The frequency of recurrent miscarriage is not low. It is defined as more than three consecutive spontaneous miscarriages that occur before 20 weeks of pregnancy. On average, 25% of women may have this situation during pregnancy. There are many reasons for recurrent miscarriage, such as infection, hormonal imbalance, chromosomal abnormalities, coagulation mechanism diseases, etc. It is currently known that the serum of such patients contains anti-phospholipid, anti-nuclear, anti-DNA or anti-sperm antibodies. The titer of antibodies in the body will be higher than that of normal people.

These antibodies often pass through the placenta and enter the fetal blood circulation, directly destroying the placenta or causing varying degrees of damage to the fetus, causing various clinical diseases such as miscarriage, fetal death, pregnancy toxemia, intrauterine growth retardation, and fetal malformations. The mechanism of miscarriage is still not understood. However, blood clots can be found in the shed decidua and placental tissue, which is suspected to be the cause of miscarriage. The current treatment for such pregnant women is daily low-dose aspirin and corticosteroids, which can effectively improve pregnancy outcomes.

Antiphospholipid Syndrome

It is a general term for a group of clinical symptoms caused by immunity. It is a group of antibodies that react with antigenic substances containing phospholipid structures. 

The mains are:

• Lupus anti-coagulant (LAC)

• Anti-cardiolipid antibody (aCL antibody)

• IgG or IgM anti-β2-glycoprotein-I (aβ2) antibodies

• Anti-phosphatidic acid antibodies and anti-phospholipid serine antibodies

These anti-phospholipid antibodies (APL antibodies), also known as thrombotic antibodies, are antibodies that cause blood clots.

Heparin has been used clinically for a long time. It is a stable injection. Its main component is a natural glycosaminoglycan anticoagulant. It can be used to treat and prevent deep vein thrombosis, pulmonary embolism, and arterial embolism. It can also be used to treat myocardial infarction and unstable angina. Common side effects of using heparin include bleeding and injection site pain, which can lead to heparin-induced thrombocytopenia (HIT). Although people with poor kidney function need to pay special attention when using heparin, heparin is quite safe for pregnant women and lactating mothers.

Its mechanism is as follows. Antithrombin III combines with heparin to cause a conformational change, causing it to inhibit coagulation factor Xa. As for the interaction between thrombin and antithrombin III, in addition to the enzyme, it also needs to be combined with heparin to form a ternary complex to achieve the inhibitory effect; the high negative electricity of this part of heparin plays an important role. Therefore, heparin must have at least eighteen sugars to have an effective effect with thrombin and antithrombin III, but only the sulfopentasaccharide sequence is needed to interact with coagulation factor Xa. Therefore, some researchers have used enzyme or chemical methods to develop low molecular weight heparin (its chemical structure is almost the same as the heparin pentasaccharide sequence): low molecular weight heparin can only inhibit coagulation factor Xa but not thrombin, which can not only fine-tune coagulation system to achieve better therapeutic effects and reduce the risk of osteoporosis and heparin-induced thrombocytopenia.

Many documents have confirmed the use of low molecular weight heparin (Enoxaparin (Clexane)) in patients with recurrent miscarriage. The use of low molecular weight heparin combined with other autoimmune drugs can increase the pregnancy rate and live birth rate, and can also reduce the miscarriage rate. and will not cause serious complications. One of the literature tables shows that there is no significant difference in age and BMI between the two groups (there is no special difference in the basic conditions of the two groups), but the table shows the first trimester, second trimester and live birth rate, and then adding low molecular weight heparin In all cases, the abortion rate was higher than that of the group without vaccination, and the miscarriage rate was lower, with significant differences.

As we from Table 2., the ongoing pregnancy rate in the group with low molecular weight heparin was 25.3% higher than the control group, and the live birth rate was also 29.5% higher.

In terms of complications, it can be clearly seen from the table below that the low molecular weight heparin group can reduce certain factors (circled in the red box), such as intrauterine fetal death (IUFD), anembryonic pregnancy, but not entirely.

If it is true as shown in the literature, the use of low molecular weight heparin combined with other immunological drugs can greatly improve the adverse effects caused by thrombosis. Currently, Stork advocates "3+ IVF", namely IVF with PGS and ERA, which can be implanted accurately and more effectively.  3+IVF with heparin and immunological drugs, may increase the pregnancy rate and bring good news to patients suffering from recurrent miscarriage.

Reference:

1.Shaaban OM, Abbas AM, Zahran KM, Fathalla MM, Anan MA, Salman SA. Low-Molecular-Weight Heparin for the Treatment of Unexplained Recurrent Miscarriage With Negative Antiphospholipid Antibodies: A Randomized Controlled Trial. Clin Appl Thromb Hemost. 2016. 23(6):567-572.

2.Maged AM, Abdelhafiz A, Mostafa WA, El-Nassery N, Fouad M, Salah E, Kotb A. The role of prophylactic use of low dose aspirin and calheparin in patients with unexplained recurrent abortion. Gynecol Endocrinol.  2016. 2(12):970-972.

3.Aynıoglu O, Isik H, Sahbaz A, Alptekın H, Bayar U. Does anticoagulant therapy improve adverse pregnancy outcomes in patients with history of recurrent pregnancy loss? Ginekol Pol.  2016. 87(8):585-91.