-
BMC Complementary Medicine and Therapies Jul 2023Misoprostol is the choice drug for inducing an abortion with intrauterine fetal death, but it has several side effects that increase with accumulating the dose received.... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the effect of vaginal misoprostol and evening primrose oil capsule with misoprostol alone on the consequences of abortion in women with intrauterine fetal death: a randomized clinical trial.
BACKGROUND
Misoprostol is the choice drug for inducing an abortion with intrauterine fetal death, but it has several side effects that increase with accumulating the dose received. Induction abortion with cheap and non-invasive methods with minimal complications is essential. This study aimed to compare the effect vaginal misoprostol plus vaginal evening primrose oil capsule with vaginal misoprostol alone on the consequences of abortion in pregnant women with intrauterine fetal death at 12-20 weeks of pregnancy.
METHODS
This study is a randomized, triple-blind clinical trial with two parallel groups at a ratio of 1:1. We randomized 82 women with indications of termination of pregnancy due to intrauterine fetal death into two groups. The experimental group (n = 42) received 200 mcg of misoprostol tablet with 1000 mg evening primrose oil capsule intravaginal. The control group (n = 40) received 200 mcg of misoprostol tablet with 1000 mg evening primrose oil placebo capsule intravaginal. Both groups received the drugs every 4 h for up to five doses. The primary outcome was the mean induction-to-fetal expulsion interval. Secondary outcomes were the mean dose of misoprostol, the highest pain intensity in the induction-to-fetal expulsion interval, the frequency of participants requiring blood transfusion, curettage, and the frequency of side effects of misoprostol or evening primrose oil. Pain intensity was measured through the Visual Analog Scale.
RESULTS
The mean age of the experimental group was 32.30 ± 6.19 years, and the control group was 30.27 ± 7.68 years. The mean gestational age of the experimental group was 15.29 ± 2.26 weeks, and the control group was 15.10 ± 1.89 weeks. The mean induction-to-fetal expulsion interval in the experimental group (3.12 ± 2.17 h) was significantly lower than that in the control group (8.40 ± 4.1 h) (p < 0.001). The mean dose of misoprostol received in the experimental group (271.42 ± 115.39 mcg) was significantly lower than that in the control group (520 ± 201.53 mcg) (p < 0.001). Also, the mean pain intensity in the experimental group (5.02 ± 0.60) was significantly lower than that in the control group (8.65 ± 1.001) (p < 0.001). The two groups were not significantly different in the frequency of blood transfusion requirements, analgesia and drug side effects. The need for curettage in the experimental group (4.8%) was significantly lower than that in the control group (47.5%) (p < 0.001).
CONCLUSIONS
Vaginal administration of evening primrose oil with misoprostol reduced duration of time of fetal expulsion, pain intensity, mean dose of misoprostol received, and the need for curettage in participants. Therefore, we suggest this method for induced abortion in women with intrauterine fetal death.
TRIAL REGISTRATION
IRCT20181207041873N3. Dated 16/2/2021 prospectively registered https://en.irct.ir/user/trial/53681/view .
Topics: Pregnancy; Female; Humans; Adult; Infant; Misoprostol; Abortion, Induced; Linoleic Acids; Fetal Death; Stillbirth
PubMed: 37468886
DOI: 10.1186/s12906-023-04082-w -
The Cochrane Database of Systematic... May 2022Medical abortion became an alternative method of pregnancy termination following the development of prostaglandins and antiprogesterone in the 1970s and 1980s. Recently,... (Review)
Review
BACKGROUND
Medical abortion became an alternative method of pregnancy termination following the development of prostaglandins and antiprogesterone in the 1970s and 1980s. Recently, synthesis inhibitors of oestrogen (such as letrozole) have also been used to enhance efficacy. The most widely researched drugs are prostaglandins (such as misoprostol, which has a strong uterotonic effect), mifepristone, mifepristone with prostaglandins, and letrozole with prostaglandins. More evidence is needed to identify the best dosage, regimen, and route of administration to optimise patient outcomes. This is an update of a review last published in 2011.
OBJECTIVES
To compare the effectiveness and side effects of different medical methods for first trimester abortion.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, Global Health, and LILACs on 28 February 2021. We also searched Clinicaltrials.gov and the World Health Organization's (WHO) International Clinical Trials Registry Platform, and reference lists of retrieved papers.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) that compared different medical methods for abortion before the 12th week of gestation. The primary outcome is failure to achieve complete abortion. Secondary outcomes are mortality, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the method.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected and evaluated studies for inclusion, and assessed the risk of bias. We processed data using Review Manager 5 software. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 99 studies in the review (58 from the original review and 41 new studies). 1. Combined regimen mifepristone/prostaglandin Mifepristone dose: high-dose (600 mg) compared to low-dose (200 mg) mifepristone probably has similar effectiveness in achieving complete abortion (RR 1.07, 95% CI 0.87 to 1.33; I = 0%; 4 RCTs, 3494 women; moderate-certainty evidence). Prostaglandin dose: 800 µg misoprostol probably reduces abortion failure compared to 400 µg (RR 0.63, 95% CI 0.51 to 0.78; I= 0%; 3 RCTs, 4424 women; moderate-certainty evidence). Prostaglandin timing: misoprostol administered on day one probably achieves more success on complete abortion than on day three (RR 1.94, 95% CI 1.05 to 3.58; 1489 women; 1 RCT; moderate-certainty evidence). Administration strategy: there may be no difference in failure of complete abortion with self-administration at home compared with hospital administration (RR 1.63, 95% CI 0.68 to 3.94; I = 84%; 2263 women; 4 RCTs; low-certainty evidence), but failure may be higher when administered by nurses in hospital compared to by doctors in hospital (RR 2.69, 95% CI 1.39 to 5.22; I = 66%; 3 RCTs, 3056 women; low-certainty evidence). Administration route: oral misoprostol probably leads to more failures than the vaginal route (RR 2.38, 95% CI 1.46 to 3.87; I = 39%; 3 RCTs, 1704 women; moderate-certainty evidence) and may be associated with more frequent side effects such as nausea (RR 1.14, 95% CI 1.03 to 1.26; I = 0%; 2 RCTs, 1380 women; low-certainty evidence) and diarrhoea (RR 1.80 95% CI 1.49 to 2.17; I = 0%; 2 RCTs, 1379 women). Compared with the vaginal route, complete abortion failure is probably lower with sublingual (RR 0.68, 95% CI 0.22 to 2.11; I = 59%; 2 RCTs, 3229 women; moderate-certainty evidence) and may be lower with buccal administration (RR 0.71, 95% CI 0.34 to 1.46; I = 0%; 2 RCTs, 479 women; low-certainty evidence), but sublingual or buccal routes may lead to more side effects. Women may experience more vomiting with sublingual compared to buccal administration (RR 1.33, 95% CI 1.01 to 1.77; low-certainty evidence). 2. Mifepristone alone versus combined regimen The efficacy of mifepristone alone in achieving complete abortion compared to combined mifepristone/prostaglandin up to 12 weeks is unclear (RR of failure 3.25, 95% CI 0.81 to 13.09; I = 83%; 3 RCTs, 273 women; very low-certainty evidence). 3. Prostaglandin alone versus combined regimen Nineteen studies compared prostaglandin alone to a combined regimen (prostaglandin combined with mifepristone, letrozole, estradiol valerate, tamoxifen, or methotrexate). Compared to any of the combination regimens, misoprostol alone may increase the risk for failure to achieve complete abortion (RR of failure 2.39, 95% CI 1.89 to 3.02; I = 64%; 18 RCTs, 3471 women; low-certainty evidence), and with more diarrhoea. 4. Prostaglandin alone (route of administration) Oral misoprostol alone may lead to more failures in complete abortion than the vaginal route (RR 3.68, 95% CI 1.56 to 8.71, 2 RCTs, 216 women; low-certainty evidence). Failure to achieve complete abortion may be slightly reduced with sublingual compared with vaginal (RR 0.69, 95% CI 0.37 to 1.28; I = 87%; 5 RCTs, 2705 women; low-certainty evidence) and oral administration (RR 0.58, 95% CI 0.11 to 2.99; I = 66%; 2 RCTs, 173 women). Failure to achieve complete abortion may be similar or slightly higher with sublingual administration compared to buccal administration (RR 1.11, 95% CI 0.71 to 1.74; 1 study, 401 women).
AUTHORS' CONCLUSIONS
Safe and effective medical abortion methods are available. Combined regimens (prostaglandin combined with mifepristone, letrozole, estradiol valerate, tamoxifen, or methotrexate) may be more effective than single agents (prostaglandin alone or mifepristone alone). In the combined regimen, the dose of mifepristone can probably be lowered to 200 mg without significantly decreasing effectiveness. Vaginal misoprostol is probably more effective than oral administration, and may have fewer side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all studies were conducted in settings with good access to emergency services, which may limit the generalisability of these results.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Spontaneous; Diarrhea; Drug Therapy, Combination; Estradiol; Female; Humans; Letrozole; Methotrexate; Mifepristone; Misoprostol; Oxytocics; Pregnancy; Pregnancy Trimester, First; Prostaglandins; Tamoxifen
PubMed: 35608608
DOI: 10.1002/14651858.CD002855.pub5 -
Reproductive Health Aug 2023Most treatments for postpartum haemorrhage (PPH) lack evidence of effectiveness. New innovations are ubiquitous but have not been synthesized for ready access. (Review)
Review
BACKGROUND
Most treatments for postpartum haemorrhage (PPH) lack evidence of effectiveness. New innovations are ubiquitous but have not been synthesized for ready access.
NARRATIVE REVIEW
Pubmed 2020 to 2021 was searched on 'postpartum haemorrhage treatment', and novel reports among 755 citations were catalogued. New health care strategies included early diagnosis with a bundled first response and home-based treatment of PPH. A calibrated postpartum blood monitoring tray has been described. Oxytocin is more effective than misoprostol; addition of misoprostol to oxytocin does not improve treatment. Heat stable carbetocin has not been assessed for treatment. A thermostable microneedle oxytocin patch has been developed. Intravenous tranexamic acid reduces mortality but deaths have been reported from inadvertent intrathecal injection. New transvaginal uterine artery clamps have been described. Novel approaches to uterine balloon tamponade include improvised and purpose-designed free-flow (as opposed to fixed volume) devices and vaginal balloon tamponade. Uterine suction tamponade methods include purpose-designed and improvised devices. Restrictive fluid resuscitation, massive transfusion protocols, fibrinogen use, early cryopreciptate transfusion and point-of-care viscoelastic haemostatic assay-guided blood product transfusion have been reported. Pelvic artery embolization and endovascular balloon occlusion of the aorta and pelvic arteries are used where available. External aortic compression and direct compression of the aorta during laparotomy or aortic clamping (such as with the Paily clamp) are alternatives. Transvaginal haemostatic ligation and compression sutures, placental site sutures and a variety of novel compression sutures have been reported. These include Esike's technique, three vertical compression sutures, vertical plus horizontal compression sutures, parallel loop binding compression sutures, uterine isthmus vertical compression sutures, isthmic circumferential suture, circumferential compression sutures with intrauterine balloon, King's combined uterine suture and removable retropubic uterine compression suture. Innovative measures for placenta accreta spectrum include a lower uterine folding suture, a modified cervical inversion technique, bilateral uterine artery ligation with myometrial excision of the adherent placenta and cervico-isthmic sutures or a T-shaped lower segment repair. Technological advances include cell salvage, high frequency focussed ultrasound for placenta increta and extra-corporeal membrane oxygenation.
CONCLUSIONS
Knowledge of innovative methods can equip clinicians with last-resort options when faced with haemorrhage unresponsive to conventional methods.
Topics: Female; Pregnancy; Humans; Postpartum Hemorrhage; Oxytocin; Misoprostol; Placenta; Hemostatics
PubMed: 37568196
DOI: 10.1186/s12978-023-01657-1 -
Infectious Diseases and Therapy Sep 2023Misoprostol is widely used for medication abortion and postpartum hemorrhage. However, it has been associated with the adverse effect of fever, which can pose challenges...
INTRODUCTION
Misoprostol is widely used for medication abortion and postpartum hemorrhage. However, it has been associated with the adverse effect of fever, which can pose challenges in management and potentially contribute to unnecessary antibiotic use. The incidence of misoprostol-induced fever in the context of medical abortion has not been extensively studied.
METHODS
This retrospective cohort study aimed to determine the incidence of fever following misoprostol administration at a tertiary care hospital in Saudi Arabia. The study included female patients who received misoprostol for pregnancy termination or management of missed or incomplete abortion between January 2017 and December 2019. Data on demographics, misoprostol dosage and route, fever characteristics, outcome of abortion, and antibiotic use were collected. Statistical analysis was preformed using appropriate tests.
RESULTS
A total of 213 patients were included in the study. The incidence of fever post-misoprostol administration was 8%. Patients who developed fever had a higher gestational age and received higher doses of misoprostol. However, no significant associations were found between other patient variables and fever incidence. Antibiotic therapy was administered to a almost half of the patients who developed fever post-misoprostol but was determined to be unnecessary in all cases.
CONCLUSION
This study contributes to the understanding of misoprostol-induced fever in the context of medical abortion. Further research is needed to explore strategies for reducing unnecessary antibiotic use in this population.
PubMed: 37704800
DOI: 10.1007/s40121-023-00865-3 -
Cureus Dec 2022In the absence of comprehensive data investigating carbetocin versus misoprostol for reducing postpartum hemorrhage (PPH) during cesarean section (CS), we performed this... (Review)
Review
In the absence of comprehensive data investigating carbetocin versus misoprostol for reducing postpartum hemorrhage (PPH) during cesarean section (CS), we performed this investigation to compare the efficiency and side events of carbetocin versus misoprostol in the protection and reduction of PPH for women who underwent CS. From inception to September 2022, we depended on searching through various databases for eligible trials involving Cochrane, Web of Science, PubMed, Scopus, and Google Scholar. From the efficacy prospect, we found that carbetocin substantially decreased intraoperative blood loss (p<0.001), hemoglobin/hematocrit levels (p<0.001), and the need for blood transfusion (p=0.002)/additional surgical interventions (p=0.003) than misoprostol. However, we revealed no substantial variation between both drugs for the need for additional uterotonic agents (p=0.08). From the safety prospect, we found that incidences of fever (p=0.002), heat sensation (p=0.007), metallic taste (p=0.01), and shivering (p=0.0002) were lower in carbetocin administration than in misoprostol. However, headache (p=0.34) and palpitation (p=0.11) incidences revealed no substantial variation between both drugs. In conclusion, from the efficacy and safety prospect, for women who underwent CS, carbetocin is more effective and safer in preventing and reducing PPH than misoprostol.
PubMed: 36578852
DOI: 10.7759/cureus.32901 -
European Journal of Obstetrics,... Feb 2022The purpose of this integrative literature review was to appraise studies conducted worldwide using misoprostol and estradiol in converting Type 3 transformation zone... (Review)
Review
The purpose of this integrative literature review was to appraise studies conducted worldwide using misoprostol and estradiol in converting Type 3 transformation zone (TZ) of the cervix into Types 1 or 2 and to assess which regimen could be more feasible in low-and-middle-income countries (LMICs). We reviewed the English language literature for peer-reviewed studies that evaluated strategies to convert Type 3 TZs to Types 1 or 2 for cervical cancer screening. Web of Science and PubMed searches were performed up to July 2020. Search terms included: "cervical colposcopy," "inadequate colposcopy", "cervical cancer screening", "transformation zone," "estrogen", "estradiol", and "misoprostol." Inclusion criteria were articles published in the English language, original research, and peer reviewed articles. A total of 127 articles were abstracted, 24 articles were reviewed, and 9 articles met all inclusion criteria. We found that intravaginal misoprostol, intravaginal estradiol, and oral estradiol can successfully convert Type 3 TZ to Types 1 or 2. A single dose of vaginal misoprostol had a similar maximum response rate (20-80%) to a multi-dose regimen over several days or weeks of both intravaginal estradiol (64-83%) and oral estradiol (50-70%). Misoprostol administration was associated with more side effects such as abdominal cramping and vaginal bleeding compared to estradiol, although these were generally mild. In conclusion, Oral estradiol, intravaginal estradiol, and intravaginal misoprostol can be used to convert Type 3 TZ to Types 1 or 2. Intravaginal misoprostol is well tolerated and more feasible in LMICs due to availability and shorter treatment schedule compared to oral or intravaginal estradiol.
Topics: Administration, Intravaginal; Cervical Ripening; Early Detection of Cancer; Estradiol; Female; Humans; Misoprostol; Oxytocics; Pregnancy; Uterine Cervical Neoplasms
PubMed: 34952401
DOI: 10.1016/j.ejogrb.2021.11.431 -
Revista Da Associacao Medica Brasileira... 2023This study aimed to analyze the effects of Foley catheter combined with misoprostol in the labor induction process. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study aimed to analyze the effects of Foley catheter combined with misoprostol in the labor induction process.
METHODS
This is a nonblinded, block randomized, controlled trial that compared the association between transcervical Foley catheter/vaginal misoprostol 25 μg combination and vaginal misoprostol 25 μg alone in normal-risk and healthy pregnant women undergoing labor induction in the south of Brazil.
RESULTS
A total of 230 patients with indications for labor induction were evaluated and classified into the "combined" group (Foley catheter plus misoprostol), consisting of 107 patients, and the "misoprostol" group (misoprostol only), consisting of 123 patients. The "combined" group was observed to have a shorter labor induction time (p=0.008). In addition, there was a lower need for misoprostol use for overall cervical ripening (p<0.001) and a lower relative risk of needing a second, third, or fourth misoprostol tablet in the "combined" group (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.71-0.91; RR 0.41; 95%CI 0.31-0.56; and RR 0.29, 95%CI 0.17-0.52, respectively) (p<0.001). No statistically significant difference was found in induction failure rate, cesarean section rate, or perinatal outcomes.
CONCLUSION
A combination of methods leads to shorter labor induction, lower need for misoprostol doses, and lower risk of cesarean section, with no increase in the rate of perinatal complications. REBEC number is RBR-7xcjz3z.
Topics: Pregnancy; Female; Humans; Misoprostol; Oxytocics; Cesarean Section; Administration, Intravaginal; Labor, Induced; Catheters
PubMed: 36629651
DOI: 10.1590/1806-9282.20220897 -
Cureus May 2024Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality, primarily attributed to uterine atony. Both the World Health Organization (WHO) and the...
Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality, primarily attributed to uterine atony. Both the World Health Organization (WHO) and the International Federation of Gynecology and Obstetrics (FIGO) endorse the use of misoprostol not only for the prevention but also for the treatment of PPH. However, the administration of misoprostol is commonly associated with transient pyrexia, attributed to a shift in the hypothalamic set point observed in certain animal studies. Misoprostol-induced hyperpyrexia can occasionally manifest with a prodrome of shivering, particularly when administered via the sublingual route, which achieves a higher and faster maximum plasma concentration compared to vaginal and rectal routes. General management strategies to reduce fever involve removing clothing and blankets, applying cool compresses, administering oral acetaminophen, and ensuring adequate hydration. While some cases have reported misoprostol-induced convulsions, hyperpyrexia leading to convulsions and subsequent rhabdomyolysis is a rare and potentially lethal side effect. In this case presentation, we emphasize a scenario where misoprostol was employed for the treatment of PPH but led to rhabdomyolysis. Our goal is to highlight the side effects of misoprostol and the significance of considering the initial combination of misoprostol with anti-pyretic management to minimize the risk of hyperthermia-related side effects and prevent additional severe complications.
PubMed: 38854268
DOI: 10.7759/cureus.59874 -
Revista Brasileira de Ginecologia E... Dec 2023To assess the efficacy, safety, and acceptability of misoprostol in the treatment of incomplete miscarriage. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the efficacy, safety, and acceptability of misoprostol in the treatment of incomplete miscarriage.
DATA SOURCES
The PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Clinical Trials databases (clinicaltrials.gov) were searched for the relevant articles, and search strategies were developed using a combination of thematic Medical Subject Headings terms and text words. The last search was conducted on July 4, 2022. No language restrictions were applied.
SELECTION OF STUDIES
Randomized clinical trials with patients of gestational age up to 6/7 weeks with a diagnosis of incomplete abortion and who were managed with at least 1 of the 3 types of treatment studied were included. A total of 8,087 studies were screened.
DATA COLLECTION
Data were synthesized using the statistical package Review Manager V.5.1 (The Cochrane Collaboration, Oxford, United Kingdom). For dichotomous outcomes, the odds ratio (OR) and 95% confidence interval (CI) were derived for each study. Heterogeneity between the trial results was evaluated using the standard test, I statistic.
DATA SYNTHESIS
When comparing misoprostol with medical vacuum aspiration (MVA), the rate of complete abortion was higher in the MVA group (OR = 0.16; 95%CI = 0.07-0.36). Hemorrhage or heavy bleeding was more common in the misoprostol group (OR = 3.00; 95%CI = 1.96-4.59), but pain after treatment was more common in patients treated with MVA (OR = 0.65; 95%CI = 0.52-0.80). No statistically significant differences were observed in the general acceptability of the treatments.
CONCLUSION
Misoprostol has been determined as a safe option with good acceptance by patients.
Topics: Pregnancy; Female; Humans; Infant; Misoprostol; Abortion, Incomplete; Abortion, Spontaneous; Pregnancy Trimester, First; Abortion, Induced
PubMed: 38141602
DOI: 10.1055/s-0043-1776029 -
BMC Pregnancy and Childbirth Aug 2023This study compares the effectiveness of administering sublingual misoprostol combined with oxytocin to that of IV tranexamic acid combined with oxytocin to reduce intra... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study compares the effectiveness of administering sublingual misoprostol combined with oxytocin to that of IV tranexamic acid combined with oxytocin to reduce intra and post-operative blood loss in high-risk women for postpartum haemorrhage (PPH) following cesarean section (CS).
METHODS
About 315 high-risk pregnant women undergoing CS participated in this trial. They were randomly assigned into three groups; tranexamic group, misoprostol group, and control group, according to the medication given in the operative theatre. All patients received oxytocin intraoperatively. They were assessed regarding intraoperative blood loss, the incidence of PPH, and the reduction in haemoglobin and hematocrit values.
RESULTS
Both tranexamic and misoprostol groups had similar results in reducing intra and post-operative blood loss. However, the reduction in haemoglobin and hematocrit were significantly lower in tranexamic and misoprostol groups compared to the control group (-0.78 ± 0.57 vs. -0.83 ± 0.52 vs. -1.32 ± 0.57 gm/dl, P < 0.001 and - 3.05 ± 1.28 vs. -3.06 ± 1.13 vs. -4.94 ± 1.82%, P < 0.001 respectively). In addition, the estimated blood loss was significantly lower in the tranexamic and misoprostol groups compared to the control group (641.6 ± 271.9 vs. 617.9 ± 207.4 vs. 1002.4 ± 340.7 ml, P < 0.001).
CONCLUSION
Both tranexamic acid and misoprostol are equally capable of reducing blood loss, but the results were significantly better compared to using oxytocin alone in high-risk patients.
CLINICAL TRIAL REGISTRATION
Registered at www.
CLINICALTRIALS
govon07/10/2019 with registration number NCT04117243.
Topics: Pregnancy; Female; Humans; Postpartum Hemorrhage; Oxytocin; Tranexamic Acid; Misoprostol; Cesarean Section; Blood Loss, Surgical; Postoperative Hemorrhage
PubMed: 37626292
DOI: 10.1186/s12884-023-05935-5