Landscape assessment of the availability of medical abortion medicines in India.

BACKGROUND: Medical abortion with mifepristone and misoprostol can be provided up to 63 days' gestation in India. This accounts for 67.5 percent of all abortions in the country. We conducted an assessment to determine the availability of medical abortion medicines, specifically the combi-pack, in India. METHODS: We applied the World Health Organization landscape assessment protocol at the national level. The assessment protocol included a five-step adaptation of an existing availability framework, including online data collection, desk review, country-level key informant interviews, and an analysis to identify barriers and opportunities to improve medical abortion availability. The assessment was conducted between August and March 2021. RESULTS: Medicines for medical abortion are included in the national essential drug list and available with prescription in India. The assessment identified 42 combi-pack products developed by 35 manufacturers. The quality of medical abortion medicines is regulated by national authorities; but as health is devolved to states, there are significant inter-state variations. This is seen across financing, procurement, manufacturing, and monitoring mechanisms for quality assurance of medical abortion medicines prior to distribution. There is a need to strengthen supply chain systems, ensure consistent availability of trained providers and build community awareness on use of medical abortion medicines for early abortions, at the time of the assessment. CONCLUSION: Opportunities to improve availability and quality of medical abortion medicines exist. For example, uniform implementation of regulatory standards, greater emphasis on quality-assurance during manufacturing, and standardizing of procurement and supply chain systems across states. Regular in-service training of providers on medical abortion is required. Finally, innovations in evidence dissemination and community engagement about the recently amended abortion law are needed.

Medical abortion is popular in India and benefits from a liberal legal context. It is important to understand the availability of quality abortion medicines in the country. Using the World Health Organization country assessment protocol and availability framework for medical abortion medicines we examined the availability of these medicines from supply to demand. We used this information to identify opportunities for increasing availability of quality-assured medical abortion medicines. We found that the context for medical abortion varies across states. Strengthening procurement and supply chain management, with a greater emphasis on quality-assurance and regulation of manufacturing should be instituted at the state-level. Training is also needed to increase provider knowledge of the latest national guidelines and laws to ensure respectful and person-centered services. Finally, the public should be informed about medical abortion as a safe and effective choice, especially for early abortions.

Misoprostol for non-alcoholic steatohepatitis: a randomised control trial.

INTRODUCTION: The management of non-alcoholic steatohepatitis (NASH) is an unmet clinical need. Misoprostol, a structural analogue of naturally occurring prostaglandin E1, has been reported to decrease proinflammatory cytokine production and may have a potential role in treating NASH. We aimed to evaluate the efficacy and safety of misoprostol in treating patients with NASH. METHODS: In this phase 2, double-blind, randomised, placebo-controlled trial, patients with NASH were randomly assigned in a 1:1 ratio to receive 200 µg of misoprostol or placebo thrice daily for 2 months. The primary endpoint was an improvement in liver function tests (LFTs), interleukin-6 (IL-6) and endotoxin levels. The secondary endpoint was improvement in insulin resistance, dyslipidaemia, hepatic fibrosis and hepatic steatosis. RESULTS: A total of 50 patients underwent randomisation, of whom 44 (88%) were males. The age range was 25-64 years (mean±SE of mean (SEM) 38.1±1.4). 19 (38%) patients had concomitant type 2 diabetes mellitus. 32 (64%) patients were either overweight or obese. At the end of 2 months' treatment, a reduction in total leucocyte count (TLC) (p=0.005), alanine aminotransferase (ALT) (p<0.001), aspartate aminotransferase (AST) (p=0.002) and controlled attenuation parameter (CAP) (p=0.003) was observed in the misoprostol group, whereas placebo ensued a decline in ALT (p<0.001), AST (p=0.018), gamma-glutamyl transferase (GGT) (p=0.003), CAP (p=0.010) and triglycerides (p=0.048). There was no diminution in insulin resistance, hepatic fibrosis (elastography) and dyslipidaemia in both groups. However, misoprostol resulted in a significant reduction in CAP as compared with the placebo group (p=0.039). Moreover, in the misoprostol group, pretreatment and post-treatment IL-6 and endotoxin levels remained stable, while in the placebo group, an increase in the IL-6 levels was noted (p=0.049). Six (12%) patients had at least one adverse event in the misoprostol group, as did five (10%) in the placebo group. The most common adverse event in the misoprostol group was diarrhoea. No life-threatening events or treatment-related deaths occurred in each group. CONCLUSION: Improvement in the biochemical profile was seen in both misoprostol and placebo groups without any statistically significant difference. However, there was more improvement in steatosis, as depicted by CAP, in the misoprostol group and worsening of IL-6 levels in the placebo group. TRIAL REGISTRATION NUMBER: NCT05804305.

Access to mifepristone, misoprostol, and contraceptive medicines in eight countries in the Eastern Mediterranean Region: descriptive analyses of country-level assessments.

BACKGROUND: Despite their importance in reducing maternal mortality, information on access to Mifepristone, Misoprostol, and contraceptive medicines in the Eastern Mediterranean Region is limited. METHODS: A standardized assessment tool measuring access to Mifepristone, Misoprostol, and contraceptive medicines included in the WHO essential medicines list (EML) was implemented in eight countries in the Eastern Mediterranean Region (Afghanistan, Iraq, Lebanon, Libya, Morocco, Palestine, Pakistan, and Somalia) between 2020-2021. The assessment focused on five access measures: 1) the inclusion of medicines in national family planning guidelines; 2) inclusion of medicines in comprehensive abortion care guidelines; 3) inclusion of medicines on national essential medicines lists; 4) medicines registration; and 5) procurement and forecasting of Mifepristone, Misoprostol, and contraceptive medicines. A descriptive analysis of findings from these eight national assessments was conducted. RESULTS: Only Lebanon and Pakistan included all 12 contraceptives that are enlisted in the WHO-EML within their national family planning guidelines. Only Afghanistan and Lebanon included mifepristone and mifepristone-misoprostol combination in post-abortion care guidelines, but these medicines were not included in their national EMLs. Libya and Somalia lacked a national regulatory authority for medicines registration. Most contraceptives included on the national EMLs for Lebanon, Morocco and Pakistan were registered. Misoprostol was included on the EMLs-and registered-in six countries (Afghanistan, Iraq, Lebanon, Morocco, Palestine, and Pakistan). However, only three countries procured misoprostol (Iraq, Morocco, and Somalia). CONCLUSION: These findings can guide efforts aimed at improving the availability of Mifepristone, Misoprostol, and contraceptive medicines in the Eastern Mediterranean Region. Opportunities include expanding national EMLs to include more options for Mifepristone, Misoprostol, and contraceptive medicines and strengthening the registration and procurement systems to ensure these medicines' availability were permitted under national law and where culturally acceptable.

Ensuring access to Mifepristone, Misoprostol, and contraceptive medicines is critical to improving women's health, and more specifically reducing maternal mortality and improving women's sexual and reproductive health in the Eastern Mediterranean Region.The aim of this study was to analyse findings from national assessments to capture information on the implementation of relevant policies and procedures. Those were the policies that ensure access to Mifepristone, Misoprostol, and contraceptive medicines in the public sector for the eight Eastern Mediterranean Region countries included in the study (Afghanistan, Iraq, Libya, Lebanon, Morocco, Palestine, Pakistan, and Somalia). The assessments were completed between 2020 and 2021.We found that most countries did not include all twelve contraceptives enlisted in the WHO essential medicines list (EML) in their national family planning guidelines. No country had developed a national abortion care guidelines nor included mifepristone (alone or in combination with misoprostol) on national EML. Libya and Somalia lacked a national regulatory authority for medicines registration. Most contraceptives included on the national EMLs for Lebanon, Morocco and Pakistan were registered. Misoprostol was included on the EMLs­and registered­in six countries (Afghanistan, Iraq, Lebanon, Morocco, Palestine, and Pakistan) yet, only three countries procured misoprostol (Iraq, Morocco, and Somalia).Our findings provide evidence on system-level barriers to availability of Mifepristone, Misoprostol, and contraceptive medicines (e.g., lack of guidelines or inclusion on EML, lack of registration and procurement) that can support policy and advocacy efforts to strengthen the pharmaceutical sector to better ensure availability of Mifepristone, Misoprostol, and contraceptive medicines to women in reproductive age at the country-level in accordance with the national law and prevailing culture.

Motivations for using misoprostol for abortion outside the formal healthcare system in Colombia: a qualitative study of women seeking postabortion care in Bogotá and the Coffee Axis.

BACKGROUND: In 2006, a Constitutional Court ruling partially decriminalized abortion in Colombia, allowing the procedure in cases of rape, risk to the health or life of the woman, and fetal malformations incompatible with life. Despite this less prohibitive law, some women and pregnant people preferred self-managing their abortions outside the formal healthcare system, often without accurate information. In 2018, we undertook a study to understand what motivated women to self-manage using medications that they acquired informally. Colombia has since adopted a progressive law in 2022, permitting abortion on request through the 24th week of pregnancy. However, the implementation of this law is still underway. Examining the reasons why women chose to informally self-manage an abortion after 2006 may not only highlight how barriers to legal services persisted at that time, but also could inform strategies to increase knowledge of the current abortion law and improve access to services going forward. METHODS: In-depth interviews were conducted in 2018 with 47 women aged 18 and older who used misoprostol obtained outside of health facilities to induce an abortion, and who were receiving postabortion care in two private clinics. Interviews explored what women knew about the 2006 abortion law which was then in effect, and the reasons why they preferred informal channels for abortion care over formal healthcare services. RESULTS: Women's motivations to use misoprostol obtained outside the formal healthcare system were influenced by lack of trust in the healthcare system along with incomplete and inaccurate knowledge of the abortion law. Conversely, women considered misoprostol obtained outside the healthcare system to be effective, affordable, and easier to access. CONCLUSIONS: Obtaining misoprostol outside the formal healthcare system offered a more accessible and appealing prospect for some women given fears of legal repercussion and stigma toward abortion. Though this preference will likely continue despite the more liberal abortion law, strategies should be implemented to broaden knowledge of the recent change in law and to combat misinformation and stigma. This would support knowledge of and access to legal abortion for those who wish to avail themselves of these services.

United Kingdom Data Deficiencies Influencing U.S. FDA Decisions.

The U.S. FDA has permanently removed the in-person prescribing requirements that previously safeguarded the use of mifepristone/misoprostol medical abortions, allowing prescribing through telemedicine or on-line ordering and distribution through the mail and pharmacies, without standard pre-abortion testing. This will increase the risk of complications due to failure to adequately determine the gestational age or rule out ectopic pregnancy by ultrasound or physical exam, failure to perform labs to document whether RhoGAM is indicated, and failure to obtain appropriate informed consent to prevent unwanted abortions, among other concerns. The FDA justified this action by referencing flawed studies with significantly undercounted complications. The details of these study deficiencies are examined in this paper.

The MISOPRED score: Development and validation of a clinical scoring system to predict the effectiveness of Misoprostol treatment for early pregnancy loss.

BACKGROUND: Misoprostol treatment for early pregnancy loss has varied success demonstrated in previous studies. Incorporating predictors in a single clinical scoring system would be highly beneficial in clinical practice. OBJECTIVE: To develop and evaluate the accuracy of a scoring system to predict misoprostol treatment outcomes for managing early pregnancy loss. STUDY DESIGN: Retrospective cohort and validation study. METHODS: Patients discharged from the gynecologic emergency department from 2013 to 2016, diagnosed with early pregnancy loss, who were treated with 800 mcg misoprostol, administrated vaginally were included. All were sonographically reevaluated within 48-72 hours. Patients in whom the gestational sac was not expelled or with endometrial lining >30 mm were offered a repeat dose and returned for reevaluation after seven days. A successful response was defined as complete expulsion. Clinical data were reviewed to identify predictors for successful responses. The scoring system was then retrospectively evaluated on a second cohort to evaluate its accuracy. Multivariate logistic regression was performed to identify factors most predictive of treatment response. RESULTS: The development cohort included 126 patients. Six factors were found to be most predictive of misoprostol treatment effectiveness: nulliparity, prior complete spontaneous abortion, gestational age, vaginal bleeding, abdominal pain, and mean sac diameter, yielding a score of 0-8 (the MISOPRED score), where 8 represents the highest-likelihood of success. The score was validated retrospectively with 119 participants. Successful response in the group with the lowest likelihood score (score 0-3) was 9%, compared with 82% in the highest likelihood score group (score 7-8). Using the MISOPRED score, approximately 15% of patients previously planned to receive misoprostol treatment can be referred for surgical management. CONCLUSIONS: MISOPRED score can be utilized as an adjunct tool for clinical decision-making in cases of Early pregnancy loss. To our knowledge, this is the first scoring system suggested to predict the success rate in these cases.

Comparing labour induction outcomes using misoprostol and dinoprostone in term pregnancies: A retrospective study at Kiambu Level 5 Hospital between 2018 and 2020.

BACKGROUND: The Maternal and Perinatal Death Surveillance and Response (MPDSR) was introduced in Kenya in 2016 and implemented at Kiambu Level 5 Hospital (KL5H) three years later in 2019. During a routine MPDSR meeting at KL5H, committee members identified a possible link between the off-label use of 200mcg misoprostol tablets divided eight times to achieve the necessary dose for labour induction (25mcg) and maternal deaths. Following this, an administrative decision was made to switch from misoprostol to dinoprostone for the induction of labour in June of 2019. This study aimed to assess the overall impact of MPDSR as well as the effect of replacing misoprostol with dinoprostone on uterine rupture, maternal and neonatal deaths at KL5H. METHODS: We conducted a retrospective cohort study of women who gave birth at KL5H between January 2018 and December 2020. We defined the pre-intervention period as January 2018-June 2019, and the intervention period as July 2019-December 2020. We randomly selected the records of 411 mothers, 167 from the pre-intervention period and 208 from the intervention period, all of whom were induced. We used Bayes-Poisson Generalised Linear Models to fit the risk of uterine rupture, maternal and perinatal death. 12 semi-structured key person questionnaires was used to describe staff perspectives regarding the switch from misoprostol to dinoprostone. Inductive and deductive data analysis was done to capture the salient emerging themes. RESULTS: We reviewed 411 patient records and carried out 12 key informant interviews. Mothers induced with misoprostol (IRR = 3.89; CI = 0.21-71.6) had an increased risk of death while mothers were less likely to die if they were induced with dinoprostone (IRR = 0.23; CI = 0.01-7.12) or had uterine rupture (IRR = 0.56; CI = 0.02-18.2). The risk of dying during childbearing increased during Jul 2019-Dec 2020 (IRR = 5.43, CI = 0.68-43.2) when the MPDSR activities were strengthened. Induction of labour (IRR = 1.01; CI = 0.06-17.1) had no effect on the risk of dying from childbirth in our setting. The qualitative results exposed that maternity unit staff preferred dinoprostone to misoprostol as it was thought to be more effective (fewer failed inductions) and safer, regardless of being more expensive compared to misoprostol. CONCLUSION: While the period immediately following the implementation of MPDSR at KL5H was associated with an increased risk of death, the switch to dinoprostone for labour induction was associated with a lower risk of maternal and perinatal death. The use of dinoprostone, however, was linked to an increased risk of uterine rupture, possibly attributed to reduced labour monitoring given that staff held the belief that it is inherently safer than misoprostol. Consequently, even though the changeover was warranted, further investigation is needed to determine the reasons behind the rise in maternal mortalities, even though the MPDSR framework appeared to have been put in place to quell such an increase.

How Effective Is Misoprostol Alone for Medication Abortion?

AbstractWith recent severe restrictions to abortion accessibility in the United States and a pending Supreme Court case challenging the Food and Drug Administration's approval of mifepristone, evidence-based strategies to protect and expand access to abortion care are needed. Two safe and effective regimens for medication abortion are widely used globally - misoprostol-only and misoprostol in combination with mifepristone. However, misoprostol-only regimens are rarely used in the United States. In 2023, the National Abortion Federation and the Society of Family Planning updated their recommended protocol for misoprostol-only for medication abortion to 800 µg of misoprostol administered buccally, sublingually, or vaginally every 3 hours for three or more doses. To characterize the data supporting this specific regimen, this article reviews the relevant literature to address the question of how effective misoprostol-only is for medication abortion. The authors conclude that the updated misoprostol regimen is highly effective and a potential strategy for expanding access to abortion.

MIFEPRISTON IN OBSTETRICS - WHY NOT?

Cervical ripening is a critical component of normal parturition. There are substantial variations in labour induction (IOL) techniques around the world. Mifepristone causes the termination of unwanted pregnancies, but there is a lack of consensus on its use for labour induction. The purpose of our study was to compare the combination of Mifepristone and Misoprostol with the combination of a Foley balloon and Misoprostol for labour induction. The study included 175 pregnant women, with gestational age 37-42 weeks. In the study group - 88 pregnant aged 21-35 (28.56±3.23), a combination of Mifepristone-Misoprostol was used. A combination of Foley catheter and Misoprostol was used in the control group - 87 pregnant aged 21-35 (29.48±3.03). The outcomes were assessed. In the study group the rate of vaginal delivery was higher and the frequency of cesarean section was lower compared to the control group (75 vs. 72, and 13 vs. 15, respectively); The total duration of labour was shorter in the study group (p<0,05); There was no difference between groups in the incidences of neonatal morbidity on the first and the fifth minute of life (p>0,05); The pain level was significantly low in the study group compared to the control group (5±0,75 vs. 8±0,96) and no cervical laceration was revealed in the study group. The Mifepristone - Misoprostol combination has advantages over the Foley balloon - Misoprostol combination for induction of labour regarding reduction in pain intensity, duration of labour, and cervical laceration.

Multi-target mechanism of misoprostol in pregnancy termination based on network pharmacology and molecular docking.

Misoprostol is a prostaglandin analogue that contracts the uterus, prompting the expulsion of the embryo. No systematic evaluation of the mechanisms of misoprostol has previously been performed. In this study, known targets of misoprostol were obtained from the DrugBank database; potential targets of misoprostol were predicted using data from the SwissTargetPrediction and PharmMapper databases; and the main targets of pregnancy termination were obtained from the GeneCards database. The protein-protein interaction (PPI) network of the shared genes between misoprostol and pregnancy termination was constructed using data from the STRING database, and the "misoprostol-pregnancy termination-pathway" network was constructed and potential targets was verified through molecular docking. We analyzed 37 shared target genes and obtained a network diagram of 134 potential targets, which the core therapeutic targets were HSP90AA1, EGFR, and MAPK1. GO functional and KEGG pathway enrichment analyses showed that misoprostol can modulate the VEGF signaling pathway, calcium signaling pathway, and NF-κB signaling pathway in pregnancy termination and mainly interferes with protein phosphorylation, cell localization, and protein hydrolysis regulation processes. This research illustrates the mechanism underlying the pharmacological effect of misoprostol, namely pregnancy termination. However, further experimental verification is warranted for optimal use of misoprostol during clinical practice.

Le misoprostol est un analogue des prostaglandines qui contracte l'utérus, provoquant l'expulsion de l'embryon. Aucune évaluation systématique des mécanismes du misoprostol n'a été réalisée auparavant. Dans cette étude, les cibles connues du misoprostol ont été obtenues à partir de la base de données DrugBank ; Les cibles potentielles du misoprostol ont été prédites à l'aide des données des bases de données SwissTargetPrediction et PharmMapper ; et les principales cibles de l'interruption de grossesse ont été obtenues à partir de la base de données GeneCards. Le réseau d'interaction protéine-protéine (IPP) des gènes partagés entre le misoprostol et l'interruption de grossesse a été construit à l'aide des données de la base de données STRING, et le réseau « voie d'interruption de grossesse-misoprostol ¼ a été construit et les cibles potentielles ont été vérifiées par amarrage moléculaire. Nous avons analysé 37 gènes cibles partagés et obtenu un diagramme de réseau de 134 cibles potentielles, dont les principales cibles thérapeutiques étaient HSP90AA1, EGFR et MAPK1. Les analyses d'enrichissement des voies fonctionnelles GO et KEGG ont montré que le misoprostol peut moduler la voie de signalisation VEGF, la voie de signalisation du calcium et la voie de signalisation NF-κB lors de l'interruption de grossesse et interfère principalement avec les processus de phosphorylation des protéines, de localisation cellulaire et de régulation de l'hydrolyse des protéines. Cette recherche illustre le mécanisme sous-jacent à l'effet pharmacologique du misoprostol, à savoir l'interruption de grossesse. Cependant, une vérification expérimentale plus approfondie est justifiée pour une utilisation optimale du misoprostol au cours de la pratique clinique.

Tratamiento médico del aborto del primer trimestre: igual eficacia, más eficiencia / Medical treatment of abortion in the first trimester: Equal effectiveness, more efficiency

Antecedentes: La pérdida gestacional precoz acontece en el 10-20% de todas las gestaciones clínicas, siendo el 85% previos a la semana 12 de amenorrea. El aborto involuntario conlleva una carga muy significativa en los recursos destinados a sanidad, alcanzado un coste económico nacional en Reino Unido de 471 millones de libras esterlinas por año (533,06 millones de euros), cifra extrapolable a otros países industrializados. Según una revisión sistemática reciente no hay ensayos bien diseñados en gestaciones del primer trimestre que arrojen una evidencia consolidada sobre cuál es el mejor método de tratamiento de aborto del primer trimestre y existen diferentes estudios que han tratado de evidenciar reducción de costes con resultados contradictorios. Material y métodos: Se realiza un estudio de diseño observacional, retrospectivo y longitudinal. Se revisaron 892 pacientes diagnosticadas de aborto espontáneo durante el primer trimestre de gestación, en el periodo comprendido entre enero de 2013 y diciembre de 2016. En nuestro estudio hemos querido evaluar la efectividad del misoprostol vaginal como tratamiento médico para el aborto espontáneo en el primer trimestre, en comparación con el legrado obstétrico/evacuador y, cuantificar la diferencia en los costos de ambos procedimientos a través de un estudio de minimización de costes. Resultados: De las 892 pacientes reclutadas, se realizó tratamiento médico con misoprostol en 517 (57,95%) y tratamiento quirúrgico mediante legrado evacuador en 375 (42,05%). La efectividad del tratamiento médico fue del 82% (426/517). Con respecto al tratamiento quirúrgico la efectividad resultó del 100%. La tasa de éxito del tratamiento médico fue superior en el subgrupo de pacientes con aborto incompleto (92,9%), en comparación con los grupos de gestación anembrionada (85,7%) y aborto diferido (78,2%). Conclusiones: El tratamiento médico del aborto es un manejo seguro y aceptado por las pacientes...(AU)

Background: Early pregnancy loss occurs in 10-20% of all clinical pregnancies, 85% being prior to week 12 of amenorrhea. Miscarriage entails a very significant burden on healthcare resources, reaching a national economic cost in the United Kingdom of £471 million per year (€533.06 million), a figure that can be extrapolated to other industrialized countries. According to a recent systematic review, there are no well-designed trials in first-trimester pregnancies that provide consolidated evidence on what is the best first-trimester abortion treatment method, and there are different studies that have tried to demonstrate cost reduction with contradictory results. Material and methods: An observational, retrospective and longitudinal design study was carried out. 892 patients diagnosed with spontaneous abortion during the first trimester of pregnancy were reviewed, in the period between January 2013 and December 2016. In our study, we wanted to evaluate the efficacy of vaginal misoprostol as a medical treatment for spontaneous abortion in the first trimester, in comparison with obstetric curettage-evacuator, and to quantify the difference in the costs of both procedures through a cost minimization study. costs. Results: Of the 892 recruited patients, medical treatment with misoprostol was performed in 517 (57.95%) and surgical treatment by curettage in 375 (42.05%). The effectiveness of medical treatment was 82% (426/517). With respect to surgical treatment the effectiveness of 100%. The success rate of medical treatment was higher in the subgroup of patients with incomplete abortion (92.9%), compared to the anembryonic gestation (85.7%) and delayed abortion (78.2%) groups. Conclusions: The medical treatment of abortion is a safe management and accepted by the patients. The adequate selection of candidate patients leads to an increase in the success rate and a decrease in costs...(AU)

Comparing the outcomes of termination of second trimester pregnancy with a live fetus using intravaginal misoprostol between women with and without previous cesarean section.

OBJECTIVE: To compare the outcomes of termination of pregnancy with live fetuses in the second trimester (14-28 weeks), using misoprostol 400 mcg intravaginal every 6 h, between women with previous cesarean section (PCS) and no previous cesarean section (no PCS). METHODS: A comparative study was conducted on a prospective database of pregnancy termination in the second trimester, Chiang Mai university hospital. Inclusion criteria included: (1) singleton pregnancy; (2) gestational age between 14 and 28 weeks; and (3) pregnancy with a live fetus and medically indicated for termination. The participants were categorized into two groups; PCS and no PCS group. All were terminated using misoprostol 400 mcg intravaginal every 6 h. The main outcomes were induction to fetal delivery interval and success rate, defined as fetal delivery within 48 h. RESULTS: A total of 238 women, including 80 PCS and 158 no PCS, were recruited. The success rate of fetal delivery within 48 h between both groups was not significantly different (91.3% vs. 93.0%; p-value 0.622). The induction to fetal delivery interval were not significantly different (1531 vs. 1279 min; p-value > 0.05). Gestational age was an independent factor for the success rate and required dosage of misoprostol. The rates of most adverse effects of misoprostol were similar. One case (1.3%) in the PCS group developed uterine rupture during termination, ending up with safe and successful surgical removal and uterine repair. CONCLUSION: Intravaginal misoprostol is highly effective for second trimester termination of pregnancy with PCS and those with no PCS, with similar success rate and induction to fetal delivery interval. Gestational age was an independent factor for the success rate and required dosage of misoprostol. Uterine rupture could occur in 1.3% of PCS, implying that high precaution must be taken for early detection and proper management. SYNOPSIS: Intravaginal misoprostol is highly effective for termination of second trimester pregnancy with a live fetus, with a comparable success rate between women with and without previous cesarean section, with a 1.3% risk of uterine rupture among women with previous cesarean section.

Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists.

We tested five chemically and metabolically stable prostaglandin (PG) receptor agonists in a mouse model of dexamethasone-induced ocular hypertension (OHT). Whilst all compounds significantly (p < 0.05, ANOVA) lowered intraocular pressure (IOP) after twice-daily bilateral topical ocular dosing (5 µg/dose) over three weeks, the time course and magnitude of the responses varied. The onset of action of NS-304 (IP-PG receptor agonist) and rivenprost (EP4-PG receptor agonist) was slower than that of misoprostol (mixed EP2/EP3/EP4-PG receptor agonist), PF-04217329 (EP2-PG receptor agonist), and butaprost (EP2-PG receptor agonist). The rank order of IOP-lowering efficacies aligned with the onset of actions of these compounds. Peak IOP reductions relative to vehicle controls were as follows: misoprostol (74.52%) = PF-04217329 (74.32%) > butaprost (65.2%) > rivenprost (58.4%) > NS-304 (55.3%). A literature survey indicated that few previously evaluated compounds (e.g., latanoprost, timolol, pilocarpine, brimonidine, dorzolamide, cromakalim analog (CKLP1), losartan, tissue plasminogen activator, trans-resveratrol, sodium 4-phenyl acetic acid, etc.) in various animal models of steroid-induced OHT were able to match the effectiveness of misoprostol, PF-04217329 or butaprost. Since a common feature of the latter compounds is their relatively high affinity and potency at the EP2-PG receptor sub-type, which activates the production of intracellular cAMP in target cells, our studies suggest that drugs selective for the EP2-PG receptor may be suited to treat corticosteroid-induced OHT.

Medical treatment for early pregnancy loss following in vitro fertilization compared to spontaneous pregnancies.

BACKGROUND: Misoprostol is a well-studied medical treatment for early pregnancy loss (EPL), with success rates ranging between 70 and 90%. However, treatment failure is associated with major patient discomfort, including the need for surgical intervention to evacuate the uterus. It was previously reported that medical treatment was especially successful among women who conceived after in vitro fertilization (IVF). We aimed to study if there is a difference in rates of medical treatment failures for EPL between pregnancies conceived by IVF and spontaneous pregnancies. METHODS: In this retrospective cohort study, we included all women who underwent medical treatment for EPL at our institute between 07/2015 and 12/2020. Treatment outcome was compared between IVF and spontaneous pregnancies. Treatment failure was defined as a need for surgical intervention, namely, dilation & curettage (D&C) and/or hysteroscopy, due to retained products of conception, which was defined as a gestational sac or endometrial thickness greater than 15 mm in a TVS scan. RESULTS: Overall, 775 patients were included, of which 195 (169/775 = 25.1%) ultimately required surgical intervention. There was no difference between the study groups in the rate of treatment failure. However, among IVF pregnancies, the rate of emergency D&C was lower (3.6% vs. 9.8%, p = 0.001), compared to spontaneous group. CONCLUSION: In cases of medical treatment for EPL, IVF pregnancies had no differences in rates of treatment failure compared to spontaneous pregnancies. That being said, IVF pregnancies have lower chances to undergo emergency D&C, compared to spontaneous pregnancies.

Methods for the induction of labor: efficacy and safety.

This review assessed the efficacy and safety of pharmacologic agents (prostaglandins, oxytocin, mifepristone, hyaluronidase, and nitric oxide donors) and mechanical methods (single- and double-balloon catheters, laminaria, membrane stripping, and amniotomy) and those generally considered under the rubric of complementary medicine (castor oil, nipple stimulation, sexual intercourse, herbal medicine, and acupuncture). A substantial body of published reports, including 2 large network meta-analyses, support the safety and efficacy of misoprostol (PGE1) when used for cervical ripening and labor induction. Misoprostol administered vaginally at doses of 50 µg has the highest probability of achieving vaginal delivery within 24 hours. Regardless of dosing, route, and schedule of administration, when used for cervical ripening and labor induction, prostaglandin E2 seems to have similar efficacy in decreasing cesarean delivery rates. Globally, although oxytocin represents the most widely used pharmacologic agent for labor induction, its effectiveness is highly dependent on parity and cervical status. Oxytocin is more effective than expectant management in inducing labor, and the efficacy of oxytocin is enhanced when combined with amniotomy. However, prostaglandins administered vaginally or intracervically are more effective in inducing labor than oxytocin. A single 200-mg oral tablet of mifepristone seems to represent the lowest effective dose for cervical ripening. The bulk of the literature assessing relaxin suggests this agent has limited benefit when used for this indication. Although intracervical injection of hyaluronidase may cause cervical ripening, the need for intracervical administration has limited the use of this agent. Concerning the vaginal administration of nitric oxide donors, including isosorbide mononitrate, isosorbide, nitroglycerin, and sodium nitroprusside, the higher incidence of side effects with these agents has limited their use. A synthetic hygroscopic cervical dilator has been found to be effective for preinduction cervical ripening. Although a pharmacologic agent may be administered after the use of the synthetic hygroscopic dilator, in an attempt to reduce the interval to vaginal delivery, concomitant use of mechanical and pharmacologic methods is being explored. Combining the use of a single-balloon catheter with dinoprostone, misoprostol, or oxytocin enhances the efficacy of these pharmacologic agents in cervical ripening and labor induction. The efficacy of single- and double-balloon catheters in cervical ripening and labor induction seems similar. To date, the combination of misoprostol with an intracervical catheter seems to be the best approach when balancing delivery times with safety. Although complementary methods are occasionally used by patients, given the lack of data documenting their efficacy and safety, these methods are rarely used in hospital settings.

Outpatient labor induction-Exploring future potential by assessing eligibility in a historical cohort.

INTRODUCTION: Labor induction rates have increased over the last decades, and in many high-income countries, more than one in four labors are induced. Outpatient management of labor induction has been suggested in low-risk pregnancies to improve women's birth experiences while also promoting a more efficient use of healthcare resources. The primary aim of this paper was to assess the proportion of women in a historical cohort that would have been eligible for outpatient labor induction with oral misoprostol. Second, we wanted to report safety outcomes and assess efficacy outcomes for mothers and infants in pregnancies that met the criteria for outpatient care. MATERIAL AND METHODS: Criteria for outpatient labor induction with oral misoprostol were applied to a historical cohort of women with induction of labor at two Norwegian tertiary hospitals in the period January 1, through July 31, 2021. The criteria included low-risk women with an unscarred uterus expecting a healthy, singleton baby in cephalic position at term. The primary outcome was the proportion of women eligible for outpatient labor induction. Secondary outcomes included reasons for ineligibility and, for eligible women, safety and efficacy outcomes. RESULTS: Overall, 29.7% of the 1320 women who underwent labor induction in a singleton term pregnancy met the criteria for outpatient labor induction. We identified two serious adverse events that potentially could have occurred outside the hospital if the women had received outpatient care. The mean duration from initiation of labor induction to administration of the last misoprostol was 22.4 h. One in 14 multiparous women gave birth within 3 h after the last misoprostol dose. CONCLUSIONS: In this historical cohort, three in ten women met the criteria for outpatient management of labor induction with oral misoprostol. Serious adverse events were rare. The average time span from the initiation of labor induction to the last misoprostol was nearly 24 h. This suggests a potential for low-risk women with an induced labor to spend a substantial period of time at home before labor onset. However, larger studies testing or evaluating labor induction with oral misoprostol as an outpatient procedure are needed to draw conclusions.

Provision of Medications for Self-Managed Abortion Before and After the Dobbs v Jackson Women's Health Organization Decision.

Importance: The Supreme Court decision in Dobbs v Jackson Women's Health Organization overturned the right to choose abortion in the US, with at least 16 states subsequently implementing abortion bans or 6-week gestational limits. Prior research indicates that in the 6 months following Dobbs, approximately 32 360 fewer abortions were provided within the US formal health care setting. However, trends in the provision of medications for self-managed abortion outside the formal health care setting have not been studied. Objective: To determine whether the provision of medications for self-managed abortion outside the formal health care setting increased in the 6 months after Dobbs. Design, Setting, and Participants: Cross-sectional study using data from sources that provided abortion medications outside the formal health care setting to people in the US between March 1 and December 31, 2022, including online telemedicine organizations, community networks, and online vendors. Using a hierarchical bayesian model, we imputed missing values from sources not providing data. We estimated the change in provision of medications for self-managed abortion after the Dobbs decision. We then estimated actual use of these medications by accounting for the possibility that not all provided medications are used by recipients. Exposure: Abortion restrictions following the Dobbs decision. Main Outcomes and Measures: Provision and use of medications for a self-managed abortion. Results: In the 6-month post-Dobbs period (July 1 to December 31, 2022), the total number of provisions of medications for self-managed abortion increased by 27 838 (95% credible interval [CrI], 26 374-29 175) vs what would have been expected based on pre-Dobbs levels. Excluding imputed data changes the results only slightly (27 145; 95% CrI, 25 747-28 246). Accounting for nonuse of medications, actual self-managed medication abortions increased by an estimated 26 055 (95% CrI, 24 739-27 245) vs what would have been expected had the Dobbs decision not occurred. Conclusions and Relevance: Provision of medications for self-managed abortions increased in the 6 months following the Dobbs decision. Results suggest that a substantial number of abortion seekers accessed services despite the implementation of state-level bans and restrictions.

Efficacy and safety of oral and vaginal administration of misoprostol for induction of labor in high-risk obese pregnant women with hypertension or diabetes mellitus.

OBJECTIVE: This study aims to compare the safety and efficacy of misoprostol administered orally and vaginally in obese pregnant women at term with either gestational hypertension or diabetes. METHODS: A total of 264 pregnant women were enrolled and categorized into two groups based on their primary condition: hypertension (134 cases) or diabetes mellitus (130 cases) and were further divided into subgroups for misoprostol administration: orally (Oral group) or vaginally (Vaginal group). The primary outcomes measured were changes in the Bishop score following treatment, induction of labor (IOL) success rates, requirement for oxytocin augmentation, duration of labor, mode of delivery, and cesarean section rates. RESULTS: Significant enhancements in Bishop scores, decreased cesarean section rates and increased success rates of IOL were noted in both administration groups. The incidence of vaginal delivery within 24 h was significantly higher in the Vaginal group compared to the Oral group. Adverse effects, including nausea, uterine overcontraction, hyperfrequency of uterine contraction and uterine hyperstimulation without fetal heart rate deceleration, were significantly more prevalent in the Vaginal group than in the Oral group. CONCLUSION: Misoprostol administration, both orally and vaginally, proves effective for labor induction in obese pregnant women with hypertension or diabetes. However, the oral route presents a lower risk of adverse maternal and neonatal outcomes, suggesting its preference for safer labor induction in this demographic.