Ectopic pregnancy has significant repercussions on women’s health, in terms of morbidity and mortality, and there have been few studies evaluating the treatments and factors associated with a worse prognosis among them in Brazil. The main objective of this study was to compare the rates of clinical, surgical, and expectant management and to evaluate severe complications of ectopic pregnancy in a university hospital in the south eastern region of Brazil over a period of 17 years.
Some studies have suggested that the use of methotrexate in the clinical treatment of ectopic pregnancy, in cases that meet the eligibility criteria (gestational sac diameter < 4 cm, serum β-hCG ≤ 5,000 IU, absence of a fetal heartbeat, hemodynamic stability, and no contraindications), has the same success rate as surgical treatment . In addition, in well-selected patients, treatment with methotrexate had a better cost-benefit ratio than surgery [3, 10, 12, 14]. Because ectopic pregnancy is being diagnosed earlier and treatment protocols based on methotrexate have been developed, there is a trend toward an increase in the number of clinical treatments, in comparison with that of surgical treatments, in several countries [3, 9, 12, 15, 16, 17]. In line with worldwide standards, the trends over the years at the university hospital studied were toward an increase in the rates of clinical treatment, possibly due to earlier diagnosis. Some studies point to an increase in expectant management rates in recent years , which was not observed in our study. The inevitable question, however, is whether all health care facilities in Brazil show similar trends or whether it is a peculiarity of university, tertiary and private care centers.
In the present study, 40.3% of the patients were diagnosed with a ruptured ectopic pregnancy at admission. Among the surgical access routes available for the surgical treatment of ectopic pregnancy, laparoscopy has less morbidity than laparotomy, provided that a trained team is available . Some studies have also suggested that patients undergoing laparoscopy require less blood transfusion and will have fewer pelvic adhesions than those who undergo laparotomy, which minimizes the impact on the reproductive future [19–22]. During the period of analysis, we observed a significant increase in the use of laparoscopy, which may be related to a greater availability of surgical instruments and a better adaptation of the team to the surgical technique. However, it is possible that the same does not happen in other health services in the country.
We found that 10.55% of the sample developed some type of serious complication associated with ectopic pregnancy. The most common complication was the need for blood transfusion, followed by admission to the intensive care unit. This frequency remained stable throughout the period of analysis, despite the increased use of clinical treatment and laparoscopy. The non-fatal complications of ectopic pregnancy are poorly studied . Some observational studies have reported surgical complications in 23.4% of cases  and blood transfusion rates of 4.8% regardless of the type of treatment .
As for the factors that were most associated with the severity of the cases, we noticed that women who had a ruptured EP at admission, who did not have vaginal bleeding, had non-tubal EP, had never undergone laparotomy or laparoscopy, and who did not smoke had a higher prevalence of complications. Clearly, delayed diagnosis tends to have an impact on the evolution of the disease, increasing the risk of rupture prior to admission and of an unfavorable evolution. During the study period, there were 270 cases in which the ectopic pregnancy had already ruptured prior to diagnosis, accounting for 40.3% of all cases. Although we have the means of early diagnosis and clinical treatment in the hospital, we are also a reference for other cities in the region, from where we usually receive many cases at advanced evolution that do not warrant other ways of management than surgery.
It is possible that the absence of vaginal bleeding can decrease the chance of early diagnosis because health professionals are looking for the classic triad of positive B-HCG, abdominal pain, and vaginal bleeding. It is possible that women, who seek emergency care for abdominal pain, without vaginal bleeding, are misdiagnosed, and the diagnosis is only made during the second consultation. In addition, irregular or unexpected vaginal bleeding tends to be an early warning sign that prompts patients to seek immediate emergency care. Another hypothesis to explain this association is related to the notion of the evolutionary nature of pregnancy; that is, pregnancies in which there is a greater amount of trophoblastic tissue (i.e., those with longer evolution) will have an ascending curve and higher levels of β-hCG. Consequently, they will have higher levels of progesterone and less vaginal bleeding due to endometrial desquamation . Ectopic pregnancy that does not present with vaginal bleeding tends to be characterized by delayed diagnosis with a potential for greater severity.
Non-tubal ectopic pregnancies also tend to be diagnosed later and present a greater degree of difficulty in the surgical approach. Unusual sites for trophoblast implantation include the cervix, cornual, and ovaries as well as abdominal scars from previous cesarean sections, the frequency of the latter being on the rise due to an increase in cesarean delivery [25, 26]. When trophoblast implantation occurs in the uterine cornus and surgery is required, the rates of associated bleeding are often higher, due to the thickness of the myometrium in this region, together with the abundant vascularization resulting from trophoblastic implantation . The difficulty in repairing it, associated with bleeding, can lead to an emergency hysterectomy [28, 29]. The ovaries are irrigated by the ovarian artery, an arterial branch of the aorta. Therefore, in addition to the risk of oophorectomy and impaired reproductive future , ovarian ectopic pregnancy carries a great risk of hemorrhage. When trophoblast implants in a cesarean scar, the risk of uterine rupture and shock is a considerable possibility, and this type of ectopic pregnancy is associated with placenta percreta in more advanced pregnancies . Cervical ectopic pregnancy presents difficulties in surgical access due to the proximity of the uterine arteries and ureters, and can present with postoperative complications such as: hemorrhage, the need for hysterectomy, and urinary tract injury . Abdominal pregnancy also presents serious risks as it can occur close to the liver, spleen, and intestinal loops, which evolve with difficulty in controlling hemorrhage and fecal peritonitis . In our study, we observed an association between the absence of abdominal surgery, no smoking and a higher occurrence of serious complications. We are not aware of any study that has previously found similar associations, and we have no hypothesis that can explain these findings. Possibly, as several associations were made between variables, there may have been multiple comparison bias. Therefore, further studies are needed to assess these possible associations.
This study illustrates 17 years of monitoring cases of ectopic pregnancy in a university hospital, permitting not only the description of the variables related to the diagnosis and management of cases, but also the observation of trends. However, it has some limitations. Due to the retrospective characteristics and the cross-sectional analysis of the data, it was not possible to establish cause-and-effect relationships. Additionally, due to the large number of variables analyzed, there may have been multiple association biases. We believe, however, that the results are valid, since we analyzed a considerable number of cases over a long period of time, thereby contributing to the discussion and analysis of the management of ectopic pregnancy cases in Brazil.
In conclusion, we observed that there was a change in the first treatment option for cases of ectopic pregnancy in the hospital during the period of analysis. This is possibly related to the development of treatment protocols based on methotrexate, in addition to the earlier diagnosis of the disease. We also observed an increase in the use of laparoscopy, which represents an improvement in the quality of care for women. Factors inherent to a disease that is more difficult to treat, such as non-tubal ectopic location together with conditions related to late diagnosis, are related to a higher frequency of serious complications. The results obtained may contribute to the reduction of maternal morbidity and mortality in our country and improve the quality of care for women.