Economic evaluation of medical versus surgical strategies for first trimester therapeutic abortion: A systematic review

Significant global efforts have been made to improve the coverage, quality, and range of maternal services for women. Information on the economic evaluation of alternative strategies to improve maternal care can serve as one important policy input to guide decisions on how to achieve newly ratified Sustainable Development Goals of reducing the maternal mortality and morbidity.[ 1 ] Notwithstanding promotions in contraceptive methods, pregnancy termination and abortion related complications remain as potentially health concern and result in significant morbidity and mortality.[ 2 ] Abortion and its nonfatal complications contribute significantly to the global burden of pregnancy termination. Women pay heavily not only with their health and their lives but also financially. Postabortion care imposes a substantial economic burden on society, annual costs of abortion, and postabortion cares ranged from 189,000 $US to 134 million $US and $23 to $564 per patient costs worldwide.[ 3 4 5 ] Pregnancy termination management includes a wide range of conditions as follows; induced abortion, managing incomplete evacuation, control postpartum hemorrhage, treatment of spontaneous abortion, miscarriage management, treatment of early pregnancy failure, management of nonviable early pregnancy, and management of early pregnancy loss.[ 6 ] Current abortion intervention options are classified as surgical (uterine curettage aspiration) or medical (the use of medications to induce uterine contractions and tissue expulsion). These options differ in treatment efficacy, costs, and patient experience. Although the traditional treatment option of pregnancy termination and induced abortion has been a surgical evacuation of the uterus, medical abortion has been gaining popularity as a noninvasive alternative in recent years.[ 7 8 ] Medical management of abortion plays a crucial role in providing access to safe, effective, and acceptable abortion and postabortion cares and encompass either a combination regimen of mifepristone and misoprostol or a misoprostol-only regimen. These medical interventions reduce the need for skilled surgical abortion providers and offer a noninvasive and highly acceptable option for pregnant women. Both surgical and medical options are currently acceptable in practice, but deciding what the best regimen is not always clear.[ 9 10 ] Economic evaluations are defined as the comparative analysis of alternative courses of action in terms of both their costs and consequences and provide clinicians, patients, policymakers, and health-care planners with important information on the available alternatives in the context of limited resources.[ 11 12 ] The aim of this study was to review previous research to determine the economic efficacy of medical and surgical strategies for women seeking pregnancy termination. This research is the first attempt to examine previous research with economic evaluation methods, including cost-effectiveness, cost-utility, cost-benefit, and cost minimization of pregnancy termination interventions. It would provide important insight to relevant stakeholders to create awareness and to implement an effective strategy to reduce the burden associated with these cares.

Overall, 538 records were retrieved (PubMed: 144, Scopus: 74, Web of Science: 91, Embase: 47, Cochrane library: 20, ProQuest: 14, ScienceDirect: 34, Google Scholar: 114). Totally, 538 articles were initially identified by designated electronic databases search. About 196 articles were duplicated and were removed. Of the remaining 342 articles, 294 records as well as additional 6 records were excluded given the irrelevant titles and abstracts, leaving 42 articles eligible for full-text review. Another 22 studies were further excluded after reviewing the full text of the retrieved articles with reasons (studies were related to abnormal pregnancies, gestational trophoblastic, contraception, like IUD interventions, neoplasm, not economic evaluation studies). Finally, 20 articles were included in this systematic review. Study selection procedures are summarized in the PRISMA flow diagram [ Figure 1 ]. PRISMA flowchart The characteristics of the selected studies were summarized as follows; author and year of study, country, sample size, intervention and alternatives for comparison, perspective and time horizon, and the incremental cost-effectiveness ratio (or cost per QALY or cost saving). Reviewed studies had been conducted from 2005 to 2021. Among the reviewed studies, three studies investigated cost-minimization analysis, three studies investigated cost-utility analysis, and 14 studies investigated cost-effectiveness analysis. The characteristics of the twenty studies included in this review were summarized in Table 1 . The largest and smallest sample sizes were 98 patients[ 23 ] and 150,000 patients,[ 27 ] respectively. About 70% of the studies (14 studies) received a score of above 85% and had “excellent” quality and had very low risk of bias[ 1 7 9 14 15 17 18 19 20 21 22 23 27 29 ] [ Appendix 2 ]. Five studies had been conducted in the United States.[ 7 9 13 14 26 ] Other studies conducted in Spain,[ 15 ] Malawi, Pakistan and Tanzania,[ 16 ] Uganda,[ 16 22 ] Netherlands,[ 17 20 ] Nigeria,[ 18 24 ] Ghana,[ 18 ] Mexico,[ 1 ] Canada,[ 19 ] South Africa,[ 21 ] Finland,[ 23 ] England,[ 25 ] Senegal,[ 27 ] and China.[ 28 ] Costs included in the studies were categorized into three type; direct medical costs (e.g., Antibiotics, medications, anesthesia, ultrasounds, surgery, diagnostic, laboratory, visits, consumables, equipment, staffing, supplies, side effects, bleeding, infection, pain control, and hospitalization costs), Direct nonmedical costs (e.g., transportation, training, and family costs), and indirect costs (e.g., patient time costs and productivity loss). We examined the economic evaluation conclusions by specific treatments and study perspectives [ Table 1 ]. The comparison of medical with surgical abortion was most frequently studied, accounting for 10 (50%) of the 20 studies included in this review. Medical abortion was cost-effective and cost-saving option in compare to the surgical abortion in all of these studies and across all perspectives.) Medical abortion (Misoprostol) saved US$ 6 to US$ 2,373 per patient's costs in South Africa[ 21 ] and Spain,[ 15 ] respectively. Also, ICER ranged from US$ 419 to US$ 4,044 in Nigeria[ 24 ] and United States,[ 9 ] respectively.

The present study, which systematically reviewed twenty authentic studies, showed that, based on various economic and clinical effectiveness, decision-making criteria used in various studies of health economic evaluation showed that the majority of research provided evidence on the advantage of pharmaceutical methods compared to surgical methods, as well as the advantages of using combination therapy compared to single therapeutic interventions. The higher completion rate in combination therapy leads to reduce in time spent on treatment, office visits and need for surgical management for persistent pregnancies, which significantly reduces the overall costs of procedures. Ethical issues Including plagiarism, informed consent, misconduct, data fabrication and/or falsification, double publication and/or submission, redundancy, etc., have been completely observed by the authors. This project was financially supported by Iran University of medical sciences as a part of PhD thesis with research code in the university system: 17515 and with Ethical Code: (IR.IUMS.REC.1399.068). There are no conflicts of interest.

To our knowledge, the present systematic review is a first attempt to comprehensively examines the results of economic evaluation studies on pregnancy termination management interventions. In this review, taking into account all economic evaluation methods, including cost-effectiveness analysis, cost-utility analysis, cost-benefit analysis as well as cost-minimization analysis, as well as we investigated all patient's situations, including induced abortion, managing incomplete evacuation, control postpartum hemorrhage, treatment of spontaneous abortion, treatment of early pregnancy failure, management of miscarriage, nonviable early pregnancy management, and management of early pregnancy loss. According to the results of Nava et al . study, medical treatment had success rates higher than 80%, mild side effects, controllable complications with additional medication, and the high degree of satisfaction. The final cost for medical treatment with misoprostol represents dramatically cost saving per patient in Spain.[ 15 ] Lince et al . provided supporting evidence on scaling up of medical pregnancy termination alongside existing manual vacuum aspiration services in South Africa.[ 21 ] In another randomized-based cost analysis study in low resource settings concluded that medical treatment of incomplete miscarriage is cost effective method with higher client acceptance and satisfaction than surgical management. However, both medical and surgical methods were effective treatment options for first-trimester incomplete miscarriage in this study.[ 24 ] Other studies have demonstrated the economic advantage of medical over the traditional surgical management methods.[ 9 ] However, no cost difference has been found between two methods in a cost minimization analysis by Xia et al .[ 28 ] Niinimaki et al . concluded that neither of medical and surgical method was economically superior or more cost effective in Finland.[ 23 ] Berkley et al . strongly verified that pretreatment with mifepristone followed by misoprostol offered a significant cost advantage over monotherapy and resulted in higher completion rate of pregnancy termination and shorter treatment time for medical management of miscarriage than treatment with misoprostol alone.[ 13 ] This result is consistent with what has been found by Hunter et al . They have demonstrated that statistical models showed a 61.3% chance that mifepristone plus misoprostol was more cost effective than surgical pregnancy termination, as well as a 90.8% chance that it was more cost effective than methotrexate plus misoprostol.[ 19 ] These findings were broadly in line with pattern of results was obtained in Nagendra et al . study. They have shown that mifepristone pretreatment is a cost-effective option for women seeking medical management for early pregnancy loss cares. However, they reported not only cost concerns but also difficulties in accessing this highly effective regimen.[ 7 ] Another trial-based economic evaluation analysis found that based on cost-effectiveness grounds, Mifepristone misoprostol combination intervention dominated the use of misoprostol alone and is more likely to be recommended by decision-makers for the medical management of women presenting with a missed miscarriage.[ 29 ] Overall, these findings are in accordance with a previously published trial-based report on medical methods of abortion by Cochran Collaboration. This report states that available medical abortion methods are safe and effective and combined regimens are more effective than single agents.[ 31 ] World Health Organization estimates that there are 14 million obstetric hemorrhages every year, and postpartum hemorrhage is the most common cause of maternal death worldwide.[ 32 ] Bradley et al . suggested that training traditional birth attendants to administer misoprostol for the treatment of postpartum hemorrhage has the potential to both save millions of dollars in countries with limited health resources, particularly in sub-Saharan Africa, and improve the mother's health across the developing world.[ 14 ] Prenatal distribution of misoprostol has been reported to be potentially cost effective in Uganda, and authors suggested that it should be considered for national level scale up for prevention of postpartum hemorrhage.[ 22 ] Vlassoff et al . demonstrated that despite equally efficacy of misoprostol and oxytocin in reducing postpartum hemorrhage, the misoprostol was more cost effective in rural health settings.[ 27 ] A similar pattern of results was obtained by Sutherland et al . They showed that misoprostol was cost-effective for the prevention of postpartum hemorrhage among women who give cares at home in India.[ 26 ] Upper genital tract infection, including the uterus and fallopian tubes, can cause complications after induced abortion and antibiotics given around the time of the pregnancy termination (prophylaxis) could prevent these related complications.[ 33 ] Routinely using antibiotic prophylaxis before surgical miscarriage management in order to prevent the infection complications was reported more effective and less expensive in less developed setting and would save millions of dollars for health-care systems.[ 4 16 ] Expectant management that defined as accurate diagnosis, counseling, 24/7 telephone advice, follow-ups and waiting for the miscarriage to happen by itself naturally,[ 34 ] has been compared with medical and surgical interventions in order to the treatment of incomplete evacuations in two studies. Finally, discordant results have been reported on the probability of being cost effective by two authors.[ 20 25 ] Thus, more studies are needed for identifying miscarriages suitable for expectant management. In addition, according to the results of Graziosi et al . the misoprostol medical treatment is less costly than curettage for early pregnancy failure after failed expectant management.[ 17 ] The strength of our review is that the included studies performed in developed countries and low- and middle-income countries and almost of studies derived their required data from relatively large trials with a high number of populations. Hence, the results are relatively generalizable and possible to comparison in order to achieve a coherent conclusion. The availability of such detailed evidence certainly will assist informed decision making and facilitated the best possible use and create maximum benefits of available resources. A limitation of this systematic review was the inclusion of only English evidence because of our limited capacity to understand non-English languages. However, avoiding to quantitatively pooling the results of included studies through a meta-analysis study because of diversity of models used and different currencies used is another limitation of this review. The availability of such detailed evidences certainly will assist informed decision making and facilitated the best possible use and create maximum benefits of available resources. Developing a comprehensive guidance handbook for all situations of abortion and pregnancy termination procedures based on economic evaluation evidence, highlighting priority areas where information from economic evaluation studies would be most useful, and training researchers, policymakers, and pregnancy termination care providers in the use of economic data are strongly desired.

PubMed, Web of Science, Scopus, Embase, Cochrane library, ProQuest and ScienceDirect databases were searched through June 2021 to obtain the required data. Key words or medical subject heading terms (MeSH) used in the search strategy were as follows: “Cost and cost analysis” or “Cost-benefit Analysis” and “Induced Abortion” or “Vacuum Curettage” or “Mifepristone” or “Misoprostol” or “Pregnancy Trimesters”. Furthermore, the search strategy developed using Boolean operators [ Appendix 1 ]. The Google scholar search engine, World Health Organization website as well as the Cochrane library protocols were searched manually for probable records that falls outside the mainstream of published journal. Furthermore, in order to maximize the comprehensiveness of the search, a reference list of the identified articles was manually explored to retrieve probably related articles. Sample search strategies developed using Boolean operators In this systematic review study, the research questions were determined based on population, intervention, comparison, and outcomes. The inclusion criteria were as follows: Original studies that performed an economic evaluation (including cost-effectiveness analysis, cost-utility analysis, cost-benefit analysis as well as cost-minimization analysis); Studies performed on medical or surgical methods of pregnancy termination management; studies which measured outcomes such as quality-adjusted life years (QALYs), disability adjusted life years or Incremental cost-effectiveness ratio or clinical outcomes such as pelvic infection, bleeding, infertility, complete or failed evacuation rate, mortality, and anemia rate. Studies with available full texts, and written only in English. There was no restriction on the year of the publication of the studies. The exclusion criteria were as follows: Studies related to neoplasms, abnormal pregnancies, maternal mortality interventions, gestational trophoblastic or contraception interventions; studies with a full-text written in languages other than English; and studies published as a review articles, conference abstracts, editorials, commentaries were excluded from this review. The duplicated articles were removed. Study selection was initially based on study titles and abstracts. Then, the full texts of the selected studies were evaluated for final inclusion. Two independent reviewers performed the entire selection process, and any discrepancy between reviewer was resolved by discussion, and when consensus was not reached, a third reviewer resolved. A data extraction form (including participants, intervention, comparator condition, outcomes, perspective, and time horizon) was designed for this systematic review [ Table 1 ]. First, one reviewer extracted characteristics of the included studies and then, the rest of the reviewers refined it. General characteristics of included studies *The “CCEMG: EPPI-Centre Cost Converter” (v. 1.6 last update: April 29, 2019) is a free web-based tool for adjusting estimates of cost expressed in one currency and price year to a specific target currency and price year. ICER=Incremental cost effectiveness ratio, EPPI=Evidence for policy and practice information, CCEMG=Campbell and Cochrane economics methods group, MVA=Manual vacuum aspiration, D and C=Dilation and curettage, DALY=Disability-adjusted life year, QALY=Quality-adjusted life year, WTP=Willingness to pay, NHS=National health service A critical quality assessment was conducted utilizing the Consolidated Health Economic Evaluation Reporting Standards checklist.[ 30 ] This tool has 24 questions that are used to assess the economic evaluation studies. Two researchers independently conducted the quality assessment. Studies with a score of above 85%, between 85% and 75%, between 75 and 55%, and below 55%, were categorized as “excellent,” “very good,” “good,” and “poor “ quality, respectively Table 1 and Appendix 2 ]. Risk of bias and quality assessment results Endnote 8 software was used to organize studies and remove duplication. Required data were extracted based on key feature using a standard electronic form. The key features included the following: Study population, alternative options for comparison, time horizon, country and year of study, perspective, cost per QALY, cost saving, and incremental cost effectiveness ratio (ICER). Articles that met all of the inclusion criteria were retained for full-text review. The latest web-based tool adjusted the estimates of costs expressed in one specific currency and price year into a specific target currency (the year 2020 US$). In order to make sensible decisions or making particular comparisons, the clinical and methodological variation across studies associated with the participants, interventions, outcomes, and study design were taken into consideration in discussion section. Furthermore, we preferred not to pooling the studies result as a meta-analysis study. To ensure provide a clinically meaningful answer, the similar enough studies subgrouped and qualitatively investigated.