Ectopic Pregnancy

Definition

An ectopic pregnancy is the implantation of a fertilised ovum at a site other than the endometrial lining of the uterine cavity (1, 7). This represents a fundamental deviation from the normal process where the blastocyst implants within the specialised endometrium of the uterus (3). Because no other site is capable of supporting gestation, an ectopic pregnancy is a non-viable pregnancy that poses a significant threat to the mother's life, primarily through the risk of rupture and catastrophic intra-abdominal haemorrhage (2, 3).

Epidemiology

Globally, ectopic pregnancy occurs in approximately 1-2% of all diagnosed pregnancies (5). While specific, comprehensive prevalence data for Malaysia is not readily available in recent national health surveys, local hospital-based studies and regional data suggest its significance. For instance, a 2019 report noted that ectopic pregnancy was the fourth leading cause of maternal death in Malaysia, underscoring its critical importance in local clinical practice (6). The incidence is known to be rising worldwide, partly due to an increase in assisted reproductive technologies (ART) and better diagnostic capabilities (7). The condition carries a high clinical burden; it is a primary differential for any woman of reproductive age presenting to the emergency department with first-trimester abdominal pain and/or vaginal bleeding (2).

Pathophysiology

The core of an ectopic pregnancy's pathophysiology is the disruption or delay of the fertilised ovum's migration through the fallopian tube (3). This is not a passive failure but an active process involving damage to the tube's transport system, which relies on microscopic cilia and smooth muscle contractions to propel the embryo (3).

The most common cause of this damage is inflammation from pelvic inflammatory disease (PID), often due to pathogens like Chlamydia trachomatis (2, 3). This inflammation leads to scarring, adhesions, and direct destruction of the cilia (3). Furthermore, the inflammatory process itself can create a pro-implantation environment in the tube by altering cytokine signalling and the expression of adhesion molecules (3). Other factors include the ciliotoxic effects of smoking and hormonal alterations from certain contraceptives or fertility treatments that impair tubal motility (2, 7).

Clinical Presentation

The classic textbook presentation is a triad of amenorrhoea, lower abdominal pain, and vaginal bleeding (7). However, it is critical to know that this complete triad is present in a minority of patients (3).

• Diagnostic Clues: While no single sign is pathognomonic, the triad should trigger a high index of suspicion. The presence of shoulder tip pain or syncope are late, ominous signs indicating significant internal bleeding (3, 7).

• Common Symptoms (>50%):

  • Abdominal/Pelvic Pain: This is the most common symptom (up to 94%), often unilateral, but its character is highly variable—dull, sharp, or crampy (2, 3).

  • Amenorrhoea: A history of a missed period is reported in nearly all cases, but a patient may mistake the abnormal bleeding of an ectopic for a light period (3).

  • Vaginal Bleeding: Occurring in up to 57% of cases, this is typically light, intermittent, dark brown spotting (3, 7).

• Less Common Symptoms (10-50%):

  • Breast tenderness and nausea (typical early pregnancy symptoms) may be present (3).

  • Dizziness or light-headedness (7).

  • Urge to defecate or rectal pressure from blood in the pelvis (3).

• ⚠️ Red Flag Signs & Symptoms:

  • Sudden, severe, sharp, and persistent abdominal pain (3).

  • Dizziness, presyncope, or frank syncope (3).

  • Haemodynamic instability (tachycardia, hypotension) (2).

  • Shoulder tip pain (referred phrenic nerve irritation) (7).

  • Abdominal rigidity, guarding, or rebound tenderness on examination (3).

Complications

Complications can be acute and life-threatening or have long-term consequences.

• Acute: The most feared complication is tubal rupture, leading to massive intra-abdominal haemorrhage, hypovolemic shock, and potentially maternal death (2).

• Treatment-Related:

  • Surgical: Risks include infection, bleeding, and injury to adjacent organs. A specific risk of conservative surgery (salpingostomy) is persistent trophoblastic disease (5-20% of cases), where retained tissue continues to grow, requiring further treatment (3).

  • Medical: Methotrexate can cause gastrointestinal side effects, fatigue, and abdominal "separation pain" (3). Rarely, it can lead to bone marrow suppression or hepatotoxicity (1).

• Long-Term:

  • Recurrent Ectopic Pregnancy: The risk of a subsequent ectopic pregnancy is significantly elevated, at approximately 10-18.5% (2, 3).

  • Impaired Fertility: While most women can conceive again, future fertility depends heavily on the condition of the remaining fallopian tube and the patient's underlying risk factors (3).

  • Psychological Trauma: The combination of pregnancy loss and a life-threatening medical emergency can lead to significant grief, anxiety, and depression (3).

Prognosis

With timely diagnosis and treatment, the mortality rate from ectopic pregnancy has fallen dramatically, but it remains a leading cause of first-trimester maternal death (2, 5). The prognosis for future fertility is generally good, with the majority of women achieving a subsequent intrauterine pregnancy (3). However, the key determinant is the patient's underlying tubal health, not necessarily the type of treatment received for the ectopic pregnancy (1, 3).

Differential Diagnosis

[Threatened or Incomplete Miscarriage]: This is a key differential due to the shared features of abdominal pain and vaginal bleeding in early pregnancy. However, the pain is often midline and crampy, like menses, and the bleeding is typically heavier and redder than the spotting seen in an ectopic pregnancy. An ultrasound showing a definitive intrauterine sac, even if irregular, points away from an ectopic diagnosis (in the absence of heterotopic pregnancy) (3).

[Ruptured Corpus Luteum Cyst]: Consider this diagnosis as it can present with sudden, unilateral pain and intra-abdominal bleeding (hemoperitoneum). It is distinguished from an ectopic pregnancy on ultrasound by the visualisation of a complex adnexal cyst that is separate from a normal-appearing ovary, whereas an ectopic mass is typically seen in the fallopian tube (2, 3).

[Ovarian Torsion]: This should be considered, especially with the sudden onset of severe, colicky unilateral pain accompanied by nausea and vomiting. Vaginal bleeding is typically absent. A transvaginal ultrasound is key, showing an enlarged ovary with abnormal Doppler flow, and a negative pregnancy test makes torsion much more likely (2, 3).

[Pelvic Inflammatory Disease (PID)]: PID can cause bilateral lower abdominal pain and cervical motion tenderness, mimicking an ectopic. However, PID is often associated with purulent cervical discharge and systemic signs of infection. Crucially, the patient's pregnancy test will be negative (2, 3).

Investigations

Immediate & Bedside Tests

• Urine hCG Test: This is the mandatory first step for any woman of reproductive age with abdominal pain or vaginal bleeding to confirm pregnancy, as a negative test effectively rules out a symptomatic ectopic pregnancy (1, 3).

• Vital Signs Assessment: This is crucial to immediately identify haemodynamic instability (hypotension, tachycardia) which indicates a potential rupture and the need for emergent surgical intervention (2).

Diagnostic Workup

• First-Line Investigations:

  • Quantitative Serum β-hCG: This provides a crucial numerical value for the pregnancy hormone, which is essential for interpreting ultrasound findings (the action) and for monitoring the progression of the pregnancy over time to assess viability (the rationale) (1, 7).

  • Complete Blood Count (CBC): This establishes a baseline haemoglobin and haematocrit to identify pre-existing anaemia or to serve as a reference point (the action) in the event of acute haemorrhage from a rupture (the rationale) (3).

  • Blood Group and Rh Status: This is a critical safety step to determine the need for Rh(D) immune globulin in Rh-negative women to prevent alloimmunization (the action) and to prepare for potential blood transfusion by performing a group and screen or cross-match (the rationale) (1, 3).

• Gold Standard:

  • Transvaginal Ultrasonography (TVUS): This is the imaging modality of choice as it provides the most detailed view of the pelvic organs to locate the pregnancy (the action) (1, 7). The definitive diagnosis is the visualisation of a gestational sac with a yolk sac or embryo outside the uterus, although the absence of an intrauterine pregnancy in the setting of a positive β-hCG above the discriminatory zone is highly suggestive (the rationale) (3).

Monitoring & Staging

• Serial β-hCG Monitoring: In a stable patient with a pregnancy of unknown location (PUL), performing serial β-hCG tests 48 hours apart is essential to assess the viability of the pregnancy (the action), as a healthy intrauterine pregnancy demonstrates a characteristic rapid rise (at least 35-50% in 48 hours), while a suboptimal rise, plateau, or fall is highly suggestive of a non-viable pregnancy, such as an ectopic or a miscarriage (the rationale) (1, 3).

Management

Management Principles

The management of ectopic pregnancy focuses on ensuring maternal safety through rapid diagnosis and intervention, while preserving future fertility whenever possible (2). The choice of treatment is dictated by the patient's haemodynamic stability, clinical signs, and investigational results (1, 7).

Acute Stabilisation (The First Hour)

This applies to any patient with suspected rupture or haemodynamic instability.

• Airway/Breathing: Administer high-flow oxygen via a non-rebreather mask to maintain SpO2 >94% (the action), which is crucial to prevent tissue hypoxia driven by haemorrhagic shock (the rationale).

• Circulation: Secure two large-bore IV cannulas (e.g., 16G or 18G) and administer a stat fluid bolus of IV Normal Saline or Hartmann's solution 20mL/kg (the action) to correct hypotension and restore vital organ perfusion (the rationale) (2, 3). Simultaneously, send blood for an urgent group and cross-match and activate massive transfusion protocols if indicated (3).

• Disability: Assess conscious level using the Glasgow Coma Scale (GCS).

• Exposure: Keep the patient warm to prevent the coagulopathy associated with hypothermia. An urgent surgical consultation is mandatory (2).

Definitive Therapy

• Medical Management: For haemodynamically stable, compliant patients with an unruptured ectopic, methotrexate (MTX) is a primary option (1, 7). It is a folate antagonist that targets rapidly dividing trophoblastic cells, causing the pregnancy to stop growing and resorb (3).

  • First-Line Treatment (Malaysia context): The standard regimen is a single intramuscular dose of MTX 50 mg/m² of body surface area (8). This approach requires strict follow-up with β-hCG levels on Day 4 and Day 7 post-injection; a successful response is marked by a >15% drop between these days (6). Studies from Malaysian hospitals have confirmed the efficacy and safety of this protocol (6, 8).

  • Contraindications: Medical management is absolutely contraindicated in haemodynamically unstable patients, in the presence of an intrauterine pregnancy, or in patients with evidence of immunodeficiency, renal, or hepatic dysfunction (1, 7). Relative contraindications include high initial β-hCG levels (e.g., >5000 mIU/mL), a large ectopic mass (>3.5-4 cm), or the presence of embryonic cardiac activity, as these are associated with a higher failure rate (1, 7).

• Surgical Management: This is the definitive treatment for any patient who is unstable, has a ruptured ectopic, has contraindications to MTX, or has failed medical therapy (1, 7).

  • First-Line Approach: Laparoscopy is the preferred surgical method in stable patients as it is minimally invasive and allows for faster recovery (3, 7). A laparotomy (open surgery) is reserved for unstable patients with significant haemoperitoneum where rapid bleeding control is the priority (3).

  • Procedure Choice:

    • Salpingectomy: This is the complete removal of the affected fallopian tube (3). It is the preferred surgery when the tube is severely damaged or ruptured, or if the patient has a healthy contralateral tube and desires future fertility, as it definitively removes the ectopic and may reduce recurrence risk without harming overall fertility potential (1, 3).

    • Salpingostomy: This is a tube-sparing procedure where an incision is made, the ectopic is removed, and the tube is left in place (3). It is the preferred option for a patient who desires future fertility and whose other fallopian tube is absent or damaged (1, 3).

Supportive & Symptomatic Care

• Analgesia: Provide adequate pain relief, typically with paracetamol or opioids. Avoid NSAIDs in patients receiving methotrexate, as they can increase its toxicity (1).

• Anti-D Prophylaxis: Administer Rh(D) immune globulin to all non-sensitised Rh-negative women to prevent future haemolytic disease of the newborn (1, 3).

• Patient Education: Counsel the patient on the diagnosis, treatment plan, side effects, and the absolute need for follow-up. For MTX, advise avoiding folic acid, alcohol, and sexual intercourse until treatment is complete (1, 3).

Key Nursing & Monitoring Instructions

• Strict hourly monitoring of vital signs (BP, HR, RR, SpO2) for any unstable patient or post-operatively.

• For stable patients managed medically, monitor for any new or worsening pain, which could signal rupture.

• Strict input/output chart monitoring, especially in cases of haemorrhage or fluid resuscitation.

• Inform medical staff immediately if systolic BP drops below 100 mmHg, heart rate rises above 100 bpm, or urine output is <0.5mL/kg/hr.

Long-Term Plan & Patient Education

The long-term plan focuses on recovery, psychological support, and planning for future pregnancies.

• Follow-up: Ensure β-hCG levels are trended to zero (<5 mIU/mL) after medical or conservative surgical management to confirm complete resolution (3, 7).

• Future Pregnancy: Advise waiting at least 2-3 menstrual cycles before attempting conception again to allow for physical and emotional healing (3). If treated with methotrexate, it is crucial to wait at least 3 months to ensure the drug is cleared and poses no teratogenic risk (3).

• Recurrence Risk: The most critical education point is the high risk of recurrence. The patient must be instructed to seek immediate medical care for an early ultrasound scan as soon as she has a positive pregnancy test in the future to confirm the location of the pregnancy (3).

• Psychological Support: Acknowledge the emotional trauma of the event, which involves both pregnancy loss and a personal health crisis. Offer referrals to support groups or mental health professionals (3).

When to Escalate

Call Your Senior (MO/Specialist) if:

• The patient is haemodynamically unstable or has signs of a ruptured ectopic (e.g., severe pain, syncope, peritonism).

• The diagnosis is uncertain after initial ultrasound and β-hCG (i.e., a complex Pregnancy of Unknown Location).

• The patient is a candidate for medical management but has relative contraindications that require senior-level decision making.

• A patient undergoing medical management develops worsening pain or fails to show the expected decline in β-hCG levels.

Referral Criteria:

• All patients with a confirmed or highly suspected ectopic pregnancy require immediate referral to the Obstetrics & Gynaecology team for management.

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References

1. ACOG Practice Bulletin No. 193: Tubal Ectopic Pregnancy. (2018). Obstetrics & Gynecology, 131(3), e91-e103. https://pubmed.ncbi.nlm.nih.gov/29470343/

2. Adhikari, S., & Gerson, L. (2024). Ectopic Pregnancy. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK539860/

3. Ectopic Pregnancy Clinical Review. (n.d.). Provided Document.

4. MIMS Malaysia. (2023). Ectopic Pregnancy: Disease Summary. https://www.mims.com/malaysia/disease/ectopic-pregnancy

5. Ministry of Health Malaysia. (n.d.). inexscreen as a screening test for ectopic pregnancy. Retrieved July 9, 2024, from https://www.moh.gov.my/index.php/database_stores/attach_download/347/250

6. Ng, Y. H., Nordin, N., & Ismail, N. A. (2022). A 10-Year Review of Methotrexate Treatment for Ectopic Pregnancy in a Malaysian Tertiary Referral Hospital. Cureus, 14(11), e30395. https://pmc.ncbi.nlm.nih.gov/articles/PMC9671276/

7. Royal College of Obstetricians and Gynaecologists. (2016). Diagnosis and Management of Ectopic Pregnancy (Green-top Guideline No. 21). RCOG. https://www.rcog.org.uk/guidance/browse-all-guidance/green-top-guidelines/diagnosis-and-management-of-ectopic-pregnancy-green-top-guideline-no-21/

8. Zainuddin, A. A., & Loh, K. Y. (2016). Single dose methotrexate for the treatment of unruptured ectopic pregnancy: experience in Kemaman Hospital, Terengganu, Malaysia. International Journal of Reproduction, Contraception, Obstetrics and Gynecology, 5(7), 2419-2422. https://www.researchgate.net/publication/303743147_Single_dose_methotrexate_for_the_treatment_of_unruptured_ectopic_pregnancy_experience_in_Kemaman_Hospital_Terengganu_Malaysia