Effect of methotrexate exposure on subsequent fertility in women undergoing controlled ovarian stimulation.

OBJECTIVE: To evaluate the pregnancy rate, ovarian responsiveness, and endometrial thickness in infertility patients with a history of methotrexate exposure who subsequently underwent controlled ovarian stimulation.

DESIGN: Retrospective cohort study.

SETTING: University reproductive endocrinology and infertility program.

SUBJECT(S): Forty-eight women with infertility undergoing ovarian stimulation after receiving methotrexate treatment for ectopic gestation.

INTERVENTION(S): Methotrexate administration and controlled ovarian stimulation.

MAIN OUTCOME MEASURE(S): Pregnancy rate, cycle day 3 FSH levels, number of oocytes retrieved, and endometrial thickness.

RESULT(S): The cumulative intrauterine pregnancy rate achieved with controlled ovarian stimulation at 2 years after methotrexate exposure was 43%, with a mean time to conceive of 181 days. Thirty-five patients with similar fertility treatments pre- and post-methotrexate were identified. Within this group, when an IVF cycle occurred within 180 days of methotrexate exposure, a significant decline in oocytes retrieved was observed. Cycles performed later than 180 days after methotrexate exposure did not exhibit a decrease in oocyte production. Endometrial development was similar at all time points examined.

CONCLUSION(S): These findings suggest a time-limited and reversible impact of methotrexate on oocyte yield. If confirmed by larger clinical series and/or animal data, these results may impact the management of ectopic gestation in the patient with a history of infertility or the timing of subsequent treatments.