Publication date: 25th July 2016
Premature ovarian insufficiency (POI) is a common complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. Modern anticancer therapy has improved the survival rate for children and young adults diagnosed with cancer in the United States to over 80% and now these cancer survivors face long-term health problems. POI causes sterility, along with consequences of lost ovarian endocrine function: premature osteopenia, muscle wasting, and accelerated cardiovascular diseases. The unique challenges associated with fertility preservation in females are primarily due to limited and non-renewable ovarian reserve. None of the clinically available fertility preservation options can restore the lost ovarian endocrine function and none are suitable for children and young adults.
Cryopreservation of ovarian tissue prior to the exposure to toxic treatments and subsequent implantation is a clinically relevant fertility preservation option. However, autotransplantation of the cryopreserved tissue in cancer patients carries a risk of re-introducing malignant cells harbored in the transplant, particularly in case of hematologic malignancies. To address some of current limitations in the area of fertility and ovarian endocrine function preservation we engineered a biomaterial-based matrix to support the development of ovarian follicles cultured in vitro or transplanted in vivo. Proteolytically degradable synthetic poly(ethylene-glycol) (PEG)-based hydrogels provided sustainable structural and biochemical support for encapsulated ovarian follicles. Our studies in mice demonstrated that early stage follicles encapsulated in PEG hydrogels and implanted in ovariectomized animals functioned as healthy ovarian tissue, responded to circulating gonadotropins and secreted sex hormones sufficient to reverse POI.
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