Strategies for Addressing Recurrent Pregnancy Loss (Virtual Symposium)-05-Piazza_When_Blood

05-Piazza_When_Blood_Betrays

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This presentation by Dr. Gregory Piazza explores the complex relationships between thrombophilia, cardiometabolic inflammation, and infertility. Thrombophilia, a condition characterized by increased blood clotting tendency, is relatively common and has been linked to pregnancy complications such as recurrent pregnancy loss, pre-eclampsia, and placental abnormalities. Common inherited thrombophilias include factor V Leiden mutation, prothrombin gene mutation, and deficiencies in protein C, protein S, and antithrombin. These conditions can interfere with proper placental development and implantation, contributing to infertility and pregnancy loss.<br /><br />Epidemiological data show that thrombophilia is more prevalent among patients with a history of venous thromboembolism (VTE) and pregnancy complications. Inflammation, particularly elevated high-sensitivity C-reactive protein (hsCRP), also contributes to increased miscarriage risk, with aspirin shown to attenuate this effect. Cardiometabolic conditions and metabolic syndrome exacerbate infertility risks, especially in women undergoing assisted reproductive technologies (ART).<br /><br />Data indicate that thrombophilia screening in women with recurrent pregnancy loss or failed IVF cycles can identify at-risk individuals. Low-molecular-weight heparin (LMWH) and aspirin have been studied as treatments to improve pregnancy outcomes in women with thrombophilia, showing promising results in reducing miscarriage rates and improving implantation and live birth rates without significant bleeding complications. However, evidence from randomized controlled trials (RCTs) remains limited, and some studies have design limitations.<br /><br />The FREYA registry is an ongoing study examining thrombophilia, inflammation, and fertility outcomes, showing improved conception and live birth rates with thromboprophylaxis in women older than 40 with thrombophilia.<br /><br />In summary, thrombophilia and cardiometabolic inflammation are underappreciated contributors to infertility. Screening for thrombophilia should be considered in recurrent pregnancy loss or unexplained infertility, and low-dose anticoagulation may offer therapeutic benefits. Further rigorous RCTs are needed to establish definitive treatment guidelines.

Keywords

thrombophilia

cardiometabolic inflammation

infertility

recurrent pregnancy loss

pre-eclampsia

factor V Leiden mutation

prothrombin gene mutation

low-molecular-weight heparin (LMWH)

aspirin therapy

assisted reproductive technologies (ART)