L26/P-345 From inflammation to implantation: GnRH agonist down-regulation reduces CD138+ plasma cells in recurrent implantation failure with adenomyosis

Abstract Study question Does GnRH agonist down-regulation reduce endometrial CD138+ plasma cell density and improve implantation outcomes in recurrent implantation failure with or without adenomyosis? Summary answer GnRH agonist pretreatment lowered CD138+ plasma cells, and greater immune normalization was associated with improved implantation, particularly in adenomyosis. What is known already Chronic endometritis (CE) is a subtle, persistent endometrial inflammation identified by CD138+ plasma cells, and it is linked to poor receptivity and recurrent implantation failure. Adenomyosis can further disturb the uterine immune environment and worsen inflammatory activity. GnRH-a down-regulation is commonly used in adenomyosis, and emerging evidence suggests it may also improve endometrial immune balance. However, real-world prospective data showing how CD138+ cell burden changes after GnRH-a therapy—and how this relates to implantation—remain limited. Study design, size, duration Prospective observational study of 120 women aged 20–42 years with RIF (≥3 failed embryo transfers), conducted during 2023–2025. The The study was conducted at a tertiary IVF center (Indira IVF, Bengaluru) Participants were categorized into two groups: - Group A: RIF only (n = 60) - Group B: RIF + MRI-confirmed adenomyosis (n = 60) Participants/materials, setting, methods Participants were grouped as RIF only (n = 60) or RIF with MRI-confirmed adenomyosis and CA-125 >35 IU/mL (n = 60). Mid-luteal (LH + 7) endometrial biopsies were performed before and after GnRH-a pretreatment using leuprolide acetate depot 3.75 mg IM monthly for 1–3 months. CD138 immunohistochemistry quantified plasma cells per 10 high-power fields (HPF); CE was defined as > 5 CD138+ cells/10 HPF. Pregnancy outcomes were correlated with immune marker changes. Main results and the role of chance At baseline, CD138+ plasma cell counts were higher in the adenomyosis group than in RIF only (14.2±4.6 vs 9.4±3.1 cells/10 HPF; p < 0.001). After GnRH-a pretreatment, CD138+ counts decreased in both groups, reaching 4.2±2.1 (adenomyosis) and 2.8±1.9 (RIF only) cells/10 HPF (between-group p = 0.02). The decline was most pronounced in women receiving ≥2 doses of leuprolide. Immune normalization (CD56/CD138) was observed in 54% with adenomyosis and 68% without adenomyosis (p = 0.04). A greater fall in CD138+ cell density correlated with higher implantation (r = −0.41; p = 0.02). Clinical pregnancy rates were 36% in the adenomyosis group and 42% in the RIF-only group (p = 0.21). Limitations, reasons for caution This was an observational study, so causality cannot be proven. Live-birth outcomes were not reported, and there was no randomized comparator (e.g., antibiotics or alternative pretreatment strategies). Wider implications of the findings GnRH-a pretreatment may help “calm” the endometrium by reducing CD138+ plasma cell infiltration in RIF, especially when adenomyosis coexists. Incorporating CD138 testing into pre-transfer assessment could support more personalized pretreatment and timing decisions to optimize receptivity. Trial registration number No