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When pregnancy either fails to occur or ends tragically…


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…the underlying causes will be investigated. Couples who failed to conceive after several IVF attempts or who experienced recurrent pregnancy loss or repeated miscarriages are under particular strain. Worldwide, IVF specialists work feverishly on analyzing the reasons for miscarriages and embryo implantation failure in order to be able to provide successful therapy.

Many conditions during pregnancy are interpreted as disorders in the vascular supply and are considered to be a mild form of a so-called thromboembolic condition, i.e. a condition in which a blood clot forms inside a vessel (about 30% of the cases are concerned).
It is therefore important to recognize what impacts congenital or acquired coagulation disorders may have on human procreation and treat them accordingly.

Congenital coagulation disorders may result in miscarriages due to the fact that thrombosis in the vessels of the placenta may lead to placental infarction, thus provoking an undersupply of the embryo. Nutrients and oxygen are transferred to the embryo through the placenta, which comes from the Latin word of cake in reference to its round, flat appearance in humans. However, since pregnancy complications also occur without preceding placental infarction, there must also be other underlying causes, such as vascular damage.

Recurrent miscarriages: more than one third occurring without any apparent reason

Since already the term “recurrent miscarriages” is not consistent with a uniform definition (sometimes the term refers to only 2, then again to 3 repeated miscarriages), this makes it difficult to compare the results of different scientific studies on coagulation abnormalities. It is, however, known that despite careful investigation (of hormonal, genetic, gynecological disorders) about 30-40% of the recurrent miscarriages remain unexplained (idiopathic), which in turn means that the women involved have to cope with a great deal of uncertainty and worry. It is therefore all the more important that IVF specialists give their very best to conduct the most comprehensive research into the causes of recurrent miscarriage. Unfortunately, however, this is not as simple as that.

Especially as far as the most common mutations of blood coagulation are concerned – Factor V Leiden and Factor II Mutation (describe the most common congenital risk of developing thrombosis) – the conclusions drawn with respect to their impact on recurrent miscarriages are very contradictory. In one study, the mutation has been associated with an incidence of miscarriages being twice as high as without the mutation. Another investigation reported that some, but not all, coagulation disorders are associated with miscarriages. Furthermore, certain investigations show that there are differences depending on the stage of pregnancy. Thus, during the first three months of pregnancy, the factors II and V together with a resistance to protein C account for the occurrence of miscarriages, whereas miscarriages later in pregnancy seem to be related to the factors II, V and a protein S deficiency. Another mutation that is associated with homocysteine metabolism (MTHFR mutation) was not in any way found to be linked to an increased risk for miscarriages.

Administration of aspirin as a prophylactic Treatment?

With regard to the therapeutic options to be applied in order to avoid miscarriages that may occur without any discernible reason, a combination therapy of aspirin and low molecular weight heparin (LMWH), as well as a therapy of aspirin alone might improve the likelihood of achieving a live birth. The British Committee for Standards in Haematology stresses, nonetheless, that treatment with any of these drugs during pregnancy is still to be considered as “experimental”, as long as not all factors contributing to the occurrence of miscarriages are known.
Experts emphasize that currently heparin and aspirin should NOT be given to pregnant women on a routine basis for the sake of preventing miscarriage. However, medical thrombosis prophylaxis, mainly around the time of birth is useful for these women. (Kuperman et al., Women`s Health, 2011;7:545-553)

Implantation issues due to coagulation abnormalities

If multiple IVF attempts have not resulted in the successful implantation of an embryo into the lining of the uterus, this is referred to as implantation failure. The causes are manifold. Coagulation disorders seem to be increasingly frequent in affected women. This is why the investigations should involve analyzes on possible coagulation abnormalities (Antiphospholipid Syndrome, Factor V Leiden and Factor II Mutation, MTHFR Mutation). Here again, heparin and aspirin seem to have a beneficial effect on the successful outcome of pregnancy.

In summary, it can be said that investigating coagulation disorders as well as treating them accordingly in the event of recurrent miscarriages and failed implantation following several attempts of in-vitro fertilization are absolutely justified. However, the standard use of heparin and aspirin should be avoided, since it is still considered as “experimental”, given the lack of sound scientific data.

→ more articles concerning this topic in the Special »Why embryo implantation did not take place – Possible causes and treatment-options«
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