Combination of Mifepristone and Misoprostol for First-Trimester Medical Abortion: A Comprehensive Review of the Literature.

Importance: Several medications have been used to achieve medical abortion in the first trimester of pregnancy. The most commonly used is the combination of mifepristone and misoprostol; however, different doses and routes of administration have been proposed. Objective: The aim of this study was to summarize published data on the effectiveness, adverse effects, and acceptability of the various combinations of mifepristone and misoprostol in medical abortion protocols in the first trimester of pregnancy. Evidence Acquisition: This was a comprehensive review, synthesizing the findings of the literature on the current use of mifepristone and misoprostol for first-trimester abortion. Results: The combination of mifepristone and misoprostol seems to be more effective than misoprostol alone. Regarding the dosages and routes, mifepristone is administered orally, and the optimal dose is 200 mg. The route of administration of misoprostol varies; the sublingual and buccal routes are more effective; however, the vaginal route (800 µg) is associated with fewer adverse effects. Finally, the acceptability rates did not differ significantly. Conclusions: Different schemes for first-trimester medical abortion have been described so far. Future research needs to focus on identifying the method that offers the best trade-off between efficacy and safety in first-trimester medical abortion.

Adjuvant misoprostol or mifepristone for cervical preparation with osmotic dilators before dilation and evacuation.

OBJECTIVES: This study aimed to compare effectiveness and safety of cervical preparation with osmotic dilators plus same-day misoprostol or overnight mifepristone prior to dilation and evacuation (D&E). STUDY DESIGN: We conducted a retrospective cohort analysis of 664 patients initiating abortion between 18 and 22 weeks at an ambulatory health center. We abstracted medical record data from two consecutive 12-month periods in 2017 to 2019. All patients received overnight dilators plus: 600 mcg buccal misoprostol 90 minutes before D&E (period 1); 200 mg oral mifepristone at time of dilators (period 2). Our primary outcome was procedure time. We report frequency of patients experiencing any acute complication, defined as unplanned procedure (i.e., reaspiration, cervical laceration repair, uterine balloon tamponade) or hospital transfer and bleeding complications. RESULTS: We observed higher mean procedure time in the mifepristone group (9.7 ± 5.3 minutes vs 7.9 ± 4.4, p = 0.004). After adjusting for race, ethnicity, insurance, body mass index, parity, prior cesarean, prior uterine surgery, gestational age, provider, trainee participation, and long-acting reversible contraception initiation, the difference remained statistically significant (relative change 1.09, 95% CI 1.01, 1.17) but failed to reach our threshold for clinical significance. The use of additional misoprostol was more common in the mifepristone group, but the use of an additional set of dilators was not different between groups. Acute complications occurred at a frequency of 4.1% in misoprostol group and 4.3% in mifepristone group (p = 0.90). CONCLUSIONS: We found procedure time to be longer with adjunctive mifepristone compared to misoprostol; however, this difference is unlikely to be clinically meaningful. Furthermore, the frequency of acute complications was similar between groups. IMPLICATIONS: Overnight mifepristone at the time of cervical dilator placement is a safe and effective alternative to adjuvant same-day misoprostol for cervical preparation prior to D&E and may offer benefits for clinic flow and patient experience.

When Do Women with Second Trimester Pregnancy Loss Need Repeated Doses of Misoprostol? Insights from a Teaching Hospital.

BACKGROUND: Cases of second trimester pregnancy loss can be treated either pharmacologically or by surgical evacuation. Misoprostol, an E1-prostaglandin analog, is used to facilitate the evacuation of the uterus. OBJECTIVES: To determine the risk factors associated with patients who were treated with five or more repeated doses of misoprostol. METHODS: We conducted a retrospective study of patients treated with vaginal misoprostol at our institution between December 2016 and October 2021 for second trimester pregnancy loss. RESULTS: In total, 114 patients were eligible for analysis; 83 were treated with < 5 doses and 31 with ≥ 5. We recorded each case in which repeated doses were administered, irrespective of predetermined conditions such as gravidity, parity, maternal age, or gestational age. Moreover, cases of five or more misoprostol dosing were not associated with an increased complications rate, except for the increased duration of hospitalization (3.1 vs. 2.2 days, P-value < 0.01). CONCLUSIONS: Repeated dosing could not be predicted before treatment among those treated with vaginally administered misoprostol for second trimester pregnancy loss. However, low complication rates of repeated dosing may reassure both physicians and patients regarding safety, efficacy, and future fertility.

Prediction of Rupture by Complete Blood Count in Tubal Ectopic Pregnancies Treated with a Single-Dose Methotrexate Protocol.

OBJECTIVE: The availability of reliable and inexpensive markers that can be used to determine the risk of rupture during methotrexate (MTX) treatment in ectopic pregnancies (EPs) is considerable. The aim of the present study is to investigate the role of systemic inflammatory markers such as leukocytes (or white blood cells, WBCs), the neutrophil-to-lymphocyte ratio (NLR), and platelet distribution width (PDW), which are among the parameters of the complete blood count (CBC), in the prediction of rupture of EPs under MTX treatment. MATERIALS AND METHODS: A total of 161 patients with tubal EP who underwent a single-dose methotrexate (MTX) protocol were retrospectively analyzed, and the control group (n = 83) included patients cured by MTX, while the ruptured group (n = 78) included patients who were operated on for tubal rupture during the MTX treatment. The features of EP, beta-human chorionic gonadotropin (ß-hCG) levels, sonographic findings, and CBC-derived markers such as WBC, NLR, and PDW, were investigated by comparing both groups. RESULTS: The NLR was found to be higher in the ruptured group, of 2.92 ± 0.86%, and significantly lower in the control group, of 2.09 ± 0.6%. Similarly, the PDW was higher (51 ± 9%) in the ruptured group, and it was significantly lower a (47 ± 13%) in the control group (p < 0.05). Other CBC parameters were similar in both groups (p > 0.05). CONCLUSION: Systemic inflammation markers derived from CBC can be easily applied to predict the risk of tubal rupture in Eps, since the CBC is an inexpensive and easy-to-apply test, which is first requested from each patient during hospitalization.

OBJETIVO: A disponibilidade de marcadores confiáveis e baratos que podem ser usados para determinar o risco de ruptura durante o tratamento com metotrexato (MTX) em gestações ectópicas (GEs) é considerável. O objetivo do presente estudo é investigar o papel de marcadores inflamatórios sistêmicos, como leucócitos (ou glóbulos brancos, glóbulos brancos), a relação neutrófilo-linfócito (NLR) e largura de distribuição de plaquetas (PDW), que estão entre os parâmetros do hemograma completo (hemograma), na predição de ruptura de PEs sob tratamento com MTX. MATERIAIS E MéTODOS: Foram analisados retrospectivamente 161 pacientes com EP tubária submetidas a protocolo de dose única de metotrexato (MTX), sendo que o grupo controle (n = 83) incluiu pacientes curadas com MTX, enquanto o grupo roto (n = 78) incluíram pacientes operadas por ruptura tubária durante o tratamento com MTX. As características de EP, beta-gonadotrofina coriônica humana (ß-hCG), achados ultrassonográficos e marcadores derivados de CBC, como WBC, NLR e PDW, foram investigados comparando os dois grupos. RESULTADOS: A RNL foi maior no grupo roto, de 2,92 ± 0,86%, e significativamente menor no grupo controle, de 2,09 ± 0,6%. Da mesma forma, o PDW foi maior (51 ± 9%) no grupo roto, e foi significativamente menor a (47 ± 13%) no grupo controle (p < 0,05). Outros parâmetros do hemograma foram semelhantes em ambos os grupos (p > 0,05). CONCLUSãO: Marcadores inflamatórios sistêmicos derivados do hemograma podem ser facilmente aplicados para predizer o risco de ruptura tubária na Eps, uma vez que o hemograma é um exame de baixo custo e fácil aplicação, solicitado primeiramente a cada paciente durante a internação.

Early pregnancy loss medical management in clinical practice.

OBJECTIVES: This study aimed to review clinical practice outcomes of early pregnancy loss (EPL) medical management using mifepristone and misoprostol outside of a clinical trial setting. STUDY DESIGN: In this retrospective cohort study, we reviewed a deidentified database of patients who received mifepristone-misoprostol for EPL from May 2018 to May 2021 at our academic center-based clinic, which was a study site for a multicenter mifepristone-misoprostol EPL trial completed in March 2018. All patients received mifepristone 200 mg orally and misoprostol 800 mcg vaginally or buccally, with clinic follow-up typically scheduled within 1 week. The primary outcome was successful medical management, defined as management without the need for aspiration, and the secondary outcomes included additional interventions and indications, follow-up ultrasonography findings, and adverse events requiring treatment. RESULTS: We treated 90 patients with a median ultrasound-measured gestational size of 49 (range 30-80) days and median time from mifepristone to misoprostol of 24 (range 8-66) hours. Follow-up was completed in clinic by 80 (88.9%), completed remotely by five (5.6%), and not completed by five (5.6%) patients. Overall, 76 (95% CI 82.9%-96.0%) of 85 patients (89.4%) with follow-up were successfully managed without uterine aspiration. Eighty patients had initial follow-up ultrasonography interpreted as gestational sac expulsion; seven (8.8%) of these ultimately underwent aspiration, including one patient who had a previously undiagnosed cesarean scar ectopic pregnancy. Two patients had significant safety outcomes: one pelvic infection and one blood transfusion during aspiration in the patient with a cesarean scar ectopic pregnancy. CONCLUSIONS: Outside of a clinical trial setting, medical management of EPL with mifepristone and misoprostol remains effective and safe. IMPLICATIONS: Medical management of EPL with mifepristone and misoprostol is effective and safe outside of a clinical trial setting. A standardized protocol based on the best available clinical trial evidence can be used in clinical practice for the medical management of EPL.

Effectiveness and safety of misoprostol-only for first-trimester medication abortion: An updated systematic review and meta-analysis.

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.

Clinical outcomes of medication abortion using misoprostol-only: A retrospective chart review at an abortion provider organization in the United States.

OBJECTIVES: This study aimed to evaluate the effectiveness and safety of medication abortion with misoprostol-only among patients treated by an abortion provider organization in the United States during the COVID-19 pandemic. STUDY DESIGN: We abstracted data from patients receiving misoprostol-only for abortion from December 2020 to December 2021. Two regimens were used, both allowing three to four doses of misoprostol 800 mcg every 3 hours but differing in the recommended administration routes (vaginal, buccal, or sublingual). We estimated the proportions of patients who had complete abortion and ongoing pregnancy in the two regimen groups in complete case analyses and after imputing missing outcomes based on pretreatment characteristics. We also estimated maximum effectiveness, assuming that all patients without known treatment failures had complete abortions. We tabulated serious adverse events. RESULTS: We ascertained abortion outcomes for 476 (52%) of the total 911 treated patients. Of the 476 patients, 389 (82%) had complete abortion confirmed by test or history, and 45 (9%) had ongoing pregnancies detected after the provision of treatment. These proportions did not differ significantly between the two regimen groups in adjusted complete case analyses (p > 0.44). The results of imputed analyses were similar. Of the total 911 patients, at most 90% (95% confidence interval 88%, 92%) had complete abortion, and at least 5% (95% confidence interval 4%, 7%) had ongoing pregnancy. Serious adverse events were reported in three patients (0.6% of 487 patients with data for this outcome). CONCLUSIONS: Our analysis suggests that the misoprostol-only regimens studied were safe and effective for most patients. Due to high loss to follow-up, observations from patients contacted after treatment likely somewhat underestimate true effectiveness. IMPLICATIONS: Medication abortion with misoprostol-only was safe and produced complete abortion in most patients with follow-up. If loss to follow-up is high, effectiveness observed by clinics may misestimate true treatment efficacy.

Risk factors and prediction of ectopic pregnancy rupture following methotrexate treatment: A retrospective cohort study.

OBJECTIVE: Ectopic pregnancy (EP) rupture after methotrexate (MTX) treatment can have severe consequences. We examined clinical characteristics and beta-hCG trends that may predict EP rupture after MTX treatment. STUDY DESIGN: In this 10-year retrospective study of 277 women with an EP, we compared clinical, sonographic and beta-hCG trends, before and after MTX treatment, between those who did and did not have an EP rupture after MTX treatment. RESULTS: EP rupture was diagnosed in 41 women (15.1%) within 25 days of MTX treatment, and was correlated with higher parity and advanced pregnancy age: 2(0-5) vs. 1(0-6), P = 0.027 and 6.6(4.2-9.8) vs. 6.1(4-9.5), P = 0.045. EP rupture was also correlated with higher beta-hCG levels on days 0, 4 and 7 of MTX treatment: (2063 vs. 920 mIU/ml), (3221 vs. 921 mIU/ml) and (2368 vs. 703 mIU/ml), respectively, P < 0.001, for all. An increase of beta-hCG by>14% during days 0-4 showed a sensitivity of 71.4% CI 95% [55.4%-84.3%] and a specificity of 67.5% CI 95% [61.1%-73.6%] for predicting EP rupture after MTX treatment. Beta-hCG > 910 mIU/ml on day 0 showed a sensitivity of 80.9% CI 95% [66.7%-90.8%] and a specificity of 70.4% CI 95% [64.1%-76.3%] for predicting EP rupture after MTX treatment. A beta-hCG increase by>14% during days 0-4, and a beta-hCG value > 910 mUI/mL on day 0 were associated with increased risks of EP rupture after MTX treatment; the odds ratios were 6.4 and 10.5, respectively. Odds ratios were 8.06 [CI 95% (3.70-17.56)], P < 0.001 for every percent rise in beta-hCG during days 0-4; 1.37 [CI 95% (1.06-1.86)], P = 0.046 for every week change in gestational age; and 1.001 [CI 95% (1.000-1.001)], P < 0.001 for every unit rise in beta-hCG at day 0. CONCLUSION: Beta-hCG > 910 mIU/ml at day 0, a rise in beta-hCG by>14% during days 0-4, and more advanced gestational age were associated with EP rupture after MTX treatment.

Maternal complications associated with second trimester medical abortion using mifepristone priming and subsequent misoprostol.

OBJECTIVES: To assess the frequency of maternal adverse events associated with second trimester medical abortion using sequential mifepristone and misoprostol. STUDY DESIGN: Retrospective analysis of medical abortions 13 to 28 weeks gestation using sequential mifepristone and misoprostol in a single center from January 2008 to December 2018. The main outcomes evaluated were the nature and incidence of adverse procedural events and the impact of gestation upon these outcomes. RESULTS: During the study period, 1393 people underwent a medical abortion with sequential mifepristone and misoprostol. The median maternal age was 31 years (IQR 27-36 years) and 21.8% had at least one prior cesarean delivery. The median gestational age at abortion commencement was 19 weeks (IQR 17-21). The main adverse maternal events were complete or partial placental retention greater than 60 minutes triggering removal in the operating room (19%), maternal hemorrhage>1000 cc (4.3%), blood transfusion (1.7%), hospital readmission (1.4%), uterine rupture (0.29%) and hysterectomy (0.07%). There were significant reductions in placental retention rates with increasing gestational age (23.3% at 13-16 weeks gestation declining to 10.1% at>23 weeks gestation, p < 0.001). CONCLUSIONS: Serious adverse maternal events associated with second trimester medical abortion with sequential mifepristone-misoprostol are uncommon. IMPLICATIONS: Second trimester medical abortion with mifepristone and misoprostol is generally safe, however, on occasions serious complications may occur. All health care units providing a medical abortion service require the facilities and expertise to deal with these adverse events in a timely manner.

Low-dose methotrexate-induced renal failure in a patient with ectopic pregnancy: a case report.

BACKGROUND: Methotrexate is an anticancer drug from the antimetabolite class. It is also used in gynecology and obstetrics for the medical treatment of ectopic pregnancies. Low-dose methotrexate-induced adverse toxic effects are rare. We report a case of toxic effect associated with severe renal insufficiency induced by LD-MTX (Low-Dose Methotrexate) for ectopic pregnancy. CASE PRESENTATION: A 46-year-old Chinese woman was in an operation for an ectopic pregnancy of tubal interstitial pregnancy. The embryo villus was so little that we were not sure if it was evacuated, then it was followed with 50 mg methotrexate injection of intramuscular adjacent the uterine horn in the operation. 48 hour later after injection the patient presented with renal failure. The personalized genetic testing showed that MTHFR (677C > T) and ABCB1 (3435T > C) were detected. Gradually, the symptoms improved after calcium leucovorin (CF) rescue, continuous renal replacement therapy (CRRT), promoting blood system regeneration, and multiple supportive treatments. CONCLUSIONS: When toxic effects are suspected, detecting the polymorphisms of an MTHFR gene and monitoring MTX concentration in blood could assist us to formulate individualized and active treatments. The management should be multidisciplinary and as much as possible within an intensive care unit.

Apoptosis versus necrosis in tubal ectopic pregnancies following Methotrexate.

Methotrexate administration for the treatment of tubal ectopic pregnancies has been shown to cause tubal mass enlargement. Our hypothesis was that, by administrating Methotrexate, a local necrotic reaction occurs, leading to hematoma formation and eventually fallopian tube rupture. Salpingectomy specimens were collected, analysed and divided into three equal groups: patients who received Methotrexate but who ultimately failed medical treatment, patients who had a viable ectopic pregnancy and patients with a self-resolving ectopic pregnancy that were operated due to other medical indications. The specimens were dyed using the Cleaved Caspase-3 (Asp175) Rabbit mA. Specimens were divided into three equal groups and analysed. The patients in self-resolving ectopic pregnancy group were older and had more pregnancies. Rates of apoptosis were found to be less than 1% per slide. Necrosis was not evident in any of the pathological specimens. It seems Methotrexate administration does not lead to a significant tubal necrotic reaction. Further studies are required.

Single dose letrozole and misoprostol for termination of pregnancy through 63 days' gestation: A pilot study.

OBJECTIVES: We conducted a pilot study to evaluate a single dose of letrozole 30 mg prior to misoprostol 800 mcg buccally for medication abortion STUDY DESIGN: We enrolled 40 participants seeking medication abortion up to 63 days' gestation at a site in Salt Lake City, UT. Participants received a single dose of letrozole 30 mg in-clinic followed 2 days later by misoprostol 800 mcg buccally at home. They took a second dose of misoprostol if they had no bleeding within 24 hours of the first. Participants returned 7 to 10 days later for assessment of abortion outcome and side effects RESULTS: Thirty-seven participants (93%) returned for follow-up and 2 (5%) went to another facility from which research staff obtained outcome data. Three-fourths (29/39, 74%, 95% CI: 60%-89%) had a complete abortion; 4 (10%, 95% CI: 0.3%-20%) had an incomplete abortion and opted for aspiration, and 6 (15%, 95% CI: 4%-27%) had an ongoing pregnancy. All subjects with follow-up reported taking the first dose of misoprostol. Ten (27%) took the second dose as well; only three did so due to no bleeding. Nineteen participants (51%) reported side effects after letrozole prior to misoprostol and two people (5%) rated these effects as severe. Side effects following misoprostol occurred in 33 participants (89%) and were as expected based on previous literature. No serious adverse events were reported CONCLUSION: A single dose of letrozole 30 mg followed by misoprostol had lower than desirable efficacy and does not warrant further study. IMPLICATIONS: A single dose of letrozole does not appear to be an effective adjunct to misoprostol for medication abortion.

Forensic Toxicological Aspects of Misoprostol Use in Pharmacological Abortions.

The aim of this study was establishment of an UHPLC-QqQ-MS/MS method for the deter-mination of misoprostol acid in biological specimens in cases of pharmacological abortions. Forensic toxicological examination was performed in three different biological samples (whole blood, placenta and fetal liver). The validation parameters of the method were as follows: limit of detection: 25 pg/mL; limit of quantification: 50 pg/mL, coefficient of determination: >0.999 (R2), intra- and interday accuracy and precision: not greater than 13.7%. The recovery and matrix effect were in the range of 88.3−95.1% and from −11.7 to −4.9%, respectively. Toxicological analysis of the mother's blood (collected two days after pregnancy termination) did not reveal any abortifacients; however, misoprostol acid was found in the placenta (793 pg/g) and fetal liver (309 pg/g). The second case involved a fetus found near a garbage container. The concentration of misoprostol acid in the placenta was 2332 pg/g. In the presented study, an extensive literature review of misoprostol pharmacokinetics studies was performed. To our knowledge, the UHPLC-QqQ-MS/MS technique presented in this paper is the first quantitative method applied for forensic toxicological purposes. In addition, postmortem concentrations of misoprostol acid in miscarried fetuses due to illegal abortions were reported for the first time.

Medical methods for first trimester abortion.

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; I2 = 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; I2= 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; I2 = 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; I2 = 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; I2 = 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; I2 = 0%; 2 RCTs, 1380 women; low-certainty evidence) and diarrhoea (RR 1.80 95% CI 1.49 to 2.17; I2 = 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; I2 = 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; I2 = 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; I2 = 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; I2 = 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; I2 = 87%; 5 RCTs, 2705 women; low-certainty evidence) and oral administration (RR 0.58, 95% CI 0.11 to 2.99; I2 = 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.

Sublingual misoprostol versus manual vacuum aspiration for treatment of incomplete abortion in Nigeria: a randomized control study.

Introduction: single-dose of sublingual misoprostol 400mcg with the participant followed-up at the gynecology clinic one week after with an ultrasound scan for the completeness of the uterine evacuation. Objective: to compare the effectiveness of single-dose sublingual misoprostol to manual vacuum aspiration in the treatment of incomplete spontaneous abortion in Enugu, Nigeria. Methods: the primary outcome measure was the incidence of complete uterine evacuation (complete abortion) after one week of treatment while the secondary outcome measures included incidence, types, and tolerability of treatment side effects as well as participants' satisfaction with the treatment received. Results: two hundred and three participants who met the study criteria and completed the study were randomised into the intervention group (n=102) received single-dose sublingual misoprostol 400mcg and the control group (n= 101) received manual vacuum aspiration. Incidence of complete abortion was 86.3% for the misoprostol group and 100.0% for the control group, RR = 0.86, (CI 95%: 0.80 - 0.93), p <0.001. The most common side effect was abdominal pain with an incidence of 27.5% versus 48.55 for the misoprostol and control groups respectively (p = 0.002). Most participants in each group (81.1% versus 77.6% for the misoprostol and control groups respectively) considered the side effects as tolerable. The mean visual analogue scale score for maternal satisfaction was higher in the misoprostol group (86.7 ± 14.11) than the control group (81.36 ± 11.10), p < 0.001. Conclusion: the treatment of incomplete spontaneous abortion with single-dose sublingual misoprostol 400mcg produced a high rate of complete abortion among women in Enugu, Nigeria. Despite having a lower complete abortion rate, maternal satisfaction was higher when compared with women that had manual vacuum aspiration of the uterus. Trial registration: trial registration number - PACTR202009857889210, date of registration - September 23rd, 2020. Retrospectively registered.

Unusual Posterior Wall Uterine Rupture with the Use of Misoprostol for Second Trimester Pregnancy Termination.

Abortion is defined as the termination of pregnancy before the fetus is viable. It is one of the most commonly performed procedures in gynecological departments worldwide. Termination of pregnancy in second trimester is one of the greatest challenges because of multiple modes of termination options with their risks of complication and making it riskier than the first trimester termination. We report this case because of a rare occurrence of posterior wall rupture which would have led to grave complication if not anticipated and detected early.

Ruptured ectopic pregnancies following methotrexate treatment: clinical course and predictors for improving patient counseling.

To determine the predictors for tubal rupture among women treated with methotrexate (MTX) for ectopic pregnancy. We performed a retrospective cohort analysis in a tertiary university-affiliated medical center. Medical records of 401 women who were diagnosed with ectopic pregnancy and were treated with MTX between January 2001 and June 2017 were reviewed. Forty-one women were diagnosed with ruptured ectopic pregnancy (study group) and 360 women with non-ruptured ectopic pregnancy (control group). Descriptive data and predictive variables for rupture ectopic pregnancy following MTX treatment were reviewed. Out of 122 women who failed MTX treatment, forty-one women had tubal rupture (33.6%). The median time interval from MTX treatment to tubal rupture was 6 days (1-25). ß-hCG percentage change in the 48 h preceding MTX treatment and ß-hCG level at day 0 were independent predictors for tubal rupture (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.04-1.12, p < 0.001 for every percent change in ß-hCG; OR = 1.001, 95% CI = 1.0003-1.002 for every unit change in ß-hCG, respectively). In a decision tree analysis model, in women with ß-hCG percentage increment >69% in the 48 h preceding methotrexate the probability for tubal rupture was 85%. Risk assessment for tubal rupture should be made before methotrexate treatment according to ß-hCG dynamics and level. The absolute risk for tubal rupture in women with ß-hCG increment<20% is low.

Risk factors of retained products of conception after miscarriage or termination with gemeprost in the second trimester of pregnancy: a retrospective case-controlled study in Japanese population.

Retained products of conception (RPOC) is a complication that occurs in the second trimester of pregnancy. We enrolled 98 women who had a miscarriage or termination with gemeprost in the second trimester of pregnancy. Eighteen cases (18.4%) were RPOC-positive. The gestational week at miscarriage or termination was earlier in the RPOC-positive group than those in the RPOC-negative group (p = .003). The period of the third stage of labour was longer in the RPOC-positive group than in RPOC-negative group (p = .040). The proportion of placental forceps use was higher in the RPOC-positive group than in RPOC-negative group (p = .003). Multivariate logistic regression analysis showed that gestational week (OR: 3.53; p = .04) and use of placental forceps at delivery (OR: 2.21; p = .012) were independent risk factors for RPOC. Earlier gestational weeks at miscarriage or termination and use of placental forceps at delivery were predictive factors for RPOC after second trimester miscarriage or termination with gemeprost.Impact StatementWhat is already known on this subject? There have been some reports on risk factors of RPOC. A previous report showed that the termination of pregnancy with misoprostol at earlier periods was associated with an increased risk of RPOC.What the results of this study add? There have been few studies on the risk factors of RPOC after miscarriage or termination with gemeprost. In this study, we evaluated the risk factors of RPOC after miscarriage or termination of pregnancy with gemeprost in the second trimester. We found that an earlier gestational age (between 12 and 17 weeks) at delivery and using placental forceps to remove placenta were significant risk factors of RPOC after miscarriage or termination of pregnancy with gemeprost in the second trimester.What the implications are of these findings for clinical practice and/or further research? An earlier gestational age and using forceps to remove placenta may be significant risk factors for RPOC. The accurate evaluation and treatment for RPOC is important for maternal life-saving efforts and subsequent pregnancies. Further research is needed to draft a standardised protocol for RPOC.