Expectant management of a cornual pregnancy followed up by serial transvaginal color power Doppler angiography and serum beta human chorionic gonadotropin levels

Abstract

Cornual or interstitial pregnancy is a rare type of ectopic pregnancy that accounts for only 2–4% of all ectopic implantations (1). Because of the thin myometrium surrounding the cornual gestation, sudden rupture and profuse bleeding make it a potentially life-threatening condition (2). Surgical treatment using either cornual resection or hysterectomy has been the traditional therapy for women with cornual pregnancies. By using the high resolution of transvaginal sonographic techniques, however, early diagnosis of cornual pregnancy is possible and conservative treatment of unruptured cornual pregnancies with methotrexate has become safer (3). With the routine monitoring of serum beta subunit human chorionic gonadotropin (β-hCG) and the new technique of power Doppler angiography to evaluate the vascular status, further conservative management options such as expectant management should be considered. A 36-year-old Asian woman, gravida 3, para 1, presented to our outpatient clinic complaining of persistent vaginal bleeding for 2 months. Mild abdominal tenderness accompanied the vaginal bleeding. The patient had had a left salpingectomy 3 years prior to admission due to an ectopic gestation. Since then, she had experienced 3 years of infertility prior to this visit. Her infertility work-up consisted of a hysterosalpingogram 1 year prior to this visit, and revealed proximal occlusion of the left tube and distal occlusion of the right tube. A urine pregnancy test was performed and showed a positive result. A quantitative serum determination of the β-subunit of human chorionic gonadotropin (β-hCG) revealed a β-hCG level of 1627 mIU/mL. The hemoglobin level was 11.7 g/dL. Pelvic examination revealed an anteverted uterus that was mildly enlarged and palpable tenderness of the right fundus. No adnexal mass was detected. Transvaginal ultrasound using an Aloka SSD-5000 scanner (Aloka Ltd, Tokyo, Japan) equipped with a 5-MHz vaginal probe capable of color power angiography and pulsed wave Doppler revealed an empty uterus with no evidence of a gestational sac within the endometrium. However, an eccentric nonhomogeneous mass measuring 3.6 × 2.9 cm in diameter was identified in the right cornual region (Fig. 1). Furthermore, an echogenic line that must be the endometrium was visualized abutting the center of the mass. Only a little fluid was noted in the cul-de-sac area. Color power Doppler angiography demonstrated prominent and chaotic aberrant blood vessels surrounding the ectopic cornual mass (Fig. 2), with low impedance and high diastolic blood flow velocity (resistance index 0.329), which were compatible with normal subtrophoblastic flow. A diagnosis of right-sided cornual pregnancy was made. Owing to the heterogeneous changes in the cornual mass without a gestational sac, a nonlive or “missed” unruptured ectopic gestation was diagnosed. An eccentric nonhomogeneous mass (arrow) was identified in the right cornual region, measuring 3.6 × 2.9 cm in diameter. An echogenic line (arrowhead) was visualized abutting the center of the mass. The cornual ectopic pregnancy mass was surrounded by prominent and chaotic aberrant blood vessels by color power Doppler at the time of diagnosis. After counseling the woman about the risks of uterus rupture and the side-effects of methotrexate treatment, she decided to undergo expectant treatment instead of surgical or medical management for the ectopic pregnancy. Serial endovaginal color power Doppler imaging and serum β-hCG monitoring were performed weekly in the first 2 weeks on an outpatient basis, and then biweekly two times and finally monthly when the β-hCG level dropped to 166 mIU/mL, until 197 days after the initial visit. The serum β-hCG levels fell to 0.5 mIU/mL (Fig. 3). Regular menstrual cycles resumed while β-hCG levels decreased below 318 mIU/mL. Hemoglobin dropped to 5.8 g/dL during the fourth month of follow-up due to persistent vaginal bleeding. Iron supplementation was given. Nevertheless, persistent prominent peritrophoblastic blood flow was observed surrounding the cornual mass with low impedance and high diastolic velocity throughout the course of the follow-up until the β-hCG level fell to 61 mIU/mL (Fig. 4). The vascular supply gradually decreased until it was undetectable at 2 weeks after treatment (Fig. 5). The ectopic mass decreased progressively in size, and complete resolution occurred within 3 months after β-hCG levels had returned to nonpregnant levels. The patient's recovery was uneventful during the follow-up period. Changes in the serum β-hCG level during expectant management. The serum β-hCG level decreased gradually and had returned to the nonpregnant level by 197 days after the initial visit. The prominent power Doppler flow of the ectopic mass slowly decreased as the β-hCG level fell to 61 mIU/mL. The vascular supply of the ectopic mass underwent completely regression 2 weeks after the β-hCG level returned to the nonpregnant level. With expectant management, we did not have histologic evaluation to prove the diagnosis of cornual pregnancy in this case. Nevertheless, the sonographic findings of an empty uterus and a right-sided cornual heterogeneous mass with an echogenic line extending into the cornual region and abutting the midportion of the interstitial mass were highly reliable signs of an ectopic pregnancy. The sensitivity and specificity of the interstitial line sign were 80% and 98%, respectively, for the diagnosis of interstitial ectopic pregnancy. The results were better than the eccentric gestational sac location sensitivity and specificity of 40% and 88%, respectively, and the myometrial thinning sensitivity and specificity of 40% and 93%, respectively (4). Furthermore, power Doppler examination showed increased vascularities with low impedance and high diastolic velocity in the cornual region, which are compatible with normal subtrophoblastic flow (5), providing additional information for the diagnosis of cornual gestation. Color power Doppler angiography, which is sensitive to slow flow, makes it possible to delineate the individual vessels of an anomalous vascular supply and its arborization pattern even in a very low flow vessel (6). Thus, color power Doppler angiography allows us to examine noninvasively uteroplacental and intervillous blood circulation of normal and abnormal pregnancies (7), which is especially useful in an ectopic pregnancy. Uteroplacental blood flow studies are important for evaluating the progression and perfusion status of an ectopic mass, and it is helpful to determine the success of the expectant management. The gradual decline of the prominent flow in power Doppler imaging and continuous fall in β-hCG levels in patients with unruptured ectopic pregnancies can be interpreted as evidence of a nonviable gestation that is in the process of spontaneous resolution. Furthermore, the important information of the power Doppler angiography in this case was that although the serum β-hCG level had declined to an undetectable level, the risk of uterine rupture with profuse hemorrhage still existed. Because of the presumed diagnosis of cornual ectopic pregnancy and to preserve the fertility of the patient, conservative treatment was requested by the patient. After explaining the risk of hemorrhagic shock and the possibility of hysterectomy to the patient if the conservative treatment failed, expectant management was performed. Although the success rate for conservative treatment is high (8, 10), hysterectomy is necessary in almost 50% of cornual pregnancies (2), and especially in a patient with hemodynamic instability or in one considering the risk for another future cornual pregnancy as our patient was “sterile” according to previous surgery and findings at hysterosalpingography. Although there are several conservative techniques available to preserve the fertility of the patient, the risks of uterine rupture on a subsequent pregnancy during advanced pregnancy or labor are great (1). Methotrexate administration has been successfully applied in patients with cornual pregnancies with an overall success rate of 83% (8); however, it may cause some side-effects. Expectant management is the only treatment that neither increases the risk of uterine rupture on future gestation nor induces drug-related side-effects. The concept of expectant management was first reported by Lund in 1955 (9). He randomized patients to receive expectant management or surgical treatment of ectopic pregnancies. Spontaneous resolution occurred in 57% of 119 patients. The most important advantage of expectant management is to decrease the rate of invasive treatment in certain patients. Nowadays, with carefully selected cases, the entry criteria for expectant management should include ectopic pregnancy of less than 5 cm in diameter with no signs of rupture or intraperitoneal hemorrhage, and a decreasing or stable β-hCG level (10-13). The success rate in the selected studies ranged from 64 to 100%. However, when the starting β-hCG level was <2000 mIU/mL, 60% of patients had success with expectant management, whereas 93.3% of patients with an initial β-hCG level of >2000 mIU/mL failed expectant management (13). The patient was defined as a failure of expectant management when she was symptomatic, had a β-hCG plateau or rise after an initial decrease, had an appearance and increase of fluid in the cul-de-sac, or had an increasing ectopic mass on serial ultrasound examinations (11-13). In our opinion, increased vascularities in the ectopic mass under power Doppler angiography after an initial decrease should be added as another indication of failure of expectant management because it probably means that recirculation and progression of the subtrophoblastic flow has occurred, which may increase the possibility of cornual rupture. Surgical or medical treatment is required to terminate the ectopic pregnancy if there is a failure of expectant management. The disadvantages of expectant management are slow decline of serum β-hCG levels, slow resolution of the ectopic mass and slow involution of the rich blood flow within the surrounding lacunar structure. The patients have to undergo long-term observation, such as was the case with our patient who had 211 days follow-up in our outpatient clinic. The patient thus has to have great patience and close cooperation with the physician so that appropriate management can be performed immediately if the expectant management fails. Furthermore, the financial cost of the long-term follow-up is high and might be considered clinically unacceptable, but may well yield less loss of overall fertility and even cost less over the reproductive life of the patient (10). In conclusion, this case has demonstrated the possible application of power Doppler angiography in evaluating vascular morphologic patterns of interstitial pregnancy during the follow-up period of expectant management. Expectant management with serial color power angiography and serum β-hCG titer monitoring has shown a high rate of success in selected cases. The greatest benefit of this mode of treatment was the avoidance of the use of an invasive treatment procedure. Finally, we agree with the opinion of Gorbman and Milad (14) that expectant management should not be used for patients with large cornual pregnancies, which are prone to catastrophic rupture and massive intraperitoneal hemorrhage. However, it may be effective for cornual ectopic gestations that are smaller than 5 cm in diameter and serum β-hCG levels <2000 mIU/mL.