ESHRE 2018: Early-Stage Research Shows Potential of Artificial Ovary for Fertility Preservation Without the Risk of Reintroducing Malignancy
Important steps in the development of an artificial ovary have been successfully completed. Researchers from the Rigshospitalet in Copenhagen, Denmark, reported that they have—for the first time—isolated and grown human follicles to a point of biofunctionality on a bioengineered ovarian scaffold made of decellularized ovarian tissue. The early-stage follicles were isolated from patients having ovarian tissue frozen for fertility preservation ahead of other medical treatments likely to compromise ovarian function.
These findings were presented by Susanne Pors, PhD, DVM, of Rigshospitalet's Laboratory of Reproductive Biology, at the 34th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) in Barcelona (Abstract O-083).
The Danish group has ovarian tissue preserved over the past 20 years from 1,100 patients, and 115 thawed transplantations performed in 90 women.
Dr. Pors said that developing an effective protocol of eliminating cells from ovarian tissue and the transfer of viable early-stage follicles would remove the possibility of reintroducing malignancies potentially present in the original tissue. Currently, most cases of fertility preservation by ovarian tissue freezing are performed ahead of cancer treatment, where radiotherapy or chemotherapy are likely to destroy ovarian function. Thawing and regrafting the original cryopreserved tissue would thus run the risk of reintroducing any malignancy. “However,” said Dr. Pors, “a bioengineered ovary would allow the growth and development of reseeded frozen-thawed early stage follicles in a tissue bed which is free of malignancies.”
Study Methods
The research was performed with ovarian tissue removed from women having fertility preservation ahead of cancer treatment. The inhabiting cells of the tissue were eliminated by a 3-day chemical process, after which decellularization was tested by DNA and collagen quantification. Removal of the inhabiting cells left an extracellular matrix scaffold of the original tissue. It was this bioengineered scaffold on which the isolated early-stage follicles were reseeded.
Tests on the functionality of the extracellular matrix showed that the tissues had been completely decellularized, with no native material evident. “We then found that ovarian cells and early-stage follicles were able to recellularize the decellularized tissue in vitro by successfully repopulating and migrating into the scaffold,” explained Dr. Pors. Transplantation experiments (into mice) showed that the decellularized matrix was able to support survival and growth of early-stage follicles.
“This is the first time that isolated human follicles have survived in a decellularized human scaffold,” said Dr. Pors, “and, as a proof-of-concept, it could offer a new strategy in fertility preservation without risk of malignant cell reoccurrence.”
The technique, she added, would be applicable to patients with cancer having cryopreserved ovarian tissue transplanted for fertility restoration.
Dr. Pors explained that the risk of recurring malignancy from frozen tissue is “real”, especially for patients with leukemia and cancers originating in the ovary. However, studies performed by the Copenhagen group and others show that the risk of transferring cancer cells from other malignancies appears to be very low.
Dr. Pors described this as a “proof-of-concept study,” showing for the first time that human follicles can survive on a human decellularized scaffold. Further studies are planned to optimize the scaffold and reseeding procedure and to evaluate the quality of the follicles for further use.
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