Medical management of early pregnancy loss with mifepristone and misoprostol in Emergency Departments compared to a Complex Family Planning office: implementation of a COVID-19 institutional policy change.

OBJECTIVES: To evaluate the implementation of mifepristone and misoprostol for medical management of early pregnancy loss (EPL) in emergency departments (EDs) by comparing efficacy, complication, and follow-up rates for patients treated in EDs to those in the Complex Family Planning (CFP) outpatient office. STUDY DESIGN: In COVID-19's first wave, we expanded medication management of EPL to our EDs. This retrospective study evaluated 72 patients receiving mifepristone and misoprostol for EPL from 4/1/2020-3/31/2021, comparing treatment success, safety outcomes, and follow-up rates by location. We did not perform a power calculation. RESULTS: Thirty-three (46%) patients received care in the ED and 39 (54%) at CFP. Treatment success was lower in the ED (23, 70%) compared to CFP (34, 87.2%), but after adjusting for insurance status and type of pregnancy (miscarriage, uncertain viability, unknown location) this was not significant: aOR 0.48 (95%CI 0.13-1.81), p=0.28. More ED patients underwent emergent interventions (3 vs 0). Complications in the ED cohort included two emergent uterine aspirations, one uterine artery embolization, and two blood transfusions. Among these, two cases were attributed to misdiagnosis (a cesarean scar and a cervical ectopic pregnancy interpreted as incomplete miscarriages) and one to guideline nonadherence (anticoagulated patient). No complications occurred in the CFP group. Follow-up rates were over 80% in both groups. More ED patients engaged in telehealth follow-up (67% vs 18.0%, p≤0.0001). CONCLUSIONS: In this small sample, we observed a trend toward lower rates of treatment success following medication management of EPL in the ED, compared to the CFP office. This analysis highlights that both correctly making uncommon diagnoses and adhering to new guidelines presented challenges during our implementation process. IMPLICATIONS: Implementing mifepristone and misoprostol for EPL in our EDs achieved lower rates of pregnancy resolution compared to outpatient management. Complex uncommon diagnoses and implementing new care pathways in EDs may have contributed to complications and highlight opportunities for improvement. Additional studies are needed to further quantify safety outcomes for EPL management in EDs. TWEETABLE ABSTRACT: ED provision of mifepristone and misoprostol for early pregnancy loss during COVID-19 was less effective than outpatient care. There were more serious complications in the ED group due to misdiagnosis and guideline nonadherence.

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.

Evaluation of the effect of Nigella sativa oil on the outcome of missed abortion in women: A randomized double-blind clinical trial.

Background and Aim: Due to the concern about the side effects of chemical drugs and their ineffectiveness, the use of natural compounds as alternatives or complementary therapies has received increasing attention. The purpose of this study was to investigate the effect of Nigella sativa oil on the outcome of missed abortion. Methods: In this double-blind clinical trial, 70 nulliparous pregnant women referred to Hajar Hospital and Imam Ali clinics of Shahrekord and had missed abortion before the 12-week gestational age were selected and randomly divided into two interventions and control groups. The intervention group received 5 g of Nigella sativa oil alone daily for up to 3 days and the control group received a placebo. In case of nonresponse, 3 days after the last dose of medication or placebo, 800 µg of misoprostol (vaginal) were used. Data were analyzed by SPSS software. The chi-square test, Fisher's exact test, independent t-test and paired t-test were used for analytical statistics. Results: According to the results, 18 cases (51.4%) in the intervention group and seven cases (20%) in the control group showed complete evacuation of uterine contents which had a significant difference (p < 0.05). The frequency of vagina physical examination and type of hemorrhage did not show any significant difference between the two groups before and after the intervention. After the intervention, human chorionic gonadotropin (HCG) was significantly decreased in the intervention group but did not change in the control group (p < 0.05). The frequency of adverse events in the intervention group was three (8.6%) and in the control group was one (2.9%) which had no significant difference. Conclusion: Nigella sativa improves the outcome of missed abortion by reducing HCG and facilitating cervix dilatation and delivery of uterine contents.

Comparative study of second-line labor induction methods in patients with unfavorable cervix after first-line low-dose oral misoprostol.

OBJECTIVE: The present study aimed to evaluate low-dose oral misoprostol induction, and compare different methods used in second-line induction in patients with a Bishop score less than 6. METHODS: This retrospective study analyzed the medical history and courses of pregnancy of all patients induced with first-line of low-dose oral misoprostol (50 µg every 4 h with a total of 200 µg/24 h) from April 2021 to June 2022 in a university hospital center, and reported outcomes according to the second-line method of induction. RESULTS: Among 437 labor inductions with low-dose oral misoprostol, 120 patients required a second-line induction. Predictive factors of first-line failure were higher body mass index (P = 0.011), absence of premature rupture of membranes (P = 0.021) and earlier term of pregnancy (P < 0.001). Regarding second methods of induction of labor, time from induction to delivery was shorter in the oxytocin group than the dinoprostone and misoprostol groups (24.0 vs. 41 and 51.0 h, respectively; P < 0.001), and was also significantly shorter in the dinoprostone than the misoprostol group (P = 0.048). Cesarean section rates did not differ between the three groups (P = 0.651). There were no clinically significant differences in adverse events between the groups. CONCLUSION: Normal body mass index, previous rupture of membranes and later term of induction of labor were the three favoring success factors during first-line oral misoprostol. In cases of a Bishop score <6, oxytocin may be the best option to reduce duration to delivery, with the same maternal-fetal outcomes, including a similar rate of vaginal delivery.

A Randomized Controlled Trial Comparing the Management of Incomplete Abortion with Oral 600 mg Misoprostol with Manual Vacuum Aspiration (MVA).

Introduction: In the first trimester, almost one in five identified pregnancies end in spontaneous miscarriage, and another 22% result in induced abortion. After a spontaneous and/or induced abortion, there may be retained products of conception (POC). Because of its relatively poor efficacy and the unpredictability of the time interval until spontaneous evacuation, expectant treatment is not often chosen by healthcare professionals. In view of these facts, the current study's objective was to weigh the effectiveness of MVA and oral misoprostol 600 mg in managing incomplete abortion. Materials and Procedures: The investigation was conducted at the tertiary care center in India. The survey was conducted for one year. Subjects were selected from those attending the department for either spontaneous or induced abortions. A total of 230 women were randomly assigned to receive the interventions of a single dose of oral misoprostol 600 mcg or MVA. They were equally distributed to two groups and observed for the various parameters of success, signs and symptoms, satisfaction, and complications. The obtained values were compared statistically for the significance at <0.05 of P values. Results: Of the 200 subjects (30 lost to follow-up), there was no significant variance in the demographics, clinical outcomes, and complications between the groups. However, the pain, fever, shivering, and satisfaction parameters were statistically variant between the groups. Fever, shivering, and pain were lower for the MISO subjects while satisfaction was reported higher from subjects in MISO group. Conclusion: MISO and MVA are acceptable, safe, and efficient therapies for first-trimester un-complicated incomplete abortion. Nonetheless, misoprostol appears to be a marginally superior option to MVA in terms of accessibility, low therapy costs, reduced pain, and reduced demand for specialized personnel or equipment.

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)

Third stage of labor: evidence-based practice for prevention of adverse maternal and neonatal outcomes.

The third stage of labor is defined as the time period between delivery of the fetus through delivery of the placenta. During a normal third stage, uterine contractions lead to separation and expulsion of the placenta from the uterus. Postpartum hemorrhage is a relatively common complication of the third stage of labor. Strategies have been studied to mitigate the risk of postpartum hemorrhage, leading to the widespread implementation of active management of the third stage of labor. Initially, active management of the third stage of labor consisted of a bundle of interventions including administration of a uterotonic agent, early cord clamping, controlled cord traction, and external uterine massage. However, the effectiveness of these interventions as a bundle has been questioned, leading to abandonment of some components in recent years. Despite this, upon review of selected international guidelines, we found that the term "active management of the third stage of labor" was still used, but recommendations for and against individual interventions were variable and not necessarily supported by current evidence. In this review, we: (1) examine the physiology of the third stage of labor, (2) present evidence related to interventions that prevent postpartum hemorrhage and promote maternal and neonatal health, (3) review current global guidelines and recommendations for practice, and (4) propose future areas of investigation. The interventions in this review include pharmacologic agents to prevent postpartum hemorrhage, cord clamping, cord milking, cord traction, cord drainage, early skin-to-skin contact, and nipple stimulation. Treatment of complications of the third stage of labor is outside of the scope of this review. We conclude that current evidence supports the use of effective pharmacologic postpartum hemorrhage prophylaxis, delayed cord clamping, early skin-to-skin contact, and controlled cord traction at delivery when feasible. The most effective uterotonic regimens for preventing postpartum hemorrhage after vaginal delivery include oxytocin plus ergometrine; oxytocin plus misoprostol; or carbetocin. After cesarean delivery, carbetocin or oxytocin as a bolus are the most effective regimens. There is inconsistent evidence regarding the use of tranexamic acid in addition to a uterotonic compared with a uterotonic alone for postpartum hemorrhage prevention after all deliveries. Because of differences in patient comorbidities, costs, and availability of resources and staff, decisions to use specific prevention strategies are dependent on patient- and system-level factors. We recommend that the term "active management of the third stage of labor" as a combined intervention no longer be used. Instead, we recommend that "third stage care" be adopted, which promotes the implementation of evidence-based interventions that incorporate practices that are safe and beneficial for both the woman and neonate.

Comparison of Misoprostol with Foley Catheter vs Misoprostol alone for Cervical Ripening and Induction of Labor in Patients with Premature Rupture of Membrane: A Randomized Clinical Trial Study.

Background: This study evaluates the effect of misoprostol alone in comparison with misoprostol with Foley catheter in preparing the cervix for induction of labor in women with premature rupture of the amniotic sac. Materials and Methods: This randomized clinical trial study was performed from 2017 to 2019 on 206 pregnant women with singleton pregnancy and gestational age more than 36 weeks, whose rupture of the amniotic sac had occurred less than 12 hours and had a Bishop score less than 4. These women were randomly assigned to two groups of Foley catheters with misoprostol (intervention group, P = 103) or misoprostol alone (control group, P = 103) to induce labor. In both groups, sublingual misoprostol (25 micrograms) was administered at intervals of 4-6 hours. The collected data were analyzed by SPSS.21 software. Results: There is no significant difference between age and Bishop score in the two groups (P = 0.19, P = 0.31, respectively). Lower doses (0 to 3) of misoprostol were used in the intervention group versus 0 to 5 doses in the control group (P = 0.001). Delivery time was shorter in the intervention group (10.83 hours vs. 13.10 hours in the control group, P = 0.001). Also, the probability of complications such as fever, tachysystole, and hospitalization of an infant in the neonatal intensive care unit (NICU) did not increase. Conclusion: An intracervical Foley catheter with misoprostol is more effective in inducing labor in pregnancies with premature rupture of the membranes than using misoprostol alone and can be a safe and effective option.

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.

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.

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.

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.

Vaginal misoprostol versus vaginal dinoprostone for cervical ripening and induction of labour: An individual participant data meta-analysis of randomised controlled trials.

BACKGROUND: Induction of labour (IOL) is common practice and different methods carry different effectiveness and safety profiles. OBJECTIVES: To compare the effectiveness, and maternal and perinatal safety outcomes of IOL with vaginal misoprostol versus vaginal dinoprostone using individual participant data from randomised clinical trials. SEARCH STRATEGY: The following databases were searched from inception to March 2023: CINAHL Plus, ClinicalTrials.gov, Cochrane Pregnancy and Childbirth Group Trial Register, Ovid Embase, Ovid Emcare, Ovid MEDLINE, Scopus and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: Randomised controlled trials (RCTs), with viable singleton gestation, no language restrictions, and all published and unpublished data. DATA COLLECTION AND ANALYSIS: An individual participant data meta-analysis was carried out. MAIN RESULTS: Ten of 52 eligible trials provided individual participant data, of which two were excluded after checking data integrity. The remaining eight trials compared low-dose vaginal misoprostol versus dinoprostone, including 4180 women undergoing IOL, which represents 32.8% of all participants in the published RCTs. Of these, 2077 were assigned to low-dose vaginal misoprostol and 2103 were assigned to vaginal dinoprostone. Compared with vaginal dinoprostone, low-dose vaginal misoprostol had a comparable rate of vaginal birth. Composite adverse perinatal outcomes did not differ between the groups. Compared with vaginal dinoprostone, composite adverse maternal outcomes were significantly lower with low-dose vaginal misoprostol (aOR 0.80, 95% CI 0.65-0.98, P = 0.03, I2 = 0%). CONCLUSIONS: Low-dose vaginal misoprostol and vaginal dinoprostone for IOL are comparable in terms of effectiveness and perinatal safety. However, low-dose vaginal misoprostol is likely to lead to a lower rate of composite adverse maternal outcomes than vaginal dinoprostone.

Desmopressin, Misoprostol, nor Carboprost Affect Platelet Aggregability Following Traumatic Brain Injury and Aspirin.

INTRODUCTION: Desmopressin (DDAVP) has been utilized clinically in patients taking aspirin (ASA) to improve drug-induced platelet dysfunction. Misoprostol and carboprost, prostaglandin analogs commonly used for postpartum hemorrhage, may also induce platelet aggregation. The aim of this study was to determine the effects of DDAVP, misoprostol, and carboprost administration on platelet aggregability following traumatic brain injury (TBI) in mice treated with ASA. METHODS: Male C57BL/6 mice were randomized into seven groups (n = 5 each): untouched, ASA only, Saline/TBI, ASA/TBI, ASA/TBI/DDAVP 0.4 µg/kg, ASA/TBI/misoprostol 1 mg/kg, and ASA/TBI/carboprost 100 µg/kg. TBI was induced via a weight drop model 4-h after ASA (50 mg/kg) gavage. Mice were given an intraperitoneal injection of DDAVP, misoprostol, or carboprost 10 minutes after TBI. In vivo testing was completed utilizing tail vein bleed. Mice were sacrificed 30-min posttreatment and blood was collected via cardiac puncture. Whole blood was analyzed via Multiplate impedance aggregometry, rotational thromboelastometry, and TEG6s. RESULTS: Mice receiving misoprostol after ASA/TBI demonstrated decreased tail vein bleeding times compared to ASA only treated mice. However, mice treated with misoprostol following ASA and TBI demonstrated decreased platelet aggregability compared to untouched mice and TBI only mice within the arachidonic acid agonist pathway. By contrast, DDAVP and carboprost did not significantly change platelet aggregability via adenosine diphosphate or arachidonic acid following ASA and TBI. However, DDAVP did decrease the platelet contribution to clot via rotational thromboelastometry. CONCLUSIONS: Reversal of medication-induced platelet inhibition has become increasingly controversial after TBI. Based on these results, DDAVP, misoprostol, nor carboprost consistently improve platelet aggregability following TBI in those also treated with ASA.

Randomized controlled study comparing oral misoprostol with intramuscular oxytocin in active management of third stage of labour.

Objective: The study aimed to compare the effectiveness and side effects of 600 µg of oral Misoprostol with 10 IU intramuscular oxytocin in managing the third stage of labor. Methods: This open-label, randomized controlled trial included 260 low-risk women in the second stage of labor with anticipated vaginal delivery. They were randomly assigned, to receive either 600 µg of misoprostol orally or 10 IU of oxytocin intramuscularly. The primary outcomes were blood loss during delivery and incidence of postpartum hemorrhage, evaluated using intention-to-treat analysis. Significance was set at P≤0.05. Results: Baseline characteristics were similar in both groups (P>0.05). The misoprostol group had a significantly lower blood loss than that of the oxytocin group (306.557±176.44 mL vs. 349.37±135.50 mL; relative difference [RD], -12.251 [95% confidence intervals [CI], -22.528 to -1.575]; P=0.012). Incidence of postpartum hemorrhage was similar in both the groups (relative risk [RR], 0.952 [95% CI, 0.543 to 1.671]; P=0.865). Additional oxytocic therapy requirement was also comparable (RR, 1.143 [95% CI, 0.671 to 1.947]; P=0.623). Nausea, shivering, and mean increase in temperature were significantly more common in the misoprostol group than in the oxytocin-parturient group. Conclusion: In this study, 600 µg oral misoprostol was superior to intramuscular 10 IU oxytocin in reducing blood loss at birth, and equally effective in preventing postpartum hemorrhage. However, misoprostol exhibited more side effects compared to that of oxytocin.

Optimal misoprostol dosing among patients with a body mass index greater than 30: a randomized controlled trial.

BACKGROUND: Patients with obesity experience an increased duration of labor with an increased risk for perinatal morbidity. When compared with parturients without obesity, they also experience fewer uterine contractions after administration of misoprostol. It is unclear if the same dose of misoprostol should be used for induction of labor in patients with obesity compared to non-obese patients. Therefore, we sought to investigate if a higher dose of misoprostol for patients with obesity is more effective. OBJECTIVE: This study aimed to determine if 50 µg compared with 25 µg of vaginal misoprostol reduced the time from induction start to delivery among patients with obesity. STUDY DESIGN: We performed a double-blinded, pragmatic randomized controlled trial, between June 1, 2022, and July 17, 2023. Patients with a body mass index ≥30 kg/m2 who underwent labor induction at ≥ 36 weeks' gestation, had a singleton gestation, and a cervical dilation ≤3 cm at admission were included. Patients were excluded if they had a contraindication to vaginal delivery or misoprostol administration. Patients were randomized to 25 or 50 µg of vaginal misoprostol, stratified by parity, body mass index <40 kg/m2 or ≥40 kg/m2, and provider intent to use mechanical dilation at the onset of labor induction. Usual labor management was followed at the discretion of the provider. The primary outcome was time from induction to delivery. A priori, we estimated that 90 subjects per group (N=180) were needed for an 85% power to detect a 3-hour difference between groups with a type I error of 5%. Analysis was by intention-to-treat. A 2-sample t test was used for the primary outcome, Cohen's d was used as a measure of effect, and P values were reported. RESULTS: Of the 180 patients randomized, 88 were assigned to the 25 µg group and 92 were assigned to the 50 µg group. Of those, 96.1% of patients received the designated intervention. The baseline characteristics were similar between groups. No difference was found in the primary outcome of time to delivery (21.6 hours vs 18.6 hours; d=.28; 95% confidence interval, -0.02 to 0.57). In a planned subgroup analysis, multiparous patients delivered faster in the 50 µg group (15.2 hours vs 12.0 hours; d=.51; 95% confidence interval, 0.04-0.97). The risk for tachysystole associated with fetal heart tracing changes was rare overall (2.2%) and not significantly different between groups. No differences in maternal or neonatal adverse effects were observed. CONCLUSION: Patients with obesity who underwent cervical ripening with 50 µg of vaginal misoprostol experienced a similar time to delivery when compared with those who received 25 µg of misoprostol. However, multiparous patients had a significantly reduced time to delivery when 50 µg was used. A higher dose of misoprostol may be a promising intervention for reducing time in labor, which warrants further study.

Triumphs and trials with the UK abortion law: The power of collaboration in abortion reform.

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.

Protective effect of misoprostol against paclitaxel-induced cardiac damage in rats.

OBJECTIVE: One of the most critical reasons for limiting cancer treatment is the toxic effects of anti-cancer drugs on healthy tissues and organs. This study aims to investigate the possible protective effects of misoprostol (MS) against the damage that arises from paclitaxel (PT), an anti-cancer pharmacological agent, in the rat heart using histopathological and biochemical analyses. METHODS: In this study, four groups, each containing seven animals, were formed by random selection from 28 Sprague Dawley female rats. Control group rats were administered 1 ml of normal saline orally and intraperitoneally (i.p.) for six days. While the PT group rats were administered PT at a dose of 2 mg/kg intraperitoneally (i.p.) on days 0, 2, 4, and 6, the MS group was administered MS at a dose of 0.2 mg/kg in 1 ml normal saline by oral gavage for six days. PT and MS were administered to the PT + MS group rats in the same dose and route as the previous groups. RESULTS: Administration of PT increased serum lactate dehydrogenase (LDH), cardiac troponin I (cTn-I), creatine kinase isoenzyme MB (CK-MB), and brain natriuretic peptide (BNP) levels. PT administration also decreased the levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in the heart tissue while increasing the level of malondialdehyde (MDA) (p < 0.05). In histopathological examinations, pathological changes, such as edema, congestion, hemorrhage, apoptosis, and degeneration, occurred in the heart tissue of PT-treated rats. The negative changes in histopathological and biochemical parameters that occurred in the PT group were almost not observed in the PT + MS group (p < 0.005). CONCLUSION: When the findings were evaluated, it was concluded that MS protects the heart tissue from the harmful effects of PT, probably due to its antioxidant, anti-apoptotic and TNF-alpha suppressive effects.

Investigating the prilling/vibration technique to produce gastric-directed drug delivery systems for misoprostol.

Prilling/vibration technique to produce oral microcapsules was explored to achieve local delivery of misoprostol (MIS), a prostaglandin E1 analogue indicated for the treatment of gastric-duodenal ulcers, at the gastric mucosa. To improve MIS chemical stability and reduce its associated systemic side effects, drug delivery systems were designed and developed as microcapsules consisting of a core of sunflower oil and MIS (Fs6 and Fs14) or a MIS complex with hydroxypropyl-beta-cyclodextrin (HP-ß-CD) (Fs18), confirmed by specific studies, and a polymeric shell. The produced microcapsules showed high encapsulation efficiencies for those with MIS solubilized in sunflower oil (>59.86 %) and for the microcapsules with MIS/HP-ß-CD (97.61 %). To demonstrate the ability of these systems to deliver MIS into the stomach, swelling and drug release experiments were also conducted in simulated gastric fluid. Among the three formulations, FS18 showed gastric release within 30 min and was the most advantageous formulation because the presence of the MIS/HP-ß-CD inclusion complex ensured a greater ability to stabilise MIS in the simulated gastric environment. In addition, these new systems have a small size (<540 µm), and good flow properties and the dose of the drug could be easily adapted using different amounts of microcapsules (flexibility), making them a passepartout for different age population groups.