Bilateral Simultaneous Tubal Ectopic Pregnancy with a Third Intrauterine Pregnancy: A Rare Case of Heterotopic Pregnancy

Introduction

Heterotopic pregnancy (HP) is defined as the coexistence of an intrauterine pregnancy and an ectopic pregnancy (i.e., the presence of simultaneous gestations at two or more implantation sites). HP was first reported in 1708 as an autopsy finding. ¹ Ectopic pregnancy occurs in 1%–2% of pregnancies. The fallopian tube is the most common site; however, a bilateral tubal ectopic pregnancy is an extremely rare phenomenon seen in ∼5 in 1 million pregnancies.^2,3 The risk of ectopic pregnancy and HP is increasing due to the increased risk of multiple pregnancies incurred by assisted reproductive technologies (ARTs). Aside from the difficulty of diagnosing the problem, management can be difficult and the condition can be life-threatening. ⁴

Case

A 23-year-old primigravida presented with a few-hour history of severe lower-abdominal pain and vomiting. She gave a history of amenorrhea for 6 weeks and 4 days following ovulation induction with clomiphene citrate. This medication was given to her to take twice daily for 5 days from the third day of her last menstrual period. There was no history of pelvic inflammatory disease, abortion, contraception use, or abdominal surgery. She was aware of being pregnant, and an ultrasound (US) scan 24 hours prior to her current presentation showed an uncomplicated viable intrauterine pregnancy.

On clinical examination, she was noted to be pale and in shock, with a pulse rate of 130 beats per minute and a blood pressure of 95/60 mm Hg. An abdominal examination revealed diffuse lower abdominal tenderness with significant guarding and rigidity. Pelvic examination revealed bilateral tender adnexal masses. Her laboratory investigations showed a hemoglobin level of 6.3 g/dL, a white cell count of 28,000/cm³, and a serum β-human chorionic gonadotropin (β-hCG) level of 95239 mIU/mL.

Urgent transabdominal and transvaginal US scans showed a viable intrauterine pregnancy of 7 weeks' gestation and a large complex mass posterior to the uterus extending to involve both ovaries, measuring 8 × 4 cm. Both ovaries appeared to be enlarged with multiple small-to-moderate–size cysts. An echogenic ringlike cystic lesion was also noted in the left adnexa with a yolk sac measuring 3 cm in diameter, suggesting a left sided ectopic pregnancy. Another less-echogenic cystic lesion was observed on the right ovary, measuring 2.5 cm, suggesting a corpus luteal cyst. Moderate-to-marked free fluid in the upper abdomen and the pelvic cavity was found, suggesting a hemoperitoneum. A provisional diagnosis of HP with a left sided ruptured tubal ectopic pregnancy was made.

Following fluid therapy to improve low blood pressure and pulse rate, an emergency laparotomy was performed. Operative findings revealed an actively bleeding ruptured left-sided tubal ectopic pregnancy and an unruptured right-sided tubal pregnancy. Both ovaries showed multiple corpus luteal cysts, with bleeding from one ruptured cyst in the right ovary. At least 1 L of blood was noted filling the peritoneal cavity. A left salpingectomy and a right salpingostomy were performed. In addition, the bleeding ruptured right corpus luteal cyst was oversewn. The extracted products of conception from the right fallopian tube and the resected part of the left fallopian tube were sent for histopathology testing. Histopathology later confirmed the presence of chorionic villi from both extracted tissues indicating simultaneous bilateral tubal ectopic pregnancies. Three units of packed red blood cells were started intraoperatively and continued postoperatively.

On the third postoperative day, the patient developed vaginal bleeding that proved to be an incomplete abortion of her concurrent intrauterine pregnancy. A transvaginal suction evacuation under general anesthesia was performed.

Results

This patient's postoperative recovery period was uneventful, and she was discharged to go home on the fifth postoperative day, with advice to undergo outpatient serial β-hCG monitoring to rule out any possibility of persistent trophoblastic disease.

On the tenth postoperative day, her serum β-hCG had dropped to 272 mIU/mL and later to 0 on the twenty-first postoperative day. An abdominal US examination revealed a normal uterus and ovaries. Consequently, after 3 weeks, she was completely well, free of any possibility of persistent trophoblasts, or any postlaparotomy or suction evacuation complications.

Discussion

To the best of the current authors' knowledge, this is the first report of an HP with three implantation sites—bilateral tubal ectopic pregnancies in addition to one intrauterine pregnancy. While unilateral tubal ectopic pregnancy is the commonest form of ectopic gestation, simultaneous bilateral tubal ectopic pregnancies comprise the rarest variety, with a reported incidence of 1 in 725–1580 ectopic pregnancies, ⁵ corresponding to 1 per every 200,000 live births. ⁶

The occurrence of an HP is considered rare in natural conception cycles, with an incidence of 0.08%, but incidence increases to as high as 1% with ARTs. ⁷

Any ectopic pregnancy is a potential medical emergency. Late or misdiagnosis can result in serious complications, such as tubal rupture, hemorrhagic shock, or death. ⁸ However, timely diagnosis especially of bilateral tubal ectopic pregnancies or heterotopic pregnancies, has proven to be particularly challenging.

Unlike unilateral ectopic pregnancies, measurement of β-hCG levels is neither a sensitive nor a reliable diagnostic marker for bilateral tubal pregnancy cases. ⁸ Furthermore, the efficacy of preoperative US for diagnosing simultaneous bilateral tubal ectopic pregnancies is also low. ⁹ Direct inspection of the contralateral tube intraoperatively is the way the diagnosis is made or confirmed. Despite this, there have been cases of missed bilateral ectopic pregnancies resulting in a second emergency surgery following a contralateral rupture. ¹⁰

As demonstrated, simultaneous bilateral tubal ectopic pregnancies are difficult from a diagnostic point of view. The situation will be more complicated if the simultaneous bilateral tubal ectopic pregnancies are associated with an intrauterine pregnancy (an HP).

The diagnosis of HP is often difficult when using US scans due to its rarity. In addition, most reports make no mention of a search for a coexistent ectopic pregnancy when evaluating intrauterine gestation, as ectopic pregnancies are commonly diagnosed by excluding an intrauterine gestation.^6,8,11 In addition, intrauterine gestation with a hemorrhagic corpus luteum can simulate an HP on US examination. ¹²

Simultaneous bilateral tubal ectopic pregnancies pose management dilemmas as both tubes are damaged, and the situation becomes more complicated if the tubal pregnancies are associated with an intrauterine pregnancy. This is what occurred in the current case.

Management of simultaneous bilateral tubal ectopic pregnancies varies, depending upon the condition of the patient, the extent of tubal damage and the patient's wish for future fertility. ¹ Surgical management has ranged from salpingectomy for one tube and linear salpingostomy for the other tube (as in the current case) to bilateral salpingostomy or bilateral salpingectomy. ⁶ If available, laparoscopy may be the best option both for diagnosis and management of simultaneous bilateral tubal ectopic pregnancies. ¹¹ Laparotomy is equally effective, and is the management of choice if the patient is hemodynamically unstable, as in what occurred in the current case. Of note, however, serial β-hCG monitoring should be performed, as there is a high chance of a persistent ectopic pregnancy, especially if a conservative surgery such as salpingostomy or milking of the tube has been performed. ¹

For the management of HP, surgical treatment has been the conventional mainstay if the HP is diagnosed late. ¹² However, successful nonsurgical management with potassium chloride injection into a tubal ectopic pregnancy has been reported in a hemodynamically stable patient with an unruptured fallopian tube. ¹³ It is a frequent practice to use methotrexate to treat ectopic pregnancies in stable patients, but this treatment in a patient with a heterotopic pregnancy would potentially compromise the intrauterine gestation, as there has been a reported survival rate of 35%–54% for the intrauterine gestation in patients treated by surgery for the heterotopic pregnancy. ¹⁴

Conclusions

Heterotopic pregnancies are rare, life-threatening, and easily missed. The current case was special because it followed simple induction of ovulation with clomiphene citrate and there were also simultaneous bilateral tubal pregnancies in addition to an intrauterine pregnancy (triple implantation). It is important when evaluating a patient for abdominal pain early in pregnancy to be aware of this condition and to conduct a full workup that includes a pelvic US with visualization of the uterine cavity and both adnexae. Early diagnosis and urgent management can save the patient's life and fertility.