Follicular development, ovulation, and corpus luteum formation in cryopreserved human ovarian tissue after xenotransplantation

Objective: To assess the competency of human frozen/thawed ovarian follicles matured in xenografts to form functioning corpora luteae after human chorionic gonadotropin (hCG) administration. Design: Prospective controlled animal study. Setting: University research laboratory. Patient(s): Three women (19, 28, and 36 years) who underwent oophorectomy. Animal(s): Nineteen female severe combined immunodeficient (SCID) mice. Intervention(s): Cryopreserved human ovarian tissues were grafted into the s.c. space of bilaterally oophorectomized SCID mice. All the animals were stimulated with pregnant mare's serum gonadotropin (PMSG) for 4 weeks starting from 16 weeks after transplantation. Twelve animals were injected with hCG at the end of gonadotropin stimulation. Main Outcome Measure(s): [1] The rate of grafts with growing follicles, with antral follicles, and/or with corpora luteae. [2] The histologic assessment of follicles and corpora luteae. [3] The serum progesterone and estradiol level in animals with corpus luteum in the grafts. Result(s): [1] The rate of grafts with growing follicles and with corpora luteae was 33% to 100%, and 28% to 50%, respectively. [2] Corpora luteae in xenografts were all morphologically normal. [3] The progesterone levels were all above 3.0 ng/mL. Conclusion(s): This study showed that the cryopreserved human ovarian follicles can be matured to a stage at which they can form functioning corpora luteae in the host animal.