Methotrexate Treatment of Ectopic Pregnancy: Prognosis at Senlis Hospital ()
1. Introduction
An ectopic pregnancy happens when a fertilized egg implants outside of the uterus, most commonly in the fallopian tube. It is a common cause of morbidity and occasionally of mortality in women of reproductive age by rupture and dangerous internal bleeding if not diagnosed and treated early. In developing countries, its incidence ranges from 2.41% to 3.45% [1] [2], and it is most often diagnosed at a late stage and is life-threatening. Thus, the management is most often surgical by laparoscopy which is not available in all hospitals, or especially by laparotomy as reported by Gabkika B. M. in Tchad where the management was mainly radical in 90.4% of cases by laparotomy [1]. Fortunately, diagnosed early, ectopic pregnancy offers the possibility of simple and inexpensive medical treatment, protecting patients from surgery complications. Thus, medical treatment with methotrexate could concern 30% to 40% of ectopic pregnancy and makes it possible to avoid first-line surgery in a large number of cases [3] [4] with a success rate ranging from 68% to 90.7% [5].
We report the experience of medical management of ectopic pregnancy at Senlis Hospital to describe the prognosis. This will allow us to inspire ourselves to better take care of our patients from our disadvantaged neighborhoods where the morbidity and mortality of ectopic pregnancies remain high.
2. Material and Methods
This was a retrospective study of cases of ectopic pregnancy treated with methotrexate at Senlis hospital from June 2020 to May 2021. We included in our study all patients admitted with biological and ultrasound confirmed ectopic pregnancy and treated with methotrexate during the study period. Were included in the study, hemodynamically stable patients with Fernandez score less than 13 (Table 1). The methotrexate was administered by intramuscular injection at a dose of 1 mg/kg, followed by a second injection one week later if the first injection fails. Data studied were Socio-demographic characteristics, diagnosis, and prognosis. Data were collected using gynecological emergency admission registers, telephone interviews, and was analyzed with epi inf 7.2.
3. Resultants
During the study, 35 patients were included.
Socio-demographic characteristics
The mean gestational age was 05 weeks 02 days.
Diagnosis
The diagnosis was made in all our patients by the clinic and vaginal ultrasound couple with level of ß-hcg. Table 2 shows the distribution of patients according to the diagnostic parameters.
The size of adnexal mass was less than 4 cm with an average size of 20 mm. The average value of ß-hcg was 1405 IU/L.
Prognosis
All patients received a single dose of methotrexate 1 mg/kg intramuscularly. For 17.1%, a second dose was administered for stagnation or re-ascension of β-hcg levels. A transient elevation of bhcg was reported in 60% of cases within 4 days following methotrexate administration. The overall success rate was 91.4%. About the other 8.6% patients, treatment was failed and laparoscopy was performed.
In the first year after treatment, 30% of patients were obtained spontaneous intra uterine pregnancy. Any complications were not notified among the patients.
4. Discussion
The incidence of ectopic pregnancy varies widely. The highest rates are observed in developing countries, particularly in Africa, with rates varying from 2.41% to 3.45% [1] [2]. In our study, the incidence of ectopic pregnancy is 2.1% reflecting the overall incidence in France which is approximately 2% [6].
Table 2. Distribution of patients according to diagnostic parameters.
The clinical signs suggestive of ectopic pregnancy are not always typical. It’s the combination of ß-hcg kinetic and vaginal ultrasound that makes it possible the early diagnosis of ectopic pregnancy, offering medical management with methotrexate [7] [8]. In our study, amenorrhea was the most clinical sign (80%), followed by pelvic pain (71.4%) and bleeding (63%). All our patients had had vaginal ultrasound coupled with the kinetics of ß-hcg. The average value of ß-hcg was 1405 IU/L. The medical treatment of ectopic pregnancy has become a therapeutic entity if the diagnosis is made early, without recourse to laparoscopy. It has been shown to be effective, both in terms of resolving ectopic pregnancy itself and subsequent fertility. This technique is reproducible, easy to use by anyone when the criteria for medical treatment, methotrexate dose to be administered and the monitoring procedures are respected [9]. A pre-therapeutic assessment (haematological, hepatic and renal) is always requested before methotrexate administration. An initial single dose of 1 mg/kg was sufficient for 82.8% patients and 17.1% required a second additional dose of 1 mg/kg of methotrexate. The overall success rate was 91.4%, comparable to that of BOTTIN P. et al. [3] who also reported a success rate of 89%.
Three patients with initial ß-hcg rate over than 5000 IU/L had secondary laparoscopy for failure of medical treatment by rupture of the ectopic pregnancy.
The kinetics of ß-hcg before and after methotrexate injection appears to have greater predictive value in the success or failure of methotrexate treatment. Thus, a decrease ß-hcg rate of 15% between 4th and 7th day would be the guarantee of success, with regular weekly monitoring of ß-hcg rate decrease [10] [11]. According to authors, a greater increase of ß-hcg rate before administration of methotrexate, and the presence of an extrauterine gestational sac with yolk sac may be a predictor of treatment failure [12] [13]. The initial ß-hcg rate is therefore a major prognostic factor for the success of treatment with methotrexate. However, the existence of a threshold value beyond which this treatment is ineffective has not been validated, due to the drop and the negativity of ß-hcg rate for 50% of patients with an initial rate more than 5000 IU/L. It is legal to offer methotrexate to patients with pre-therapeutic ß-hcg rate of 5000 IU/L or less, without cardiac activity or visible gestational sac [5] [14]. In addition, the patient should be informed of the risk of significant failure if the rate is greater than 2000 IU/L with the potential need for surgical management. Regarding monitoring, we used the standard protocol of Stovall [10] with monitoring ß-hcg rate at 1st, 4th and 7th, then weekly until negative after injection of a single dose of methotrexate. The decision for a second dose is taken when ß-hcg rate decrease of less than 15% between 4th and 7th day and or, an increase or stagnation of this rate between two weekly dosages. After methotrexate injection, a transient increase between 1st and 4th day or a plateau is reported in 86% of cases [10]. The same observations were reported in our study where a transient increase of ß-hcg rate was observed in 60% of cases.
The prognosis of fertility is more related to the patient herself than the choice of treatment. Regarding the subsequent prognosis, the size of the adnexal mass, the location, the notion of tubal rupture or the initial volume of the hemoperitoneum do not appear to affect the prognosis of fertility. On the other part, the personal history of ectopic pregnancy, salpingitis, single tubes, tubal surgery, or the existence of adhesions or alteration of the contralateral tube would profoundly modify the subsequent prognosis [4]. For patients without history, the rate of intrauterine pregnancies is around 90%, while it is only 30% to 40% in the case of a pathological history [4]. In our study, 30% of patients had obtained spontaneous intra uterine pregnancy.
5. Conclusion
From our study and through publications, it appears that the success rate of methotrexate treatment for ectopic pregnancy is high in meeting the eligibility criteria for treatment. The subsequent fertility prognosis, relative to medical treatment, is generally maintained. Thus, in the light of the results of this work, we wish to encourage the early detection of ectopic pregnancies for medical treatment.