Inflammation and the Immune System

We recently in the VOICE announced CHR’s new Reproductive Immunology Initiative, pointing out that recent research in other areas of medicine induced CHR to make reproductive immunology, once again, a priority of the center’s research and clinical practice since many findings in other areas of medicine had potential clinical implications for reproductive biology and reproductive medicine.

How correct a decision this was became apparent at the recent Ovarian Club meeting in December of 2017 in Hong Kong, when Canadian colleague Marc-André Sirard gave a wonderful talk on the three main reasons for poor ovarian response and poor oocyte quality in IVF cycles. Remarkably, in a complex genomic analysis of failed IVF cycles, his research group identified inflammatory genetic pathways among the most important key contributors to adverse IVF outcomes. In other words, “it’s the immune system, stupid!

For CHR investigators this, of course, does not come as a big surprise. After all, we identified inflammatory markers as predictors of IVF outcomes quite a while ago, with elevated C-reactive protein (CRP) denoting decreased pregnancy chances in IVF and elevated interleukin-6 (IL-6) associated with significantly increased miscarriage rates following IVF (Barad et al., unpublished data).

The finding of Sirad and colleagues are, nevertheless, important because they offer totally unbiased, and for the investigators actually very surprising information, confirming how essential a normally functioning female immune system is for normal conception. We have made this point before many times over in these pages, and consider CHR’s emphasis on understanding pregnancy as an immunologically-mediated temporary state of immunological tolerance as yet another very important contribution of our center to reproductive medicine, as most of the field over the last two decades has been rather dismissive of reproductive immunology.

This attitude is, fortunately, changing. Discoveries in organ transplantation and, even more so, discoveries in how malignant tumors evade recognition by the host’s immune system, have major potential significance for normal human pregnancy but also for implantation failure and increased miscarriage risks. A recent study demonstrated almost eerie similarities in the genomics of the microenvironment of invading tumors and pregnancy [Nehar-Belaid et al., J Immunol 2016;196(2):678-679].

CHR’s Medical Director and Chief Scientist, Norbert Gleicher MD, was recently invited to write a commentary in LeapsMag, an online life sciences publication (above), in which he noted that he started his research career in the late 1970s researching common immunological denominators between pregnancy and malignancy, only to return to exactly the same theme approximately 40 years later. The cycle, thus, closes but also demonstrates how much our understanding of the immune system has improved. It now appears high time to put this knowledge to work in clinical reproductive medicine.

This is a part of the January 2018 CHR VOICE.