REPRODUCTIVE LOSSES OF THE FETUS IN MODERN OBSTETRICS-GYNECOLOGY AND REPRODUCTOLOGY

Abstract

The issue of reproductive losses remains a firmly established and pressing concern in modern obstetrics–gynecology and reproductive medicine. Among obstetric pathologies, one of the least studied yet most significant due to the severity of its consequences is fetal antenatal loss, caused by genetic, endocrine, anatomical abnormalities, and infection-related changes. To this list have been added pathologic conditions associated with coagulation disorders, including congenital and acquired thrombophilia and the complications arising from it: recurrent pregnancy loss, gestosis, preeclampsia/eclampsia, premature detachment of a normally implanted placenta, Intrauterine Growth Restriction (IUGR), HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), and Disseminated Intravascular Coagulation (DIC).

Since hereditary thrombophilia represents a group of genetic disorders that promote thrombosis and contribute to a hypercoagulable state, and despite the fact that hereditary thrombophilia accounts for 20–30% of venous thromboembolism cases, universal screening does not exist; however, testing is essential in individuals with high-risk profiles (burdened family history of thrombosis, recurrent venous thromboembolism, pregnancy, or planned surgical intervention). Furthermore: Factor V Leiden mutation (resistance to activated protein C) is the most common form of hereditary thrombophilia (5–7% in Caucasians). A mutation in the F5 gene renders coagulation factors resistant to protein C. Prothrombin gene mutation (G20210A) has a prevalence of 2–3% in Caucasians. The F2 gene mutation increases prothrombin levels and the risk of hypercoagulation. Protein C deficiency is a rare form of hereditary thrombophilia (0.2–0.5%). Protein C inactivates factors Va and VIIIa; deficiency leads to excessive activity of clotting factors and thrombus formation. Protein S deficiency is also rare (0.1–0.7%). Protein S functions as a cofactor for protein C; its deficiency increases the risk of thrombosis. Antithrombin deficiency is another rare inherited thrombophilia (0.02–0.2%). Antithrombin inhibits thrombin and factors Xa, IXa, and XIa; deficiency leads to excessive activity of these factors and development of hypercoagulation.

Rare forms include dysfibrinogenemia and hyperhomocysteinemia. Clinical manifestations involve venous thromboembolism (pulmonary embolism, deep vein thrombosis). Thrombosis may also develop in unusual sites—cerebral veins, or veins of internal organs. Thrombophilia is frequently associated with recurrent pregnancy losses at various gestational ages. It is noteworthy that hereditary thrombophilia tends to manifest at a younger age compared with acquired forms.

Our aim was to discuss this issue: 1. By reviewing our own retrospective cases (women treated in our clinic during 2023–2025); 2.By summarizing the positive outcomes in the management of relatively complex cases and assessing treatment effectiveness: a. Based on the obtained results, abnormalities of the coagulation–vascular and fibrinolytic systems were identified, requiring treatment both during preconception planning and b. Throughout pregnancy, childbirth, and the postpartum period, with dynamic monitoring of hemostasis markers until full correction; 3. Mathematical modeling of the data was performed using the three-component inclusion–exclusion principle known in combinatorial analysis.