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Updated: Jun 29, 2026

Fertility Preservation Through Oocyte Vitrification: Clinical and Laboratory Perspectives
Published on: September 16, 2021
Effect of methotrexate exposure on subsequent fertility in women undergoing controlled ovarian stimulation
Janet F McLaren1, Richard O Burney, Amin A Milki
1Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, California, USA.
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.
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