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

Abstract

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 (β-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 β-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, β-hCG, and ultrasound scan at the moment of the diagnosis were recorded. In one of the cases, the β-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 β−hCG>10.000 mIU/mL, it was chosen that the administration of Mifepristone combined with a double dose of MTX. β-hCG levels and ultrasound examinations were performed weekly until a complete resolution of the IP. Results. In the first case, β-hCG dropped down in 5 days and became undetachable in 30 days. In the second case, β-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 β-hCG.

Management of Non-Tubal Ectopic Pregnancies: A Single Center Experience

“…From our analysis it emerged that medical management with MTX IM regimen isolated or combined with mifepristone (600 mg orally administered) can be considered a good option in women with IP and a strong motivation for future conceptions [24].…”

Interstitial Ectopic Pregnancy: The Role of Mifepristone in the Medical Treatment

“…Management of interstitial pregnancies remains a debated topic, with no clear guidelines on the best approach. Advances in TVUS and availability of quantitative β -hCG allow diagnosis of interstitial pregnancy at an earlier gestational age [ 4 ]. TVUS has been reported to have a high sensitivity at 6.9 weeks’ gestation.…”

“…Firstly, it reduces the risk of bleeding during an eventual invasive procedure. Secondly, the large vascularization increases drug capacity to reach the trophoblast [ 4 ]. Systemic MTX can be administered following single-dose, double-dose, or multiple-dose protocols.…”

“…The most common symptoms of interstitial pregnancy are abdominal pain and vaginal bleeding. A percentage of patients do not have any clinical manifestation [ 4 ]. The great spectrum of presentation leads to a difficult diagnosis: the challenge is distinguishing an interstitial pregnancy from an intra-uterine or isthmic pregnancy.…”

“…In this manuscript we present a case of interstitial pregnancy treated totally medically with the use of methotrexate (MTX) and mifepristone and folinic acid. This medical approach was reported two more times in literature by Gomez Garcia et al in 2012 and by our research group in 2020 when we have presented two precedent cases successfully treated with this medical protocol at our department [ 4 ]. Reviewing literature this is the case of interstitial pregnancy with the highest Beta Human Chorionic Gonadotropin ( β -hCG) treated with mifepristone, MTX, and folinic acid.…”