Specialised Unit in Implantation Failure and Recurrent Miscarriage

Different solutions for different situations

At Ginemed’s Specialised Unit in Implantation Failure and Recurrent Miscarriage we are dedicated to finding the solution to complex cases involving previous implantation failure, rare pathologies and undiagnosed cases (‘’unexplained infertility‘’) which have resulted in undesired outcomes.

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Dr. Juan Manuel Jiménez
Reproduction Specialist
Ginemed

Phases of the Process

Case Study

Diagnosis

Approach treatment from a multidisciplinary point-of-view

Who are the High Complexity Case Consultations intended for?

La salud es lo primero
Implantation Failure

Patients who have transferred a minimum of 4 good quality embryos over the course of at least 3 embryo transfers, with at least one being the transfer of a blastocyst embryo.

La edad importa
Recurrent Miscarriage.

Patients who have had 3 consecutive miscarriages or who have been diagnosed with a condition following a second miscarriage.

Descartamos enfermedades genéticas
Unexplained Infertility

Patients whose infertility has no known cause after having undergone the Basic Infertility Study.

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Private 45-minute consultation

Frequently Asked Questions

We often have good quality, healthy embryos, but in spite of this we are unable to obtain a viable pregnancy (cases of repeated implantation failure), or we obtain a pregnancy but it does not progress (cases of recurrent miscarriage). Although not always the case, there are often underlying immune problems which prevent the mother from accepting the embryo.

Immunology is one of the physiological pillars essential to achieving a pregnancy, as the success of a pregnancy depends on correct immune balance.

Pregnancy is a challenge and an immunological paradox for the mother, as her immune system must allow a semiallogeneic embryo to implant (an embryo that shares 50% of her genetic material) or even an allogeneic embryo to implant (100% of the embryo’s genetic material is different from the mother’s). According to the laws of transplantation immunology, the mother should reject this different genetic material. However, under normal conditions embryo implantation is tolerated.

What role do immune factors play in reproduction?

Why is my immune system rejecting my embryos?

The necessary immune tolerance processes which prevent the mother from rejecting the embryo are extremely complex, and at present we do not even understand all the mechanisms which allow for normal implantation and development of the embryo inside the mother’s womb.

Immune system tolerance or rejection conditions implantation. In reproductive immunology we strive to pinpoint the factors involved in the early stages of pregnancy so that we can adjust them as necessary to offer personalised solutions on a case-by-case basis.

Several groups around the world are studying these processes of tolerance and rejection, as well as how changes in the immune system make it possible for abnormal embryos to implant but to later end in miscarriage, or how they prevent genetically healthy embryos from implanting.

We also study whether interaction between the mother and the embryo is correct or not, as this can lead to gestations that stop developing before they can be seen with an ultrasound (chemical pregnancy) or after they’ve already been seen on an ultrasound (anembryonic gestation – blighted ovum - or delayed miscarriages).

New studies are showing the relationship between implantation issues and pregnancy conditions such as pre-eclampsia or intrauterine growth restrictions.

What happens when the immune system fails?

How can reproductive medicine change this?

Several types of immune cells have been identified at the maternal-foetal interface, including Uterine Natural Killer (uNK) cells (70%), macrophages (20%), T lymphocytes (10%), dendritic cells and B lymphocytes (very few). The number of cells present and the role they play change throughout the different stages of pregnancy.

NK cells are the lymphocytes which have the greatest impact on maternal-foetal tolerance. NK cell function is regulated by a series of receptors that produce different signals. Among the NK cell receptors identified is a family of receptors similar to immunoglobulin (KIRs); these receptors bind to proteins such as HLA-C (C-class histocompatibility antigens).

HLA is one of the identification systems the body uses to recognise its own materials and protect itself from foreign materials. Both KIRs and HLA-C are polymorphic and certain combinations could negatively impact the success of a pregnancy. Several promising lines of research are investigating the very likely impact of HLA-G, HLADQ and E systems on achieving a pregnancy.

What specific studies are ordered in cases of Implantation Failure and Recurrent Miscarriage?

Personalised treatment plans are essential in cases of implantation failure and recurrent miscarriage. For this reason, the studies and tests ordered by the doctor will depend on each patient’s personal and family medical history. The main types of studies are:

Immune Studies
Endometrial NK cell study.
Autoantibody and serum immunoglobulin alterations.
Cytokines and Interleukins related to the lymphocyte response. (Th1/Th2 ratio).
Complement system study.
Study of maternal/embryo compatibility via maternal KIR genotype and paternal HLA-C haplotype.
Non-Immune Studies
Thrombophilia study.
Alterations in the coagulation cascade.
Coagulation factor mutations.
Uterine contractility study.
Endometrial Studies

These studies involve taking a sample of endometrial tissue to improve receptivity or to carry out further testing such as:

Endometrial cultures.
Study of endometrial NK cells.
Study of plasma cells.
Anatomical pathology study.
Endometrial synchronisation test (ER Map / ERA).

We could say that when we study failure to achieve pregnancy we should keep the following in mind:

Pro-inflammatory states, which would result in an imbalance of implantation tolerance mechanisms (Th1/Th2).
Imbalance of the correct proportions of permissive and cytotoxic NK cells (CD56, CD16, CD69).
HLA/KIR combinations which easily trigger immune rejection.
Imbalances in regulation factors which control or act as mediators in the immune process.
Systemic diseases which have a direct impact on immune control.
Psychological situations with acute stress that have a direct impact on immune system control.

Although this is a new field of reproductive medicine, we are seeing an increasing number of studies, treatments and improved results, thus making it possible for most people to have a child.

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