Subclinical depletion of primordial follicular reserve in mice treated with cyclophosphamide: clinical importance and proposed accurate investigativetool

Studies have shown that ovarian failure is a common side-effect of chemothe rapy treatment; however, continuation of regular menses post-treatment does not necessarily imply that the ovaries have escaped damage. This animal st udy measures directly the primordial follicle (PMF) loss following exposure to chemotherapy and evaluates reproductive outcome following significant d estruction of the PMF population. Inbred Balb/c mice aged 5-6 weeks were ad ministered different doses of an alkylating agent, cyclophosphamide, and th e total number of PMF remaining in both ovaries was counted. Results show t hat cyclophosphamide causes PMF destruction in proportion to increasing dos e (P = 0.0001). Reproductive performance was assessed after exposure to 75 mg/kg cyclophosphamide, a dose which destroys similar to 50% of PMF reserve , by evaluation of ovulation, mating and pregnancy rates. Reproductive pote ntial of treated mice was not affected compared with controls despite the s ignificant loss of PMF. Our results indicate that reproductive performance is not an accurate parameter for assessing ovarian injury. Rather, histolog ical counting of PMF number more directly reflects the damage caused by che motherapy to the ovary. This method can be used as a sensitive, inexpensive tool to gauge the damage to fertility caused by new chemotherapy agents or protocols.