Is the Placenta an Immune Battlefield in Oocyte Donation? Histological Evidence of Graft-Versus-Host-like Phenomena in Triplet Pregnancies and the Development of PARS (Placental Allograft Rejection-like Score).

Background/

Objectives

Oocyte donation (OD) pregnancies involve complete maternal-fetal genetic disparity and are associated with increased placental dysfunction and adverse perinatal outcomes. However, a unified histopathological framework to characterize alloimmune-mediated placental injury in OD gestations is lacking. This study evaluates immune and vascular alterations in OD triplet placentas and proposes a structured scoring system, the Placental Allograft Rejection-like Score (PARS), to quantify immunovascular dysregulation.

Methods

This retrospective study included all OD triplet pregnancies with placental examination performed during 24 years at a tertiary referral center. Maternal, obstetric, fetal, neonatal, and pathological variables were analyzed at the pregnancy level. Histological and immunohistochemical features previously shown to differ between OD and non-OD pregnancies were grouped into six domains: innate immunity, adaptive immunity, checkpoint regulation, vascular remodeling, complement activation, and trophoblastic behavior. Binary thresholds, immunoreactive scores or established morphological cut-offs, were applied to construct a 20-point score classified into three grades.

Results

Forty-five OD triplet pregnancies were analyzed. Intra-pregnancy concordance for PARS components was high, with intraclass correlation coefficient ≥0.70 in 87.3% pregnancies. Increasing PARS grades demonstrated a clear clinical gradient. Grade 3 pregnancies had significantly lower birthweight, higher rates of prematurity (<34 weeks), and increased fetal growth restriction. Placental weight decreased progressively with higher PARS. Histologically, grade 3 placentas showed significantly increased accelerated villous maturation and intervillous fibrin deposition.

Conclusions

PARS integrates immune and vascular placental lesions into a structured and reproducible framework that correlates with clinically relevant perinatal outcomes and may support future clinical risk stratification, although further validation in larger, multicenter prospective cohorts is required.