Successful Delivery Following Ex Vivo Organoid Drug Testing for Unexplained Recurrent Pregnancy Loss.

Objective: To address the critical unmet need in managing unexplained recurrent pregnancy loss (URPL), where current empiric therapies exhibit limited efficacy, by leveraging patient-derived organoids (PDOs) for personalized therapeutic discovery. This single-case report serves as a proof-of-concept application of PDO-guided precision therapy in URPL. Methods: A 29-year-old woman who experienced six consecutive pregnancy losses underwent endometrial PDO-based drug testing. Organoids and stromal cells were cultured from proliferative-phase endometrial biopsies, and growth responses were subsequently quantified using RNA-seq and functional assays. Results: Histological examination of the endometrium revealed increased fibrosis alongside reduced stromal cell and CD3+ T-cell infiltration at the maternal-fetal interface. Initial observations of the PDOs indicated that epithelial growth was delayed. A synergistic triple-therapy regimen (aspirin + low-dose heparin + almuabumab) was identified as a candidate for restoring uterine homeostasis. Combination therapy achieved an ongoing pregnancy. Following conservative management of intrahepatic cholestasis and preeclampsia, a cesarean delivery was performed at 34 Conclusion: This study pioneered the use of PDOs as an innovative therapeutic model for URPL, targeting immune-thrombotic dysregulation and enabling precision therapy. These findings establish a precision medicine paradigm that integrates organoid pharmacology with dynamic pregnancy surveillance for refractory cases of URPL. However, these data are derived from a single patient and should thus be interpreted with caution, warranting confirmation in larger, prospective cohorts.