Ab1405 Adverse Pregnancy Outcomes Beyond the Antiphospholipid Antibody Syndrome: The Role of Complement Activation

Background: Complement activation is associated with adverse pregnancy outcomes (APOs) in antiphospholipid antibody syndrome (APS). However, its role in APOs among patients with recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) is not well understood beyond specific maternal conditions. Objectives: To study the role of complement activation (C3 and C4 levels before conception) as a possible tool to stratify and guide the best therapeutic approach in women with adverse pregnancy outcomes, beyond the APS setting. Methods: Data from a total of 208 patients were prospectively collected. They entered the "Recurrent Pregnancy Loss and Recurrent Implantation Failure Clinic" between October 2018 and December 2022 and the "Patologia della Gravidanza Clinic" between January 2008 and December 2022, both at San Raffaele Hospital (Milan). We collected data on pregnancies or PMA cycles in patients who tested C3 and C4 levels preconceptionally (within 6 months of conception). Results: Among the 208 patients with RPL and/or RIF without antiphospholipid autoantibodies (aPL), 114 successfully conceived. 51/114 patients had ANA and/or anti-thyroid autoantibodies positivity (autoAc+), while 63/114 were classified as autoAc- patients. In 14/51 (27%) autoAc+ patients, we measured low C3/C4 levels. 8/14 delivered live babies, and 29% experienced miscarriages. On the contrary, 25/37 autoAc+ patients with normal complement levels had pregnancies, with 22% experiencing miscarriages. In autoAc- patients, 11/63 (17%) had low complement levels. Among these patients, we recorded 6/11 babies born alive (including one preterm delivery and three IUGR), 4/11 miscarriages, and 1/11 implant failure. In the 52/63 autoAc- patients with normal complement levels, we observed 20/52 babies born alive (with no preterm delivery and one IUGR), 20/52 miscarriages, and 12/52 implant failures. Overall, APOs appeared to occur more frequently in autoAc- patients with low C3/C4 levels when compared with the other group (see Table 1). In particular, we observed a higher rate of IUGR in autoAc- patients with low C3/C4 levels compared to those with normal C3/C4 levels (27% vs. 2%), irrespective of the presence of autoimmunity (autoAc+ patients with low complement levels had 0 IUGR, while those with normal C3/C4 levels had 3% IUGR). Moreover, we observed that hypocomplementemia is significantly associated with a higher probability of treatment with low-dose aspirin (LDA), low-molecular-weight heparin (LMWH), hydroxychloroquine (HCQ), or their combinations. Conclusion: Preconceptional complement assessment is a simple and cost-effective tool for identifying patients at risk of APOs. In our study, even in patients without underlying autoimmune disease, hypocomplementemia was associated with a higher rate of treatment and a higher rate of APOs, particularly IUGR. Personalized diagnostic and therapeutic approaches are crucial for RPL and RIF patients, irrespective of the presence of APS. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.