Ectopic Pregnancies in Unusual Locations

Thomas A Molinaro, M.D.; Kurt T Barnhart,M.D.,M.S.C.E.

Disclosures

Semin Reprod Med. 2007;25(2):123-130. 

In This Article

Cervical Ectopic Pregnancy

Cervical ectopic pregnancies account for less than 1% of all pregnancies, with an estimated incidence of one in 2500 to one in 18,000.[5,6,7] In the past, cervical ectopic pregnancy was associated with significant hemorrhage and was treated presumptively with hysterectomy. Improved ultrasound resolution and earlier detection of these pregnancies has led to the development of more conservative treatments that attempt to limit morbidity and preserve fertility. Predisposing factors for the development of cervical pregnancy include previous instrumentation of the endocervical canal, anatomic anomalies (myomas, synechiae), intrauterine device (IUD) use, in vitro fertilization (IVF), and diethylstilbestrol exposure.[8,9] However, the strength of these associations and cervical ectopic pregnancy generally is very imprecise.

In the past, the diagnosis of cervical pregnancy was made primarily at the time of histological analysis of the hysterectomized uterus. Previous authors have attempted to define criteria that would help to distinguish cervical ectopic pregnancy from intrauterine pregnancies with low implantation sites or in the midst of spontaneous expulsion.[10] Cervical pregnancy can present as (1) a hemorrhagic mass, (2) a gestational sac, or (3) with the presence of a fetus (with or without cardiac activity).[6,7] Ultrasound diagnosis is integral to the early detection of cervical pregnancy. Findings characteristic of cervical pregnancy include the so-called hourglass uterus or dilated cervix.[5] The use of Doppler flow sonography is only helpful in distinguishing abortions in progress from those with vascular implantation in the cervix.[11] The sliding sac sign has been mentioned as a sign of cervical pregnancy that helps to distinguish it from an abortion in progress.[12]

Similar to tubal ectopic pregnancies, early detection is the key factor in conservative treatment of cervical pregnancy. Cervical pregnancies before 12 weeks, without fetal cardiac activity and with lower serum human chorionic gonadotropin (hCG) levels seem more amenable to conservative treatment.[8,13] Conservative measures have become the standard first-line approach to treatment of women who desire fertility preservation. Mechanical disruption of the pregnancy and chemotherapy have been combined with the use of hemostatic methods of tamponade. Traditional curettage, hysteroscopic resection, and ultrasound-guided drainage have been reported as methods of tissue disruption that provide a key aspect to cytoreduction of the ectopic pregnancy.[6]

Most reports of successful conservative therapy involve the use of systemic chemotherapy in combination with cervical evacuation and the use of hemostatic techniques (balloon tamponade, uterine artery ligation, cerclage, cervical stay sutures). Local injections of various chemotherapeutic agents including methotrexate, etoposide, actinomycin D, and cyclophosphamide have met with various degrees of success.[8,12] Systemic methotrexate in addition to curettage has been used successfully by several authors.[5,14] Spitzer et al[8] reported using curettage followed by injection of prostaglandin F2α. Prostaglandins are believed to increase uterine contractions, promote vasoconstriction, and therefore, reduce hemorrhage. Intra-amniotic injections of methotrexate, hyperosmolar glucose, and KCl have been used as adjunctive treatments when the pregnancy has fetal cardiac activity.

Methotrexate has long been used as an acceptable conservative treatment for tubal ectopic pregnancy in single- and multiple-dose protocols.[15,16] The efficacy of methotrexate (a folic acid antagonist well studied in the treatment of cervical ectopic pregnancy) has been examined by Kung et al.[17] In this meta-analysis, 62 cases of cervical pregnancy treated with methotrexate were culled from the literature. Although there was no standard protocol of methotrexate used, successful cases required concomitant surgical debulking with either dilation and evacuation, hysteroscopic resection, or local injection with methotrexate in combination with systemic therapy. This study estimated the efficacy of systemic methotrexate administration to be approximately 91% in the treatment of cervical ectopic pregnancy.[11] In a similar meta-analysis, Hung et al[17] examined 42 reports of cervical pregnancies treated with methotrexate. Gestational age greater than 9 weeks, hCG levels above 10,000 mlU/mL, crown–rump length greater than 10 mm, and fetal cardiac activity were associated with increased chance of primary failure. Intra-amniotic injection in combination with systemic methotrexate seemed to increase the chance of successful treatment. Nevertheless, there is no clear recommendation about the optimal dosage or route of administration.[14]

The use of curettage followed by locally acting hemostatic agents provides another alternative therapy. Flystra et al[9] reported two cases in which precurettage vasoconstriction was obtained with local injection of vasopressin and cerclage. A Foley balloon was placed postoperatively to mechanically tamponade the operative site. Cervical stay sutures have been described as an additional method of cervical tamponade.[18] There have also been reports of hysteroscopy used in the visualization of cervical pregnancy prior to resection.[19,20]

Uterine artery ligation and uterine artery embolization (UAE) have been used as adjunctive techniques to control hemorrhage from curettage procedures.[21] Kung et al[11] reported a series of six patients treated with laparoscopic uterine artery ligation and hysteroscopic resection of cervical pregnancy. Honey et al[22] reported the case of a patient with cervical pregnancy treated with local KCl injection and UAE who later became septic and required a hysterectomy. Trambert et al[23] reported a series of eight patients who presented with vaginal bleeding and cervical pregnancy. These patients were treated successfully with UAE followed by intracervical or systemic methotrexate. Fetal cardiac activity prolonged the time to resolution. There was a 75% chance of delayed bleeding after the procedure. Cosin et al[13] reported using UAE to control bleeding with success after local injection of methotrexate. Suzumori et al[24] reported the use of UAE to preserve the uterus of a woman who failed methotrexate combined with cervical cerclage. Complications after UAE included infection, uterine infarction, sciatic nerve injury, and necrosis of the bladder or rectum.[13,23]

Although the potential complications of cervical pregnancy primarily involve hemorrhage, the impact on future fertility is largely unknown due to the rarity of cervical pregnancy and the infrequency with which women are observed posttreatment. There are several reports of successful live births after conservative management of cervical pregnancy.[11,20,25] In a review of 120 published cases of cervical pregnancy, Ushakov et al[7] found 34 pregnancies identified after conservative management of cervical pregnancy. However, there are also reports of cervical incompetence requiring cerclage. Due to the low incidence of cervical pregnancy, pregnancy rates after treatments are relatively unknown. It is also unclear if there is an increased risk of recurrence.

In summary, although many treatment approaches have been advocated, the optimal treatment of cervical ectopic pregnancy is largely unknown. There are many case reports of conservative treatment, using a combination of modalities. It seems reasonable to treat these pregnancies with a combination of surgical removal familiar to the operator and chemotherapy. A plan for emergent attainment of hemostasis such as UAE or local tamponade is also necessary.

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