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

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.

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.

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⁺¹ weeks, resulting in the birth of a healthy neonate.

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.