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Heterotopic Intrauterine and Cervical Pregnancy: Case Report and Literature Review

Ka Wai Ng 1# , Bai-zhou Chen,1# , Kai-di Tao1# , En-de Ni2, Ting-ting Xiang3, Teng-fei Long3*

¹Zhongshan School of Medicine, Sun Yat-sen University, Yuexiu District, Zhongshan 2nd Road, No.74, Guangzhou, China
²Department of Pathology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Yuexiu District, Yanjiang West Road, No.107, Guangzhou, China
³Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Yuexiu District, Yanjiang West Road, No.107, Guangzhou, China

#The authors contributed equally to this work.

*Corresponding author

*Teng-fei Long, PhD, MD, Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Yuexiu District, No.107 Yanjiang West Road, Guangzhou 510120, China.

Abstract

Objective: Heterotopic intrauterine and cervical pregnancy is a rare but life-threatening gynecological condition. Given that there are no protocols for the management of heterotopic intrauterine and cervical pregnancy due to its rarity, we presented our three cases of heterotopic intrauterine and cervical pregnancy, and further conducted a literature review, aiming to figure out the most effective treatment approach.

Case Report: Both case 1 and 2 underwent surgical removal of both intrauterine and cervical pregnancies after prior uterine artery embolization, while case 3 underwent cervical pregnancy reduction by manual forceps evacuation, and a healthy male baby weighing 3350 g was delivered by elective cesarean section at 39+3 weeks of gestation. For all the three cases, no significant post-operative adverse events were found.

Conclusion: Individualized surgical approach based on the patient’s condition is the preferred treatment for patients with heterotopic intrauterine and cervical pregnancy.

Keywords: Cervical pregnancy; Heterotopic pregnancy; Hysteroscopic resection; Manual forceps evacuation; Transvaginal ultrasound examination; Vacuum aspiration

Introduction

Cervical pregnancy is rare in pregnancies with an occurrence of 1:1,000-95,000, representing less than 1% of all ectopic pregnancies[1]. Misdiagnosis or improper handling of cervical pregnancy can result in hemorrhagic shock, which requires hysterectomy or arterial embolization to save patients’ lives. Twin pregnancies contribute to 3% of the births while experiencing more morbidity and mortality than singleton pregnancies[2]. Twin pregnancy of cervical pregnancy and intrauterine pregnancy is rarely reported and easily misdiagnosed, making it difficult for clinicians to figure out a more satisfactory and safer treatment. Currently, there are no clinical guidelines for heterotopic intrauterine and cervical pregnancy.

In this case report, we present three cases of heterotopic intrauterine and cervical pregnancy, one by spontaneous fertilization, two by assisted reproductive technology in-vitro fertilization and embryo transfer (IVF-ET). We aim to figure out the indications for pregnancy-preserving treatment and provide experiences for clinicians through our cases to maximize the benefits of patients.

Case Presentation

Case 1

With the clinical manifestations, the β-hCG level and the ultrasound examination result, theheterotopic intrauterine and cervical pregnancy was considered as the diagnosis.Surgical termination of pregnancy was established according the patient’s requirement. To prevent life-threatening haemorrhage during the surgery, prior uterine artery embolization was carried out using the granular gelfoam, and 50 mg of methotrexate (MTX) was injected in the cervix. Hysteroscopic resection was performed 2 days later to remove both the intrauterine and cervical pregnancy. Postoperatively, 10 IU of oxytocin was injected into the cervix to facilitate hemostasis. The operation was successful. Histopathological examination results verified the decidua and chorion in excision (Fig. 1E-H). Her β-hCG levels were 35922.09 IU/L and 4244.61 IU/L respectively 1 day before and 1 day after the operation.The patient had a well off recovery, postoperative condition is described in Supplemental Material (Section: Case 1 -General information & Treatment - Outcome).

Case 2

A 39-year-old woman, gravida 3, abortion 2, presented to our center with amenorrhea for 45 days, vaginal bleeding and mild lower abdominal pain for 4 days. She had a history of IVF with two embryos transferred 28 days ago for her primary infertility. Her gynecological history included an abdominal myomectomy 12 years ago and a diagnostic curettage for endometrial polyp last year. Her obstetric history included two spontaneous abortions during early pregnancy. Her blood group was Rhesus B negative.

On speculum examination, about 300 ml of blood was found in the vagina, and the appearance of cervix was normal, with a closed external os.

Laboratory examination revealed the serum β-hCG was 93043.43 IU/L, and the serum progesterone was more than 42.60 μg/L. Transvaginal ultrasound examination revealed two visible gestational sacs (Fig. 2A-D), detailed information as shown in Table 1.

With the clinical manifestations, the β-hCG level and the ultrasound examination result, the heterotopic intrauterine and cervical pregnancy was considered as the diagnosis. Uterine artery embolization was performed, followed by an intramuscular injection of 300 μg Rho(D) immune globulin. Segmental aspiration of cervix and uterine cavity was then performed 2 days later, followed by an injection of 20 IU oxytocin into the cervix after the aspiration. Operation went smoothly and the histology verified the decidua and chorion in excision (Fig. 2E-H). Her β-hCG was 23856.61 IU/L 1 day after the operation. The patient had a well off recovery, postoperative condition is described in Supplemental Material (Section: Case 2 - General information & Treatment - Outcome).

Case 3

A 36-year-old woman, gravida 1, presented to our center with amenorrhea for 52 days. She had a history of IVF with two embryos transferred 35 days ago. Her previous menstrual cycle was normal. Both her gynecological and obstetrics history were unremarkable, except primary infertility was indicated.

Transvaginal ultrasound examination revealed two visible gestational sacs (Fig. 3A,B), detailed information as shown in Table 1.

Table 1: Sonographic information of the three cases’ gestational sacs

Two days later, she developed vaginal bleeding without obvious cause. On speculum examination, a moderate amount of blood was found in the vagina, and a dilated externalos was visualized with a tissue about 1cm×2cm incarcerated inside. On laboratory examination, the serum β-hCG was 172621.88 IU/L, and the serum progesterone was more than 42.60 μg/L.

With the clinical manifestations, the β-hCG level and the ultrasound examination result, the heterotopic intrauterine and cervical pregnancy was considered as the diagnosis. Selective termination of the cervical pregnancy but preserving the concurrent intrauterine pregnancy was preferred. Manual forceps evacuation of the cervical pregnancy was performed, with the following histology showed the excision included decidua and chorionic villus (Fig. 3C,D). The serum β-hCG levels were 164164.06 IU/L and 172621.88 IU/L respectively 2 days before and 1 day after the evacuation. However, vaginal bleeding persisted and remained no signs of remission 1 week after the surgery, and an abnormal echo in the cervix was revealed by the transvaginal ultrasound examination, suggesting the possibility of the retained materials from the cervical pregnancy. Therefore, 8 days after the first manual forceps evacuation, a second manual forceps evacuation with the aim to remove the persistent trophoblastic materials was carried out. The operation went smoothly and the following histology showed the excision was the residue from the pregnancy (Fig.3E,F). On laboratory examination, the serum β-hCG levels were 179835 IU/L and 207773.98 IU/L respectively 9 hours before and 4 days after the second evacuation.

The patient had a well-off recovery. The cervical pregnancy was successfully removed with the preservation of the intrauterine embryo. Regular obstetric follow-ups were done for the intrauterine pregnancy, and a healthy male infantweighting 3350 g was delivered by cesarean sectionat the 39+3weeks of gestation. Her serum β-hCG had been monitored from 10 days after the ET to 4 days after the second manual forceps evacuation, the trend as shown in Fig. 4.

Table 2: Review of literature

Discussion

Currently, no protocols have yet been published on heterotopic intrauterine and cervical pregnancy. Treatment decision on whether to preserve the intrauterine pregnancy should be based on the patient's wishes, maternal life safety consideration and whether the intrauterine pregnancy can survive.

Provided that the preservation of the intrauterine pregnancy is not required or possible, the focus of treatment is on how to avoid uncontrollable hemorrhage during pregnancy removal. Preoperative uterine artery embolization is the most used approach, as practiced in case 1 and 2. However, ischemia induced by occlusion of uterine artery may cause inflammatory responses and local necrosis[3]-5], which in turn poses potentially adverse effects on the endometrium and ovaries. For patients who desire future pregnancies, transvaginal ligation of the cervicovaginal branches of the uterine artery maybe a feasible alternative. Injection of oxytocin into the cervix postoperatively is also a recommended approach to facilitate hemostasis, as practiced in case 1 and 2.

To preserve the intrauterine pregnancy, no conclusions have yet been reached on the best treatment approach to date. Generally, higher serum β-hCG and progesterone levels generally reveal higher viability of the intrauterine embryo[6]-[8]. Moreover, an intrauterine gestational sac with size that matches the theoretical gestational age, a gestational-age-appropriate CRL, and a fetal pole with cardiac activity visualized on ultrasound examination also suggest a better development embryo, which favor the intrauterine pregnancy preservation.

Literature review of heterotopic intrauterine and cervical pregnancy are presented in Table 2. A variety of treatment approaches of heterotopic intrauterine and cervical pregnancy had been described in the literature, which can be classified mainly into pharmacological and surgical treatment.

Pharmacological treatment appears to be the most commonly used method for selective termination of cervical pregnancy from the existing case reports. Common methods include injection of potassium chloride[9--[13], high-concentration sodium chloride[14], hyperosmolar glucose[15] or absolute ethanol[16] into the ectopic embryo sac under ultrasound guidance. Although there had also been reports[13]],[17]of methotrexate used, it is not recommended as local absorption into the blood may still have teratogenic effect on the persistent intrauterine embryo. Although pharmacological treatment has the advantage of being less invasive, complications such as long-term ectopic pregnancy mass rupture[10]-[13],[15], local infection and subsequent intrauterine infection may occur due to the unabsorbed tissue from the cervical pregnancy. Therefore, pharmacological treatment is not yet a satisfactory treatment approach.

Surgical treatment is a more effective approach for heterotopic intrauterine and cervical pregnancy. Common surgical methods include vacuum aspiration[18],[22], curettage[22],[23], manual forceps evacuation[24],[25], hysteroscopic resection[26],[27], etc.[28],[29]However, no specific surgical method can be recognized as the best. At the earliest stages of cervical pregnancy, especially when the cervical sac is still a fluid sonolucent area in sonography, vacuum aspiration is an ideal method as it poses only little mechanical stimulation to the cervix. When the cervical sac develops and becomes larger, curettage is a more feasible method to resolve the cervical pregnancy; hysteroscopic resection is also an ideal method, with the advantages of direct vision and thorough removal of cervical pregnancy, but these two methods may pose greater mechanical stimulation to the cervix. When the cervical sac becomes much larger or the implantation site of the cervical sac is low enough to cause spontaneous opening of the external cervical os, manual forceps evacuation is preferential. In case 3, the external cervical os had opened, and the cervical sac could be seen through the external os. Therefore, manual forceps evacuation, as a direct, economical method, and most importantly, the method that could induce the least stimulation to the uterus in this situation, was the best treatment option. Our experience also suggests that the presence of retained trophoblast materials may lead to persistent vaginal bleeding, which requires prompt examination and treatment. Uterine artery embolization is not suitable for hemostasis in pregnancy-preserving treatment as ionizing radiation emitted during angiography may affect the intrauterine pregnancy. In addition, progesterone and uterine contraction inhibitors can be used to support the intrauterine pregnancy after the removal of cervical pregnancy.

Previous study[30] suggested that surgical treatment does not increase the miscarriage rate, it is the timing of treatment that affects the live birth rate. In our opinion, treatment at an earlier gestational age reduces the needs of invasive procedure, thereby reduces the risk of uterine contractions and subsequent miscarriage of the intrauterine pregnancy. Hence, the importance of ultrasound and serum β-hCG examination should be emphasized. An accurate and early diagnosis based on ultrasound and serum β-hCG can prompt treatment to increase the possibility of preserving the concurrent intrauterine pregnancy.

In conclusion, surgical removal of cervical pregnancy is preferred for heterotopic intrauterine and cervicalpregnancy patients who wish to preserve the intrauterine pregnancy, but patient-based risk balance is required.

Statements & Declarations

Acknowledgments:

Not applicable.

Conflicts of Interest and Funding/Support Statement:

The authors have no conflicts of interest relevant to this article.

Ethics Approval and Consent to Participate:

This study was performed in line with the principles of the Declaration of Helsinki.Approval was granted by the Ethics Committee of Sun Yat-sen Memorial Hospital of Sun Yat-sen University (2023.02.01/NoSYSKY-2023-078-01).Informed consent was obtained from all individual participants included in the study.

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