Typing of endometrial lymphocytes of (unexplained) recurrent miscarriage patients

Recurrent miscarriages (RM) occurs in 1-3% of all women trying to conceive.
Unfortunately, around half of the recurrent miscarriage cases remains
unexplained, leaving the couples with the burden of uncertainty and clinicians
without treatment options. It is well accepted that the immune system plays an
important role in the implantation of the embryo into the uterus wall.
Interaction between natural killer (NK) cells in the uterine lining and
invading extravillous trophoblast cells (EVT) is important for proper
placentation. When invasion of trophopblast cells is defective, the placenta is
not formed properly which can lead to disorders like miscarriages. It has been
suggested that women who experience RM lack certain receptors that recognize
EVTs on their uterine NK cells. Also, some specific combinations of maternal
KIR2D and fetal HLA-C have been correlated with pregnancy related complications.
Besides NK cells, also other cells present in the endometrium or early decidua
are thought to play a role, such as regulatory T cells (Treg) that can
specifically suppress immune responses. A tightly regulated Th1/Th2/Th17/Treg
balance is required for successful pregnancy as it has been shown that Treg
were decreased while higher levels of Th17 have been found in peripheral blood
and decidua of women with RM.
Up till now research into this problem has focused on peripheral blood and
decidual tissue. Few have examined endometrial lymphocytes due to ethical
constrictions related to taking biopsies. Our new technique to obtain
endometrial cells via menstrual blood collection, now offers the unique
opportunity to examine this tissue in more detail in RM patients versus
controls.
In this project we aim to determine immunological causes of unexplained
recurrent miscarriage. These results will help to identify these patients and
to eventually develop effective therapies.

a. To investigate the phenotype and function of immunological cells present in
endometrial and peripheral blood of women with a history of recurrent
miscarriages and women without any known pregnancy complications.

b. To investigate the association between the maternal KIR and the paternal
HLA-C genotype in recurrent miscarriages and uncomplicated pregnancies.

The ultimate goal will be to investigate whether menstrual blood can be used to
detect patients that will likely suffer from a miscarriage in their next
pregnancy.

Characterisation of the immunological cells present in menstrual and peripheral
blood of recurrent miscarriage patients and controls.

In this study we will investigate endometrial blood from recurrent miscarriage
patients and from women who had uncomplicated pregnancies. Patients and women
without known pregnancy complications will be asked to collect menstrual blood
during 1.5 day in 3 blocks of 12 hour. In addition, a peripheral blood sample
will be asked during a regular visit to the Radboudumc. The male partner, i.e.
the biological father of the child, of these women are asked to use a buccal
swab to collect DNA to determine the HLA-C genotype

There are no direct benefits of this study for the participating subjects. The
benefits may be related to the future understanding of the role of
immunological cells in successful pregnancy.
The risk for the subjects associated with this study is minimal. The
participant will be asked to get one blood withdrawal (1 tube of 10mL) during a
regular visit to the Radboudumc. The use of the menstrual cup to collect
menstrual blood is completely safe, there is no risk for toxic shock syndrome
like with the use of tampons.
The male partner, i.e. biological father of the child, will be asked to collect
DNA by the use of a buccal swab. This is completely safe and can be done at
home. The only burden the partner will have is that he can*t eat anything 30
minutes before taking the swab.