Early Pregnancy Loss Treatment Research Articles

Changes in Language Used for Ultrasound Reports in Early Pregnancy Loss After Initiation of Restrictive Abortion Laws [ID 2683508

INTRODUCTION: This study compared language used to describe early pregnancy loss (EPL) in ultrasound reports at a single teaching hospital before and after the passage of Texas Senate Bill 8 (SB8) in September 2021. METHODS: We conducted a retrospective cohort study of pregnant patients presenting to the emergency department (ED) between January 2020 and March 2023. Charts were screened using ICD-10 codes for pregnancy and first-trimester diagnoses and included if diagnosis of EPL was present. Abstracted data from ultrasound reports included the following: diagnosis assigned by radiology and confidence of qualifying language (“diagnostic of,” “suggestive of,” or omitted diagnosis). Evidence-based diagnosis was assigned based upon ultrasound review by two independent ob-gyn providers using established ultrasound criteria for EPL. This protocol was approved for IRB exemption by the University of Texas at Austin Dell Medical School. RESULTS: A total of 185 charts were identified, N=103 prior to SB8 versus 82 after. After SB8, radiology-assigned diagnosis was discordant with evidence-based diagnosis more often (55% versus 45%; P=.08) and radiology impressions used less confident qualifying language (61% versus 47%; P=.03). CONCLUSION: Restrictive abortion laws like SB8, compounded by the Dobbs decision, may affect the diagnostic accuracy and confidence of qualifying language for diagnosis used in ultrasound reports for EPL. Language in ultrasound reports became significantly less confident after SB8 with a decrease in correct diagnosis despite clear diagnostic criteria. Failure to correctly diagnose EPL on radiology reports may delay recognition and treatment of EPL.

Medical treatment for early pregnancy loss following in vitro fertilization compared to spontaneous pregnancies.

Misoprostol is a well-studied medical treatment for early pregnancy loss (EPL), with success rates ranging between 70 and 90%. However, treatment failure is associated with major patient discomfort, including the need for surgical intervention to evacuate the uterus. It was previously reported that medical treatment was especially successful among women who conceived after in vitro fertilization (IVF). We aimed to study if there is a difference in rates of medical treatment failures for EPL between pregnancies conceived by IVF and spontaneous pregnancies. In this retrospective cohort study, we included all women who underwent medical treatment for EPL at our institute between 07/2015 and 12/2020. Treatment outcome was compared between IVF and spontaneous pregnancies. Treatment failure was defined as a need for surgical intervention, namely, dilation & curettage (D&C) and/or hysteroscopy, due to retained products of conception, which was defined as a gestational sac or endometrial thickness greater than 15 mm in a TVS scan. Overall, 775 patients were included, of which 195 (169/775 = 25.1%) ultimately required surgical intervention. There was no difference between the study groups in the rate of treatment failure. However, among IVF pregnancies, the rate of emergency D&C was lower (3.6% vs. 9.8%, p = 0.001), compared to spontaneous group. In cases of medical treatment for EPL, IVF pregnancies had no differences in rates of treatment failure compared to spontaneous pregnancies. That being said, IVF pregnancies have lower chances to undergo emergency D&C, compared to spontaneous pregnancies.

Geographic Access to Early Pregnancy Loss Management.

Early pregnancy loss (EPL) is common, but patients face barriers to the most effective medication (mifepristone followed by misoprostol) and procedural (uterine aspiration) management options. This cross-sectional geospatial analysis evaluated access in New Mexico to mifepristone and misoprostol and uterine aspiration in emergency departments (comprehensive) and to uterine aspiration anywhere in a hospital (aspiration) for EPL. Access was defined as a 60-minute car commute. We collected data from hospital key informants and public databases and performed logistical regression to evaluate associations between access and rurality, area deprivation, race, and ethnicity. Thirty-five of 42 (83.3%) hospitals responded between October 2020 and August 2021. Two hospitals (5.7%) provided comprehensive management; 24 (68.6%) provided aspiration. Rural and higher deprivation areas had statistically significantly lower adjusted odds ratios for comprehensive management (0.03-0.07 and 0.3-0.4, respectively) and aspiration (0.03-0.06 and 0.1-0.3, respectively) access. Mifepristone and uterine aspiration implementation would address disparate access to EPL treatment.

The MISOPRED score: Development and validation of a clinical scoring system to predict the effectiveness of Misoprostol treatment for early pregnancy loss.

Misoprostol treatment for early pregnancy loss has varied success demonstrated in previous studies. Incorporating predictors in a single clinical scoring system would be highly beneficial in clinical practice. To develop and evaluate the accuracy of a scoring system to predict misoprostol treatment outcomes for managing early pregnancy loss. Retrospective cohort and validation study. Patients discharged from the gynecologic emergency department from 2013 to 2016, diagnosed with early pregnancy loss, who were treated with 800 mcg misoprostol, administrated vaginally were included. All were sonographically reevaluated within 48-72 hours. Patients in whom the gestational sac was not expelled or with endometrial lining >30 mm were offered a repeat dose and returned for reevaluation after seven days. A successful response was defined as complete expulsion. Clinical data were reviewed to identify predictors for successful responses. The scoring system was then retrospectively evaluated on a second cohort to evaluate its accuracy. Multivariate logistic regression was performed to identify factors most predictive of treatment response. The development cohort included 126 patients. Six factors were found to be most predictive of misoprostol treatment effectiveness: nulliparity, prior complete spontaneous abortion, gestational age, vaginal bleeding, abdominal pain, and mean sac diameter, yielding a score of 0-8 (the MISOPRED score), where 8 represents the highest-likelihood of success. The score was validated retrospectively with 119 participants. Successful response in the group with the lowest likelihood score (score 0-3) was 9%, compared with 82% in the highest likelihood score group (score 7-8). Using the MISOPRED score, approximately 15% of patients previously planned to receive misoprostol treatment can be referred for surgical management. MISOPRED score can be utilized as an adjunct tool for clinical decision-making in cases of Early pregnancy loss. To our knowledge, this is the first scoring system suggested to predict the success rate in these cases.

Ultrasound-guided manual vacuum aspiration (USG-MVA) with cervical preparation for early pregnancy loss: A cost-effectiveness analysis.

Approximately one in four women will experience a miscarriage in their lifetime. Ultrasound-guided manual vacuum aspiration (USG-MVA) is an ideal outpatient surgical treatment alternative to traditional surgical evacuation. We aimed to examine the cost-effectiveness of US-MVA with cervical preparation for treatment of early pregnancy loss from the perspective of public healthcare provider of Hong Kong. A decision-analytic model was designed to simulate outcomes in a hypothetical cohort of patients with early pregnancy loss on four interventions: (1) US-MVA, (2) misoprostol, (3) surgical evacuation of uterus by dilation and curettage (surgical evacuation), and (4) expectant care. Model inputs were retrieved from published literature and public data. Model outcome measures were total direct medical cost and disutility-adjusted life-year (DALY). Base-case model results were examined by sensitivity analysis. The expected DALYs (0.00141) and total direct medical cost (USD736) of US-MVA were the lowest of all interventions in base-case analysis, and US-MVA was the preferred cost-effective option. One-way sensitivity analysis showed that the misoprostol group became less costly than the US-MVA group if the evacuation rate of misoprostol (base-case value 0.832) exceeded 0.920. In probabilistic sensitivity analysis, At the willingness-to-pay (WTP) threshold of 49630 USD/DALY averted (1x gross domestic product per capita of Hong Kong), the US-MVA was cost-effective in 72.9% of the time. US-MVA appeared to be cost-saving and effective for treatment of early pregnancy loss from the perspective of public healthcare provider of Hong Kong.

USP7 promotes decidualization of ESCs by STAT3/PR axis during early pregnancy

Decidualization is an essential process for embryo implantation during early pregnancy. Defective decidualization is a critical leading cause of early pregnancy loss (EPL). Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that is involved in uterine function. This study aimed to explore the underlying mechanism by which USP7 regulates decidualization in EPL. We found that USP7 was downregulated in the decidual tissue of EPL patients. Upregulation of USP7 enhanced decidualization in endometrial stromal cells (ESCs), with increased decidualized biomarkers IGFBP1 and PRL and progesterone receptor A/B (PR-A/B) expression. Moreover, we found that signal transducer and activator of transcription 3 (STAT3) is a direct target of USP7 in ESCs. USP7 bound to STAT3 by deubiquitination and increased STAT3 levels in ESCs. Suppression of STAT3 impeded the USP7-promoted cell viability, decidualization, and PR-A/B expression of ESCs. USP7 promoted the decidualization of ESCs through the STAT3/PR signaling pathway during early pregnancy, which provides new insight into the pathological mechanism of EPL and may contribute to the clinical treatment of EPL.

Geospatial Analysis of Access to Evidence-Based Early Pregnancy Loss Management in New Mexico [ID: 1377363

INTRODUCTION: Little is known about availability of evidence-based early pregnancy loss (EPL) treatment in emergency departments (EDs), where patients often first seek care. We evaluated geographic access to mifepristone/misoprostol and uterine aspiration in New Mexican hospitals. METHODS: We used an enhanced two-step floating catchment area method to model accessibility from census block groups’ population-weighted centroids to hospitals. Our primary outcome was access to mifepristone/misoprostol and uterine aspiration in EDs; our secondary outcome was access to in-hospital aspiration, both outcomes defined as less than a 60-minute commute. We surveyed all EDs in New Mexico and used public databases to compute census block groups’ demographic, transportation, rurality, and area deprivation data. We used logistic regression to evaluate the associations between access and race and ethnicity, area deprivation, and rural location. The University of New Mexico IRB approved this study. RESULTS: Thirty-five (83%) of 42 hospitals responded. Two (6%) provided in-ED treatment, and 24 (69%) in-hospital aspiration. Half of reproductive-aged women had access to in-ED treatment, and 90% to in-hospital aspiration. Census block groups with higher quartile proportions of American Indian/Native Alaskan reproductive-aged women had higher adjusted odds ratios of accessing in-ED treatment (2.5–7.3, P<.05). Rural areas and higher area deprivation quartiles had lower in-ED access adjusted odds ratios (0.03–0.07 [P<.05] and 0.3–0.4 [P<.05], respectively) compared with urban and lower area deprivation quartiles. In-hospital aspiration results were similar to in-ED treatment results across all categories. CONCLUSION: By prioritizing rural areas and areas with higher socioeconomic deprivation, EPL treatment implementation efforts can improve equitable care access and equity for patients.

The association between abortion restrictions and patient-centered care for early pregnancy loss at US obstetrics-gynecology residency programs

Early pregnancy loss is a common medical problem, and the recommended treatments overlap with those used for induced abortions. The American College of Obstetricians and Gynecologists recommends the incorporation of clinical and patient factors when applying conservative published imaging guidelines to determine the timing of intervention for early pregnancy loss. However, in places where abortion is heavily regulated, clinicians who manage early pregnancy loss may cautiously rely on the strictest criteria to differentiate between early pregnancy loss and a potentially viable pregnancy. The American College of Obstetricians and Gynecologists also notes that specific treatment modalities that are frequently used to induce abortion, including the use of mifepristone in medical therapy and surgical aspiration in an office setting, are cost-effective and beneficial for patients with early pregnancy loss. This study aimed to determine how US-based obstetrics and gynecology residency training institutions adhere to the American College of Obstetricians and Gynecologists recommendations for early pregnancy loss management, including the timing and types of interventions, and to evaluate the relationship with institutional and state abortion restrictions. From November 2021 to January 2022, we conducted a cross-sectional study of all 296 US-based obstetrics and gynecology residency programs by emailing them and requesting that a faculty member complete a survey about early pregnancy loss practices at their institution. We asked about location of diagnosis, use of imaging guidelines before offering intervention, treatment options available at their institution, and program and personal characteristics. We used chi-square tests and logistic regressions to compare the availability of early pregnancy loss care based on institutional indication-based abortion restrictions and state legislative hostility to abortion care. Of the 149 programs that responded (50.3% response rate), 74 (49.7%) reported that they did not offer any intervention for suspected early pregnancy loss unless rigid imaging criteria were met, whereas the remaining 75 (50.3%) programs reported that they incorporated imaging guidelines with other factors. In an unadjusted analysis, programs were less likely to incorporate other factors with imaging criteria if they were in a state with legislative policies that were hostile toward abortion (33% vs 79%; P<.001) or if the institution restricted abortion by indication (27% vs 88%; P<.001). Mifepristone was used less often in programs located in hostile states (32% vs 75%; P<.001) or in institutions with abortion restrictions (25% vs 86%; P<.001). Similarly, office-based suction aspiration use was lower in hostile states (48% vs 68%; P=.014) and in institutions with restrictions (40% vs 81%; P<.001). After controlling for program characteristics, including state policies and affiliation with family planning training programs or religious entities, institutional abortion restrictions were the only significant predictor of rigid reliance on imaging guidelines (odds ratio, 12.3; 95% confidence interval, 3.2-47.9). In training institutions that restrict access to induced abortion based on indication for care, residency programs are less likely to holistically incorporate clinical evidence and patient priorities in determining when to intervene in early pregnancy loss as recommended by the American College of Obstetricians and Gynecologists. Programs in restrictive institutional and state environments are also less likely to offer the full range of early pregnancy loss treatment options. With state abortion bans proliferating nationwide, evidence-based education and patient-centered care for early pregnancy loss may also be hindered.

Mifepristone-misoprostol combination treatment for early pregnancy loss after embryo transfer: a case series

Evidence strongly supports the use of mifepristone-misoprostol combination treatment for early pregnancy loss (EPL) among pregnancies conceived without assisted reproductive technologies. No literature exists, however, regarding the efficacy of this treatment in the medical management of EPL among pregnancies after invitro fertilization and embryo transfer (IVF-ET). These patients differ as some use exogenous hormonal supplementation to provide pregnancy support. Thus, the management for EPL may differ between unassisted conceptions and those after ET. Mifepristone, a progesterone receptor antagonist, may demonstrate an altered treatment effect when used with misoprostol to manage EPL in assisted reproductive technologie-conceived pregnancies. To describe our institution's experience using mifepristone-misoprostol to manage EPL after invitro fertilization with embryo transfer IVF-ET. Retrospective case series. Single academic institution from 2020 to2022. Nine patients with ultrasound confirmed EPL after IVF-ET. All 9 patients underwent invitro fertilization followed by fresh or frozen embryo transfer. All 9 received 200 mg of mifepristone 24 hours before 800 μg of misoprostol. Incomplete abortion, need for surgical management, number of days to negative serum human chorionic gonadotropin (hCG). Of the 9 subjects included, one had a programmed frozen embryo transfer cycle, 6 had modified natural frozen embryo transfer cycles, and 2 underwent fresh ET. Eight subjects had successful expulsion of tissue with one dose of treatment, and one required uterine aspiration. No subjects required additional dosing of misoprostol. The mean number of days elapsed from mifepristone treatment to tissue expulsion was 4.89 ± 11.30 days and the mean days to negative-range serum hCG was 36.89 ± 18.59 days. At the initial ultrasound, all pregnancies had one gestational sac seen; 5/9 had a yolk sac; only 3 had fetal cardiac activity. The mean gestational age at the time of EPL diagnosis was 55.22 ± 8.77 days, with the majority (8/9) having completed 7 weeks gestation. Mifepristone-misoprostol combination treatment appears to be a reasonable option for those with EPL after IVF-ET. Future, larger-scale studies are needed comparing combination treatment with misoprostol only among various ET protocols.

Predictor assessment of complete miscarriage after medical treatment for early pregnancy loss in women with previous cesarean section.

This study aimed to evaluate clinical predictors associated with complete miscarriage after medical treatment for early pregnancy loss (EPL) in women with previous cesarean section.Patients with retained uterine content after expulsion followed by administration of mifepristone and misoprostol were included if they chose continued medical treatment rather than surgical intervention. Clinical characteristics including maternal age, gravidity, parity, history of previous cesarean section and ultrasound findings regarding average diameter of the gestational sac, uterine position, width, and blood flow signal of the residual uterine content after expulsion of the gestational sac were included in the analysis to determine predictors of complete miscarriage. A recursive partitioning analysis (RPA) was used to divide the patients into probability groups and assess their probability of complete miscarriage.A total of 89 patients were analyzed. The complete miscarriage rate was 58.43% overall. Multivariable logistic regression analysis showed that the width and blood flow signal of the residual after expulsion were both independent predictors for complete miscarriage (all P < .05). Patients were divided into high-probability (no blood flow signal, width of residual <1 cm), intermediate-probability (no blood flow signal, width of residual ≥1 cm; blood flow signal, width of residual <1 cm), and low-probability (blood flow signal, width of residual ≥ 1 cm) groups by RPA according to these 2 factors. The incidences of complete miscarriage were 88.24%, 67.57%, and 34.29%, respectively, P < .001).Surgical evacuation may be avoided in patients without ultrasonic blood flow of the uterine residual and width of the residual <1 cm. More active treatment could be recommended for patients with ultrasonic blood flow of the uterine residual and width of the residual ≥ 1 cm. Clinicians and patients should be aware of these differences when proceeding with medical treatment for EPL patients with previous cesarean section.

Mifepristone Followed by Misoprostol Compared with Placebo Followed by Misoprostol as Medical Treatment for Early Pregnancy Loss (the Triple M trial): A Double-Blind Placebo-Controlled Randomised Trial

Background: Worldwide, millions of women seek treatment for early pregnancy loss (EPL) annually. Medical management with misoprostol is widely used, but only effective 60% of the time. Pre-treatment with mifepristone prior to misoprostol might improve the success rate of medical management. Methods: This was a multi-centre, double-blind, placebo-controlled randomised trial in 17 Dutch hospitals. Women with a non-viable pregnancy between 6 and 14 weeks of gestation were eligible for inclusion after at least one week of expectant management. Participants were randomised (1:1) between oral mifepristone 600 mg or an oral placebo tablet. Participants took 400 mg misoprostol orally, repeated after four hours on day two and, if necessary, day three. Primary outcome was expulsion of gestational sac and endometrial thickness &lt;15 mm after 68 weeks. Analyses were done according to intention-to-treat principles. This trial is registered with ClinicalTrials.gov, NCT03212352. Findings: Between June 28th 2018 and January 8th 2020, 175 women were randomised to mifepristone and 176 to placebo, including 344 in the intention-to-treat analysis. In the mifepristone group 136 (79.1%) of 172 participants reached complete evacuation compared to 101 (58.7%) of 172 participants in the placebo group (p&lt;0.0001, RR 1.35, 95% CI 1.16-1.56). Incidence of serious adverse events was significantly lower in the mifepristone group with 24 (14%) patients affected versus 55 (32%) in the placebo group (p = 0.0005). Interpretation: Pre-treatment with mifepristone prior to misoprostol was more effective than misoprostol alone in managing EPL.

Surgical intervention after medical treatment for early pregnancy loss according to gestational size.

To study the rate of surgical intervention for unsuccessful medical treatment in early pregnancy loss (EPL), according to gestational size by ultrasound (GS-US). This was a retrospective cohort study. All women who were treated with misoprostol for EPL between July 2015 and December 2020 were included. The cohort was divided according to GS-US: group 1: gestational sac without an embryonic pole; group 2: an embryonic pole with crown-rump length (CRL) compatible with <7 weeks; group 3: CRL compatible with 7+0 -7+6 weeks; group 4: CRL compatible with 8+0 -8+6 weeks; group 5: CRL compatible with ≥9 weeks. We compared the rate of any surgical intervention due to treatment failure. Overall, 783 patients were included: group 1, 236 (30.1%); group 2, 319 (40.7%); group 3, 115 (14.7%); group 4, 78 (10.0%); and group 5, 35 (5.0%) patients. The rate of any surgical intervention was significantly lower in groups 1-4 (54, 22.9%; 85, 26.6%; 28, 24.3%; and 22, 28.2%, respectively) compared with group 5 (17, 48.6%; P= 0.030). On multivariant analysis, GS-US greater than 9 weeks was independently associated with the need for surgical intervention (adjusted odds ratio 1.23, 95% confidence interval 1.01-1.51; P= 0.040). When treating EPL medically, GS-US greater than 9 weeks increases the risk of undergoing additional surgical intervention compared with younger weeks.

Medical management of early pregnancy loss is cost-effective compared with office uterine aspiration

Early pregnancy loss, also referred to as miscarriage, is common, affecting approximately 1 million people in the United States annually. Early pregnancy loss can be treated with expectant management, medications, or surgical procedures-strategies that differ in patient experience, effectiveness, and cost. One of the medications used for early pregnancy loss treatment, mifepristone, is uniquely regulated by the Food and Drug Administration. This study aimed to compare the cost-effectiveness from the healthcare sector perspective of medical management of early pregnancy loss, using the standard of care medication regimen of mifepristone and misoprostol, with that of office uterine aspiration. We developed a decision analytical model to compare the cost-effectiveness of early pregnancy loss treatment with medical management with that of office uterine aspiration. Data on medical management came from the Pregnancy Failure Regimens randomized clinical trial, and data on uterine aspiration came from the published literature. The analysis was from the healthcare sector perspective with a 30-day time horizon. Costs were in 2018 US dollars. Effectiveness was measured in quality-adjust life-years gained and the rate of complete gestational sac expulsion with no additional interventions. Our primary outcome was the incremental cost per quality-adjust life-year gained. Sensitivity analysis was performed to identify the key uncertainties. Mean per-person costs were higher for uterine aspiration than for medical management ($828 [95% confidence interval, $789-$868] vs $661 [95% confidence interval, $556-$766]; P=.004). Uterine aspiration more frequently led to complete gestational sac expulsion than medical management (97.3% vs 83.8%; P=.0001); however, estimated quality-adjust life-years were higher for medical management than for uterine aspiration (0.082 [95% confidence interval, 0.8148-0.08248] vs 0.079 [95% confidence interval, 0.0789-0.0791]; P<.0001). Medical management dominated uterine aspiration, with lower costs and higher confidence interval. The probability that medical management is cost-effective relative to uterine aspiration is 97.5% for all willingness-to-pay values of ≥$5600/quality-adjust life-year. Sensitivity analysis did not identify any thresholds that would substantially change outcomes. Although office-based uterine aspiration more often results in treatment completion without further intervention, medical management with mifepristone pretreatment costs less and yields similar quality-adjust life-years, making it an attractive alternative. Our findings provided evidence that increasing access to mifepristone and eliminating unnecessary restrictions will improve early pregnancy care.

“There’s only one use for it”: Stigma as a Barrier to Mifepristone Use for Early Pregnancy Loss [A31

INTRODUCTION: Mifepristone combined with misoprostol has superior efficacy for early pregnancy loss (EPL) treatment compared to misoprostol alone. Mifepristone access is restricted by the U.S. Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy program, and its use may be further limited by logistical and interpersonal barriers due to its association with abortion, especially in states with restrictive policies. Understanding barriers to incorporation of mifepristone in EPL care is key for developing interventions to improve care quality. METHODS: We conducted semi-structured interviews with 19 obstetrician-gynecologists in Alabama who manage EPL. Interviews explored participants’ knowledge of and experience with mifepristone use for EPL and abortion, along with barriers to and facilitators of clinical mifepristone use. Interviews were coded by multiple study staff using inductive and deductive thematic coding. This study was deemed exempt by the Harvard Medical School Institutional Review Board. RESULTS: Nearly all interviewees identified abortion-related stigma as a barrier to mifepristone use. Interviewees often attributed stigma to a lack of knowledge about the clinical use of mifepristone for EPL. Stigmatization of mifepristone due to its association with abortion was related to religious and politic objections. Many also described stigma associated with misoprostol use. Although providers believed mifepristone use for abortion would not be accepted in their practice, most felt that mifepristone could be successfully used for EPL after practice-wide education on its use. CONCLUSION: Mifepristone is strongly associated with abortion stigma, which is a barrier to its use for EPL. Interventions to increase clinical knowledge of mifepristone use and decrease stigma are needed to optimize EPL care.

Predicting the likelihood of successful medical treatment of early pregnancy loss: development and internal validation of a clinical prediction model.

STUDY QUESTIONWhat are clinical predictors for successful medical treatment in case of early pregnancy loss (EPL)?SUMMARY ANSWERUse of mifepristone, BMI, number of previous uterine aspirations and the presence of minor clinical symptoms (slight vaginal bleeding or some abdominal cramps) at treatment start are predictors for successful medical treatment in case of EPL.WHAT IS KNOWN ALREADYSuccess rates of medical treatment for EPL vary strongly, between but also within different treatment regimens. Up until now, although some predictors have been identified, no clinical prediction model has been developed yet.STUDY DESIGN, SIZE, DURATIONSecondary analysis of a multicentre randomized controlled trial in 17 Dutch hospitals, executed between 28 June 2018 and 8 January 2020.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen with a non-viable pregnancy between 6 and 14 weeks of gestational age, who opted for medical treatment after a minimum of 1 week of unsuccessful expectant management. Potential predictors for successful medical treatment of EPL were chosen based on literature and expert opinions. We internally validated the prediction model using bootstrapping techniques.MAIN RESULTS AND THE ROLE OF CHANCE237 out of 344 women had a successful medical EPL treatment (68.9%). The model includes the following variables: use of mifepristone, BMI, number of previous uterine aspirations and the presence of minor clinical symptoms (slight vaginal bleeding or some abdominal cramps) at treatment start. The model shows a moderate capacity to discriminate between success and failure of treatment, with an AUC of 67.6% (95% CI = 64.9–70.3%). The model had a good fit comparing predicted to observed probabilities of success but might underestimate treatment success in women with a predicted probability of success of ∼70%.LIMITATIONS, REASONS FOR CAUTIONThe vast majority (90.4%) of women were Caucasian, potentially leading to less optimal model performance in a non-Caucasian population. Limitations of our model are that we have not yet been able to externally validate its performance and clinical impact, and the moderate accuracy of the prediction model of 0.67.WIDER IMPLICATIONS OF THE FINDINGSWe developed a prediction model, aimed to improve and personalize counselling for medical treatment of EPL by providing a woman with her individual chance of complete evacuation.STUDY FUNDING/COMPETING INTEREST(S)The Triple M Trial, upon which this secondary analysis was performed, was funded by the Healthcare Insurers Innovation Foundation (project number 3080 B15-191).TRIAL REGISTRATION NUMBERClinicaltrials.gov: NCT03212352.

Economic evaluation of a randomized controlled trial comparing mifepristone and misoprostol with misoprostol alone in the treatment of early pregnancy loss.

In case of early pregnancy loss (EPL) women can either choose for expectant, medical or surgical management. One week of expectant management is known to lead to spontaneous abortion in approximately 50% of women. Medical treatment with misoprostol is known to be safe and less costly than surgical management, however less effective in reaching complete evacuation of the uterus. Recently, a number of trials showed that prompt treatment with the sequential combination of mifepristone with misoprostol is superior to misoprostol alone in reaching complete evacuation. In this analysis we evaluate whether the sequential combination of mifepristone with misoprostol is cost-effective compared to misoprostol alone, in the treatment of EPL. A cost-effectiveness analysis (CEA) from a healthcare perspective was performed alongside a randomised controlled trial (RCT) in which standard treatment with misoprostol only was compared with a combination of mifepristone and misoprostol, in women with EPL after a minimum of one week of unsuccessful management. A limited societal perspective scenario was added. This RCT, the Triple M trial, was a multicentre, randomized, double-blinded, placebo-controlled trial executed at 17 hospitals in the Netherlands. The trial started on June 27th 2018, and ended prematurely in January 2020 due to highly significant outcomes from the predefined interim-analysis. We included 351 women with a diagnosis of EPL between 6 and 14 weeks gestation after at least one week of unsuccessful expectant management. They were randomized between double blinded pre-treatment with oral mifepristone 600mg (N = 175) or placebo (N = 176) taken on day one, both followed by misoprostol orally. In both groups, an intention-to-treat analysis was performed for 172 patients, showing a significant difference in success rates between participants treated with mifepristone and misoprostol versus those treated with misoprostol alone (79.1% vs 58.7% respectively). In this cost-effective analysis we measured the direct, medical costs related to treatment (planned and unplanned hospital visits, medication, additional treatment) and indirect costs based on the IMTA Productivity Cost Questionnaire (iPCQ). Quality Adjusted Life Years (QALY's) were calculated from participants' scores on the SF-36 questionnaires sent digitally at treatment start, and one, two and six weeks later. We found medical treatment with placebo followed by misoprostol to be 26% more expensive compared to mifepristone followed by misoprostol (p = 0.001). Mean average medical costs per patient were significantly lower in the mifepristone group compared to the placebo group (€528.95 ± 328.93 vs €663.77 ± 456.03, respectively; absolute difference €134.82, 95% CI 50,46-219,18, p = 0.002). Both indirect costs and QALY's were similar between both groups. The sequential combination of mifepristone with misoprostol is cost-effective compared with misoprostol alone, for treatment of EPL after a minimum of one week of unsuccessful expectant management.

Primary Hysteroscopic Treatment of Early Pregnancy Loss

<h3>Study Objective</h3> To demonstrate safety and feasibility of primary hysteroscopic treatment of first trimester miscarriage <h3>Design</h3> A surgical video reviewing the evidence supporting a hysteroscopic approach to surgical treatment of miscarriage followed by a step-by-step demonstration of two cases of miscarriage successfully treated with hysteroscopic resection. <h3>Setting</h3> Operating room and office. <h3>Patients or Participants</h3> We present two patients presenting with pregnancy loss at 7 weeks and 9 weeks gestation. <h3>Interventions</h3> Both patients are managed surgically with hysteroscopic resection of miscarriage. <h3>Measurements and Main Results</h3> Our hysteroscopic approach to the treatment of first trimester miscarriage has been highly successful, and so far, we have treated 45 patients with this approach. We are able to achieve complete resection in one procedure and follow up shows no intrauterine adhesions or remnant products of conception. Additionally, as prior evidence has demonstrated, with a directed biopsy approach we see a much higher rate of successful genetic analysis. This technique is both highly efficacious and feasible. <h3>Conclusion</h3> Primary hysteroscopic treatment of first trimester miscarriage is superior to blind suction D&C as it allows directed retrieval of products of conception, leading to comparatively minimal rates of intrauterine adhesions, remnant products of conception, and higher rates of successful genetic analysis. Adopting this alternative surgical approach is a natural and necessary step in the evolution of the treatment paradigm.

Misoprostol treatment for early pregnancy loss: an international survey

Research questionWhat is the global variability in misoprostol treatment for the management of early pregnancy loss (EPL)? DesignAn international web-based survey of fertility specialists and obstetrics and gynaecology clinicians was conducted between August and November 2020. The survey consisted of 16 questions addressing several aspects of misoprostol treatment for EPL. ResultsOverall, 309 clinicians from 80 countries participated in the survey, of whom 67.3% were fertility specialists. Nearly one-half (47.9%) of the respondents let the patient choose the first line of treatment (expectant management, misoprostol treatment or surgical aspiration) according to her own preference. The 248 respondents who administer misoprostol in their daily practice were asked further questions; 59.7% of them advise patients to take the medication at home. The most common dose and route of administration is 800 µg administered vaginally. Only 28.6% of participants use mifepristone pretreatment. Variation in the timing of the first follow-up visit after misoprostol administration was wide, ranging from 24 h to 1 week in most clinics. In case of incomplete expulsion, only 42.3% of the respondents routinely administer a second dose. The timing of the final visit and the definition of successful treatment also differed greatly among respondents. ConclusionsThere is large variability in the use of misoprostol for the management of EPL. High-quality research is necessary to examine several aspects of the treatment. Particularly, the timing and effectiveness of a second dose administration and the criteria to decide on treatment failure or success deserve more research in the future.

Mifepristone followed by misoprostol compared with placebo followed by misoprostol as medical treatment for early pregnancy loss (the Triple M trial): A double-blind placebo-controlled randomised trial.

BackgroundWorldwide, millions of women seek treatment for early pregnancy loss (EPL) annually. Medical management with misoprostol is widely used, but only effective 60% of the time. Pre-treatment with mifepristone prior to misoprostol might improve the success rate of medical management.MethodsThis was a multi-centre, double-blind, placebo-controlled randomised trial in 17 Dutch hospitals. Women with a non-viable pregnancy between 6 and 14 weeks of gestation were eligible for inclusion after at least one week of expectant management. Participants were randomised (1:1) between oral mifepristone 600 mg or an oral placebo tablet. Participants took 400 μg misoprostol orally, repeated after four hours on day two and, if necessary, day three. Primary outcome was expulsion of gestational sac and endometrial thickness <15 mm after 6–8 weeks. Analyses were done according to intention-to-treat principles. This trial is registered with ClinicalTrials.gov, NCT03212352.FindingsBetween June 28th 2018 and January 8th 2020, 175 women were randomised to mifepristone and 176 to placebo, including 344 in the intention-to-treat analysis. In the mifepristone group 136 (79•1%) of 172 participants reached complete evacuation compared to 101 (58•7%) of 172 participants in the placebo group (p<0•0001, RR 1•35, 95% CI 1•16–1•56). Incidence of serious adverse events was significantly lower in the mifepristone group with 24 (14%) patients affected versus 55 (32%) in the placebo group (p = 0•0005) (Table 3).InterpretationPre-treatment with mifepristone prior to misoprostol was more effective than misoprostol alone in managing EPL.FundingHealthcare Insurers Innovation Foundation, Radboud University Medical Centre, Canisius Wilhelmina Hospital.

Provision of Early Pregnancy Loss Care in New York Federally Qualified Health Centers.

Office-based early pregnancy loss (EPL) care is safe and suitable to Federally Qualified Health Centers (FQHCs); prevalence of provision in FQHCs is unknown. We conducted a mailed site-level survey of FQHCs in New York State (n = 405). Sites that offered prenatal care were eligible for analysis. Questions included provision of and barriers to providing EPL care options. Content analysis was used for write-in responses to barriers. We conducted bivariate analyses using Fisher's Exact tests and risk ratios to investigate associations between EPL care provision and the independent variables site urbanicity, prenatal clinician type, and ultrasound access. Of 181 mailings returned, 63 sites were eligible (response rate 44.7%); 88.9% provided expectant management, 53.9% medication management, and 23.8% uterine aspiration. Common barriers included lack of clinical infrastructure, poor ultrasound access, and insufficient training. Some held perceived barriers regarding uterine aspiration. Sites with regular ultrasound access were 1.85 times as likely to provide uterine aspiration as sites without regular ultrasound access (95% CI, 1.16-2.95). Few New York FQHCs provided comprehensive EPL care. Supporting FQHCs to overcome barriers may expand access to EPL treatment in primary care and increase continuity and patient centeredness.