Immunological work-up

Assessment and management of couples with recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) is often a great challenge for the clinician and the patients. For a patient, losing one or more pregnancies without giving birth to a healthy child brings enormous emotional pressure. Lack of diagnosis and uncertain prognosis do not make things easier. All available tests and treatment options do not guarantee the birth of a healthy baby. Recurrent miscarriages and implantation failures are a problem on their own, but 5% of couples experience significant reproductive disorders. Unfortunately, our knowledge on RPL and RIF is scarce, and only up to 50% of couples receive a definitive diagnosis.


RPL causes and risks

In about 50% of cases, we can define the causes and risks of RPL and fertility disorders, i.e.:

  • advanced maternal age,
  • genetic anomalies,
  • autoantibodies
  • endocrine disorders,
  • uterine anomalies.

The importance of the endometrium and immunological response

Current data shows the essential role of the endometrium in the immune dialogue between the mother and the fertilized egg (embryo). It is the basis for the development and continuation of pregnancy. The immunological processes at the mother-fetal interface within the endometrium in the early stages of pregnancy are very complex. They involve many types of immune cells and molecules with immunoregulatory properties.


We know that many RPL, RIF, and fertility disorders are associated with immune pathology through chronic disruption of multiple immune pathways. In this context, the endometrium plays an important role. RPL and embryo implantation in the uterus are closely correlated. The influence of immunological processes on the development of pregnancy begins with the fertilization of the egg, and its disturbing course leads to pregnancy failures.

The role of NK cells (natural killers) in the early stages of pregnancy

NK (natural killers) cells are specialized lymphocytes. Their main role is to kill abnormal cells, e.g., neoplastic or infected with viruses. They also participate in the processes of immunoregulation and immune surveillance, e.g., in reproduction processes. The place of significant accumulation of NK cells in the uterine mucosa in the 2nd phase of the menstrual cycle (after ovulation) and the temporal mucosa at the early stages of pregnancy is observed. Shortly after implantation, a special population of NK cells (uNK) begins to flow in and will be present in large numbers throughout the first trimester and then gradually disappear. These observations suggest that the role of NK cells is closely related to the initial stages of pregnancy development and proper vascularization of the placenta.

Immunological work-up

Detailed testing of the immune system may identify possible causes of reproductive failures and early pregnancy losses.

If necessary, the doctor may suggest sequential testing of the immune system and selected genetic disorders:

1st step in immunological diagnosis:

  • number of NK cells (cytometry),
  • antinuclear (ANA) and anti-thyroid antibodies,
  • antiphospholipid syndrome,
  • other autoantibodies (anti-sperm).

2nd step:

  • endocrine disorders, incl. thyroid panel,
  • cytokine profile,
  • NK cells in early pregnancy,
  • HLA, antibodies to HLA, MLR.

3rd step:

  • genetic testing,
  • von Willebrand disease, thrombocythemia.

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