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.     

Laparoscopic methotrexate treatment of ectopic pregnancy: feasibility, efficacy, safety and intrauterine pregnancy rates.

We set out to investigate efficacy, methotrexate (MTX) plasma concentrations, and toxicity following a single injection of MTX into the gestational site in the treatment of ectopic pregnancy. This was a non-randomised, non-blinded prospective clinical trial. Eighteen women with unruptured tubal pregnancies and in stable haemodynamic condition were studied. MTX 1 mg/kg was injected into the ectopic pregnancy guided by laparoscopy. Serum betahCG levels were estimated before MTX treatment and on days 1, 4 and 13. In 14 patients plasma MTX was determined 1 h and 6 h after the injection. We found an adequate decline in betahCG was achieved in 17 (94%) patients, and tubal surgery avoided in 15 (83%). At 6 hours following drug administration, mean plasma MTX concentration (0.36+/-0.21 microM) was only 12% of mean peak level (3.1+/-1.0 microM). Six (39%) demonstrated slightly elevated, but completely reversible liver enzymes. None reported any subjective adverse effects. At the 4-7 year follow-up nine of 12 (75%) women had delivered healthy babies. It is concluded that intratubal injection of 1 mg/kg MTX appears to be an effective and safe treatment of ectopic pregnancy.     

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.     

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.     

Single high dose of local methotrexate for the management of relatively advanced ectopic pregnancies

Objective: To evaluate the limits of the conservative management of relatively advanced ectopic pregnancies (EPs) with local methotrexate given at a higher than standard dose.

Design: Nonrandomized prospective study.

Setting: A tertiary teaching hospital and an affiliated infertility center.

Patient(s): We treated 118 EPs of up to 56 days’ gestation (8 weeks) regardless of the presence of fetal heart activity, the size of the gestational mass, and the initial β-hCG levels.

Intervention(s): Transvaginal intraamniotic or laparoscopic intratubal injection of 100 mg of methotrexate as a single dose.

Main Outcome Measure(s): β-hCG levels, red and white blood cell count, and liver function tests before and after methotrexate injection, followed by repeat transvaginal color Doppler assessments.

Result(s): Treatment was successful in 105 (88.98%) of the 118 patients included in the study. In 7 of them with persistent fetal cardiac activity after the methotrexate injection, treatment was concluded with a complementary intracardiac injection of 10% KCl. No grade 3 or important clinical, hematologic, or biochemical toxicities occurred.

Conclusion(s): Local administration of a single high dose of methotrexate (100 mg) proved safe and effective in the medical management of relatively advanced and unselected EPs, including cases with fetal heart activity, with high initial β-hCG levels, and with a gestational mass beyond the standard maximum of 3.5 cm. Complementary hypertonic KCl proved to be effective in cases with persistent cardiac activity.     

Late complications after systemic methotrexate treatment of unruptured ectopic pregnancies: a report of three cases

Background: The use of methotrexate (MTX) by systemic administration in the treatment of unruptured ectopic pregnancy has been reported as a safe and effective method. Cases: We report three cases (one hematosalpinx and two pelvic hematocoeles) of complications after the use of MTX in the treatment of unruptured ectopic pregnancies. All three cases came to our observation for pelvic pain, abnormal bleeding and a pelvic mass after an interval of 3–5 months, subsequent to the disappearance of symptoms and normalization of serum human chorionic gonadotropin β-subunit (β-hCG) levels. Conclusions: These findings suggest that: (a) such complications should be considered before selecting the mode of treatment for ectopic pregnancy; and (b) that an early ultrasonographic control should be performed after MTX treatment even when the decline in β-hCG levels suggests a successful resolution. This would permit an early diagnosis of these late complications.     

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.     

Transvaginal Methotrexate Injection for the Treatment of Cesarean Scar Pregnancy: Efficacy and Subsequent Fecundity

Study ObjectiveTo investigate the efficacy of local methotrexate (MTX) injections under transvaginal ultrasound guidance for treatment of cesarean scar pregnancy (CSP) and to assess fecundity after treatment.DesignRetrospective review (Canadian Task Force classification II-3).SettingUniversity hospital.PatientsEight women with CSP.InterventionTransvaginal MTX injection.Measurements and Main ResultsWe retrospectively reviewed 8 CSP cases treated with local MTX injection under transvaginal ultrasonographic guidance. In all cases, the serum human chorionic gonadotropin concentration was monitored and the gestational sac was evaluated using ultrasonography after treatment. Magnetic resonance imaging was performed as necessary. Patient clinical characteristics, clinical course after treatment, treatment efficacy, and fecundity after treatment in patients desiring subsequent pregnancies were evaluated. All 8 women were successfully treated without the need for blood transfusions or surgical procedures, although 2 required additional MTX therapy via local injection or systemic administration. The mean (SD) time to human chorionic gonadotropin normalization was 78.5 (37.7) days (range, 42–166 days). Four of 5 patients desiring subsequent pregnancies after the treatment had uneventful parturition, and recurrent CSP was diagnosed in 1 patient.ConclusionsTransvaginal MTX injection was effective and safe as sole treatment of CSP. Although the treatment course tended to be long, this method can be considered the first choice of treatment in patients desiring future pregnancies. However, careful attention should be paid to the possibility of CSP recurrence.     

Current issues in medical management of ectopic pregnancy

This review focuses on current medical therapy for unruptured ectopic pregnancy. Recently emerging issues include early diagnosis, treatment costs, intratubal methotrexate injection, medical treatment of cervical and interstitial ectopic pregnancies, and future fertility potential after methotrexate therapy. In addition, new clinical practice guidelines identify optimal candidates for medical therapy.     

Human chorionic gonadotropin patterns after a single dose of methotrexate for ectopic pregnancy

Objective: The great variability in human chorionic gonadotropin (HCG) levels after a single dose of methotrexate (MTX) for ectopic pregnancy makes it difficult to predict treatment failure. We describe different patterns of HCG levels. Study design: Fifty patients were injected i.m. with 50 mg/m² of MTX for an ectopic pregnancy. Venous blood samples for HCG detection were obtained on the day of treatment (day 0), day 3 and day 7 and weekly until values were undetectable. Patients were classified as: group 1, persistent pathology (n=11); group 2, complete resolution with a decrease of HCG levels at day 3 (n=30); group 3, complete resolution after a rise of HCG values at day 3 (n=9). Statistical analysis was performed using the Mann–Whitney non-parametric test with 95% confidence intervals. Results: Values of day 0 were similar for all the groups. HCG levels of group 3 decreased rapidly after day 3 and at day 7 they were significantly different from levels of group 1. Differences in HCG levels between groups 2 and 3 became indistinguishable from day 21. Conclusion: The observation of patients undergoing resolution after an initial increase of HCG levels justify an expectant management for 1 week in clinically stable patients. The strategy to separate HCG curves in patients undergoing resolution may shed light on the different clinical responses to therapy for ectopic pregnancies. However, the phenomenon of the immediate rise of HCG should be better investigated.     

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.     

Successful rescue of an early interstitial pregnancy after failed systemic methotrexate treatment: a case report

BACKGROUND: Interstitial (cornual) pregnancy is a rare and life-threatening disease. Although systemic treatment with methotrexate (MTX) in an unruptured interstitial pregnancy has been used to preserve the entirety of the uterus, surgery is often used as a rescue method in failed cases. Use of an ultrasound-guided local injection can be a good alternative to surgery. CASE: A 30-year-old woman, gravida 1, para 0, with an interstitial pregnancy at 10 weeks of gestation, was successfully treated with an ultrasound-guided 100-mg MTX injection after a failed response to 3-dose intramuscular 100-mg MTX treatment (300 mg in total). Regular menstruation occurred 1 month after the local MTX injection. The serum beta-human chorionic gonadotropin level was undetectable 49 days later, and the residual mass had disappeared 6 months later, CONCLUSION: Local injection of MTX may be a good means of managing an unruptured interstitial pregnancy to preserve the entirety of the uterus after failed systemic MTX treatment. Use of a local MTX injection may be a better choice than that of systemic MTX treatment.     

Single dose methotrexate therapy: application to interstitial ectopic pregnancy

A woman with a small (6-mm gestational sac) interstitial pregnancy had complete resolution after medical therapy alone. A single cycle of methotrexate 50 mg/m² was used as outpatient treatment without any operative procedure either for diagnosis or intervention. The guidelines that have evolved for selection of women for single dose methotrexate treatment for both intrauterine and tubal ectopic pregnancies may be applicable to interstitial ectopic pregnancy as well. A suggested framework for treatment decisions is presented.     

Transvaginal ultrasound-guided treatment of cervical pregnancy

OBJECTIVE: To describe our experience with sonographically guided injection of methotrexate and potassium chloride (KCl) to treat early cervical pregnancy. METHODS: We prospectively reviewed all cases of cervical pregnancies treated conservatively through transvaginal ultrasound-guided therapy at our institutions. Thirty-eight cases were identified, from 1993 through 2004. All cases were managed with transvaginal intra-amniotic and intrachorionic injection of 50 mg of methotrexate under ultrasound guidance. An additional intracardiac fetal injection of 2 mL KCl was given for those cervical pregnancies with documented cardiac activity. Follow-up sonographic examinations and serum beta-hCG measurements were performed twice weekly for 2 weeks after the procedure, then weekly. RESULTS: The mean initial beta-hCG level was 38,948 milli-International Units/mL and ranged from 5,608 to 103,256 milli-International Units/mL for 22 cases with fetal heart activity and from 2,765 to 18,648 milli-International Units/mL for 16 cases without. Gestational age ranged from 5.4 to 14 weeks (mean 8.8 weeks). All cervical pregnancies were successfully aborted, with an average resolution of the cervical mass in 49 days. Postoperative beta-hCG declined to less than 5 milli-International Units/mL within a mean of 38 days. A mean 4.5-year follow-up showed that, of 21 patients who desired pregnancy, 18 had achieved subsequent successful pregnancies. CONCLUSION: Cervical pregnancies can be successfully managed without surgical intervention through local injection of methotrexate and KCl. This treatment not only ablates the ectopic pregnancy but also preserves the uterus for subsequent pregnancies.     

多胎妊娠早期选择性减胎术的临床研究

目的 研究多胎妊娠早期选择性减胎术的技术可靠性、安全性及其对妊娠结局的影响。方法 以超声引导下穿刺,少量氯化钾胚囊注射方法实施多胎妊娠早期选择性产硬盘减胎术患者２５例,其中１例经腹穿刺术,其中余２４例经阴穿刺术。结果 ２５例患者减胎术后,获得足月分娩者１５例,两个阶段中,初期减胎术１０例,成功率仅为３０．０％;第二阶段为临床应用期,实施１５例,分娩率达８０．０％,流产率降至６．７％。结论技术成熟的     

A Novel Approach to Management of Angular Pregnancies: A Case Series

Cornual, interstitial, and angular pregnancies are terms that are often used interchangeably in both the literature and clinical setting to describe various ectopic pregnancies. The diagnosis of these pregnancies can be difficult, and fear of disrupting an intrauterine pregnancy can cause hesitation during evaluation and management. In our 2 cases, a combination of transvaginal and 3-dimensional ultrasound images provided assistance in the accurate diagnosis of angular ectopic pregnancies. Traditional management of these pregnancies includes a wedge resection for pregnancy resolution. In this set of 2 cases, we describe a unique surgical approach to resolve these pregnancies using operative hysteroscopy.     

Intratubal methotrexate for prevention of persistent ectopic pregnancy after salpingotomy

STUDY OBJECTIVE: To investigate whether frequency of persistent ectopic pregnancy after linear salpingotomy can be reduced by prophylactic administration of a single intraoperative injection of local methotrexate. DESIGN: Prospective, randomized, controlled trial (Canadian Task Force classification I). SETTING: University-affiliated hospital. PATIENTS: Sixty-five women with unruptured ectopic pregnancy. INTERVENTION: Laparoscopic salpingotomy with or without a single intratubal dose of methotrexate 1 mg/kg. MEASUREMENTS AND MAIN RESULTS: In the prophylaxis group, 22 patients received a single dose of intratubal methotrexate 1 mg/kg after linear salpingotomy; 43 controls had only linear salpingotomy. Six women (14%) in the control group developed persistent ectopic pregnancy, compared with none in the prophylaxis group (p <0.05). CONCLUSION: In our opinion, intratubal methotrexate injection during laparoscopic salpingotomy is a practical option for women with unruptured ectopic pregnancy.     

Transverse myelitis following methotrexate treatment of ectopic pregnancy: a case report

Objective: Ectopic pregnancy is a common condition in the field of gynaecology, often treated with methotrexate. Adverse effects are common and usually mild. Severe adverse events are rare amongst patients treated with MTX for this condition.

Case: A 26-year-old healthy woman was admitted and treated medically with MTX for an ectopic pregnancy. The patient was treated in the standard drug labelled protocol with an intramuscular injection of 78?mg of MTX according to body surface area. Soon after, the patient presented to the emergency department with symptoms of bilateral paresthesia of the lower limbs which ascended to the pelvis. After a thorough work up and imaging via MRI a diagnosis of transverse myelitis was made. Treatment was successful with corticosteroids and symptoms subsided.

Conclusions: We propose that MTX should be used with caution and severe toxicity should be kept in mind with high index of awareness for any symptom development following treatment, especially neurological one.     

Laparoscopy with ultrasonographic guidance of intraamniotic methotrexate injection for ectopic pregnancy. A report of two cases

BACKGROUND: The efficacy of laparoscopic intratubal injection of methotrexate is reportedly controversial. CASES: A 29-year-old woman with an interstitial-isthmic pregnancy and a 30-year-old woman with an ampullary pregnancy surrounded by dense adhesions were treated with intraamniotic injection of methotrexate with ultrasonographically guided laparoscopy (LUS). The ectopic pregnancies resolved quickly, without further intervention. The human chorionic gonadotropin concentrations were negligible by 18 and 25 days. CONCLUSION: Intraamniotic methotrexate injection with LUS is an effective treatment for unruptured interstitial and tubal pregnancies in patients with dense adhesions.     

Medical therapy (methotrexate and mifepristone) alone or in combination with another type of therapy for the management of cervical or interstitial ectopic pregnancy

Objective

To describe cases of cervical or interstitial ectopic pregnancy managed conservatively with combined medical treatment (methotrexate and mifepristone) alone or in association with other minimally invasive strategies.

Study design

We describe four cervical and two interstitial ectopic pregnancies at our hospital between 2006 and 2010. All received combined treatment with methotrexate and mifepristone. A search of MEDLINE is also described.

Results

The literature search identified only four previous cases of cervical ectopic pregnancies and no cases of interstitial ectopic pregnancy managed with combined therapy. In our study, all patients were successfully treated and had no adverse reactions with intramuscular methotrexate 50 mg/m² and oral mifepristone 600 mg, either alone or in association with minimally invasive treatment (uterine artery embolization and evacuation dilation and curettage). All patients remained asymptomatic with β-HCG levels that decreased and became negative within 14–49 days: the median hospital stay was 5.5 days. We also describe the first patient with a cervical ectopic pregnancy treated with methotrexate and mifepristone, followed by vaginal misoprostol 800 mcg for cervical evacuation.

Conclusion

Methotrexate–mifepristone, either alone or in combination with other minimally invasive strategies, could be considered an option for the treatment of both cervical and interstitial ectopic pregnancy. An individualized approach should be used in each patient, however, given the wide variety of possible clinical situations and the potential seriousness of ectopic pregnancy.