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Objective <p>This review aimed to assess the efficacy and safety of letrozole, administered either as monotherapy or combined with methotrexate, for the treatment of ectopic pregnancy (EP).</p> Methods <p>Following established guidelines (PRISMA), a systematic review and meta-analysis was conducted. Major online research databases (Web of Science, PubMed, Scopus, and Cochrane Library) were searched for studies comparing letrozole to methotrexate in women diagnosed with EP via ultrasound, from the earliest available records up to November 5, 2024. The combined results were analyzed using risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). The quality of the included studies was evaluated using ROB-2 and ROBINS-I tools.</p> Results <p>Eight studies (five randomized and three non-randomized trials) involving 548 participants were included. Letrozole monotherapy achieved a higher treatment success rate compared to methotrexate (6 studies, 376 patients, RR 1.10, 95% CI [1.01, 1.20], <i>p</i> = 0.03). Combining letrozole with methotrexate showed comparable success rates to methotrexate alone (2 studies, 161 patients, RR 1.09, 95% CI [0.96, 1.23], <i>p</i> = 0.17). On day 4, β-human chorionic gonadotropin (β-hCG) levels decreased faster in both the letrozole monotherapy (5 studies, 291 patients, MD -131.15 mIU/mL, 95% CI [-220.77, -41.52], <i>p</i> = 0.004) and combination groups (2 studies, 136 patients, MD -188.79 mIU/mL, 95% CI [-242.07, -135.52], <i>p</i> &lt; 0.00001). Letrozole monotherapy resulted in a smaller reduction in platelet count (2 studies, 76 patients, MD 81.61 × 10³/µL, 95% CI [40.11, 123.10], <i>p</i> = 0.0001) and better-preserved liver enzymes, such as ALT (3 studies, 76 patients, MD -21.27 IU/L, 95% CI [-24.42, -18.12], <i>p</i> &lt; 0.00001). No differences were noted in anti-Müllerian hormone (AMH) levels (2 studies, 39 patients, MD -0.01 ng/mL, 95% CI [-0.40, 0.38], <i>p</i> = 0.97).</p> Conclusions <p>Letrozole, especially when used as the only treatment, may be a more effective and potentially safer alternative to methotrexate for medically treating EP. However, larger, higher-quality research studies are necessary to confirm these findings and to determine the best way to use letrozole.</p>

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The efficacy of letrozole in the medical management of ectopic pregnancy: a systematic review and meta-analysis

  • 期刊论文

  • 发表日期：

    2026年6月27日

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  • Derar H. Abdel-Qader,
  • Nada K. Abdelsattar,
  • Abdullah Albassam,
  • Khalid Awad Al-Kubais,
  • Esra’ Taybeh,
  • Nadia Al Mazrouei,
  • Rana Ibrahim,
  • Osama Mohamed Ibrahim,
  • Taha Abd-ElSalam Ashraf Taha

摘要

Objective

This review aimed to assess the efficacy and safety of letrozole, administered either as monotherapy or combined with methotrexate, for the treatment of ectopic pregnancy (EP).

Methods

Following established guidelines (PRISMA), a systematic review and meta-analysis was conducted. Major online research databases (Web of Science, PubMed, Scopus, and Cochrane Library) were searched for studies comparing letrozole to methotrexate in women diagnosed with EP via ultrasound, from the earliest available records up to November 5, 2024. The combined results were analyzed using risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). The quality of the included studies was evaluated using ROB-2 and ROBINS-I tools.

Results

Eight studies (five randomized and three non-randomized trials) involving 548 participants were included. Letrozole monotherapy achieved a higher treatment success rate compared to methotrexate (6 studies, 376 patients, RR 1.10, 95% CI [1.01, 1.20], p = 0.03). Combining letrozole with methotrexate showed comparable success rates to methotrexate alone (2 studies, 161 patients, RR 1.09, 95% CI [0.96, 1.23], p = 0.17). On day 4, β-human chorionic gonadotropin (β-hCG) levels decreased faster in both the letrozole monotherapy (5 studies, 291 patients, MD -131.15 mIU/mL, 95% CI [-220.77, -41.52], p = 0.004) and combination groups (2 studies, 136 patients, MD -188.79 mIU/mL, 95% CI [-242.07, -135.52], p < 0.00001). Letrozole monotherapy resulted in a smaller reduction in platelet count (2 studies, 76 patients, MD 81.61 × 10³/µL, 95% CI [40.11, 123.10], p = 0.0001) and better-preserved liver enzymes, such as ALT (3 studies, 76 patients, MD -21.27 IU/L, 95% CI [-24.42, -18.12], p < 0.00001). No differences were noted in anti-Müllerian hormone (AMH) levels (2 studies, 39 patients, MD -0.01 ng/mL, 95% CI [-0.40, 0.38], p = 0.97).

Conclusions

Letrozole, especially when used as the only treatment, may be a more effective and potentially safer alternative to methotrexate for medically treating EP. However, larger, higher-quality research studies are necessary to confirm these findings and to determine the best way to use letrozole.