P-506 Administration of low molecular weight heparin alleviate immune physiology in recurrent implantation failure modulating CCL2-CCR2 axis during frozen embryo transfer: effort from clinic to bench

Abstract Study question Does low molecular-weight heparin (LMWH) administration modulate CCL2-CCR2 axis in recurrent implantation failure (RIF) patients undergoing frozen embryo transfer (FET) to improve pregnancy salvage? Summary answer LMWH treatment attests beneficial immunological tolerance vivo and vitro through modulation of suggesting possible restoration weak pro-inflammatory response RIF. What is known already Immune imbalance proportion activated macrophages (M1) alternatively (M2) impede endometrial receptivity contribute CCL2 (M2-asscociated) - CCR2 (t-helper-2 associated) orders macrophage polarization by influencing expression functionally relevant associated genes down-modulate cytokine production. Immunological effects regulate pregnancy-promoting processes at foetal-maternal interface provide an appropriate process; outcomes being controversial. We aim investigate the potential immunoregulatory properties with RIF FET, particular regard on T-helper (Th) cells; two key players promoting immune during pregnancy. design, size, duration This prospective cohort study constituted 121 women (≥3 failed transfer) FET Institute Reproductive Medicine between January October 2022. An incremental dose (4-12mg/day) estradiol (Group A; n = 62) or without B; 59) (40 mg/day) from d2 d12 sequential ultrasound following intra-muscular progesterone (100mg/day) for 4 days was administered all participants. Blood samples were collected isolate plasma peripheral-blood-mononuclear-cells (PBMCs). Participants/materials, setting, methods Monocytes purified PBMCs cultured GM-CSF M-CSF analyze factor/s which control along flow cytometry. Influence GM-CSF-cultured (GM-MØ) M-CSF-cultured (M-MØ) specific gene markers analysed using quantitative RT-PCR (qRT-PCR). To assess in-vivo, Th-specific profile/s respective chemokines measured Luminex xMAP technology. Statistical significance set p < 0.05. Main results role chance The clinical rate higher group A. (A vs B: 37.09% vs. 27.11%, 0.24). exposure significantly decreased secretion (p 0.01) CCL22 0.001) macrophages, while it increased CCL2, CCL20 production both GM-MØ M-MØ. However, CCL7 lower M-MØ generated CD14+ CD16+ monocytes CD14 ++ CD16- respectively under exposure. qPCR analysis revealed a significant increase various GM-MØ–specific including EGLN3, SERPINE1 supernatant post treatment. Expression M-MØ-specific marker/s such as IGF1, FOLR2, HTR2B, up-regulated Group B. A, although documented concentration/s (pg/ml) Th17-type cytokine/s (IL-6 (1.88 ± 0.65 0.91 0.43; 0.04 IL-23 (17.94 9.76 7.78 3.43; 0.01)), end treatment, concentration TGF-β (3909.05 1248.35 2469.83 1058.71; cue probable maintenance balance inflammatory time implantation. No differences observed Th1-type level/s (IFN-γ TNF-α). CXCL10, CXCL11, CXCL1, CXCL8, CCL17, do not differ vivo. Limitations, reasons caution Beneficial good sample size are clearly needed confirm this hypothesis; hence result/s should be dealt caution. Further this, inclusion other arm/s (corticosteroids, intralipid and/or intravenous immunoglobulin) will make much robust conclusive. Wider implications findings identification atypical Th1-associated drives evaluate limit potentiate activation RIF; especially where anticoagulant effect primary goal. Further, modification expression/s might novel strategy derived deregulated polarization. Trial registration number Not Applicable