Ectopic pregnancy (EP) is a potentially life-threatening condition affecting up to two percent of pregnancies, where a fertilised egg implants outside the uterine cavity ¹. Between 2015 and 2017 in Australia, a single maternal death was attributed to ectopic pregnancy, corresponding to a maternal mortality ratio of 0.2 per 100,000 live births during that period ^2.

EP predominantly occurs in the fallopian tube, especially within the ampullary region. The management of ectopic pregnancy is guided by several fundamental principles that emphasise timely diagnosis, patient stabilisation, and personalised care to meet both immediate clinical requirements and long-term health considerations ^1,3.

Diagnosing Pregnancy in Early Stages

The primary objective of early pregnancy assessment is to determine whether the pregnancy is intrauterine and viable. When transvaginal ultrasound (TVUS) fails to confirm the pregnancy’s location, it is categorised as a pregnancy of unknown location (PUL). Conversely, if an intrauterine pregnancy is observed but its viability is unclear, it is referred to as an intrauterine pregnancy of uncertain viability (IPUV). These classifications inform subsequent investigations and interventions aimed at achieving a definitive diagnosis^{1, 3}.

Early pregnancy can be a challenging time for patients, and the availability of high-resolution gynaecological ultrasound improves timely and accurate assessment. In cases of EP, ultrasound findings may include:

• Absence of an intrauterine gestational sac in a patient with a positive pregnancy test.
• An adnexal mass with features suggestive of an EP, such as a tubal ring sign, a heterogeneous mass adjacent to the ovary, or a live extrauterine embryo.
• Free fluid in the pelvis or Morison’s pouch, which may indicate rupture and intra-abdominal bleeding.
• An empty uterus with a thickened endometrium, at times showing a pseudo-gestational sac with fluid in the uterus too.

Key Risk Factors for Ectopic Pregnancy

Studies indicate that the following conditions increase the chances of having an EP:

• History of EP: Women who have previously experienced an EP have an approximately 10% chance of recurrence ⁴.
• Pelvic inflammatory disease (PID): Infections such as Chlamydia Trachomatis can cause damage to the fallopian tubes raising the risk ⁴.
• Tubal surgery or infertility treatments: Procedures that affect the fallopian tubes or assistive reproductive technologies may predispose individuals to ectopic implantation⁴.
• Older age and endometriosis: Both are linked to structural or functional changes in the reproductive system ⁴.
• Surgical history: Abdominal surgeries, including caesarean sections or appendectomies, may disrupt normal tubal function ⁴.
• Contraceptive failure: While intrauterine devices (IUDs) and emergency contraception lower the overall risk of pregnancy, they may present a higher relative risk of ectopic pregnancy in cases of conception⁴.
• Cigarette smoking: Smoking can disrupt tubal motility by increasing levels of proteins such as PROKR¹, which may impede the movement of the fertilised egg.

Principles of Management

1. 1. Early Diagnosis and Clinical Vigilance
      The foundation of managing EP lies in a prompt and accurate diagnosis. Any woman of reproductive age who presents with pelvic pain and a positive pregnancy test should be assumed to have an EP until proven otherwise. It is essential to consider the possibility of EP even in the absence of risk factors, as about half of women with EP do not exhibit any identifiable risk factors ⁵.Key diagnostic tools include:
      • History taking: Detailed assessment of amenorrhea duration, symptoms such as pain, bleeding, or dizziness, and clarification of whether the pregnancy was planned and is wanted.
      • Transvaginal ultrasound: This supports determining the location of the pregnancy. In a normally progressing intrauterine pregnancy, an intrauterine sac is typically visible when the quantitative β-hCG level exceeds 1,500 mIU/mL (the discriminatory zone) ³.
      • Quantitative β-hCG testing: Serial measurements may better help distinguish between viable intrauterine pregnancy, ectopic pregnancy, and pregnancy of unknown location (PUL) by analysing patterns of change, we tell patients it is like a piece of the puzzle that helps clarify what is going on, in addition to the ultrasound results ¹.
   2. Stabilisation of Hemodynamically Unstable Patients and Surgical Procedure SelectionFor patients with signs of hemodynamic instability, including severe pain, hypotension, and tachycardia, immediate resuscitation and surgical intervention are critical. Management steps include:
      • Resuscitation and transfusion
        Activation of massive transfusion protocols where needed ensures timely blood/ product replacement.
      • Focused Assessment with Sonography in Trauma (FAST)
        Identifies free fluid or blood in the abdomen, a sign of rupture.
      • Surgical intervention
        The decision between laparoscopy and laparotomy is influenced by maternal stability, surgical expertise, and the available resources. Laparoscopy is typically preferred where possible, whereas laparotomy may be the best fit when managing significant patient deterioration. When surgical treatment is indicated for women with an EP, it should be performed laparoscopically whenever possible, considering the condition of the woman and the complexity of the surgical procedure^1,3.
      • NICE guidelines recommend:
        • Offering salpingectomy (removal of the affected fallopian tube) to women undergoing surgery for EP, unless there are infertility risks ¹.
        • Salpingotomy (removal of the ectopic pregnancy while preserving the fallopian tube) should be considered for those with risk factors for infertility, such as contralateral tube damage ¹.
        • Women undergoing salpingotomy should be informed that up to 20% may require further treatment with methotrexate and/or further salpingectomy ¹.
        • Women who have had a salpingotomy should take one serum hCG measurement at seven days after surgery, then one serum hCG measurement per week until a negative result is obtained ¹.
        • Advise women who have had a salpingectomy that they should take a urine pregnancy test after three weeks. Advise women to return for further assessment if the test is positive. Hence, it is important to note that a salpingostomy may necessitate additional treatment (up to 1:5 women), such as methotrexate or a salpingectomy if follow-up hCG levels do not decline as expected ¹.
      • Postoperative monitoring: High-dependency or intensive care units may be required for fluid and blood loss management. Fluid input-output monitoring and close observation are essential.Stable patients have a broader range of management options, in addition to surgical ones:
        • Medical Management with Methotrexate
          This approach is appropriate for select patients with unruptured EP who present without active heavy bleeding, and β-hCG < 5000 IU/L3,4. Methotrexate is a folate antagonist that inhibits DNA synthesis and cell replication, primarily inhibiting the proliferation of quickly dividing trophoblastic cells in EPs ³. Most women would only need one dose of methotrexate. However, about 15% will need a second dose one week later 5. Methotrexate can be administered via two routes in Queensland according to the guideline, depending on the β-hCG levels: intramuscularly if β-hCG is ≤ 3000 IU/L, and intravenously if β-hCG is > 3000 IU/L 6. However, in New South Wales it is usually done through intramuscular injection in the buttocks ³. Nonetheless, it is important to regularly monitor β-hCG levels to ensure the effectiveness of the treatment.
        • Expectant Management
          This approach is suitable for patients with declining β-hCG levels between 1000 and 1500 IU/mL, minimal symptoms, and no indications of rupture. It is important to note that different guidelines specify varying thresholds for expectant management regarding β-hCG levels; for instance, New South Wales guidelines indicate a level of <1000 IU/L, while Queensland guidelines specify <1500 IU/L3,6. This method necessitates careful monitoring, thorough follow-up with the patient, and comprehensive education on the process.
        • As per the NICE guidelines, ‘advise women that, based on limited evidence, there seems to be no difference following expectant or medical management in the rate of EPs ending naturally, the risk of tubal rupture, the need for additional treatment, but that they might need to be admitted urgently if their condition deteriorates and health status, depression or anxiety scores change.  Advise women that the time taken for ectopic pregnancies to resolve and future fertility outcomes are likely to be the same with either expectant or medical management ¹.
   3. Supportive Care and Emotional WellbeingEP can have significant emotional and psychological effects, particularly for individuals who wish to maintain their fertility. Statistically, about 65% of women achieve a healthy pregnancy within 18 months after an ectopic pregnancy, with this likelihood increasing to over 80% over two years. However, it is also important to note that the risk of recurrent EP is approximately 10-15%, increasing to 30% after two ectopic pregnancies. Hence the need for an early dating ultrasound in any subsequent pregnancy ⁵.Therefore, it is an essential part of the process to provide emotional support and clear communication. Patients should receive counselling about their condition, the available treatment options, and the potential for future pregnancies. Referral to a psychologist or counselling may be helpful for some women.
   4. Long-Term Follow-UpFollow-up care is essential for ensuring the complete resolution of the pregnancy and offers a chance to address any underlying risk factors or conditions. Professionals should counsel patients on strategies to reduce the risk of recurrence, such as managing sequelae of pelvic infections, quitting smoking and avoiding sexual intercourse immediately after treatment for an ectopic pregnancy. Furthermore, individuals treated via salpingostomy, medically, expectantly should undergo serial β-hCG testing until their hormone levels return to baseline.^1,3

Conclusion

EP is a complex condition that necessitates a patient-centred approach, emphasising safety, timely diagnosis, and tailored care. Patients who are hemodynamically unstable benefit from immediate surgical intervention, while those who are stable may have a wider array of management options available, including medical or expectant strategies. By integrating comprehensive clinical assessments, evidence-based treatment protocols, and supportive care, healthcare providers can enhance patient outcomes and effectively address the physical and emotional challenges of those navigating this difficult condition.

Some resources that may be helpful for patients include:

• National Health Service Ectopic Pregnancy ⁴.
• The Ectopic Pregnancy Trust ⁵.
• Healthdirect ectopic pregnancy information ⁷.