Ectopic Pregnancy: Current Approaches to Clinical Management

• DOI: https://doi.org/10.22533/at.ed.15952625140720

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• Abstract:

  INTRODUCTION
      Ectopic pregnancy (EP), defined as the implantation of the embryo outside the uterine endometrial cavity, represents an important obstetric emergency and corresponds to approximately 2% of all clinically recognized pregnancies. (Leziak et al., 2022), 2022)The most common locations include the fallopian tube, although atypical forms, such as cervical pregnancy (CG) and pregnancy over a caesarean scar, have also been described with significant associated morbidity. (Stabile et al., 2020) EG is the leading cause of maternal mortality in the first trimester, accounting for up to 10% of pregnancy-related deaths, mainly due to tubal rupture and intra-abdominal bleeding. (Mullany et al., 2023)
  Early diagnosis is essential to avoid serious complications, including hemodynamic instability, loss of fertility and maternal death. However, diagnosis can be challenging, as the symptoms - abdominal pain, vaginal bleeding and menstrual delay - are non-specific and often mimic other acute abdominal conditions. The diagnosis of choice is based on clinical correlation with serial dosages of the hormone β-human chorionic gonadotrophin (β-hCG) and imaging tests, especially transvaginal ultrasound. In selected cases, an endometrial biopsy can be performed by means of a uterine curettage, which can help to exclude intrauterine pregnancy and increase the accuracy of the diagnosis. (Mullany et al., 2023) In cases classified as pregnancy of unknown location (PUL), which represent up to 31% of initial consultations with suspected ectopic pregnancy, diagnostic confirmation depends on the evolution of β-hCG levels and serial ultrasound examinations. In recent protocols, such as the one published by the Journal of Obstetrics and Gynaecology Canada, serial monitoring of β-hCG and transvaginal ultrasound has been recommended to adequately stratify risk, allowing expectant, medical (with the use of methotrexate) or surgical management (in cases of clinical instability, rupture or failure of drug treatment) according to hormonal progress, clinical signs and response to treatment (Po et al., 2021; Wiesenfeld et al., 2020).
  Therapeutic strategies for the management of GE include a clinical, surgical or expectant approach, with the choice guided by parameters such as serum β-hCG levels, hemodynamic stability and the presence of embryonic cardiac activity. (Mullany et al., 2023) Clinical treatment with methotrexate (MTX) has been shown to be effective in  up to 90% of selected cases, 2023) Clinical treatment with methotrexate (MTX), in single or multiple dose regimens, has been shown to be effective in up to 90% of selected cases, and is preferred because of its potential to preserve fertility and because it avoids the risks inherent in surgery. (Abdelfattah-Arafa et al., 2024; Leziak et al., 2022) However, therapeutic failures have been reported, especially in patients with elevated β-hCG, the presence of severe pelvic pain or embryonic cardiac activity, leading to the need for subsequent surgical intervention. Factors such as advanced maternal age and high initial β-hCG levels have been associated with a higher risk of clinical treatment failure (Abdelfattah-Arafa et al., 2024). More specifically, Abdelfattah-Arafa et al. (2024) identified that initial β-hCG levels of more than 2500 IU/L, the presence of severe abdominal pain and an adnexal mass greater than 35 mm are independent predictors of MTX treatment failure in tubal ectopic pregnancies, highlighting the importance of careful selection to avoid adverse outcomes.
   Therapeutic and diagnostic innovations have evolved significantly, including the development of new pharmacological agents and the improvement of minimally invasive techniques, with the aim of improving maternal safety and preserving fertility (Mullany et al., 2023).
  The search for therapeutic alternatives to MTX includes the use of drugs such as letrozole and gefitinib, as well as locally administered agents such as potassium chloride (KCl) and absolute ethanol. These agents have shown promise, especially in ectopic pregnancies of unusual location, such as cervical pregnancy or over uterine scarring. Recently, Leziak et al. (2022) highlighted letrozole as an emerging option in the conservative management of EG, as it interferes with estrogen synthesis and promotes regression of trophoblastic tissue. Although still in the experimental phase, letrozole has shown promising results in reducing β-hCG levels and favoring non-surgical resolution, especially in selected cases of tubal and cervical GE. A significant advance has been the combination of the systemic use of methotrexate with the local administration of agents - such as potassium chloride (KCl) or methotrexate injected under ultrasound guidance - which has shown high clinical success. A study of 82 patients with viable tubal pregnancies achieved a success rate of 93.3%, considerably higher than systemic treatment alone (73%) (Del Martel & Stanwood, 2014). Hysteroscopy, alone or in combination with MTX, has also been explored as an effective conservative strategy in early GC, promoting a faster drop in serum β-hCG levels and shortening the time to resolution of the clinical picture (Stabile et al., 2020). GC, despite its rarity, represents a clinical challenge due to the high risk of severe bleeding. Stabile et al. (2020) point out that, in cases diagnosed early, conservative treatment with local or systemic MTX associated with hysteroscopy enables effective control, reducing hysterectomy rates and optimizing future reproductive outcomes.
  In addition, it is worth highlighting the importance of individualized nutritional monitoring in the run-up to pregnancy, throughout pregnancy and also in the postpartum period.
  Future prospects in the management of ectopic pregnancy include the development of personalized protocols based on biomarkers and new pharmacological therapies. According to Leziak et al. (2022), in addition to letrozole, agents such as gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, are being studied for their ability to induce regression of ectopic gestational tissue with less toxicity. At the same time, the incorporation of artificial intelligence and predictive algorithms promises to improve diagnostic accuracy and optimize therapeutic decisions, contributing to greater maternal safety and fertility preservation (Mullany et al., 2023).
  Given the diversity of clinical presentations and therapeutic approaches, it is essential to critically review the current evidence related to the diagnosis and clinical management of ectopic pregnancy. This article aims to summarize the main diagnostic, therapeutic and prognostic advances related to EG, with an emphasis on approaches aimed at preserving fertility and reducing maternal morbidity and mortality (Abdelfattah-Arafa et al., 2024; Leziak et al., 2022; Mullany et al., 2023; Stabile et al., 2020).