Introduction: Premature ovarian failure and infertility are major side effects of chemotherapy treatments in young cancer patients. The "burn-out" mechanism of dormant follicles recruitment and loss post cyclophosphamide administration was recently demonstrated to be the major cause of follicle loss and reduced ovarian reserve in mice. Aim: To investigate the effects of chemotherapy treatments in vivo on human ovarian follicles among young female cancer patients undergoing ovarian tissue cryopreservation (OTCP) for fertility preservation.
Materials & Methods: Ovarian cortical tissues originated from young cancer patients (n=10) undergoing OTCP were analyzed in two groups: Those who received chemotherapy treatment up to six months prior to OTCP compared to their age-matched untreated patients (age range 15-36). Distribution of follicles in histological sections (n=30) and classification of follicles as dormant or growing was performed by two independed observers. Activation of dormant follicles was expressed as an increase in the ratio between growing follicles (GF) to total follicle counts (GF/Total). Statistical analysis was performed using the Fisher Exact test with P value lower than 0.05 as statistical significance.
Results: Higher numbers of GF were observed in patients recently exposed to chemotherapy compared to their age-matched untreated controls (168 and 72 in exposed and unexposed respectively, p<0.05). The GF/Total ratio increased from 26% in the untreated patients to 39% in the chemo-exposed women. The changes in follicle populations were not observed in one patient who was treated with chemotherapy only two weeks prior to OTCP and her PMF population was not altered (i.e. the effects of chemotherapy on this follicle population was not expressed yet).
Conclusions: This study demonstrates follicles recruitment and "burn-out" after chemotherapy in human ovaries. The changes in follicle populations observed are in accordance with our results in mice. Further confirmation with immunohistological staining and protein analysis will enable promoting targeted ovarian protection which may result in higher ovarian reserve and better chances for future fertility.
