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Invasive ultrasound in the management of cervical ectopic pregnancy

  • G. Guzowski
    Correspondence
    Corresponding author at: Piotrkowska street 182/554 Łódź, Poland. Tel.: +48 601 926 572.
    Affiliations
    Department of Fetal Medicine and Gynecology and Department of Gynecology and Obstetrics, Medical University of Lodz, 4 Kościuszki St., 90-419 Lodz, Poland
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  • P. Sieroszewski
    Affiliations
    Department of Fetal Medicine and Gynecology and Department of Gynecology and Obstetrics, Medical University of Lodz, 4 Kościuszki St., 90-419 Lodz, Poland
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Published:November 08, 2013DOI:https://doi.org/10.1016/j.ejogrb.2013.10.016

      Abstract

      Invasive ultrasound management of a 6-week live cervical pregnancy in a 26-year old primipara is described. The patient was given methotrexate three times at seven-day intervals with no effect. Then 15% KCl was administered intra-amniotically via the transvaginal and transcervical route under ultrasound guidance. The procedure was successful, causing fetal death and loss of trophoblastic blood flow on Doppler examination. Over the subsequent four weeks, there was a steady decrease of serum β-hCG concentration. After four weeks, curettage of the cervical canal and uterine cavity was performed successfully. This method of treatment enabled avoidance of invasive surgical procedures, which might have limited future fertility.

      Keywords

      Case report

      A healthy 26-year-old primipara at 6 weeks of pregnancy reported to the Department of Fetal Medicine and Gynecology, Medical University of Lodz, with a five-day history of vaginal spotting and pain localized to the lower abdomen. She had no relevant previous gynecological or surgical history and had conceived spontaneously. She had never been treated for infertility. Examination revealed a short cervix, which was expanded in the upper part with the uterus to the size of a 6-week pregnancy. Serum β-hCG concentration was 42,042 mIU/ml. Vaginal ultrasound scan revealed a normal uterus with a wide decidual reaction (14 mm), a gestational sac located in the proximal part of the cervical canal, and a living embryo with a crown-rump length (CRL) of 6.6 mm, corresponding to six weeks of pregnancy. Doppler examination showed a rich vascularity of the cervix and the typical trophoblastic flow around the gestational sac.
      Due to the patient's nulliparity and young age, we decided to try to use methotrexate (MTX) but an alternative surgical treatment algorithm was also planned in case of possible failure of conservative treatment. Basic blood tests (haemoglobin, hematocrit, liver function tests, blood type, Rhesus status, urea and electrolytes, and serum creatinine) were done before and during MTX therapy, and all results were within normal limits. MTX was given intravenously at a dose of 95 mg in 100 ml 0.9% NaCl (50 mg/m2). The patient weighed 85 kg and the dose was determined with the oncologist–chemotherapist. Over the next seven days the routine checks of β-hCG concentrations in serum showed an upward trend (Fig. 1), and ultrasound showed a steady growth of the embryo. The patient received MTX intravenously for the second time at a dose 95 mg in 100 ml 0.9% NaCl. Over the next week a further upward trend of β-hCG concentrations in serum was observed, as well as continued growth to a CRL of 29 mm, equivalent to 8.6 weeks’ gestation. The patient received a third dose of 95 mg MTX.
      Figure thumbnail gr1
      Fig. 1Concentration of β-hCG in the bloodserum in the subsequent days of treatment.
      Two days after the third dose of MTX, with fetal heart activity still visible and β-hCG 64,112 mIU/ml, the patient underwent puncture of the amniotic sac under ultrasound guidance and administration of 15% KCl to terminate the pregnancy. Intraamniotic administration of KCl solution was decided upon due to lack of response to MTX treatment. According to our protocols MTX, KCl solution or hyperosmolar glucose could be applied here: we chose KCl solution to radically modify the previous treatment. Under ultrasound guidance, a Tuohy needle (18G, 25 cm long) was introduced into the amniotic sac by means of a transvaginal probe, and 10 ml of 15% KCl solution was given, causing cardiac arrest of the embryo. The needle was not put through the cervical canal but laterally through the cervix itself to avoid a separation of the trophoblast and consequent massive bleeding.
      After 2 days an ultrasound scan showed extrachorionic/retroplacental hematoma formation with a diameter of about 65 mm. After discussion with chemotherapist, due to persistent high levels of β-hCG five days after KCl administration, the patient received a fourth dose of MTX (95 mg). Thereafter a significant decrease in β-hCG was observed and seven days later trophoblastic flow ceased on Doppler ultrasound scan. The patient reported no pain except slight vaginal spotting. On ultrasound monitoring a continuous reduction in the hematoma size was observed with gradual collapse of gestational sac, but spontaneous abortion did not occur. It was therefore decided to empty the cervical canal surgically.
      In the operating theatre under ultrasound control, curettage of the cervical canal was performed. The whole blastocyst was removed intact and sent for histological examination. Bleeding after surgery was within the normal range. The patient was prescribed hormonal contraception for six months. Ultrasound assessment of the cervical canal showed no abnormalities. Seven months after surgery diagnostic hysteroscopy to exclude adhesions revealed no pathological findings in the cervical canal and uterine cavity.

      Comments

      Cervical pregnancy is the least common type of ectopic pregnancy, comprising less than 1% of all ectopic pregnancies. It represents a significant threat to the health, fertility and life of the woman. Most patients present with massive vaginal bleeding. The risk factors are: a history of uterine curettage or cesarean section, use of the intrauterine device, or assisted reproductive techniques [
      • Malinowski A.
      • Maciolek-Blewniewska G.
      • Szaflik K.
      • Cieslak J.
      • Pawlowksi T.
      Conservative treatment of a 12-week cervical pregnancy.
      ]. The diagnosis is based on a clinical finding of an expanded uterine cervix and soft, non-enlarged corpus uteri. On transvaginal ultrasound cervical pregnancies are recognized around 6–8 weeks of pregnancy [
      • Ferrara L.
      • Belogolovkin V.
      • Gandhi M.
      • et al.
      Successful management of a consecutive cervical pregnancy by sonographically guided transvaginal local injection: case report and review of the literature.
      ], allowing treatment before the onset of life-threatening bleeding.
      The treatment of choice was hysterectomy until Raskin first described the ultrasound picture of the cervical pregnancy in 1978 [
      • Raskin M.M.
      Diagnosis of cervical pregnancy by ultrasound: a case report.
      ]. In the literature we can now find examples of effective conservative treatment, preserving the patient's fertility. MTX is generally used and locally KCl is administered into the amniotic sac: ligation or embolization of uterine arteries or internal iliac arteries is done, hemostatic sutures are applied to the cervix from the vaginal side and amputation of the cervix is performed [
      • Bekane N.
      • Moutafoff-Borie C.
      Impact of previous uterine artery embolization on fertility.
      ].
      We believe that the gold-standard treatment of cervical pregnancy is local transvaginal therapy [
      • Andrés M.P.
      • Campillos J.M.
      • Lapresta M.
      • Lahoz I.
      • Crespo R.
      • Tobajas J.
      Management of ectopic pregnancies with poor prognosis through ultrasound guided intrasacular injection of methotrexate, series of 14 cases.
      ]. According to the literature, in 81% of cases transvaginal therapy does not produce complications, in 5% bleeding occurs requiring additional interventions and only in 1% of cases is it necessary to remove the uterus [
      • Ferrara L.
      • Belogolovkin V.
      • Gandhi M.
      • et al.
      Successful management of a consecutive cervical pregnancy by sonographically guided transvaginal local injection: case report and review of the literature.
      ]. High-dose systemic therapy with intravenous MTX has been reported to give good results [
      • Song M.J.
      • Moon M.H.
      • Kim J.A.
      • Kim T.J.
      Serial tranvaginal sonographic findings of cervical ectopic pregnancy treated with high-dose methotrexate.
      ] but this did not occur in our case.
      The following factors affect MTX therapy adversely: pregnancy over 9 gestational weeks, β-hCG levels greater than 10,000 U/l, CRL greater than 10 mm and presence of fetal heart activity. In our case, the only adverse factor was visible fetal heart activity but because of the patient's childlessness and future procreation plans, we tried a cytotoxic rather than cytostatic method. The treatment protocol allows single (50 mg/m2) or multi-dose (1 mg/kg MTX + 0.1 mg/kg folinic acid) regimes and we decided on the former. The dose of 50 mg/m2 was administered every seven days because there was no decrease, and indeed an increase, of β-hCG, and fetal cardiac activity was still present. Stoval et al. proposed checking β-hCG between day 4 and day 7 and if there is no decrease of more than 15%, applying another single dose [
      • Stovall T.G.
      • Ling F.W.
      Single dose MTX: an expanded clinical trial.
      ]. MTX arrests the growth of the trophoblast by inhibiting DNA synthesis [
      • Malinowski A.
      • Maciolek-Blewniewska G.
      • Szaflik K.
      • Cieslak J.
      • Pawlowksi T.
      Conservative treatment of a 12-week cervical pregnancy.
      ,
      • Raskin M.M.
      Diagnosis of cervical pregnancy by ultrasound: a case report.
      ,
      • Song M.J.
      • Moon M.H.
      • Kim J.A.
      • Kim T.J.
      Serial tranvaginal sonographic findings of cervical ectopic pregnancy treated with high-dose methotrexate.
      ,
      • Stovall T.G.
      • Ling F.W.
      Single dose MTX: an expanded clinical trial.
      ]. A review reported that the majority of successfully cured cases were treated with KCl, not MTX, applied intraamniotically under ultrasound guidance [
      • Andrés M.P.
      • Campillos J.M.
      • Lapresta M.
      • Lahoz I.
      • Crespo R.
      • Tobajas J.
      Management of ectopic pregnancies with poor prognosis through ultrasound guided intrasacular injection of methotrexate, series of 14 cases.
      ], which is considered to be a safer alternative to MTX.
      Embolization of the uterine arteries combined with MTX is an optional non-surgical method of treatment. Hirakawa at al. report [
      • Hirakawa M.
      • Tajima T.
      • Yoshimitsu K.
      • et al.
      Uterine artery embolization along with the administration of methotrexate for cervical ectopic pregnancy: technical and clinical outcomes.
      ] that three women with a history of uterine artery embolization due to cervical pregnancy became pregnant within two years and two of them gave birth to live children. A study conducted on sheep [
      • Yamagami T.
      • Yoshimatsu R.
      • Matsumoto T.
      • et al.
      Fertility after uterine artery embolization: investigation using a sheep model.
      ] showed no difference in fertility after embolization of the uterine arteries, but intrauterine growth retardation of fetuses [
      • Bekane N.
      • Moutafoff-Borie C.
      Impact of previous uterine artery embolization on fertility.
      ]. Prospective studies are needed of women after embolization of uterine arteries and also internal iliac artery ligation to be able to unambiguously determine whether these measures do not restrict their fertility. Until then, uterine artery embolization procedures and ligation of the internal iliac arteries should be performed only in a life-threatening situation.
      A literature review showed that the majority of cases were treated surgically (41%) or conservatively (36%) and a minority of cases with a combination of both methods (18%). Following this we decided to use conservative treatment, which takes time to achieve results. Moragianni et al. conclude that conservative treatment minimizes the risk of haemorrhage, and furthermore inclusion of chemotherapy is better than radical surgical procedures [
      • Ferrara L.
      • Belogolovkin V.
      • Gandhi M.
      • et al.
      Successful management of a consecutive cervical pregnancy by sonographically guided transvaginal local injection: case report and review of the literature.
      ,
      • Leeman L.M.
      • Wendland C.L.
      Cervical ectopic pregnancy: diagnosis with endo vaginal ultrasound examination and successful treatment with MTX.
      ,
      • Moragianni V.A.
      • Hamar B.D.
      • McArdle C.
      • Ryley D.A.
      Management of a cervical heterotopic pregnancy presenting with first-trimester bleeding: case report and review of the literature.
      ].
      Clinical practice guidelines are not available. The treatment of cervical pregnancy should be tailored to the needs of the patient and above all the presence of profuse hemorrhage [
      • Kaminopetros P.
      • Watson A.J.S.
      • Martinez D.
      • Rand R.J.
      • Thornton J.G.
      Combined systemic and intra-amniotic treatment of cervical pregnancy by methotrexate. A report of two cases.
      ,
      • 13.Bianchi P.
      • Salvatori M.M.
      • Torcia F.
      • Cozza G.
      • Mossa B.
      Cervical pregnancy.
      ]. There are various therapeutic options and no standard guidelines exist regarding optimum treatment. In most cases, treatment is a combination of regimens. Overall, all one can say at this stage is that conservative management of asymptomatic cervical pregnancy using MTX seems superior to surgical intervention. We advocate establishment of treatment centers for unusual ectopic pregnancies to enable optimum treatment to be formulated. We recommend the above-described non-surgical treatment associated with the use of interventional transvaginal ultrasound, which allowed the patient to retain her fertility.

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