CHR’s new reproductive immunology initiative: Announcement

Approximately 15 years ago, CHR reached a crucial point in its history, when a decision was reached to concentrate the center’s resources on what was felt to be the cutting-edge issue in reproductive medicine at that point: the aging ovary. This decision proved prophetic and succinct, and over the following years led to worldwide recognition of CHR as the fertility center with, likely, the most advanced expertise in treating “older ovaries.”

As we reported before in these pages, CHR earned this respect by making the aging ovary the center of CHR’s research effort but also by concentrating the center’s clinical care on women with “older ovaries,” whether due to age or premature ovarian aging (POA). The consequence was that research and clinical care started feeding upon each other: New research led to new treatments which, in turn, improved outcomes, which increased patient load and revenue, allowing for more research, etc. The desired end result, advancing our ability to establish pregnancies with use of autologous oocytes at increasingly advanced ages, has been met with rather spectacular success: When our initiative started, like most IVF centers still today, we rarely were able to establish pregnancies in women above age 42. Today, we report on the cover page of this issue of the VOICE the birth of a healthy child to a woman who was 47 years and 10 months at time of her embryo transfer, likely the oldest IVF pregnancy ever recorded. At CHR, 42-year-old women are now considered “young,” and usually still experience excellent pregnancy chances with their own eggs.

While CHR is continuing to concentrate on “older ovaries,” CHR, after lengthy discussion, has recently concluded that the time was ripe for a concentrated additional initiative in an area of reproductive medicine, in which CHR has conducted research and held a prominent position for decades, namely, Reproductive Immunology.

Considering that CHR has been conducting research and has been extensively publishing in reproductive immunology for decades, the question may be asked: Why then a special initiative, and why now? The simple answer is that, considering recent progress in tumor and transplantation immunology as well as genetics, like 15 years ago with “aging ovaries,” the time, now seems, simply, “ripe.” CHR now considers the time opportune to start applying all of this new knowledge, garnered in other areas of medicine, to the fertility and pregnancy experience.

CHR has a very distinguished history in the field of Reproductive Immunology. Norbert Gleicher, MD, CHR’s Medical Director and Chief Scientist, was one of the initial founders of the American Society for Reproductive Immunology and the society’s Founding Vice-President. He also served for ca. 15 years as the Founding Editor of the American Journal of Reproductive Immunology (AJRI) and, therefore, on the Society’s board. In addition, he in 1979 established in New York City’s Mount Sinai Medical Center the first Division of Reproductive Immunology in the country. Other prominent reproductive immunologists over the years also joined CHR, among those Alan Beer, MD and Carolyn Coulam, MD.

CHR, therefore, has been treating patients with presumed immunological problems for many decades. Indeed, like in other areas of infertility, many of these patients have failed “immune treatments” elsewhere, and have been coming to CHR from long-distances, often from overseas. Our treatments have, however, hardly changed in the last 20 years and, while we consider them in many clinical circumstances quite successful, we have to acknowledge that much of what we (and others) currently do clinically in the reproductive immunology field is quite outdated in comparison to applications of new immunological knowledge in other areas of medicine.

For the longest time, we have not seen potential entry points for research into reproductive immunology that would allow us to discover new potential translational treatment improvements. Recent developments, however, for the first time in decades make such discoveries appear feasible.

CHR already in 2016 initiated research with that in mind by starting a prospective study of immune pathway induction via Influenza vaccinations. Initiation of this study even attracted the attention of Science, with this leading science publication dedicating a whole article to the project.

Initiating such a second major directional initiative at CHR, of course, also creates significant additional expense for the center. We, for example, at quite significant cost are currently exploring the acquisition of an automated cell-sorting system, which would allow identification of immune pathways, associated with development of early tolerance toward the paternal semi-allograft, an absolutely essential step for implantation. Fortunately, we are expecting outside grant-support for such a purchase.

Largely by its own faults, reproductive immunology has obtained an image of scientific un-seriousness. Browsing the Internet, one comes across some of the most imaginative claims by practitioners with allegedly special expertise in reproductive immunology. Where those expertise comes from, what peer-reviewed evidence suggests proposed treatments and, indeed, often even what the practitioners’ own outcome data are, is often hard to come by. For lack of alternative, the public, however, frequently, is left with accepting these rather baseless claims.

Over the last 20-30 years, reproductive immunology has, therefore, existed in somewhat of a scientific purgatory, on the one side often represented by pseudoscientists, and on the other side, understandably, ignored by many academic reproductive endocrinologists for lack of evidence-based treatments and/or even most basic understanding of why immunology is of great importance for successful reproduction: With the fetus being 50% “foreign,” there would be no pregnancy, if the female immune system did not have the unique ability to reprogram itself from rejection to tolerance.

Like 15 years ago, when deciding to tackle the seemingly insurmountable problem of the aging ovary, CHR over the coming years will be attempting to bridge this divide by tackling one of the most basic, still unresolved biological questions, namely, how the maternal immune system reprograms itself in a way that allows it to tolerate an incredibly quickly growing “parasitic” pregnancy which, under basic solid organ transplantation rules, should be rapidly and violently rejected. Understanding the immune pathways induced to achieve this goal in normal pregnancy will not only help identify the pathophysiology of many cases of implantation failure and repeated pregnancy loss but, likely, also what causes most of premature labor (i.e., early termination of tolerance), preeclampsia and other late pregnancy pathologies. Once the responsible immune pathways have been identified, treatment options will become obvious.

With this Reproductive Immunology Initiative, CHR hopes to be able to replicate the incredible success of its Ovarian Aging Initiative of 15 years ago. If even only partially as successful, CHR will over the next few years develop radically new ways to treat immunological reproductive failure (IRF) that will help women for whom currently there is no help. CHR’s infertility practice is strongly data-driven, brutally honest in disclosures of what we do and do not know, and can or cannot do. We, therefore, hope to be able to return some of the credibility to the important field of reproductive immunology that it enjoyed during the first decade after its establishment as an independent research specialty in reproductive biology in the late 1970s and early 1980s.

Finally, many of the most important observations CHR made in improving treatments of older ovaries, were brought to our attention by patients. We, therefore, always welcome the help of our patients in pursuing new knowledge, and learn from every new patient we meet. If you believe you suffer from immunological causes of infertility and pregnancy loss, come and see us at CHR!

This is a part of the October 2017 VOICE.

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned reproductive endocrinologist, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.