the Mifepristone Risk Evaluation and Mitigation Strategy (REMS) Program imposed by the US Food and Drug Administration (FDA). Additionally, mifepristone's affiliation with abortion was a barrier to its use in EPL for some obstetrician‐gynecologists. Conclusion: The FDA Mifepristone REMS Program presents substantial barriers to obstetrician‐gynecologists incorporating mifepristone into their EPL care. [ABSTRACT FROM AUTHOR]

A single‐dose, open‐label, randomized, two‐period crossover‐design study was conducted to evaluate the bioequivalence of the reference and test formulations of mifepristone tablets. Each subject was randomized at the beginning to receive a 25‐mg tablet of the test or the reference mifepristone under fasting conditions during the first period, then received the alternate formulation during the second period following a 2‐week washout period. A validated high performance liquid chromatography‐tandem mass spectrometry (HPLC‐MS/MS) method was used to determine the plasma concentrations of mifepristone and its two metabolites (RU42633 and RU42698). Fifty‐two healthy subjects were enrolled in this trial, 50 of whom completed the study. The 90% confidence intervals for the log‐transformed Cmax, AUC0‐t, and AUC0‐∞ fell within the accepted 80%–125% range. Throughout the study period, a total of 58 treatment‐emergent adverse events were reported. No serious adverse event was observed. In conclusion, the test and reference mifepristone were bioequivalent and well tolerated under fasting conditions. [ABSTRACT FROM AUTHOR]

In the 2022 Abortion Care Guideline, the World Health Organization (WHO) undertook systematic evidence reviews of seven law and policy interventions to assess their health and social impacts. Distinct recommendations were formulated for each. The present article highlights how the Guideline reconceptualizes abortion regulation as a complex structural intervention that shapes clinical care and service delivery and distributes risks and resources within these systems and in the care relations that define them. It then presents the Guideline recommendations and summarizes their evidence base, drawing on recent legal and policy developments to emphasize their real‐world significance. The article concludes by anticipating the future of abortion law and policy, focusing on service delivery innovations and diverse care models, drug regulation and the supply of abortion pills, and protective interventions crafted in the context of political crisis and immediate need that serve policy objectives and take regulatory forms different from the past. Synopsis: Analysis of the law and policy recommendations of the 2022 WHO Abortion Care Guideline, while anticipating future policy objectives and legal frameworks for abortion care. [ABSTRACT FROM AUTHOR]

Summary: Endometritis is recognised as one of the major causes of reproductive failure, specifically infertility and abortions, in mares. Infectious agents are the most common cause of endometritis, mainly bacteria. Here, we describe a case of an unexplained reproductive failure caused by an uncommon bacterium, A. hippocoleae, in a 15‐year‐old Thoroughbred mare with an oscillating reproductive history from Southern Brazil. Strain A. hippocoleae_LBV077/21 was isolated from the mare's uterus swab and identified by MALDI‐TOF (Matrix‐Assisted Laser Desorption Ionisation – Time of Flight) and 16 S rDNA sequencing. The antimicrobial susceptibility test showed that the strain was susceptible to ampicillin, ceftiofur, cephalexin, ciprofloxacin, rifampicin, penicillin, sulfamethoxazole/trimethoprim, tetracycline and vancomycin. Partial 16 S rDNA sequence phylogenetic analysis indicated a well‐supported position of A. hippocoleae_LBV077/21 in an exclusive clade of A. hippocoleae, whilst all other Arcanobacterium species were positioned in a separated clade, highlighting the lower syntenic relationship of the species A. hippocoleae to the other Arcanobacterium species. The present study reaffirms the importance of the isolation and identification of infectious agents in mares in cases of reproductive failure because uncommon agents can impede successful treatment and the improvement of reproductive failures. [ABSTRACT FROM AUTHOR]

Bowenoid papulosis (BP) is a benign and possibly carcinogenic disease associated with human papillomavirus (HPV) infection, which has been increasingly recognised and paid attention to in recent years, but the potential mechanisms still remain unclear. In our study, three patients who were diagnosed with BP were enrolled into our research. Skin biopsies were taken and were separated into two parts, one part was for HE staining and the others were for RNA‐sequencing (RNA‐seq). All the three patents were human papillomavirus (HPV) positive and HE staining revealed typical skin histopathological changes in BP, including dyskeratosis, hyperplasia and hypertrophy of the granular and spinous layers, atypical keratinocytes. RNA‐seq analysis demonstrated that a total of 486 differentially expressed genes (DEGs) were detected between the skin tissues from BP and the controls, among which, 320 genes were significantly upregulated and 166 genes were dramatically downregulated. GO enrichment revealed that antigen binding, cell cycle, immune response and keratinisation to be the most notably altered pathways, whereas KEGG analysis indicated that cell cycle cytokine‐cytokine receptor interaction, ECM receptor interaction and p53 signalling pathway to be the most significantly changed signalling pathways in BP. Furthermore, metabolism‐associated enrichment analysis showed that cholesterol metabolism, metabolism of xenobiotics by cytochrome p450 and pyrimidine metabolism to be the most dramatically dysregulated metabolic pathways in BP as compared to normal controls. Our study revealed that inflammation, metabolism and cell proliferation signalling pathways might be the most important pathways for BP disease, targeted inhibiting of these signals might be a potential method for BP treatment. [ABSTRACT FROM AUTHOR]

Background: Endometrial injury is a common disease in women caused by intrauterine inflammation, infections, and endocrine disorders. Human endometrial stromal cells (hEndoSCs) can maintain endometrial homeostasis and play an important role in repairing endometrial injury. Mifepristone, a steroidal anti‐progesterone drug, is widely used in the field of reproductive medicine worldwide. Mifepristone‐induced hEndoSC injury has been used to study endometrial injury in vitro. At present, the pathogenesis and potential regulatory mechanisms of oxycodone in endometrial injury remain unknown. Aims: We aimed to evaluate the functions of oxycodone in mifepristone‐stimulated hEndoSC injury and analyze its potential molecular mechanism. Materials & Methods: hEndoSC viability, cytotoxicity, and apoptosis were analyzed using the methyl thiazolyl tetrazolium assay, the lactate dehydrogenase assay, and flow cytometry, respectively. Furthermore, the levels of cleaved‐Caspase3, Keap1, Nrf2, HO‐1, and NQO1 were assessed using reverse transcription quantitative polymerase chain reaction and western blot analysis, and the release of inflammatory cytokines was determined using the enzyme‐linked immunosorbent assay. Results: We observed that oxycodone had no adverse effects on hEndoSCs; rather, it protected hEndoSCs against mifepristone‐induced endometrial damage, as confirmed by the enhanced cell viability, reduced number of apoptotic cells, decreased Caspase3 activity and inflammatory cytokine secretion, and increased Keap1/Nrf2/HO‐1 pathway‐related protein expression. In addition, we found that the protective effects of oxycodone on mifepristone‐induced hEndoSC injury were inhibited by ML385 (a Keap1/Nrf2/HO‐1 inhibitor). Conclusion: In summary, we confirmed that oxycodone alleviates mifepristone‐induced hEndoSC injury by activating the Keap1/Nrf2/HO‐1 signaling pathway. [ABSTRACT FROM AUTHOR]

Preclinical and clinical work suggests that mifepristone may be a viable treatment for alcohol use disorder (AUD). This was a Phase 1/2, outpatient, cross‐over, randomized, double‐blind, placebo‐controlled trial with non‐treatment‐seeking individuals with AUD (N = 32). We assessed safety, alcohol craving and consumption, after 1‐week mifepristone 600 mg/day administration, in a human laboratory study comprised of a single oral yohimbine administration (32.4 mg), a cue‐reactivity procedure and alcohol self‐administration. Safety was monitored by adverse events and hemodynamic parameters, alcohol craving by alcohol craving questionnaire and cue‐induced saliva output. During the alcohol self‐administration, we assessed alcohol pharmacokinetics, subjective effects and consumption. Outcomes were assessed using Generalized Estimating Equations and mediation analysis. Mild‐moderate adverse events were reported in both conditions. There was no statistically significant difference between mifepristone and placebo in alcohol pharmacokinetics and subjective effects. Furthermore, blood pressure increased only in the placebo condition after the stress‐induced laboratory procedures. Mifepristone, compared to placebo, significantly reduced alcohol craving and increased cortisol levels. Mifepristone‐induced cortisol increase was not a mediator of alcohol craving. Mifepristone, compared to placebo, did not reduce alcohol consumption in the laboratory or in a naturalistic setting. This study successfully translated a developed preclinical procedure to a human laboratory study, confirming the safety of mifepristone in people with AUD and providing evidence to its role in reducing alcohol craving under stress procedures. The lack of effects on alcohol drinking may be related to the selection of non‐treatment seekers and suggests future treatment‐oriented trials should investigate mifepristone in people with AUD. [ABSTRACT FROM AUTHOR]

Aims: To assess clinical outcomes and complications in women with ≥1 prior caesarean delivery (CS) during mid‐pregnancy medical abortion with misoprostol following mifepristone priming. Materials and Methods: Retrospective analysis of abortions at 13–28 weeks gestation using sequential mifepristone and misoprostol at a single centre from 1/2008–12/2018. Procedural outcomes were compared between cases with no prior CS, one prior and ≥2 prior CS. Results: There were 1399 consecutive women who underwent a medical abortion, with 304 (21.7%) having ≥1 prior lower segment CS (241 one, 49 two, 12 three, one four) and one a prior classical CS. Median gestation was 19 weeks (interquartile range (IQR) 17–21) among nulliparas, multiparas with no prior CS and multiparas with prior CS, P = 0.505. Compared with nulliparas (median procedural duration 10.8 h, IQR 7.5–16.5; adjusted hazards ratio (aHR) = 1.20 95%CI 1.04–1.40, P = 0.015), multiparas with prior CS had a shorter procedural duration (9.5 h, IQR 6.5–13.5) while multiparas with no CS had the shortest duration (7.0 h, IQR 5.0–9.8; aHR = 2.28 95%CI 2.01–2.58, P < 0.001). Complications were more frequent with prior CS: estimated blood loss (medians: 100 cc no CS vs 150 cc ≥1 CS, P = 0.002), blood loss >1000 cc (3.6% no CS vs 7.2% ≥1 CS; odds ratio (OR) = 2.11 95%CI 1.23–3.62, P = 0.007) and placental retention (17.3% no CS vs 25.3% ≥1 CS; adjusted OR = 1.44 95%CI 1.05–1.99, P = 0.024). Uterine rupture occurred in 4/304 women with ≥1 prior CS (1.3%). Conclusions: Mifepristone‐misoprostol abortion in women with prior CS is generally safe but associated with an increased risk of procedural complications. Lowering of the misoprostol dosage with prior CS may reduce uterine rupture, although this hypothesis requires ongoing research. [ABSTRACT FROM AUTHOR]

This study investigated whether muscle contraction induces expression of regulated in development and DNA damage 1 (REDD1), a potent inhibitor of mTORC1, in mice muscle. Gastrocnemius muscle was unilaterally and isometrically contracted with electrical stimulation, and changes in muscle protein synthesis, mTORC1 signaling phosphorylation, and REDD1 protein, and mRNA were measured at time points of 0, 3, 6, 12, and 24 h after the contraction. At time point 0 and 3 h, muscle protein synthesis was blunted by the contraction, accompanied by a decrease in phosphorylation of 4E‐BP1 at time point 0 h, suggesting suppression of mTORC1 was involved in blunting of muscle protein synthesis during and shortly after the contraction. REDD1 protein was not increased in the contracted muscle at these time points, but at time point 3 h, both REDD1 protein and mRNA were increased in the contralateral non‐contracted muscle. The induction of REDD1 expression in the non‐contracted muscle was attenuated by RU‐486, an antagonist of the glucocorticoid receptor, suggesting that glucocorticoids are involved in this process. These findings suggest that muscle contraction induces temporal anabolic resistance in non‐contracted muscle, potentially increasing the availability of amino acids for contracted muscle, allowing for the synthesis of muscle protein. [ABSTRACT FROM AUTHOR]

Introduction: The administration of mifepristone, followed by misoprostol, is widely used for medical abortion. Many studies have demonstrated home abortion to be safe in pregnancies up to 63 days of gestation, and recent data support its safety when extended to more advanced pregnancies. We studied the efficacy and acceptability of home use of misoprostol up to 70 days of gestation in a Swedish setting and compared the outcomes between pregnancies with a gestational age of up to 63 days and pregnancies with gestational age 64–70 days. Material and methods: This prospective cohort study was performed between November 2014 and November 2021 at Södersjukhuset and Karolinska University Hospital, Stockholm, and some patients were also recruited from Sahlgrenska University Hospital, Göteborg and Helsingborg Hospital. The primary outcome was the rate of complete abortions and was defined as complete abortion without any need for surgical or medical intervention and assessed by clinical assessment, pregnancy test and/or vaginal ultrasound. Secondary objectives were assessed by daily self‐reporting in a diary and included pain, bleeding, side effects and women's satisfaction and perception of home use of misoprostol. A comparison of categorical variables was made with Fisher's exact test. The significance level was set to a p‐value ≤0.05. The study was registered at Clinicaltrials.gov on July 14, 2014 (NCT02191774). Results: During the study period we enrolled 273 women opting for medical abortion with home use of misoprostol. In the early group, up to 63 days of gestation, 112 women were included with a mean gestational length of 45 days and in the late group, 64–70 days of gestation, 161 women with a mean gestations length of 66.3 days were included. Complete abortion occurred in 95% (95% CI 89–98) of women in the early group and in 96% (95% CI 92–99) in the late group. No differences were found regarding side effects and acceptability was similarly high in both groups. Conclusions: Our results show high efficacy and acceptability of medical abortion when misoprostol is administered at home up to 70 days of gestation. This supports previous findings about maintained safety when misoprostol is administered at home even past a very early pregnancy. [ABSTRACT FROM AUTHOR]

Background: Many reproductive‐aged North Americans use antibiotics in the weeks preceding conception or during early pregnancy. Antibiotic use may influence risk of spontaneous abortion (SAB) by disrupting the reproductive tract microbiome or treating harmful infections. However, this association has not been extensively studied. Objective: To determine the extent to which periconceptional antibiotic use is associated with the risk of SAB. Methods: We analysed data from an internet‐based preconception cohort study of pregnancy planners. Eligible participants self‐identified as female, were aged 21–45 years, resided in the USA or Canada, and conceived during 12 months of follow‐up (n = 7890). Participants completed an enrolment questionnaire during June 2013–September 2021 and bimonthly follow‐up questionnaires for up to 12 months or until a reported pregnancy, whichever came first. Pregnant participants completed questionnaires in early (~8–9 weeks) and late (~32 weeks) gestation. We assessed antibiotic use, including type (penicillins, nitrofurantoin, cephalosporins and macrolides) and indication for use, during the previous 4 weeks on preconception questionnaires. Participants reported pregnancies and SAB on follow‐up and pregnancy questionnaires. We used Cox proportional hazards regression models with gestational weeks as the time scale to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between periconceptional antibiotic use and SAB, controlling for potential demographic, medical, and lifestyle confounders. Results: Nineteen percent (n = 1537) of pregnancies ended in SAB. Participants reported periconceptional antibiotic use in 8% of pregnancies ending in SAB and 7% not ending in SAB. Periconceptional antibiotic use was not appreciably associated with SAB (adjusted HR 1.06, 95% CI 0.88, 1.28). We observed no strong associations between antibiotic type, indication for use, or recency of exposure and SAB risk. Conclusions: Periconceptional antibiotic use was not appreciably associated with SAB in this study. This association is likely complicated by antibiotic type and dosage, timing of conception, and the individual's overall health. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to study serum beta‐human chorionic gonadotropin level trends after medical abortion using mifepristone and misoprostol in the early first trimester. Methods: We enrolled women at ≤63 days of gestation who were indicated for pregnancy termination. We excluded women with incomplete abortions, nonviable pregnancies, extrauterine pregnancies, and contraindications for mifepristone/misoprostol use. Women received oral mifepristone (200 mg), followed by vaginal misoprostol (800 mcg) after 48 h. Serum beta‐human chorionic gonadotropin levels were monitored pre‐mifepristone administration (day 1); 48 h post‐mifepristone, pre‐misoprostol administration (day 3); day 10; and weekly after day 10, until negative beta‐human chorionic gonadotropin levels (<25 mIU/mL) were achieved. Results: Among 39 enrolled women, 36 (92.3%) who underwent complete abortion without further interventions were included. The median gestational age was 51 (32–61) days. Three phases of beta‐human chorionic gonadotropin levels were observed: an increase of up to 5.1% within 48 h of taking mifepristone, before misoprostol administration; a rapid decline on day 10 (by 98.5% compared with initial levels); and a slow decline after day 10 until negative results were attained within 7 weeks. Conclusion: Serum beta‐human chorionic gonadotropin levels minimally increased 48 h after taking mifepristone, rapidly declined within 1 week of misoprostol administration, and slowly declined until negative within 7 weeks post‐abortion. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the short‐term efficacy and safety of a combined mifepristone‐misoprostol regimen in individuals seeking medical abortion at up to 63 days of gestational age. Methods: This open‐label, multicenter, prospective study evaluated the short‐term efficacy and safety of medical abortion, with the primary outcome being the abortion success rate 24 h after misoprostol administration. The participants received 200 mg of mifepristone orally and 800 μg of misoprostol buccally in the hospital/clinic 36–48 h later. Bleeding and lower abdominal pain, which are the main symptoms associated with medical abortion, were recorded. Results: The abortion success rate was 93.3% (95% confidence interval [CI]: 87.3–97.1%) within 24 h of misoprostol administration, 63.3% (95% CI: 54.05–71.94%) within 4 h, and 90.0% (95% CI: 83.18–94.73%) within 8 h. The median time from misoprostol administration to a successful abortion was 3.93 h. Bleeding was most commonly observed 0–4 h prior to the confirmation of gestational sac (GS) expulsion. The most intense lower abdominal pain occurred 0–1 h before the confirmation of GS expulsion. Conclusion: The combined regimen of mifepristone and buccal misoprostol for medical abortion showed short‐term efficacy and a favorable safety profile. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to: (a) describe current use of mifepristone for early pregnancy loss (EPL) management in Utah, (b) identify predictors of knowledge pre-and posteducational video, and (c) explore postvideo impacts on the likelihood to use mifepristone. Mifepristone is subject to the Food and Drug Administration's (FDA) Risk Evaluation and Mitigation Strategy (REMS) requirements. Methods: Between September 2020 and March 2021 we surveyed Utah clinicians from six specialties caring for people experiencing EPL, recruited through professional organizations and hospital listservs. Participants viewed a 3.5-minute educational video on mifepristone for EPL and completed pre-and postvideo questionnaires. We evaluated predictors of high prevideo and improved postvideo knowledge using random forest regression conditional importance measures and partial dependency plots. We described current mifepristone use and video effects on likelihood to use mifepristone. Results: Of 506 participants, most specialize in emergency medicine (172, 34%) and practice in private settings (253, 51%). Two-thirds had heard of mifepristone (328/471, 70%). Of 176/471 (37%) attempting provision of mifepristone, actual provision occurred for 59% (104/176). Baseline knowledge scores were low (mean 4.81/13 [37%] correct). Predictors of high prevideo knowledge include provision or attempted provision of mifepristone, having heard of mifepristone, providing EPL management expectantly or via medication, and specialty type. Mean postvideo knowledge scores improved by 3.27 points (68% improvement, paired t-test; 95% confidence interval 2.82-3.72, p < 0.0001). Postvideo, 66% (242/364) stated they are much more or somewhat more likely to use mifepristone, with compliance with FDA requirements cited as a barrier to utilization. Conclusions: Among Utah providers, baseline mifepristone knowledge and use for EPL management are low. An educational video improved knowledge and likelihood of use, but FDA REMS requirements continue to be a barrier to including mifepristone in medication management of EPL. [ABSTRACT FROM AUTHOR]

This book review discusses "Abortion pills go global: Reproductive freedom across borders" by Sydney Calkin. The author examines the movement of medication abortion (MA), also known as abortion pills, across physical and metaphorical borders, and its impact on abortion rights and access. Calkin explores the geography of abortion and the laws governing abortion in different states and countries, drawing on interviews with activists, providers, lawyers, and politicians. The book focuses on the circulation of MA in the United States, Poland, Ireland, and Northern Ireland, highlighting its transformative potential and the challenges faced in accessing safe and effective abortions. While the book primarily focuses on majority-white countries in the Global North, it provides valuable insights into abortion politics, pharmaceutical circulation, and comparative policy. [Extracted from the article]

A study published in the International Journal of Gynecology & Obstetrics examined the quality of mifepristone and misoprostol, two medications commonly used for medical abortions, in 11 countries. The study found that there were excess levels of impurities in both medications in eight of the countries. The impact of these impurities on safety and efficacy is not well understood. The study also identified a falsified version of the medication Cytotec®, which lacked any active ingredient. The presence of impurities in these medications could reduce their effectiveness and potentially cause harm to users. The study emphasizes the need for improved regulations and quality assurance standards for medical abortion medications to ensure the safety and efficacy of these drugs. [Extracted from the article]

Abortion mobilities emerged within political geography and the reproductive mobilities scholarship to address extant theoretical and empirical gaps in these fields. This paper seeks to highlight and assess the abortion mobilities scholarship to date. Starting with a working definition of abortion mobilities, this paper argues for the relevance of abortion to political geography and outlines three key themes in political geography that abortion mobilities address: borders, states and anti‐genderism, intersectional politics and reproductive justice, and activism and abortion pills. [ABSTRACT FROM AUTHOR]

In the present study, an electroanalytical method that permits the optimization of factors affecting SWV for sensitive detection of mifepristone at glassy carbon electrode (GCE) using response surface methodology (RSM) with desirability function (DF) is presented. Factors selected for optimization after screening using full factorial design were frequency (X1), amplitude (X2), and pH (X3). The central composite design as a response surface methodology with desirability function (DF) was applied for obtaining the optimum level. The optimum conditions were obtained as follows: Frequency (X1=50 Hz), amplitude (X2=33.4 mV), and pH (X3=9.4), with an overall desirability function of 0.97. Subsequently, confirmatory experiments were performed in triplicates to validate the optimum conditions. The results obtained were satisfactory and agreed well with less only 11.9 % deviation from the values predicted by the model. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.54 and 1.80 ppm, respectively. The proposed method was applied for a quantitative determination of mifepristone in spiked tap water samples. The recovery tests showed that the detection of mifepristone at GC could be evaluated on environmental samples. [ABSTRACT FROM AUTHOR]

Objective: To illustrate the predictive value of peripheral blood α1-acid glycoprotein (AAG) in abortion outcomes with mifepristone and the relativity of concentration. Methods: A total of 134 patients who met the criteria were enrolled. The AAG and mifepristone concentrations were determined, and Student's t-test was used to assess significant differences in the levels of AAG between the complete and incomplete abortion groups. Results: The decrease in AAG concentration was associated with incomplete abortion, whereas the increase in AAG concentration was related to complete abortion (P < 0.01). In addition, the concentration of AAG was correlated with the concentration of mifepristone (r = 0.7375, P < 0.001). Conclusion: Our preliminary results suggest that AAG may serve as a biomarker for the prediction of incomplete abortions. [ABSTRACT FROM AUTHOR]

Medication abortion with pills (mifepristone and misoprostol) challenges the spatiality of abortion provision because it creates the possibility for safe, self‐managed abortion outside of clinical infrastructure. This possibility has been contested by pro‐ and anti‐abortion actors for as long as medication abortion has been in existence. In this paper, I offer a legal geography account of medication abortion technology that examines how medication abortion has been regulated in the United States. Conceptually, the paper uses a legal geography methodology to probe the social spatialities that abortion laws construct. Empirically, the paper analyses trends in legislation to restrict medication abortion and two significant court challenges where abortion providers brought suit against medication abortion restrictions. Drawing on legislation and litigation over mifepristone, I demonstrate that restrictions on it function by anchoring mifepristone inside the clinical spaces and regulatory frameworks established for surgical abortion. In this way, mifepristone regulations circumscribe its availability in order to prevent the creation of alternative models for abortion provision that could re‐arrange its geography and expand abortion access. Medication abortion pills challenge the spatiality of abortion provision because they create the possibility for safe, self‐managed abortion outside of clinical infrastructures. This paper offers a legal geography account of medication abortion technology that examines how medication abortion has been regulated in the United States. The paper analyses trends in legislation to restrict medication abortion and two significant court challenges where abortion providers brought suit against medication abortion restrictions. [ABSTRACT FROM AUTHOR]

Stress, a major regulator and precipitating factor of cognitive and emotional disorders, differentially manifests between males and females. Our aim was to investigate the mechanisms underlying the sexual dimorphic effects of acute restraint stress (RS) on males and females on the function of the prefrontal cortex (PFC). Adult male and female mice were subjected to RS or left in their home‐cage (NR), and then tested in the light‐dark test followed by the temporal order object recognition (TOR) task. Female mice exhibited increased anxiety‐like levels, whereas male mice only showed deficits in the TOR task. When the behavioural tests were conducted 24 hr following restraint stress (RS24), only the reduced performance in the TOR task in male mice persisted. In a different cohort, evoked field excitatory postsynaptic potentials (fEPSPs) were recorded in layer II of acute PFC slices, immediately or 24 hr after RS. Long‐term potentiation (LTP) was significantly reduced in RS and RS24 male, but not female, compared with their respective NR group. LTP in PFC slices incubated with corticosterone showed significantly reduced LTP only in males. To determine whether glucocorticoid signalling is implicated in the RS‐induced behavioural effects, a different cohort of mice was administered mifepristone, a corticosterone receptor antagonist. Mifepristone administration 1 hr before RS prevented the effects of RS on the TOR task in males, but not anxiety. In conclusion, RS has differential effects on recency memory and anxiety, in males and females, which are partly mediated by the effects of corticosterone signalling on synaptic plasticity. [ABSTRACT FROM AUTHOR]

Breast cancer is the leading cause of cancer death among women and almost all of the breast cancer‐caused mortality is related to metastasis. It has been reported that glucocorticoid facilitates the metastasis of breast cancer in mice, and mifepristone can antagonize the effect of glucocorticoid. Paclitaxel is one of the important drugs in the treatment of breast cancer. Mifepristone combined with paclitaxel could be an effective strategy for inhibiting breast cancer metastasis. However, their inherent defects, in terms of short blood circulation half‐life and lack of tumor targeting, not only limit their effectiveness but also cause adverse reactions. Therefore, our aim is to explore a novel protocol against breast cancer metastasis, further optimize its therapeutic efficacy by a nanodelivery system, and explore its mechanism. Herein, a paclitaxel‐conjugated and mifepristone‐loaded hydrogel (PM‐nano) was prepared by self‐assembly. Its characterizations were studied. The antimetastatic effect was evaluated in vitro and in vivo and its mechanism was also explored by western blot assay. The resultant PM‐nano was developed with favorable water solubility and good biocompatibility. Moreover, PM‐nano displayed increased cell uptake properties and stimulated drug release in the tumor micro‐acidic environment. The PM‐nano was more effective in inhibiting the proliferation and metastasis of breast cancer than other groups in vitro and in vivo. The PM‐nano might inhibit metastasis through glucocorticoid receptor/receptor tyrosine kinase‐like orphan receptor 1 and MMPs. Taken together, PM‐nano showed superior antimetastatic effects against breast cancer and excellent biocompatibility in vitro and in vivo, providing a new option for limiting metastasis. [ABSTRACT FROM AUTHOR]

Objective: To provide a descriptive overview and evaluate changes in the use and outcome of abortions provided worldwide by telemedicine in the past 10 years. Design: Retrospective cohort study. Setting: Multi‐country. Population/Sample: 30 344 women who completed the follow‐up survey of the telemedical abortion service Women on Web from January 2009 till January 2020. Methods: Analyses of follow‐up surveys, binary logistic regressions to test the association between year and outcomes. Main outcome measures: Rate of complete abortions, surgical interventions, ongoing pregnancies, blood transfusions per year, socio‐economic situation, knowledge on medical abortion, acceptability of receiving service, appropriateness of method and the likelihood of recommending the service to a friend. Results: Medical abortions were provided to 81 683 women, of whom 30 344 (37.2%) completed the follow‐up survey. In total, 26 076 women reported doing the medical abortion, of whom 1.5% reported an ongoing pregnancy, 10.2% a surgical intervention and 0.6% a blood transfusion. Acceptability of the service was 99%, and 59.2% of the users reported previous knowledge of medical abortion. We found a significant increase in complete abortions in 2019 (odds ratio 1.92; 95% CI 1.59–2.31) and decrease in surgical interventions (odds ratio 0.49; 95% CI 0.40–0.60) compared with 2009. Conclusion: Low follow‐up rates present a limitation in analysing trends in telemedical abortion usage. However, our findings suggest that it is a highly acceptable method around the world and that there has been an increase in complete abortions by telemedical abortions and a decrease in surgical interventions in the last 10 years. In the last 10 years, there has been an increase in complete abortions and decrease in surgical interventions of telemedical abortion. In the last 10 years, there has been an increase in complete abortions and decrease in surgical interventions of telemedical abortion. Linked article This article is commented on by Patricia A. Lohr, p. 160–161 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471-0528.16905. [ABSTRACT FROM AUTHOR]

Objective: To investigate the optimal dose of mifepristone and lithospermum combination regimen on medical abortion in early pregnancy rats without increasing side effects. Study Design: Sixty sexually mature female Sprague Dawley (SD) rats with early pregnancy were randomly allocated into 10 groups, including a control group (treated with 0.5% CMC‐Na) and nine experiments (treated with 1 mg/kg mifepristone, and 90, 180, 270, and 540 mg/kg lithospermum, and 90/180/270/540 mg/kg lithospermum +1 mg/kg mifepristone, respectively). The hormone levels, factors associated with endometrial bleeding, oxidative stress, and apoptotic proteins in the endometrium, were then investigated. Results: The results demonstrated that 540 mg/kg lithospermum plus 1 mg/kg mifepristone treatment significantly improved the abortion rate when compared with the control group. Compared with the 1 mg/kg mifepristone, 540 mg/kg lithospermum plus 1 mg/kg mifepristone treatment did not induce significant increase in factors associated with abnormal endometrial bleeding, such as matrix metalloproteinase‐9 (MMP9). However, mifepristone and lithospermum combination regimen promoted the expression level of malondialdehyde (MDA), activated caspase 3, caspase 9 and Bax, meanwhile, reduced the expression of superoxide dismutase (SOD) and Bcl‐2. Conclusion: These findings provided strong evidence that mifepristone and lithospermum combination regimen can obtain satisfactory abortion effect without increasing the expression level of bleeding‐related factors. [ABSTRACT FROM AUTHOR]

Objective: To assess the cost‐effectiveness of mifepristone and misoprostol (MifeMiso) compared with misoprostol only for the medical management of a missed miscarriage. Design: Within‐trial economic evaluation and model‐based analysis to set the findings in the context of the wider economic evidence for a range of comparators. Incremental costs and outcomes were calculated using nonparametric bootstrapping and reported using cost‐effectiveness acceptability curves. Analyses were performed from the perspective of the UK's National Health Service (NHS). Setting: Twenty‐eight UK NHS early pregnancy units. Sample: A cohort of 711 women aged 16–39 years with ultrasound evidence of a missed miscarriage. Methods: Treatment with mifepristone and misoprostol or with matched placebo and misoprostol tablets. Main outcome measures: Cost per additional successfully managed miscarriage and quality‐adjusted life years (QALYs). Results: For the within‐trial analysis, MifeMiso intervention resulted in an absolute effect difference of 6.6% (95% CI 0.7–12.5%) per successfully managed miscarriage and a QALYs difference of 0.04% (95% CI −0.01 to 0.1%). The average cost per successfully managed miscarriage was lower in the MifeMiso arm than in the placebo and misoprostol arm, with a cost saving of £182 (95% CI £26–£338). Hence, the MifeMiso intervention dominated the use of misoprostol alone. The model‐based analysis showed that the MifeMiso intervention is preferable, compared with expectant management, and this is the current medical management strategy. However, the model‐based evidence suggests that the intervention is a less effective but less costly strategy than surgical management. Conclusions: The within‐trial analysis found that based on cost‐effectiveness grounds, the MifeMiso intervention is likely to be recommended by decision makers for the medical management of women presenting with a missed miscarriage. The combination of mifepristone and misoprostol is more effective and less costly than misoprostol alone for the management of missed miscarriages. The combination of mifepristone and misoprostol is more effective and less costly than misoprostol alone for the management of missed miscarriages. [ABSTRACT FROM AUTHOR]

Objective: To compare 1‐ and 2‐day drug administration interval between mifepristone and misoprostol for second‐trimester pregnancy termination and provide evidence‐based recommendations. Methods: Search strategy: the search was performed in Pubmed, EMBASE, and Cochrane Library for the relevant published studies from their establishment to March 2020. Selection criteria: randomized controlled trials (RCTs) comparing 1‐ and 2‐day time interval of mifepristone‐misoprostol for termination of pregnancy during second‐trimester pregnancy were considered. Data were processed using Revman 5.3 software. Results: Meta‐analyses of three RCTs showed no significant difference was reported in the induction‐to‐abortion time and successful abortion rate between 1‐ and 2‐day mifepristone and misoprostol intervals. Statistical difference was not identified in the induction‐to‐abortion time between the two drug administration intervals in nulliparous or parous women. Conclusions: Both 1‐ and 2‐day dosing intervals between mifepristone and misoprostol are suitable for clinical use for second‐trimester medical termination of pregnancy. Synopsis: This study compared 1‐ and 2‐day administration interval between mifepristone and misoprostol for mid‐trimester pregnancy termination and indicated that both dosing intervals are suitable. [ABSTRACT FROM AUTHOR]

Aims: Glucocorticoids rapidly provoke serotonin (5‐HT) release in vivo. We aimed to investigate molecular mechanisms of glucocorticoid receptor (GR)‐triggered 5‐HT release. Methods: Employing 1C11 cells to model 5‐HT neurotransmission, immunofluorescence and Pearson's Correlation Coefficient were used to analyze colocalization of GR, 5‐HT, vesicle membrane protein synaptotagmin 1 and vesicle dye FM4‐64FX. FFN511 and FM4‐64FX dyes as well as calcium imaging were used to visualize vesicular 5‐HT release upon application of GR agonist dexamethasone, GR antagonist mifepristone and voltage‐gated calcium channel (VGCC) inhibitors. Results: GR, 5‐HT, synaptotagmin 1 and FM4‐64FX showed overlapping staining patterns, with Pearson's Correlation Coefficient indicating colocalization. Similarly to potassium chloride, dexamethasone caused a release of FFN511 and uptake of FM4‐64FX, indicating vesicular 5‐HT release. Mifepristone, calcium depletion and inhibition of L‐type VGCC significantly diminished dexamethasone‐induced vesicular 5‐HT release. Conclusions: In close proximity to 5‐HT releasing sites, activated GR rapidly triggers L‐type VGCC‐dependent vesicular 5‐HT release. These findings provide a better understanding of the interrelationship between glucocorticoids and 5‐HT release. [ABSTRACT FROM AUTHOR]

A letter to the editor discusses the findings of a study on the quality of abortion drugs, mifepristone and misoprostol, in 11 countries. The study reveals that these drugs have low quality in lower- and middle-income countries (LMICs), which raises concerns about safety and efficacy. The article emphasizes the need for further research to understand the implications of these quality issues, such as unknown side effects and increased complications. It also highlights the importance of regulating medical abortion drugs in LMICs to ensure that women have access to high-quality and safe drugs. [Extracted from the article]

Background: There are uncertainties about the benefit of routine cervical preparation and/or cervical dilatation before outpatient hysteroscopy. Objective: To determine if cervical preparation and/or routine mechanical dilatation reduces pain during outpatient hysteroscopy. Search strategy: MEDLINE, EMBASE, CINAHL and CENTRAL were searched on 19 October 2020, using keywords 'hysteroscopy', 'cervical preparation', 'cervical ripening', 'cervical dilatation', 'outpatient', 'office' and/or 'ambulatory' and associated medical subject headings. Selection criteria: Randomised controlled trials investigating the benefit of cervical preparation and/or cervical dilatation on pain in women undergoing outpatient hysteroscopy were included. Data collection and analysis: Two independent reviewers selected eligible trials and extracted data on pain, feasibility, adverse events and satisfaction/acceptability for meta‐analysis. Main results: The literature search yielded 807 records, of which 24 were included for review and 19 provided data for meta‐analysis. No trials investigated the role of routine mechanical cervical dilatation. Cervical preparation significantly reduced pain during outpatient hysteroscopy; standard mean difference (SMD) ‒0.67, 95% confidence interval (CI) ‒1.05 to ‒0.29. Feasibility also improved as priming provided significantly easier hysteroscopic entry (SMD 0.89, 95% CI 0.32–1.46), greater cervical dilatation (SMD 0.81, 95% CI 0.08–1.53) and shorter procedural times (SMD ‒0.51, 95% CI ‒0.88 to ‒0.13). Cervical preparation, however, incurred significantly more adverse effects, mainly comprising genital tract bleeding, abdominal pain and gastrointestinal symptoms (odds ratio 2.94, 95% CI 1.58–5.47). There were limited data regarding satisfaction, acceptability and complications. Conclusions: Cervical preparation reduces pain and improves feasibility associated with outpatient hysteroscopy but increases the risk of adverse effects. Cervical preparation before outpatient hysteroscopy reduces pain, enhances feasibility but increases adverse effects. Cervical preparation before outpatient hysteroscopy reduces pain, enhances feasibility but increases adverse effects. [ABSTRACT FROM AUTHOR]

Latin American countries have slowly enacted laws decriminalizing abortion in three circumstances: Life‐threatening risk for the pregnant woman, extra‐uterine non‐viability of malformed foetus, and pregnancy due to rape or incest. Chile is one of the last countries to adopt such a law, formulated in an increasingly restrictive format. Conservative politicians and Church‐related healthcare institutions promptly announced individual and institutional conscientious objection based on the right of private facilities to obey their ideology and personal moral integrity. Juridical consultations and Constitutional Court rulings allowed private hospitals to uphold their objection even if contracted to provide some public health services. Under these conditions, only a few hundred women requested and obtained a legal abortion, while an estimated 100,000 continued to depend on unsafe procedures. Bioethical debate was silenced by the unfettered drive for conscientious objection that continues to limit women's autonomy, and fails to ease the public health scourge of massive unsafe clandestine abortions. [ABSTRACT FROM AUTHOR]

Introduction: The safety and acceptability of medical abortion using mifepristone and misoprostol at home at ≤9+0 weeks' gestation is well established. However, the upper gestational limit at which the procedure remains safe and acceptable at home is not known. To inform a national guideline on abortion care we conducted a systematic review to determine what gestational limit for expulsion at home offers the best balance of benefits and harms for women who are having medical abortion. Material and methods: We searched Embase, MEDLINE, Cochrane Library, Cinahl Plus and Web‐of‐Science on 2 January 2020 for prospective and retrospective cohort studies with ≥50 women per gestational age group, published in English from 1995 onwards, that included women undergoing medical abortion and compared home expulsion of pregnancies of ≤9+0 weeks' gestational age with pregnancies of 9+1‐10+0 weeks or >10+1 weeks' gestational age, or compared the latter two gestational age groups. We assessed risk‐of‐bias using the Newcastle‐Ottowa scale. All outcomes were meta‐analyzed as risk ratios (RR) using the Mantel‐Haenszel method. The certainty of the evidence was assessed using GRADE. Results: Six studies (n = 3381) were included. The "need for emergency care/admission to hospital" (RR = 0.79, 95% confidence interval [CI] 0.45‐1.4), "hemorrhage requiring transfusion/≥500 mL blood loss" (RR = 0.62, 95% CI 0.11‐3.55), patient satisfaction (RR = 0.99, 95% CI 0.95‐1.03), pain (RR = 0.91, 95% CI 0.82‐1.02), and "complete abortion without the need for surgical intervention" (RR = 1.03, 95% CI 1‐1.05) did not differ statistically significantly between the ≤9+0 and >9+0 weeks' gestation groups. The rates of vomiting (RR = 0.8, 95% CI 0.69‐0.93) and diarrhea (RR = 0.85, 95% CI 0.73‐0.99) were statistically significantly lower in the ≤9+0 weeks group but these differences were not considered clinically important. We found no studies comparing pregnancies of 9+1‐10+0 weeks' gestation with pregnancies of >10+0 weeks' gestation. The certainty of this evidence was predominantly low and mainly compromised by low event rates and loss to follow up. Conclusions: Women who are having a medical abortion and will be taking mifepristone up to and including 10+0 weeks' gestation should be offered the option of expulsion at home after they have taken the misoprostol. Further research needs to determine whether the gestational limit for home expulsion can be extended beyond 10+0 weeks. [ABSTRACT FROM AUTHOR]

An editorial is presented on induced abortion being presumably one of the most common gynaecological procedures in Australia. Topics include increasing use of medical abortion not reflecting an overall increase in the abortion rate which in fact appears to be declining in Australia; and restricting access to abortion serves increasing the number of unsafe abortions and the associated maternal morbidity.