Implantation Profile

Implantation Profile testing checks factors that prevent an embryo from implanting in the lining of the womb (endometrium).
For an embryo to implant and for the pregnancy to continue, a woman's immune system must be suppressed with regards to the uterus and growing embryo. This special type of immunosuppression is unique to pregnancy.
The growing embryo is genetically different to the mother and these cells would normally be targeted by the mother's immune system.
A delicate balance between coagulation and fibrinolysis is needed to 'allow' the embryo to invade the endometrium and access the mother's blood system. Ovulation will cause blood vessels to grow into the top layer of the endometrium. Once the embryo attaches itself to the endometrium it burrows deep into this tissue and opens itself up to these blood vessels for nourishment.
Sometimes an increased tendency for blood to clot (thrombophilia) will prevent the embryo from integrating into the thickened endometrium and establishing a healthy placenta through which it can feed. This results in recurrent implantation failure.

What Causes Blood to Clot?
Coagulation is a process where the blood forms a clot to prevent it's flow.
Fibrinolysis is a process that prevents blood clots from growing.
Coagulation happens through what's called a 'Coagulation Cascade' which involves coagulation factors. Coagulation factors are numbered from Factor I to Factor XIII. When a wound occurs or tissue is damaged (i.e. an embryo invading the endometrium), factors are released from nearby tissues which cause the conversion of soluble fibrinogen in the blood to change to insoluble fibrin. Fibrin forms a mesh around where a blood vessel is damaged, which traps platelets (small circulating cellular fragments) and blood cells. These harden to form a solid clot and prevent the flow of blood. In the case of pregnancy, clotting of placental vessels, prevents the embryo accessing the mother's blood supply.

Thrombophilia is a condition in which there is an increased tendency for blood to clot.
Thrombophilic gene mutations can cause recurrent miscarriage due to clotting of placental vessels. Fibrinolysis balances coagulation by preventing clots from growing. Some thrombophilic gene mutations affect fibrinolysis by interfering with factors involved in the 'Coagulation Cascade'. (see image below)

Some thrombophilic markers tested as part of an 'Implantation Profile' include:

Wikimedia Commons Coagulation
  • Factor V Leiden [G1691A]
  • Factor II prothrombin [G20210A]
  • MTHFR (Methylenetetrahydrofolate Reductase) [C677T] and [A1298C] mutations
  • PAI-1 (Plasminogen Activator Inhibitor-1) [4G/5G]
  • β-fibrinogen [–455G→A]
  • HPA1 (Human Platelet Antigen 1) [a/b9L33P)]
  • Protein C levels
  • Protein S levels
  • Activated Protein C activity
  • Factor XIII mutation
  • Beta-2 Glycoprotein

Some thrombophilic markers explained:

  • Factor V Leiden is present in 5% of Northern Europeans, but more rare in Asian and African populations. The mutated Factor V cannot be switched off by Activated Protein C and this leads to thrombophilia.
  • Factor II Prothrombin G20210A mutation can cause an increase in prothrombin levels which doubles or triples the risk of blood clots forming in the veins. Approximately 2-3% of Caucasians carry this mutation.
  • The MTHFR gene is involved in folic acid and vitamin B metabolism. It is also important for the conversion of the amino acid homocysteine to methionine. MTHFR mutations lead to elevated levels of homocysteine in the blood which plays a role in thrombosis.
  • PAI-1 functions as the principal inhibitor of tPA (tissue plasminogen activator) which activates plasminogen and hence fibrinolysis (the breakdown of blood clots).

Diabetes and Recurrent Implantation Failure
Diabetes is a condition where the body cannot control blood sugar levels either because a person can't produce enough insulin, or because cells do not respond to the insulin that is produced (insulin resistance).
Diabetes increases the risk of thrombosis due to platelet hyper-reactivity and increased activation of coagulation factors coupled with decreased fibrinolysis.
An impaired coagulation/fibrinolysis response leads to problems with embryo implantation.
HbA1c or Glycated hemoglobin is used to measure the average plasma glucose over prolonged periods of time. It is an important test for the management of diabetes. Several studies have found HbA1c levels >8% are associated with increased rates of miscarriage.
This is why HbA1c and insulin testing can also be included in an 'Implantation Profile' panel of tests.

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