Treatment of ectopic pregnancy with a single intramuscular dose of methotrexate

This study evaluates the outcome of unruptured ectopic pregnancies treated with single-dose intramuscular methotrexate injection. There were 77 women with unruptured non-laparoscopically diagnosed ectopic pregnancies who were prospectively followed after receiving a single dose of 50 mg/m2 intramuscular methotrexate. Diagnosis required transvaginal ultrasound and serial quantification of beta subunit of human chorionic gonadotropin (betahCG). A repeat dose was given if the weekly drop of betahCG was less than 30%. Therapy was considered successful if complete resolution of betahCG to a level below 25 IU/L was achieved without surgical intervention. Treatment in 73 (95%) cases was successful. The mean pre-treatment level of betahCG was 2592 +/- 3771 IU/L (177-15000 IU/L), the mean diameter of ectopic mass was 2.4 +/- 1.0 cm (1.7-3.5 cm). The average resolution period was 3.2 +/- 1.0 weeks (1-6 weeks) and this significantly correlated with the pre-treatment betahCG level. With strict criteria of inclusion and follow-up, single-dose intramuscular methotrexate is a successful method for the treatment of selected cases of ectopic pregnancy.     

Risk factors associated with the rupture of tubal ectopic pregnancy

OBJECTIVE: To identify risk factors that may lead to the rupture of ectopic pregnancies. STUDY DESIGN: A retrospective chart review was performed on patients with ectopic pregnancies at the University of Miami/Jackson Memorial Hospital between 1/1/1995 and 3/1/2002. 738 patients were identified with ectopic pregnancies. Women with tubal rupture were compared to those without rupture. Variables analyzed were demographic data, patient-related risk factors (history of pelvic surgery, bilateral tubal ligation, history of pelvic inflammatory disease, previous ectopic pregnancy, intrauterine device use) and beta-human chorionic gonadotropin (betahCG) measurement. RESULTS: There were 439 (59%) cases with a ruptured and 299 (41%) cases with an unruptured ectopic pregnancy. Multivariate logistic regression analysis revealed that previous ectopic pregnancy (OR 2.88; 95% CI 1.92, 4.33) and betahCG level >or=5,000 mIU/ml (OR 1.85; 95% CI 1.12, 3.06) were the only significant risk factors for tubal rupture. CONCLUSION: Patients with betahCG levels >or=5,000 mIU/ml and patients with a history of a previous ectopic pregnancy are significantly more likely to experience a tubal rupture.     

Conservative management of ectopic pregnancy: prospective randomized clinical trial of methotrexate versus prostaglandin sulprostone by combined transvaginal and systemic administration

In a prospective randomized study, 21 patients with an unruptured tubal pregnancy were treated with local and systemic injection. On the day of diagnosis, methotrexate (MTX) (1 mg/kg) or sulprostone (500 micrograms) were injected into the gestational sac under transvaginal sonographic control. The systemic component consisted of an intramuscular injection of MTX (1 mg/kg) 3, 5, and 7 days after local injection or of sulprostone (500 micrograms) on the 1st 2 postlocal injection days. Methotrexate therapy was successful in 8 of 12 patients and sulprostone therapy in 6 of 9. Laparoscopy was then performed on the 7 unsuccessful patients: 3 of them had pain and hemoperitoneum and 4 of them had rising human choriogonadotropin (hCG) levels. One stomatitis after MTX and one cramping abdominal pain were observed. Thirteen of 14 successfully treated patients had initial hCG levels less than 5,000 mIU/mL. At subsequent hysterosalpinography, 13 of 14 patients had normal tubal configuration and patency. Three of 10 patients who desired another pregnancy had already achieved a normal intrauterine pregnancy. These results suggest that MTX and sulprostone were equally effective, and medical approach for the unruptured ectopic pregnancy may be restricted to patients with hCG less than 5,000 mIU/mL.     

Treatment of ectopic pregnancy by transvaginal intratubal methotrexate administration

Twelve women with tubal pregnancies were treated with intratubal transvaginal methotrexate injection (1 mg/kg body weight). Serum beta-hCG levels decreased in all patients, and the resolution time from injection to undetectable beta-hCG levels was 14-120 days. In spite of declining serum beta-hCG and unruptured tubal pregnancy, two patients subsequently requested definitive treatment for their ectopic pregnancies and underwent surgery. Four of six women found to have a living embryo in their gestational sacs required a repeat methotrexate injection; one of these also required a local potassium chloride injection. The tubal pregnancies resolved in nine patients treated with methotrexate alone. During resolution, we noted a gradually increasing resistance index of the blood flow in the region of the gestation, but the tube became distended to 4.4 +/- 0.4 cm before gradually decreasing in size. No complications or side effects were encountered. These findings suggest that intratubal transvaginal methotrexate administration can provide a safe alternative to surgical treatment for patients with early unruptured tubal ectopic pregnancy. However, the presence of a living embryo makes the ectopic pregnancy more resistant to methotrexate treatment.     

Treating cornual pregnancy with a single methotrexate injection: a report of 3 cases

BACKGROUND: Cornual pregnancy is a rare type of ectopic pregnancy. Methotrexate (MTX) has been used successfully for the treatment of tubal pregnancies; however, its use for interstitial pregnancies is less common. CASES: Three cases of cornual pregnancy were successfully treated with a single MTX injection (50 mg/m2), without complications. CONCLUSION: A single MTX injection as medical treatment is an alternative to surgical treatment of cornual pregnancies.     

A new predictive scoring system including shock index for unruptured tubal pregnancy patients

OBJECTIVE: Shock index (SI) and predictive score grading system including it for predicting medical treatment failure of tubal pregnancies have been studied. STUDY DESIGN: Eighty-eight patients were diagnosed as nonruptured tubal pregnancies. Shock index was calculated as the ratio of heart rate to systolic arterial pressure. A predictive score was used based on four parameters including initial level of beta-human chorionic gonadotropin (betahCG), aspect of the image on ultrasound, size of the ectopic mass and shock index value at admission. RESULTS: Forty patients have undergone to surgery because of tubal gestational sac size > or =4 cm and/or presence of fetal heart activity. Nineteen patients were managed expectantly. Twenty-four patients received single dose methotrexate (MTX) and five patients received second dose MTX. Success rate for single dose MTX therapy was 72% (21/29). The cut-off shock index value for tubal rupture was 0.77 with 89% sensitivity and 61% specifity. CONCLUSION: In this study, we demonstrated that tubal pregnancy patients who were managed with nonsurgical measures at admission and who had SI values lower than 0.77 and predictive score grades greater and equal to 6.5 did not experience tubal rupture and did not need surgical intervention during nonsurgical management.     

Unsuccessful methotrexate treatment of a tubal pregnancy with a live embryo.

Two cases with unsuccessful local and systemic methotrexate (MTX) therapy of tubal pregnancy with fetal heart rate activity are reported. The three modes of therapy, the first with local potassium chloride solution injection, the second with local MTX injection, and the third with systemic MTX injection, failed in the resolution of viable ectopic pregnancy. Therapy of MTX in cases of tubal pregnancy with demonstrable fetal heart rate beats, should be reconsidered.     

Treatment of unruptured tubal pregnancy by local injection of methotrexate under transvaginal sonographic control.

Seventeen unruptured tubal gestations were managed on an outpatient basis using local methotrexate (MTX) injection. A single 50-mg dose of MTX was injected into the gestational sac under transvaginal sonographic control. Follow-up included serial assays of the beta-subunit of human chorionic gonadotropin (beta-hCG), clinical and sonographic evaluation. Resolution was obtained in 13 out of 17 patients. The regression curve between days after treatment versus beta-hCG (y = 82.2 - 10.8x + 0.37x2) demonstrated a significant negative correlation (R2 = 0.77; R = 0.88; P less than or equal to 0.02). The mean beta-hCG level on day 15 was 3.2% +/- 3.1% of the initial value. Laparoscopy was performed in 4 patients. Pathological findings suggested that resolution was underway in these four cases despite a slow decline in beta-hCG. No systemic side effects were observed in any of the 17 patients. Long-term follow-up is needed to evaluate tubal patency and reproductive outcome. Our experience suggests that local injection of MTX may be an effective alternative for the treatment of unruptured ectopic pregnancy.     

Alternative to surgery of treatment of unruptured interstitial pregnancy: 15 cases of medical treatment

Objective: To evaluate medical treatment of interstitial pregnancy. Methods: This series was a retrospective study of medical treatment of interstitial pregnancies which was managed in two French Departments of Obstetrics and Gynecology (Bichat public Hospital, Paris and A. Béclère public Hospital, Clamart, France). Fifteen patients with clear evidence of an unruptured interstitial pregnancy were treated by injection of methotrexate (MTX) or potassium chloride (KCL) without surgery since January 1988. The diagnosis was established either by sonography and laparoscopic confirmation in eight cases or by only transvaginal ultrasound in seven cases. Three out of 15 cases in this series, had a heterotopic pregnancy who were treated by transvaginal ultrasound-guided injection of KCL. Others received systemic MTX injection in four cases, and local MTX injection in eight cases under either laparoscopy or transvaginal ultrasound guidance. Four different protocols of MTX (Ledertrexate^R) administration was performed in this series with time: at the beginning of our experience, MTX1 protocol, 15 mg i.m. daily for 5 days was used; and after MTX2 protocol, 1 mg/kg body weight i.m. daily for 4 days; MTX3 protocol, 1 mg/kg body weight intratubal associated with 1 mg/kg body weight i.m. daily for 3 days; and now MTX4 protocol, only intratubal 1 mg/kg body weight is especially used. The success was defined as declining serum human chorionic gonadotropin (hCG) to undetectable levels, and no further surgical management was required. Outcome of subsequent fertility was also evaluated. Results: Complete resolution was obtained in 13 (86.6%) out of 15 interstitial pregnancies. Two out of 15 patients, with medical treatment's failure required secondary surgery. No severe side effects of medical treatment were observed. Follow-up hysterosalpingography was performed in 12 patients showing 91.7% tubal patency on the side of interstitial pregnancy. Outcome of intra-uterine pregnancy of the three patients who had heterotopic gestation, was two miscarriages and one delivery at term. Out of the other 12 patients in this series, nine became pregnant within 1 year: eight pregnancies at term, and one induced abortion. At present, among the last three patients, two have no desire to conceive. Conclusion: Our results suggest that unruptured interstitial pregnancies now can be managed with local MTX administration of 1 mg/kg body weight under transvaginal ultrasound or under laparoscopy procedure. This approach is particularly attractive in these patients, where the only alternative to therapy is laparotomy with cornual resection.     

Transvaginal intratubal methotrexate treatment of ectopic pregnancy.

OBJECTIVE: To evaluate the efficacy of transvaginal intratubal methotrexate (MTX) treatment of tubal ectopic pregnancy (EP). SETTING: Outpatient setting in University Hospital. PATIENTS: Forty women with early EP and rising serum beta-human chorionic gonadotropin (beta-hCG) levels. INTERVENTION: Transvaginal intratubal administration of MTX (1 mg/kg body weight). MAIN OUTCOME MEASURES: Success was defined as declining serum beta-hCG to undetectable levels, no tubal dilatation on ultrasound examination, and no further intervention was required. RESULTS: Treatment was associated with a 70% success rate. No difference was found in the success rate between women with an embryo (76.9%) and those with no embryo in their fallopian tubes (66.7%). The initial serum beta-hCG levels were also not different between patients who were successfully treated and those who failed to respond to the treatment. Despite declining serum beta-hCG levels, tubal rupture occurred in two patients. CONCLUSIONS: Treatment of EP by transvaginal MTX administration is associated with a 70% success rate. This is independent of the presence of an embryo or the initial serum beta-hCG levels. Rupture of EP can still occur despite low and declining serum beta-hCG levels.     

Histopathology of five tubes after treatment with methotrexate for a tubal pregnancy.

OBJECTIVE: To investigate whether treatment with a local high dose of methotrexate (MTX) for a tubal pregnancy hampers tubal repair. DESIGN: From a total of 67 cases treated with MTX for their tubal pregnancy, two tubes ruptured shortly after the MTX injection and were removed. One patient insisted on a removal of the affected tube in spite of the fact that serum human chorionic gonadotropin was negative. Two patients had her tube removed +/- 1 year after the MTX treatment during a salpingo-oophorectomy because of endometriosis and cystic enlarged ovary. RESULTS: In the ruptured tubes there were no findings supporting the idea that tubal rupture occurred because of the injection of MTX into the tube. There were also no signs of a hampered tubal-tissue response to the insult of invading chorionic tissue. Macroscopic and microscopic evaluation of the unruptured tubes showed no residual tubal destruction. In the tubal wall, all layers were normal and continuous, all unruptured tubes were gracile without distention. CONCLUSION: Methotrexate applied in a high local dose does not seem to hamper tubal response against the insult of invading chorionic tissue or to interfere with the ultimate tubal repair.     

Heterotopic pregnancy: successful management with aspiration of cornual/interstitial gestational sac and instillation of small dose of methotrexate

OBJECTIVES: Terminating a corneal pregnancy without jeopardizing a coexistent intrauterine pregnancy. METHODS: A 29-year-old woman with a 4-year history of primary infertility became pregnant after in-vitro fertilization and embryo transfer. A heterotopic pregnancy with a left cornual and intrauterine sacs was confirmed by early transvaginal scan examinations. The ectopic sac was aspirated under ultrasound guidance followed by local injection of 12.5 mg methotrexate. This was followed by serial ultrasound scans and serum betahCG assays. RESULTS: The fetal pole in the ectopic pregnancy disappeared following the procedure. She had no significant vaginal bleeding or any other unusual symptoms. The intrauterine pregnancy progressed satisfactorily until spontaneous onset of labour and vacuum extraction delivery at 39 weeks. The baby weighed 2.9 kg. CONCLUSIONS: Local injection of low-dose methotrexate following aspiration of a cornual pregnancy proved effective in halting the ectopic trophoblasts' growth without adversely affecting a coexistent intrauterine pregnancy. The injected ectopic trophoblasts resolved quickly despite the small dose of methotrexate used. This technique avoided a more costly surgical treatment with its associated risks in subsequent pregnancies.     

甲氨蝶呤治疗输卵管妊娠后的再孕率分析

目的 总结甲氨蝶呤（MTX）治疗输卵管妊娠后的再孕率。方法 收集我院1985年3月至1999年8月确诊为未破裂输卵管妊娠、有生育要求的患者129例,中期60例为MTX全身治疗成功,69例为患侧输卵管切除,按每5年1个时间段回顾分析,随诊1－15年。结果 MTX治疗者,宫内妊娠73％（44例）,异位妊娠8％（5例）;输卵管切除者,宫内妊娠70％（48例）,异位妊娠4％（3例）。两者比较,差异无显著性（P＞0．05）。结论 MTX保守治疗的效果和一侧输卵管切除术相似,没有提高再孕率。     

Use of methotrexate in ectopic pregnancy. Results in 55 patients treated

BACKGROUND: The opportunity of conservative therapeutic approaches for the treatment of ectopic pregnancy diagnosed early with the use of transvaginal ultrasound. A number of papers came out in the last 15 years, showing successful medical therapies for ectopic pregnancies using methotrexate (MTX) in particular, an analog of folic acid with particular tropism for the trophoblast. METHODS: In this retrospective study, the results of 55 consecutive cases of tubaric pregnancy, treated by endovenous administration of 50 mg/m2 MTX, are presented. RESULTS: The percent of global success was 91% (50/55 patients). A single dose of MTX was able to resolve the tubaric pregnancy in 48 women (89%), while a second administration was necessary in the other seven cases. The percent of success was complete (100%) in patients with six weeks of amenorrhea; these values drop to 72% in patients with seven-eight weeks of amenorrhea; in fact in 5 patients there was a tubal damage. CONCLUSIONS: The results obtained show the possibility to treat electively with MTX patients with ectopic pregnancy at six weeks of amenorrhea, and with good possibilities to save the tubaric patency. For patients with a longer amenorrhea the therapy with MTX remains alternative.     

甲氨蝶呤治疗输卵管妊娠后的生殖状态

目的 总结甲氨蝶呤(MTX)治疗输卵管妊娠后的生殖状态。方法 收集我院1997年3月-2002年8月确诊为输卵管妊娠并符合保守条件的患者6l例，应用MTX全身治疗，对其中46例随诊1-7年。结果 MTX治疗后宫内妊娠率71．7％，异位妊娠率8．7％。初孕即为输卵管妊娠者，保守治疗后宫内妊娠率为74．2％，再次异位妊娠率6．5％；第2次为输卵管妊娠者，保守治疗后宫内妊娠率为58．3％，再次异位妊娠率16．7％；第3次为输卵管妊娠者，保守治疗后无妊娠。结论 选择合适的早期患者采用MTX治疗是安全、价廉、可靠的治疗方法，也可获得满意的远期生殖状态。     

近10年输卵管妊娠临床特点、诊断和治疗的变化(附4299例报告)

目的:探讨最近10年输卵管妊娠的临床特点、发生率和诊治方法的变化。方法:回顾性分析我院过去10年输卵管妊娠病例的临床特点,并对不同的治疗方法进行比较,随访并分析影响生育的各种因素。结果:异位妊娠与同期分娩数之比从1995年的1∶7.38升高到2004年的1∶4.12。输卵管妊娠占总数的94.23%。有停经史的占86.4%,阴道流血占87.3%,腹痛占59.1%。腹腔镜治疗从1995年的1.6%上升到2005年的78.7%。较经腹手术组,腹腔镜手术具有手术时间短的优势(P<0.05)。MTX治疗成功率为91.40%,保守手术治疗成功率为96.57%。有异位妊娠史、输卵管或者盆腔手术史是影响治疗后生育的最重要因素。结论:异位妊娠发生率在升高。停经、阴道流血和腹痛是异位妊娠最主要的临床表现。腹腔镜手术、保守性手术是治疗异位妊娠的趋势。对不同患者应采取个性化的治疗方案以提高日后生育几率。     

Studies on non-surgical therapy of tubal pregnancy

8 cases of tubal pregnancy in the pre-abortional stage were detected by B-scope examination. The administration of MTX (total doses: 60-300mg) resulted in complete remission in 7 cases; the other received tubectomy because of the progression of abortion. The dose of MTX used to obtain remission is responsible for the HCG titer of urine before the treatment; 60-150mg of MTX was sufficient in cases which showed a titer below 1,000iu/l, although 75-300mg was necessary in cases over 4,000iu/l. The patency of tubes after the regimen was confirmed in 4 out of 5 cases with hystero-salpingography. Serious side effects were not observed in the present study in spite of the great efficacy; transient suppression of liver has been observed in 2 cases. Two patients had normal intra-uterine pregnancy subsequent to the treatment; one had a matured full-term female neonate and the other received D & C in 9 gestational weeks. These results suggest that the MTX regimen is practical for the treatment of patients with tubal pregnancy. This is characterized by unimpaired fertility following the treatment, although the detection of patients in the pre-abortional stage is absolutely necessary.     

Fertility outcome following combined methotrexate treatment of unruptured extrauterine pregnancy

Objective To assess the effectiveness of systemic treatment with methotrexate in combination with local injection for unruptured tubal pregnancy, and to evaluate reproductive function following treatment.
Design Prospective, open clinical study.
Setting University clinic.
Population Sixty-seven women with unruptured tubal pregnancy.
Methods Systemic methotrexate (intramuscular methotrexate 0.5 mg/kg for up to five days) in combination with local application of 12.5 mg methotrexate via laparoscopy.
Main outcome measures The subsequent surgical intervention required and future fertility.
Results In 89.6% of women no further surgical intervention was required and 47 women (81%) experienced subsequently an intrauterine pregnancy. In 39 of 40 women who underwent hysterosalpingo-graphy following treatment, patency of the affected tube was observed.
Conclusions Combined local and systemic methotrexate treatment for unruptured tubal pregnancy seems to be more effective than each therapeutic modality alone.     

Interstitial pregnancy treated by transcervical aspiration of the gestational sac combined with systemic and local administration of methotrexate

Interstitial pregnancy, which is a rare form of tubal ectopic pregnancy, can grow larger than those within the fallopian tube because the surrounding myometrium is more expandable than the tube; many cases are advanced and treated with surgical resection or a large amount of methotrexate (MTX). This report presents a case of an advanced interstitial pregnancy treated with systemic MTX and laparoscopic local MTX injection combined with transcervical aspiration of the gestational sac. A 27-year-old nulliparous female presented with an interstitial pregnancy. Serum human chorionic gonadotropin (hCG) level was 90000 IU/L. MTX was given systemically (50 mg/m(2) i.m.) and the gestational sac was aspirated transcervically under laparoscopic guidance followed by local injection of 25 mg MTX. The patient received a total of only 95 mg MTX. The gestational sac disappeared and serum hCG became undetectable. The patient became pregnant spontaneously six months later, and delivered a live 2482-g infant in good condition by planned cesarean section at 36 weeks and 3 days of gestation. No defect of the myometrium was seen during the surgery. This therapy may be effective for interstitial pregnancy and can be performed safely with laparoscopy.     

Predictors of treatment failure for ectopic pregnancy treated with single-dose methotrexate

OBJECTIVE: To determine variables that predict treatment failure after methotrexate (MTX) treatment of ectopic pregnancy. DESIGN: Retrospective cohort study. SETTING: Canadian teaching hospital. PATIENT(S): Sixty patients diagnosed with and treated for ectopic pregnancy. INTERVENTION(S): A single dose of methotrexate (50 mg/m(2)) by i.m. injection. MAIN OUTCOME MEASURE(S): Resolution of serum beta-hCG or clinical evidence of treatment failure. RESULT(S): Treatment failure was observed following methotrexate administration in 65% of cases when initial beta-hCG was >4000 IU/L, but in only 7. 5% of patients when serum beta-hCG was <4000 IU/L (OR = 52.06, 95% CI 4.88-555.56). Patients who presented with pelvic pain without tenderness had treatment failure 56% of the time versus only 17% in those without pain (OR = 9.20, 95% CI 1.02-82.60). Treatment failure also occurred in 53% of patients presenting with vaginal bleeding versus 16% without bleeding (OR = 6.18, 95% CI 0.73-51.93). CONCLUSION(S): Methotrexate should not be used to treat ectopic pregnancy when initial beta-hCG is >4000 IU/L. Caution should also be exercised in using methotrexate for ectopic pregnancy when the patient presents with bleeding or pain even without tenderness.