The incidence of Repeated Miscarriages is 2% and almost 10% of patients undergoing IVF treatment have Recurrent IVF Failures. The available investigations help to detect the underlying cause in only about 50% of the patients. So, in the remaining about 50% of patients the exact cause is not known and is labelled as “unexplained”. These so called “unexplained” cases can be due to an Immunological factor known as Allo-immune rejection of pregnancy. Certain tests help us to diagnose the allo-immune factor and indicate whether immunomodulatory treatment will be beneficial. First, we have to rule out all other known causes.


The investigations are as follows.


  1. Lymphocyte crossmatch: This is a crossmatch of Lymphocytes between the husband and wife. A negative crossmatch indicates that the treatment will be beneficial
  2. Natural Killer (NK) cells in peripheral blood: Raised CD3 cells and low CD 16+56 cells indicate an allo-immune problem.
  3. Sr. TNF α: TNF α is a Th1 (inflammatory) cytokine that plays an important role in the protective mechanisms of our immune systems. However, raised levels of TNF α overcome the Th1 (anti-inflammatory) response of immune system (Immune tolerance) required to maintain the pregnancy. This leads to miscarriage or IVF Failure
  4. Endometria NK Cells (CD 57): Presence of endometrial CD 57 cells is an indication underlying alloimmune problem. This is detected by doing a D&C procedure during luteal phase (19th – 23rd day of cycle) and endometrium is tested for CD57 cells by Immunohistochemistry (IHC).
  5. Th1 / Th2 cytokine ratio: Higher ratio is indicative of allo-immune problem.
  6. Treg Cell estimation: Treg cells are important in maintenance of pregnancy. They help by developing immune tolerance. Low or falling levels of T-reg cells are indicative failing pregnancy due to allo-immune problem.