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Engineered Environments for Ovarian Follicle Transplantation

Site: Northwestern University

Principal Investigator: Lonnie D. Shea, PhD

Rationale

Compared to their age-matched peers, the five-year relative survival rate of cancer patients is now at 68%, improved from 50% thirty years ago. At least one in 250 women of reproductive age are cancer survivors. Today, 90% of these young women will be cured of their cancer. Unfortunately, the chemotherapies that save their life are fertility-threatening; in particular, alkylating agents and platinum-based drugs are highly associated with post-treatment infertility as they cause DNA damage to the oocytes that comprise the ovarian reserve.

Most young women with cancer are highly interested in trying to preserve their fertility so they might have children in the future. The cryopreservation and autotransplantation of ovarian tissue is emerging as a powerful approach for preserving fertility for patients that are losing ovarian function. Ovarian tissue transplantation has preserved fertility (at least 22 live births to date); however, for cancer patients, transplantation may not be possible due to the risk of re-seeding disease.

The objectives of this project are to:

Refine the procedures for follicle isolation to enable large-scale recovery of primordial follicles, and subsequently investigate the engraftment and function by transplanted follicles within a range of biomaterials.

Investigate strategies to modulate the initial recruitment of follicles that would deplete the ovarian reserve, and thereby enhance the duration of graft function.

Investigate the transplantation of follicles from post-pubertal animals, and determine the contribution of age and obesity of the recipient on the engraftment and function of transplanted follicles.

Investigate the transplantation of ovarian follicles from mice with metastatic disease, which simulates the clinical situation of re-seeding cancer cells.