Ectopic pregnancies must be treated well to terminate pregnancy and to prevent future mortality and infertility(19). Currently, common treatments for this disease are medical therapy using methotrexate with different doses and surgery to remove the mass(20). This study was conducted to determine and compare the cost-effectiveness and cost-utility of the three aforementioned methods for the treatment of ectopic pregnancies to propose the best options for the physicians and policymakers to choose the most cost-effective method for terminating pregnancy and reducing damage to the uterine tubes. Based on the findings of the cost components (Table 2), the mean costs of treatment via single-dose methotrexate, double-dose methotrexate, and surgery were $2675, $3362, and $3159 per single round of treatment. Therefore, the mean cost of treatment per patient treated with single-dose methotrexate was lower than the mean cost of treatment per patient treated by the other two therapies. It seems that the main reasons for the differences in the costs are the higher success rate, lack of the need for secondary treatments, fewer side effects, and lower costs. Given that double-dose methotrexate is prone to higher rates of failure, the direct and indirect medical costs are increased and the patient has to spend more time to treat the illness and recover, which in turn increases the indirect costs(21, 22). Therefore, the results of this study are consistent with those of the Creinin et al.’s study that compared the costs of treatment via single-dose methotrexate and surgery(23), and also Sowter et al.’s study that compared direct and indirect costs of single-dose methotrexate and laparoscopic surgery(24). Therefore, as the results showed, direct medical costs, direct non-medical costs, and indirect costs, respectively, accounted for 64%, 16%, and 20% of the total costs spent by the patients receiving single-dose methotrexate, 60%, 20%, and 20% of the total costs spent by the patients receiving double-dose methotrexate, and 74%, 7%, and 19% of the total costs spent by the patients undergoing surgery. Thus, direct medical costs account for the highest cost in all the three treatment methods. In patients receiving single-dose and double-dose methotrexate, the costs of hospital stay accounted for the highest share of direct medical costs, while for the patients who had surgeries the operation costs accounted for the highest share of direct medical costs. These findings are in line with the results of the published study performed by Foulk et al. (25). Furthermore, it seems that the higher costs of surgery is because of the high operation expenses, services, and drugs that the patients take after discharge from the hospital(26). As calculated, the direct medical costs accounted for a higher percentage of the costs(27), and although about 99% of the patients undergoing surgical treatment were covered by insurance companies, they incurred high direct medical costs that may be attributed to the high costs of operation(28). Therefore, the costs associated with ectopic pregnancy are relatively high.
The results showed that the rate of treatment success was 721% for single-dose methotrexate, 71% for double-dose methotrexate, and 87% for surgery; the findings of this study are in line with the results of Hajenius et al.’s study that compared the effectiveness of laparoscopy, as a surgical procedure, with methotrexate therapy(29), Chaychian's study that compared single-dose and multi-dose methotrexate(30), and Mergenthal et al.’s study that compared the effectiveness of single dose and double-dose methotrexate(31). However, our results are not consistent with those of Al Yasin et al.’s study that compared single-dose and double-dose methotrexate; they found that double-dose methotrexate had a higher success rate than single-dose methotrexate(32). These different results may be induced by the different methods of patient selection. In our study if the BhcG titers were higher, or size of the ectopic mass was larger or the first methotrexate dose was not effective a second dose were give. So, it is logical that these patients would have lower chances to be cured by the medical therapy.
Moreover, results of our study showed that the mean cost of surgery and single-dose methotrexate was $2850 and $1984, and their treatment success rates were 87% and 721%, respectively. In other words, surgery was more costly and more cost-effective, but since the ICER was below the threshold, this method was identified as a cost-effective option. This finding is not in line with the results of the studies conducted by Morlock, Alexander, and Yao; they compared methotrexate therapy with laparoscopy and concluded that methotrexate was more-cost effective than surgery (25, 33, 34) However, Mol et al. compared methotrexate and laparoscopic surgery and found that a particular type of surgery was more cost-effective than methotrexate (35, 36).
According to the data obtained from the three groups of patients using the EQ-5D questionnaire, the results showed that the patients who received single-dose methotrexate had higher scores in their utility because they underwent less invasive procedures and needed a shorter period of rest after discharge from the hospital. Results of the present study showed that the highest utility scores were observed in single-dose methotrexate group (0.827), double-dose methotrexate group (0.81), and surgery group (0.81), respectively. Moreover, the results of ICER analysis of utility in all the three groups of patients showed that, among the treatment strategies used in the county, single-dose methotrexate had the higher level of cost and QALYs than the surgery method; but the ICER is greater than the per capita GDP and thus, the surgical treatment method is considered as a more cost-effective option. So far, to our knowledge no study has investigated the utility outcome.
The results of sensitivity analysis showed that ICER is not sensitive to the most of parameters which confirms the robustness of the results of the study. As the results of one-way sensitivity analysis revealed that ICER is more sensitive to single-dose methotrexate but low sensitive to other parameters. Although the single-dose effectiveness parameter had the greatest impact on ICER value by 20% increase on ICER as it increased the baseline ICER from 5812 to approximately $14000 PPP, however, the new ICER value is still below the threshold level and as a result the surgery is the dominant option.
Besides, scatter plots also demonstrated that surgery in 82% and 96% of simulations was at the acceptable region compared with single dose and double-dose methotrexate, respectively and below the threshold. It was identified as the more cost effective strategy. Furthermore, the acceptability curves showed that in 81.4% of simulations, surgery was the most cost effective treatment for thresholds less than 21011 PPP dollars
In the present study, we directly estimated direct medical costs, direct non-medical costs, indirect costs and effectiveness using patient-level data instead of using data from the published literature. This approach is also seen in Bastani and Kiadaliri in the methodology of their study in two groups of breast cancer patients using adjuvant therapy(36).
This study has also some limitations. As presented in the data collected on demographic characteristics of patients and their background diseases, none of the files reported a history of pelvic infection; this indicates that women are not paying enough attention to such issues or deny and feel embarrassed about it. Women with ectopic pregnancy are worried about the complications such as repeated ectopic pregnancy and subsequent infertility(37). In addition, the number of patients treated with double-dose methotrexate was lower than those treated via the other two methods.
Concerning the generalizability of the results, since methotrexate and surgery in Iran are used for the treatment of ectopic pregnancies and their prices are the same throughout the country, the results of this study can be generalized to other provinces and the whole country. However, in order to generalize the results of this study to other countries, it is necessary to address different issues such as epidemiology of the disease, demographic structure, availability of resources, prices, evaluation of outcomes by individuals, thresholds, and the use of various indicators of effectiveness in different studies that may affect the results of the study. Therefore, one must be cautious in generalizing the results to other countries.