interstitial pregnancy refers to an ectopic pregnancy ( ep ) that is implanted in the interstitial portion of the fallopian tube . it represents almost 2 - 4% of all ectopic pregnancies , but its incidence is unclear and is increasing because of the large use of assisted reproductive techniques in recent years . other risk factors include pelvic inflammatory disease , previous ipsilateral or bilateral salpingectomy , previous ep , previous tubal sterilization , uterine anomalies and a history of sexually transmitted infections . diagnosis can be delayed due to the difficulty of distinguishing an interstitial pregnancy from an intrauterine pregnancy ( in particular an angular pregnancy ) in the early ultrasound ( us ) scanning . the mortality rate is as high as 2.5% ( 7 times higher than that of ectopic pregnancies in general ) . thus , early detection and a high index of suspicion are crucial to reduce morbidity and mortality . interstitial pregnancies present a difficult management problem with no absolute standard of care ; several treatments are proposed , both medical and surgical , but the most appropriate technique for the treatment of these pregnancies remains controversial . in this report , we describe a case of unruptured interstitial pregnancy successfully treated with a single - dose of systemic methotrexate with subsequent us and serum beta human chorionic gonadotropin ( b - hcg ) monitoring . a 36-year - old chinese woman , gravida 2 para 1 , was admitted in 2013 to our tertiary center ( careggi university hospital , florence , italy ) at 6  4 weeks of amenorrhea for a suspicion of ep . she was affected by essential hypertension in therapy with nifedipine given orally at a dose of 30 mg once daily . at 17-year - old she underwent a tubal ligation with clip method in china because she did nt desire any other children in that period ; 2 years before admission she decided to remove it . her general conditions were stable , and she did not refer any abdominal - pelvic symptom . the abdominal and vaginal examination did not reveal the pain . a mild vaginal bleeding was noted . at the time of admission , serum level of hcg was 8681 iu / l and hemoglobin was 13.6 g / dl . transvaginal us revealed an empty uterus with two anterior fibroids of < 2 cm . in the left uterine horn , a mass of 37 mm  34 mm with a hypoechoic central area was present without sign of the fetal pole . the color doppler showed the presence of a vascular ring , which proved an intense peripheral vascularization . mass in the left uterine horn at patient admission with ( a ) and without ( b ) color doppler all blood tests were analyzed in the same laboratory ( careggi university hospital , florence , italy ) and all the transvaginal us were performed by the same person . iu / l ) , the patient 's stable hemodynamic state , the size of the mass ( diameter < 4 cm ) , the absence of abdominal free fluid and the absence of hepatic , renal and hematological impairment , according with the patient we decided for conservative management and we performed medical therapy with methotrexate ( a single - dose of intramuscular methotrexate 1 mg / kg , according to the protocol of our center , prepared by the centralized unit for cytotoxic drug preparations of careggi university hospital ) . she did nt have any side effects after treatment . at follow - up us 6 days after treatment the mass reached a size of 46 mm  37 mm and did nt present a recognizable cleavage plane with the myometrium . the patient was hospitalized for 11 days after treatment and remained asymptomatic throughout the hospital stay . this prolonged hospitalization was linked to the suspicion of poor compliance of the patient and to the need for accurate monitoring during the 1 days after this kind of treatment . the us check at discharge revealed two necrosis areas inside the mass and a reduction of peripheral vascularization [ figure 2 ] . mass in the left uterine horn after treatment at patient discharge ( in the context of the mass two areas of necrosis are visible ) the hcg level became negative 2 months later [ table 1 ] . human chorionic gonadotropin ( hcg ) values curve during 65 days after medical treatment ( the serum level of hcg was analyzed in the same laboratory during hospitalization and during follow - up after the discharge ) the patient continued to be followed at the us center with transvaginal us performed every 2 weeks for the first 3 months and then monthly for further 3 months by the same operator that had performed us during hospitalization . she remained asymptomatic during the entire period of follow - up . at follow - up us 3 months after discharge the size of the mass in the left uterine horn was reduced to 32 mm  27 mm with the persistence of a minimal vascularization . the us check performed 6 months after discharge showed an important reduction of the mass ( 19 mm  16 mm ) with the absence of vascularization [ figure 3 ] . we suggested the patient not to become pregnant for further 6 months after the period of follow - up . mass in the left uterine horn at follow - up visit 6 months after treatment with ( a ) and without ( b ) color doppler the patient came to our center for routine gynecological visit in view of a future pregnancy about 1-year after treatment . the us check showed the complete resolution of the mass , so she could try to have a new pregnancy . interstitial pregnancy is an ep at high hemorrhagic risk , due to the rich vascular pattern of the interstitial portion of the fallopian tube supplied by ovarian and uterine arteries . even if its prevalence is uncertain , due to a difficult differential diagnosis with angular pregnancies , an interstitial pregnancy should be considered in case of presence of risk factors for this disease : in our case , the patient had a previous tubal sterilization that is a high risk condition . it 's important to consider that trophoblastic tissue produces b - hcg almost 8 days after conception , with a normal doubling period of approximately 48 h , and an intrauterine sac should be viewed with us when b - hcg are equal ore more than 1000 iu / l . when an interstitial pregnancy is suspected , on the basis of clinical signs or the presence of risk factors , a us exam should be performed as soon as possible . several us features allow an early diagnosis such as an eccentric gestational sac surrounded by asymmetric and thin ( < 5 mm ) myometrial layer , an empty uterine cavity and a thin echogenic line (  interstitial line sign  ) that originates from the endometrium and carries on the edge of the bulking interstitial mass . in case of uncertain diagnosis three - dimensional us or magnetic resonance imaging can be performed but for our patient the diagnosis was clearly identified using transvaginal us ; the us evaluation , performed by an expert staff , showed the typical features of interstitial pregnancies [ figure 1 ] . while an interstitial pregnancy is implanted in the uterine portion of the tube , angular pregnancy is an intrauterine pregnancy located near the utero - tubal junction . these two ectopic pregnancies cause a different uterine distortion : usually the angular pregnancy leads to a bulge medial to the round ligament , and the interstitial one determines a lateral bulge . ultrasound differential diagnosis is based on the features of the myometrium adjacent to the gestational sac . myometrium is thicker in angular pregnancies and surrounds all sides of the sac while in interstitial pregnancies it is present only in the supero - lateral portion of the sac . the most common symptom of ep is vaginal bleeding associated with pain and lower abdominal cramps . women with interstitial pregnancy could remain asymptomatic for several weeks because the interstitial portion of the tube can expand a lot before rupture , more than other tubal segments . in the present patient , however , vaginal bleeding was an early symptom since it appeared before 7 weeks of amenorrhea , even if it was minimal at examination . this kind of surgery was considerably invasive and associated with high morbidity and negative effects on future woman fertility . laparoscopic cornual resection is well - described in literature , it is generally an effective and quite safe procedure if performed by an expert surgeon , but it could be complicated by important bleeding ; additionally , surgery leaves a scar in an already weakened uterine wall and subsequently women are advised that future pregnancies should be delivered by elective caesarean section to avoid the risk of uterine rupture . the development of high - resolution us evaluation and rapid quantitative b - hcg assays has allowed the early detection of interstitial pregnancy , before the rupture , which has made possible a conservative , noninvasive treatment , represented by medical treatment . medical management with methotrexate has been used as first - line treatment in appropriate cases . it has strict inclusion criteria ( early gestation , diameter < 4 cm , b - hcg < 10,000 iu / l , no evidence of rupture ) and success rates vary widely . this conservative treatment can be a successful option in cases that satisfy these criteria and in women who are able to be monitored for a quite long time after treatment and treated further if required . in the present case , all treatment options were considered , both conservative treatments ( expectant management , systemic methotrexate , local injection of methotrexate or potassium chloride , selective uterine artery embolization ) and surgical treatments ( laparoscopic cornual resection , mini - cornual excision , cornuostomy , salpingotomy , transcervical suction evacuation , cornual wedge resection , hysterectomy ) . the choice was depended on the gestational age at diagnosis , the clinical features and the patient 's desire for future fertility . since the diagnosis was early and made before rupture , a nonsurgical treatment option was chosen in order to avoid the uterine scar caused by surgical intervention and to give the patient the chance of a future vaginal delivery . in addition , the avoidance of anesthesia , necessary for a surgical strategy , would result in less morbidity for the patient . it was decided for systemic methotrexate , a folic acid antagonist that inactivates dihydrofolate reductase resulting in depletion of nucleic acid synthesis . the single - dose protocol was chosen , because it requires a shorter treatment with the use of a lower dose of the drug , and it results in fewer side effects while maintaining an efficacy equal to that of multiple - dose regimes . our patient underwent an intramuscular single injection of methotrexate at a dose of 1 mg / kg although several therapeutic regimes are described in the literature . main side effects linked to methotrexate administration , such as tubal rupture or hemoperitoneum , were evaluated and an intensive follow - up was conducted for the early detection of pregnancy persistence and possible complications with both serial measurements of serum hcg and transvaginal us performed by an expert operator . human chorionic gonadotropin - value curves are used for monitoring patients treated conservatively and they are considered as an accurate marker for the identification of success or failure of the procedure . human chorionic gonadotropin levels after methotrexate show a high variability and a rapid increase in hcg values is not strictly predictive of unsuccessful treatment since it occurs in a certain percentage of cases undergoing the resolution . as the french study of bottin et al . showed , in our patient a 20% of decrease in hcg values between day 1 and day 4 after treatment seemed to be a predictive positive factor [ table 1 ] . in conclusion , the early detection of interstitial ep with transvaginal us and sensitive serum b - hcg assays is the key for a successful management because it allows conservative methods instead of conventional surgical management , reducing the potential consequences on morbidity and subsequent fertility . our case report confirmed the evidences of other studies , showing that invasive treatment should not be the first - line management of interstitial pregnancy in hemodynamically stable patients and that single - dose of systemic methotrexate may be a safe , effective and successful option in women who satisfy specific criteria . sc contributed in the conception of the work , in the acquisition , analysis , and interpretation of data for the work , conducting the study , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work . fp contributed in the conception of the work , in the acquisition , analysis , and interpretation of data for the work and agreed for all aspects of the work . cb contributed in the conception of the work , conducting the study , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work . mc contributed in the conception of the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work . lm contributed in the conception of the work , in the acquisition , analysis , and interpretation of data for the work and agreed for all aspects of the work . gm contributed in the design of the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work . mec contributed in the conception and design of the work , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work .
interstitial pregnancy is an ectopic pregnancy at high hemorrhagic risk . 
 it often poses a diagnostic and therapeutic challenge to the clinician , with a significant risk of morbidity and mortality . 
 it presents a difficult management problem with no absolute standard of care ; the most appropriate treatment technique for these pregnancies remains controversial . 
 we describe a case of unruptured interstitial pregnancy successfully treated with a single - dose of systemic methotrexate with subsequent ultrasound and serum beta human chorionic gonadotropin monitoring 
 . medical management can be a safe and successful option in selected cases that satisfy specific criteria and in women who are able to be monitored after treatment .