Infertility is the medical term for the inability of a couple to achieve pregnancy after an active search for at least one year and is due to numerous causes. One of the main causes of infertility is recurrent miscarriage, i.e. the consecutive loss of two to three pregnancies before the 20th week of gestation, which takes a heavy emotional toll on the couple. The diversity of the causes of recurrent miscarriages means that the waiting time for a healthy baby at home is extended until the right treatment can be found. For this reason, it is essential to carry out studies on the main known causes in order to find the origin of infertility as soon as possible.
Thrombophilias are one of the main causes of repeated miscarriages. Thrombophilia is defined as a pathology clinically characterised by an increase in blood coagulation, which facilitates the formation of blood clots and the subsequent development of thrombi. Alterations in thrombogenic factors have been shown to have a negative impact on fertility, with a number of implications:
– Embryo implantation failure: Increased clotting can lead to increased formation of small thrombi in the blood vessels of the uterus, interfering with embryo implantation.
– Miscarriages: The formation of small thrombi in the placenta can lead to placental insufficiency and affect blood flow to the foetus, triggering gestational loss.
– Other complications in the development of pregnancy: Thrombogenic factors have been linked to complications such as pre-eclampsia, intrauterine growth restriction or placental abruption.
Therefore, the preventive study of thrombogenic factors in couples with repeated miscarriages or infertility of unknown origin is of utmost importance. Although thrombophilias are divided into two types, acquired or genetic, in this article we will focus on thrombophilias of genetic origin.
The genetic origin of thrombophilias related to infertility lies mainly in alterations in four genes that encode thrombogenic factors: Factor II or prothrombin, Factor V Leiden, Factor XII and the MTHFR gene. Genetic variants in these genes that alter the correct functioning of thrombogenic factors will trigger an increase in clotting and, therefore, a greater likelihood of developing thrombi.
However, whether the patient is a carrier (heterozygous) or affected (homozygous) of one or more of the pathogenic variants in these genes may determine the severity of the condition. Therefore, professional societies recommend the study of the four most relevant pathogenic variants in these four genes:
– Factor II or prothrombin (Variant G20210A).
– Factor V Leiden (Variant G1691A)
– Factor XII (C46T)
– MTHFR gene (C677T)
In conclusion, thrombogenic factors play an important role in human infertility. Early diagnosis of these pathogenic variants will be beneficial for couples who are diagnosed with repeated miscarriages or infertility of unknown origin. With proper treatment in these couples, the chances of conception and carrying a pregnancy to term can be significantly increased and be a solution to their fertility problem.
