Survival and growth of human preantral follicles after cryopreservation of ovarian tissue, follicle isolation and short-term xenografting

In women, chemotherapy and radiotherapy can be harmful to the ovaries, causing loss of endocrine and reproductive functions. When gonadotoxic treatment cannot be delayed, ovarian tissue cryobanking is the only way of preserving fertility. This technique, however, is not advisable for patients with certain types of cancer, because of the risk of reintroducing malignant cells present in the cryopreserved tissue. Our objective is therefore to develop a transplantable artificial ovary. To this end, cryopreserved human preantral follicles were isolated and embedded in fibrin formulations prepared with 50 mg/ml fibrinogen and 10 IU/ml thrombin supplemented or not with 3% hyaluronic acid, and respectively xenografted to specially created right and left peritoneal pockets in eight nude mice. On days 0 and 7, the animals were killed and the matrices retrieved. On day 7, no difference was observed in the recovery rate of follicles embedded in fibrin alone (23.4%) or fibrin-hyaluronic acid (20.5%). Ki67 staining confirmed growth of the grafted follicles and terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling assay revealed 100% of the follicles to be viable in both groups on day 7. In conclusion, fibrin seems to be a promising material for creation of an artificial ovary, supporting follicle survival and development.