Each year, ASRM and its affiliated societies are excited to be able to award grant opportunities to new investigators in the field of reproductive medicine. The primary purpose of ASRM Research Grant programs is to provide funds for investigators to establish independent research programs. Without the support of donors, these research grants would not be possible.
Take a moment to learn about 2016 grant recipient, Kara Goldman, M.D., and the work and research she has accomplished thanks to donations to the ASRM Member Impact fund.
When did you acquire your ASRM research grant, and what was the process like?
I initially applied for an ASRM research grant during my second year of fellowship and was not awarded the grant. This was my first grant application and grant rejection, but the process of writing, editing, and submitting my first grant was an educational experience in itself. I was committed to making my project work and knew that ASRM funding would be critical to moving the project forward, so I re-applied in 2015 and was fortunate to receive the award. My goal was to fund myself so that I could continue doing research when I completed my NYU fellowship and joined the faculty. This grant provided an important bridge to allow me to build on the work I had begun as a fellow.
What kind of research did the grant go toward or how is it being used now? If your research is complete, what was the outcome?
The ASRM research grant funded our work investigating mTOR inhibitors in mice to preserve fertility during gonadotoxic chemotherapy. Current options for female fertility preservation are limited to oocyte or embryo cryopreservation, and there are no effective pharmacologic agents to preserve fertility during chemotherapy. We hypothesized that mTOR inhibitors, which downregulate the PI3K/AKT/mTOR pathway, could prevent primordial follicle activation and maintain the follicles in a quiescent state during chemotherapy, thus preserving primordial follicles and fertility. mTOR inhibitors are widely available agents, currently FDA approved for the treatment of a number of benign and malignant conditions. These agents thus represent an attractive option for co-treatment with chemotherapy. We used a mouse model of chemotherapy-induced gonadotoxicity to demonstrate that co-treatment with mTOR inhibitors preserves primordial follicles, AMH, and most importantly, fertility, compared to mice treated with chemotherapy alone. This work received the Scientific Program Prize Paper award at the ASRM 2016 Scientific Congress & Expo, as well as the Fertility Preservation Special Interest group prize paper, and was published in Proceedings of the National Academy of Sciences in March 2017.
Why do you believe this research is important for healthcare professionals and patients?
Chemotherapy often leads to subfertility, infertility, and primary ovarian insufficiency in reproductive-aged women exposed to chemotherapy. Unfortunately, cancer is not uncommon in reproductive-aged women, and the chemotherapy agents typically used in the treatment of these cancers are particularly gonadotoxic (particularly Cyclophosphamide, the agent used in our study). Oocyte and embryo cryopreservation are proven methods of fertility preservation, but they preserve a limited number of oocytes or embryos without protecting ovarian function. The ideal fertility preservation method would preserve not only fertility, but also ovarian function. Our findings may represent a feasible, effective pharmacologic fertility preservation agent to protect ovaries during gonadotoxic chemotherapy. The only class of pharmacologic agents currently available, GnRH agonists, have been extensively studied for fertility preservation with controversial results. Physiologically, GnRH agonists protect gonadotropin-sensitive follicles, only a fraction of the total ovarian follicle pool, without protecting the critical primordial follicle pool. An agent that could maintain follicles in the primordial follicle state would therefore represent a novel and more effective approach to the preservation of not only fertility but ovarian function.
Have you discovered any new information that you didn’t know or were unsure of before?
Given the findings of our study, and the knowledge that mTOR inhibitors have been proven to prolong lifespan in multiple species, we then hypothesized that mTOR inhibitors could potentially prolong reproductive longevity in mice. Mice treated with dual mTORC1/2 inhibitors at a young reproductive age had significantly more litters and prolonged longevity compared to mice experiencing physiologic ovarian aging. These agents may represent a pharmacologic means to prolong reproductive longevity, but this warrants future study. We submitted our findings for presentation at the ASRM 2017 Scientific Congress & Expo. Our initial work opened the door to a number of possible studies regarding the role of mTOR and fertility, and I am hoping to pursue these intriguing research questions, if given the opportunity.
Will you be doing more research related to this topic, and if so, how has this grant allowed you to progress?
I am completing a study assessing the impact of mTOR inhibitors on reproductive longevity and am working to further explore the relationship between the mTOR pathway and physiologic ovarian aging. To further our work on mTOR inhibitors for fertility preservation, we are developing a study assessing ovarian reserve in women currently treated with mTOR inhibitors. Because these agents are clinically used for a number of benign and malignant conditions, this presents an ideal opportunity to study the impact of these agents on ovarian reserve parameters in women already taking them before moving to a clinical trial. Ultimately, we hope to move to a clinical trial in order to assess the impact of co-treatment with mTOR inhibitors for fertility preservation in women exposed to gonadotoxic agents. Our previous work utilized a mouse model, and ultimately, only a clinical trial will definitively tell us if this approach would be safe and effective in humans.
The generous research grant from the American Society for Reproductive Medicine allowed me to seamlessly continue my research after completing fellowship and beginning my faculty position at NYU. This grant funding provided a critical bridge for me to continue studying pharmacologic fertility preservation, and for that I am extremely grateful.