Medical treatment for early fetal death (less than 24 weeks).

BACKGROUND: In most pregnancies that miscarry, arrest of embryonic or fetal development occurs some time (often weeks) before the miscarriage occurs. Ultrasound examination can reveal abnormal findings during this phase by demonstrating anembryonic pregnancies or embryonic or fetal death. Treatment has traditionally been surgical but medical treatments may be effective, safe, and acceptable, as may be waiting for spontaneous miscarriage. This is an update of a review first published in 2006. OBJECTIVES: To assess, from clinical trials, the effectiveness and safety of different medical treatments for the termination of non-viable pregnancies. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (24 October 2018) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials comparing medical treatment with another treatment (e.g. surgical evacuation), or placebo, or no treatment for early pregnancy failure. Quasi-randomised studies were excluded. Cluster-randomised trials were eligible for inclusion, as were studies reported in abstract form, if sufficient information was available to assess eligibility. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: Forty-three studies (4966 women) were included. The main interventions examined were vaginal, sublingual, oral and buccal misoprostol, mifepristone and vaginal gemeprost. These were compared with surgical management, expectant management, placebo, or different types of medical interventions were compared with each other. The review includes a wide variety of different interventions which have been analysed across 23 different comparisons. Many of the comparisons consist of single studies. We limited the grading of the quality of evidence to two main comparisons: vaginal misoprostol versus placebo and vaginal misoprostol versus surgical evacuation of the uterus. Risk of bias varied widely among the included trials. The quality of the evidence varied between the different comparisons, but was mainly found to be very-low or low quality.Vaginal misoprostol versus placeboVaginal misoprostol may hasten miscarriage when compared with placebo: e.g. complete miscarriage (5 trials, 305 women, risk ratio (RR) 4.23, 95% confidence interval (CI) 3.01 to 5.94; low-quality evidence). No trial reported on pelvic infection rate for this comparison. Vaginal misoprostol made little difference to rates of nausea (2 trials, 88 women, RR 1.38, 95% CI 0.43 to 4.40; low-quality evidence), diarrhoea (2 trials, 88 women, RR 2.21, 95% CI 0.35 to 14.06; low-quality evidence) or to whether women were satisfied with the acceptability of the method (1 trial, 32 women, RR 1.17, 95% CI 0.83 to 1.64; low-quality evidence). It is uncertain whether vaginal misoprostol reduces blood loss (haemoglobin difference > 10 g/L) (1 trial, 50 women, RR 1.25, 95% CI 0.38 to 4.12; very-low quality) or pain (opiate use) (1 trial, 84 women, RR 5.00, 95% CI 0.25 to 101.11; very-low quality), because the quality of the evidence for these outcomes was found to be very low.Vaginal misoprostol versus surgical evacuation Vaginal misoprostol may be less effective in accomplishing a complete miscarriage compared to surgical management (6 trials, 943 women, average RR 0.40, 95% CI 0.32 to 0.50; Heterogeneity: Tau² = 0.03, I² = 46%; low-quality evidence) and may be associated with more nausea (1 trial, 154 women, RR 21.85, 95% CI 1.31 to 364.37; low-quality evidence) and diarrhoea (1 trial, 154 women, RR 40.85, 95% CI 2.52 to 662.57; low-quality evidence). There may be little or no difference between vaginal misoprostol and surgical evacuation for pelvic infection (1 trial, 618 women, RR 0.73, 95% CI 0.39 to 1.37; low-quality evidence), blood loss (post-treatment haematocrit (%) (1 trial, 50 women, mean difference (MD) 1.40%, 95% CI -3.51 to 0.71; low-quality evidence), pain relief (1 trial, 154 women, RR 1.42, 95% CI 0.82 to 2.46; low-quality evidence) or women's satisfaction/acceptability of method (1 trial, 45 women, RR 0.67, 95% CI 0.40 to 1.11; low-quality evidence).Other comparisonsBased on findings from a single trial, vaginal misoprostol was more effective at accomplishing complete miscarriage than expectant management (614 women, RR 1.25, 95% CI 1.09 to 1.45). There was little difference between vaginal misoprostol and sublingual misoprostol (5 trials, 513 women, average RR 0.84, 95% CI 0.61 to 1.16; Heterogeneity: Tau² = 0.10, I² = 871%; or between oral and vaginal misoprostol in terms of complete miscarriage at less than 13 weeks (4 trials, 418 women), average RR 0.68, 95% CI 0.45 to 1.03; Heterogeneity: Tau² = 0.13, I² = 90%). However, there was less abdominal pain with vaginal misoprostol in comparison to sublingual (3 trials, 392 women, RR 0.58, 95% CI 0.46 to 0.74). A single study (46 women) found mifepristone to be more effective than placebo: miscarriage complete by day five after treatment (46 women, RR 9.50, 95% CI 2.49 to 36.19). However the quality of this evidence is very low: there is a very serious risk of bias with signs of incomplete data and no proper intention-to-treat analysis in the included study; and serious imprecision with wide confidence intervals. Mifepristone did not appear to further hasten miscarriage when added to a misoprostol regimen (3 trials, 447 women, RR 1.18, 95% CI 0.95 to 1.47). AUTHORS' CONCLUSIONS: Available evidence from randomised trials suggests that medical treatment with vaginal misoprostol may be an acceptable alternative to surgical evacuation or expectant management. In general, side effects of medical treatment were minor, consisting mainly of nausea and diarrhoea. There were no major differences in effectiveness between different routes of administration. Treatment satisfaction was addressed in only a few studies, in which the majority of women were satisfied with the received intervention. Since the quality of evidence is low or very low for several comparisons, mainly because they included only one or two (small) trials; further research is necessary to assess the effectiveness, safety and side effects, optimal route of administration and dose of different medical treatments for early fetal death.

Cost-effectiveness of curettage vs. expectant management in women with an incomplete evacuation after misoprostol treatment for first-trimester miscarriage: a randomized controlled trial and cohort study.

INTRODUCTION: Curettage is more effective than expectant management in women with suspected incomplete evacuation after misoprostol treatment for first-trimester miscarriage. The cost-effectiveness of curettage vs. expectant management in this group is unknown. MATERIAL AND METHODS: From June 2012 until July 2014 we conducted a randomized controlled trial and parallel cohort study in the Netherlands, comparing curettage with expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for first-trimester miscarriage. Successful treatment was defined as a sonographic finding of an empty uterus 6 weeks after study entry, or an uneventful course. Cost-effectiveness and cost-utility analyses were performed. We included costs of healthcare utilization, informal care and lost productivity. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated using bootstrapping. RESULTS: We included 256 women from 27 hospitals; 95 curettage and 161 expectant management. Treatment was successful in 96% of the women treated with curettage vs. 83% of the women after expectant management (mean difference 13%, 95% confidence interval 5-20). Mean costs were significantly higher in the curettage group (mean difference €1157; 95% C confidence interval €955-1388). The incremental cost-effectiveness ratio for curettage vs. expectant management was €8586 per successfully treated woman. The cost-effectiveness acceptability curve showed that at a willingness-to-pay of €18 200/extra successfully treated women, the probability that curettage is cost-effective is 95%. CONCLUSIONS: Curettage is not cost-effective compared with expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment. This indicates that curettage in this group should be restrained.

Factors influencing women's preferences for subsequent management in the event of incomplete evacuation of the uterus after misoprostol treatment for miscarriage.

STUDY QUESTION: What affects women's treatment preferences in the management of an incomplete evacuation of the uterus after misoprostol treatment for a first-trimester miscarriage? SUMMARY ANSWER: Women's treatment preferences in the management of an incomplete evacuation of the uterus after misoprostol treatment for miscarriage are most strongly influenced by 'the risk of a reduced fertility' followed by 'the probability of success'. WHAT IS KNOWN ALREADY: Available treatment options in miscarriage are surgical, medical or expectant management. Treatment with misoprostol leads to an incomplete evacuation of the uterus and additional surgical treatment in 20-50% of women. To our knowledge, women's preferences for subsequent treatment of an incomplete evacuation of the uterus after misoprostol treatment for miscarriage have not been studied yet. STUDY DESIGN, SIZE, DURATION: Between April 2014 and January 2015, we conducted a prospective nationwide multicentre discrete-choice experiment (DCE). DCEs have become the most frequently applied approach for studying patient preferences in health care. In our DCE, which considerers five attributes, a target sample size was calculated including 20 patients per attribute for the main analysis. We intended to include 25% more patients, i.e. a total of 125 thus enabling us to assess heterogeneity of treatment choices. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women visiting the outpatient clinic with first-trimester miscarriage or incomplete miscarriage were invited to participate in the study. Women under 18 years of age, women who were unable to understand the Dutch questionnaire or women who already had received a treatment for the current miscarriage were excluded. Women's preferences were assessed using a DCE. A literature review, expert opinions and interviews with women from the general population were used to define relevant treatment characteristics. Five attributes were selected: (i) certainty about the duration of convalescence; (ii) number of days of bleeding after treatment; (iii) probability of success (empty uterus after treatment); (iv) risk of reduced fertility and (v) risk of complications requiring more time or readmission to hospital. Fourteen scenarios using these attributes were selected in the DCE. Each of these scenarios presented two treatment options, while treatment characteristics varied between the 14 scenarios. For each scenario, respondents were asked to choose the preferred treatment option. The importance of each attribute was analysed, and preference heterogeneity was investigated through latent-class analysis. MAIN RESULTS AND THE ROLE OF CHANCE: One hundred and eighty-six women were included of whom 128 completed the DCE (69% response rate). The two attributes with the greatest effect on their preference were, probability of success and risk of reduced fertility. The latent-class analysis revealed two subgroups of patients with different preference patterns. Forty per cent of women were more influenced by treatment success and 59% were more influenced by risk. LIMITATIONS, REASONS FOR CAUTION: Most women were highly educated and were of Dutch origin, which limits the generalizability of our findings. Women with lower education levels, other cultural backgrounds and/or different previous experiences may differ from our findings. WIDER IMPLICATIONS OF THE FINDINGS: Patients preferences should be addressed when counselling patients with an incomplete miscarriage after misoprostol treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was embedded in the MisoREST trial, and funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-82310-97-12066. There were no conflicts of interests. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR3310, http://www.trialregister.nl. TRIAL REGISTRATION DATE: 27 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 12 June 2012.

Value of scintigraphy for assessing delayed gastric emptying after pancreatic surgery.

BACKGROUND: Delayed gastric emptying (DGE) occurs frequently after pancreatic surgery. Recently a consensus definition of DGE was introduced, and this grading system is currently widely used. The aim of this study was to compare results of gastric emptying scintigraphy with the grade of DGE after pancreatic surgery. METHODS: In 44 patients undergoing exploration for a pancreatic head or periampullary tumor, 28 pancreatoduodenectomies (PDs) and 16 double-bypass procedures were performed. All patients underwent preoperative and postoperative gastric emptying scintigraphy. We investigated whether the incidence of DGE was correlated with the results of gastric emptying scintigraphy. RESULTS: DGE occurred in 19 (43 %) patients. Clinically relevant DGE (grades B and C) prevailed in the PD group. Median postoperative residual activity at t = 2 h (%RA120) in these groups was 36 % (no DGE), 75 % (grade A), 93 % (grade B), and 95 % (grade C). DGE grade B or C was found in 7 of 10 patients with %RA120 of ≥94 % on postoperative day (POD) 7. CONCLUSIONS: Postoperative %RA120 on scintigraphy is positively associated with severity of DGE. Gastric emptying scintigraphy on POD 7 can predict the severity of DGE. When postoperative gastric emptying scintigraphy shows high residual radioactivity, the likelihood of further progression to grade B or C DGE is high and warrants investigation for underlying causes.

Surgical versus expectant management in women with an incomplete evacuation of the uterus after treatment with misoprostol for miscarriage: the MisoREST trial.

BACKGROUND: Medical treatment with misoprostol is a non-invasive and inexpensive treatment option in first trimester miscarriage. However, about 30% of women treated with misoprostol have incomplete evacuation of the uterus. Despite being relatively asymptomatic in most cases, this finding often leads to additional surgical treatment (curettage). A comparison of effectiveness and cost-effectiveness of surgical management versus expectant management is lacking in women with incomplete miscarriage after misoprostol. METHODS/DESIGN: The proposed study is a multicentre randomized controlled trial that assesses the costs and effects of curettage versus expectant management in women with incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage.Eligible women will be randomized, after informed consent, within 24 hours after identification of incomplete evacuation of the uterus by ultrasound scanning. Women are randomly allocated to surgical or expectant management. Curettage is performed within three days after randomization.Primary outcome is the sonographic finding of an empty uterus (maximal diameter of any contents of the uterine cavity < 10 millimeters) six weeks after study entry. Secondary outcomes are patients' quality of life, surgical outcome parameters, the type and number of re-interventions during the first three months and pregnancy rates and outcome 12 months after study entry. DISCUSSION: This trial will provide evidence for the (cost) effectiveness of surgical versus expectant management in women with incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. TRIAL REGISTRATION: Dutch Trial Register: NTR3110.

[Endometriosis in an episiotomy scar]. / Endometriose in een episiotomielitteken.

A 34-year-old woman had a recurrent bleu colored painful swelling in the episiotomy scar. Pathological examination showed endometriosis. Six months later, a second recurrence occurred. The lesion was again removed with a larger margin, the wound treated with argon plasma coagulation to reduce chance of recurrence.

Effectiveness, complications, and reproductive outcomes after cesarean scar pregnancy management: a retrospective cohort study.

BACKGROUND: There is a dramatic rise in cesarean deliveries worldwide, leading to higher complication rates in subsequent pregnancies. One of these complications is a cesarean scar pregnancy. During the last decades, treatment options for cesarean scar pregnancies have changed, and less invasive interventions have been employed to preserve fertility and reduce morbidity. However, the optimal treatment approach and the influence of various treatments on reproductive outcomes have to be determined. OBJECTIVE: This study aimed to evaluate the short- and long-term outcomes after cesarean scar pregnancy management. STUDY DESIGN: We conducted a retrospective cohort study of women determined to have a cesarean scar pregnancy from 2010 to 2021 at a tertiary referral center, the Amsterdam University Medical Center, in the Netherlands. Outcomes of the following management strategies were compared: expectant management, methotrexate, curettage with temporary cervical cerclage, or a laparoscopic niche resection. We performed a curettage if the cesarean scar pregnancy did not cross the serosal line of the uterus, and a laparoscopic niche resection was performed if the cesarean scar pregnancy crossed the serosal line. The main outcomes were treatment efficacy and time to subsequent ongoing pregnancy or pregnancy leading to a live birth. RESULTS: Of the 60 included women, 5 (8.3%) were managed expectantly, 8 (13.3%) were treated with methotrexate, 31 (51.8%) were treated with a curettage, and 16 (26.7%) with a laparoscopic niche resection. The groups were not comparable. The gestational age and human chorionic gonadotropin levels were generally higher in women who received methotrexate or a laparoscopic niche resection. Additional treatment in the conservative group was needed for 4 (80%) women after expectant management and for 7 (87.5%) women after methotrexate treatment. In the surgical group, all 31 women treated with a curettage and all 16 treated with a laparoscopic niche resection did not require additional treatment. The subsequent ongoing pregnancy rate after cesarean scar pregnancy management was 81.1% (30/37) among women who wished to conceive, with a live birth rate of 78.4% (29/37); 1 woman was in her third trimester of pregnancy at the time of analyses. The time between cesarean scar pregnancy management and subsequent ongoing pregnancy was 4 months (interquartile range, 3-6; P=.02) after expectant management, 18 months (interquartile range, 13-22) after initial methotrexate treatment, 5 months (interquartile range, 3-14; P=.01) after a curettage, and 6 months (interquartile range, 4-15; P=.03) after a laparoscopic niche resection. CONCLUSION: Surgical treatment of a cesarean scar pregnancy led to a high success rate without additional interventions, high pregnancy rates with a short time interval between treatment, and subsequent pregnancy leading to an ongoing pregnancy or live birth. Conservative management, both with expectant management and methotrexate treatment, led to high (re)intervention rates. Different management approaches are indicated for different types of cesarean scar pregnancies.

MisoREST: Surgical versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage: A cohort study.

OBJECTIVE: To assess the effectiveness of curettage versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. STUDY DESIGN: We conducted a multicenter cohort study alongside a randomized clinical trial (RCT) between June 2012 until July 2014. 27 Dutch hospitals participated. Women with an incomplete evacuation after misoprostol treatment for first trimester miscarriage who declined to participate in the RCT, received treatment of their preference; curettage (n=65) or expectant management (n=132). A successful outcome was defined as an empty uterus on sonography at six weeks or uneventful clinical follow-up. We furthermore assessed complication rate and (re)intervention rate RESULTS: Of the 197 women who declined to participate in the RCT, 65 preferred curettage and 132 expectant management. A successful outcome was observed in 62/65 women (95%) in the surgical group versus 112/132 women (85%) in the expectant group (RR 1.1, 95% CI 1.03-1.2), with complication rates of 6.2% versus 2.3%, respectively (RR 2.7, 95% CI 0.6-12). CONCLUSION: In women with an incomplete evacuation of the uterus after misoprostol treatment, expectant management is an effective and safe option. This finding could restrain the use of curettage in women that have used misoprostol in the treatment of first trimester miscarriage.

Systematic review and meta-analysis of intrauterine adhesions after miscarriage: prevalence, risk factors and long-term reproductive outcome.

BACKGROUND: Approximately 15-20% of all clinically confirmed pregnancies end in a miscarriage. Intrauterine adhesions (IUAs) are a possible complication after miscarriage, but their prevalence and the contribution of possible risk factors have not been elucidated yet. In addition, the long-term reproductive outcome in relation to IUAs has to be elucidated. METHODS: We systematically searched the literature for studies that prospectively assessed the prevalence and extent of IUAs in women who suffered a miscarriage. To be included, women diagnosed with a current miscarriage had to be systematically evaluated within 12 months by hysteroscopy after either spontaneous expulsion or medical or surgical treatment. Studies that included women with a history of recurrent miscarriage only or that evaluated the IUAs after elective abortion or beyond 12 months after the last miscarriage were not included. Subsequently, long-term reproductive outcomes after expectant (conservative), medical or surgical management were assessed in women with and without post-miscarriage IUAs. RESULTS: We included 10 prospective studies reporting on 912 women with hysteroscopic evaluation within 12 months of miscarriage and 8 prospective studies, including 1770 women, reporting long-term reproductive outcome. IUAs were detected in 183 women, resulting in a pooled prevalence of 19.1% [95% confidence interval (CI): 12.8-27.5%]. The extent of IUAs was reported in 124 women (67.8%) and was mild, moderate and severe respectively in 58.1, 28.2 and 13.7% of cases. Relative to women with one miscarriage, women with two or three or more miscarriages showed an increased risk of IUAs by a pooled OR of 1.41 and 2.1, respectively. The number of dilatation and curettage (D&C) procedures seemed to be the main driver behind these associations. A total of 150 congenital and acquired intrauterine abnormalities were encountered in 675 women, resulting in a pooled prevalence of 22.4% (95% CI: 16.3-29.9%). Similar reproductive outcomes were reported subsequent to conservative, medical or surgical management for miscarriage, although the numbers of studies and of included women were limited. No studies reported long-term reproductive outcomes following post-miscarriage IUAs. CONCLUSIONS: IUAs are frequently encountered, in one in five women after miscarriage. In more than half of these, the severity and extent of the adhesions was mild, with unknown clinical relevance. Recurrent miscarriages and D&C procedures were identified as risk factors for adhesion formation. Congenital and acquired intrauterine abnormalities such as polyps or fibroids were frequently identified. There were no studies reporting on the link between IUAs and long-term reproductive outcome after miscarriage, while similar pregnancy outcomes were reported subsequent to conservative, medical or surgical management. Although this review does not allow strong clinical conclusions on treatment management, it signals an important clinical problem. Treatment strategies are proposed to minimize the number of D&C in an attempt to reduce IUAs.

[Treatment options for early miscarriage; new insights]. / Behandelopties voor vroege miskramen; nieuwe inzichten.

Miscarriage is the most common complication during the first trimester of pregnancy. Three treatment options are available for women who experience early miscarriage: expectant management, curettage, or medical treatment. Curettage has traditionally been the usual treatment, but both expectant management and medical management with misoprostol are more cost-effective. Curettage increases the risk of surgical complications and intra-uterine adhesions (Asherman syndrome), and is associated with preterm birth. After adequate counselling, the woman's preference is a decisive factor; the choice of treatment for early miscarriage lends itself ideally to shared decision making. The Netherlands lacks a multidisciplinary guideline on the treatment of women following miscarriage.

Practice variation in the management of first trimester miscarriage in the Netherlands: a nationwide survey.

Objectives. To survey practice variation in the management of first trimester miscarriage in The Netherlands. Methods. We sent an online questionnaire to gynecologists in eight academic, 37 nonacademic teaching, and 47 nonteaching hospitals. Main outcome measures were availability of a local protocol; estimated number of patients treated with curettage, misoprostol, or expectant management; misoprostol regimen; and estimated number of curettages performed after initial misoprostol treatment. Outcomes were compared to the results of a previous nationwide survey. Results. The response rate was 100%. A miscarriage protocol was present in all academic hospitals, 68% of nonacademic teaching hospitals, and 38% of nonteaching hospitals (P = 0.008). Misoprostol was first-choice treatment for 41% of patients in academic hospitals versus 34% and 27% in teaching-and nonteaching hospitals (P = 0.045). There were 23 different misoprostol regimens. Curettage was first-choice treatment in 29% of patients in academic hospitals versus 46% and 50% in nonacademic teaching or nonteaching hospitals (P = 0.007). In 30% of patients, initial misoprostol treatment was followed by curettage. Conclusions. Although the percentage of gynaecologists who are aware of the availability of misoprostol for miscarriage treatment has doubled to almost 100% since 2005, practice variation is still large. This practice variation underlines the need for a national guideline.