Influence of high‐dose methotrexate therapy on the primordial follicles of the mouse ovary

Objective:  High-dose methotrexate (MTX) is one of the most prescribed agents in many malignant diseases affecting girls and young women of reproductive ages. This animal study directly measures the primordial follicle loss following exposure to high-dose MTX. Study Design:  Nine inbred Balb/c mice aged 7–8 weeks in the study group were administered 5 gr/m2 MTX as a single agent intraperitoneally, whereas nine mice in the control group received saline. Seven days later the mice were killed and total numbers of the primordial follicles remaining in both ovaries were counted. Result:  In the high-dose MTX group, the mean number of primordial follicles (mean ± standard deviation) was significantly different (202 ± 38) versus the control group (327 ± 81.7; P = 0.002). Conclusions:  Our study shows that high-dose MTX causes damage to the primordial follicles of the ovaries of mice. This result may be important because young women taking high-dose MTX may suffer diminished reproductive performance and premature cessation of menses in the years following therapy.