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.

Conservative management of interstitial pregnancies: experience of a single centre.

The aim of this study was to compare the effect of local intracavitary methotrexate (MTX) injection and laparoscopic (L/S) cornuostomy in the treatment of interstitial pregnancy (IP) in terms of clinical and reproductive outcome. The data of patients with IP (n:10) who were treated between September 2011 and December 2016 with either an intra-amniotic MTX injection (n:7) or L/S cornuostomy (n:3) were retrospectively evaluated. All cases (7/7) in the local injection group and two (2/3) in the L/S group were successfully treated with the initial treatment. One case (1/3, 33%) in L/S group needed systemic MTX due to an elevated ß-hCG. No serious complication or secondary surgical intervention was observed in the study group. Five (71.4%) women in MTX group and two (66%) women in the L/S group had pregnancy after index case (p > .05). Post-treatment (hysterosalpingography) HSG results revealed that tubal patency was significantly higher in the MTX group (7/7 (100%) vs. 0/3 (0%) p < .05). Conservative treatment of IP with both methods was generally successful with regard to maternal morbidity and reproductive function. However, local MTX was superior for tubal patency compared to L/S cornuostomy. Since this is a retrospective study including a small study population, our results should be confirmed with larger prospective studies. Impact Statement What is already known on this subject? Earlier diagnosis of an interstitial pregnancy (IP) enables clinicians to pursue more conservative treatment modalities that can prevent morbidity (severe bleeding, rupture and massive transfusion, etc.) and loss of fertility. MTX treatment and conservative laparoscopic surgical procedures are gaining importance. High serum ß-hCG levels and positive foetal cardiac activity are known as unfavourable pre-treatment prognostic predictors for systemic MTX treatment in patients with an ectopic pregnancy. Local MTX treatment is widely used for caeserean scar pregnancies or cervical pregnancies. L/S cornuostomy is an attractive alternative to L/S cornual resection, because it preserves the normal uterine myometrium. What the results of this study add? In the present study, we showed that the local MTX and laparoscopic cornuostomy were successful methods in IP patients and did not impair the fertility potential of the patients. We also demonstrated that local MTX application is superior to L/S cornuostomy in terms of the post-treatment tubal patency and this fact should be kept in mind when tailoring the treatment in patients desiring pregnancy. What the implications are of these findings for clinical practice and/or further research? The value of local MTX injection in cases with IP and high ß-hCG levels should be further clarified.

Magnetic resonance imaging for diagnosis and management of unruptured interstitial pregnancy.

AIM: The aim of this study was to evaluate the value of magnetic resonance imaging (MRI) for the diagnosis and management of suspicious unruptured interstitial pregnancy. MATERIAL AND METHODS: Only patients with unruptured interstitial pregnancy evaluated by MRI and observed for at least a year after surgery were included. Initial evaluation was performed by measurement of serum ß-human chorionic gonadotrophin level and ultrasonography. In suspicious cases, emergency MRI was performed to diagnose interstitial pregnancies with the exclusion of rudimentary horn pregnancy and angular pregnancy. Three-dimensional computed tomographic (CT) angiography was additionally performed if the uteroplacental neovascularization needed to be evaluated. Then, management procedures were individually determined along with the need for preoperative transcatheter arterial chemoembolization for immediate devascularization, and for the local or systemic administration of methotrexate. Either laparoscopic cornuostomy or cornual resection was chosen to excise the gestational mass. RESULTS: Five consecutive women with unruptured interstitial pregnancy were enrolled. One case each of rudimentary horn pregnancy and angular pregnancy was excluded. Three-dimensional CT angiography was performed in three cases due to increased vascular flow on color Doppler ultrasonography. Preoperative devascularization by transcatheter arterial chemoembolization was performed in two cases, in which a prominent neovascularized gestational mass was identified. Uterine preservation was achieved by cornuostomy or cornual resection in all cases. Two patients with a desire to become pregnant conceived spontaneously thereafter, followed by successful cesarean birth. CONCLUSION: This small case series emphasizes that precise localization of gestational products in the interstitial portion of the fallopian tube by MRI can facilitate the minimally invasive management of unruptured interstitial pregnancy for uterine preservation.

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.

Effectiveness of medical treatment with methotrexate for interstitial pregnancy.

BACKGROUND: In the last three decades, systemic methotrexate (MTX) has become widely accepted as the primary treatment for unruptured tubal pregnancy. This has prompted investigations into the use of MTX in the management of interstitial pregnancy. AIM: To determine the effectiveness of methotrexate for treatment of interstitial pregnancy. METHODS: We retrospectively reviewed 17 haemodynamically stable women admitted to our tertiary, university-affiliated medical centre with an intact interstitial pregnancy from January 2003 through February 2013. First-line treatment consisted of intramuscular MTX 1 mg/kg/day x4 alternating with folinic acid 0.1 mg/kg or, in cases of low beta-human chorionic gonadotropin (ß-hCG) and no embryonic pole, one dose of 50 mg/m(2) body surface area. Uterine artery MTX injection was administered on the ipsilateral side of the pregnancy followed by uterine artery embolisation as second-line treatment. Failure criteria were <15% decrease in ß-hCG or sonographic evidence of pregnancy development. Second-line failures were referred for surgery. RESULTS: Twelve women (70.5%) underwent successful first-line treatment and 5 (29.5%) required second-line treatment. Baseline characteristics were similar except for a higher rate of two previous ectopic pregnancies in the first-line failures (80% versus 8.3%, P = 0.01). Two women eventually required surgery, both with two previous ectopic pregnancies. Of the three women with fetal cardiac activity on admission, two had successful first-line treatment and one required surgery. CONCLUSION: Systemic MTX is effective for treatment of intact interstitial pregnancy in haemodynamically stable women. The success rate is increased with uterine artery MTX injection as second-line treatment.