Interstitial pregnancy management: A multicentric analysis of 98 patients from the FRANCOGENT group comparing surgery and medical treatment.

OBJECTIVE: To evaluate the outcomes associated with each therapeutic option for patients diagnosed with interstitial pregnancy (IP). METHODS: We conducted a multicentric retrospective cohort study within the departments of Gynecology and Obstetrics involved in the Francogent research group. Women treated for an interstitial pregnancy between January 2008 to December 2019 were included. Three therapeutic options were evaluated: surgical treatment (ST); in situ methotrexate combined with systemic methotrexate (IS-MTX); and systemic methotrexate (IM-MTX). Success of first-line treatment was defined by hCG negativation (<5I U/L). Secondary outcomes included the need for secondary surgical procedure, secondary medical treatment, emergency surgery, postoperative complications, duration of hospitalization, and delay before hCG negativation. RESULTS: A total of 98 patients were managed for IP: 42 (42.9%) patients had IM-MTX; 34 (34.7%) had IS-MTX; and 22 (22.4%) had ST. First-line treatment was successful in all patients of the ST group (22/22, 100%), in 31% of patients within the IM-MTX group (13/42) and 70.6% (24/34) in the IS-MTX group. The sole parameter associated with the risk of treatment failure was the mode of methotrexate administration. The size of the gestational sac or the presence of fetal heartbeat was not associated with decreased medical treatment (IS or IM-MTX) efficiency. CONCLUSION: Either ST or IS-MTX are good options for IP treatment associated with high success rates. A single-dose regimen of IM-MTX is less efficient than IS-MTX or ST. Symptomatic patients with severity criteria should always undergo emergency surgery. IP remains a high-risk condition that should be managed, whenever possible, in referral centers to potentialize the chances of favorable outcomes.

Uso de mifepristona en embarazo ectópico intersticial: un reporte de caso / Use of mifepristone in an interstitial ectopic pregnancy: a case report

Introducción: El embarazo ectópico intersticial es una forma de presentación poco frecuente, con una incidencia del 2-4% de los embarazos ectópicos; sin embargo, a pesar de su baja incidencia la mortalidad es cinco veces mayor, impactando en las cifras de mortalidad materna y representando en torno al 10-15% de los casos. Objetivo: Presentar un caso de embarazo ectópico intersticial, cuya ocurrencia es poco frecuente, así como el abordaje satisfactorio del manejo médico con mifepristona y metotrexato. Caso clínico: Mujer de 28 años con antecedente de resección tubárica por quiste paraovárico derecho, quien acudió a urgencias por hallazgo en ecografía obstétrica de sospecha de embarazo intersticial izquierdo y se le administró manejo farmacológico con dosis de metotrexato y mifepristona, con éxito. Conclusiones: El manejo médico con metotrexato y mifepristona para el embarazo ectópico intersticial parece ser una elección eficaz en los casos con estabilidad hemodinámica y deseo de conservación de la fertilidad.

Background: Interstitial ectopic pregnancy represents a rare form of presentation, with an incidence of 2-4% of all ectopic pregnancies. However, despite its low incidence, it is associated with a five-fold increase in mortality, significantly impacting maternal mortality rates, accounting for approximately 10-15% of cases. Objective: To present a case of interstitial ectopic pregnancy, which is a rare occurrence, as well as the successful medical management approach with mifepristone and methotrexate. Case report: A 28-year-old women with a history of right paraovarian cyst tubal resection presented to the emergency department due to suspected left interstitial pregnancy identified on obstetric ultrasound. The patient was successfully managed with pharmacological treatment using doses of methotrexate and mifepristone. Conclusions: Medical management with methotrexate and mifepristone for interstitial ectopic pregnancy appears to be an effective choice in cases with hemodynamic stability and a desire for fertility preservation.

Interstitial ectopic pregnancy successfully treated with methotrexate.

An ectopic pregnancy (EP) occurs when the fertilised ovum implants outside the endometrial cavity. An EP has an incidence of 1%, with the majority occurring in the fallopian tube. It has a maternal mortality of 0.2 per 1000, with about two-thirds of these deaths associated with substandard care. An interstitial pregnancy occurs when the EP implants in the interstitial part of the fallopian tube. An interstitial ectopic pregnancy (IEP) shows few early clinical symptoms, hence it is associated with serious or fatal bleeding and a mortality rate up to 2.5%. With the advent of transvaginal ultrasound scan (TV USS), correlated with serum beta human chorionic gonadotropin (BHCG) assay, earlier diagnosis of an EP can be established. An EP is often diagnosed in women who are trying to conceive; therefore, the prognosis of future fertility is one of the main concerns associated with this diagnosis. Management can be surgical, expectant or medical with methotrexate (MTX). However, the best approach is tailored to the woman's individual case. The authors present the case of a primigravida woman presenting with abdominal pain and vaginal bleeding at 6 weeks gestation following assisted reproduction. Her BHCG showed a suboptimal rise. Her TV USS showed no evidence of an intrauterine pregnancy. There was no evidence of an adnexal mass or free fluid. As her BHCG remained static, she underwent a diagnostic laparoscopy. A right sided IEP was identified. Due to the high risk of bleeding requiring transfusion or hysterectomy and her desire to preserve her fertility, she received medical management with MTX. Indeed, research has shown that women successfully managed expectantly achieve better reproductive outcomes, with the shortest time to achieve a subsequent intrauterine pregnancy. This case acts as a cautionary reminder of the challenges associated with identifying an IEP on TV USS. A high index of clinical suspicion is required to prevent maternal morbidity and mortality.

Interstitial Pregnancy Treated with Mifepristone and Methotrexate with High Serum ß-hCG Level in a Patient Wishing to Preserve Fertility: Time to Define Standardized Criteria for Medical/Surgical Therapy?

Interstitial pregnancy (IP) accounts for 2% of all ectopic pregnancies and has a mortality rate of 2-2.5%. The diagnosis is made by a transvaginal ultrasound and the treatment can be medical or surgical. We report the case of a 36-year-old primigravida who was 6 + 5 weeks pregnant, diagnosed with interstitial pregnancy by ultrasound, who had a very high serum ß-hCG level (31,298 mIU/mL) and wanted to preserve her fertility. The patient was treated with one dose of mifepristone and a double dose of methotrexate since the decrease in the ß-hCG serum level was less than 15% after the first dose. At the beginning, medical therapy was effective, as no embryonal cardiac activity was detected and serum ß-hCG levels decreased early, but on the 20th day of hospitalization, the patient underwent surgery for her clinical symptoms and the evidence of free fluid in the Douglas pouch at a transvaginal ultrasound exam. Our experience showed that medical treatment should be considered, especially in women wishing to preserve their fertility. Further studies are needed to establish a standardized protocol and maybe a clinical score that can be useful in predicting the patients in which medical therapy could be most successful.

Interstitial Pregnancy Managed with Single-dose Systemic Methotrexate: A Case Report.

Interstitial pregnancy is a rare type of ectopic pregnancy with a high risk of massive hemorrhage on rupture as compared to ectopic on other sites. The mortality rate for the ruptured interstitial pregnancy is high. Therefore, early diagnosis of such pregnancy before the rupture occurs facilitates appropriate management and avoids life-threatening complications. With the advancement in diagnostic imaging modalities, early diagnosis and more conservative management for interstitial pregnancy have become possible. Here, we report a case of primigravida diagnosed with interstitial pregnancy with ultrasonography and successfully managed with a single dose of methotrexate.

Conservative Treatment of Interstitial Ectopic Pregnancy with the Combination of Mifepristone and Methotrexate: Our Experience and Review of the Literature.

INTRODUCTION: Interstitial pregnancy (IP) is an ectopic pregnancy (EP) located in the portion of the fallopian tube that penetrates the uterine muscular layer. Incidence increased in the last two decades with the widespread use of the assisted reproductive techniques. It is estimated in 1-6% of all the EPs, with a maternal mortality rate of 2.0-2.5%. Clinical presentation, gestational age at diagnosis, beta-human chorionic gonadotropin (ß-hCG) levels, ultrasound features, and patient preference, should be considered to determine the best management: surgical, medical treatment, or close observation. We report two cases of IP successfully managed with systemic MTX and Mifepristone: in one case ß-hCG was >10.000 mIU/mL and a vital embryo was present. MATERIALS AND METHODS: A literature search was carried out on MEDLINE, EMBASE, and PUBMED. We identified two cases of IP referred to the Institute for Maternal and Child Burlo Garofolo, Trieste. Data related to clinical presentation, ß-hCG, and ultrasound scan at the moment of the diagnosis were recorded. In one of the cases, the ß-hCG level was >10.000 mIU/mL, and a vital embryo was testified at an ultrasound scan. The patient was asymptomatic and she was treated using multidose systemic Methotrexate (MTX) combined with Mifepristone. In the second case, in the presence of a clinically stable patient with ß - hCG > 10.000 mIU/mL, it was chosen that the administration of Mifepristone combined with a double dose of MTX. ß-hCG levels and ultrasound examinations were performed weekly until a complete resolution of the IP. RESULTS: In the first case, ß-hCG dropped down in 5 days and became undetachable in 30 days. In the second case, ß-hCG became undetectable in 47 days. The first-line therapy in asymptomatic women could be addressed to a combined protocol, consisting of a systemic multidose MTX regimen with a single oral dose of Mifepristone. CONCLUSIONS: Clinical management of IP remains a debated topic. In selected cases, a systemic multidose MTX regimen combined with a single oral dose of Mifepristone could be considered also in the presence of high serum ß-hCG.

Combination methotrexate and gefitinib: A potential medical treatment for inoperable nontubal ectopic pregnancy.

Nontubal ectopic pregnancies present as a therapeutic challenge. A 35-year-old primigravida at 7 weeks gestation had a live interstitial ectopic pregnancy and contraindications to surgery. The patient was treated with a multidose methotrexate regimen combined with oral gefitinib (250 mg daily for 7 days). The peak human chorionic gonadotropin (hCG) of the patient was recorded at 19 510 IU/L and began declining from day 4 of combination therapy (day 6 of initial treatment). Successful resolution of the ectopic was demonstrated by cessation of the fetal heart by day 15 and hCG falling to 23 IU/L by day 42. A 10-year review of all nontubal ectopic pregnancies treated with methotrexate identified 46 cases, which had a comparable time to resolution to combination therapy. However, for cases where cardiac activity was present, the median time to resolution following methotrexate treatment was 64 days (47-87 days), 22 days longer than combination therapy. Combination therapy may provide a safe medical treatment for inoperable nontubal ectopic pregnancy.

Embarazo ectópico intersticial tratado con metotrexato y cirugía: caso clínico / Interstitial ectopic pregnancy treated with methotrexate and surgery: clinical case

RESUMEN Antecedentes: El embarazo intersticial es muy inusual y representa <2,4% de todos las gestaciones ectópicas. Objetivo: Se presenta el caso de un embarazo ectópico intersticial tratado de forma médica y quirúrgica. Se realiza una revisión literaria sobre las opciones de manejo y tratamiento. Caso clínico: Paciente primigesta de 36 años con gestación ectópica cornual derecha tras 11 días de la transferencia de un embrión criopreservado. Se decide tratamiento con metotrexato (MTX) sin éxito y con progresión del embarazo, obligándonos por lo tanto a realizar una evacuación quirúrgica de la gestación, exponiendo a la paciente tanto a los efectos secundarios del tratamiento médico como a los del abordaje quirúrgico. Conclusión: El embarazo ectópico intersticial sigue siendo un reto para el ginecólogo. El diagnóstico muy temprano de estas patologías, aunque difícil, podría evitar la opción quirúrgica, siendo el MTX más eficaz en los casos tratados precozmente.

ABSTRACT Background: Interstitial pregnancy is very unusual, and it represents <2,4% of all ectopic pregnancies. Objective: We present the case of an interstitial ectopic pregnancy treated medically and surgically. A literary review is also made about the management and treatment options. Clinical case: A 36-year-old patient with a diagnosis of right cornual ectopic pregnancy after 11 days of a cryopreserved embryo's transfer. Methotrexate (MTX) treatment was applied as the initial step but without lasting results. Because of the progression of the pregnancy, further therapy was focused on its surgical evacuation exposing the patient to the side effects of both medical treatment and surgical approach. Conclusion: Interstitial ectopic pregnancy remains a challenge for the gynecologist. Very early diagnosis of these pathologies, although difficult, could avoid the surgical outcome, being MTX more effective in cases intervened initially.

Successful transvaginal aspiration of interstitial pregnancy after failed methotrexate treatment.

Interstitial pregnancy is an uncommon condition that is challenging, not only in making an accurate diagnosis, but also in the choice of treatment. Systemic methotrexate (MTX) treatment has been favored to prevent scarring of the uterus. Nevertheless, surgery is generally indicated when this treatment fails. Transvaginal aspiration of the gestational tissue has been proposed as an alternative to surgery. The authors present a case of interstitial pregnancy in which the patient failed to respond to multidose MTX treatment and was successfully treated with transvaginal sonography-guided transvaginal aspiration of the gestational tissue, thereby bypassing the risk associated with undergoing major surgery. Transvaginal aspiration of conceptive tissue may be a novel treatment for patients with unruptured interstitial pregnancy.

Management of interstitial ectopic pregnancy with intravenous methotrexate: An extended study of a standardised regimen.

BACKGROUND: Interstitial ectopic pregnancy is a rare but potentially life threatening condition. Of the three management options for this condition (expectant, medical and surgical treatment) methotrexate therapy in several regimens has been reported to be effective and beneficial. AIM: To assess the safety and efficacy of intravenous bolus and infusion of methotrexate with folinic acid rescue for the treatment of interstitial ectopic pregnancy. MATERIALS AND METHODS: A retrospective cohort study of women with interstitial ectopic pregnancy treated with methotrexate at the Royal Brisbane and Women's Hospital from April 2000 to December 2012. The treatment regimen comprised of a bolus dose of methotrexate 100 mg followed by 200 mg of methotrexate infusion over 12 h. Four doses of 15 mg oral folinic acid rescue were given post-treatment. Success of methotrexate therapy was confirmed by either a negative serum beta-human chorionic gonadotropin (ß-hCG) level or subsequent uneventful pregnancy. RESULTS: Of 33 women with interstitial ectopic pregnancy who were treated with this regimen, 31 (93.9%) were treated successfully, including women with a high ß-hCG level up to 106 634 IU/L and the presence of fetal cardiac activity. Minor side effects were documented in three cases. CONCLUSIONS: Intravenous methotrexate therapy with folinic acid rescue is well tolerated and highly effective.

Interstitial pregnancy: a 'road map' of surgical treatment based on a systematic review of the literature.

An electronic search concerning the surgical approach in cases of interstitial pregnancy from January 2000 to May 2013 has been carried out. Fifty three studies have been retrieved and included for statistical analysis. Conservative and radical surgical treatments in 354 cases of interstitial pregnancy are extensively described. Hemostatic techniques have been reported as well as clinical criteria for the medical approach. Surgical outcome in conservative versus radical treatment were similar. When hemostatic techniques were used, lower blood losses and lower operative times were recorded. Conversion to laparotomy involved difficulties in hemostasis and the presence of persistent or multiple adhesions. Laparoscopic injection of vasopressin into the myometrium below the cornual mass was the preferred approach.

Transabdominal ultrasound-guided injection of methotrexate in the treatment of ectopic interstitial pregnancies.

PURPOSE: In a retrospective observational study, we evaluated the feasibility and safety of medical therapy with transabdominal ultrasound-guided injection of methotrexate (MTX) into the gestational sac (GS) in patients with interstitial ectopic pregnancies. METHODS: Fourteen interstitial ectopic pregnancies were treated with transabdominal ultrasound-guided injection of MTX (25 mg). All patients were hemodynamically stable. In all patients, the 10-cm distance between the GS and vaginal fornices was ≥10 cm, making transvaginal injection difficult. To evaluate feasibility and safety of the procedure, we assessed complications clinically and with imaging during a 1-year follow-up. RESULTS: In all 14 patients, MTX injected locally into the GS successfully terminated the interstitial pregnancy, thereby avoiding surgery. There was no complications during follow-up. CONCLUSIONS: The successful outcome in our patients suggests that the transabdominal route is feasible and safe as a nonsurgical option for terminating an ectopic interstitial pregnancy in patients in whom the transvaginal route is contraindicated or difficult, provided the patients are properly selected and operators have sufficient experience with the technique.