Twin interstitial ectopic pregnancy following ipsilateral tubal pregnancy: a case report

Abstract

Background

Interstitial pregnancy has an estimated maternal mortality rate seven times greater than the mortality rate for ectopic pregnancies in general. For this reason, early diagnosis is the key to successful treatment and favorable outcomes in patients with this type of ectopic pregnancy. We report the rare case of a Portuguese white woman with a spontaneous twin interstitial pregnancy with embryonic cardiac activity, its diagnosis, and surgical management, as well as a literature review on the specificities of this scenario.

Case presentation

A Portuguese white woman in her early forties presented at our hospital for early pregnancy assessment 3 months after having got a salpingectomy for a tubal pregnancy. Transvaginal ultrasound revealed an empty uterine cavity and an eccentric gestational sac within the uterine serosa, containing two yolk sacs and two embryonic poles with cardiac activity. These findings were suggestive of a twin interstitial pregnancy. A cornuostomy was performed, using proximal uterine artery clipping and a purse-string suture around the cornual area as hemostatic measures. No surgical or postoperative complications occurred.

Conclusions

Twin tubal pregnancy is a rare occurrence, particularly in spontaneous gestations. Although interstitial pregnancies are more common after ipsilateral salpingectomy, early diagnosis is challenging. The best therapeutic approach is yet to be determined, but surgery, when indicated, offers a definitive treatment. Cornuostomy presents the advantage of removing the ectopic pregnancy while preserving uterine architecture and maintaining fertility. This case report states the relevance of early pregnancy assessment in women with risk factors for ectopic pregnancy. If performing surgery as treatment, it is advisable to adopt less invasive approaches such as cornuostomy. Also, one cannot forget the importance of maintaining a good hemostasis, considering the bleeding potential associated with this type of pregnancy.

Background

Interstitial pregnancy refers to an ectopic pregnancy implanted in the proximal or interstitial tubal segment crossing the myometrium, including cases of implantation of trophoblastic tissue in the tubal stump after salpingectomy [1]. Interstitial pregnancies account for 2–4% of all tubal pregnancies [2, 3]. The incidence of ectopic pregnancies is generally increasing, but there also appears to be a concurrent increase in the proportion of interstitial pregnancies [4]. This increase is likely related to better diagnosis, ipsilateral salpingectomy, existing damage from previous ectopic pregnancy, use of assisted reproductive technologies (ART), and increased prevalence of pelvic inflammatory disease, with some of these being known risk factors for ectopic pregnancy in general [3, 5, 6].

Interstitial pregnancy has an estimated maternal mortality rate as high as 2.5%, which is seven times greater than the mortality rate for ectopic pregnancies [7]. The increased morbimortality is due to the risk of catastrophic hemorrhage. On the one hand, in the cornual area there are important vascular anastomosis between uterine and ovarian vessels, namely the arcuate vessels. On the other hand, compared with the other segments of the tube, the interstitial part has a significantly greater capacity to expand before rupture, contributing to the absence of symptoms until later, reaching a rate of uterine rupture of 20% in pregnancies that progress beyond 12 weeks [3, 8].

Due to technological advances, namely high-resolution transvaginal ultrasound and highly sensitive quantitative beta-human chorionic gonadotropin (β-hCG) assays, interstitial pregnancies can now be diagnosed as early as 6.9–8.2 weeks[3], particularly if there is a high index of clinical suspicion. Early diagnosis is the key to successful treatment and favorable outcomes in patients with this type of ectopic pregnancy [8].

We report the rare case of a spontaneous twin interstitial pregnancy with embryonic cardiac activity, its diagnosis and surgical management, as well as a literature review on the specificities of this scenario.

Case presentation

A healthy Portuguese white woman in her early forties (gravida 2, para 0) with an history of an uneventful right laparoscopic salpingectomy for tubal isthmic ectopic pregnancy 3 months earlier presented at our hospital for early pregnancy assessment. She was asymptomatic but had amenorrhea of 6 weeks and 4 days and a positive urine β-hCG test. No blood β-hCG assessment was performed.

She was hemodynamically stable, and physical examination was unremarkable. Transvaginal ultrasound revealed an empty uterine cavity and an eccentric gestational sac on the right side of the uterine fundus within the uterine serosa but separated from the endometrial cavity by a thin band of myometrium (Fig. 1). The gestational sac dimensions were in accordance with the last menstrual period. It contained two yolk sacs and two embryonic poles with cardiac activity. No amniotic membrane was observed (Fig. 2). These ultrasonographic findings were suggestive of a twin right interstitial pregnancy.

Fig. 1.

Transvaginal transverse scan of the uterus shows a right-sided (R) eccentrically located gestational sac separated from the endometrial cavity (E) by a thin band of myometrium (arrow), suggesting a right interstitial pregnancy

Fig. 2.

a Transvaginal scan revealing a gestational sac with two yolk sacs and two embryonic poles (asterisks), without visible amniotic membrane; b, c both embryos presented cardiac activity

After presenting the ultrasound findings to the patient, along with their implications, management options, and prognosis, treatment possibilities were discussed, namely expectant management, systemic methotrexate (MTX) administration, and surgical intervention. Given the presence of viable embryos, expectant management was excluded. Although there were no contraindications to either medical or surgical treatment, only systemic MTX was considered as a medical therapy, as our center has no experience with local administration. However, the presence of embryonic cardiac activity, which is known to reduce the effectiveness of MTX, along with the patient’s preference for a definitive, fertility-sparing approach, led to the decision for surgical treatment.

With the patient under general anesthesia, a four-port laparoscopy with optic trocar entry was performed 1 day after hospital admission. During inspection, an unruptured bulging mass of approximately 25 mm was visualized in the right uterotubal junction, supporting the diagnosis of interstitial pregnancy (Fig. 3). After confirming the location of the pregnancy, a uterine manipulator was inserted. Proximal temporary bilateral uterine artery clipping was performed (Fig. 4) and a 1–0 polyglactin suture was passed around the right cornual area, proximal to the ectopic pregnancy, in a purse-string fashion, which was tightened with an extracorporeal knot. Afterwards, a cornuostomy was performed: a full-thickness linear incision along the cornual mass and distal to the suture was made with a monopolar hook, allowing the removal of the trophoblastic material without entering the endometrial cavity. Bleeding was controlled with scarce use of bipolar cauterization, and the edges of the cornuostomy were sutured with a one-layer 1–0 polyglactin thread. An absorbable adhesion barrier was placed above the suture, and the uterine artery clips were removed. Blood loss during the procedure was estimated around 100 mL. The patient was discharged on the second postoperative day. Adjunct treatment was not necessary, and the patient was asymptomatic 6 weeks after the surgery in the postoperative visit. Histological examination confirmed the diagnosis of interstitial gestation. One year after the diagnosis, the patient was still pursuing a spontaneous pregnancy.

Fig. 3.

Laparoscopic view of the bulging mass located over the right uterotubal junction

Fig. 4.

Temporary clipping of the left uterine artery at its origin

Discussion and conclusions

Regarding the designation of this kind of ectopic pregnancy, the indiscriminate use of the terms “angular” or “cornual” to refer to interstitial pregnancies should be abandoned since they are not synonyms, and their complication rates vary greatly. Angular pregnancy is not a clinical entity itself and refers to an eutopic pregnancy that is implanted in the upper lateral aspect of the uterine cavity [9], medial to the uterotubal junction. In parallel, the term “cornual” has been used inconsistently to describe both normally sited pregnancies in the lateral aspect of the uterine cavity and ectopic pregnancies, namely interstitial pregnancies or gestations located in the rudimentary horn of an unicornuate uterus, with the latter being the only one that should receive this designation [9, 10].

Here, we describe the case of a spontaneous unilateral twin pregnancy. This is a rare occurrence, and it has a calculated incidence of 1 in every 125,000 pregnancies [11]. Unlike our report, ART is the main reason for the increase in twin ectopic pregnancy in recent years, even though currently there are limited cases of twin ectopic pregnancies reported in the literature [12].

In our case, a single gestational sac containing two yolk sacs and two embryonic poles with cardiac activity was observed, consistent with a monochorionic twin pregnancy. Although the number of yolk sacs is sometimes used to infer amnionicity in early gestation, this marker is not always reliable [13]. Moreover, the absence of a visible amniotic membrane at this stage does not exclude diamnioticity, as sonographic identification may be delayed [14]. Therefore, while monochorionicity is confirmed, amnionicity cannot be definitively determined.

The diagnosis of interstitial pregnancy may be challenging, and it results from the combination of clinical suspicion, serum β-hCG assays, transvaginal ultrasound findings and eventually diagnostic laparoscopy.

A case report described a clinical scenario marked by diagnostic challenges, in which the patient’s elevated β-hCG levels did not correlate with the clinical presentation, and imaging findings were nonspecific for interstitial pregnancy [15]. Ultrasound revealed a heterogeneous mass near the ovary and Fallopian tube, while computed tomography (CT) showed no pathological changes in the uterus but identified a heterogeneous, vascularized mass in the ovarian region. Given the suspicion of ectopic pregnancy, diagnostic laparoscopy was performed, ultimately confirming the presence of an interstitial pregnancy. In contrast to our case, where the diagnosis was established preoperatively, this case highlights that the diagnosis is not always confirmed before surgery, increasing the uncertainty of both management and surgical planning.

Although not every interstitial pregnancy shows the classic characteristics with conventional ultrasound [16], there are three diagnostic criteria using this imaging method: the gestational sac being implanted outside the uterine cavity, the gestational sac being surrounded at least partially by myometrium, and being able to visualize the interstitial line sign [17]. This sign is based on the visualization of an intramural segment of the Fallopian tube adjoining the medial aspect of the gestational sac and the lateral aspect of the uterine cavity [18]. Even though most interstitial pregnancies expand into the isthmus of the Fallopian tube, some are confined to the interstitial tube and tend to be relatively small, making them more difficult to detect [9]. Rarely, these pregnancies spread out medially and eventually start to protrude into the upper lateral aspect of the uterine cavity, making them often very hard to differentiate from laterally implanted normally sited (angular) pregnancies [9].

Yi-Lin et al. [19] described a case in which three-dimensional (3D) ultrasound demonstrated a gestational sac located in the cornual region, clearly separated from the endometrial cavity. This proved highly valuable in establishing the diagnosis of interstitial pregnancy, particularly in a scenario where the relationship between the gestational sac and the uterus was difficult to determine using two-dimensional (2D) ultrasound. While conventional sonography remains the primary diagnostic tool for interstitial pregnancy, 3D ultrasound can play a crucial role in accurately identifying the location of the gestational sac. In our case, the diagnosis was achieved without the use of 3D imaging; however, it remains a valuable adjunct in cases where diagnostic uncertainty exists.

Some reasons have been pointed out to explain the increased prevalence of interstitial pregnancy following ipsilateral salpingectomy, particularly when they occur after a laparoscopic procedure. Firstly, when using this approach, the tube is removed using bipolar electrocauterization and scissors without suture or peritonization of the tubal stump. Consequently, the possibility of patency after salpingectomy cannot be excluded. This technique can also result in reduced blood supply and delayed healing at the uterotubal junction, inducing a higher frequency of recanalization or fistula at the tubal stump [20], promoting implantation in the remaining interstitial portion of the tube. Although less likely, other proposed mechanism by Ota et al., based on the anatomopathological findings of a case they reported, involves the occurrence of fertilization in the contralateral tube, followed by transperitoneal migration of the fertilized egg from the serosa into the interstitial portion of the tube before nidation [21]. Finally, the use of electrocoagulation causes local inflammation, with upregulation of inflammatory cytokines, promoting embryo adhesion and invasion of the uterine horn [22], particularly in case of recent surgery, as occurred in our case.

A decrease in the rate of subsequent ipsilateral interstitial pregnancy following salpingectomy may be achieved through performance of peritonization and cornual suture at the time of laparoscopic salpingectomy, in association with a decreased use of electrocoagulation [23]. However, the benefits of these procedures must be balanced since they are associated with increased operative time and surgical complexity.

The best therapeutic approach to interstitial pregnancy is yet to be determined. Expectant management is an option for asymptomatic patients with nonviable interstitial pregnancies and declining serum β-hCG levels, irrespective of ectopic mass size and initial serum β-hCG levels [8]. This approach should be abandoned in cases of clinical deterioration. Medical management is the first-line option for asymptomatic patients with an unruptured interstitial pregnancy, diagnosed by ultrasound early in the first trimester [3]. It includes the administration of MTX, both systemically (intravenous and intramuscular) or locally. Local MTX administration can be performed under ultrasound guidance. This technique is more invasive than systemic administration and requires special facilities and trained personnel, making it more operator-dependent, less widely available, and more costly than systemic MTX administration [4]. The main advantage of the local administration is the reduction of systemic side effects while maintaining its effectiveness.

Surgical management offers a definitive treatment. Usually, it is indicated in the presence of hemodynamic instability, significant symptoms, cornual rupture, large pregnancies, or heterotopic pregnancies [24]. Historically, hysterectomy and cornual resection by laparotomy have been used as the surgical treatment for interstitial pregnancy. Currently, considering a meta-analysis published by Marchand et al. [25], laparoscopy can be considered the first-line option in most cases since it is associated with less blood loss, less operative time, and shorter hospital stay compared with laparotomy. In fact, following the overall surgical trend, the technique is evolving to become less invasive, with laparoscopic cornual wedge resection or even cornuostomy being performed when possible. Cornual resection may carry the risk of uterine rupture in following pregnancies due to the loss of myometrium and extensive uterine scarring [4]. Recent studies favor cornuostomy over cornual resection [4], particularly in women with the desire for pregnancy, since it presents the advantage of removing the ectopic pregnancy while preserving uterine architecture and maintaining fertility [8], with fewer cases of subsequent uterine rupture. However, increased risk of persistent ectopic and recurrent interstitial pregnancy are reported with this technique [8]. The simultaneous use of prophylactic MTX may reduce the risk of persistent ectopic pregnancy, particularly in patients who have experienced rupture and high preoperative hCG levels [23]. However, cornual resection should be considered in cases of rupture with significant bleeding or in patients who do not desire pregnancy [8].

In this case, we decided to perform a laparoscopic cornuostomy with hemostatic control measures due to the presence of embryos with heartbeat and the desire for a subsequent pregnancy.

When treating an interstitial pregnancy surgically, blood loss is one of the main concerns because of the involvement of a highly vascularized area with high risk of rupture. Both the duration of amenorrhea and number of previous pregnancies appear to be risk factors leading to increased bleeding [25]. Several approaches have been described for hemostatic control during surgery. All techniques have both advantages and disadvantages, and they have been used either alone or in combination. There are currently no guidelines and there is no robust evidence stating the optimal approach, but the adoption of hemostatic control measures is essential to decrease patient morbidity [7]. These measures allow the performance of an adequate cornual repair with clear visualization without unnecessary tissue dissection, trauma, and electrocoagulation, which affect uterine integrity and future fertility [26]. In our case, we performed the bilateral reversible occlusion of the ascending branch of the uterine arteries and the purse-string suture together. The uterine artery clamping was firstly described as an effective bleeding control technique for laparoscopic myomectomy [27], and the rationale behind its use is the reversibility of the occlusion, which appears effective [26]. However, the circumferential purse-string suture, beyond its hemostatic purpose, has the intention of strengthening the uterine wall for the stress of a future pregnancy [28].

The meta-analysis by Marchand et al. [25] supports laparoscopy as the preferred surgical approach for patients with interstitial pregnancy. According to their findings, this technique was associated with an average blood loss of 168 mL and an average hospital stay of 3.7 days. In comparison, our case resulted in lower blood loss (100 mL) and a shorter hospitalization period (3 days). The study also emphasizes the need for further interventional research with larger sample sizes and longer follow-up periods to generate more robust and generalizable conclusions.

This case report highlights many aspects related to the approach in a rare type of ectopic pregnancy. Firstly, it shows the relevance of an early pregnancy assessment in women with risk factors for ectopic pregnancy, namely a previous ectopic pregnancy, which is the most important risk factor. Special attention should be paid if the treatment was surgical and performed recently, as occurred in this case. Although more likely after ART, when the diagnosis of ectopic pregnancy is established, the possibility of multiple ectopic pregnancies should be considered, trying to find all the probable ectopic foci. If performing surgery as treatment, whenever possible, it is advisable to adopt less invasive approaches such as cornuostomy, particularly in women with the desire for pregnancy. Finally, to decrease morbidity, one cannot forget the importance of maintaining a good hemostasis, considering the high bleeding potential associated with this type of pregnancy.

Abbreviations

ART

Assisted reproductive technologies

β-hCG

Beta-human chorionic gonadotropin

MTX

Methotrexate

2D

Two-dimensional

3D

Three-dimensional

Author contributions

MIS collected the data and was a major contributor in writing the manuscript. AA, SS, SS, and RM provided constructive discussion. LGM performed the ultrasounds, and RB performed the surgery. All authors read and approved the final manuscript.

Funding

The authors have not received any financial support and have no conflicts of interest to declare.

Availability of data and materials

Data sharing is not applicable to this article, as no datasets were generated or analyzed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.