Administration of cyclophosphamide at different stages of follicular maturation in mice: effects on reproductive performance and fetal malformations

This study assessed reproductive performance, fetal viability and teratogen icity in female mice exposed to cyclophosphamide across a timeline correspo nding to different stages of follicle maturation. Pregnancies were establis hed in female Balb/c mice 1-4 weeks after administration of a non-sterilizi ng dose of cyclophosphamide (75 mg/kg), Each mating group represented a dif ferent stage of follicular growth at the time of cyclophosphamide exposure. The number of corpora lutea, pregnancies and fetal resorptions were determ ined. Surviving fetuses were evaluated for gross malformations. Results ind icated that conceptions attributable to follicles exposed to cyclophosphami de at a mature stage had a significantly lower number of implantation sites , 4.82 +/- 1.01 versus 8.27 +/- 0.81 in controls (P = 0.001) and a high res orption rate, 56% +/- 0.11 versus 34% +/- 0.07 in controls (P = 0.05), The proportion of corpora lutea in this group which resulted in viable fetuses was extremely low, 0.2 +/- 0.06 versus 0.51 +/- 0.07 in controls (P = 0.001 ), Malformation rate was more than 10 times higher in all treated groups (P < 0.05) and a particularly high incidence of 33% (P = 0.0014) was observed in conceptions attributable to oocytes exposed to cyclophosphamide at the earliest stages of follicle growth. With an extended interval between expos ure and mating the malformation rate gradually decreased towards normal val ues in the 12th week group. This study suggests that the effect of cyclopho sphamide on female gametes and subsequently on future reproduction is influ enced by the stage of oocyte maturation at the time of exposure. Early fert ilization post-chemotherapy can result in a high rate of pregnancy failure and high malformation rate. This should be taken into account when consider ing the use of oocyte retrieval, IVF and embryo cryopreservation in patient s currently undergoing chemotherapy.