Temsirolimus and antimüllerian hormone protect fertility and the ovarian reserve against chemotherapy-induced damage in a murine model.

OBJECTIVE

To investigate the effects of temsirolimus (Tem) and recombinant antimüllerian hormone (AMH) on fertility and the ovarian reserve when associated with chemotherapy.

DESIGN

Thirty-seven female mice were assigned to one of three treatment groups: control group; chemotherapy group; and gonadoprotection group. Five weeks after treatment, the mice underwent ovarian stimulation and were mated with males to evaluate residual fertility. Two days after mating, the animals were euthanized for embryo collection, and the ovaries were retrieved to assess the ovarian reserve and follicle damage.

SUBJECTS: Thirty-seven Naval Medical Research Institute mice.

EXPOSURE: The control group (n = 10) was given a 100-μL injection of phosphate-buffered saline. The chemotherapy group (n = 13) received a single 100-μL injection of chemotherapy (120-mg/kg cyclophosphamide and 12-mg/kg busulfan). The gonadoprotection group (n = 14) was administered five injections of 5-mg/kg Tem over 1 week prior to chemotherapy, followed by a chemotherapy injection and then five injections of 5-μg recombinant AMH over the next 24 hours.

MAIN OUTCOME MEASURES: Embryo count, follicle count and morphology, and immunostaining for apoptosis (cleaved caspase-3), follicle activation (phospho-Akt), and proliferation (Ki67).

RESULTS

The control group showed the highest mean number of retrieved embryos (41.40 ± 14.74), closely followed by the gonadoprotection group (36.27 ± 17.22), whereas the chemotherapy group exhibited a significant reduction (20.63 ± 12.12) compared to both groups. Regarding the ovarian reserve, the control group showed the highest total follicle count (897.4 ± 392.8), with no difference compared to the gonadoprotection group (714.4 ± 283.9); however, there was a significant decline in the chemotherapy group (320.7 ± 145.5) compared with those in both groups. In terms of follicle apoptosis and activation, no significant difference was observed between groups. Follicle proliferation rates were significantly higher in the chemotherapy group (59.38% ± 14.67%) than in the control group (20.72% ± 10.52%); but gonadoprotective treatment did curtail follicle proliferation (42.23% ± 18.37%) compared with the chemotherapy group.

CONCLUSION

Our findings suggest that Tem and AMH show promise as gonadoprotective agents, potentially protecting the ovarian reserve against chemotherapy and thereby preserving fertility. This could offer patients who cannot benefit from currently available techniques brand new fertility preservation options.