{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:44:49Z","timestamp":1760060689002,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Ectopic pregnancy (EP) is a serious condition often treated with methotrexate. Letrozole, a safer aromatase inhibitor, may offer an effective alternative. This study presents a meta-analysis comparing the efficacy and safety of single-agent letrozole versus methotrexate for EP management. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. Six sources of information underwent screening until 12 June 2025. Risk of bias and evidence certainty of evidence were assessed. Primary outcome was treatment success rate. Results were presented as mean difference (MD) or risk ratio (RR) along with a 95% confidence interval (CI) using a random-effects model. Results: Six studies (three randomized controlled trials and three nonrandomized prospective cohort studies) comprising seven arms and 260 patients (letrozole = 130, methotrexate = 130) were included. Almost all studies (n = 5) had overall moderate or high risk. Treatment success rates were comparable between groups (n = 7 arms; RR = 1.05; 95% CI: [0.94, 1.17]; p = 0.40). Letrozole was associated with significantly lower \u03b2-hCG levels on day 4 (n = 5 arms; MD = \u221295 mIU\/mL; 95% CI: [\u2212189.7, \u22120.91]; p = 0.048), day 7 (n = 5 arms; MD = \u221286.24 mIU\/mL; 95% CI: [\u2212143.1, \u221229.36]; p &lt; 0.001), and day 14 (n = 3 arms; MD = \u22129.15 mIU\/mL; 95% CI: [\u221217.24, \u22121.06]; p = 0.03); however, the differences were not clinically meaningful. Letrozole showed a better safety profile with higher platelet counts and lower liver enzymes. AMH levels were similar between groups. Most analyses were consistent, though secondary outcomes were less stable. Overall evidence certainty was rated \u2018very low\u2019 due to seriousness of risk of bias and imprecision. Conclusions: While letrozole shows comparable efficacy to methotrexate and a potentially better safety profile in the management of EP, the certainty of evidence is \u2018very low\u2019 due to risk of bias and imprecision. Therefore, these findings should be interpreted with caution, and further high-quality studies are urgently needed to confirm the results.<\/jats:p>","DOI":"10.3390\/jcm14186523","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T08:03:47Z","timestamp":1758096227000},"page":"6523","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of Monotherapy Letrozole Versus Methotrexate for the Management of Ectopic Pregnancy: A Systematic Review and Meta-Analysis of Comparative Studies"],"prefix":"10.3390","volume":"14","author":[{"given":"Ahmed","family":"Abu-Zaid","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohannad","family":"Alsabban","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Nazer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5539-3820","authenticated-orcid":false,"given":"Safa","family":"Alabdrabalamir","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed Ziad","family":"Jamjoom","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, King Fahad Armed Forces Hospital, Jeddah 23311, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saad M. S.","family":"Alqarni","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, King Faisal Armed Forces Hospital, Khamis Mushait 62413, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hedaya","family":"Albelwi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, College of Medicine, Tabuk University, Tabuk 47512, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0427-8758","authenticated-orcid":false,"given":"Saeed","family":"Baradwan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Jeddah 23433, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seham Mabrouk","family":"Ebeid","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Security Forces Hospitals Program, General Directorate of Medical Services, Ministry of Interior, Riyadh 11134, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Abuzaid","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Al Birk General Hospital, Al Birk 63525, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afnan","family":"Baradwan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Al Salama Hospital, Jeddah 22233, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osama","family":"Alomar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"},{"name":"Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Committee on Practice Bulletins\u2014Gynecology (2018). 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