Patient-centered care is one of the six aims for improvement in health care quality outlined by the National Academy of Medicine (previously known as the Institute of Medicine). We propose an algorithm for patients who are presenting with a pregnancy of unknown location that emphasizes pregnancy desiredness to improve patient-centered care. Health care professionals should assess pregnancy desiredness at a patient's initial consultation for evaluation of pregnancy of unknown location; desiredness, along with other clinical criteria, should guide management. For women with an undesired pregnancy, health care professionals should offer expedient active management. Uterine aspiration will allow for quick clinical diagnosis and resolution of the pregnancy. Alternatively, for women with a desired pregnancy or for those who are ambivalent, we recommend careful conservative management. Adopting this algorithm will recenter the patient in the complex management of pregnancy of unknown location.

Background

Medical management of early pregnancy loss is an alternative to uterine aspiration, but standard medical treatment with misoprostol commonly results in treatment failure. We compared the efficacy and safety of pretreatment with mifepristone followed by treatment with misoprostol with the efficacy and safety of misoprostol use alone for the management of early pregnancy loss.

Methods

We randomly assigned 300 women who had an anembryonic gestation or in whom embryonic or fetal death was confirmed to receive pretreatment with 200 mg of mifepristone, administered orally, followed by 800 μg of misoprostol, administered vaginally (mifepristone-pretreatment group), or 800 μg of misoprostol alone, administered vaginally (misoprostol-alone group). Participants returned 1 to 4 days after misoprostol use for evaluation, including ultrasound examination, by an investigator who was unaware of the treatment-group assignments. Women in whom the gestational sac was not expelled were offered expectant management, a second dose of misoprostol, or uterine aspiration. We followed all participants for 30 days after randomization. Our primary outcome was gestational sac expulsion with one dose of misoprostol by the first follow-up visit and no additional intervention within 30 days after treatment.

Results

Complete expulsion after one dose of misoprostol occurred in 124 of 148 women (83.8%; 95% confidence interval [CI], 76.8 to 89.3) in the mifepristone-pretreatment group and in 100 of 149 women (67.1%; 95% CI, 59.0 to 74.6) in the misoprostol-alone group (relative risk, 1.25; 95% CI, 1.09 to 1.43). Uterine aspiration was performed less frequently in the mifepristone-pretreatment group than in the misoprostol-alone group (8.8% vs. 23.5%; relative risk, 0.37; 95% CI, 0.21 to 0.68). Bleeding that resulted in blood transfusion occurred in 2.0% of the women in the mifepristone-pretreatment group and in 0.7% of the women in the misoprostol-alone group (P=0.31); pelvic infection was diagnosed in 1.3% of the women in each group.

Conclusions

Pretreatment with mifepristone followed by treatment with misoprostol resulted in a higher likelihood of successful management of first-trimester pregnancy loss than treatment with misoprostol alone. (Funded by the National Institute of Child Health and Human Development; PreFaiR ClinicalTrials.gov number, NCT02012491 .).

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.

Importance

Early pregnancy loss (EPL) is the most common complication of pregnancy. A multicenter randomized clinical trial compared 2 strategies for medical management and found that mifepristone pretreatment is 25% more effective than the standard of care, misoprostol alone. The cost of mifepristone may be a barrier to implementation of the regimen.

Objective

To assess the cost-effectiveness of medical management of EPL with mifepristone pretreatment plus misoprostol vs misoprostol alone in the United States.

Design, setting, and participants

This preplanned. prospective economic evaluation was performed concurrently with a randomized clinical trial in 3 US sites from May 1, 2014, through April 30, 2017. Participants included 300 women with anembryonic gestation or embryonic or fetal demise. Cost-effectiveness was computed from the health care sector and societal perspectives, with a 30-day time horizon. Data were analyzed from July 1, 2018, to July 3, 2019.

Interventions

Mifepristone pretreatment plus misoprostol administration vs misoprostol alone.

Main outcomes and measures

Costs in 2018 US dollars, effectiveness in quality-adjusted life-years (QALYs), and treatment efficacy. Incremental cost-effectiveness ratios (ICERs) of mifepristone and misoprostol vs misoprostol alone were calculated, and cost-effectiveness acceptability curves were generated.

Results

Among the 300 women included in the randomized clinical trial (mean [SD] age, 30.4 [6.2] years), mean costs were similar for groups receiving mifepristone pretreatment and misoprostol alone from the health care sector perspective ($696.75 [95% CI, $591.88-$801.62] vs $690.88 [95% CI, $562.38-$819.38]; P = .94) and the societal perspective ($3846.30 [95% CI, $2783.01-$4909.58] vs $4845.62 [95% CI, $3186.84-$6504.41]; P = .32). The mifepristone pretreatment group had higher QALYs (0.0820 [95% CI, 0.0815-0.0825] vs 0.0806 [95% CI, 0.0800-0.0812]; P = .001) and a higher completion rate after first treatment (83.8% vs 67.1%; P < .001) than the group receiving misoprostol alone. From the health care sector perspective, mifepristone pretreatment was cost-effective relative to misoprostol alone with an ICER of $4225.43 (95% CI, -$195 053.30 to $367 625.10) per QALY gained. From the societal perspective, mifepristone pretreatment dominated misoprostol alone (95% CI, -$5 111 629 to $1 801 384). The probabilities that mifepristone pretreatment was cost-effective compared with misoprostol alone at a willingness-to-pay of $150 000 per QALY gained from the health care sector and societal perspectives were approximately 90% and 80%, respectively.

Conclusions and relevance

This study found that medical management of EPL with mifepristone pretreatment was cost-effective when compared with misoprostol alone.

Trial registration

ClinicalTrials.gov Identifier: NCT02012491.

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.

Background

Early 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.

Objective

This 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 design

We 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.

Results

Overall, 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).

Conclusion

No 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.

Objective

To evaluate the real-world safety of hysteroscopic compared with laparoscopic surgical sterilization.

Methods

We conducted a retrospective cohort study of Medicaid claims for hysteroscopic or laparoscopic sterilization procedures performed in California, 2008-2014, among women aged 18-50 years. After excluding postpartum procedures, we applied log-linear (Poisson) event-history regression models for clustered person-period data, weighted for propensity to receive either sterilization procedures, and adjusted for sociodemographic and clinical characteristics that may affect outcomes of interest to patients and physicians. We assessed the following outcomes: procedural complications, additional surgical procedures (eg, hysterectomy), repeat sterilization procedures, pelvic pain, pelvic inflammatory disease (PID), abdominal pain, nonabdominal pain, and abnormal uterine bleeding.

Results

We identified 5,906 women who had undergone hysteroscopic and 23,965 who had undergone laparoscopic sterilization. After adjusting for sociodemographic and health history, women who had hysteroscopic sterilization were less likely to have claims for procedural complications (eg, transfusion, P<.001) on the day of surgical sterilization and additional surgical procedures (eg, hysterectomy, P=.002 at day 2-3 months postprocedure) than laparoscopic sterilization. Claims for a repeat attempt at sterilization were more common after hysteroscopic sterilization within 1 year (adjusted incident rate ratio 3.48, 95% CI 2.69-4.27) and within 5 years (adjusted incident rate ratio 2.32, 95% CI 1.84-2.79) than laparoscopic sterilization. Claims for pelvic pain (adjusted incident rate ratio 0.77, 95% CI 0.65-0.92 at 2 years), abdominal pain (adjusted incident rate ratio 0.80, 95% CI 0.68-0.93 at 7-12 months), and PID (adjusted incident rate ratio 0.55, 95% CI 0.33-0.93 at 2 years) were less common after hysteroscopic than laparoscopic sterilization. Although abnormal uterine bleeding claims were more common after hysteroscopic than laparoscopic sterilization up to 12 months postprocedure (adjusted incident rate ratio 1.37, 95% CI 1.06-1.77 at 7-12 months), there were no significant differences between methods 1 year after the procedure.

Conclusion

Compared with laparoscopic sterilization, hysteroscopic sterilization was followed by more claims for repeat sterilization procedures and abnormal uterine bleeding, but fewer procedural complications and fewer claims for pelvic or abdominal pain.

Clinical trial registration

ClinicalTrials.gov, NCT03438682.

Objective

To compare real-world effectiveness of hysteroscopic to laparoscopic sterilization.

Design

Retrospective cohort of Medicaid claims for hysteroscopic or laparoscopic sterilization procedures performed in California, 2008-2014. After excluding postpartum procedures, we applied log-linear (Poisson) event-history regression models for clustered person-period data, weighted for propensity to receive either sterilization procedures, and adjusted for sociodemographic and clinical variables to examine the poststerilization pregnancy rates.

Setting

Clinics, hospitals.

Patient(s)

Women aged 18-50 years with Medicaid claims between January 1, 2008, and August 31, 2014.

Intervention(s)

Hysteroscopic or laparoscopic sterilization procedure.

Main outcome measure(s)

Poststerilization pregnancy measured by pregnancy-related claims.

Result(s)

Among women with hysteroscopic (n = 5,906) or laparoscopic (n = 23,965) sterilization, poststerilization pregnancy claims were identified for 4.74% of women after hysteroscopic sterilization and 5.57% after laparoscopic sterilization. The pregnancy rates decreased over time after either procedure. Twelve months after the procedure, the crude incidence of pregnancy claims was higher for hysteroscopic sterilization than for laparoscopic sterilization (3.26 vs. 2.61 per 100 woman-years), but the propensity-weighted adjusted incidence rate ratio was 1.06 (95% confidence interval [CI], 0.85-1.26). Between 13 and 24 months after the procedure, there were fewer pregnancies for women after hysteroscopic sterilizations than for those after laparoscopic sterilizations (adjusted incidence rate ratio, 0.63 [95% CI, 0.45-0.88]), with no statistically significant differences in later years. The cumulative pregnancy rates 5 years after sterilization were lower with hysteroscopic sterilization than with laparoscopic sterilization (6.26 vs. 7.22 per 100 woman-years; propensity-weighted, adjusted risk ratio, 0.76 [95% CI, 0.62-0.90]). The poststerilization pregnancy rates varied by age and race/ethnicity.

Conclusion(s)

The pregnancy rates after female sterilization are higher than expected, whether performed hysteroscopically or laparoscopically. These findings are reassuring that the effectiveness of hysteroscopic sterilization was not inferior to laparoscopic sterilization.

Clinical trial registration number

NCT03438682.