Revisiting the Link Between Factor XII and Recurrent Pregnancy Loss: A Scoping Review

ABSTRACT Pregnancy loss affects approximately 23% of women, with 1%–3% experiencing recurrent pregnancy loss (RPL), defined as two or more consecutive miscarriages. Despite extensive research, up to 50% of RPL cases remain unexplained, making it a complex issue in reproductive medicine. Coagulation Factor XII (FXII) a key component of the contact activation pathway, has been suggested to play a role in RPL. Low FXII levels may lead to placental dysfunction and hypercoagulability, increasing the risk of adverse pregnancy outcomes, including RPL. This scoping review aimed to evaluate the association between FXII levels and RPL. Literature was retrieved from the PubMed database and EMBASE by a systematic search. A total of 218 studies were identified, of which 12 met the inclusion criteria published between 1992 and 2015, encompassing a total of 2362 RPL patients. They investigated FXII activity ( n = 7), the C46T polymorphism ( n = 3), or autoantibodies to FXII ( n = 2) association to RPL. Available evidence suggests a potential association between low FXII levels, FXII antibodies, and RPL, probably via a prothrombotic mechanism as indicated by studies conducted 10–30 years ago. This highlights the need for further and more recent research to better elucidate the role of FXII in reproductive health and pregnancy outcomes.