Management of early pregnancy loss with mifepristone and misoprostol: clinical predictors of treatment success from a randomized trial.

BackgroundEarly pregnancy loss is a common event in the first trimester, occurring in 15%-20% of confirmed pregnancies. A common evidence-based medical regimen for early pregnancy loss uses misoprostol, a prostaglandin E1 analog, with a dosage of 800 μg, self-administered vaginally. The clinical utility of this regimen is limited by suboptimal effectiveness in patients with a closed cervical os, with 29% of patients experiencing early pregnancy loss requiring a second dose after 3 days and 16% of patients eventually requiring a uterine aspiration procedure.ObjectiveThis study aimed to evaluate clinical predictors associated with treatment success in patients receiving medical management with mifepristone-misoprostol or misoprostol alone for early pregnancy loss.Study designWe performed a planned secondary analysis of a randomized trial comparing mifepristone-misoprostol with misoprostol alone for management of early pregnancy loss. The published prediction model for treatment success of single-dose misoprostol administered vaginally included the following variables: active bleeding, type of early pregnancy loss (anembryonic pregnancy or embryonic and/or fetal demise), parity, gestational age, and treatment site; previous significant predictors were vaginal bleeding within the past 24 hours and parity of 0 or 1 vs >1. To determine if these characteristics predicted differential proportions of patients with treatment success or failure, we performed bivariate analyses; given the small proportion of treatment failures in the combined treatment arm, both arms were combined for analysis. Thereafter, we performed a logistic regression analysis to assess the effect of these predictors collectively in each of the 2 treatment groups separately as well as in the full cohort as a proxy for the combined treatment arm. Finally, by using receiver operating characteristic curves, we tested the ability of these predictors in association with misoprostol treatment success to discriminate between treatment success and treatment failure. To quantify the ability of the score to discriminate between treatment success and treatment failure in each treatment arm as well as in the entire cohort, we calculated the area under the curve. Using multivariable logistic regression, we then assessed our study population for other predictors of treatment success in both treatment groups, with and without mifepristone pretreatment.ResultsOverall, 297 evaluable participants were included in the primary study, with 148 in the mifepristone-misoprostol combined treatment group and 149 in the misoprostol-alone treatment group. Among patients who had vaginal bleeding at the time of treatment, 15 of 17 (88%) in the mifepristone-misoprostol combined treatment group and 12 of 17 (71%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. Among patients with a parity of 0 or 1, 94 of 108 (87%) in the mifepristone-misoprostol treatment group and 66 of 95 (69%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. These clinical characteristics did not predict treatment success in the combined cohort alone (area under the curve=0.56; 95% confidence interval, 0.48-0.64). No other baseline clinical factors predicted treatment success in the misoprostol-alone treatment arm or mifepristone pretreatment arm. In the full cohort, the significant predictors of treatment success were pretreatment with mifepristone (adjusted odds ratio=2.51; 95% confidence interval, 1.43-4.43) and smoking (adjusted odds ratio=2.15; 95% confidence interval, 1.03-4.49).ConclusionNo baseline clinical factors predicted treatment success in women receiving medical management with misoprostol for early pregnancy loss. Adding mifepristone to the medical management regimen of early pregnancy loss improved treatment success; thus, mifepristone treatment should be considered for management of early pregnancy loss regardless of baseline clinical factors

Six-month Expulsion of Postplacental Copper Intrauterine Devices Placed After Vaginal Delivery

Background Immediate placement of an intrauterine device after vaginal delivery is safe and convenient, but longitudinal data describing clinical outcomes have been limited. Objective We sought to determine the proportion of TCu380A (copper) intrauterine devices expelled, partially expelled, malpositioned, and retained, as well as contraceptive use by 6 months postpartum, and determine risk factors for expulsion and partial expulsion. Study Design In this prospective, observational study, women who received a postplacental TCu380A intrauterine device at vaginal delivery were enrolled postpartum. Participants returned for clinical follow-up at 6 weeks, and for a research visit with a pelvic exam and ultrasound at 6 months. We recorded intrauterine device outcomes and 6-month contraceptive use. Partial expulsion was defined as an intrauterine device protruding from the external cervical os, or a transvaginal ultrasound showing the distal end of the intrauterine device below the internal os of the cervix. Multinomial logistic regression models identified risk factors associated with expulsion and partial expulsion by 6 months. The area under the receiver operating characteristics curve was used to assess the ability of a string check to predict the correct placement of a postplacental intrauterine device. The primary outcome was the proportion of intrauterine devices expelled at 6 months. Results We enrolled 200 women. Of 162 participants with follow-up data at 6 months, 13 (8.0%; 95% confidence interval, 4.7–13.4%) experienced complete expulsion and 26 (16.0%; 95% confidence interval, 11.1–22.6%) partial expulsion. Of 25 malpositioned intrauterine devices (15.4%; 95% confidence interval, 10.2–21.9%), 14 were not at the fundus (8.6%; 95% confidence interval, 5.2–14.1%) and 11 were rotated within the uterus (6.8%; 95% confidence interval, 3.8–11.9%). Multinomial logistic regression modeling indicated that higher parity (odds ratio, 2.05; 95% confidence interval, 1.21–3.50; P = .008) was associated with expulsion. Provider specialty (obstetrics vs family medicine; odds ratio, 5.31; 95% confidence interval, 1.20–23.59; P = .03) and gestational weight gain (normal vs excess; odds ratio, 9.12; 95% confidence interval, 1.90–43.82; P = .004) were associated with partial expulsion. Long-acting reversible contraceptive method use at 6 months was 80.9% (95% confidence interval, 74.0–86.6%). At 6 weeks postpartum, 35 of 149 (23.5%; 95% confidence interval, 16.9–31.1%) participants had no intrauterine device strings visible. Sensitivity of a string check to detect an incorrectly positioned intrauterine device was 36.2%, and specificity of the string check to predict a correctly positioned intrauterine device was 84.5%. This corresponds to an area under the receiver operating characteristics curve of 0.5. Conclusion This prospective assessment of postplacental TCu380A intrauterine device placement, with ultrasound to confirm device position, finds a complete intrauterine device expulsion proportion of 8.0% at 6 months. The association of increasing parity with expulsion is consistent with prior research. The clinical significance of covariates associated with partial expulsion (provider specialty and gestational weight gain) is unclear. Due to the observational study design, any associations cannot imply causality. The proportion of partially expelled and malpositioned intrauterine devices was high, and the area under the receiver operating characteristics curve of 0.5 indicates that a string check is a poor test for assessing device position. Women considering a postplacental intrauterine device should be counseled about the risk of position abnormalities, as well as the possibility of nonvisible strings, which may complicate clinical follow-up. The clinical significance of intrauterine device position abnormalities is unknown; future research should evaluate the influence of malposition and partial expulsion on contraceptive effectiveness and side effects

Timing and efficacy of mifepristone pretreatment for medical management of early pregnancy loss

ObjectivesTo determine the time interval between mifepristone and misoprostol administration associated with the most efficacious early pregnancy loss (EPL) management.Study designWe performed a secondary analysis of a randomized trial. Participants with EPL were instructed to take 200 mg oral mifepristone followed by 800 mcg vaginal misoprostol 24 hours later. The primary outcome was gestational sac expulsion at the first follow-up visit (1-4 days after misoprostol use) after a single dose of misoprostol and no additional intervention within 30 days after treatment. Despite specification of drug timing, participants used the medication over a range of time. We graphed sliding average estimates of success and assessed the proportion of treatment successes over time to define timing interval cohorts for analysis. We used multivariable generalized linear regression to assess the association between time interval and success.ResultsOf 139 eligible participants, 70 (50.4%) self-administered misoprostol before 24 hours, and 69 (49.6%) at or after 24 hours. We defined the following time intervals: 0 to 6 hours (n = 22); 7 to 20 hours (n = 29); and 21 to 48 hours (n = 88). Success occurred in 96.6% of the 7- to 20-hour cohort compared to 54.6% and 87.5% of the cohorts self-administering misoprostol earlier or later, respectively. When adjusting for race, gestational age, diagnosis, bleeding at presentation, insurance status, and enrollment site, participants administering misoprostol between 0 and 6 hours (adjusted risk ratio 0.58, 95% CI 0.40-0.85) and 21 to 48 hours (adjusted risk ratio 0.91, 95% CI 0.72-0.99) had a lower risk of success when compared to participants administering 7 to 20 hours after mifepristone.ConclusionsThese data suggest that medical management of EPL has the highest likelihood of success when misoprostol is self-administered 7 to 20 hours after mifepristone.ImplicationsThese preliminary data suggest that patients have the highest likelihood of success when misoprostol is taken between 7 and 20 hours after mifepristone. In contrast with medical abortion, simultaneous medication administration may not be as effective as delayed. Future research is needed to confirm the optimal medication time interval

The effect of mifepristone pretreatment on bleeding and pain during medical management of early pregnancy loss

ObjectivesTo compare participant-reported bleeding and pain with two medication regimens for early pregnancy loss (EPL).Study designWe performed a secondary analysis of a randomized trial in which participants took either mifepristone 200 mg orally followed by misoprostol 800 mcg vaginally 24 hours later or misoprostol alone for medical management of EPL. Participants reported bleeding and pain (Numeric Pain Rating Scale, NPRS, 0-10) with daily paper diaries and at study visits on trial days 3, 8, and 30. We used, Fisher's exact, Pearson chi-square, Wilcoxon rank sum, and Student's t-tests to compare onset, duration, and severity of bleeding and pain symptoms between trial arms after misoprostol administration.ResultsAmong 291 participants who submitted diary data, 143 received mifepristone pretreatment. A larger proportion of this group reported moderate or heavy bleeding on trial day 2, the day of misoprostol administration, compared with those who did not receive pretreatment (73% vs 47%, p < 0.01). Between days 4 and 8, more mifepristone-pretreatment participants reported mild or no bleeding, compared with the misoprostol-only arm (78% vs 61%, p < 0.01). Average pain score for trial days 2-4 was higher for the pretreatment group compared with the misoprostol-only group (6.9 vs 6.0, p = 0.01), and there was a trend toward shorter total duration of pain (15 vs 19 hours, p = 0.08). These differences remained after controlling for treatment success across arms.ConclusionsMifepristone pretreatment increased the severity of pain but not bleeding and resulted in a shorter trajectory of symptoms during medical management of EPL.ImplicationsMifepristone pretreatment decreases the duration of heavy bleeding and there was a trend toward decreased duration of pain during medical management of miscarriage, indicating that this medication improves the efficiency, in addition to the efficacy, of this treatment

Management of early pregnancy loss with mifepristone and misoprostol: clinical predictors of treatment success from a randomized trial.

BackgroundEarly pregnancy loss is a common event in the first trimester, occurring in 15%-20% of confirmed pregnancies. A common evidence-based medical regimen for early pregnancy loss uses misoprostol, a prostaglandin E1 analog, with a dosage of 800 μg, self-administered vaginally. The clinical utility of this regimen is limited by suboptimal effectiveness in patients with a closed cervical os, with 29% of patients experiencing early pregnancy loss requiring a second dose after 3 days and 16% of patients eventually requiring a uterine aspiration procedure.ObjectiveThis study aimed to evaluate clinical predictors associated with treatment success in patients receiving medical management with mifepristone-misoprostol or misoprostol alone for early pregnancy loss.Study designWe performed a planned secondary analysis of a randomized trial comparing mifepristone-misoprostol with misoprostol alone for management of early pregnancy loss. The published prediction model for treatment success of single-dose misoprostol administered vaginally included the following variables: active bleeding, type of early pregnancy loss (anembryonic pregnancy or embryonic and/or fetal demise), parity, gestational age, and treatment site; previous significant predictors were vaginal bleeding within the past 24 hours and parity of 0 or 1 vs >1. To determine if these characteristics predicted differential proportions of patients with treatment success or failure, we performed bivariate analyses; given the small proportion of treatment failures in the combined treatment arm, both arms were combined for analysis. Thereafter, we performed a logistic regression analysis to assess the effect of these predictors collectively in each of the 2 treatment groups separately as well as in the full cohort as a proxy for the combined treatment arm. Finally, by using receiver operating characteristic curves, we tested the ability of these predictors in association with misoprostol treatment success to discriminate between treatment success and treatment failure. To quantify the ability of the score to discriminate between treatment success and treatment failure in each treatment arm as well as in the entire cohort, we calculated the area under the curve. Using multivariable logistic regression, we then assessed our study population for other predictors of treatment success in both treatment groups, with and without mifepristone pretreatment.ResultsOverall, 297 evaluable participants were included in the primary study, with 148 in the mifepristone-misoprostol combined treatment group and 149 in the misoprostol-alone treatment group. Among patients who had vaginal bleeding at the time of treatment, 15 of 17 (88%) in the mifepristone-misoprostol combined treatment group and 12 of 17 (71%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. Among patients with a parity of 0 or 1, 94 of 108 (87%) in the mifepristone-misoprostol treatment group and 66 of 95 (69%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. These clinical characteristics did not predict treatment success in the combined cohort alone (area under the curve=0.56; 95% confidence interval, 0.48-0.64). No other baseline clinical factors predicted treatment success in the misoprostol-alone treatment arm or mifepristone pretreatment arm. In the full cohort, the significant predictors of treatment success were pretreatment with mifepristone (adjusted odds ratio=2.51; 95% confidence interval, 1.43-4.43) and smoking (adjusted odds ratio=2.15; 95% confidence interval, 1.03-4.49).ConclusionNo baseline clinical factors predicted treatment success in women receiving medical management with misoprostol for early pregnancy loss. Adding mifepristone to the medical management regimen of early pregnancy loss improved treatment success; thus, mifepristone treatment should be considered for management of early pregnancy loss regardless of baseline clinical factors

The Role of Subcutaneous Depot Medroxyprogesterone Acetate in Equitable Contraceptive Care

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, health care professionals have made swift accommodations to provide consistent and safe care, including emphasizing remote access to allow physical distancing. Depot medroxyprogesterone acetate intramuscular injection (DMPA-IM) prescription is typically administered by a health care professional, whereas DMPA-subcutaneous has the potential to be safely self-injected by patients, avoiding contact with a health care professional. However, DMPA-subcutaneous is rarely prescribed despite its U.S. Food and Drug Administration approval in 2004 and widespread coverage by both state Medicaid providers and many private insurers. Depot medroxyprogesterone acetate users are disproportionately non-White, and thus the restriction in DMPA-subcutaneous prescribing may both stem from and contribute to systemic racial health disparities. We review evidence on acceptability, safety, and continuation rates of DMPA-subcutaneous, consider sources of implicit bias that may impede prescription of this contraceptive method, and provide recommendations for implementing DMPA-subcutaneous prescribing

Utility and Limitations of Human Chorionic Gonadotropin Levels for Remote Follow-up After Medical Management of Early Pregnancy Loss

Early pregnancy loss can be treated medically with mifepristone followed by misoprostol, with ultrasonographic confirmation of pregnancy expulsion. Alternative strategies that ascertain treatment success remotely are needed. We compared percent decline in human chorionic gonadotropin (hCG) level with treatment success or failure between patients who received mifepristone pretreatment followed by misoprostol or misoprostol alone for early pregnancy loss between 5 and 12 weeks of gestation to determine a threshold decline that might predict success. Early pregnancy loss treatment success was associated with a greater percent hCG level decline compared with treatment failure, but no threshold was able to predict success. Additional research is needed to understand hCG trends after medical management of early pregnancy loss to develop reliable protocols for remote follow-up

Guilt, blame and responsibility: men's understanding of their role in the transmission of BRCA1/2 mutations within their family

Men and women who have a family history of breast and/or ovarian cancer may be offered a predictive genetic test to determine whether or not they carry the family specific BRCA1/2 mutation. The sons and daughters of mutation carriers have a 50 per cent chance of inheriting a mutation, which will increase their risk of developing cancer. Little is known about at-risk men's feelings about the part they play in the transmission of BRCA1/2 mutations within their families. This study investigated high risk men's responses to BRCA1/2 predictive genetic testing. Seventeen in-depth interviews were undertaken with carrier (n= 5) and non-carrier men (n= 12). All men described genetic testing as a familial duty. It is observed that carriers and non-carriers mobilised differing explanations about their role in the aetiology of risk. It is noted that men engage in a form of narrative reconstruction in which they draw upon discourses of guilt and blame or fate and predestiny in an effort to present themselves as morally responsible or blameless. It is argued that narrative reconstruction enables these men to reconcile their genetic identity, self and family