Comparative Study of the Efficacy of Misoprostol and Oxytocin Im in the Prevention of Post-Partum haemorrhage in a Low-Resource Setting

Background: In developing countries, postpartum hemorrhage is responsible for 30% of maternal deaths. Although the World Health Organization recommends the use of oxytocin for the prevention of postpartum hemorrhage, the use of misoprostol is increasingly common. The objective of this study was to determine the frequency of postpartum hemorrhage in parturients delivering at Saint-Vincent Hospital and to compare the effectiveness of misoprostol use versus oxytocin in preventing postpartum hemorrhage. Material and Methods: We conducted a comparative longitudinal study at the Saint Vincent Hospital comparing 10 units of intramuscular oxytocin with 600 micrograms of sublingual misoprostol. The study was conducted from 01 January 2017 to 31 December 2019, a period of 3 years. The study population consisted of 2161 consenting women. Of these, 1289 received 10 IU of intramuscular oxytocin and 872 received 600 micrograms of misoprostol. The collected data were entered using Microsoft Excel 2013 and analysed using SPSS version 21 software. Results: The frequency of administration of Misoprostol and oxytocin in parturients was 40.4% and 59.6% respectively in this study. One hundred and fourteen cases of postpartum hemorrhage (114/2161 or 5.3%) were noted among the parturients. The average age of parturients who received oxytocin was 24.36 ± 4.45 years vs 24.63 ± 5.11 years among parturients who received Misoprostol;(p = 0.190). The mean parity was 2.52 ± 1.46 vs 2.66 ± 1.44;(p = 0.020). We noted a high proportion (78.3%) of postpartum hemorrhage from the oxytocin group vs. 21.7% from the Misoprostol group (OR 2.5-fold), with a statistically significant difference (p 0.001). We noted high proportions of uterine atony (92.3%) from the oxytocin group vs 7.7% from the Misoprostol group (p = 0.004). Uterine atony was the actual factor associated with postpartum hemorrhage (OR = 10.0895% CI: 1.78 - 57.10;p = 0.009). Conclusion: Misoprostol 600 Microgram administered sublingually immediately after neonatal expulsion and before delivery was 2.5 times more effective than oxytocin 10 IU/IM. Misoprostol is therefore a good alternative to oxytocin and offers more advantages in management, use and outcome than oxytocin.

Knowledge and Level of Use of Misoprostol by Health Care Providers in the Maternity Wards of South Kivu in the Practice of Obstetrics

Post-partum haemorrhage (PPH) is one of the leading causes of maternal death in sub-Saharan Africa. In developing countries, PPH is responsible for about 30% of maternal deaths. The main causes of PPH are uterine atony, placental implantation anomalies and coagulation disorders. Acting on the causes of post-partum haemorrhage would significantly reduce maternal mortality. To prevent PPH, the World Health Organization (WHO) recommends the use of uterotonics as a preventive measure. Although parenteral Oxytocin is recommended as the first line Oxytocic for the prevention of PPH, the use of misoprostol is increasingly used in gynaecology and obstetrics, not only for the prevention of postpartum haemorrhage, but also for many other obstetric indications. The aim of this study was to assess the knowledge and level of use of misoprostol by healthcare providers in the gynaecology and maternity departments of South Kivu in the practice of gynaecology and obstetrics. Materials and methods We conducted a descriptive study from January 03 up to February 04, 2023. The study of population was made up of healthcare workers in South Kivu. A questionnaire containing questions relating to socio-demographic informations and knowledge of misoprostol was prepared and encoded in the kobo collect software. To access the questionnaire, it was compulsory to read the research protocol and give consent by ticking the “yes” button. All those who ticked “no” were denied access to the questionnaire. The link was sent, with a request to take part in the survey, to groups in the social networks of doctors and midwives in South Kivu. For areas not covered by the internet, a printed format was distributed and then encoded by data entry operators. For the paper format, respondents were also asked to indicate their consent by ticking the “yes” box. All the encoded data was automatically compiled on the server and then analysed and interpreted by the research team. Results: Nearly all (95.8%) healthcare workers in South Kivu knew about Misoprostol, and only 4.2% did not. The majority (90.1%) of healthcare workers had already used Misoprostol. Providers were aware of the obstetrical indications for Misoprostol, but in most cases, they did not know the dosage recommended by FIGO. For the prevention of post-Partum haemorrhage, only 39.9% use the correct dosage, 42.7% for the treatment of incomplete miscarriage and 49.3% for the treatment of post-Partum haemorrhage. 10% to 21% of providers know the indications of misoprostol but have no idea about dosage. Providers were aware of all routes of administration, but in most cases, they prescribed Misoprostol via the sublingual route (84.5%). The side effects observed by the providers were those already observed in other studies.

Misoprostol新用途:人工流产术前应用效果分析

目的;探讨Misoprostol(Miso)在人工流产术(妊娠8～12w)前应用的临床效果。方法:人工流产术前30min～2h口服Miso400～600μg,观察术时宫口大小、出血量、手术时间、子宫收缩和人工流产综合征的发生率。结果:术前口服Miso使宫口松弛、子宫收缩良好、出血量减少,平均手术时间短、人工流产综合征发生率低,术后随访阴道流血时间短,无子宫穿孔和不全流产。结论:口服Miso简便、安全、有效、价廉,可作为人工流产术前常规用药。

口服Misoprostol与Ru486配伍抗早孕临床研究

对50例妊娠≤49天的健康妇女,应用Ru486和Misoprostol(又称米索前列醇)终止妊娠。结果完全流产率98％,6小时内绒毛球完整排出占89.8％,副反应轻微。口服Misoprostol与Ru486配伍抗早孕方法简便、高效、安全、价格低廉,值得推广应用。

米非司酮加Misoprostol终止早孕220例临床分析

妊娠12周末以前称为早孕。近20余年来,世界各国采用最广泛的终止早孕方法是负压吸宫术,但具有一定的危险性与并发症。

米非司酮配伍Misoprostol终止早孕440例临床观察

选择４４０例停经７周以内的健康正常早孕妇女，门诊口服米非司酮配伍Ｍｉｓｏｐｒｏｓｔｏｌ终止早孕．结果显示完全流产率９６．７％，无不全流产致大出血需要清宫者；阴道出血量与孕周、胎囊和胎芽小成正相关（Ｐ＜０．０１）；用药越早、出血越少，效果越好．证实米非司酮配伍Ｍｉｓｏｐｒｏｓｔｏｌ终止早孕是一种安全、方便可靠的好方法．阴道超声检查对指导临床用药和早期诊断早早孕有重要临床价值．

米非司酮配伍Misoprostol终止早孕临床应用研究

近几年来,由于药物米非司酮的问世,在终止早孕的研究上有了突破性进展,有研究显示：在终止妊娠7周内的早孕上,前列腺素与米非司酮配伍使用可达到90%以上的成功率[1,2],并且用药时间和临床疗效之间存在显著相关性,但同时也发现部分病人存在出血时间较长,出血多,需急诊清宫等亟待解决的问题。因此,为进一步研究药物使用与阴道出血量和妊娠周数之间的关系,本研究通过常规阴道超声检查,在服药前对早孕者进行快速诊断监测,

Clinical Observation on Termination of Early Pregnancy of 213 Cases after Caesarian Section with Repeated Use of Mifepristone and Misoprostol

Objective To investigate the efficacy and safety in women after caesarian section for termination of early pregnancies by treatment, or repeated treatment with mifepristone and misoprostol. Subjects and Methods A total of 213 pregnant women with amenorrhea of 34~69 d after caesarian section who asked for medical abortion were recruited, including 63 cases undergoing their second medical abortion. A total amount of mifeprisstone of 150 mg given in separate doses (25 mg×4 and 50 mg at the first time) was administered orally within 3 d, followed by misoprostol of 0.6 mg orally in the morning of d 3. Results The complete abortion rate was 92.5%, incomplete abortion was 4.7% and failure was 2.8%. Conclusion The sequential use of mifepristone and misoprostol could be successfully and repeatedly used for induced abortion in those women with a caesarian section history. Its efficacy was similar to that for ordinary population. Its safety and effectiveness were satisfactory.

Development of Misoprostol Suppositories for Postpartum Hemorrhage

Misoprostol is a prostaglandin E1 analogue used to prevent and treat gastric ulcers. It has been commonly used in gynecology and obstetrics, especially for the management of postpartum hemorrhage (PPH). For this purpose, 1000 μg intrarectal (insertion of five 200 μg tablets) has been recommended as the third line after injectable oxytocin and methylergometrine. We proposed to manufacture a 1000 μg misoprostol suppository by determining formulation, release and stability. The administration facility was also evaluated. Several formulations of misoprostol suppositories were set up and evaluated. Misoprostol tablets and lipophilic bases (Hard fat—Adeps solidus Ph. Eur., Witepsol? H15 and Suppocire? AM and AS2X) were used to obtain suppositories. Surfactants were also tested (polysorbates Tween? 20, Tween? 80 and sodium lauryl sulfate (SLS)). The formula was monitored by the misoprostol release curve with an in vitro test and dosed by a HPLC method. Stability was determined by evaluating the percentage of misoprostol content remaining over the time in suppositories stored at 4℃ and 25℃. Facility of use versus tablets was evaluated by obstetricians of a Swiss regional hospital using a questionnaire. Misoprostol release was facilitated by adding surfactant to the lipophilic base. After 30 minutes, 59% ± 1.4% and 57% ± 8.2% of misoprostol was released with Adeps solidus + 1% SLS and Adeps solidus + 5% Tween 20 respectively. SLS was discarded to the final formula because of its irritating effect. After 7 months, suppositories still contained 94% ± 3.7% misoprostol with storage at 4℃. The administration was considered easier and faster compared with intra rectal use of tablets. The formula, consisting of 5 crushed misoprostol tablets dispersed in a suppository base made of Adeps solidus + 5% Tween? 20, is stable for at least 7 months at 4?C and facilitates the rectal administration of misoprostol in the treatment of PPH.

Neuroprotection by misoprostol against rotenone-induced neurotoxicity in rat brain

Objective: To investigate the effect of the prostaglandin E1 analogue misoprostol on oxidative stress and neurodegeration caused by subcutaneous rotenone administration in rats. Methods:Rotenone was administered in a dose of 1.5 mg/kg every other day for 2 weeks. Starting from the 1 st day of rotenone injection, rats were subcutaneously treated with misoprostol at doses of10, 100 or 1 000 μg/kg. Rats were evaluated for brain lipid peroxidation(malondialdehyde:MDA), reduced glutathione(GSH), nitric oxide(NO) levels, and paraoxonase-1(PON-1) activity.The concentrations of the anti-apoptotic protein B cell/lymphoma-2(Bcl-2) were determined in the striatum. Histopathologic examination and the expression of inducible nitric oxide synthase(iNOS) in the cerebral cortex and striatum were also performed. Results: Compared with the vehicle-treated group, rotenone caused a significant increase in brain lipid proxidation(MDA)by 61%(P<0.05) accompanied by an increase in NO by 73.1%(P<0.05) and a decrease in GSH concentration by 29.4%(P<0.05). In addition, brain PON-1 activity significantly decreased by63.0%(P<0.05) and striatal Bcl-2 significantly decreased by 27.9%(P<0.05) with respect to the corresponding control value. Brain sections from rotenone treated rats showed extensive dark pyknotic and apoptotic nuclei in neurons, shrunken cytoplasm and perineuronal vacuolation.Rotenone also caused pronounced expression of iNOS in the cerebral cortex and striatum.Treatment with misoprostol at doses of 100 and 1 000 μg/kg resulted in decreased brain MDA(by 16.5%-23.0%)(P<0.05) and NO levels(by 37.1%-40.7%)(P<0.05) and increased GSH concentrations(by 18.8%-30.1%)(P<0.05). PON-1 activity was significantly increased by80.0%-114.8%(P<0.05) by misoprostol at 100 and 1 000 μg/kg, respectively. In addition,misoprostol treatment restored striatal Bcl-2 concentrations to its normal value. Misoprostol treatment resulted in markedly reduced brain injury and decreased iNOS expression in the cerebral cortex and striatum of rotenone intoxicated rats. Conclusions: These data suggest that misoprostol prevents the rotenone-induced neurodegeneration in rat brain by reducing brain oxidative stress.

Role of Oral Misoprostol in First Trimester Abortion: A Prospective Study at CMH, Dhaka, Bangladesh

Background: Misoprostol has been used for medical abortion. We conducted this prospective study to see the efficacy of oral misoprostol in our tertiary Hospital. Objective: Objective of this study was to assess the efficiency, safety and compliance of misoprostol in first trimester abortion. Materials and Methods: This prospective study was undertaken in obstetrics and gynecology dept of CMH Dhaka, Bangladesh from July 2014 up to Dec 2014. A total 50 patients of incomplete abortion (54%), missed abortion (30%), anembryonic pregnancy (14%) and inevitable abortion (2%) of s of gestation were the targeted population. Study population was diagnosed from history, physical examination and ultrasonogram had received 600 microgram misoprostol orally. If the pregnancy was not completely evacuated at this time another dose of misoprostol was given. All women returned for follow-up care 7 days later. If the pregnancy was not completely evacuated at this time, women underwent immediate surgical evacuation. Efficacy was defined as the percent of women discharged from the study without need for surgical intervention. Results: 30 patients had complete evacuation after 1st dose, 12 cases needed 2nd dose and only 2 cases needed 3rd dose. Remaining 6 cases needed surgical evacuation. Efficacy was satisfactory (85%) and analysis revealed statistically significant (p 0.05). Conclusion: Management of first trimester abortion with oral misoprostol is highly effective and highly acceptable.

Oral Misoprostol 2 Hourly for Labor Induction

The objective of this study was to assess the efficacy and safety of the 2 hourly oral misoprostol for labor induction. Between May and November 2013, the hospital records of 83 women who were induced for labor and met the eligibility criteria were retrospectively reviewed. Eligibility criteria were singleton pregnancy of at least 34 weeks’ gestation and a baseline Bishop score 6. Women with a previous cesarean section or other uterine surgery, severe pregnancy-induced hypertension, and parity of 4 or more were excluded. Oral misoprostol was administered as 20 μg 2 hourly unless active labor. A maximum of 12 doses was allowed. The age of the women was 27.9 ± 5.3 years (mean ± SD). Vaginal delivery within 24 hours occurred in 38 (45.8%) women. Cesarean delivery occurred in 17 (20.5%) women. Although more parous women achieved vaginal delivery within 24 hours (52.6%) compared with nulliparous women (40.0%), the difference was not significant (P = .35). Uterine tachysystole occurred in 12 (14.5%) women. No perinatal deaths or neonatal intensive care unit admission occurred in the study group. Evidence supporting an optimal regimen is lacking, and additional research is warranted to optimize the use of oral misoprostol for the induction of labor.

Comparison between Preoperative and Postoperative Sublingual Misoprostol for Prevention of Postpartum Hemorrhage during Cesarean Section: A Randomized Clinical Trial

Background: Blood loss is one of the important complications during cesarean section (CS). Previous reports have shown that misoprostol is effective in reducing blood loss during and after CS. However, the optimum time for its administration to decrease the amount of PPH is still under discussion. Objective: To compare the effect of preoperative and postoperative administration of sublingual misoprostol (400 μg) in reducing the amount of blood loss during and 24 hours after CS. Setting: Obstetrics and Gynecology Department, Faculty of Medicine, Assiut University, Assiut, Egypt, between January 2017 and July 2018. Study Design: A prospective, randomized clinical trial. Methods: Four-hundred thirty women fulfilling the inclusions criteria: elective lower segment CS at term (≥37 weeks) with normal fetal heart tracing who accepted to participate in the study. Patients were divided into two groups;Patients assigned to group 1 received 400 μg sublingual misoprostol immediately after urinary catheterization and before skin incision, while patients assigned to group 2 received sublingual misoprostol immediately after skin closure. The primary outcome was the estimation of intraoperative and postoperative blood loss for 24 hours. Results: There was a significant reduction in the intraoperative blood loss in group 1 compared with group 2 (403.51 ± 72.99 vs. 460.99 ± 74.66 ml, respectively). Also, there was a significant reduction in postoperative blood loss in group 1 compared with group 2 with a statistical significance (169.45 ± 12.03 vs. 195.77 ± 13.34 ml, respectively). Postoperative hemoglobin and Hematocrit values were significantly higher in group 1 compared with group 2. Conclusions: Preoperative administration of sublingual misoprostol (400 μg) during CS is better than postoperative administration as it is associated with a reduction in the amount of intraoperative and postoperative blood loss and drop in hemoglobin level.

Foley Balloon Catheter versus Oral Misoprostol for Induction of Labour after Prelabour Rupture of Membranes: A Retrospective Data Analysis

Objectives: The Foley balloon catheter (FC) is a viable method for cervical ripening, but concerns about infection risk restrict its use in cases of prolonged prelabour rupture of membranes (PROM). This study aims to evaluate the efficacy and safety of the FC compared to oral misoprostol for cervical ripening after PROM. Study Design: A retrospective data-analysis of 128 pregnant women was conducted. Of these, 49 underwent cervical ripening with an FC and 79 with oral misoprostol. We included all women with a vital singleton pregnancy at 37 - 42 weeks of gestation who underwent cervical ripening after ≥ 24 hours of PROM in specific time frames in two Dutchsecondary care and teaching hospitals. The primary outcome was the incidence of intrapartum infection, a composite of maternal and neonatal infection. In addition, we evaluated the mode of delivery, duration of priming and priming-to-delivery interval. Secondary endpoints included uterine hyperstimulation, umbilical cord prolapse, birth weight, Apgar scores, length of admission to the neonatal low dependency unit, admission to the (neonatal) Intensive Care Unit (ICU) and mortality. Statistical analyses included bivariate and multivariate techniques. Results: Cervical ripening with FC, compared with oral misoprostol, showed a higher incidence of intrapartum infection, respectively 32.7% (n = 16) vs. 12.7% (n = 10) (p = 0.006). However, after adjusting for epidural anaesthesia and pregestational BMI, the association was no longer significant. No difference was found in mode of delivery and total priming-to-delivery interval (median 21.3 hours vs. 22.0, p = 0.897). Furthermore, FC, compared with oral misoprostol, showed a longer duration of cervical ripening and hence a shorter duration of active labour (p 0.001). Apart from the 1-min Apgar score, secondary maternal and neonatal outcomes did not differ between the groups. Conclusion: In women who require cervical ripening after prolonged PROM at term, the FC and oral misoprostol are similar in terms of efficacy and safety. Advantages associated with the FC are its safe application in women with a history of caesarean section, although we did not study these women, and an implied shorter duration of active labour. Our study adds to the limited available data on the use of the FC after the rupture of membranes and a large randomized controlled trial is needed to strengthen our findings.

Clinical Observation of Misoprostol before and after Painless Induced Abortion

Background: Though painless abortion is a safe, effective and excellent method of artificial abortion, intravenous anesthesia cannot effectively expand the cervix. Hard and tight cervix often affects the operation and easily inducesabortion complications. Misoprostol can induce uterine contraction and soften the cervix. Objective: To investigate the clinical effect of misoprostol on abortion before and after painless induced abortion. Methods: 600 case pregnant women were divided into three groups: A, B and C, 200 case in each group. All patients were anesthetized. In group A, misoprostol 0.2 ug was placed in the posterior fornix of vagina 2 hours before the operation of induced abortion;in group B, misoprostol 0.2 ug was not only placed in the posterior fornix of vagina 2 hours before the operation of induced abortion but also taken orally 2 hours and 6 hours after the operation;in group C, misoprostol was not used before and after the operation. The operation time, intraoperative bleeding volume, postoperative bleeding, the percentage of cervical relaxation and the rate of incomplete abortion among the three groups were compared. Results: Compared with group A and group B, the operation time of group C was longer and the amount of bleeding was more (P < 0.05), but there was no significant difference between group A and group B (P > 0.05). The duration of bleeding in group B was less than that in group A (P < 0.05). The percentage of cervical relaxation in group A and B was higher than that in group C (P < 0.05). The rate of incomplete abortion in group B < group A < group C (P < 0.05), and there was no residual uterine cavity in group B. Conclusion: The use of misoprostol before and after painless induced abortion can not only shorten the time of operation, reduce intraoperative and postoperative vaginal bleeding, but also has not incurred incomplete abortion(primary outcome).

Individualized misoprostol dosing for labor induction or augmentation: A review

Cesarean birth rates are greater than 20% in many developed countries. The main diagnoses contributing to the high rate of cesarean births in nulliparous women are dystocia and prolonged labor. Traditionally, a policy of vaginal dinoprostone for the treatment of unripe cervix or early amniotomy with oxytocin administration for a ripened cervix has been associated with a modest reduction in the rate of cesarean births due to arrest disorders. However, the course of vaginal dinoprostone is tedious and oxytocin should be administered through an infusion pump, which may be inconvenient in certain settings. Because misoprostol has powerful uterotropic and uterotonic effects, and has become a common agent used in the practice of obstetrics and gynecology, the United States Food and Drug Administration removed the absolute contraindication of the drug during pregnancy from its label in April 2002. However, excessive uterine contractility resulting in tachysystole or fetal distress is always a concern with the oral or vaginal use of fixeddosage misoprostol. Therefore, misoprostol should be administered with caution to ensure that fetal hypoxia does not occur. A pilot trial examining the use of very small, frequent, titrated oral misoprostol dosages administered every 2 h was fi rst conducted by Hofmeyr et al in 2001. Given women's different metabolisms and responses tomisoprostol, another method of titrating individualized oral misoprostol with dosing administered every hour relative to uterine response was then developed by Cheng in 2006. Based on previous studies, this titration method is potentially an ideal alternative to traditional dinoprostone, oxytocin or the previously established misoprostol dosing method for labor induction or augmentation.

Misoprostol与SHA-S配伍用于中期妊娠引产的临床研究

本文报道Ｍｉｓｏｐｒｏｓｔｏｌ与蒂洛安（ＤＨＡ－Ｓ）配伍用于中期妊娠引产５０例的临床效果。结果显示，用药后宫颈Ｂｉｓｈｏｐ评分与用药前比较有显著性提高（Ｐ＜０．０１），服Ｍｉｓｏｐｒｏｓｔｏｌ后平均临产时间为２．９７±０．９２ｈ，引产成功率为８８％，均较对照组（分别为３５．８６±０．７８ｈ、６２．５％）有非常显著性差异；而两组出血量比较，差异无显著性（Ｐ＞０．０５）。提示Ｍｉｓｏｐｒｏｓｔｏｌ与ＤＨＡ－Ｓ配伍是终止中期妊娠的比较理想的药物引产方法。

Cervical Ripening in the Third Trimester of Pregnancy with Intravaginal Misoprostol: A Double-blind, Randomized,Placebo-controlled Study

To evaluate the safety and efficacy of intravaginal misoprostol for cervical ripening in the third trimester, a randomized, double-blind, placebo-controlled trial was conducted in 85 patients indicated for induction of labor and with unfavorable cervices. They were randomly assigned to receive either intravaginal misoprostol (100 mg) or placebo placed in the posterior vaginal fornix. The Bishop score, fetal heart rate and Doppler blood flow velocity waveforms were measured before and 12 h after drug administration. Placenta and decidu were histopathologically observed in some cases. Among 85 patients enrolled, 43 received misoprostol and 42 received placebo. Whereas the mean initial Bishop scores were not significantly different between the two growps, the mean Bishop score in misoprostol group was significantly better than those in placebo group.The mean change in Bishop score was also significantly different (4. 4 for misoprostol versus 1. 0 for placebo, P<0.01 ). The prevalence of spontaneous onset of labor within 12 h after drug insertion in misoprostol group (67. 4%, 29/43)was significantly higher than that in placebo group (14. 3%, 6/42), P<0.01.The average DOppler velocity systolic to diastolic (S/D) ratios of umbilical artery,middle cramal artery, renal artery were not significantly different before and 12 h after drug insertion between both groups. There was no significant difference in frequency of abnormal fetal heart rate tracings or fetal distress and in the mean Apgar scores between the two groups. Except the presence of vasodilation in villi vessels in the misoprostol group, the placental and decidual histopathological changes had no significantly difference between two groups. It is concluded that intravaginal misoprostol may be an effective and safe cervical ripening agent in the third trimester of pregnancy.