Home use of mifepristone for medical abortion: a systematic review.

BACKGROUND: In many countries, persons seeking medical abortion with mifepristone followed by misoprostol can self-administer the second drug, misoprostol, at home, but self-administration of the first drug, mifepristone, is not allowed to the same extent. OBJECTIVES: This systematic review aims to evaluate whether the efficacy, safety and women's satisfaction with abortion treatment are affected when mifepristone is self-administered at home instead of in a clinic. SEARCH STRATEGY: A literature search covered CINAHL, Cochrane Library, Embase, Ovid MEDLINE and APA PsycInfo in October 2022. SELECTION CRITERIA: Eligible studies focused on persons undergoing medical abortion comparing home and in-clinic mifepristone intake. Outcomes included abortion effectiveness, compliance, acceptability, and practical consequences for women. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed eligibility and risk of bias. Meta-analysis included similar studies while those differing in design were synthesised without meta-analysis. RESULTS: Six studies (54 233 women) of medical abortions up to 10 weeks were included. One randomised controlled trial and one retrospective register study had moderate risk of bias, and four non-randomised clinical trials where women could choose the place for intake of mifepristone had serious risk of bias. There was no difference in abortion effectiveness (high confidence) or compliance (moderate confidence) between mifepristone administered at home or in-clinic. No differences in complications were detected between groups and most women who chose home administration of mifepristone expressed a preference for this approach. CONCLUSIONS: Our systematic review demonstrates that the effectiveness of medical abortion is comparable regardless of mifepristone administration and intake, at home or in the clinic.

"Trust Women": Characteristics of and learnings from patients of a Shield Law medication abortion practice in the United States.

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.

Identification of Lipomatous Metaplasia in a Cortisol-secreting Adrenocortical Adenoma Treated With Mifepristone.

Adrenal adenomas are benign tumors of the adrenal cortex that may secrete excess hormones, such as cortisol. They are most commonly discovered during imaging studies for unrelated problems. Lipomatous metaplasia is a rare degenerative change in adrenal adenomas, characterized by the presence of adipose tissue and hematopoietic elements within the tumor. In this report, we present a case of an adrenal adenoma with lipomatous metaplasia in a patient with hypertension, hyperlipidemia, and type II diabetes mellitus. The discovery of this adrenal mass was prompted by an evaluation of the patient's progressive hirsutism. The tumor was found to be secreting cortisol, leading to Cushing syndrome. The patient subsequently underwent surgical resection of the mass after being treated with mifepristone. The histopathological examination confirmed it to be an adrenal cortical neoplasm with lipomatous metaplasia, characterized by uncertain malignant potential. The patient did well postoperatively. Three months after left adrenalectomy, the patient's hirsutism, A1c, and hypertension improved, allowing a reduction in antihypertensives. Her body mass index stabilized, her triglyceride decreased, and her dehydroepiandrosterone sulfate level normalized. She continued to do well at follow-up visits. Overall, this was a rare case of a functioning adrenal adenoma with lipomatous metaplasia, presenting both diagnostic and therapeutic challenges.

Management of early pregnancy loss by reproductive endocrinologists: does access to mifepristone matter?

Objective: To describe patterns and variations in the medical and procedural management of early pregnancy loss (EPL) among reproductive endocrinology and infertility specialists, with attention to mifepristone use. Design: Cross-sectional. Setting: Online survey. Patients: Society for Reproductive Endocrinology and Infertility members. Intervention: Not applicable. Main Outcome Measure: Preferred management for EPL. Results: Of 101 completed surveys (response rate: 12.2%), 70.3% of respondents reported diagnosing EPL at least once per week. Half (50.5%) of respondents preferred medical management compared with 27.7% who preferred procedural management and 21.8% who preferred expectant management. Approximately one-quarter (26.7%) of respondents offer mifepristone for medical management of EPL. The most common reason cited for not prescribing mifepristone was a lack of access to the medication. Mifepristone prescribers were more likely to work in a hospital or university setting than private practice. Increasing years in practice was also associated with mifepristone use. The use of mifepristone for EPL did not vary by the respondent's age, gender, prior abortion training, or practice region. Conclusion: The most effective method of medical management uses both mifepristone and misoprostol. However, nearly three-quarters of reproductive endocrinology and infertility physicians do not offer mifepristone, which may be linked to access issues.

Pharmacokinetics and bioequivalence of two formulations of mifepristone tablets in healthy Chinese subjects under fasting conditions: a single-center, open, randomized, single-dose, double-period, two-sequence, crossover trial.

Objective: A bioequivalence (BE) study was performed to evaluate the pharmacokinetics, safety, and bioequivalence of two formulations of mifepristone tablets in healthy Chinese volunteers under fasting conditions. Methods: A single-center, open, randomized, single-dose, double-period, two-sequence, crossover study in healthy subjects under fasting conditions was performed. The subjects received a single fasting dose of mifepristone (10 mg/tablet) during the first and second periods, followed by a 14-day washout period, during which frequent pharmacokinetic (PK) sampling occurred up to 120 h. The pharmacokinetic parameters of mifepristone were calculated based on the plasma drug concentration-time profile. Primary endpoints were the BE of major pharmacokinetic parameters (AUC0-t and AUC0-∞) and the maximum observed serum concentration (Cmax). Secondary endpoints were safety parameters. Results: Forty subjects (34 male and 6 female subjects) were randomly assigned to treatment, with 39 completing the two-period study. After the single administration of mifepristone tablets (test preparation vs. reference preparation) under fasting conditions, the geometric mean ratios (GMRs) of Cmax, AUC0-t, and AUC0-∞ were 98.76%, 104.28%, and 104.83%, respectively. The primary metabolites of mifepristone (RU42633 and RU42698),the GMRs of Cmax, AUC0-t, AUC0-∞ were 102.33% and 100.97%, 103.17% and 103.71%, 104.02% and 103.84%, respectively. Similarly, for another metabolite of mifepristone (RU42698), the GMRs of Cmax, AUC0-t, and AUC0-∞ were 100.97%, 103.71%, and 103.84%, respectively. All 90% confidence intervals (CIs) for the test/reference AUC ratio and Cmax ratio were within the acceptable range (80%-125%) for BE, which met the requirements of bioequivalence. No serious adverse events (AEs) occurred, and all AEs were classified as level 1 or 2. Conclusion: The PK parameters of mifepristone and its metabolites (RU42633 and RU42698) were measured using the (GMRs) of AUC0-t, AUC0-∞, and Cmax and were similar between the test and reference drug. The two formulations of mifepristone showed good tolerability and a similar safety profile. Clinical Trial Registration: chinadrugtrials.org.cn, identifier CTR20182413.

Conservative treatment of cesarean scar pregnancy with the combination of methotrexate and mifepristone: A systematic review.

BACKGROUND: Cesarean scar pregnancy (CSP) has become more frequent as a direct consequence of the increased number of cesarean deliveries and the advances in imaging. Although some cases are characterized by spontaneous resolution, unrecognized or mishandled CSP has the potential to cause both fetal and maternal morbidity and mortality. However, due to its infrequency, there is no agreement on the best management. OBJECTIVE: The purpose of this study was to evaluate the safety, the risks and effectiveness of medical therapy with methotrexate and mifepristone to better understand its role in CSP therapy. DESIGN: This study is a systematic review. DATA SOURCES AND METHODS: The electronic databases PubMed, Medline, and Scopus were comprehensively searched until December 2023. Medical Subject Headings terms (Cesarean scar pregnancy) AND (Methotrexate) AND (Mifepristone) AND (Medical Therapy) were used to identify the relevant records. Due to the rarity of this pathology, the studies included are all case reports or case series. The methodological quality of the included studies was assessed using the JBI Critical Appraisal Checklist for case reports. RESULTS: We included in our review a total of seven cases reported in five manuscripts at the end of the screening process. Our review suggests that this type of combination treatment can be considered. The success rate is 71.4%. Treatment seems to be most effective when beta human chorionic gonadotropin (B-hCG) is below 5,000 mUi/ml and when the gestational sac is less than 20 mm. The absence of fetal heartbeat seems to be a positive prognostic factor for a positive outcome. CONCLUSION: Methotrexate and mifepristone administration can be considered as an alternative first-line effective treatment, especially in case of pregnancy with B-hCG <5,000 mUi/ml and when the gestational sac is less than 20 mm. It is important to individualize the management and treatment according to the clinical condition, the patient's age, number of previous cesarean deliveries, willingness to have other children, and the physicians' experience.

Unrecognized Cesarean Scar Pregnancy has the potential to cause both fetal and maternal morbidity and mortality. Methotrexate (MTX) and Mifepristone administration can be considered as an alternative first-line effective treatment especially in case of pregnancy with a low BHCG and when the gestational sac is less than 20 mmCesarean scar pregnancy (CSP) has become more frequent as a direct consequence of the increased number of Cesarean deliveries and the advances in imaging. Unrecognized CSP has the potential to cause both fetal and maternal morbidity and mortality. However, there is no agreement on the best management. The purpose of this study was to evaluate the safety, the risks, and effectiveness of medical therapy with methotrexate and mifepristone. The electronic databases PubMed, Web of Science, and Scopus were comprehensively searched until December 2023. We included in our review a total of seven cases reported in five5 manuscripts at the end of the screening process. Our review suggests that this type of combination treatment can be considered. The success rate is 71.4%. Treatment seems to be most effective when B-hCG is below 5000 mUi/ml and when the gestational sac is less than 20 mm. methotrexate (MTX) and mifepristone administration can be considered as an alternative first-line effective treatment.

Feasibility and acceptability of outpatient medical induction at 13-18 weeks' gestation in public sector hospitals in Nepal: a prospective cohort study.

PURPOSE: To evaluate the feasibility and acceptability of outpatient medical induction at 13-18 weeks' gestation to limit overnight hospital stays. METHODS: In this prospective cohort study, participants with 13-18-week pregnancies seeking abortions at two government hospitals swallowed mifepristone 200 mg and self-administered misoprostol 400 mcg buccally 24-48 h later, 1-2 h before returning to the outpatient clinic (OPD). Repeat misoprostol was dosed every 3 h until expulsion. Participants requiring care beyond OPD hours were admitted as inpatients. Acceptability was evaluated by exit interview before discharge. Participants were contacted two weeks later to assess any subsequent issues. RESULTS: Ninety-eight (82%) of 120 participants had successful outpatient abortions using a median two (IQR 2, 3) misoprostol doses. The median induction-to-abortion time was five hours (IQR 4, 7.5). Eleven (9%) participants expelled before clinic arrival. Twenty-two (18%) participants were transferred as inpatients at OPD closing. Transferred participants remained inpatient for a median 18 h (IQR 18, 21.25). There were no serious adverse events and satisfaction with the abortion process was high. CONCLUSIONS: Although the outpatient model did not meet statistical expectations, it is clinically feasible, acceptable, and improves efficiency, expands access, and reduces burdens for women and providers. Operational adjustments may facilitate higher outpatient success.

Outpatient medical induction at 13-18 weeks' gestation is feasible, improves efficiency, expands access, reduces staff and patient burdens, and aligns guidelines and practice with evidence.

Mifepristone and misoprostol versus misoprostol alone for induction of labor in women with intrauterine fetal death: A meta-analysis and systematic review.

BACKGROUND: 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. OBJECTIVES: To compare mifepristone and misoprostol lines of treatment. SEARCH STRATEGY: Pubmed, Embase, Cochrane and Web of Science databases were systematically searched until April 9, 2024. SELECTION CRITERIA: 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 COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. CONCLUSION: 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.

Primary Care Clinicians' Interest In, and Barriers To, Medication Abortion.

PURPOSE: Providing medication abortion in the primary care setting is a promising way to increase access to abortion, a threatened service in many States. This study aimed to characterize primary care clinicians' interest in prescribing medication abortion, what barriers they face in adding this service, and what support they need. METHODS: Data were collected from 162 practicing primary care clinicians in Minnesota using an online survey with closed- and open-ended response options. Data were analyzed using descriptive statistics, group comparison analyses, and content analysis for the open-ended questions. RESULTS: Participants represented a diverse range of ages, years in practice, credentials, genders, and urban/rural practice settings, and held mixed knowledge and attitudes around medication abortion. All demographic groups surveyed expressed interest in prescribing medication abortion, with the strongest interest represented among younger respondents, women, and those practicing in urban settings. Clinicians who provide prenatal care or who already work with these medications in other contexts were more likely to want to add medication abortion to their practices. The most common barrier to providing medication abortion was a lack of knowledge about organizational policies and about the medications themselves. To empower clinicians to provide medication abortion, respondents voiced needing their health systems to build clear processes and wanting supportive networks of other clinicians for collaboration. CONCLUSIONS: Given the interest of primary care clinicians in providing medication abortion, health systems have a valuable opportunity to increase access.

Promising selective progesterone receptor modulators: what's new in female contraception?

INTRODUCTION: Selective progesterone receptor modulators (SPRMs), such as mifepristone and ulipristal acetate (UPA), have demonstrated high efficacy and safety as single dose treatments for medication abortion and emergency contraception (EC). Other obstetrical and gynecologic applications have emerged, both for episodic and ongoing uses. The potential of these compounds to provide estrogen-free, ongoing contraception is promising; however, the rare, but serious, hepatic injury cases seen with UPA have put at least a temporary halt to further research in this area. AREAS COVERED: This paper reviews the biophysical impacts and clinical applications of SPRMs in women's reproductive health, with a focus on the roles of mifepristone and UPA in family planning. Given the political environment, especially in the United States where these applications may be threatened, extensive description is dedicated to mechanisms of action of these agents. EXPERT OPINION: Both mifepristone and ulipristal acetate are first-line options for single use applications. There continues to be a need for estrogen-free ongoing contraception that does not have unpopular impacts on bleeding caused by contraceptive methods and for treatments for heavy menstrual bleeding. However, current restrictions on UPA limit longer term use. Perhaps other SPRMs without hepatic impacts may emerge to fill this need.

Spatial Disparities in Mifepristone Use for Early Miscarriage and Induced Abortion Among Obstetrician-Gynecologists Practicing in Massachusetts.

Background: About 25% of pregnancies end in early miscarriage or abortion annually in the United States. While mifepristone is part of the most effective medication regimen for miscarriage and abortion, regulatory burdens and legal restrictions limit its provision in obstetric-gynecological practice. The extent of geographic disparities in mifepristone use is unknown. Objectives: We sought to ascertain whether regional "deserts" for mifepristone-based miscarriage and abortion care exist in Massachusetts using geographic regions specified by the Commonwealth's Executive Office of Health and Human Services. Methods: We fielded a cross-sectional survey of obstetrician-gynecologists practicing in Massachusetts. We weighted survey data to account for differential nonresponse by provider sex, region, and years in independent practice. Results: Among obstetrician-gynecologists in independent practice with region data (n = 148), 51.0% reported using mifepristone for miscarriage and 43.5% for abortion. Significant differences in reported use were observed across regions (p < 0.001 for both indications). Barriers to using mifepristone for miscarriage management also varied across regions. Respondents outside of Boston and Western Massachusetts were more likely to report gaps in knowledge about regulations and prescribing and had less prior experience using mifepristone. In a multivariable model adjusting for provider sex and practice type, obstetrician-gynecologists outside of Boston had significantly lower odds of using mifepristone for miscarriage (adjusted odds ratio [aOR] = 0.14, 95% confidence interval [95% CI] = 0.08-0.25) and abortion (aOR = 0.46, 95% CI = 0.26-0.82), compared to Boston-based obstetrician-gynecologists. Conclusion: Mifepristone provision varies significantly by Massachusetts region. This may lead to spatial disparities in reproductive health outcomes.

Mifepristone and rapamycin have non-additive benefits for life span in mated female Drosophila.

The drugs mifepristone and rapamycin were compared for their relative ability to increase the life span of mated female Drosophila melanogaster. Titration of rapamycin indicated an optimal concentration of approximately 50 µM, which increased median life span here by average +81%. Meta-analysis of previous mifepristone titrations indicated an optimal concentration of approximately 466 µM, which increased median life span here by average +114%. Combining mifepristone with various concentrations of rapamycin did not produce further increases in life span, and instead reduced life span relative to either drug alone. Assay of maximum midgut diameter indicated that rapamycin was equally efficacious as mifepristone in reducing mating-induced midgut hypertrophy. The mito-QC mitophagy reporter is a previously described green fluorescent protein (GFP)-mCherry fusion protein targeted to the outer mitochondrial membrane. Inhibition of GFP fluorescence by the acidic environment of the autophagolysosome yields an increased red/green fluorescence ratio indicative of increased mitophagy. Creation of a multi-copy mito-QC reporter strain facilitated assay in live adult flies, as well as in dissected midgut tissue. Mifepristone was equally efficacious as rapamycin in activating the mito-QC mitophagy reporter in the adult female fat-body and midgut. The data suggest that mifepristone and rapamycin act through a common pathway to increase mated female Drosophila life span, and implicate increased mitophagy and decreased midgut hypertrophy in that pathway.

Targeting delivery of mifepristone to endometrial dysfunctional macrophages for endometriosis therapy.

Endometriosis seriously affects 6-10 % of reproductive women globally and poses significant clinical challenges. The process of ectopic endometrial cell colonization shares similarities with cancer, and a dysfunctional immune microenvironment, characterized by non-classically polarized macrophages, plays a critical role in the progression of endometriosis. In this study, a targeted nano delivery system (BSA@Mif NPs) was developed using bovine serum albumin (BSA) as the carrier of mifepristone. The BSA@Mif NPs were utilized to selectively target M2 macrophages highly enriched in ectopic endometrial tissue via the SPARC receptor. This targeting strategy increases drug concentration at ectopic lesions while minimizing its distribution to normal tissue, thereby reducing side effects. In vitro studies demonstrated that BSA@Mif NPs not only enhanced the cellular uptake of M2-type macrophages and ectopic endometrial cells but also improved the cytotoxic effect of mifepristone on ectopic endometrial cells. Furthermore, the BSA@Mif NPs effectively induced immunogenic cell death (ICD) in ectopic endometrial cells and repolarized M2-type macrophages toward the M1 phenotype, resulting in a synergistic inhibition of ectopic endometrial cell growth. In vivo experiments revealed that BSA@Mif NPs exhibited significant therapeutic efficacy in endometriosis-bearing mice by increasing drug accumulation in the endometriotic tissues and modulating the immune microenvironment. This targeted biomimetic delivery strategy presents a promising approach for the development of endometriosis-specific therapies based on existing drugs. STATEMENT OF SIGNIFICANCE: Macrophages play an essential role in immune dysfunctional microenvironment promoting the occurrence and progression of endometriosis and can be a crucial target for developing immune microenvironment regulation strategies for the unmet long-term management of endometriosis. The albumin nanoparticles constructed based on SPARC overexpression in macrophages and endometrial cells and albumin biosafety can achieve the targeted therapy of endometriosis by increasing the passive- and active-mediated drug accumulation in ectopic endometrium and remodeling the immune microenvironment based on macrophage regulation. This study has the following implications: i) overcoming the inherent shortcomings of clinical drugs by nanotechnology is an alternative way of developing medication; ii) developing microenvironment modulation strategies based on macrophage regulation for endometriosis management is feasible.

The efficacy of mifepristone-misoprostol regimen versus misoprostol-only for medication abortion at 22 + 0/7 to 30 + 0/7 weeks' gestation.

OBJECTIVE: This study aimed to compare duration of medication abortion after pretreatment with mifepristone versus misoprostol-only regimens at 22 + 0/7 to 30 + 0/7 weeks. METHODS: This retrospective cohort study included patients admitted for medication abortion from 2014 to 2022. Patients underwent feticide due to genetic or anatomical abnormalities at gestational age of 22 + 0/7 to 30 + 0/7 weeks. Excluded from this study were patients admitted at gestational age < 22 + 0/7 or > 30 + 0/7 weeks, with multiple gestation, with diagnosis of intrauterine fetal demise before feticide, with contraindication for vaginal delivery, and who were administered a medical regimen other than the mifepristone-misoprostol or misoprostol-only protocol. Information collected included patients' demographics, clinical outcomes, additional procedural interventions, and complications. Data of patients treated with mifepristone-misoprostol versus misoprostol-only were compared. RESULTS: The study group included 46 patients in the mifepristone-misoprostol group and 35 in the misoprostol-only group. Median interval from first dose of misoprostol to fetal expulsion was shorter in the mifepristone-misoprostol group (10.6 vs. 15.3 h; p = 0.007) with shorter duration of hospitalization (3.5 ± 1.1 vs. 4.1 ± 1.2 days; p = 0.013). Study groups did not differ in terms of complications. Patients in the mifepristone-misoprostol group had a younger gestational age (23.8 ± 1.69 vs. 25.37 ± 2.4 weeks; p = 0.002). However, multivariable Cox regression found that mifepristone was independently associated with shorter abortion time (OR 1.7, 95% CI 1.03-2.9, p = 0.03). CONCLUSION: Medication abortion with mifepristone-misoprostol was associated with shorter time to fetal expulsion at gestational ages 22 + 0/7 to 30 + 0/7 weeks, compared with misoprostol-only regimen.

Hormonal methods for emergency contraception.

The World Health Organization includes oral emergency contraception (EC) in the list of essential medicines. Ulipristal acetate (UPA) and levonorgestrel (LNG) are the recommended oral methods. UPA has superior efficacy and a comparable side effect profile compared with LNG. Both work by inhibiting or delaying ovulation, so that sperm present in the reproductive tract will have lost their fertilising ability by the time the oocyte is eventually released. Neither LNG nor UPA at the EC doses have significant effects on the endometrium and are unable to prevent implantation. Mifepristone can also be used for EC but its availability is limited to few countries. LNG is less effective in women with a body mass index over 26 kg/m2 or weight over 70 kg. Hormonal contraception can be quickstarted immediately following LNG, or five days following UPA. LNG-releasing intrauterine devices and cyclo-oxygenase inhibitors are promising options for EC to be further studied.

Does the stress axis mediate behavioural flexibility in a social cichlid, Neolamprologus pulcher?

Behavioural flexibility plays a major role in the way animals cope with novel situations, and physiological stress responses are adaptive and highly efficient mechanisms to cope with unpredictable events. Previous studies investigating the role of stress responses in mediating behavioural flexibility were mostly done in laboratory rodents using stressors and cognitive challenges unrelated to the ecology of the species. To better understand how stress mediates behavioural flexibility in a natural context, direct manipulations of the stress response and cognitive tests in ecologically relevant contexts are needed. To this aim, we pharmacologically blocked glucocorticoid receptors (GR) in adult Neolamprologus pulcher using a minimally invasive application of a GR antagonist. GR blockade prevents the recovery after a stressful event, which we predicted to impair behavioural flexibility. After the application of the GR antagonist, we repeatedly exposed fish to a predator and tested their behavioural flexibility using a detour task, i.e. fish had to find a new, longer route to the shelter when the shortest route was blocked. While the latencies to find the shelter were not different between treatments, GR blocked fish showed more failed attempts during the detour tasks than control fish. Furthermore, weak performance during the detour tasks was accompanied by an increase of fear related behaviours. This suggests that blocking GR changed the perception of fear and resulted in an impaired behavioural flexibility. Therefore, our results support a potential link between the capacity to recover from stressors and behavioural flexibility in N. pulcher with potential consequences for an effective and adaptive coping with changing environments.

Effect of the addition of exogenous progesterone and the progesterone receptor inhibitor (RU 486) on boar cryopreservation semen extenders.

Cryopreservation of porcine spermatozoa is detrimental due to their high sensitivity to cold shock, leading to changes akin to capacitation, known as cryocapacitation. These changes, including the acrosomal reaction, hypermotility induction, and protein phosphorylation, might be influenced by the presence of progesterone in seminal plasma and egg yolk, used in most freezing extenders. We tested the effect of various progesterone concentrations added to the freezing extenders (1, 10, and 100 µg/mL). At 100 µg/mL, progesterone decreased the proportion of straightness and tended to reduce viability and the proportion of progressive motility (p < 0.1). At 10 µg/mL, it increased reacted acrosomes in dead sperm (p < 0.05), protein phosphorylation rate (p < 0.05), and tended (p < 0.1) to enhance linear movement compared to the control. To counteract the capacitating effect of progesterone, we examined the effect of antiprogesterone mifepristone (RU 486) at concentrations of 5, 10, 20, 50, 100, and 200 µM, and co-incubated 10 µM of RU 486 with 10 µg/mL of progesterone. RU 486 maintained capacitation levels and motility parameters similar to the control, although high concentrations (100 µM) tended (p = 0.152) to increase protein phosphorylation. Co-incubation reduced the acrosome reaction in dead sperm, and RU 486 appeared to prevent hypermotility stabilizing motility and viability parameters compared to samples with progesterone alone. Protein phosphorylation increased and RU 486 could not restore capacitation to control levels due to its competitive antagonism for progesterone receptors, having less affinity than progesterone, which displaces RU 486 at high concentrations, allowing normal sperm capacitation.

Effect of Mifepristone on Migration and Proliferation of Oral Cancer Cells.

Glucocorticoid receptor (GR) overexpression has been linked to increased tumour aggressiveness and treatment resistance. GR antagonists have been shown to enhance treatment effectiveness. Emerging research has investigated mifepristone, a GR antagonist, as an anticancer agent with limited research in the context of oral cancer. This study investigated the effect of mifepristone at micromolar (µM) concentrations of 1, 5, 10 and 20 on the proliferation and migration of oral cancer cells, at 24 and 48 h. Scratch and scatter assays were utilised to assess cell migration, MTT assays were used to measure cell proliferation, Western blotting was used to investigate the expression of GR and the activation of underlying Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signalling pathways, and immunofluorescence (IF) was used to determine the localisation of proteins in HaCaT (immortalised human skin keratinocytes), TYS (oral adeno squamous cell carcinoma), and SAS-H1 cells (squamous cell carcinoma of human tongue). Mifepristone resulted in a dose-dependent reduction in the proliferation of HaCaT, TYS, and SAS-H1 cells. Mifepristone at a concentration of 20 µM effectively reduced collective migration and scattering of oral cancer cells, consistent with the suppression of the PI3K-Akt and MAPK signalling pathways, and reduced expression of N-Cadherin. An elongated cell morphology was, however, observed, which may be linked to the localisation pattern of E-Cadherin in response to mifepristone. Overall, this study found that a high concentration of mifepristone was effective in the suppression of migration and proliferation of oral cancer cells via the inhibition of PI3K-Akt and MAPK signalling pathways. Further investigation is needed to define its impact on epithelial-mesenchymal transition (EMT) markers.

Safety and Efficacy of Oral Mifepristone for Cervical Ripening and Induction of Labor.

Background Labor induction, a common practice to prevent maternal and fetal complications from prolonged labor, involves stimulating contractions before they begin naturally. This can be achieved through medications, mechanical methods, or surgical interventions. Cervical ripening is crucial for successful delivery. When the cervix is not sufficiently ripe, drugs are often used to augment this process chemically. Objective To evaluate the safety and efficacy of mifepristone for cervical ripening and induction of labor. Method A sample size of 200 was used in this single-blind randomized control trial. Primarily, pregnant women with term pregnancies, Bishop scores <6, and cephalic fetal presentation were included in the study. The study population was randomly divided into test and control groups. The test group (n=100) was administered 200 mg of mifepristone orally, while the control group (n=100) received a placebo. The Bishop score was reassessed 24 hours after mifepristone administration. Patients were taken for labor induction if their Bishop score was >6. For individuals with a Bishop score of <6, 1 mg of dinoprostone gel was administered intracervically once every six hours. Safety and efficacy were assessed by analyzing several parameters associated with labor progression, maternal outcomes, and fetal outcomes. Results The mean age of patients in the test group was 26±4.5 years, while in the control group, it was 26±5 years. The induction-to-delivery interval was notably shorter in the test group (18.8±2.3 hours) than in the control group (19.24±1.8 hours, p<0.0001). After the administration of 200 mg mifepristone, the mean Bishop score in the test group was 5.74±0.8, compared to 5.13±0.76 in the control group. The increase in the Bishop score after mifepristone treatment was significantly higher in the test group than in the control group (p-value=0.013). In the study, 73 (73%) patients in the test group had a normal vaginal delivery (NVD), whereas NVD accounted for 64 (64%) patients in the control group. Instrumental deliveries were less frequent in the test group, accounting for 14 (14%) patients, compared to 16 (16%) patients in the control group. The frequency of lower segment cesarean section (LSCS) was also lower in the mifepristone-treated group at 13 (13%) compared to the control group at 20 (20%). Fetal distress in five (38%) patients and non-progression of labor in 11 (55%) patients were the most frequent indications for LSCS in the test and control groups, respectively. There was no significant difference in neonatal outcomes between the test and control groups. Meconium-stained liquor was the most frequent complication in both the test group (10, 10%) and the control group (5, or 5%). Conclusion Administration of mifepristone effectively increased the Bishop scores and reduced the induction-to-delivery interval compared to controls, highlighting its potential as a cervical ripening agent.