Chemotherapy-Induced Follicle Activation and Loss in Human Ovarian Tissue. First Documentation of the "Burn-Out" Effect in Clinical Cases - AWARD NOMINEE

Introduction-

Ovarian failure infertility is a substantial complication of chemotherapy treatment. Recent studies have postulated that the main mechanism of primordial follicle (PMF) reserve loss is by follicle activation alongside with PMF depletion. Those in vivo studies have used rodent models treated with alkylating or Platine agents.

Aim-

To investigate whether chemotherapy-induced follicle activation can be demonstrated in ovaries of women exposed to alkylating agents.

Materials & Methods-

Cortical samples were evaluated from women who stored ovarian tissue to preserve fertility. Study group- ovarian tissue samples of women who underwent chemotherapy protocols containing alkylating agents

Results-

The study group were 13 cases and 26 controls. Mean patients` age was 27.5 (range 15-38y). High reliability between all the examiners was noted (alpha-0.995). There were less absolute PMF counts/slide in chemotherapy group 6.4 vs. 12 in controls but not reaching statistical significance (p=0.08). A significant difference was observed between growing follicles (primary plus secondary) versus total follicles, which includes primordial (p-0.001, CI 0.3-0.48).

Conclusion-

This study demonstrate for the first time that alkylating agents activate the growth of the quiescent PMF pool in human ovaries exposed to chemotherapy. These human results combined with animal studies, support the hypothesis of chemotherapy induced follicle "Burn- Out` effect and point to an optional target for medications that might reduce chemotherapy sterilizing effects.