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Cureus Nov 2023Mifepristone and misoprostol are globally used medications that have become disparaged through the stigmatization of reproductive healthcare. Patients are hindered from... (Review)
Review
Mifepristone and misoprostol are globally used medications that have become disparaged through the stigmatization of reproductive healthcare. Patients are hindered from receiving prompt treatment in clinical scenarios where misoprostol and mifepristone are the drugs of choice. It is no exaggeration to emphasize that in cases where reproductive healthcare is concerned. The aim of this paper is to discuss the different indications of mifepristone and to delineate where the discrepancy in accessibility arises. For this systematic review, we included publications citing clinical trials involving the use and efficacy of mifepristone published in English within the date range of 2000 to 2023. Five databases were searched to identify relevant sources. These databases are Google Scholar, MEDLINE with full text through EBSCO, and three National Center for Biotechnology Information (NCBI) databases (NCBI Bookshelf, PubMed, and PubMed Central). Twenty-three records were ultimately included in this review. Mifepristone has been shown to have therapeutic effects in the treatment of psychiatric disorders, such as major depressive disorder and psychotic depression. There was a significant decrease in depression and psychiatric rating symptoms for patients taking mifepristone versus placebo with no adverse events. Mifepristone has also been shown to improve treatment course in patients with Cushing's disease (CD) who failed or are unable to undergo surgical treatment. In addition, mifepristone has been shown to be a successful treatment option for adenomyosis and leiomyomas. Patients had a statistically significant decrease in uterine volumes following mifepristone treatment, which aided in the alleviation of other symptoms, such as blood loss and pelvic discomfort. Mifepristone is a synthetic steroid that has immense potential to provide symptomatic relief in patients suffering from a wide array of complicated diseases. Historically, mifepristone has been proven to have an incredible safety profile. While further research is certainly needed, the politicization of its medical use for only one of its many indications has unfortunately led to the willful ignorance of its potential despite its evidence-based safety profile and efficacy.
PubMed: 38060710
DOI: 10.7759/cureus.48372 -
Medicine Aug 2023Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases, laparoscopic fertility preservation surgery is considered a common treatment for EMT. The present study aimed to evaluate the efficacy and safety of dienogest, leuprolide, danazol, gestrinone, mifepristone and levonorgestrel intrauterine system (LNG-IUS) in relieving symptoms and delaying the recurrence of EMT cysts after fertility protection surgery.
METHODS
We searched PubMed, the Cochrane Library, Web of Science, EMBase, China National Knowledge Infrastructure, VIP Database, China Biology Medicine disc, WanFang Data databases to collect randomized controlled trials (RCT) related to dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS as a follow-up treatment after fertility preserving surgery for EMT. After literature screening, data extraction and quality evaluation, effective rate, recurrence rate, pregnancy rate and adverse reaction rate were used as outcome indicators to evaluate the efficacy and safety of drugs. Evidence networks included in the study were drawn and publication bias was assessed. The drugs most likely to be the best postoperative treatment were explored through mixed comparison of different drugs and efficacy ranking.
RESULT
Effective rate: dienogest, leprerelin, gestrinone and LNG-IUS were better than placebo after EMT fertility preservation surgery; dienogest was superior to mifepristone and danazol. LNG-IUS is superior to danazol. LNG-IUS has the highest potential for improving the effectiveness of EMT symptoms. Recurrence rate: the application of dienogest, leuprolide, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was lower than that of placebo; dienogest and LNG-IUS were lower than danazol. The recurrence rate of dinorgestrel was the last place with the highest performance. Pregnancy rate: in the cases with fertility requirements, dienogest and,leuprolide were better than placebo after EMT fertility preservation surgery; dienogest was superior to danazol, gestrinone and mifepristone. Leuprolide is superior to danazol and gestrinone. The first rank of dienogest pregnancy rate was the highest. Adverse reaction rate: the application of dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was higher than that of placebo. After placebo, LNG-IUS had the highest adverse reaction rate.
CONCLUSION
For patients after fertility preserving surgery for EMT, the recurrence rate of dienogest was the last place with highest preference. The first rank of dienogest pregnancy was the highest.
Topics: Female; Humans; Endometriosis; Danazol; Gestrinone; Leuprolide; Mifepristone; Network Meta-Analysis; Levonorgestrel
PubMed: 37543781
DOI: 10.1097/MD.0000000000034496 -
Contraception Nov 2023This study aimed to update our 2019 systematic review of data on the effectiveness and safety of misoprostol-only for first-trimester abortion. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study aimed to update our 2019 systematic review of data on the effectiveness and safety of misoprostol-only for first-trimester abortion.
STUDY DESIGN
We searched PubMed on December 18, 2022, to find published articles describing the outcomes of treatment with misoprostol-only for abortion of viable intrauterine pregnancy at ≤91 days of gestation. From each article identified, two authors independently abstracted relevant data about each group of patients treated with a distinct regimen. We assessed the risk of bias using four defined indicators. We estimated the proportion of patients with treatment failure using meta-analytic methods as well as the proportion hospitalized or transfused after treatment. We examined associations between treatment failure and selected characteristics of the groups.
RESULTS
We identified 49 papers with 66 groups that collectively included 16,354 evaluable patients, of whom 2960 (meta-analytic estimate 15%, 95% CI 12%, 19%) had treatment failures. Of 9228 patients assessed for ongoing pregnancy after treatment, 521 (meta-analytic estimate 6%, 95% CI 5%, 8%) had that condition. Failure risk was significantly associated with misoprostol dose, the total allowed number of doses, the maximum duration of dosing, and certain indicators of risk of bias. Among 11,007 patients allowed to take at least three misoprostol doses, the first consisting of misoprostol 800 mcg administered vaginally, sublingually, or buccally, the meta-analytic estimate of the failure risk was 11% (95% CI 8%, 14%). At most, 0.2% of 15,679 evaluable patients were hospitalized or received transfusions.
CONCLUSIONS
Although some studies in this updated review were adjudicated to have a high risk of bias, the results continue to support the key conclusion of our 2019 analysis: misoprostol-only is effective and safe for the termination of first-trimester intrauterine pregnancy.
IMPLICATIONS
Misoprostol-only is a safe and effective option for medication abortion in the first trimester if mifepristone is unavailable or inaccessible.
Topics: Pregnancy; Female; Humans; Misoprostol; Abortifacient Agents; Pregnancy Trimester, First; Mifepristone; Abortion, Induced; Abortifacient Agents, Nonsteroidal
PubMed: 37517447
DOI: 10.1016/j.contraception.2023.110132 -
Obstetrics and Gynecology Dec 2023To assess the risk difference of uterine rupture when using current mifepristone and misoprostol regimens for second-trimester abortion among individuals with prior... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the risk difference of uterine rupture when using current mifepristone and misoprostol regimens for second-trimester abortion among individuals with prior cesarean birth compared with those without prior cesarean birth.
DATA SOURCES
We searched the terms second trimester, induction, mifepristone, and abortion in PubMed, EMBASE, POPLINE, ClinicalTrials.gov , and Cochrane Library from inception until December 2022.
METHODS OF STUDY SELECTION
We included randomized trials and observational studies including a mixed cohort, with and without uterine scar, of individuals at 14-28 weeks of gestation who used mifepristone and misoprostol to end a pregnancy or to manage a fetal death. We excluded case reports, narrative reviews, and studies not published in English. Two reviewers independently screened studies.
TABULATION, INTEGRATION, AND RESULTS
Absolute risks with binomial CIs were calculated from pooled data. Using R software, we estimated total risk difference by the Mantel-Haenszel random-effects method without continuity correction. For studies with zero events, a continuity correction of 0.5 was applied for individual risk differences and plotted graphically with forest plots. Statistical heterogeneity was assessed with Higgins I2 statistics. Funnel plot assessed for publication bias. Of 198 articles identified, 22 met the inclusion criteria: seven randomized trials (n=923) and 15 observational studies (n=6,195). Uterine rupture risk with prior cesarean birth was 1.1% (10/874) (95% CI 0.6-2.1) and without prior cesarean birth was 0.01% (2/6,244) (95% CI 0.0-0.12). The risk difference was 1.23% (95% CI 0.46-2.00, I2 =0%). Of the 12 reported uterine ruptures, three resulted in hysterectomy.
CONCLUSION
Uterine rupture with mifepristone and misoprostol use during second-trimester induction abortion is rare, with the risk increased to 1% in individuals with prior cesarean birth.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42022302626.
Topics: Pregnancy; Female; Humans; Misoprostol; Mifepristone; Pregnancy Trimester, Second; Uterine Rupture; Abortion, Induced
PubMed: 37884011
DOI: 10.1097/AOG.0000000000005259 -
BJOG : An International Journal of... Jan 2024Tubal ectopic pregnancy (TEP) is a common gynaecological emergency. Several medical and surgical treatment options exist, but it is not clear which is the safest and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tubal ectopic pregnancy (TEP) is a common gynaecological emergency. Several medical and surgical treatment options exist, but it is not clear which is the safest and most effective treatment.
OBJECTIVES
To compare the effectiveness of expectant, medical and surgical treatment options for TEP using a systematic review and network meta-analysis.
SEARCH STRATEGY
MEDLINE, EMBASE, and CENTRAL from inception till September 2022.
SELECTION CRITERIA
Randomised trials that evaluated any treatment option for woman with a TEP.
DATA COLLECTION AND ANALYSIS
We performed pairwise and network meta-analyses using a random effect model. We assessed the studies' risk of bias, heterogeneity and network inconsistency. We reported primarily on TEP resolution and treatment failure using relative risk (RR) and 95% confidence-intervals (CI).
MAIN RESULTS
We included 31 randomised trials evaluating ten treatments (n = 2938 women). Direct meta-analysis showed no significant benefit for using methotrexate compared to expectant management for TEP resolution. Network meta-analysis showed similar effect-size for most conservative treatment options compared to expectant management for TEP resolution (glucose intra-sac instillation vs. expectant RR 0.84, 95% CI 0.63-1.12; methotrexate intra-sac instillation vs. expectant RR 0.91, 95% CI 0.75-1.10; multi-dose methotrexate vs. expectant RR 1.00, 95% CI 0.88-1.15; prostaglandin intra-sac instillation vs. expectant RR 0.75, 95% CI 0.53-1.07; salpingotomy vs. expectant RR 0.99, 95% CI 0.84-1.16; single dose methotrexate vs. expectant RR 0.97, 95% CI 0.85-1.10; single dose methotrexate + mifepristone vs. expectant RR 1.09, 95% CI 0.89-1.33). All treatment options showed a higher risk of failure compared to salpingectomy.
CONCLUSIONS
There is insufficient evidence to support the use of any medical treatment option for TEP over expectant management.
Topics: Pregnancy; Female; Humans; Methotrexate; Network Meta-Analysis; Mifepristone; Prostaglandins; Pregnancy, Ectopic
PubMed: 37443463
DOI: 10.1111/1471-0528.17594 -
American Journal of Obstetrics and... Mar 2024Several systematic reviews and meta-analyses have summarized the evidence on the efficacy and safety of various outpatient cervical ripening methods. However, the method... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Several systematic reviews and meta-analyses have summarized the evidence on the efficacy and safety of various outpatient cervical ripening methods. However, the method with the highest efficacy and safety profile has not been determined conclusively. We performed a systematic review and network meta-analysis of published randomized controlled trials to assess the efficacy and safety of cervical ripening methods currently employed in the outpatient setting.
DATA SOURCES
With the assistance of an experienced medical librarian, we performed a systematic search of the literature using MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov. We systematically searched electronic databases from inception to January 14, 2020.
STUDY ELIGIBILITY CRITERIA
We considered randomized controlled trials comparing a variety of methods for outpatient cervical ripening.
METHODS
We conducted a frequentist random effects network meta-analysis employing data from randomized controlled trials. We performed a direct, pairwise meta-analysis to compare the efficacy of various outpatient cervical ripening methods, including placebo. We employed ranking strategies to determine the most efficacious method using the surface under the cumulative ranking curve; a higher surface under the cumulative ranking curve value implied a more efficacious method. We assessed the following outcomes: time from intervention to delivery, cesarean delivery rates, changes in the Bishop score, need for additional ripening methods, incidence of Apgar scores <7 at 5 minutes, and uterine hyperstimulation.
RESULTS
We included data from 42 randomized controlled trials including 6093 participants. When assessing the efficacy of all methods, 25 μg vaginal misoprostol was the most efficacious in reducing the time from intervention to delivery (surface under the cumulative ranking curve of 1.0) without increasing the odds of cesarean delivery, the need for additional ripening methods, the incidence of a low Apgar score, or uterine hyperstimulation. Acupressure (surface under the cumulative ranking curve of 0.3) and primrose oil (surface under the cumulative ranking curve of 0.2) were the least effective methods in reducing the time to delivery interval. Among effective methods, 50 mg oral mifepristone was associated with the lowest odds of cesarean delivery (surface under the cumulative ranking curve of 0.9).
CONCLUSION
When balancing efficacy and safety, vaginal misoprostol 25 μg represents the best method for outpatient cervical ripening.
Topics: Pregnancy; Female; Humans; Misoprostol; Oxytocics; Cervical Ripening; Network Meta-Analysis; Outpatients; Labor, Induced
PubMed: 38462254
DOI: 10.1016/j.ajog.2022.09.043 -
BMJ Sexual & Reproductive Health Jan 2024We sought to determine whether there is evidence to recommend progesterone for individuals not wishing to complete a medication abortion after taking mifepristone.
BACKGROUND
We sought to determine whether there is evidence to recommend progesterone for individuals not wishing to complete a medication abortion after taking mifepristone.
METHODS
We undertook an updated systematic review including a primary search for studies in which individuals received progesterone to reverse the effects of mifepristone, and a secondary search for studies in which individuals received mifepristone alone. We searched PubMed, Embase, Cochrane, CINAHL and grey literature up to December 2022. We used the Joanna Briggs Institute critical appraisal tools for risk of bias assessment. We compared ongoing pregnancy rates among individuals treated with progesterone to those managed expectantly.
RESULTS
We did not find new studies in our secondary search. For the main search, we included three case series and one randomised controlled trial. Data were available for 561 individuals who received progesterone after mifepristone, of whom 271 (48%) had ongoing pregnancies. The quality of the evidence in the case series was low due to methodological and ethical issues. Enrollment in the randomised trial stopped early due to bleeding events in both arms. The ongoing pregnancy rate for individuals ≤7 weeks who received progesterone was 42% (95% CI 37-48) compared with 22% (95% CI 11-39) for mifepristone alone. At 7-8 weeks, the ongoing pregnancy rate was 62% (95% CI 52-71) in the progesterone group and 50% (95% CI 15- 85) in the mifepristone alone group.
CONCLUSION
Based mostly on poor-quality data, it appears the ongoing pregnancy rate in individuals treated with progesterone after mifepristone is not significantly higher compared to that of individuals receiving mifepristone alone.
Topics: Pregnancy; Female; Humans; Progesterone; Mifepristone; Abortion, Induced; Pregnancy Rate
PubMed: 37863512
DOI: 10.1136/bmjsrh-2023-201875 -
American Journal of Obstetrics &... Feb 2024This study aimed to assess if the use of mechanical dilation at the time of induction termination is associated with changes in the time from initiation of labor to... (Review)
Review
OBJECTIVE
This study aimed to assess if the use of mechanical dilation at the time of induction termination is associated with changes in the time from initiation of labor to expulsion of the fetus (induction-to-expulsion interval) and with the frequency of health complications when compared with medication management alone.
DATA SOURCES
PubMed, CINAHAL, Scopus, and the Cochrane Central Register of Controlled Trials were queried from January 2000 to May 2023.
STUDY ELIGIBILITY CRITERIA
We included randomized controlled trials of individuals who were assigned to undergo mechanical dilation (ie, laminaria, Dilapan-S, and intracervical Foley balloon catheter) in combination with the use of medication and compared it with the outcomes of medication use (eg, prostaglandins, antiprogestins, oxytocin) alone.
METHODS
The primary outcome was the induction-to-expulsion interval. The secondary outcomes were the incidence of clinical chorioamnionitis, sepsis, hemorrhage, the need for blood transfusion and uterotonics, cervical laceration, the need for adjunctive procedures (eg, dilation and curettage), failed induction termination, uterine rupture, intensive care unit admission, or death. Assessment of bias was performed using the Cochrane Risk of Bias tool. A subgroup analysis was performed among studies deemed to be at low risk of bias.
RESULTS
Of 864 abstracts identified, 11 met the inclusion criteria. Five studies demonstrated a shorter induction-to-expulsion interval among those randomized to mechanical dilation, whereas 6 studies demonstrated a similar or longer induction-to-expulsion interval. There were no significant differences reported in the frequency of any adverse outcomes between the trial arms. In addition, most studies (8/11) exhibited moderate to high levels of bias. In an analysis of the 3 studies deemed to have a low risk of bias, 1 (n=60) demonstrated a longer induction-to-expulsion interval with adjunctive laminaria, 1 (n=60) demonstrated a shorter induction-to-expulsion interval with adjunctive intracervical Foley balloon catheter use, and 1 demonstrated no difference in the induction-to-expulsion interval with adjunctive Dilapan-S use (n=180).
CONCLUSION
Only a small number of studies, most of which were of low quality, assessed mechanical dilation for induction termination. The results of these studies were inconsistent in terms of the induction-to-expulsion interval of adjunctive mechanical methods in comparison with medication management alone. Studies did not reveal significant differences between the groups in adverse outcomes. Further research should investigate the use of mechanical dilation at the time of induction termination using high-quality methods.
Topics: Pregnancy; Female; Humans; Dilatation; Oxytocics; Labor, Induced; Oxytocin; Misoprostol; Randomized Controlled Trials as Topic
PubMed: 38128782
DOI: 10.1016/j.ajogmf.2023.101263