{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:44:59Z","timestamp":1791647099423,"version":"4.3.4"},"reference-count":28,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Caesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy in which the early pregnancy implants at the site of the uterine scar. Methotrexate (MTX) in lower doses can be used to treat CSPs. However, MTX administration is associated with a spectrum of side effects that include hematological toxicities. This case report presents a CSP treated with an intragestational injection of MTX and subsequently developed pancytopenia. Materials and Methods: A 23-year-old woman at six weeks and six days of pregnancy was referred as a potential case of CSP. After establishing the diagnosis, she was treated with a transvaginal ultrasound-guided intragestational administration of 80 mg MTX (adjusted to 50 mg\/m2 body surface area) under sedation. Results: On day four after the MTX injection, she developed oral ulcers, fever, and pruritic phlyctenular maculopapular rash. Subsequently, the patient developed febrile neutropenia and was admitted to the Intensive Care Unit. On day six, a subsequent exacerbation of the rash was observed with the formation of blisters and purplish spots with concurrent odynophagia and sialorrhea. Ultimately, the patient developed pancytopenia due to bone marrow suppression. Fifteen days after MTX administration, the patient recovered and was discharged from the hospital hemodynamically stable, afebrile, with dropping \u03b2-hcg levels, and in good clinical condition. Conclusions: Although methotrexate administration is the preferred option for the treatment of cesarean scar pregnancies, clinicians should be aware of the fact that its use entails potential risks, even when it is used locally. To our knowledge, this case is the first description of pancytopenia due to bone marrow suppression following a single low dose of intragestational methotrexate injection.<\/jats:p>","DOI":"10.3390\/medicina60111900","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T03:57:04Z","timestamp":1732075024000},"page":"1900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Methotrexate-Induced Toxicity After Ultrasound-Guided Intragestational Injection in a Patient with Caesarean Scar Pregnancy\u2014A Case Report"],"prefix":"10.3390","volume":"60","author":[{"given":"Sofoklis","family":"Stavros","sequence":"first","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, University General Hospital \u201cATTIKON\u201d, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7716-1521","authenticated-orcid":false,"given":"Anastasios","family":"Potiris","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, University General Hospital \u201cATTIKON\u201d, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeliki","family":"Gerede","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Democritus University of Thrace, 691 00 Campus, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9553-6803","authenticated-orcid":false,"given":"Athanasios","family":"Zikopoulos","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, University General Hospital \u201cATTIKON\u201d, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Giourga","sequence":"additional","affiliation":[{"name":"First Department of Obstetrics and Gynecology, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8992-8793","authenticated-orcid":false,"given":"Christina","family":"Karasmani","sequence":"additional","affiliation":[{"name":"First Department of Obstetrics and Gynecology, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Karpouzos","sequence":"additional","affiliation":[{"name":"First Department of Obstetrics and Gynecology, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4829-9190","authenticated-orcid":false,"given":"Theodoros","family":"Karampitsakos","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, University General Hospital \u201cATTIKON\u201d, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyridon","family":"Topis","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, University General Hospital \u201cATTIKON\u201d, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismini","family":"Anagnostaki","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, University General Hospital \u201cATTIKON\u201d, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8391-0850","authenticated-orcid":false,"given":"Konstantinos","family":"Louis","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, University General Hospital \u201cATTIKON\u201d, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4337-7871","authenticated-orcid":false,"given":"Ioannis","family":"Tsakiridis","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, General Hospital Ippokratio, Medical School, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2863-5839","authenticated-orcid":false,"given":"Themistoklis","family":"Dagklis","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, General Hospital Ippokratio, Medical School, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Drakakis","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, University General Hospital \u201cATTIKON\u201d, Medical School, National and Kapodistrian University of Athens, 124 62 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8899-3040","authenticated-orcid":false,"given":"Ekaterini","family":"Domali","sequence":"additional","affiliation":[{"name":"First Department of Obstetrics and Gynecology, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1093\/humupd\/dmp057","article-title":"Current knowledge of the aetiology of human tubal ectopic pregnancy","volume":"16","author":"Shaw","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"B9","DOI":"10.1016\/j.ajog.2022.06.024","article-title":"Electronic address, p.s.o. Society for Maternal-Fetal Medicine Consult Series #63: Cesarean scar ectopic pregnancy","volume":"227","author":"Miller","year":"2022","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"44.e1","DOI":"10.1016\/j.ajog.2012.04.018","article-title":"The diagnosis, treatment, and follow-up of cesarean scar pregnancy","volume":"207","author":"Monteagudo","year":"2012","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e9087","DOI":"10.1002\/ccr3.9087","article-title":"Ectopic pregnancy with full implantation of the gestational sac in the caesarean section scar managed successfully with laparotomy","volume":"12","author":"Machairiotis","year":"2024","journal-title":"Clin. Case Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2327569","DOI":"10.1080\/14767058.2024.2327569","article-title":"Treatments for cesarean scar pregnancy: A systematic review and meta-analysis","volume":"37","author":"Alameddine","year":"2024","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.jbspin.2018.07.004","article-title":"Methotrexate mechanism in treatment of rheumatoid arthritis","volume":"86","author":"Friedman","year":"2019","journal-title":"Jt. Bone Spine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1097\/01.AOG.0000218690.24494.ce","article-title":"Cesarean scar ectopic pregnancies: Etiology, diagnosis, and management","volume":"107","author":"Rotas","year":"2006","journal-title":"Obstet. Gynecol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1634\/theoncologist.2015-0164","article-title":"Preventing and Managing Toxicities of High-Dose Methotrexate","volume":"21","author":"Howard","year":"2016","journal-title":"Oncologist"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.jmig.2009.03.015","article-title":"Hysteroscopic surgery of ectopic pregnancy in the cesarean section scar","volume":"16","author":"Yang","year":"2009","journal-title":"J. Minim. Invasive Gynecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"263","DOI":"10.4293\/108680813X13654754535197","article-title":"Laparoscopic management or laparoscopy combined with transvaginal management of type II cesarean scar pregnancy","volume":"17","author":"Wang","year":"2013","journal-title":"J. Soc. Laparoendosc. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/uog.4058","article-title":"Efficacy of Shirodkar cervical suture in securing hemostasis following surgical evacuation of Cesarean scar ectopic pregnancy","volume":"30","author":"Jurkovic","year":"2007","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1002\/uog.15857","article-title":"Surgical treatment of Cesarean scar ectopic pregnancy: Efficacy and safety of ultrasound-guided suction curettage","volume":"47","author":"Jurkovic","year":"2016","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1177\/030006051204000533","article-title":"Caesarean scar pregnancy: Treatment with bilateral uterine artery chemoembolization combined with dilation and curettage","volume":"40","author":"Zhang","year":"2012","journal-title":"J. Int. Med. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"152.e1","DOI":"10.1016\/j.ajog.2009.04.038","article-title":"Uterine artery embolization compared with methotrexate for the management of pregnancy implanted within a cesarean scar","volume":"201","author":"Zhuang","year":"2009","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_15","first-page":"e15","article-title":"Diagnosis and Management of Ectopic Pregnancy: Green-top Guideline No. 21","volume":"123","author":"Elson","year":"2016","journal-title":"BJOG"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"601","DOI":"10.7863\/ultra.34.4.601","article-title":"Cesarean scar pregnancies: Experience of 60 cases","volume":"34","author":"Khatib","year":"2015","journal-title":"J. Ultrasound Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1097\/FPC.0b013e32834ded2a","article-title":"Methylene tetrahydrofolate reductase gene polymorphisms and their association with methotrexate toxicity: A meta-analysis","volume":"22","author":"Spyridopoulou","year":"2012","journal-title":"Pharmacogenet Genom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/uog.13282","article-title":"Cesarean scar pregnancy and early placenta accreta share common histology","volume":"43","author":"Monteagudo","year":"2014","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/j.fertnstert.2015.12.130","article-title":"Cesarean scar pregnancy: A systematic review of treatment studies","volume":"105","author":"Hoffmann","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1365-2133.1990.tb02890.x","article-title":"Methotrexate side-effects","volume":"122","author":"Zachariae","year":"1990","journal-title":"Br. J. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s00404-013-2765-4","article-title":"Transvaginal sono-guided aspiration of gestational sac concurrent with a local methotrexate injection for the treatment of unruptured cesarean scar pregnancy","volume":"288","author":"Seow","year":"2013","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_22","first-page":"17455057241290424","article-title":"Conservative treatment of cesarean scar pregnancy with the combination of methotrexate and mifepristone: A systematic review","volume":"20","author":"Stabile","year":"2024","journal-title":"Womens Health"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/0029-7844(96)00252-9","article-title":"Life-threatening neutropenia following methotrexate treatment of ectopic pregnancy: A report of two cases","volume":"88","author":"Isaacs","year":"1996","journal-title":"Obstet. Gynecol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"475","DOI":"10.5114\/aoms.2016.58844","article-title":"Methotrexate-induced pancytopenia in a patient with ectopic pregnancy","volume":"14","author":"Shao","year":"2018","journal-title":"Arch. Med. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.therap.2015.12.006","article-title":"Fatal methotrexate toxicity in a patient treated for an ectopic pregnancy","volume":"71","author":"Gaies","year":"2016","journal-title":"Therapie"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s00228-013-1608-3","article-title":"Almost a tragedy: Severe methotrexate toxicity in a hemodialysis patient treated for ectopic pregnancy","volume":"70","author":"Willner","year":"2014","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1097\/01.AOG.0000172374.72125.3e","article-title":"A cautionary tale: Fatal outcome of methotrexate therapy given for management of ectopic pregnancy","volume":"107","author":"Kelly","year":"2006","journal-title":"Obstet. Gynecol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1089\/gtmb.2016.0326","article-title":"Association Between MTHFR C677T Polymorphism and Methotrexate Treatment Outcome in Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis","volume":"21","author":"Shao","year":"2017","journal-title":"Genet. Test. Mol. Biomark."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/11\/1900\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:35:45Z","timestamp":1760114145000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/11\/1900"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":28,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["medicina60111900"],"URL":"https:\/\/doi.org\/10.3390\/medicina60111900","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,20]]}}}