Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at -196 C

We have previously demonstrated that ovarian function and fertility can be preserved in sheep after castration by autotransplantation of cryopreserved strips of ovarian cortex. In the current experiments we have investigated the long term survival of such grafts by detailed measurements of ovarian f unction for a period of nearly 2 yr after autotransplantation. After ovarie ctomy and transplantation of frozen/thawed grafts, the concentrations of FS H and LH rose to castrate levels for about 14 weeks before falling graduall y to reach near-normal levels at about 60 weeks. In the breeding season Fro m October 1994 to March 1995, all ewes had 5-10 estrous cycles that were si milar in length to those in the 4 control ewes. Luteal function as indicate d by the progesterone concentration was identical before and 11 months afte r transplantation. In contrast, the basal concentrations of FSH and LH were persistently raised throughout the luteal phase, but showed a normal decli ne during the follicular phase. The concentration of inhibin A in ovarian v enous plasma measured at the end of the experiment 22 months after transpla ntation was significantly lower than that in control ewes (mean +/- SE, 409 +/- 118 vs. 1914 +/- 555 pg/ml; P < 0.004). Transplantation of frozen/thaw ed ovarian tissue to SCID mice demonstrated that about 28% of primordial fo llicles survived the procedure. All of the ovaries transplanted into sheep contained large antral follicles and/or cysts, but very few primordial oocy tes when recovered at autopsy after 22 months. These results demonstrate that despite a drastic reduction in the total num ber of primordial follicles, cyclical ovarian function is preserved in shee p after autotransplantation of frozen/thawed ovarian tissue and provide exp erimental confirmation that such a technique could provide a means of prese rving fertility in women undergoing chemo- or radiotherapy for malignant di sease.