Migration of a subdermal contraceptive implant into a subsegmental pulmonary artery and etonogestrel serum concentration over time – a case report

Background

In Scandinavia the use of long-acting contraception including implants is increasing and progressively replacing the conventional oral contraceptive pills [1]. The Nexplanon® (also known as Implanon NXT®) implant is a 4 cm long and 2 mm-thick nonbiodegradable rod containing Etonogestrel (ENG). It is coated with barium sulphate making it detectable on X-ray and Computed Tomography (CT) [2]. Nexplanon® has a Pearl index of 0.0 (95% confidence interval, 0.0–0.2) making it a highly effective contraceptive method [3].

The Nexplanon® The implant is inserted subdermally superficial of the triceps muscle in the non-dominant upper arm approximately 8–10 cm cranially to the medial epicondyle of the humerus and posterior of the bicipital sulcus using a device supplied by the manufacturer. Complications following insertion and extraction of the implant are rare and if present most commonly minor and localized at the implantation site [4].

Merck advises to use X-ray based methods such as plain X-ray or computed tomography for visualization as first line method (summary of products characteristics for Nexplanon).®). It then states that ultrasound using a specific probe ‘may also be used’. A known and extremely rare complication is intravascular migration of the contraceptive implant to the pulmonary vessels. The risk of intravascular insertion is estimated at 1.3 per million Nexplanon® implants sold globally [5].

To this date there has been at least 12 previously published cases of contraceptive implant intravascular migration causing implant pulmonary embolism. However, the exact number of cases worldwide is unknown and reports of etonogestrel concentrations are lacking [6]. We report the first Scandinavian case of asymptomatic Nexplanon® Migration to a pulmonary artery in a 24-year-old woman. The report follows the CARE guidelines [7].

Case presentation

In September 2017 a 24-year-old Caucasian woman sought medical care to remove her Nexplanon® single rod contraceptive implant. This was her third consecutive implant and it had been in place for a duration of approximately 3 years. The patient had previously been anorectic and was recovering at the time of her third implant insertion. She was however underweight according to the patient and provider. Neither current weight nor BMI at this time were documented. According to the patient she had never been able to palpate the third implant but had always experienced amenorrhoea during implant use. On palpation by health care professionals the implant could not be found in her left upper arm. Subsequently, she underwent an MRI of the upper arm and ultrasound of the upper and lower arm with a 10 MHz linear probe. Initial investigations were inconclusive but discussed ‘structures’ which could indicate an implant in the upper left arm. As a consequence of these inconclusive diagnostic procedures the patient underwent an unsuccessful attempt of removal in the operating room. It was assumed that the implant was localized under the fascia of the muscle and a referral was sent to the orthopedic department. Before attempting removal, an X-ray was performed of the upper left arm. No implant was identified and the patient was referred back to the gynecological department. The responsible obstetrician gynaecologist then contacted the manufacturer Merck Sharpe and Dohme (MSD). MSD recommended a chest X-ray which was performed with a new X-ray of the upper left arm. None of the investigations could identify the implant. After discussion with MSD the decision was taken to perform an analysis of the serum concentration of the active substance etonogestrel to be able to determine if the implant was located within the patient.

In the end of July 2018, the lab analysis data of the patient showed that the serum concentration of etonogestrel was 110.91 pg/mL with a detection level of 25 pg/mL. Data from previous studies suggest that the serum level of etonogestrel required to suppress ovulation is 90 pg/ml [8]. As the patient had not used any other contraceptive medications or implants during the time the result was interpreted as indicative of a Nexplanon® implant rod located within the patient.

Upon request for a second opinion of the previously performed chest X-ray, and a clarified question specifically asking for an implant location within the lungs, a suspected 4 cm long structure could be identified in the left lower lobe on the previous chest X-ray from the beginning of the year (Figures 1 and 2). A CT scan was performed and clearly visualized the Nexplanon® implant rod being lodged in a dorsal subsegmental pulmonary artery in the left lower lobe (Figure 3).

Figure 1. Chest X-ray, frontal view.

Figure 2. Chest X-ray, sagittal view.

Figure 3. Computer tomography, sagittal view.

In our case and according to the journal entry by the midwife performing the insertion procedure the third Nexplanon® implant device was inserted through the removal site of the second implant. It is considered most likely that the third implant was inadvertently placed into the basilic vein passing and migrated through the veins of the upper limb the right side of the heart and lodging in a subsegmental pulmonary artery of the left lower lobe.

Upon detailed history taking the patient could not remember any symptoms of dyspnoea or chest discomfort after the implant insertion or during the period the implant had been in situ, nor did she remember any haematoma occurring at the insertion site. There was no sign of parenchymal damage eg, necrosis, infection or other pulmonary pathology within the lung adjacent to the implant rod or elsewhere on chest CT.

The patient was referred to a vascular surgeon in October 2018, and after a consultation an attempt to remove the implant endovascular approach with loop snare to retrieve the Nexplanon® implant rod was made in March 2019. The rod was reached and visualized but was firmly lodged in surrounding tissue and could not be removed.

As the patient was currently not interested in becoming pregnant, more invasive options such as thoracoscopy or lobectomy were not considered suitable. It was decided to leave the implant in situ and to measure serum concentrations to determine when levels below ovulation inhibition would be reached. Etonogestrel serum concentrations were analysed in March 2020 (146.5 pg/mL) and May 2021 (detected but <50pg/mL). The assay detection limit was 25 pg/mL and all lab analyzes were performed by the same lab (Columbia University Medical Centre, Clinical Pharmacology and Toxicology Laboratory).

The patient is currently experiencing spotting and sporadic bleeding but has not returned to having regular bleedings. The oestrogen level has been lowest at <80 pmol/l in October 2018 and at its highest in June 2020 at 156 pmol/l, indicating a hypothalamic suppression most likely due to a current eating disorder rather than an effect of the implant. The patient has been referred to gain weight and has been to eating disorder specialists.

Discussion

Asymptomatic migration of this implant into a vessel days or months after the insertion is considered highly unlikely. Thus, the most apparent explanation for implant migration is insertion into the basilic vein at the time of insertion. Endovascular approach is the recommended first option for retrieving implants that have migrated to the pulmonary arteries due to low post operative morbidity and reasonable success rate. Thoracoscopy and lobectomy are other more invasive treatment options that can be considered when the endovascular approach is unsuccessful. In several cases the decision has been made to leave the implant in situ as the benefits are regarded as greater than the operative risks. As this patient did not attempt to become pregnant the decision was taken in agreement with the patient to leave the implant in situ.

As in a previous case report [6], we find it likely that the extreme lack of subcutaneous tissue due to the eating disorder (clearly visible in Figure 3) posed a greater hypothetical risk of implant device migration. BMI levels below 17.5 have been discussed as a prominent risk factor. Therefore, special consideration should be taken in patients with lower BMI and most definitely in anorectic patients.

The etonogestrel serum concentration level, close to 7 years after the implant insertion, remains detectable, although lower than the limit required to suppress ovulation.

As the implant rod is a thin structure, it can easily resemble a vascular structure or be partly covered by one depending on the X-ray projection and the implant localization. The recommendations for implant localization were not followed as Merck now advises to use X-ray based methods such as plain X-ray or computed tomography for visualization as first line method (summary of products characteristics for Nexplanon®). It then states that ultrasound using a specific probe ‘may also be used’. Traditionally, ultrasound was used to localise the non X-ray visible previously used Implanon® implant. In this case, the use of ultrasound and MRI delayed the diagnosis of implant migration and an unnecessary surgical removal attempt was performed. A clear question to the radiologist of ‘implant in lung’ is preferable. In our case the initial chest X-ray radiological report was negative. The original report was written by a resident in radiology but according to local guidelines the X-ray was also assessed and countersigned by a consultant in radiology. However, the reported ‘no subcutaneous implants detectable’ should have prompted a reaction from the referring gynaecologist that the assessors had not properly searched for the implant in the lung arteries. Other pulmonary abnormalities could also make it make it more difficult to distinguish the implant on a regular chest X-ray. Therefore, in our opinion, when ENG levels are detected and the implant is clearly not localised in the arm or armpit, the use of chest CT, preferably with CT angiography as the first choice, should be the next step

Most implants are likely to migrate quickly after insertion. Advise to palpate implants at regular time intervals lacks evidence base. According to the instructions for users, women who at any point cannot palpate the implant should immediately contact their health care provider. We conclude that underweight patients most likely have a higher risk of intravascular implant migration. Guidelines for implant detection should be followed and precise questions are necessary for proper evaluation and assessment of radiological diagnostic procedures.

Consent

The patient has given her informed consent in written form for publication of this article.

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