Multimodal Conservative Management of Nulliparous Female with Cervical Ectopic Pregnancy: A Case Report

Introduction

Cervical ectopic pregnancy is an extremely rare subtype of ectopic pregnancy, accounting for approximately 1% of all ectopic pregnancies, and occurs in approximately one in 1000 pregnancies [¹,²]. Various risk factors have been identified, including previous endometrial or cervical surgeries, aggressive dilatation and curettage, intrauterine device use, and $\geq$ 2 cesarean sections. Prior ectopic pregnancy, chromosomal abnormalities, and in vitro fertilization are also considered risk factors. Despite these known risk factors, cases involving nulliparous women without any predisposing factors have been reported [³,⁴,⁵,⁶,⁷].

Early diagnosis of cervical ectopia is mandatory due to the risk of catastrophic vaginal bleeding, which may necessitate hysterectomy [¹]. Transvaginal ultrasound, often supplemented with 3D imaging, is the gold standard for distinguishing cervical abortion from cervical ectopic abortion. Key distinguishing features include an empty endometrium, the presence of the gestational sac within the cervical canal, a closed internal os, a partially opened external os, peritrophoblastic blood flow visualized by colour Doppler, and a negative sliding test of the gestational sac against the cervical canal, which is positively observed in cases of cervical abortion [⁸,¹,⁹].

Many treatment modalities exist, but none have been proven to be superior to the others. These modalities include intramuscular methotrexate injection, either as a single dose or in a multidose regimen. Additionally, options such as ultrasound-guided injection of potassium chloride alone or in combination with local methotrexate into the conceptus, followed by dilatation and evacuation, with or without dilute vasopressin cervical infiltration, and either ultrasound or hysteroscopic-guided evacuation, followed by Foley catheter placement or cerclage acting as a tamponade, are available. Laparoscopic resection and uterine artery embolization followed by evacuation are also viable options [⁹,²]. Methotrexate injection alone can be ineffective in patients whose beta-hCG concentration exceeds 10,000 IU/L and/or whose gestational age is greater than 9 weeks. Multimodal conservative management, which involves more than one line of treatment, is a relatively new area with satisfactory results, especially in young, stable, nulliparous patients, where preservation of fertility is a primary concern [¹⁰,⁸,¹¹].

In this case report, we present a unique case of cervical ectopic pregnancy in a 22-year-old nulliparous female, highlighting the challenges in diagnosis and management, as well as the utilization of multimodal conservative treatment approaches to preserve fertility and achieve favorable outcomes.

Case presentation

A 22-year-old nulliparous female patient at 8 weeks of gestation presented to our outpatient clinic at El Shatby Maternity Hospital (a tertiary referral center in Alexandria, Egypt) on February 6, 2024. She was referred by her private doctor to our hospital after the diagnosis of cervical ectopic pregnancy and received two doses of intramuscular methotrexate 2 days a day. $\beta$hCG levels of 43,000, 61,000, and 57,000 mIU/mL on January 25, January 28, and February 4, 2024, respectively. The initial 42% rise (43,000$\rightarrow$61,000 mIU/mL) indicated methotrexate resistance, while the subsequent 7% decline (61,000$\rightarrow$57,000 mIU/mL) showed minimal treatment response, necessitating alternative management. Ultrasound imaging was performed at our specialized ultrasound unit, confirming the diagnosis of a viable ectopic pregnancy at 8 weeks of gestation. The scan revealed a gestational sac with a pulsating fetal pole surrounded by peritrophoblastic vascularity, an empty uterus, a closed internal os, and a free adnexa (Figure 1, Figure 2, Figure 3). The patient was admitted to the ward, where she underwent thorough general and local examinations, which revealed only minimal painless vaginal bleeding. Vital signs on admission were stable: blood pressure 120/75 mmHg, heart rate 82 bpm, temperature 36.8$^\circ$C. The complete blood count showed a hemoglobin level of 12.1 g/dL and a hematocrit of 36.2%. A comprehensive pelvic ultrasound excluded other ectopic sites. No comorbidities were identified.

The laboratory results were unremarkable. Following consultation with ultrasound specialists, the diagnosis was confirmed, and a consensus was reached to pursue multimodal conservative management due to the patient’s young age, nulliparity, and stable general condition. The decision was discussed with the patient, and informed consent was obtained.

Discussion

Ectopic cervical pregnancy (CP) results from the implantation of a fertilized ovum in the endocervical canal below the level of the internal os, with a reported incidence of less than 0.01% of all pregnancies [¹²]. Risk factors include cervical and uterine abnormalities, prior procedures such as curettages or cesarean sections, smoking, tubal infertility, or IVF treatments [¹³]. Asymptomatic patients often seek medical attention due to significant painless vaginal bleeding. Despite advancements in diagnostic modalities and reductions in current maternal mortality rates, CP remains a life-threatening condition [¹⁴]. The defined criteria for diagnosing cervical pregnancy: uterine bleeding without cramping pain following a period of amenorrhea, disproportionately enlarged soft cervix equal to or larger than the fundus (hourglass appearance), products of conception entirely within and firmly attached to the endocervical canal, a closed internal os, and a partially opened external os [¹⁵]. According to Ushakov et al., transvaginal ultrasound (TVS) has 87.5% diagnostic accuracy, with MRI serving as a viable alternative in some instances [¹⁶]. Differential diagnosis may confuse cervical pregnancy with spontaneous abortion if pregnancy tissue is detected within the cervical canal [¹]. In our patient, ultrasonography confirmed all diagnostic criteria, obviating the need for further tests. In contrast, spontaneous abortion typically involves an open internal os, absence of elongation or enlargement of the cervix, bleeding accompanied by pain, and the presence of blood or remnants inside the endometrial cavity [¹⁷].

Treatment approaches for cervical pregnancy vary. Methotrexate may suffice for patients with mild symptoms, while curettage is often preferred for those experiencing vaginal bleeding. In life-threatening situations, a hysterectomy becomes necessary [¹⁸]. Patients should be educated about the risks of future ectopic pregnancy and spontaneous abortion due to potential cervical insufficiency. The conservative management of cervical ectopic pregnancy encompasses various treatment modalities, none of which have been proven to be superior to the others. Options include intramuscular methotrexate injection, ultrasound-guided injection of potassium chloride alone or in combination with local methotrexate, and dilatation and evacuation with or without dilute vasopressin cervical infiltration. Additionally, hysteroscopic-guided evacuation, Foley catheter placement, cerclage, laparoscopic resection, and uterine artery embolization are available options depending on the clinical scenario [⁹,²]. In our case, repeated local methotrexate injections were not considered optimal due to the high $\beta$-hCG level (57,000 mIU/mL), which correlates with treatment failure rates $>$80% for single-agent therapy. Multiple injections would increase the risk of cervical necrosis and delay definitive treatment. Uterine artery embolization, while effective, was not readily available at our institution and would incur significantly higher costs with the need for specialized interventional radiology expertise [¹³].

Foley catheter placement and cerclage are only viable after dilatation and evacuation. In our case, the patient underwent a multimodal conservative approach, including local potassium chloride and methotrexate intrafetal injection followed by dilatation and evacuation. Despite initial successful management with the injection, the patient experienced severe vaginal bleeding after two days, necessitating further intervention with dilatation and evacuation, and cerclage placement for hemostasis [¹⁹]. When acute bleeding occurred, immediate source control was prioritized. D&E was selected over conservative management due to the urgent need for trophoblastic tissue removal, as retained products would perpetuate haemorrhage. The addition of cervical cerclage provided an immediate tamponade effect while preserving uterine anatomy. Hysterectomy would have eliminated fertility potential, and continued expectant management posed unacceptable risks of life-threatening haemorrhage in this young nulliparous patient [⁴].

Fortunately, the bleeding was controlled, and the patient’s condition stabilized without the need for hysterectomy. Multimodal conservative management is increasingly recognized as a viable approach for select patients with cervical ectopic pregnancy, particularly young, stable nulliparous women who desire to preserve fertility. However, it is essential to recognize the limitations of conservative management, especially in patients with high beta-hCG levels or advanced gestational age, for whom surgical intervention may be necessary to prevent life-threatening complications [²⁰].

Conclusion

Fertility preservation is the most challenging point when dealing with cervical ectopic pregnancy, especially in young nulliparous women. However, the best way to manage cervical ectopic pregnancy has not yet been confirmed, and multimodal conservative management can be an effective method. Close follow-up is mandatory, as catastrophic sequelae can occur if timely management of complications is not appropriate.