Summary of ASRI/ISIR meeting by BRI scientists

Posted By Braverman IVF & Reproductive Immunology || 4-Jul-2016

Braverman Reproductive Immunology research team attends the triennial meeting of the International Society of Immunology of Reproduction

Two members of our research team, Dr. Darren Ritsick and Dr. Nadéra Mansouri-Attia recently attended the13th Congress of the International Society for Immunology of Reproduction, jointly held together with the annual meeting of the European Society for Reproductive Immunology (ESRI) in Germany.
The joint meeting regrouped world-renowned clinicians and scientists in the field of reproductive Immunology.

Our team had the opportunity to present our most recent data showing the role of IL-17 producing CD8+ T cells and NK cells in infertility and pregnancy complications including miscarriage. Our scientists were also able to attend seminars and poster sessions, and exchange opinions with other scientists about the most recent scientific and technological advances in the field of reproductive immunology.

Many of the most interesting talks presented during the meeting can be grouped into the following categories:

  • Novel insight on pregnancy complications such as pre-eclampsia

Many talks highlight the possible causes of pre-eclampsia (besides a shallow implantation), including:

- protein misfolding and aggregation
- the secretion of toxic factors such as High mobility group box 1 (HMGB1) released by the trophoblast and contributing to endothelial cells activation
- the downregulation of the cluster of differentiation (CD74) in placental macrophages leading to an altered interaction between the placenta and the macrophages. This leads to poor placenta morphology and an impaired spiral artery remodeling due to a bias towards pro-inflammatory macrophages.

  • Oocyte donation as a major challenge for the maternal immune system

A very interesting talk presents the oocyte donation as a cause of pregnancy complications such as pre-eclampsia.
Pregnancy could be considered as a semi-allograft as the fetus expresses paternal and maternal antigens.
In a context of egg donation, the mother is carrying a 100% non-self fetus and the number of HLA mismatches could be significantly high thus further challenging and activating the maternal immune system. This can induce the production of anti-HLA antibodies linked to a poor pregnancy outcome.

  • Immunometabolism

Many studies have shown that maternal diet can alter metabolic function and have dramatic consequences on immune modulation during pregnancy leading to poor pregnancy outcome.
A maternal diet rich in fat negatively affects the glucose pathway and negatively structured the gut and placenta microbiome (community of microorganisms). These dysregulation lead to inflammation and cause placental damages inducing pre-eclampsia.
The maternal diet more that the maternal weight (obesity) has by itself long-lasting effects on the neonate’s health.

  • New immunomodulatory treatments for APS

A presentation has shown the beneficial effects of statins in APS patients by inhibiting neutrophil and trophoblast injuries.
In particular, pravastatin has been shown to prolong the pregnancy for 13 weeks once the clinical signs of pre-eclampsia were detected in APS patients who did not respond to anti-thrombic therapy. It can also reverse poor outcome in pregnancy with abnormal Doppler (reverse ADV, bilateral notching) by restoring the uterine flow.

Although this study is not a large clinical trial, the use of pravastatin in APS pregnant patients is very promising.

  • Novel tools in the diagnosis of implantation failure

Some work has been presented on diagnosis tools to better determine the endometrial receptivity in patient suffering from recurrent implantation failure.

The endometrial receptivity array (ERA) has been shown to help clinicians in determining the optimal time for embryo transfer in an IVF cycle (either natural or stimulated). Unfortunately, the ERA is not useful, for now, in patients treated by immunotherapies, as no data are yet available for these patients.

A novel study exploring 4 factors involved in uNK cells activation, angiogenesis and inflammation in endometrial biopsies showed that the analysed group is more likely to be successful than the control group after adequate therapies to optimize the uterine receptivity in women suffering from recurrent implantation failure.

Our Research Department is constantly tracking the latest discoveries in the field of reproductive immunology. Moreover, we apply these new findings to better understand the molecular events playing a key role in a pregnancy success and offer a better diagnostic and monitoring to our patients. Further, the latest therapies are thoroughly studied (clinical trial analysis, effect on immune parameters, administration protocol, safety) to determine if these recent advances could be potentially apply to clinical practice and help our patients to achieve successful pregnancy.
Dr. Mansouri-Attia will soon attend the 2016 meeting of the European Society of Human Reproduction and Embryology (ESHRE) in Helsinki, Finland where she will present our latest data regarding the role for Treg cells in pregnancy success or failure and the effects of our immune treatment protocols on regulating these cells.
We will update you with all of the exciting research advances presented at this meeting and will explain you how they can help us to better help you achieving a healthy pregnancy

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