Treating Ectopics with Methotrexate =================================== - Magee-Women's Hospital Protocol (given by OB-GYN, not EM) <6500 quant <3.5 cm mass no cardiac activity hemodynamically stable patient - [Slaughter JL, Grimes DA. Methotrexate therapy: Nonsurgical management of ectopic pregnancy. West J Med 1995;162:225-228.] - Medical College of PA protocol: "I'll do my best to describe the MCP protocol for methotrexate therapy in ectopic pregnancy. The patient must have a beta HCG over 1200, with no intrauterine pregnancy demonstrated by trans-vaginal U/S. This is the only way they are comfortable ensuring they aren't aborting a viable pregnancy." "There should be no co-morbid disease." "There is a maximum size requirement, I think its 3 cm in largest dimension. Anything larger is disqualified." "The patient returns in a set period of time (1 week I think, but it might be sooner) and a repeat beta HCG is drawn. If it isn't dropping, the patient gets a second shot of methotrexate. If it still fails to drop, they go to surgery." "The protocol doesn't address ruptured or leaking ectopics, I would object strenuously to non-surgical treatment of such a condition. To the best of my knowledge, it has never been suggested. "The treatment is never given by the EM staff without OB-Gyn involvement, after all, they gotta follow the patient. "The drug is given IM. Side effects (they tell me) are rare; most commonly oral ulcers. I don't know the dose. "Aboout 14 months ago, an attending physician from the Gyn department came to discuss the protocol, this after a renegade Gyn resident gave methotrexate to a woman who had several of the exclusion criteria. He said they had treated over 100 patients with this protocol, there were no ruptures and only 2 subsequently went to surgery." --Howard Blumstein, MCP ED - Comment: "Methotrexate has its limitations. Frequently the patients continue with vaginal bleeding, lower abdominal cramping, and has elevated B-HCG's often in the 20-100 range, sometimes for several months. The condition is termed chronic ectopic, and one could expect to see it after methotrexate administration for ectopic pregnancy." --Barry Brenner, MD PHD FACEP Vice-Chairman Department of Emergency Medicine The Brooklyn Hospital Center ----------- I think that this is well established therapy. Studies have shown that the higher the level of HCG the more likely it is that 2 or even 3 injections of MTX will have to be given or that medical therapy will fail altogether. Some have used 5000 (1) and others 1500 (2) as the cutoff. Obviously someone with a level of 11000 is much less likely to respond to this treatment. Some have proposed a multivariate score for predicting success based upon several parameters including HCG, extent of hemoperitoneum, size of hematosalpinx etc (3). The presence of a mass on US does not exclude sucessful treatment. About a year ago someone posed a similar question and H. Blumstein suggested that at his institution only ectopics less than 3 cm in size were judged to be appropriate candidates. Patients are followed weekly to confirm falling HCG levels. If they remain stable or rise then a second or third injection is given or they go to laparotomy or laparoscopy. H. Louzon MD (1) Stika CS, Anderson L, Frederiksen MC Single-dose methotrexate for the treatment of ectopic pregnancy: Northwestern Memorial Hospital three-year experience. Am J Obstet Gynecol 1996 Jun;174(6):1840-6; discussion 1846-8 OBJECTIVE: Our purpose was to evaluate the effectiveness of single-dose intramuscular methotrexate in the treatment of ectopic pregnancies by physicians in the Department of Obstetrics and Gynecology of Northwestern Memorial Hospital and to compare the results with those of previously published studies. STUDY DESIGN: A retrospective chart review was performed of 50 patients with ectopic pregnancies treated with single-dose methotrexate according to the protocol of Stovall et al. from January 1992 to February 1995. RESULTS: The mean pretreatment level of beta-human chorionic gonadotropin was 1896.4 +/- 2399 mlU/ml. Only 32 women (64%) were successfully treated with a single dose of methotrexate. An additional 7 women required a second or third injection. The combined success rate for medical management of ectopic pregnancy with one to three doses of methotrexate was 78% (39 women). Pretreatment beta-human chorionic gonadotropin levels were significantly lower in women who responded to single-dose therapy than in those who required either two or three doses or who had failure of medical management (p = 0.0011). The mean time to resolution of beta-human chorionic gonadotropin was 26.5 +/- 17 days. Higher pretreatment levels correlated with longer resolution time (r = 0.83, p < 0.001). Eleven women (22%) with failure of medical management required surgery. CONCLUSIONS: In our series single-dose methotrexate was only 64% successful. Women with a pretreatment beta-human chorionic gonadotropin level >5000 mlU/ml had a greater probability of requiring either surgical intervention or multiple doses of methotrexate. The potential for emergency surgery remains an important risk. (2) Corsan GH, Karacan M, Qasim S, Bohrer MK, Ransom MX, Kemmann E Identification of hormonal parameters for successful systemic single-dose methotrexate therapy in ectopic pregnancy. Hum Reprod 1995 Oct;10(10):2719-22 Single-dose methotrexate is an alternative to surgery in treating ectopic pregnancy. Because success rates vary, we sought to identify factors which predict treatment outcome. A total of 44 women with ectopic gestation were treated. The non-laparoscopic diagnosis of ectopic pregnancy was made following history, physical examination, ultrasound, endometrial biopsy and the measurement of serial beta-human chorionic gonadotrophin (HCG) and progesterone concentrations. Methotrexate (50 mg/m2 i.m.) was administered, with a second dose given 1 week later in patients with plateauing or rising beta-HCG concentrations. Of 44 patients, 23 (52.3%) were successfully treated with one dose. An additional 10 women (22.7%) were also successfully managed but required a second dose, giving an overall success rate of 75.0%. In all, 11 women (25.0%) required surgery, four of whom experienced tubal rupture. Receiver operator curves were constructed to optimally select pretreatment beta-HCG and progesterone cut-off concentrations for successful treatment. Using beta-HCG < 1500 IU/l or progesterone < 7.0 ng/ml (22.3 nmol/l) as a cut-off concentration produced a diagnostic test with a sensitivity of 87.5%, a specificity of 90.0%, a positive predictive value of 96.6% and a negative predictive value of 69.2%. Conversely, this model predicts that patients with serum beta-HCG concentrations > or = 1500 IU/l and progesterone concentrations > or = 7.0 ng/ml are at far greater risk of failing single-dose methotrexate therapy. (3) Fernandez H, Lelaidier C, Fournet P, Frydman R [Must we still operate on ectopic pregnancies?] Contracept Fertil Sex 1993 Jan;21(1):53-7 Non surgical management of ectopic pregnancy has recently become an alternative to surgery. We have investigated a pretherapeutic score to define the indication for non-surgical and surgical treatment in 123 patients with ectopic pregnancy. The score was performed before the patients' inclusion in a non-surgical management scheme. The score used six criteria which were evaluated on a scale from 1 to 3: gestational age, human chorionic gonadotrophin (hCG) level, progesterone level, abdominal pain, haemoperitoneum volume and haematosalpinx diameter (estimated by laparoscopy or transvaginal ultrasound). Three scores, 10, 11 and 12 were studied in order to define a threshold beyond which surgical treatment should be performed. For each one, sensitivity, specificity and positive and negative predictive values were analysed. The success rate of non-surgical treatment was 82.1% (101/123). For patients undergoing medical treatment with a score < or = 12, the success rate was significantly higher compared with a success rate of 56% when the score was > 12. We conclude that a score < or = 12 permits non-surgical management with a success rate of 87%. A score > 12 indicates that laparoscopic surgery may be more suitable. The choice between different non-surgical approaches, did not influence the success rate. When ultrasound reveals embryo heart activity, medical treatment is always possible if the score is < or = 12.