Heterotopic pregnancy – how easily you can go wrong in diagnosing? A case study

Heterotopic pregnancy (HP) is defined as the presence of an intrauterine pregnancy (IUP) that coexists with an ectopic pregnancy (EP)⁽¹⁾. HP can occur in several forms, e.g. one-sided tubal pregnancy, bilateral pregnancy, etc. (all with IUP)^(2,3).

The diagnosis of HP is still one of the biggest challenges in modern gynecology. The incidence of those pregnancies in natural conception is about 1:30000⁽¹⁾, but in assisted reproduction it is much higher (1:100 – 1:500)⁽⁴⁾.

The most common risk factors for ectopic pregnancy include pelvic inflammatory disease, intrauterine devices, adhesions, a history of ectopic pregnancy, assisted reproduction techniques and ovarian hyperstimulation syndrome^(5,6). Also, for women covered by an assisted reproduction program there are additional factors, such as higher incidence of multiple ovulation, higher incidence of tubal malformation and/or tubal damage, and technical factors in embryo transfer which may increase the risk for ectopic and heterotopic pregnancy⁽⁷⁾. Our patient presented with a single, idiopathic adhesion, but the rest of her medical history was negative.

Most common clinical symptoms of HP include abdominal pain, an adnexal mass, peritoneal irritation and an enlarged uterus. In contrast to ectopic pregnancy, vaginal bleeding is an extremely rare condition⁽⁸⁾. HP can result in severe and potentially fatal complications, including intraabdominal bleeding, uterine rupture, preterm delivery or miscarriage^(9,10).

A 34-year-old primipara was admitted to clinic at 13 weeks of gestation with severe abdominal pain. About 6 weeks earlier, the patient had been diagnosed with a dichorionic twin pregnancy (Fig. 1 A and Fig. 1 B). At 7 and 11 weeks of gestation, the patient had presented with abdominal pain, which was treated by drotaverine, and resolved permanently. The patient had been treated at a public hospital, where a transvaginal scan (TVS) had been performed, yet in the exam report data about both adnexa were unavailable. On admission to our hospital, the patient presented with acute abdomen symptoms. Clinical examination revealed painful, enlarged right appendages. Blood examination revealed anemia with a hemoglobin concentration of 9.1 g/dl. TVS revealed fluid in the pouch of Douglas, as well as two gestational sacs. The first gestational sac was an intrauterine pregnancy with a fetus of 70 mm in crown-rump length (CRL). The second gestational sac with a living fetus was located behind the posterior uterine wall, within the right fallopian tube. This fetus had a CRL of 64 mm, and presented with bradycardia. Due to severe symptoms and the suspicion of heterotopic pregnancy (HP), the clinical team decided to perform a diagnostic laparotomy. Hemoperitoneum was found and a right-sided heterotopic pregnancy was confirmed (Fig. 1 C). The right fallopian tube was attached to the lower part of the posterior uterine wall by a small adhesion. The adhesion was removed, and a salpingectomy was performed for ruptured tubal ectopic pregnancy (Fig. 1 D). The patient was discharged after 6 days. Follow-up was performed at an outpatient clinic. The intrauterine pregnancy (IUP) proceeded without complications to a full-term vaginal delivery.

Fig. 1.

According to Tal et al., 70% of HPs are diagnosed between 5 and 8 weeks of gestation⁽¹¹⁾. The presence of an IUP complicates the diagnosis of a heterotopic pregnancy. Most clinicians think that the presence of IUP excludes an ectopic one, and after the diagnosis of IUP fail to examine the appendages at all. According to Talbot’s data, 71% cases of HP had one risk factor and 10% had three or more risk factors. That is why a careful assessment of risk factors may lead to a correct diagnosis, but nothing can be done without a careful ultrasound scan⁽¹²⁾. TVS is a gold standard in diagnosis, yet it is effective in the hands of an experienced examiner. However, it has a low sensitivity – from 26.3% to 92.4%^(12–14). Difficulties can occur in differentiating HP from a corpus luteum cyst or hemorrhagic cyst⁽¹²⁾. Transvaginal sonographic examination is recommended in early pregnancy, especially in patients who conceived with the use of assisted reproduction techniques⁽¹⁵⁾. Lyu et al. advise to perform transvaginal scan in every woman after in vitro fertilization 4 weeks after embryo transfer⁽¹⁶⁾. The diagnostic role of human chorionic gonadotropin concentration in HP is debatable. In this case, the heterotopic pregnancy was mistaken for a healthy dichorionic pregnancy, probably because none of the sonographers examined the appendages.

The management of HP depends on the week of gestation. The key point of treatment is to preserve the IUP and resolve the EP⁽¹⁵⁾. In asymptomatic, stable patients expectant management might be considered^(13,17), but the risk of the rupture of HP is high. According to a study by Li JB, 20% of expectant management cases resulted in the rupture of HP⁽¹⁵⁾.

Surgery is still the most frequently chosen method of treatment. In most cases, it involves salpingectomy and depends on the actual clinical condition^(10,12). During surgery the manipulation of the uterus should be minimal, to preserve the IUP from complications. Data of 139 HP cases, treated mostly by surgery, revealed that the IUP survival rate was 66%⁽¹¹⁾. In women with unstable hemodynamic parameters, emergency surgery for HP rupture is strongly recommended⁽¹⁵⁾. Surgery involves mainly salpingectomy, salpingotomy or oophorectomy, but in some difficult cases it might also require even hysterectomy, with the risk of abortion in the group managed surgically being higher⁽¹⁸⁾. According to Li JB, the overall abortion rate in the group managed surgically was up to 14.8%⁽¹⁵⁾.

Ultrasonographically guided aspiration is a less invasive method with good effectiveness^(19,20). The problem is whether the location of the pregnancy is accessible by a needle. Potassium chloride or hyperosmolar glucose are agents of choice^(19,20). Pharmacological treatment with methotrexate should be avoided, due to the risk of its teratogenicity^(15,17), but there are some reports that show a good therapeutic effect of methotrexate⁽²¹⁾. Clinicians should be vigilant, as the incidence of this pathology rises, probably due to the higher number of pregnancies after assisted reproduction⁽⁷⁾. Follow-up ultrasound scans are recommended due to the risk of failure or pregnancy rupture⁽¹⁵⁾.

The presence of an IUP does not mean that an ectopic pregnancy is absent. Clinicians should always keep in mind that a heterotopic pregnancy may occur in a woman of reproductive age. In the presented case, the pregnancy mimicked a dichorionic pregnancy and was thus unrecognized. This could have been avoided, if a detailed scan of the pelvic structures had been performed earlier. In our opinion, the appendages of each pregnant woman should be scanned, in whom clinical symptoms like abdominal pain, fluid in the pouch of Douglas or hypovolemic shock are present, or if the woman is in the high risk group. The surgical management of HP can result in a successful IUP and maternal outcome when early diagnosed.