Heterotopic Pregnancy

Abstract

Spontaneous heterotopic pregnancy is a rare clinical and potentially dangerous condition in which intrauterine (IU) and extra-uterine pregnancies occur at the same time. It can be a life-threatening condition and can be easily missed, with the diagnosis being overlooked. A high index of suspicion is needed in women with risk factors for an ectopic pregnancy and in low-risk women with an IU gestation who have free fluid with or without an adnexal mass or in those presenting acute abdominal pain and shock. The ectopic component is usually treated surgically and the IU one is expected to continue normally. Salpingectomy is the standard surgical approach of a coexistent tubal pregnancy and should be the first line of treatment in patients with hemodynamic instability or other signs of tubal rupture. In expert hands, an unruptured ectopic pregnancy can be treated with local feticidal injection under sonographic guidance.

1. Introduction

Spontaneous heterotopic pregnancy is a rare clinical but a potentially dangerous phenomenon where intrauterine (IU) and extra-uterine pregnancies occur at the same time. This is a life-threatening condition and can be easily missed, with the diagnosis usually being overlooked. A high index of suspicion is needed in women with risk factors for an ectopic pregnancy and in low-risk women with an intra-uterine gestation who have free fluid with or without an adnexal mass or in those presenting acute abdominal pain and shock. The ectopic component is usually treated surgically and the IU one is expected to continue normally if it is live.

Case: A 20-year-old woman, prime-gravid, was admitted to the gynaecology ward at 10 weeks of amenorrhea, with vaginal bleeding for 2 days, dyspnea and hypotension. Her pregnancy occurred spontaneously. Her past history did not suggest previous history of pelvic inflammatory disease, abortions, infertility or abdominal surgery or trauma. The physical examination revealed a conscious woman however with severe pallor of the palms, conjunctivae, mucous membranes of the buccal cavity and palms. She had hypotension of 75 mmHg systolic blood pressure, respiratory rate of 24 breaths per minute, SPO2 of 92%, cold sweat, and a thin thready rapid pulse of 136 beats per minute. Per abdomen did not suggest intra-abdominal haemorrhage as there was only moderate tenderness and no features of peritonism. Vaginal examination revealed active per vaginal bleeding with visible clots of fresh blood, products of conception hanging in the cervical canal. A clinical diagnosis of an incomplete abortion was made and patient was prepared for an emergency uterine evacuation, which was done with a blunt curettage and curetted plenty of products of conception. Laboratory evaluation showed a normal range white blood cell count, a haematocrit of 18% and haemoglobin concentration of 6.1 g/dL, with a normal blood platelet level (390,000/mm³), a blood urea of 44 mg/dL and a creatinine level of 1.09 mg/dL. The patient was admitted to the high dependency unit (HDU) after uterine evacuation with a continuous assessment of her airway, breathing and circulation and administration of 2.0 L of crystalloid fluids over the next 4 h. She was also given 3 units of whole blood. However her haemodynamic observations remained unstable and she developed features of acute abdomen including moderate abdominal distension with positive fluid thrill, severe tenderness with guarding and rigidity. An emergency bedside abdominal ultrasound scan (USS) was done, which demonstrated free intra-peritoneal fluid and an ill-defined right adnexal mass measuring 69.79 mm in diameter. The uterine cavity was however empty following uterine evacuation. These USS findings (free intra-peritoneal fluid and adnexal mass) in a hypovolemic-shocked patient with peritonism but no history of trauma made us think about the presence of a possible concurrent ectopic pregnancy that was not initially thought about. Also, the patient’s shock did not respond to fluid resuscitation with increasing abdominal distension. Repeat complete blood count revealed further fall in the patient’s haematocrit and haemoglobin concentration. The patient was thus prepared and taken to the operation theatre for an emergency exploratory laparotomy to establish and control the source of intra-abdominal haemorrhage. At laparotomy under general anaesthesia, through a sub-umbilical midline incision, revealed a ruptured right tubal gestation with active bleeding. At least 1.5 L of clots of fresh blood was evacuated from the peritoneal cavity right and left ovaries and the left tube were grossly normal. Total right tubal excision (salpingectomy) as shown in Figure 1, with suction of the haemoperitoneum and peritoneal lavage with saline water. Eight litres of whole blood was transfused to the patient during and after the operation. The patient recovered fully with no recorded complications. Both the tubal pregnancy and intrauterine pregnancy were confirmed at histological analysis of the salpingectomy specimen and endometrial curetting specimens that were sampled. The patient recovered uneventfully and was discharged from the hospital within 4 days.

Figure 1.

Salpingectomy specimen.

2. Definition

Heterotopic pregnancy is defined as the presence of multiple gestations, with one being present in the uterine cavity and the other extra-uterine, commonly in the fallopian tube and uncommonly in the cervix or ovary [1, 2, 3].

3. Incidence and risk factors

Initially described in 1708 as a postmortem discovery [4]. Under normal circumstances, with natural conception cycles, heterotopic pregnancy is an unusual occurrence with an incidence of <1/30,000 pregnancies [2, 4, 5, 6]. It accounts for 0.08% of all pregnancies [7]. The frequency of heterotopic pregnancy has increased to between 1/100 and 1/500 with assisted reproduction techniques [5, 8]. Its occurrence is 5% of conception achieved after in vitro fertilisation (IVF) [4]. Triplet heterotopic pregnancy has also been seen following natural conceptions [9]. A case, of ectopic gestation in both tubes bilaterally with an intra-uterine pregnancy has also been reported [10]. The diagnoses of heterotopic gestations are frequently made at gestation age of 5–34 weeks with 70% at 5–8 weeks, 20% at 9–10 weeks and only 10% >11 weeks of gestation [8, 11, 12].

4. Clinical presentation and diagnosis

The early detection of heterotopic pregnancy is usually very problematic due to non-specific clinical symptoms as signs of the intra-uterine pregnancy always predominate [11]. Mainly, the four cardinal clinical features common in most literature are: abdominal pain, adnexal mass, features of peritonism and an enlarged uterus [1, 11]. About 83% of heterotopic pregnancies report abdominal pain alone while 13% present with hypovolemic shock together with abdominal tenderness. More than half of the pregnant patients with heterotopic gestations do not present with vaginal bleeding though it may be retrograde from the extra-uterine pregnancy due to intact endometrium of the intrauterine pregnancy [8, 13]. Increasing knowledge and skills in trans-vaginal ultrasound scanning has eased early and timely detection of heterotopic gestations. Trans-vaginal ultrasound scanning is an important tool in timely and accurate detection of heterotopic gestations. However its sensitivity in detecting heterotopic gestation is as low as 56% at 5–6 weeks [14]. Diagnosis a heterotopic gestation is confirmed at trans-vaginal sonography if there is an intra-uterine pregnancy together with an ectopic gestation (Figure 2) [14]. In a retrospective review of ultra-sonographic findings it was discovered that a fallopian tubal ring (an adnexal mass with a concentric echogenic rim of tissue, a gestational sac, surrounding a hypo-echoic empty center) was present in 68% of the ectopic pregnancies in which the tube had not ruptured [15]. If the pregnancy is >6 weeks, confirmation of the diagnosis is made on the presence of a cardiac activity. Sometimes, even with trans-vaginal ultrasonography, the adnexal mass is mistaken for a hemorrhagic corpus luteum or ovarian cyst, especially in ovarian hyper-stimulation [16]. In these cases, a heterotopic gestation becomes unnoticed in the presence of intra-uterine gestation. Therefore, when the levels of human chorionic gonadotropin (β-hCG) are higher for the period of gestation with an intra-uterine pregnancy, one has to find out for a possible coexistence of a tubal gestation. Occasionally, there are no concrete adnexal findings and the diagnosis of ectopic gestation is then based on other sonographic findings like haemoperitoneum, haematosalpinx which present as free fluid in the peritoneal cavity or the pelvis; e.g., in the pouch of Douglas (Figure 3). Usually, the identification of an intra-uterine gestation causes shift of attention from the possibility of a concurrent ectopic gestation. Even on suspicion of its existence, identification of ectopic component of heterotopic gestation at ultrasonography is usually much more difficult with the presence of a big haemoperitoneum. In a patient with even a confirmed intra-uterine gestation and presents with acute lower abdominal pain, the likelihood of an ectopic component of a heterotopic gestation must be seriously thought about. Heterotopic gestation is uncommon in natural cycles but it still happen. With the increasing application of assisted reproductive techniques, clinicians must be aware of the fact that identifying an intra-uterine or ectopic gestation clinically or sonographically does not exclude a concurrent existence of ectopic or intrauterine gestation pregnancy, respectively [17, 18].

Figure 2.

Image of a trans-vaginal sonography of the uterus (transverse section) showing an intrauterine gestation (black arrow) coexisting with an ectopic cornual pregnancy (*) with a sac of 25 mm in diameter, containing an embryo with a crown rump length of 13 mm.

Figure 3.

Ultrasonography demonstrating free fluid adjacent to the kidney, consistent with a large amount of hemoperitoneum in a patient with ruptured ectopic pregnancy.

5. Differential diagnosis

In a patient with an intrauterine pregnancy, the differential diagnosis of uterine bleeding and/or abdominal pain includes threatened abortion, ruptured corpus luteum cyst, and heterotopic pregnancy. The correct diagnosis depends on careful sonographic assessment. Free fluid in the abdomen is a nonspecific finding as it could reflect cyst rupture, tubal pregnancy rupture, or ascites associated with ovarian hyper-stimulation syndrome during ART [16]. Patients with an intrauterine pregnancy may also develop abdominal pain from appendicitis, nephrolithiasis, or urinary tract infection, but these disorders can be distinguished from ectopic pregnancy by history, physical examination, and imaging and laboratory results. In unstable pregnant patients with abdominal pain and bleeding, surgical evaluation continues to play a key role in the diagnosis of heterotopic pregnancies.

6. Treatment

As soon as the diagnosis is made, the extra-uterine pregnancy is always managed surgically especially with features of rupture and the intrauterine component is left to continue normally. With unruptured extra-uterine pregnancy, other treatment options like expectant management with aspiration and installation of potassium chloride or prostaglandin into the ectopic gestational sac can be tried. Methotrexate (MTX) (systemic or local injection) is avoided in heterotopic pregnancy due to its toxicity. Laparoscopic technique is another feasible approach for both cases without disruption to the progression of an intra-uterine pregnancy.

7. Outcome

There appears to be a higher risk of spontaneous abortion of the intrauterine pregnancy of a heterotopic pregnancy than in an isolated intrauterine pregnancy [19]. In a literature review of 11 cases of heterotopic tubal and intrauterine pregnancy treated with Potassium chloride injection, 6 of 11 cases (55%) failed this therapy and required surgical intervention.

8. Conclusion

Clinicians should be aware that the presence of an intra-uterine pregnancy sonographically or clinically should not and does not necessarily exclude the possibility of an ectopic pregnancy which should be thought about in any pregnant patient presents with abdominal pain plus unexplained hypovolemic shock.

9. Summary

Heterotopic pregnancy refers to simultaneous pregnancies at two different implantation sites: an intrauterine and an extra-uterine pregnancy. Heterotopic intrauterine and tubal pregnancies should be suspected when ultrasound examination shows an intrauterine pregnancy and a complex adnexal mass, especially after assisted reproduction technology (ART) is used for conception. The diagnosis is confirmed when the adnexal mass contains a yolk sac or embryo/fetal pole. The clinical presentation closely mimics the symptoms of threatened abortion and isolated ectopic pregnancy. The uterus is enlarged consistent with gestational age and there may be abdominal pain, vaginal bleeding, and/or an adnexal mass. Patients are usually diagnosed late after becoming symptomatic and are often diagnosed at a more advanced gestational age than isolated tubal pregnancy. Rupture can result in acute abdomen and hemodynamic shock. The ectopic pregnancy should be terminated. Treatment of the ectopic pregnancy is tailored to the site of implantation and should utilise the least invasive therapy in order to preserve the concomitant intrauterine pregnancy. Salpingectomy is the standard surgical approach of a coexistent tubal pregnancy and should be the first line of treatment in patients with hemodynamic instability or other signs of tubal rupture. In expert hands, an unruptured ectopic pregnancy can be treated with local feticidal injection under sonographic guidance.