Successful management of three cases of interstitial pregnancies with local instillation of potassium chloride: avoiding a potential cornuostomy

Abstract

Here, we present three cases of women with interstitial pregnancy who were managed with local instillation of potassium chloride. These women were in their 20s–30s and presented in stable condition. Of them, two had a history of previous ectopic pregnancy. Interstitial pregnancy was diagnosed by transvaginal sonography which showed an empty uterine cavity with a gestational sac 1 cm away from the lateral edge of the uterine cavity, with <5 mm myometrium surrounding it in all planes. Two of the three cases failed to respond to methotrexate injection. Due to the presence of high-end ultrasound machine and technical expertise, local instillation of potassium chloride was offered as an alternative to surgical treatment, which is definitive, and all three patients had a successful outcome. One patient returned with pain in the abdomen, which required inpatient monitoring and was later diagnosed with urinary tract infection and was given appropriate antibiotics.

Background

The incidence of interstitial pregnancy varies from 1% to 6.3% of ectopic pregnancies.^1–3 It is an enigma as it poses diagnostic and management dilemmas. Diagnosis is based on a high index of clinical suspicion. It can be easily missed in the first trimester for an eccentrically implanted gestational sac, and second trimester diagnosis is mainly based on clinical presentation with major catastrophic haemorrhage requiring immediate measures for tackling the unforeseen and devastating complications. It has 7 times higher rate of complications than other ectopic pregnancies and is associated with maternal mortality which is 15 times higher.^{4 5}

The gestational age, the level of serum β-human chorionic gonadotropin (β-hCG) and the clinical presentation of the patient dictate the management options. Expectant, local or systemic methotrexate injections, and laparoscopic or hysteroscopic approaches are the proposed first lines of management in the first trimester of pregnancy. With late diagnosis, management options become limited and purely surgical.⁶

Local intracardiac/intra-amniotic instillation of potassium chloride (KCl), alone or in combination with other drugs, has been used for the treatment of live ectopic pregnancies and in heterotopic pregnancies.⁷ This seems to be a less invasive approach with minimal adverse effects and can be considered as a treatment option. Here, we report three live interstitial pregnancy cases who were diagnosed accurately early and managed successfully with KCl instillation.

Case presentation

Case 1: A multiparous woman in her 30s with one caesarean delivery and a laparoscopic salpingectomy for right ectopic pregnancy was referred as a case of pregnancy of unknown location. At 35 days of amenorrhoea, her urine pregnancy test was positive, but a transvaginal scan failed to show an intrauterine gestational sac. β-hCG done at that time was 714.2 mIU/mL. Repeat β-hCG 48 hours later was 1632 mIU/mL, and the scan revealed a 5-mm ring-like structure in the right uterine fundus outside the endometrial lining. Otherwise, she was asymptomatic at presentation. General physical and abdominal examination was unremarkable, with a pulse of 68 beats per minute and blood pressure of 120/80 mm Hg.

Case 2: She was a multiparous woman in her 20s with one vaginal delivery and one medical termination of pregnancy, as she was on treatment for Crohn’s disease. Though her third pregnancy was planned, she had inevitable abortion and had to undergo a manual vacuum aspiration for retained products of conception. Following this, she had only one menstrual cycle during which she bled minimally, which lasted 2–3 days. She now presented at 32 days of amenorrhoea. Currently, she is on homeopathic treatment for Crohn’s disease. Her vital signs were stable and abdominal findings were unremarkable.

Case 3: A multiparous women in her 30s with a history of laparotomy for previous ectopic pregnancy with no living children with antiphospholipid antibody-positive status was referred from a local hospital as a case of right cornual ectopic pregnancy. It was a natural conception with urine pregnancy test positive at 40 days of amenorrhoea. She had some amount of nausea and vomiting. She had minimal spotting per vaginam at 42 days of amenorrhoea, and the scan done showed a gestational sac of ~19 mm, yolk sac and fetal pole with cardiac activity in the right cornua and was referred for further management.

Investigations

The ultrasound in all three patients when the final diagnosis was reached showed an empty uterine cavity with a gestational sac 1 cm away from the lateral edge of the uterine cavity, with <5 mm of the myometrium surrounding it in all planes. However, the initial scans in cases 1 and 2 had diagnostic dilemmas.

Case 1: As the diagnosis was not evident initially, β-hCG and scan were repeated 48 hours later. β-hCG was 2766 mIU/mL, and the scan showed a 8 mm gestational sac with yolk sac, but no fetal pole/cardiac activity. In view of previous right ectopic pregnancy with the present scan findings, an interstitial pregnancy was diagnosed and she received 75 mg intramuscular methotrexate after confirming a normal liver (aspartate transaminase (AST), 16 IU/L; alanine transaminase (ALT), 16 IU/L; alkaline phosphatase (ALP), 66 U/L) and renal function (urea, 17 mg/dL; creatinine, 0.7 mg/dL).

Case 2: The first scan done showed 3.8 mm anechoic ring at the fundus. She was called at intervals of 10 days for repeat scans as it was initially thought that it was a very early intrauterine gestation. The second scan also showed a gestation sac of 14 mm very high at the fundus with yolk sac, but no fetal pole. The third scan done revealed a gestational sac of 20 mm, with yolk sac and fetal pole of 7.8 mm with cardiac activity with 4.5 mm of myometrium surrounding it, and interstitial pregnancy was confirmed.

Case 3: Although she was referred as a case of cornual pregnancy, the diagnosis was straightforward because at 7 weeks interstitial pregnancy was confirmed with yolk sac, fetal pole and cardiac activity. There was no mullerian anomaly to call it a cornual pregnancy (video 1).

Video 1.

Download video file ^{(4.4MB, mp4)}

DOI: 10.1136/bcr-2020-239918.video01

Differential diagnosis

In case 1, though she was suspected as a case of pregnancy of unknown location, sequential appearance of structures within the gestational sac in the portion of the tube removed during previous laparoscopic salpingectomy made us initially suspect and later on confirm the diagnosis.

In case 2, in the initial scans, pregnancy of unknown location was diagnosed, and then a suspicion of early intrauterine gestational sac was made, which later turned out to be an interstitial pregnancy with fetal pole and cardiac activity.

Case 3 showed all the evidence of interstitial pregnancy where we could document an empty uterine cavity with gestational sac with fetal pole and cardiac activity in <1 cm from the lateral edge of the uterine cavity.

Treatment

Case 1: She received 75 mg intramuscular methotrexate after confirming a normal liver (AST, 1 6 IU/L; ALT, 16 IU/L; ALP, 66U/L) and renal function (urea, 17 mg/dL, creatinine, 0.7 mg/dL). Day 4 following methotrexate, β-HCG showed a 87% rise to 5325 mIU/mL. So a scan done showed a right interstitial pregnancy with a yolk sac and 2.3 mm fetal pole and cardiac activity (figure 1). She was counselled regarding further options available to her, and an option of local instillation of KCl was discussed and informed decision of intracardiac instillation of KCl was planned. A Voluson P8 transvaginal ultrasound probe from GE Healthcare in fetal echo mode was used for intracardiac instillation of KCl, and a dose of 0.6 mEq was required to document asystole (figure 2). β-hCG 4 days later showed a declining trend with a value of 3789 mIU/mL.

Figure 1.

Case 1: interstitial pregnancy with yolk sac, fetal pole and cardiac activity before instillation of potassium chloride.

Figure 2.

Case 1: collapsed interstitial pregnancy sac after potassium chloride.

Case 2: She was planned directly for local instillation of KCl. After informed choice, KCl was instilled into the embryonic heart and a collapsed gestational sac was seen at the end of the procedure with 1 mEq of KCl.

Case 3: Here, though a cardiac activity was documented in the interstitial pregnancy and she was planned for local instillation, the day prior to KCl instillation, 80 mg of intramuscular methotrexate was given after confirming normal renal and liver function. Next day, 0.6 mEq of KCl was injected into the intra-amniotic sac which collapsed the gestational sac and caused the disappearance of cardiac activity.

Outcome and follow-up

Case 1: It took 46 days for the β-hCG to fall to normal levels from 5235 mIU/mL. She was on weekly follow-up (1865/1211/682/297.6/7.1 mIU/mL). After the value of β-hCG was <10 mIU/mL, she was not recalled for follow-up. She was given an option of repeat methotrexate (2nd dose) or watchful expectancy in the follow up period and also counselled that she might have to follow-up for 6 weeks due to slow falling trend. The patient decided on watchful expectancy. The patient is currently doing fine.

Case 2: The patient had a quick recovery with β-hCG returning to normal levels by 35 days from 59 380 mIU/mL. The higher dose of 1 mEq KCl instilled might have caused a faster falling trend (59 380/3574/203.9/26.3/2.3 mIU/mL). Six days after KCl instillation, the β-hCG was 3574 mIU/mL. She was called on weekly basis.

Case 3: She was on serial follow-up with β-hCG, which showed a declining trend. She came after 1 month with pain in the abdomen and was planned on surgical intervention if symptoms did not subside. But she was diagnosed with urinary tract infection and received appropriate antibiotics. Her initial β-hCG was 38 582 mIU/mL, and after 82 days it came down to normal level. As she had previous surgery and due to the COVID-19 pandemic, the patient was not keen on surgery and a diligent follow-up protocol was advocated. This patient is doing fine and is stable.

Discussion

The rarity of interstitial pregnancy makes its diagnosis and treatment a challenge. Various imaging modalities and options of treatment have been proposed. Here, we report three such cases of interstitial pregnancy.

Interstitial pregnancy is associated with assisted reproductive techniques, but in our cases no unique identifiable risk factors separate interstitial pregnancy from other ectopics. A high index of clinical suspicion with good-resolution ultrasound machine and an extremely well-trained personnel in obstetric ultrasound made an early diagnosis possible. In the first case, a previous history of right ectopic pregnancy managed by laparoscopy raised our suspicion. The ultrasonographic (USG) features of an empty uterine cavity and a chorionic sac separate and at least 1 cm from the lateral edge of the uterine cavity with <5 mm of the surrounding myometrium in all planes assured an accurate diagnosis.^{8 9} These ultrasound features were found to have a specificity of 88%–93% but carried a sensitivity of only 40%. Ackerman et al described the interstitial line sign, which refers to the visualisation of an echogenic line that runs from the endometrial cavity to the cornual region, abutting the interstitial mass or gestational sac. This echogenic line has been reported to be 80% sensitive and 98% specific for the diagnosis of interstitial pregnancy.¹⁰ The above signs were seen in our cases, and so three-dimensional USG and MRI modalities were not used for further confirmation.

As the number of interstitial pregnancy are very few and until now only around 300 odd cases have been reported, with no randomised controlled trial, the optimal management for an interstitial pregnancy is lacking. Currently, expectant, conservative and surgical options have been described, depending on the levels of β-hCG, clinical presentation and gestational age.^{11 12}

Athough surgical management offers a definitive treatment, they are associated with a lot of morbidity. Traditional management with wedge resection was associated with haemorrhage and sometimes hysterectomy. So, less invasive cornual resection and cornuostomy have replaced it. Laparoscopic surgery has replaced open surgery. Cornual resection is associated with loss of myometrium and extensive scarring, which puts a poor outlook to future pregnancy outcomes. There seems to be an increased incidence of uterine dehiscence/rupture in future pregnancy.¹³ Currently, laparoscopic cornuostomy has shown promise, in terms of being less invasive and traumatic with an option of future fertility with fair pregnancy outcomes.¹⁴ However, the smaller the interstitial pregnancy, the more difficult it is to treat with cornuostomy as there is a higher chance of persistent interstitial pregnancy.

Expectant management can be an option in a few selected cases, in whom the β-hCG level was initially low and shows a falling trend. The potential benefits of this line of management are the avoidance of surgical risks and the absence of a scar on the uterus, which might have a favourable impact on future fertility prospects. However, the risk of rupture leading to haemorrhage during the waiting period and the need for close follow-up for a prolonged period of time need to be counselled while obtaining informed consent. Facilities only where anaesthesia, surgical expertise and blood are available 24 hours can offer this management.¹⁵ So a careful selection of cases is of supreme importance.

The overall success rate for conservative treatment is 85.7%, and local methotrexate carries higher success than systemic.¹⁶ As in other ectopics single-dose methotrexate has a good success rate, multidose regimen is proposed to be highly effective in interstitial pregnancy.^17–19 Caution needs to be addressed during its use due to drug reactions and serious adverse effects such as transitory peripheral neuropathy, severe constipation and deterioration in liver function.²⁰ The availability of newer and better-resolution USG machines has broadened our options of management. Local methotrexate is a possibility where the side effects can be minimised.¹⁶ An alternative to this might be intracardiac KCl instillation to induce asystole. The studies on KCl show that it has been used especially in heterotopic pregnancy where methotrexate was not a viable option due to its antifolate property. As this is injected locally, the side effect profile is also minimal. These factors make it a viable and good option which needs to be researched and explored further. The need of high- resolution USG machine and trained personnel for precise injection limits its wider applicability. Also, the patient compliance is of utmost importance for diligent follow-up of the serum β-hCG levels.

As our cases were keen on future pregnancy, conservative and surgical approaches were discussed and a consensual agreement on conservative management was arrived. Twenty milliequivalents of 10 mL KCl was diluted in 10 mL of distilled water so that 20 mEq was in 20 mL and each millilitre had 1 mEq. Two 1 mL insulin syringes were loaded. After informed consent and under USG guidance, intracardiac/intra-amniotic instillation of KCl was done. In each of the cases, the patient tolerated the procedure well and had a quick and satisfactory recovery.

Appropriate case selection, with detailed counselling and motivating patients for follow-up, is essential for success in this line of management.

Conclusion

Interstitial pregnancies are rare. It poses a diagnostic and a therapeutic challenge. It is associated with 7 times higher morbidity and 15 times higher mortality than other tubal pregnancies. Early diagnosis offers a wide range of options in management. Instillation of KCl into the cardiac/gestational sac is a feasible option in the first trimester in a clinically stable patient. This technique offers an option of fertility conservation with a favourable outcome in future pregnancies. It is impertinent to appropriately counsel the patient of the importance of follow-up until the β-hCG levels fall to normal. The need for sophisticated machine and trained experts in the field might be a major deterrent for its routine and wider applicability of use.

Patient’s perspective.

Case 1 and case 3 recovered well and had a positive feedback.

Case 1: I was anxious at the commencement of treatment but was reassured by the falling blood levels of pregnancy hormones.

Case 3: I was not keen on surgery at this COVID-19 time and was very happy that the surgery could be avoided.

Case 2: After the fall of hormonal levels to normal, the patient was lost to follow-up

Learning points.

• A history of previous ectopic pregnancy and risk factors should make us suspect recurrence.

• Diagnosis can be made successfully with ultrasound by documenting a thin rim of myometrium around it.

• Though surgical management offers definitive treatment there are anaesthetic/surgical risks involved. So if the patient is compliant then with the required machine and expertise local instillation of potassium chloride can be offered.

• It should be reiterated that follow-up with β-human chorionic gonadotropin is a must till it comes to normal levels, and she should also be counselled that there might be failure in some cases where surgical treatment becomes the gold standard.