Recurrent abortion is a bothersome condition that many couples suffer from. It is even more painful than infertility. For some time now, the structural abnormalities of the uterus have been recognized as one of the reasons for recurrent abortion within the science of gynecology. These structural abnormalities usually result in an miscarriage by the second trimester of the pregnancy.

Recurrent Spontaneous Abortion and Habitual abortion are the most common disorders in this field and they put an immense amount of pressure on couples who seek children.

Recurrent abortion refers to 3 and more cases of abrupt pregnancy end in a row, or with a fetus age of less than 20 week or a weight of less than 500 milligrams. 

miscarriage causes are unknown in more than 50 percent of all cases. 50 percent of all miscarriages happen in the first three months and due to chromosome related disorders, these can be diagnosed using a karyotype test. The fetus will be examined and in the case of the test being unfinished, then the karyotype test will be advised for the parents themselves.

Causes of Abortion

Considering the massive mental and spiritual damages that a miscarriage can have on the family lives of people, diagnosing the cause will do greatly to help cure the disorder and avoid future miscarriages. In cases which the cause of miscarriage is related with Thrombophilia, using folate, aspirin and other anticoagulants can prove to be useful. There are many cases that showcase the existence of thrombosis in thin arteries to be deciding factor of causing of undiagnosed miscarriages.

The cause of thrombosis itself is also related with Thrombophilia. In general, the causes of thrombophilia can be put in two different categories:

• Disorders in different variables of the coagulation system, genetic causes and immunologic reasons as secondary factors
• Arterial and coronary reasons which contribute to increased coagulation and blood clots

According to recent studies and research, mutation in several genes also plays a role as reasons for recurrent abortions these are:

 MTHFR A1298C & C677T:

Single nucleotide polymorphisms in genes encoding enzymes that regulate important metabolic pathways such as methylene tetrahydrofolate reductase (MTHFR) are considered as a contributing factor in thrombophilia. A reduction of activity in the MTHFR enzyme leads to a decrease in substrate for methionine synthetase and following this it will cause a stoppage to Homocysteine formation and therefore increased levels of Homocysteine. The increase of this amino acid in the plasma is incredibly toxic.

PAI-1:

Palsminogen activation inhibitors of type PAI-1 are involved in the development of venous thrombosis. PAI-1 has an inhibitory effect on tissue type and urokinase type plasminogen activators. This prevents the conversion of pulsminogen to pulsmin. Increased PAI-1 in plasma is one of the major causes of fibrinolytic dysfunction. Two polymorphisms known as 4G and 5G have been identified in these genes that have been linked to abortion.
Factor V Leiden & Factor II Prothrombin:

People with mutations in the factor V and prothrombin genes are at increased risk for thrombotic signs. Among the genes involved in this disorder are factor V Leiden, protein C deficiencies, protein S, as well as prothrombin mutations.

Each of these defects is involved in abortion in different fetal periods (first, second or final trimester). Carriers of mutations in the prothrombin or factor V Leiden gene have a twice as high risk of recurrent miscarriage as women without these mutations. Women with second-trimester miscarriages should be screened for inherited thrombophilia, including mutations in factor V Leiden, factor II (prothrombin), and protein S.

Factor XIII:

One of the most important factors in the coagulation system is factor XIII (fibrin stabilizing factor). This factor is a transglutaminase, which plays a pivotal role in the coagulation process. Congenital factor XIII deficiency is one of the rare coagulation disorders that can lead to recurrent miscarriage.

The disease manifests itself as spontaneous and delayed bleeding under presence of normal coagulation tests. In addition to heavy and prolonged menstruation periods, women with this disease are at risk of various pregnancy complications, including abortion and miscarriage.

Ways to treat recurrent Miscarriage

Fortunately, today, abortions due to immune system dysfunction are largely preventable, and couples who wish to become parents will benefit from various diagnostic tests and examinations, taking into account the type of immune system disorder they may be having. These treatments include:

• Aspirin: is an anticoagulant that prevents thrombosis by increasing the E2 prostaglandin and increasing blood flow to the placenta. It has been used for many years for autoimmune diseases such as antiphospholipid syndrome.

• Heparin: in addition to its anticoagulant effect Heparin also helps through inhibiting the conversion of prothrombin to thrombin and increasing antithrombin 3. It has immunological effects and acts like IL-3, increasing the invasion and the conversion of cytrophoblasts to senescence trophoblasts. It also reduces IL-2, TNF, -INFγ and Complement 2. With its diluent properties, heparin can be used to prevent recurrent abortions that happen due to antiphospholipid syndrome by preventing thrombosis by itself or in combination with aspirin. Heparin molecules do not cross the placenta and do not cause problems for the fetus.

• Prednisone: is a steroidal mixture used to suppress the immune system, as well as to reduce inflammation of the decidua and villitis in ANA- positive patients and patients suffering from antiphospholipid syndrome.

• Vitamin D: helps with Immunomodulation and reduces IL-2, TNF, INFγ levels.

• Lymphocyte therapy or Paternal leukocyte immunization: This treatment is more commonly used for patients who lack the ability to produce Blocking Ab and APCA due to the similarity of paternal and maternal HLA. Its success rate varies 20 to 68%. One of the treatment methods for APCA positive patients is  the injection of 0.5 ml of paternal lymphocytes subcutaneously in the arm or forearm twice with 3 weeks intervals between the injections.
  
  
• IntraVenous ImmunoGlobulin (IVIG) injection reduces the binding of T cells to FC receptors and extracellular matrix such as collagen, elastin and fibronectin and balances Th2 to Th1 ratio; which leads to a decrease in NK cell activity. It is also used to treat a group of patients with high CD56 + or NK cell activity.

However, in this group of patients, who have corticosteroid receptors with increased NK cell absorption, prednisolone can help control these cells. Some studies have shown that the use of injectable immunoglobulin reduces recurrent abortions and reduces preeclampsia cases and IUGR. But researchers in their clinical studies have not seen much difference in pregnancy outcome with immunoglobulin therapy. There is much debate about the effectiveness of injectable immunoglobulin in improving postpartum success in patients who have had unsuccessful IVFs.

A systematic study and meta-analysis conducted in 2006 on the effectiveness of injectable immunoglobulin in patients with recurrent IVF failure showed that the use of this treatment is significantly associated with an increase in pregnancy after embryo transfer. This method of treatment uses low doses (at least 200 mg per kg per month) in patients with deficiency of different subclasses of IgG. It has led to successful pregnancies in over 90% of these patients.

• Other immunosuppressive methods include Intralipid and Nefidipine injections. It suppresses the immune system, although their effectiveness is still in question.

 Stimulation of the Immune System: Using methods that can stimulate the mother’s immune system to produce blocking antibodies, or APCA. These include Membrane Trophoblast infusion, Seminal plasma suppositories and Killed Streptococcal Preparation. Thes have been tested and the yielded results are positive.