ECTOPIC PREGNANCY ASSOCIATED WITH THE USE OF A LEVONORGESTREL-RELEASING INTRAUTERINE SYSTEM (LNG-IUS, JAYDESS): CASE REPORT AND CLINICAL IMPLICATIONS

UDC 618.3-06:618.11-007.43-089.87

 

ECTOPIC PREGNANCY ASSOCIATED WITH THE USE

OF A LEVONORGESTREL-RELEASING INTRAUTERINE SYSTEM (LNG-IUS, JAYDESS): CASE REPORT AND CLINICAL IMPLICATIONS

 

Mihalcean Luminița, MD, PhD, Associate Professor Department of Obstetrics and Gynecology

Nicolae Testemitanu State Medical and Pharmacy University

(Moldova, Chisinau, Blvd. Stefan cel Mare, 165)

E-mail: luminita.mihalcean@usmf.md

 

Corolcova Natalia, MD, PhD, Associate Professor Department of Obstetrics and Gynecology

Nicolae Testemitanu State Medical and Pharmacy University

(Moldova, Chisinau, Blvd. Stefan cel Mare, 165)

E-mail: natalia.corolcova@usmf.md

 

Burac Mihaela, Assistant Professor Department of Obstetrics and Gynecology

Nicolae Testemitanu State Medical and Pharmacy University

(Moldova, Chisinau, Blvd. Stefan cel Mare, 165)

E-mail: mihaela.burac@usmf.md

 

Cotelea Veronica, MD, PhD, Assistant Professor, Department of Obstetrics and Gynecology

Nicolae Testemitanu State Medical and Pharmacy University

(Moldova, Chisinau, Blvd. Stefan cel Mare, 165)

E-mail: veronica.cotelea@usmf.md

 

Аbstract. Ectopic pregnancy remains a major cause of maternal morbidity in early gestation and poses significant diagnostic and therapeutic challenges. Although levonorgestrel-releasing intrauterine systems (LNG-IUS) are among the most effective contraceptive methods, pregnancies occurring with the device in situ are disproportionately ectopic. This article presents a clinical case of tubal ectopic pregnancy in a 31-year-old woman using Jaydess (13.5 mg LNG-IUS), complicated by tubal rupture and hemoperitoneum. The report analyses current international evidence regarding ectopic pregnancy risk associated with low-dose LNG-IUS, diagnostic strategies based on ultrasound and β-hCG dynamics, and management options. The novelty of the study lies in the comprehensive assessment of concomitant endocrine disorders and their potential impact on reproductive outcomes. The findings highlight the importance of early clinical suspicion, individualized diagnostic algorithms, and multidisciplinary management in women using hormonal intrauterine contraception.

Keywords: ectopic pregnancy, levonorgestrel intrauterine system, Jaydess, tubal rupture, hypothyroidism, case report.

 

Introduction. Ectopic pregnancy (EP) is a gynaecological emergency and remains the leading cause of maternal deaths in the first trimester of pregnancy. Most cases occur in the fallopian tube, and early diagnosis is crucial to minimise complications and preserve fertility [1, 2]. In recent years, the use of levonorgestrel-releasing intrauterine systems (LNG-IUS) has increased significantly, with younger women preferring Jaydess (13.5 mg) due to its safety profile and low hormonal dose.

Several reports indicate that although LNG-IUS significantly reduces the overall risk of pregnancy, the likelihood of ectopic implantation is higher compared to the general population in the event of conception [2, 3]. Previous research conducted in the Republic of Moldova demonstrated the role of endometrial processes and chronic inflammatory factors in female infertility, including the presence of plasma cells in the endometrium of women with primary infertility [4].

Recent studies confirm that LNG-IUS substantially reduces the absolute risk of both intrauterine and ectopic pregnancy; however, in rare cases of contraceptive failure, the proportion of ectopic implantations is higher than in the general population [2, 3]. A nationwide cohort study published in JAMA showed a dose-dependent gradient, with Jaydess (13.5 mg) associated with the highest rate of ectopic pregnancy per 10,000 person-years, compared with devices containing 19.5 mg and 52 mg [1].

Clinical reports describe cases of tubal ectopic pregnancy in Jaydess users, sometimes occurring within the first year after insertion [3, 7]. These observations underscore the necessity of heightened clinical vigilance in all IUD users who present with a positive pregnancy test.

The etiology of ectopic pregnancy includes impaired tubal motility, ciliary dysfunction, and alterations of the uterine microenvironment [2]. LNG-IUS acts mainly through local mechanisms, including cervical mucus thickening and endometrial suppression. Some hypotheses suggest that this anti-implantation effect may, in rare cases, facilitate ectopic implantation; however, empirical data regarding the influence of levonorgestrel on tubal ciliary activity remain inconsistent [2, 3].

The association between hypothyroidism and ectopic pregnancy remains insufficiently studied. An observational study reported significantly lower FT3 levels in women with ectopic pregnancy compared to those with intrauterine gestation, suggesting a possible association; however, methodological limitations restrict causal interpretation. Currently, hypothyroidism is recognised primarily as a risk factor for infertility, miscarriage, and obstetric complications, rather than ectopic implantation per se [1].

Luteal phase deficiency (LPD), characterised by inadequate progesterone secretion, is associated with infertility and early pregnancy loss. Nevertheless, the ASRM Practice Committee concluded that there is no strong evidence linking LPD directly to the risk of tubal implantation [2].

Diagnosis of ectopic pregnancy relies on the integration of transvaginal ultrasound and β-hCG dynamics. Current NICE and HSE guidelines recommend avoiding fixed β-hCG thresholds and using algorithms for pregnancy of unknown location (PUL) [8, 10].

In confirmed pregnancies among IUD users, FSRH guidelines recommend removal of the device when strings are visible to reduce complications [9]. Management options for ectopic pregnancy include expectant management, methotrexate therapy in selected stable patients, and surgical treatment in cases of haemodynamic instability or tubal rupture [8, 10].

Case Presentation

On July 2, 2025, a 31-year-old female patient presented to the emergency department of Gheorghe Paladi Municipal Hospital in Chișinău, complaining of mild pain in her left iliac fossa, which had begun 24 hours earlier, and intermittent brown vaginal discharge, which had persisted for three weeks.

The patient's history revealed irregular menstrual cycles (with intervals of up to 180 days), with her last menstrual period occurring on April 17, 2025. Previously, she had become pregnant twice after treatment with progesterone to regulate her menstrual cycle, both pregnancies culminating in normal full-term deliveries. In the past year, she had used a levonorgestrel-releasing intrauterine system (LNG-IUS) as a method of contraception.Medical history: primary hypothyroidism treated with Euthyrox 75 µg/day since the age of 20. On 1–2 July, she performed two pregnancy tests, both yielding positive results.

Clinical findings: The general condition was relatively stable, with normal haemodynamic parameters. On abdominal examination, slight tenderness was noted in the left iliac fossa, with no signs of peritonitis. Vaginal examination revealed tenderness in the left adnexa, with a moderately painful, mobile mass measuring 3 cm.

Laboratory findings: Complete blood count and coagulation profile were within normal limits. Transvaginal ultrasound showed a uterus of normal size, with an intrauterine device in the correct position, no free pelvic fluid, and a 20 mm gestational sac in the left fallopian tube containing a viable foetus (6 mm, fetal heart rate 128 bpm), equivalent to a gestation of 6 weeks and 3 days.

An emergency laparoscopy was performed, revealing approximately 300 ml of blood in the peritoneum. The left fallopian tube appeared deformed, cyanotic, and ruptured in the ampullary portion, containing an ectopic pregnancy. The left fallopian tube was resected, with complete removal of the ectopic pregnancy. Final diagnosis: ectopic pregnancy in the left fallopian tube (tubal abortion type) complicated by peritoneal hemorrhage. Postoperative course was positive under antibiotic and anti-inflammatory treatment (ceftriaxone, ketoprofen, clavulanic acid), with gradual clinical improvement.

It has been confirmed that the patient's history of hypothyroidism was well controlled and is still considered a risk factor for infertility, spontaneous abortion, missed abortion and obstetric complications, but without strong evidence of a causal relationship with ectopic pregnancy [1, 11].

3. Discussion

This clinical case supports international evidence indicating a relatively increased risk of ectopic pregnancy in rare cases of LNG-IUS contraceptive failure [1]. The timing of presentation, less than one year after insertion, is consistent with previously reported cases [3, 7].

Diagnostic and therapeutic decisions were aligned with contemporary international recommendations, which favour ultrasound-based confirmation and prompt surgical management in cases of viable tubal pregnancy with haemoperitoneum [4-6].

Histopathological and clinical data suggest a multifactorial mechanism involving hormonal milieu, endometrial status, and tubal function [2, 4]. Although endocrine disorders such as hypothyroidism and luteal phase deficiency may complicate reproductive outcomes, current evidence does not support a direct causal relationship with ectopic implantation [1, 9].

Lessons Learned

1. Early clinical suspicion and targeted examination. In this patient's case, the presence of mild abdominal pain and brown vaginal discharge, although not specified, was sufficient to raise suspicion of an ectopic pregnancy, due to positive pregnancy tests and the use of LNG-IUS. Lesson learned: Clinicians should immediately rule out ectopic pregnancy with β-hCG and transvaginal ultrasound, even when symptoms are mild, for all women of reproductive age who use intrauterine hormonal contraception and present with pain or abnormal discharge.
2. Multimodal diagnosis improves accuracy. Transvaginal ultrasound findings (pregnancy sac with viable foetus in the left fallopian tube) combined with clinical and laboratory stability allowed for rapid and accurate diagnosis before catastrophic rupture. Lesson learned: This confirms the advantage of combining β-hCG dynamics and ultrasound, rather than relying on a fixed threshold for β-hCG.
3. Surgical decision based on viability and stability. Given the presence of a viable foetus and intra-abdominal bleeding, conservative or medical treatment (methotrexate) was not recommended. Lesson learned: Laparoscopic surgery was appropriate and evidence-based, preventing further haemorrhagic complications.
4. Managing comorbidities and improving health prior to pregnancy. The patient's hypothyroidism was controlled, but its presence alongside corpus luteum insufficiency may have contributed to a complex hormonal environment that affected reproductive outcomes. Lesson learned: Although hormonal imbalances are not a direct cause of ectopic pregnancy, they should be corrected before pregnancy to prevent infertility, spontaneous abortion, or obstetric complications.
5. Patient counseling and informed choice of contraception. This case highlights the importance of informed consent and post-insertion counseling for LNG-IUS users. Lesson learned: Patients should be informed that although LNG-IUS is one of the most effective methods of contraception, pregnancies that occur are mostly ectopic.

Conclusions

1. Although the intrauterine device that releases levonorgestrel (Jaydess, 13.5 mg) is an effective method of contraception, it may be associated with a relative increase in the risk of ectopic pregnancy in rare cases of contraceptive failure.
2. An integrated diagnostic approach combining transvaginal ultrasound and β-hCG monitoring, in accordance with NICE (2023) and HSE (2024) recommendations [5, 6], remains essential for early detection.
3.  Endocrine disorders, such as hypothyroidism and luteal phase deficiency, do not directly cause ectopic pregnancy, but they complicate the reproductive process, underscoring the need for multidisciplinary management and hormone optimisation prior to pregnancy to reduce overall obstetric risks.

 

REFERENCES

1. Aksin, S., et al. Thyroid hormones in ectopic pregnancy. Eurasian Journal of Medicine. 2024.
2. ASRM Practice Committee. Diagnosis and treatment of luteal phase deficiency. Fertility and Sterility. 2021.
3. Babiker, A. Ectopic pregnancy with levonorgestrel-releasing intrauterine device (Jaydess) in situ. Irish Medical Journal. 2024.
4. Burac, M., Corolcova, N., Mihalcean, L., Cotelea, V. Aprecierea plasmocitelor în endometrul femeilor cu infertilitate primară. Sănătate Publică, Economie și Management în Medicină. 2024; 98(1): 60.
5. Chong, K.Y., et al. Ectopic pregnancy. Nature Reviews Disease Primers. 2024. Available at: https://www.nature.com/articles/ (accessed 15.12.2025).
6. Chu, Y.Q., et al. Early intrauterine pregnancy with an intrauterine device in situ: case report and review. BMC Pregnancy and Childbirth. 2024.
7. Faculty of Sexual and Reproductive Healthcare (FSRH). Clinical Guideline: Intrauterine Contraception. 2023. Available at: https://www.fsrh.org/ (accessed 15.12.2025).
8. Health Service Executive (HSE). National Clinical Guideline: Diagnosis and Management of Ectopic Pregnancy. 2024. Available at: https://www.hse.ie/ (accessed 15.12.2025).
9. Meaidi, A., et al. Ectopic pregnancy risk in users of levonorgestrel-releasing intrauterine systems: a nationwide cohort study. JAMA. 2023. Available at: https://pmc.ncbi.nlm.nih.gov/ (accessed 15.12.2025).
10. Mullany, T., et al. Overview of ectopic pregnancy diagnosis, management, and innovation. Frontiers in Global Women’s Health. 2023.
11. Tabuica, U., Mihalcean, L. Estimarea factorilor de risc pentru survenirea sarcinii stagnate în evoluţie. Buletinul Academiei de Ştiinţe a Moldovei. Ştiinţe Medicale. 2009; 21(2): 246–252.

 

REFERENCES

1.   Aksin S., et al. Thyroid hormones in ectopic pregnancy. Eurasian Journal of Medicine. 2024.

2.   ASRM Practice Committee. Diagnosis and treatment of luteal phase deficiency. Fertility and Sterility. 2021.

3.   Babiker A. Ectopic pregnancy with levonorgestrel-releasing intrauterine device (Jaydess) in situ. Irish Medical Journal. 2024.

4.   Burac M., Corolcova N., Mihalcean L., Cotelea V. Aprecierea plasmocitelor în endometrul femeilor cu infertilitate primară. Sănătate Publică, Economie și Management în Medicină. 2024; 98(1): 60.

5.   Chong K.Y., et al. Ectopic pregnancy. Nature Reviews Disease Primers. 2024. Available at: https://www.nature.com/articles/ (accessed 15.12.2025).

6.   Chu Y.Q., et al. Early intrauterine pregnancy with an intrauterine device in situ: case report and review. BMC Pregnancy and Childbirth. 2024.

7.   Faculty of Sexual and Reproductive Healthcare (FSRH). Clinical Guideline: Intrauterine Contraception. 2023. Available at: https://www.fsrh.org/ (accessed 15.12.2025).

8.   Health Service Executive (HSE). National Clinical Guideline: Diagnosis and Management of Ectopic Pregnancy. 2024. Available at: https://www.hse.ie/ (accessed 15.12.2025).

9.   Meaidi A., et al. Ectopic pregnancy risk in users of levonorgestrel-releasing intrauterine systems: a nationwide cohort study. JAMA. 2023. Available at: https://pmc.ncbi.nlm.nih.gov/ (accessed 15.12.2025).

10. Mullany T., et al. Overview of ectopic pregnancy diagnosis, management, and innovation. Frontiers in Global Women’s Health. 2023.

11. Tabuica U., Mihalcean L. Estimarea factorilor de risc pentru survenirea sarcinii stagnate în evoluţie. Buletinul Academiei de Ştiinţe a Moldovei. Ştiinţe Medicale. 2009; 21(2): 246–252.

 

Материал поступил в редакцию 26.12.25

 

 

ВНЕМАТОЧНАЯ БЕРЕМЕННОСТЬ, АССОЦИИРОВАННАЯ

С ПРИМЕНЕНИЕМ ВНУТРИМАТОЧНОЙ СИСТЕМЫ С ВЫСВОБОЖДЕНИЕМ ЛЕВОНОРГЕСТРЕЛА (ЛНГ-ВМС, JAYDESS):

КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ И КЛИНИЧЕСКИЕ ИМПЛИКАЦИИ

 

Михалчян Луминица, кандидат медицинских наук, доцент кафедры акушерства и гинекологии

Государственный медицинский и фармацевтический университет имени Николая Тестемицану

(Молдова, Кишинёв, бул. Штефан чел Маре, 165)

E-mail: luminita.mihalcean@usmf.md

 

Королкова Наталья, кандидат медицинских наук, доцент кафедры акушерства и гинекологии

Государственный медицинский и фармацевтический университет имени Николая Тестемицану

(Молдова, Кишинёв, бул. Штефан чел Маре, 165)

E-mail: natalia.corolcova@usmf.md

 

Бурак Михаэла, ассистент кафедры акушерства и гинекологии

Государственный медицинский и фармацевтический университет имени Николая Тестемицану

(Молдова, Кишинёв, бул. Штефан чел Маре, 165)

E-mail: mihaela.burac@usmf.md

 

Котелеа Вероника, кандидат медицинских наук, ассистент кафедры акушерства и гинекологии

Государственный медицинский и фармацевтический университет имени Николая Тестемицану

(Молдова, Кишинёв, бул. Штефан чел Маре, 165)

E-mail: veronica.cotelea@usmf.md

 

Аннотация. Внематочная беременность остается одной из ведущих причин материнской заболеваемости в ранние сроки гестации и представляет собой значимую диагностическую и терапевтическую проблему. Несмотря на то что внутриматочные системы с высвобождением левоноргестрела (ЛНГ-ВМС) относятся к числу наиболее эффективных методов контрацепции, беременность, наступающая при наличии устройства in situ, непропорционально чаще является внематочной. В статье представлен клинический случай трубной внематочной беременности у 31-летней пациентки, использующей систему Jaydess (ЛНГ-ВМС 13,5 мг), осложненной разрывом маточной трубы и гемоперитонеумом. Проведен анализ современных международных данных о риске внематочной беременности, ассоциированной с применением низкодозированных ЛНГ-ВМС, диагностических стратегий, основанных на ультразвуковом исследовании и динамике уровня β-ХГЧ, а также тактики ведения пациенток. Новизна исследования заключается в комплексной оценке сопутствующих эндокринных нарушений и их возможного влияния на репродуктивные исходы. Полученные результаты подчеркивают важность ранней клинической настороженности, индивидуализированных диагностических алгоритмов и мультидисциплинарного подхода к ведению женщин, использующих гормональную внутриматочную контрацепцию.

Ключевые слова: внематочная беременность, внутриматочная система с левоноргестрелом, Jaydess, разрыв маточной трубы, гипотиреоз, клинический случай.