Clinical Outcomes Associated With Methotrexate Use in Conservatively Managed Placenta Accreta Spectrum: A Retrospective Comparative Study
Shizuki Daiho, Yutaka Iwagoi, Akihito Sagara, Risa Shimokawa, Saori Yoshimura, Masaru Kobayashi, Miyuki Ochiai, Yasuhiro Yamamoto, Munekage Yamaguchi, Haruta Mogami, Eiji KondohABSTRACT
Aim
Conservative management with the placenta left in situ has emerged as an alternative approach for placenta accreta spectrum (PAS). Methotrexate (MTX) is sometimes used to facilitate placental resorption; however, its clinical benefit remains uncertain.
Methods
We conducted a retrospective cohort study at two tertiary centers including patients with PAS managed conservatively with the placenta left in situ after cesarean delivery between April 2011 and March 2026. Patients were divided into MTX and non‐MTX groups. The primary outcome was a composite adverse outcome, defined as cytopenia, bloodstream infection (BSI), late postpartum hypofibrinogenemia (LPH), therapeutic uterine artery embolization (UAE), or delayed hysterectomy. Secondary outcomes included suspected intrauterine infection and time to serum human chorionic gonadotropin (hCG) normalization.
Results
Seventeen patients were included (MTX, n = 8; non‐MTX, n = 9). The composite adverse outcome occurred in 50.0% of patients in the MTX group and 44.4% in the non‐MTX group, with no significant difference (RR 1.13, 95% CI 0.40–3.10; p = 1.00). Cytopenia was observed only in the MTX group (37.5% vs. 0%; p = 0.08). Other outcomes, including BSI, LPH, UAE, hysterectomy, and suspected intrauterine infection, were similar between groups. The median time to hCG normalization did not differ significantly between groups (66.5 vs. 64.0 days; p = 0.76).
Conclusions
MTX use in conservatively managed PAS was not associated with improved clinical outcomes and may be associated with increased hematologic toxicity. These findings suggest that routine MTX administration does not appear to provide clinical benefit and may increase toxicity.