Monoamine oxidases activity maintains endometrial monoamine homeostasis and participates in embryo implantation and development.

BACKGROUND: Monoamine oxidases (MAOs) is an enzyme that catalyzes the deamination of monoamines. The current research on this enzyme is focused on its role in neuropsychiatric, neurodevelopmental, and neurodegenerative diseases. Indeed, MAOs with two isoforms, namely, A and B, are located on the outer mitochondrial membrane and are widely distributed in the central nervous system and peripheral tissues. Several reports have described periodic changes in the levels of this enzyme in the human endometrial tissue. RESULTS: The novel role of MAOs in endometrial receptivity establishment and embryonic development by maintaining monoamine homeostasis was investigated in this study. MAOs activity was observed to be enhanced during the first trimester in both humans and mice under normal conditions. However, under pathological conditions, MAOs activity was reduced and was linked to early pregnancy failure. During the secretory phase, the endometrial stromal cells differentiated into decidual cells with a stronger metabolism of monoamines by MAOs. Excessive monoamine levels cause monoamine imbalance in decidual cells, which results in the activation of the AKT signal, decreased FOXO1 expression, and decidual dysfunction. CONCLUSIONS: The findings suggest that endometrial receptivity depends on the maintenance of monoamine homeostasis via MAOs activity and that this enzyme participates in embryo implantation and development.

The association between history of retained placenta and success rate of misoprostol treatment for early pregnancy failure.

BACKGROUND: To date, the association between retained placenta and treatment success rate of misoprostol for early pregnancy failure has yet to be evaluated. The aim of this study was to evaluate this association and further investigated the connection between medical, clinical and sonographic parameters and treatment success. METHODS: We conducted a retrospective cohort study of women with early pregnancy failure treated with misoprostol from 2006 to 2021. The success rate of misoprostol treatment was compared between patients with history of retained placenta including women who underwent manual lysis of the placenta following delivery or patients who were found to have retained products of conception during their post-partum period (study group) and patients without such history (controls). Demographic, clinical, and sonographic characteristics as well as treatment outcomes were compared between the groups. RESULTS: A total of 271 women were included in the study (34 women in the study group compared to 237 women in the control group). Two-hundred and thirty-three women (86.0%) presented with missed abortion, and 38 (14.0%) with blighted ovum. Success rates of misoprostol treatment were 61.8% and 78.5% for the study and control groups, respectively (p = 0.032). Univariate analysis performed comparing successful vs. failed misoprostol treatment showed advanced age, gravidity, parity and gestational sac size (mm) on TVUS were associated with higher misoprostol treatment failure rate. Following a multivariate logistic regression model these variables did not reach statistical significance. CONCLUSION: Women who have an event of retained placenta following childbirth appear to have decreased success rate of treatment with misoprostol for early pregnancy failure. Larger studies are needed to confirm this finding.

Retroperitoneal ectopic pregnancy: successful expectant management in condition of early pregnancy failure.

BACKGROUND: Retroperitoneal ectopic pregnancy (REP) refers to abnormal implantation of the fertilized egg in the retroperitoneal cavity. REP can be divided into pelvic and abdominal positions. Extremely rare, the incidence of REP is less than 1% of ectopic pregnancy (EP). Herein, we report the first case of paraaortic-located REP in association with successful expectant management, thus raising awareness among healthcare providers, particularly in low-resource settings. CASE PRESENTATION: A reproductive-age woman presented at our tertiary referral hospital because of amenorrhea and a positive pregnancy test. Based on serial serum ß-hCG levels and imaging modalities including transabdominal ultrasound, transvaginal sonography, and magnetic resonance imaging (MRI), a REP of 7-9 weeks of gestational age adherent to abdominal paraaortic region was detected. Since the pregnancy was spontaneously arrested without clinical symptoms, expectant management was first indicated following careful evaluation. After a 1-month follow-up, the ectopic mass naturally degenerated without complications and her ß-hCG concentration returned to a negative value. Therefore, the patient recovered completely and avoided unnecessary surgery as well as toxicity of medical treatment when using systemic methotrexate. CONCLUSIONS: In addition to transvaginal and transabdominal ultrasound, MRI is necessary for the diagnosis of nonviable REP. Alongside the great vessels in the abdominal cavity should be taken into consideration in all suspected cases relating to this rare entity. Expectant management may be carefully indicated in conditions of nonviable REP and unruptured REP, where applicable.

The performances of serum activins and follistatin in the diagnosis of ectopic pregnancy: A prospective case-control study.

BACKGROUND: The diagnosis of ectopic pregnancy (EP) is challenging and 40-50% of patients are initially misdiagnosed. METHODS: This prospective case-control study measured activin-A, activin-B, activin-AB and follistatin for the diagnosis of EP, spontaneous abortion (SAB) and normal intrauterine pregnancy (IUP). Sera were collected from 120 women with symptoms suggesting early pregnancy failure and who were clinically diagnosed as IUP, SAB or EP (n = 40/group). The markers were measured by ELISA and their area under the curve (AUC), cut-off value, sensitivity and specificity were determined by receiver-operating characteristic curve. The results were compared with serum ß-human chorionic gonadotropin and progesterone. RESULTS: Activin-A and activin-B decreased significantly, while activin-AB and follistatin increased, in the EP and SAB groups than the IUP group. Activin-AB (AUC = 0.961) and progesterone (AUC = 0.973) were the best markers for EP and SAB, respectively. Activin-AB (≥61.5 pg/mL) showed 92.5% sensitivity, 85% specificity, 75.5% positive predictive value (PPV) and 95.8% negative predictive value (NPV) for EP. Progesterone (≤6.3 ng/mL) had 100% sensitivity, 86.2% specificity, 78.4% PPV and 100% NPV for SAB. CONCLUSIONS: Serum activins and follistatin were significantly altered with EP and activin-AB could be a promising marker for the diagnosis of EP.

Genetic abnormalities seen on CVS in early pregnancy failure.

Objective: To determine the frequency and distribution of chromosome abnormalities in women with early pregnancy failure (EPF) detected by cytogenetic testing on chorionic villus sampling.Method: Retrospective observational cohort study of chromosomal analysis from transvaginal chorionic villus sampling (CVS) or reflex products of conception (POC) karyotype. CVS was offered as a training tool for Maternal Fetal Medicine fellows prior to manual vacuum aspiration for EPF 9-week gestation. POC were analyzed for cytogenetics if no results were obtained on CVS.Results: One hundred thirty samples were collected from December 2011 to April 2015. 33 (27.3%) cases had a normal karyotype and 88 (73.0%) cases had an abnormal karyotype. The most common group of abnormalities were trisomy, (n = 50, 41.3%), triploidy/tetraploidy, (n = 17, 14.0%), monosomy (n = 15, 12.4%), and structural rearrangements (n = 6, 5.0%). Nine (6.9%) samples were maternal decidua only. Abnormal karyotype in EPF was significantly increased in women by age group (p < .01) but not in women with a history of prior miscarriage (p = .5).Conclusion: Our cohort had a high detection rate of aneuploidy. The most common chromosomal abnormalities in EPF were: trisomy, followed by triploidy/tetraploidy, monosomy, and structural rearrangements. Maternal age had the strongest correlation with EPF associated with aneuploidy.

Mifepristone and misoprostol versus misoprostol alone for uterine evacuation after early pregnancy failure: study protocol for a randomized double blinded placebo-controlled comparison (Triple M Trial).

BACKGROUND: Early pregnancy failure (EPF) is a common complication of pregnancy. If women do not abort spontaneously, they will undergo medical or surgical treatment in order to remove the products of conception from the uterus. Curettage, although highly effective, is associated with a risk of complications; medical treatment with misoprostol is a safe and less expensive alternative. Unfortunately, after 1 week of expectant management in case of EPF, medical treatment with misoprostol has a complete evacuation rate of approximately 50%. Misoprostol treatment results may be improved by pre-treatment with mifepristone; its effectiveness has already been proven for other indications of pregnancy termination. This study will test the hypothesis that, in EPF, the sequential combination of mifepristone with misoprostol is superior to the use of misoprostol alone in terms of complete evacuation (primary outcome), patient satisfaction, complications, side effects and costs (secondary outcomes). METHODS: The trial will be performed multi-centred, prospectively, two-armed, randomised, double-blinded and placebo-controlled. Women with confirmed EPF by ultrasonography (6-14 weeks), managed expectantly for at least 1 week, can be included and randomised to pre-treatment with oral mifepristone (600 mg) or oral placebo (identical in appearance). Randomisation will take place after receiving written consent to participate. In both arms pre-treatment will be followed by oral misoprostol, which will start 36-48 h later consisting of two doses 400 µg (4 hrs apart), repeated after 24 h if no tissue is lost. Four hundred sixty-four women will be randomised in a 1:1 ratio, stratified by centre. Ultrasonography 2 weeks after treatment will determine short term treatment effect. When the gestational sac is expulsed, expectant management is advised until 6 weeks after treatment when the definitive primary endpoint, complete or incomplete evacuation, will be determined. A sonographic endometrial thickness < 15 mm using only the allocated therapy by randomisation is considered as successful treatment. Secondary outcome measures (patient satisfaction, complications, side effects and costs) will be registered using a case report form, patient diary and validated questionnaires (Short Form 36, EuroQol-VAS, Client Satisfaction Questionnaire, iMTA Productivity Cost Questionnaire). DISCUSSION: This trial will answer the question if, in case of EPF, after at least 1 week of expectant management, sequential treatment with mifepristone and misoprostol is more effective than misoprostol alone to achieve complete evacuation of the products of conception. TRIAL REGISTRATION: Clinicaltrials.gov (d.d. 02-07-2017): NCT03212352. Trialregister.nl (d.d. 03-07-2017): NTR6550. EudraCT number (d.d. 07-08-2017): 2017-002694-19. File number Commisie Mensgebonden Onderzoek (d.d. 07-08-2017): NL 62449.091.17.

The role of repeat misoprostol dose in the management of early pregnancy failure.

PURPOSE: We aimed to assess the role of repeat misoprostol administration in those with thickened endometrium in the management of early pregnancy failure (EPF). METHODS: A retrospective cohort study in two university hospitals among women receiving misoprostol treatment for EPF. Those with thickened endometrium at the first follow-up visit, who received a repeat 800 µg dose of vaginal misoprostol in institution B and no treatment in institution A, constituted the study group. The primary outcome was treatment success, defined as complete uterine evacuation without the need for any operative intervention RESULTS: Overall, 608 women with thickened endometrium as assessed by transvaginal ultrasonography 2 days following initial misoprostol administration for EPF were included. Of them, 427 did not receive repeat misoprostol dose, and 181 received repeat misoprostol dose. The rate of surgical intervention did not differ between those who received a repeat misoprostol dose (6.1%) and those who did not (4.3%) (P = 0.32). The median endometrial thickness was similar in those that did and did not require subsequent surgical intervention (P = 0.65), and was a poor predictor of treatment outcome. CONCLUSIONS: Repeat misoprostol administration among women with thickened endometrium following initial misoprostol administration for EPF was not associated with improved treatment success rates.

Current and future expectations of mifepristone treatment in early pregnancy failure: a survey among Dutch gynaecologists.

To investigate the current and future addition of mifepristone to misoprostol treatment in case of early pregnancy failure (EPF), a digital questionnaire was distributed to a representative sample of all Dutch hospitals (25/79). In non-teaching centres, the presence of a local protocol was significantly lower compared to academic and teaching hospitals (p=.012). If a local protocol was present, the first choice of treatment was medical in 54.5%. Four respondents (16%) always prescribed mifepristone in case of EPF. The most common reason not prescribing mifepristone was the lack of sufficient scientific evidence. An average increase in success rate of 21.7% was desired to prescribe mifepristone in the future for EPF. Completeness of evacuation of products of conception from the uterus was usually assessed after 1 week by ultrasonography combined with clinical signs. If a complete evacuation was not achieved by the initial medical treatment, expectant management was proposed just as often as surgical intervention. Impact Statement What is already known on this subject? In case of early pregnancy failure (EPF), women can choose from both expectant medical (misoprostol, whether or not combined with mifepristone) and surgical (D and C) treatment. In The Netherlands, a national guideline concerning the treatment of EPF is still lacking. A questionnaire performed by Verschoor et al. ( 2014 ) showed there was a large practice variety between Dutch clinics. What the results of this study add? In this study, a representative sample of all Dutch clinics received a questionnaire about the treatment of EPF. The results confirm a large practice variation regarding treatment of EPF. The first choice of treatment, the medical treatment regimen, and the assessment of whether or not the treatment have been variations of successful between clinics. With regards to the addition of mifepristone to the medical treatment regime with misoprostol, gynaecologists are willing to consider mifepristone if an improvement of efficacy of approximately 20% is scientifically proven. What the implications are of these findings for clinical practice and/or further research? In our opinion, these results emphasise the need for a national guideline concerning the treatment of EPF. Our results also demonstrate that, if the addition of mifepristone to medical treatment with misoprostol proves to be more efficient than misoprostol alone, gynaecologists are willing to prescribe mifepristone in the future. Whether the addition is indeed more effective than misoprostol alone, will be the subject of a multicentre, double-blind, placebo-controlled randomised controlled trial, planned to begin in the first half of 2018.

Management of early pregnancy loss, with a focus on patient centered care.

Early pregnancy loss is the most common complication in pregnancy. Management options for miscarriage include expectant management, medical intervention, or surgical aspiration. Non-surgical and surgical management are all safe and acceptable options for medically uncomplicated patients. Patient and provider preferences contribute profoundly to clinical decisions about miscarriage management. Shared-decision making and evidence based counseling have been shown to significantly improve patient satisfaction with early pregnancy loss care. This review article will discuss the epidemiology and risk factors of early pregnancy loss, current evidence and clinical practice guidelines around management options, and provider and patient preferences for early pregnancy loss management.

Pregnancy of unknown location: Evaluation and management.

Early diagnosis of an extrauterine pregnancy is important for safe and effective management. However, a pregnancy's location often cannot be easily determined with abnormal implantations or prior to 5-6 weeks' gestation. Multiple testing strategies exist to diagnose an abnormal pregnancy when location is unknown, but caution needs to be used to avoid a false diagnosis. Medical treatment is optimal when an abnormal pregnancy is diagnosed early. Because most of these pregnancies are intrauterine, additional testing to localize the pregnancy will allow the correct choice of therapy and avoids unnecessary exposure to a toxic therapy. This testing strategy should be reserved for patients with significant concern for ectopic pregnancy, based on either risk factors or clinical findings. Overuse of this approach can lead to interruption of normal pregnancies.

Miscarriage information available on the internet: a content analysis of leading consumer websites.

OBJECTIVE: The objective of this content analysis was to explore the accuracy and completeness of information provided about miscarriage on consumer-facing websites. STUDY DESIGN: We identified the most popular consumer websites for health information and the leading medical and nursing professional association websites. We reviewed each website for content on miscarriage aimed at consumers and compared the website content to the information contained in the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin on Early Pregnancy Loss. We used a simple scoring method to compare the accuracy and completeness of the content on each website with the ACOG Practice Bulletin. RESULTS: Sixty percent (n = 9) of the top 15 consumer websites for health information had dedicated webpages on miscarriage. Of the nine leading professional association websites, two had dedicated pages on miscarriage. On average, each site provided information on 64% of the key messages from the ACOG Practice Bulletin. Sites commonly emphasized and provided overall accurate and complete information on risk factors of miscarriage. The key messages with the most limited or inaccurate information pertained to diagnosis of miscarriage; treatment, including medical management with mifepristone and misoprostol; instructions postmiscarriage and prevention of miscarriage. CONCLUSIONS: The majority of popular health websites include consumer-facing content on miscarriage, and the information presented is a mostly complete and accurate representation of the ACOG Practice Bulletin. The lack of information on treatment options may affect patients' ability to make informed choices about their care. The missing information points to areas that patients may feel underprepared to discuss with healthcare providers. IMPLICATIONS: More effort is needed to ensure that internet-based consumer information about miscarriage reflects the best scientific evidence.

Comparison of Mifepristone Followed by Misoprostol with Misoprostol Alone for Treatment of Early Pregnancy Failure: A Randomized Double-Blind Placebo-Controlled Trial.

Objective: To compare the efficacy and safety of mifepristone followed by misoprostol with misoprostol alone in the management of early pregnancy failure (EPF). Study Design: A randomized double-blind placebo-controlled clinical trial. Methods: Ninety-two women with EPF ≤12 weeks were recruited and randomly allocated to receive either mifepristone 200 mg (n = 46) or placebo (n = 46). Forty-eight hours later, patients in both the groups were given 800 µg misoprostol per-vaginum. If no expulsion occurred within 4 h, repeat doses of 400 µg misoprostol were given orally at 3-hourly interval to a maximum of 2 doses in women ≤9 weeks by scan and 4 doses in women >9 weeks by scan. Results: Pre-treatment of misoprostol with mifepristone significantly increased the complete abortion rate (86.7 vs. 57.8%, p = 0.009) and, hence, reduced the need for surgical evacuation (13.3 vs. 42.2%, p = 0.002), induction to expulsion interval (4.74 ± 2.24 vs. 8.03 ± 2.77 h, p = 0.000), mean number of additional doses of misoprostol required (0.68 vs. 1.91, p = 0.000), and side effects. Conclusion: Use of mifepristone prior to misoprostol in EPF significantly improves the efficacy and reduces the side effects of misoprostol alone.

Marked improvement in the success rate of medical management of early pregnancy failure following the implementation of a novel institutional protocol and treatment guidelines: a follow-up study.

PURPOSE: To analyze the success rate, time to passage of tissue and subjective patient experience of a newly implemented protocol for medical management of early pregnancy failure (EPF) over a 2-year period. METHODS: A retrospective chart review of all patients with early pregnancy failure primarily opting for medical management was performed. 200 mg mifepristone were administered orally, followed by a single vaginal dose of 800 mcg misoprostol after 36-48 h. We followed-up with our patients using a written questionnaire. RESULTS: 167 women were included in the present study. We observed an overall success rate of 92 %, defined as no need for surgical management after medication administration. We could not identify predictive values for success in a multivariate regression analysis. Most patients (84 %) passed tissue within 6 h after misoprostol administration. The protocol was well tolerated with a low incidence of side effects. Pain was managed well with sufficient analgesics. Responders to the questionnaire felt adequately informed prior to treatment and rated their overall experience as positive. CONCLUSION: The adaption of the institutional medical protocol resulted in a marked improvement of success rate when compared to the previously used protocol (92 vs. 61 %). We credit this increase to the adjusted medication schema as well as to targeted physician education on the expected course and interpretation of outcome measures. Our results underscore that the medical management of EPF is a safe and effective alternative to surgical evacuation in the clinical setting.

Predicting first trimester pregnancy outcome: derivation of a multiple marker test.

OBJECTIVE: To predict first trimester pregnancy outcome using biomarkers in a multicenter cohort. DESIGN: Case-control study. SETTING: Three academic centers. PATIENT(S): Women with pain and bleeding in early pregnancy. INTERVENTION(S): Sera from women who were 5-12 weeks' gestational age with ectopic pregnancy (EP), viable intrauterine pregnancy (IUP), and miscarriage/spontaneous abortion (SAB) was analyzed by ELISA and immunoassay for activin A, inhibin A, P, A Disintegrin And Metalloprotease-12, pregnancy-associated plasma protein A (PAPP-A), pregnancy specific B1-glycoprotein (SP1), placental-like growth factor, vascular endothelial growth factor, glycodelin (Glyc), and hCG. Classification trees were developed to optimize sensitivity/specificity for pregnancy location and viability. MAIN OUTCOME MEASURE(S): Area under receiver operating characteristic curve, sensitivity, specificity, and accuracy of first trimester pregnancy outcome. RESULT(S): In 230 pregnancies, the combination of trees to maximize sensitivity and specificity resulted in 73% specificity (95% confidence interval (CI) 0.65-0.80) and 31% sensitivity (95% CI 0.21-0.43) for viability. Similar methods had 21% sensitivity (95% CI 0.12-0.32) and 33% specificity (95% CI 0.26-0.41) for location. Activin A, Glyc, and A Disintegrin And Metalloprotease-12 definitively classified pregnancy location in 29% of the sample with 100% accuracy for EP. Progesterone and PAPP-A classified the viability in 61% of the sample with 94% accuracy. CONCLUSION(S): Multiple marker panels can distinguish pregnancy location and viability in a subset of women at risk for early pregnancy complications. This strategy of combining markers to maximize sensitivity and specificity results in high accuracy in a subset of subjects. Activin A, ADAM12, and Glyc are the most promising markers for pregnancy location; P and PAPP-A for viability.

The added value of mifepristone to non-surgical treatment regimens for uterine evacuation in case of early pregnancy failure: a systematic review of the literature.

OBJECTIVE(S): Early pregnancy failure (EPF) is a common complication of pregnancy. Surgical intervention carries a risk of complications and, therefore, medical treatment appears to be a safe alternative. Unfortunately, the current medical treatment with misoprostol alone has complete evacuation rates between 53% and 87%. Some reports suggest that sequential treatment with mifepristone and misoprostol leads to higher success rates than misoprostol alone. STUDY DESIGN: To evaluate the added value of mifepristone to current non-surgical treatment regimens in women with EPF we performed a systematic literature search. Electronic databases were searched: PubMed, Cochrane Library, Current Controlled Trials, and ClinicalTrials.gov. Clinical studies, both randomised and non-randomised trials, reporting on the added value of mifepristone to current non-surgical treatment regimens in women with EPF were included. Data of sixteen studies were extracted using a data extraction sheet (based on the Cochrane Consumers and Communication Review Group's data extraction template). The methodological quality was assessed using the Cochrane Collaboration Risk of Bias tool. RESULTS: In five randomised and eleven non-randomised trials, success rates of sequential treatment with mifepristone and misoprostol in case of EPF varied between 52% and 95%. Large heterogeneity existed in treatment regimens and comparators between studies. CONCLUSION(S): The existing evidence is insufficient to draw firm conclusions about the added value of mifepristone to misoprostol alone. A sufficiently powered randomised, double blinded placebo-controlled trial is urgently required to test whether, in EPF, the sequential combination of mifepristone with misoprostol is superior to misoprostol only.

Serum biomarkers may help predict successful misoprostol management of early pregnancy failure.

In order to simplify management of early pregnancy loss, our goal was to elucidate predictors of successful medical management of miscarriage with a single dose of misoprostol. In this secondary analysis of data from a multicenter randomized controlled trial, candidate biomarkers were compared between 49 women with missed abortion who succeeded in passing their pregnancy with a single dose of misoprostol and 46 women who did not pass their pregnancy with a misoprostol single dose. We computed the precision of trophoblastic protein and hormone concentrations to discriminate between women who succeed or fail single dose misoprostol management. We also included demographic factors in our analyses. We found overlap in the concentrations of the individual markers between women who succeeded and failed single-dose misoprostol. However, hCG levels ≥ 4000 mIU/mL and ADAM-12 levels ≥ 2500 pg/mL were independently associated with complete uterine expulsion after one dose of misoprostol in our population. A multivariable logistic model for success included non-Hispanic ethnicity and parity <2 in addition to hCG ≥ 4000 mIU/mL and ADAM-12 ≥ 2500 pg/mL and had an area under the receiver operating characteristic (ROC) of 0.81 (95% confidence interval: 72-90%). Categorizing women with a predicted probability of ≥ 0.65 resulted in a sensitivity of 75.0%, specificity 77.1% and positive predictive value of 81.8%. While preliminary, our data suggest that serum biomarkers, especially when combined with demographic characteristics, may be helpful in guiding patient decision-making regarding the management of early pregnancy failure (EPF). Further study is warranted.

Problems of modern approaches to management of early pregnancy failure.

In the last 20 to 30 years, early diagnosis of pregnancy has markedly decreased ectopic pregnancy-related maternal mortality, and the necessity for surgical treatment. With modern approaches in the treatment of ectopic pregnancy, surgical therapy has been replaced by medical therapy and medical treatment by spontaneous follow-up in appropriate cases. However, this current trend has led to some problems, including the maximization of ultrasonographic interpretations, misunderstandings in serial human koryonik gonadotropin hormon measurements, and complications due to inappropriate methotrexate use. The aim of the present study was to review the literature relating to the diagnosis and follow-up of early pregnancies, to underline some of the important considerations, and to help avoid possible iatrogenic errors.

Sequential use of mifepristone and misoprostol in treatment of early pregnancy failure appears more effective than misoprostol alone: a retrospective study.

OBJECTIVE: Is treatment of early pregnancy failure (EPF) with sequential use of mifepristone and misoprostol more effective than treatment with misoprostol alone? STUDY DESIGN: In a retrospective cohort study at the Department of Obstetrics and Gynaecology of the Radboud University Medical Centre, 301 women with early pregnancy failure receiving medical treatment between January 2008 and March 2013 were included. Of these, 199 women were pre-treated with 200mg mifepristone (orally) followed by 2 consecutive doses of 800mcg misoprostol (vaginally) and 102 women were treated with 2 consecutive doses of 800mcg misoprostol (vaginally) alone. RESULTS: Complete expulsion was achieved in 66.8% of the women treated with a sequential combination of mifepristone and misoprostol versus 54.9% of the women treated with misoprostol alone. The difference in rates of complete expulsion was 11.9% (P<0.05; 95% CI 0.3-23.6%). CONCLUSIONS: Medical treatment of early pregnancy failure with a sequential combination of mifepristone and misoprostol was more effective than treatment with misoprostol alone. Our findings will have to be confirmed by a large prospective multicentre double blinded-randomized trial.

[Obtaining of uterine vacuity in pregnancy loss]. / Obtention de la vacuité utérine dans le cadre d'une perte de grossesse.

OBJECTIVE: To assess early and late benefits and harms of different management options for first trimester miscarriage and for induction of labor and obtaining of uterine vacuity in case of fetal death beyond of 14weeks of gestation. METHODS: French and English publications were searched using PubMed and Cochrane Library. RESULTS: Concerning missed miscarriage, expectant management is not recommended (LE1) because it increases the risk of failure, need of unplanned surgical procedure and blood transfusion (LE1). Surgical uterine evacuation remains more effective than medical treatment using misoprostol (LE1), but both techniques involve rare and comparable risks (EL1). When chosen, medical treatment should be a vaginal dose of 800µg of misoprostol, possibly repeated 24 to 48hours later (EL2). Administration of mifepristone prior to misoprostol is not recommended (EL2). In case of incomplete miscarriage, expectant management can be offered because it does not increase the risk of complications, neither haemorrhagic nor infectious (EL1). Medical treatment using misoprostol is not recommended (EL2) because it does not improve the evacuation rate when compared to our first option, and does not reduce the risk of complications (EL2). Surgical uterine evacuation leads to high evacuation rate (97-98%) and low risk of complications, haemorrhagic and infectious (<5%) (EL1). However, this option should not be the only one because of the good efficiency of the expectant management (more than 75% of evacuation) and comparably low risk of complications (EL1). Surgical aspiration should be favoured to curettage because it is quicker, less painful and leads to less bleeding (EL2). After a first trimester miscarriage future fertility is identical with each treatment (EL2). When a trophoblastic retention is suspected, a diagnostic hysteroscopy is recommended (EL2). In case of late intrauterine foetal death beyond 14weeks of gestation and without a past caesarean section, the most efficient protocol seems to be vaginal administration of misoprostol 200 to 400µg every 4 to 6hours (EL2). Twenty-four hours prior to misoprostol the administration of 200mg of mifepristone is recommended (EL3) because it improves the induction-expulsion time and diminishes the quantity of needed misoprostol (and so the complications linked to it) (EL3).

[Association of mifepristone and misoprostol for the medical management of early pregnancy failure]. / Évaluation de l'association mifépristone-misoprostol pour la prise en charge médicale des fausses couches retardées.

OBJECTIVES: A retrospective monocentric clinical trial was performed to evaluate the efficacy of the association of mifepristone and misoprostol for the management of early pregnancy failure. PATIENTS AND METHODS: Ninety-two women with early pregnancy failure or anembryonic pregnancy were first treated with 600 mg of mifepristone and 48 hours later with 400 µg of misoprostol by oral administration. Successful treatment, defined as an empty uterus, was searched at day 3, with the association of misoprostol-mifepristone alone or with complementary medical treatment, prostaglandins or ocytocine. RESULTS: The overall treatment success was 82% (75 of 92 women) with 69 successful cases at day 3 (75%). Six of 92 women (7%) needed a second-line medical treatment. For the last 17 women (18%), the failure of the associated tested medical treatment lead to a secondary surgery. No prognostic factor for the successful medical treatment has been highlighted. DISCUSSION AND CONCLUSION: A high efficacy for the management of early pregnancy failure is demonstrated for the mifepristone and misoprostol medical treatment. The specific contribution of mifepristone, although proven in the cases of termination of evolutive pregnancies, should be further evaluated in the future for the specific management of early pregnancy failure. Nevertheless, no prognostic factor for the success of the propose treatment can be determined, as the amount of patients enrolled in this study was not sufficient.