Thrombophilia and multiple miscarriages

Article written by Doctor Do Huy Duong - Vinmec High-Tech Center

Recurrent pregnancy loss (RPL) is a huge disappointment for married couples. Unfortunately, in many cases, the exact pathogenesis of multiple miscarriages remains unknown.

At the present time, the Practice Committee of the American Society of Reproductive Medicine defines multiple miscarriages as having 2 or more miscarriages, but the European Society of Reproduction and Embryology recommends Three or more miscarriages are considered multiple miscarriages.
Due to the heavy psychological burden on couples with miscarriage, RPL is the most difficult and challenging area of ​​reproductive medicine. Because the etiology of the disease remains unclear, diagnostic and therapeutic strategies are limited. Suggested causes include: chromosomal abnormalities, uterine abnormalities, endometrial infections, endocrine abnormalities, antiphospholipid syndromes, hereditary thrombophilia, allergies, genetic factors , exposure to environmental factors and stress factors. Therefore, it is emphasized that an appropriate study of RPL patients is needed to assess potential risks and appropriate treatments. Mutations caused by a change in the position of a single base pair increase prothrombin levels, thereby increasing the risk of thromboembolism. Two types of polymorphisms were identified due to the low yield of the MTHFR enzyme. In homozygous individuals, the performance level was reduced by 35% compared to normal. Meanwhile, enzyme efficiency was also reduced in heterozygous individuals, although not to the same extent.

In patients with placental vascular disease, the risk of thrombophilia is increased. For example, in pregnant women with intrauterine growth retardation, such as preeclampsia, late miscarriage and placental abruption can be observed.
Grees et al suggested that disrupted plasminogen could lead to RPL derived from proteolysis. Plasminogen is a 92 kDa protein present in the blood that is an inactive precursor of the plasmin serine protease. Plasminogen is converted to plasmin by the urokinase (uPA) plasminogen-activated receptor. The activation of plasminogen by uPA is the major pathway leading to fibrin clot lysis. The team suggests that plasminogen disruption increases fiber accumulation in the early placental circulation and limits the growth of trophoblasts, thus leading to RPL. “Fibrinolysis” can also cause preeclampsia, fetal growth restriction (FGR), placental abruption, and stillbirth. Studies have shown that, during trophoblastic invasion, the plasminogen-activated receptor urokinase and plasminogen-activated inhibitor-1 (PAI-1) control proteolysis of structures and remodeling mother tissue.

The main current research directions involve meta-analysis of hereditary thrombophilia, the association between thrombophilia gene polymorphism and recurrent miscarriage, the use of low molecular weight heparin , the association of prothrombin mutation G20210A with recurrent miscarriage, factor V Leiden mutation in women with early recurrent miscarriage, and the association between plasminogen activator inhibitor-1 (PAI-1) gene polymorphism. and repeated miscarriages.
Women with a history of miscarriage need to be extra cautious in subsequent pregnancies. In order to maximize the possibility of conception and ensure a healthy pregnancy, before planning a pregnancy, both husband and wife should have a reproductive health checkup from 3-5 months. You will be examined for fertility, sexual health, screening for sexually transmitted diseases, and screening for genetic diseases. In particular, this examination process will be able to detect early causes that can lead to infertility and infertility so that early intervention measures can be taken. Doctors will also advise on the best time to give birth and measures to be able to give birth to healthy and intelligent children.
Vinmec International General Hospital is implementing a pre-pregnancy health care and counseling program to help mothers prepare for the best health before pregnancy. With this program, you will receive:
General health examination, especially gynecological examination, to help assess the possibility of conception as well as the health of mother and baby during pregnancy. Vaccination before pregnancy, helps prevent many dangerous diseases, especially Rubella. Genetic counseling helps identify risk factors, helps clients and families make decisions, and prevents occurrence or re-emergence in the family. Screening detects healthy people carrying disease genes, especially hemolytic anemia. Doctors will analyze the results and provide specific genetic counseling for you to proactively take preventive and intervention measures.

References: Barut MU, Bozkurt M, Kahraman M, et al. Thrombophilia and Recurrent Pregnancy Loss: The Enigma Continues. Med Sci Monit. 2018;24:4288-4294. Published 2018 Jun 22. doi:10.12659/MSM.908832