Cost-effectiveness of mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage: an economic evaluation based on the MifeMiso trial.

OBJECTIVE: To assess the cost-effectiveness of mifepristone and misoprostol (MifeMiso) compared with misoprostol only for the medical management of a missed miscarriage. DESIGN: Within-trial economic evaluation and model-based analysis to set the findings in the context of the wider economic evidence for a range of comparators. Incremental costs and outcomes were calculated using nonparametric bootstrapping and reported using cost-effectiveness acceptability curves. Analyses were performed from the perspective of the UK's National Health Service (NHS). SETTING: Twenty-eight UK NHS early pregnancy units. SAMPLE: A cohort of 711 women aged 16-39 years with ultrasound evidence of a missed miscarriage. METHODS: Treatment with mifepristone and misoprostol or with matched placebo and misoprostol tablets. MAIN OUTCOME MEASURES: Cost per additional successfully managed miscarriage and quality-adjusted life years (QALYs). RESULTS: For the within-trial analysis, MifeMiso intervention resulted in an absolute effect difference of 6.6% (95% CI 0.7-12.5%) per successfully managed miscarriage and a QALYs difference of 0.04% (95% CI -0.01 to 0.1%). The average cost per successfully managed miscarriage was lower in the MifeMiso arm than in the placebo and misoprostol arm, with a cost saving of £182 (95% CI £26-£338). Hence, the MifeMiso intervention dominated the use of misoprostol alone. The model-based analysis showed that the MifeMiso intervention is preferable, compared with expectant management, and this is the current medical management strategy. However, the model-based evidence suggests that the intervention is a less effective but less costly strategy than surgical management. CONCLUSIONS: The within-trial analysis found that based on cost-effectiveness grounds, the MifeMiso intervention is likely to be recommended by decision makers for the medical management of women presenting with a missed miscarriage. TWEETABLE ABSTRACT: The combination of mifepristone and misoprostol is more effective and less costly than misoprostol alone for the management of missed miscarriages.

Mifepristone Combination Therapy Compared With Misoprostol Monotherapy for the Management of Miscarriage: A Cost-Effectiveness Analysis.

OBJECTIVE: To assess whether mifepristone pretreatment adversely affects the cost of medical management of miscarriage. METHODS: Decision tree analyses were constructed, and Monte Carlo simulations were run comparing costs of combination therapy (mifepristone and misoprostol) with monotherapy (misoprostol alone) for medical management of miscarriage in multiple scenarios weighing clinical practice, patient income, and surgical evacuation modalities for failed medical management. Rates of completed medical evacuation for each were obtained from a recent randomized controlled trial. RESULTS: In every scenario, combination therapy offered a significant cost advantage over monotherapy. Using a Monte Carlo analysis, cost differences favoring combination therapy ranged from 6.3% to 19.5% in patients making federal minimum wage. The cost savings associated with combination therapy were greatest in scenarios using a staged approach to misoprostol administration and in scenarios using in-operating room dilation and curettage as the only modality for uterine evacuation, a savings of $190.20 (99% CI 189.35-191.07) and $217.85 (99% CI 217.19-218.50) per patient in a low-income wage group, respectively. A smaller difference was seen in scenarios using in-office manual vacuum aspiration to complete medical management failures. As patients' wages increased, the difference in cost between combination therapy and monotherapy increased. CONCLUSION: Mifepristone combined with misoprostol is, overall, more cost effective than monotherapy, and therefore cost should not be a deterrent to its adoption in the management of miscarriage.

The costs and cost effectiveness of providing second-trimester medical and surgical safe abortion services in Western Cape Province, South Africa.

BACKGROUND: In South Africa, access to second-trimester abortion services, which are generally performed using medical induction with misoprostol alone, is challenging for many women. We aimed to estimate the costs and cost effectiveness of providing three safe second-trimester abortion services (dilation and evacuation (D&E)), medical induction with mifepristone and misoprostol (MI-combined), or medical induction with misoprostol alone (MI-misoprostol)) in Western Cape Province, South Africa to aid policymakers with planning for service provision in South Africa and similar settings. METHODS: We derived clinical outcomes data for this economic evaluation from two previously conducted clinical studies. In 2013-2014, we collected cost data from three public hospitals where the studies took place. We collected cost data from the health service perspective through micro-costing activities, including discussions with site staff. We used decision tree analysis to estimate average costs per patient interaction (e.g. first visit, procedure visit, etc.), the total average cost per procedure, and cost-effectiveness in terms of the cost per complete abortion. We discounted equipment costs at 3%, and present the results in 2015 US dollars. RESULTS: D&E services were the least costly and the most cost-effective at $91.17 per complete abortion. MI-combined was also less costly and more cost-effective (at $298.03 per complete abortion) than MI-misoprostol (at $375.31 per complete abortion), in part due to a shortened inpatient stay. However, an overlap in the plausible cost ranges for the two medical procedures suggests that the two may have equivalent costs in some circumstances. CONCLUSION: D&E was most cost-effective in this analysis. However, due to resistance from health care providers and other barriers, these services are not widely available and scale-up is challenging. Given South Africa's reliance on medical induction, switching to the combined regimen could result in greater access to second-trimester services due to shorter inpatient stays without increasing costs.

Women's experiences with medication for menstrual regulation in Bangladesh.

Menstrual regulation has been legal in Bangladesh since 1974, but the use of medication for menstrual regulation is new. In this study, we sought to understand women's experiences using medication for menstrual regulation in Bangladesh. We conducted 20 in-depth interviews with rural and urban women between December 2013 and February 2014. All interviews were audiotaped, transcribed, translated, computer recorded and coded for analysis. The majority of women in our study had had positive experiences with medication for menstrual regulation and successful outcomes, regardless of whether they obtained their medication from medicine sellers/pharmacies, doctors or clinics. Women were strongly influenced by health providers when deciding which method to use. There is a need to educate not only women of reproductive age, but also communities as a whole, about medication for menstrual regulation, with a particular emphasis on cost and branding the medication. Continued efforts to improve counselling by providers about the dose, medication and side-effects of medication for menstrual regulation, along with education of the community about medication as an option for menstrual regulation, will help to de-stigmatise the procedure and the women who seek it.

Reaching women where they are: eliminating the initial in-person medical abortion visit.

The requirement that every woman desiring medical abortion must come in person to a clinical facility to obtain the drugs is a substantial barrier for many women. To eliminate this requirement in the United States, two key components of the standard initial visit would need to be restructured. First, alternatives to ultrasound and pelvic exam would need to be identified for ensuring that gestational age is within the limit for safe and effective treatment. This is probably feasible: for example, data from a large study suggest that in selected patients menstrual history is highly sensitive for this purpose. Second, the Food and Drug Administration would need to remove the medically unwarranted restriction on distribution of mifepristone. These two changes could allow provision of the service by a broader range of providers in nontraditional venues or even by telemedicine. Such options could have profound benefits in reducing cost and expanding access to abortion.

Medical treatment of ectopic pregnancy: a committee opinion.

Methotrexate, a folic acid antagonist, is an effective treatment for early unruptured ectopic pregnancy. Several treatment regimens are available. Methotrexate is more effective when used to treat ectopic pregnancies with lower human chorionic gonadotropin (hCG) levels. However, there is no consensus on a threshold value that best predicts success or failure. Methotrexate can be used to treat ectopic pregnancies that occur in cornual, cervical, and cesarean scar locations, and it does not adversely affect ovarian reserve or subsequent fertility. This document replaces the previous document of the same name, last published in 2008 (Fertil Steril 2008;90:S206-12).

Medication abortions among New York City residents, 2001-2008.

CONTEXT: Population-level research on trends in medication abortions and the association of patient characteristics and facility type with procedure choice is limited. Surveillance is necessary to ensure accurate reporting and understanding of service availability. METHODS: New York City induced abortion data for 2001-2008 were used to calculate medication abortion prevalence among women undergoing early abortions (i.e., at nine or fewer weeks of gestation). Multiple logistic regression analysis was used to assess associations between selected characteristics and having a medication, as opposed to surgical, abortion. Proportions of patients who went to clinics or hospitals that did not offer medication abortions were also calculated. RESULTS: Five percent of early abortions were medication procedures in 2001; the proportion rose to 13% by 2008. Eighty-two percent of medication abortions in 2008 were performed at freestanding clinics, and 10% at doctors' offices. The likelihood of having had a medication abortion, rather than a surgical one, was lower among blacks and Hispanics than among whites (odds ratios, 0.5 and 0.7, respectively). Medication abortions were more likely among women with more than 12 years of education than among those with less than a high school education (2.1), and more likely among those who went to doctors' offices than among clinic patients (3.6). Throughout 2001-2008, medication abortions were not available at 50% of hospitals and 31% of clinics that provided early abortions. CONCLUSIONS: The increasing prevalence of medication abortions highlights the importance of active surveillance. Because many facilities do not offer the procedure, a better understanding of barriers to provision is needed.

Medical versus surgical abortion methods for pregnancy in China: a cost-minimization analysis.

BACKGROUND: Both medical and surgical abortions are popular in developing countries. However, the monetary costs of these two methods have not been compared. METHODS: 430 women seeking abortions were recruited in 2008. Either a medical or surgical method was used for the abortion. We adopted the perspective of a third-party payer. Cost-minimization analysis was used based on all charges for the overall procedures in an out-patient clinic in Guangzhou, China. RESULTS: 219 subjects (51%) chose a medical method (mifepristone and misoprostol), whereas 211 subjects (49%) chose a surgical method. The efficacy in the surgical group was significantly higher than in the medical group (100 vs. 90%, p < 0.001). Surgical abortion incurred much more costs than medical abortion on average after initial treatment. When the subsequent costs were accumulated within the 2-week follow-up, the mean total cost in the medical group increased significantly due to failure of abortion and persistent bleeding. Patients undergoing medical abortion eventually incurred equivalent expenses compared to patients undergoing surgical abortion (p = 0.42). CONCLUSIONS: There was no difference in the mean final costs between the two abortion methods. Complications of persistent bleeding and failure to abort (requiring surgical intervention) in the medical treatment group increased the final mean total cost substantially.

Comparing two early medical abortion regimens: mifepristone+misoprostol vs. misoprostol alone.

BACKGROUND: Nonsurgical abortion methods have the potential to improve access to high-quality abortion care. Until recently, availability and utilization of mifepristone medical abortion in low-resource countries were restricted due to the limited availability and perceived high cost of mifepristone, leading some providers and policymakers to support use of misoprostol-only regimens. Yet, this may not be desirable if misoprostol-only regimens are considerably less effective and ultimately more costly for health care systems. This study sought to document the differences in efficacy between two nonsurgical abortion regimens. STUDY DESIGN: This double-blind randomized placebo-controlled trial enrolled women with gestational ages up to 63 days seeking early medical abortion from August 2007 to March 2008 at a large tertiary hospital in Ho Chi Minh City, Vietnam. Eligible consenting women received either (1) two doses of 800 mcg buccal misoprostol 24 h apart or (2) 200 mg mifepristone and 800 mcg buccal misoprostol 24 h later. Participants self-administered all study drugs and returned to the hospital for follow-up 1 week later. The trial is registered at ClinicalTrials.gov as NCT00680394. RESULTS: Four hundred women were randomized to either misoprostol-only (198) or mifepristone+misoprostol (202). Complete abortion occurred for 76.2% (n=147) of women allocated to misoprostol-only vs. 96.5% (n=194) of those given mifepristone+misoprostol (RR 0.79, 95% CI 0.73-0.86). Ongoing pregnancy was documented for 16.6% (32) of misoprostol-only users and 1.5% (3) of mifepristone+misoprostol users (1.62, 0.68-3.90). Side effects were generally similar for both groups, although significantly more women allocated to misoprostol-only reported diarrhea. CONCLUSIONS: Mifepristone+misoprostol is significantly more effective than use of misoprostol-alone for early medical abortion. The number of ongoing pregnancies documented with misoprostol-only warranted an early end of the trial after unblinding of the study at interim analysis. Policymakers should advocate for greater access to mifepristone. Future research should prioritize misoprostol-only regimens with shorter dosing intervals.

Which approach for first trimester miscarriage?

Around 15% of all known pregnancies miscarry during the first trimester. Historically, first trimester miscarriage was managed surgically to remove all retained products of conception, with the aim of minimising the likelihood of blood loss and infection from retained tissue. Nowadays, medical management (use of drugs such as mifepristone and misoprostol) and expectant management (i.e. allowing the miscarriage to conclude naturally) have become alternatives to a surgical procedure for managing women with early miscarriage. Here, we review the evidence on these three methods to assess the benefits and disadvantages of each.

Management strategies for abnormal early pregnancy: a cost-effectiveness analysis.

OBJECTIVE: To assess the potential effectiveness and costs of 4 commonly used strategies to manage abnormal early pregnancies (AEPs). STUDY DESIGN: A decision analysis model was constructed to compare 4 strategies to manage AEPs: (1) observation, (2) medical management, (3) manual vacuum aspiration (MVA), and (4) dilation and curettage (D&C). RESULTS: MVA was the most cost-effective strategy, at dollar 793 per cure, for a total cost of dollar 377 million per 500,000 women and a cure rate of 95%. D&C was more effective than MVA, with a cure rate of 99%, but was more expensive (dollar 2,333 per cure, for a total cost of dollar 1.2 billion). D&C cured 20,000 more patients than MVA; however, at a substantial cost of dollar 38,925 per additional cure. With other estimates at baseline, MVA remained more cost-effective than D&C until the efficacy of MVA was < 82% or the cost of D&C was < dollar 240. CONCLUSION: MVA is the most cost-effective strategy for managing AEP and would be appropriate in settings in which resources are limited. D&C remains a reasonable strategy; however, one must spend dollar 38,925 per additional cure. In the United States, MVA would save dollar 779 million per year relative to D&C.

Second trimester pregnancy termination including fetal death: comparison of five different methods.

OBJECTIVE: To compare the efficacy of methods for second trimester pregnancy termination. METHODS: A prospective randomized study of women undergoing pregnancy termination between 14 and 28 weeks gestation. Three hundred and forty patients with poor cervical condition (Bishop score < or = 4) in whom one of five termination methods were used were assessed: (i) extraamniotic administration of ethacridine lactate (82 patients); (ii) intracervical prostaglandin (PG) E2 gel (100 patients); (iii) intravenous infusion of concentrated oxytocin (36 patients); (iv) vaginal misoprostol (49 patients); and (v) balloon insertion (73 patients). Oxytocin infusion was used in all but concentrated oxytocin group to augment labor, when necessary. Patients in whom effective uterine contractions and cervical dilatation was not obtained within 48 h with the primary termination method were registered as failures. RESULTS: The efficacy of each method were evaluated in terms of abortion within time. Abortion within 48 h were achieved in 98.8% (81/82) of the patients in ethacridine group; 97.3% (35/36) of the patients in concentrated oxytocin group; 90.0% (90/100) of the patients in PGE2 group; 97.2% (71/73) of the patients in balloon group; 77.5% (38/49) of the patients in misoprostol group (P = 0.000, P < 0.01, Wilcoxon (Gehan) statistic). The overall median induction-abortion interval +/- S.D. (in h) in each group were as follows: ethacridine lactate: 15.7 +/- 9.6, PGE2 gel: 20.0 +/- 14.5, concentrated oxytocin: 12.2 +/- 14.4, misoprostol: 24.0 +/- 22.2, balloon: 16.0 +/- 15.4 (one way ANOVA, P = 0.003, P < 0.01). CONCLUSION: In comparison with the five methods, the use of extraamniotic ethacridine, intravenous concentrated oxytocin, and balloon was found to provide more effective treatment than intracervical PGE2 and misoprostol in terms of achievement of abortion within 24 and 48 h.

PIP: The efficacy of 5 methods of second-trimester pregnancy termination was compared in a prospective, randomized study of 340 women admitted to a High Risk Pregnancy Unit in Ankara, Turkey, with an unfavorable cervical state. The women were between 14 and 28 weeks' gestation. Termination methods assessed included: extra-amniotic administration of ethacridine lactate (82 women), cervical ripening through use of prostaglandin (PG) E2 gel (100 women), intravenous infusion of concentrated oxytocin (36 women), intravaginal misoprostol (49 women), and balloon insertion (73 women). Oxytocin infusion was used to augment labor, where necessary, in all but the concentrated oxytocin group. The main indications for pregnancy termination were fetal death (50%) and fetal anomaly (25%). Abortion within 48 hours was achieved in 98.8% of women in the ethacridine group, 97.3% of those in the concentrated oxytocin group, 90.0% of women in the PGE2 group, 97.2% of patients in the balloon group, and 77.5% of those in the misoprostol group. The median induction-abortion intervals were: ethacridine lactate, 15.7 +or- 9.6 hours; PGE2 gel, 20.0 +or- 14.5 hours; concentrated oxytocin, 12.2 +or- 14.4 hours; misoprostol, 24.0 +or- 22.2 hours; and balloon, 16.0 +or- 15.4 hours. Overall, these results suggest that mid-trimester induced abortion with extraamniotic ethacridine, balloon application, or intravenous concentrated oxytocin are the most effective techniques and should be considered as alternatives to misoprostol and PGE2.