Local Methotrexate Administration Research Articles

Cesarean Scar Pregnancy Treated by Systemic or Local Methotrexate Administration Followed by Hysteroscopic Removal: A Comparative Pilot Study

Background: Cesarean Scar Pregnancy (CSP) is a life-threatening condition following an ectopic implantation within the scar of a previous cesarean delivery and no guideline is shared about optimal treatment options. Methods: We present a retrospective study comparing the outcomes of patients with CSP diagnosed before the 10th week of gestation treated by systemic or local Methotrexate (MTX) for pregnancy termination, followed by hysteroscopic placental removal. After MTX administration, the weekly decrease-rate of beta Human Chorionic Gonadotropin subunit (β-HCG) was adopted as criterion to indicate a repeated MTX dose (less than 25% decline after 2 weeks) and to surgery timing (50% decline in two consecutive assessments). Results: Fourteen patients satisfied the inclusion criteria. Eight and six of them underwent systemic (group A) and local (group B) MTX administration, respectively. No significant difference was found in pre-treatment and intra-operative variables. Group B showed significantly accelerated times in weekly halving of β-HCG with respect to group A (p-value = 0.005). Accordingly, the elapsing time between MTX and surgery was found to be significantly longer in the group A than in the group B (p-value = 0.016). In group B no patient required further MTX administration whereas 3 out of 8 patients from group A required an additional MTX dose. In all patients hysteroscopic surgery resulted uneventful and no further treatment was required. Conclusions: When followed by hysteroscopic placental removal, systemic or local MTX administration resulted effective to treat CSP. Local MTX allows quicker trophoblastic demise, leading to significant anticipation of surgery with respect to systemic administration.

Transvaginal Ultrasound-Guided Methotrexate Instillation for Failed Medical Management of Ectopic Pregnancies in Subfertile Women.

ABSTRACTBackground:Ectopic pregnancy (EP) defined as extrauterine implantation of the embryo can be managed medically or surgically. Medical management entails systemic administration of the antineoplastic drug methotrexate (MTX) which, if not successful, surgical management is resorted to. However, we carried out this study wherein the failed medical management cases were given intra-gestational sac MTX instead of surgery.Aim:The aim of this study was to assess the efficacy of intra-gestational MTX administration as a treatment modality for failed medical management of ectopic pregnancies.Study Setting and Design:It was a prospective interventional study carried out at the Reproductive Medicine Centre of a tertiary care hospital.Materials and Methods:It was a prospective interventional study wherein 12 patients of EP with failed medical management (as per established criteria) were administered intra-gestational MTX with follicle aspiration needle under transvaginal sonography guidance.Statistical Analysis Used:Data were collected in Microsoft Excel. Numerical continuous variables were expressed as mean ± standard deviation. Categorical variables were expressed as count/percentage.Results:All the patients responded to the local administration of MTX, with none requiring rescue surgery. In addition, no one had any complication of the local instillation. However, one patient required an additional dose of MTX.Conclusion:Intra-gestational MTX administration is a viable non-surgical modality for treatment of ectopic pregnancies even in cases of failed medical management with an added benefit of tubal preservation.

Conservative treatment of abnormally located intrauterine pregnancies (cervical and cesarean scar pregnancies): a multicenter analysis (Polish series)

Objectives: To analyze the effectiveness and outcome of conservative treatment in cases of abnormally located intrauterine pregnancies (cervical and cesarean scar).Study design: A retrospective analysis was performed of 30 pregnant women hospitalized due to abnormally located intrauterine pregnancies. The analyzed group comprised 24 pregnant women with abnormally located pregnancies. The patients were divided into two groups: the first group consisted of patients treated systemically with methotrexate, while the second of those treated locally by administration of methotrexate (MTX) and/or potassium chloride (KCl) by gestational sac puncture.Results: The analyzed group comprised 24 pregnant women with abnormally located pregnancies. Eight patients were diagnosed with cervical pregnancy (CP) and 16 patients were diagnosed with cesarean scar pregnancy (CSP). Six patients were excluded from the study: two with spontaneous abortions, two heterotopic pregnancies, and two cornual pregnancies. Twelve analyzed patients underwent MTX systemic administration (five patients with CP, seven with CSP). In five patients, systemic treatment was ineffective; they were qualified for additional local therapy with gestational sac (GS) puncture and MTX or KCl administration to the sac and additional administration of MTX to the trophoblast area. In second group of 12 patients (three CP, nine CSP), local treatment (GS puncture with MTX or MTX + KCl) was used as the first line treatment. One patient underwent combined treatment (local + systemic).Conclusions: Conservative treatment should be the gold standard procedure in abnormally located intrauterine pregnancies. It is noticeable that MTX / KCl is more effective in a direct administration to the GS. In four cases, systemic MTX did not produce the desired effects. In these cases, the treatment was assisted by local administration of MTX or KCl, resulting in the termination of an abnormally located pregnancy.

Methotrexate mitgates UHMWPE-induced inflammatory osteolysis in murine calvaria model, more than anti-TNF or anti-IL-1R treatments: Implications for extending implant lifetimes

Event Abstract Back to Event Methotrexate mitgates UHMWPE-induced inflammatory osteolysis in murine calvaria model, more than anti-TNF or anti-IL-1R treatments: Implications for extending implant lifetimes Lauryn A. Samelko1, 2, Kyron Mcallister1, Joshua J. Jacobs1 and Nadim Hallab1, 2 1 Rush University, Dept of Orthopedic Surgery, United States 2 Rush University, Dept of Immunology, United States Wear-debris induced osteolysis has been recognized as the primary cause of long term total joint replacement (TJR) failure[1]-[3]. To date, it remains unclear what the most effective strategy for treatment of debris induced periprosthetic osteolysis, with no drugs currently approved for use. Potent anti-inflammatory drugs such as anti-TNF-α, IL-1Ra (Anakinra), and methotrexate (MTX) are used to treat rheumatoid arthritis (RA) and show promise for use in treatment of periprothestic osteolysis, but have yet to be comparatively analyzed and thoroughly investigated. Basic questions remain, such as which drug is more effective and what is the most effective delivery method (local or systemic)? We hypothesize that local administration of MTX will reduce UHMWPE induced-inflammatory osteolysis more than systemic MTX, local anti-TNFa or anti-IL1R, due the pleiotropic anti-inflammatory effects of MTX. To test this, we used an established in vivo murine model of particle-induced osteolysis using UHMWPE particles and subsequently evaluated the degree of particle-induced osteolysis between the different regimens that either received local administration of: (1) sham surgery (did not receive UHMWPE nor biologic treatment; negative control), (2) PBS (positive control), (3) anti-mTNF-α, (4) anti-mIL-1R and (5) MTX (local) and compared that to weekly systemic administration of (6) MTX (systemic), where this latter method has been previously demonstrated to reduce particle induced osteolysis[4]. The greatest and most significant (p<0.02) amount of quantifiable osteolysis in the murine model was observed in the positive control group that received UHMWPE particles +PBS, with 32.5% of bone resorption (Fig. 1b). In contrast, local daily administration of either MTX (10.12% Osteolysis) or anti-mIL-1R (11.59% Osteolysis) to murine calvaria that also received UHMWPE particles, did not significantly increase osteolysis compared to the sham-negative control group (6.23% Osteolysis) (Fig. 1c,e,g). While local anti-mTNF-α (18.54%) administration did not significantly decrease the percentage of osteolysis to sham group but was significantly less compared to the UHMWPE particle +PBS treatment, as well as MTX and anti-mIL-1R treatment group at p<0.02 (Fig. 1d,g). However, there was no statistical significance between osteolysis of anti-mTNF-α and anti-mIL-1R group. The local MTX treatment group had significantly less bone resorption though in comparison to anti-mTNF-α (p=0.05) but not to anti-mIL-1R group. Moreover, systemic administration of MTX was not effective, for the amount of osteolysis is similar to UHMWPE group that did not receive any drug agent, and had significantly more bone resorption compared to local MTX treatment (p=0.008; Fig. 1c,f,h). Our results support our hypothesis that daily local administration of MTX will mitigate UHMWPE-induced inflammatory osteolysis the greatest compared to both local treatment of anti-mTNF-α and anti-mIL-1R or systemic MTX. Local MTX demonstrated to be the most preventive treatment of osteolysis, with bone resorption at only 10.12% and therefore most comparable to that of sham group at 6.23%. More importantly, MTX was more protective given locally as opposed to systemically (p=0.008). Therefore, based on these results, local MTX demonstrates superior promise for use in countering wear-debris induced osteolysis and aseptic loosening. NIH/NIAMS: AR060782.

Transvaginal ultrasound-guided local methotrexate administration as the first-line treatment for cesarean scar pregnancy: Follow-up of 18 cases.

Cesarean scar pregnancy (CSP) is a rare type of ectopic pregnancy, which occurs in previous cesarean section scar tissue, with an incidence of 1 in 1800-3000 pregnancies. Transvaginal ultrasound-guided local methotrexate (MTX) administration presents as a non-systemic option with possible better penetration to the pregnancy site. We present the management of 18 patients with CSP solely by transvaginal ultrasound-guided local MTX administration. All patients were treated with local MTX with a dose of 50 mg/m(2) . Eleven (61.1%) of the patients did not need any further intervention. Four patients (22.2%) were treated with additional single-dose systemic MTX due to inadequate alteration in blood β-human chorionic gonadotrophin levels. Three patients (16.7%) required hysteroscopy and/or laparotomy. We suggest that transvaginal ultrasound-guided local MTX treatment may be considered as a first-line treatment for CSP.

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.

Diagnosis and Treatment of Cesarean Scar Pregnancy

To investigate the early diagnosis and treatment of cesarean scar pregnancy (CSP). Clinical data of 28 patients with CSP in Peking Union Medical College Hospital from January 1994 to April 2007, including age, interval from the last cesarean delivery to diagnosis, clinical presentation, location of the lesion, process of diagnosis and treatment, outcome, and follow-up, were retrospectively analyzed. CSP constituted 1.05% of all ectopic pregnancies, and the ratio of CSP to pregnancy was 1:1221. The mean age of the group was 31.4 years. Twenty-six women had only one prior cesarean delivery. The interval from the last cesarean delivery to diagnosis ranged from 4 months to 15 years. The most common presenting symptoms of CSP were amenorrhoea and vaginal bleeding. Seventeen cases were misdiagnosed as early intrauterine pregnancies and 2 were misdiagnosed as gestational trophoblastic tumor. The other 9 were diagnosed definitely before treatment The diagnosis was made based on cesarean delivery history, gynecologic examination, ultrasound, and magnetic resonance imaging (MRI). The treatment of CSP included systemic or local methotrexate administration, conservative surgery, and hysterectomy. The conservative treatment was successful in 24 cases. All of the 28 women were cured through individual therapies. CSP is rare and usually misdiagnosed as other diseases. Ultrasound is valuable for diagnosing CSP, and MRI can be used as an adjunct to ultrasound scan. Early diagnosis offers the options of conservative treatment and greatly improves the outcome of patients. Individual therapy is strongly recommended.

Three-dimensional power Doppler ultrasound diagnosis and conservative treatment of ectopic pregnancy in a cesarean section scar

To describe three-dimensional ultrasonographic features of an ectopic pregnancy in a cesarean scar. Description of a case. Case report of one patient. A 38-year-old women with three previous cesarean deliveries. Three-dimensional ultrasonography was performed for diagnosis and treatment. Local administration of methotrexate under ultrasonographic guidance. Ultrasonographic study revealed a gestational sac in the anterior wall of the uterine isthmus with peritrophoblastic flow. It was treated conservatively and successfully with local methotrexate administration under ultrasonographic guidance. The early diagnosis of ectopic cesarean scar pregnancy allows the conservative treatment with local administration of methotrexate under ultrasonographic guidance.

An early diagnosis and successful local medical treatment of a rudimentary uterine horn pregnancy: a case report

A unicornuate uterus with a rudimentary horn is a rare Mullerian anomaly. The great majority of the rudimentary horns are of non-communicating type (72-85%). The incidence is estimated at 1 per 100000 to 140000 pregnancies. It has poor outcome and rupture usually occurs in the second trimester leading to maternal morbidity and/or fetal mortality. This is the first case of rudimentary horn pregnancy treated with local methotrexate administration. (excerpt)

Methotrexate and fallopian tubes in ectopic pregnancy

The condition of ectopic pregnancy is presented from different points of view, bringing out physiological explanations for its occurrence in primates and the striking absence in other mammals. Ectopic pregnancies have been described in several animal species such as cats, sheep, cows, horses gerenuks, pigs, hamsters, rats, rabbits, marmosets, baboons, squirrel monkeys, owl monkeys and rhesus macaque. Methotrexate (MTX) has anticancer antibacterial, antifungal, antiparasitic, immunosuppressive, antimitotic embryotoxic and teratogenic effects. Methotrexate has species-specific effects. The purpose of this study was to investigate the medical treatment outcome of ectopic pregnancy by local administration of methotrexate and the adverse effects of increasing levels of MTX on the epithelium of the Fallopian tube as viewed by light microscopy. We treated patients with local and systemic regimen of methotrexate. Local applications were performed by direct injection of 0,5 mg/kg or 1 mg/kg methotrexate into the amniotic sac under sonographic control. Fallopian tubes were removed in patients with methotrexate treatment failure. The histological features we observed in the Fallopian tube were similar in all groups. In particular, histological findings showed necrosis and inflammatory infiltrate that was not quantitatively parallel to the increase in MTX dose. Fallopian tubes in human pregnancy could be resistant to the influence of MTX.

Extra-uterine pregnancy following assisted conception treatment.

Ectopic pregnancy may be the only life-threatening disease in which prevalence has increased as mortality has declined. The most prominent theory to explain this phenomenon involves increased sensitivity of serum beta-human chorionic gonadotrophin (HCG) immunoassay and improved quality of transvaginal ultrasound, combined with a heightened awareness and increased suspicion of the condition among clinicians which has allowed early detection of ectopic pregnancy. Laparotomy, once the standard treatment of ectopic pregnancy, has been replaced almost entirely by operative laparoscopy. This is associated with a shorter hospital stay, fewer post-operative analgesic requirements, reduced costs and lower risk of adhesion formation. Laparotomy, however, remains necessary in cases with haemodynamic instability and with exceptional locations, e.g. cervical, abdominal and interstitial implantation. In selected cases, non-surgical management has also obtained high success rates. Among medical therapies, the most common is systemic or local administration of methotrexate. The other option is expectant management involving follow-up using serial serum HCG measurements and ultrasound scans. Thus, life-threatening ectopic pregnancy is now evolving into a medical disease, with the possibility of lower-cost treatment, faster recovery and higher subsequent fertility. In this review we assess the risk of extra-uterine implantation after assisted conception treatment, the accuracy of various diagnostic tools and focus on the efficacy, safety and the fertility outcomes of surgical and nonsurgical management of ectopic pregnancy.

Local Application of Methotrexate for Ectopic Pregnancy with a Percutaneous Puncturing Technique

Management of ectopic pregnancy remains traditionally surgical. Early detection of unruptured ectopic pregnancies, using both ultrasound techniques and β-human chorionic gonadotropin (β-hCG) assays, allows a more conservative treatment. Twenty-six tubal pregnancies, which were managed with local methotrexate (MTX) injection, are presented. A single dose of 10–12.5 mg of MTX was percutaneously injected into the gestational sac under abdominal sonographic control. Complete resolution was obtained in all our patients. Four of them required a second percutaneous administration 4 days after the first one. Negligible serum β-hCG levels (<10 mIU/ml) were reached within 42 days after treatment. No systemic side effects were observed. Local administration of MTX under abdominal sonographic control seems to be an effective alternative for the treatment of ectopic pregnancy. The main potential advantages of the method are (1) a greater antitrophoblastic effect; (2) a shorter treatment period; (3) reduced dosage, and (4) absence of side effects.

R-083. Comparison of three different methods of local methotrexate administration in early ectopic pregnancy

R-083. Comparison of three different methods of local methotrexate administration in early 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.

Successful treatment of an advanced interstitial pregnancy by sequential systemic and local administration of methotrexate

A patient is presented with an advanced interstitial pregnancy, diagnosed by transvaginal ultrasound and confirmed by laparoscopy. Amenorrhoea at the time of diagnosis was 57 days. Methotrexate was given systemically (4 x 50 mg i.m.). Because of persisting viability of the fetus, systemic methotrexate treatment was followed by local instillation of methotrexate into the gestational sac (50 mg). Follow-up revealed rapid human chorionic gonadotrophin regression but slow regression of fetal remnants.

Conservative Treatment of Ectopic Pregnancy and Its Effect on Corpus luteum Activity

Corpus luteum activity was monitored in 15 women undergoing nonsurgical management of ectopic pregnancy with local methotrexate injection followed by alternating oral methotrexate and citrovorum factor (group A, n = 8) or local methotrexate injection alone (group B, n = 7). All patients initially demonstrated a viable corpus luteum (plasma progesterone ranged from 1.4 to 19 ng/ml). The treatment was successful in 14, with the exception of one whose tube ruptured 11 days after local administration of methotrexate, despite a continuous decrease in beta human chorionic gonadotropin, 17 beta-estradiol and plasma progesterone levels. There seems to be no correlation between the success of the treatment and the behavior of beta human chorionic gonadotropin, 17 beta-estradiol and plasma progesterone. Three patients from group A and two from group B displayed an initial rise in beta human chorionic gonadotropin following the initiation of the therapy, but the corpus luteum response differed. In group B patients, 17 beta-estradiol and plasma progesterone levels increased in parallel with beta human chorionic gonadotropin. Group A patients displayed a continuous decrease in 17 beta-estradiol and plasma progesterone levels despite the elevation of beta human chorionic gonadotropin, suggesting a possible effect of the systemic methotrexate on corpus luteum activity.