Transplantation of cryopreserved human ovarian tissue results in follicle growth initiation in SCID mice

Abstract

Objective: To determine the long-term survival of frozen-thawed human ovarian tissue as xenografts in severe-combined-immunodeficiency (SCID) mice. Design: Animal study. Setting: Animal and laboratory facilities at an academic center. Patient(s): Ovarian tissue obtained from a 27-year-old woman. Intervention(s): Grafting of frozen-thawed ovarian tissue in SCID mice for 22 weeks. Main Outcome Measure(s): Follicle counts and growth by morphology and PCNA staining in frozen-thawed grafts and fresh controls. Result(s): All three grafts were recovered intact after 22 weeks. Their stroma was devoid of necrotic cells and contained healthy follicles. The ratio of primordial-total follicles decreased significantly after grafting (0.94 ± 0.02 to 0.87 ± 0.01, control vs. grafting). Compared with controls, after 22 weeks of grafting, a higher percentage of follicles had initiated growth (5.6 ± 2.4 vs. 12.5 ± 1.9), but there was still a significant number of primordial follicles/graft (75 ± 6.8). Follicle stages were similar between two groups; only primordial and one-layer follicles were seen in the xenografts. In the controls, except for one two-layer follicle, the most advanced follicle was at the one-layer stage. Conclusion(s): Human primordial follicles survive freeze-thaw and long-term xenografting procedures and retain their capacity to initiate growth. These findings encourage future attempts for human autologous ovarian transplantation.