Methotrexate does not affect ovarian reserve or subsequent assisted reproductive technology outcomes

  • Christina E. BootsEmail author
  • Micah J. Hill
  • Eve C. Feinberg
  • Ruth B. Lathi
  • Susan A. Fowler
  • Emily S. Jungheim
Fertility Preservation



The purpose of this research was to study whether methotrexate (MTX) as treatment for ectopic pregnancy (EP) impacts the future fertility of women undergoing assisted reproductive technology (ART)


In a systematic review and multi-center retrospective cohort from four academic and private fertility centers, 214 women underwent an ART cycle before and after receiving MTX as treatment for an EP. Measures of ovarian reserve and responsiveness and rates of clinical pregnancy (CP) and live birth (LB) were compared in the ART cycles prior and subsequent to MTX.


Seven studies were identified in the systematic review, and primary data from four institutions was included in the final analysis. Women were significantly older in post-MTX cycles (35.3 vs 34.7 years). There were no differences in follicle stimulating hormone, antral follicle count, duration of stimulation, oocytes retrieved, or fertilization rate between pre- and post-MTX cycles. However, post-MTX cycles received a significantly higher total dose of gonadotropins (4206 vs 3961 IU). Overall, 42 % of women achieved a CP and 35 % achieved a LB in the post-MTX ART cycle, which is similar to national statistics. Although no factors were identified that were predictive of LB in young women, the number of oocytes retrieved in the previous ART cycle and current AFC were predictive of LB (AUC 0.76, 0.75) for the older women.


MTX does not influence ovarian reserve, response to gonadotropin stimulation, and CP or LB rate after ART. MTX remains a safe and effective treatment option for women with asymptomatic EPs.


Methotrexate Ectopic pregnancy Ovarian reserve In vitro fertilization Pregnancy rate 



C.E.B. received support from the National Research Training Program in Reproductive Medicine sponsored by the National Institute of Health (T32 HD040135-13) and the Scientific Advisory Board of Vivere Health. E.S.J. received support from the Women’s Reproductive Health Research Program sponsored by the National Institute of Health (K12 HD063086), the Institute of Clinical and Translational Sciences at Washington University (UL1 TR000448), the Barnes Jewish Hospital Foundation, and the March of Dimes. This work was supported, in part, by the Program in Reproductive and Adult Endocrinology, NICHD, NIH, Bethesda, MD.

Compliance with ethical standards

Authors from each institution obtained ethical approval from their Institutional Review Board. In addition, IRB approval was obtained from Washington University prior to the chart review and data extraction.

Conflict of interest

There are no conflicts of interest to declare.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Christina E. Boots
    • 1
    Email author
  • Micah J. Hill
    • 2
  • Eve C. Feinberg
    • 3
  • Ruth B. Lathi
    • 4
  • Susan A. Fowler
    • 5
  • Emily S. Jungheim
    • 1
  1. 1.Obstetrics and GynecologyWashington UniversitySt. LouisUSA
  2. 2.Program in Reproductive and Adult EndocrinologyNational Institute of HealthBethesdaUSA
  3. 3.Reproductive Endocrinology and InfertilityFertility Centers of IllinoisHighland ParkUSA
  4. 4.Obstetrics and GynecologyStanford UniversityPalo AltoUSA
  5. 5.Bernard Becker Medical LibraryWashington UniversitySt. LouisUSA

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