Retrievable hydrogels for ovarian follicle transplantation and oocyte collection
Rios, Peter D.; Kniazeva, Ekaterina; Lee, Hoi Chang; Xiao, Shuo; Oakes, Robert S.; Saito, Eiji; Jeruss, Jacqueline S.; Shikanov, Ariella; Woodruff, Teresa K.; Shea, Lonnie D.
2018-08
Citation
Rios, Peter D.; Kniazeva, Ekaterina; Lee, Hoi Chang; Xiao, Shuo; Oakes, Robert S.; Saito, Eiji; Jeruss, Jacqueline S.; Shikanov, Ariella; Woodruff, Teresa K.; Shea, Lonnie D. (2018). "Retrievable hydrogels for ovarian follicle transplantation and oocyte collection." Biotechnology and Bioengineering 115(8): 2075-2086.
Abstract
Cancer survivorship rates have drastically increased due to improved efficacy of oncologic treatments. Consequently, clinical concerns have shifted from solely focusing on survival to quality of life, with fertility preservation as an important consideration. Among fertility preservation strategies for female patients, ovarian tissue cryopreservation and subsequent reimplantation has been the only clinical option available to cancer survivors with cryopreserved tissue. However, follicle atresia after transplantation and risk of reintroducing malignant cells have prevented this procedure from becoming widely adopted in clinics. Herein, we investigated the encapsulation of ovarian follicles in alginate hydrogels that isolate the graft from the host, yet allows for maturation after transplantation at a heterotopic (i.e., subcutaneous) site, a process we termed in vivo follicle maturation. Survival of multiple follicle populations was confirmed via histology, with the notable development of the antral follicles. Collected oocytes (63%) exhibited polar body extrusion and were fertilized by intracytoplasmic sperm injection and standard in vitro fertilization procedures. Successfully fertilized oocytes developed to the pronucleus (14%), two‐cell (36%), and four‐cell (7%) stages. Furthermore, ovarian follicles cotransplanted with metastatic breast cancer cells within the hydrogels allowed for retrieval of the follicles, and no mice developed tumors after removal of the implant, confirming that the hydrogel prevented seeding of disease within the host. Collectively, these findings demonstrate a viable option for safe use of potentially cancer‐laden ovarian donor tissue for in vivo follicle maturation within a retrievable hydrogel and subsequent oocyte collection. Ultimately, this technology may provide novel options to preserve fertility for young female patients with cancer.The authors present an alginate hydrogel as a retrievable technology to mature ovarian follicles subcutaneously and to prevent escape and subsequent metastasis of cancer cells. Early stage follicles were transplanted within hydrogels, matured in vivo, and oocytes subsequently collected. Fertilized oocytes progressed to the 2‐cell and 4‐cell embryo stages. These findings demonstrate retrievable hydrogels as a novel approach to mature follicles and obtain fertilizable oocytes, but also to alleviate concerns related to re‐seeding disease from cryopreserved auto‐transplanted ovarian tissue.Publisher
American Cancer Society Wiley Periodicals, Inc.
ISSN
0006-3592 1097-0290
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