Abstract
Purpose
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)
Methods
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.
Results
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.
Conclusions
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.
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Acknowledgments
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.
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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.
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Additional information
Capsule As treatment for an ectopic pregnancy, methotrexate does not affect ovarian reserve, response to gonadotropin stimulation, clinical pregnancy, or live birth rates in subsequent assisted reproductive tenchology cycles.
Appendix
Appendix
Embase
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‘methotrexate’/exp OR ‘methotrexate’ OR ‘mtx’ OR ‘4 amino 10 methylfolic acid’ OR ‘4 amino 10 methylpteroylglutamic acid’ OR ‘4 amino n10 methylpteroylglutamic acid’ OR ‘a methopterine’ OR ‘abitrexate’ OR ‘amethopterin’ OR ‘amethopterine’ OR ‘ametopterine’ OR ‘antifolan’ OR ‘biotrexate’ OR ‘canceren’ OR ‘cl 14377’ OR ‘cl14377’ OR ‘emtexate’ OR ‘emthexat’ OR ‘emthexate’ OR ‘emtrexate’ OR ‘enthexate’ OR ‘farmitrexat’ OR ‘farmitrexate’ OR ‘farmotrex’ OR ‘folex’ OR ‘ifamet’ OR ‘imeth’ OR ‘lantarel’ OR ‘ledertrexate’ OR ‘maxtrex’ OR ‘metex’ OR ‘methoblastin’ OR ‘methohexate’ OR ‘methotrate’ OR ‘methotrexat’ OR ‘methotrexato’ OR ‘methoxtrexate’ OR ‘methrotrexate’ OR ‘methylaminopterin’ OR ‘methylaminopterine’ OR ‘meticil’ OR ‘metoject’ OR ‘metothrexate’ OR ‘metotrexat’ OR ‘metotrexate’ OR ‘metotrexin’ OR ‘metrex’ OR ‘mexate’ OR ‘mpi 5004’ OR ‘mpi5004’ OR ‘neotrexate’ OR ‘novatrex’ OR ‘nsc 740’ OR ‘nsc740’ OR ‘reumatrex’ OR ‘rheumatrex’ OR ‘texate’ OR ‘texorate’ OR ‘trexall’ OR ‘xaken’ OR ‘zexate’ AND (‘ovarian reserve’/exp OR ‘oocyte development’/exp OR ‘ovary function’/de OR ‘ovary follicle’/exp OR ‘ovary cycle’/exp OR ‘follitropin’/exp OR ‘muellerian inhibiting factor’/exp OR ‘oocyte reserve’ OR ‘ovarian reserve’ OR ‘ovarian responsiveness’ OR ‘ovarian stimulation’ OR ‘ovarian cycle’ OR ‘ovulation cycle’ OR ‘reproductive cycle’ OR ‘ovarian activity’ OR ‘ovarian function’ OR ‘ovarium function’ OR ‘egg development’ OR ‘oocyte growth’ OR ‘oocytogenesis’ OR ‘oogenesis’ OR ‘ovogenesis’ OR ‘ovum development’ OR ‘oocyte maturation’ OR ‘egg maturation’ OR ‘follicle maturation’ OR ‘fertiline’ OR ‘fertinom p’ OR ‘follicle stimulating hormone’ OR ‘follicotropin’ OR ‘folliculostimulating hormone’ OR ‘follitrophin’ OR ‘follitropine’ OR ‘folltropin’ OR ‘fsh’ OR ‘ovagen’ OR ‘super ov’ OR ‘ovarian follicles’ OR ‘ovarian follicle’ OR ‘graafian follicle’ OR ‘graafian follicles’ OR ‘atretic follicle’ OR ‘atretic follicles’ OR ‘hfsh’ OR ‘anthrogon’ OR ‘antral follicle count’ OR ‘afc’ OR ‘anti-mullerian hormone’ OR ‘amh’ OR ‘anti mullerian hormone’ OR ‘antimuellerian hormone’ OR ‘antimullerian hormone’ OR ‘muellerian inhibiting substance’ OR ‘muellerian inhibitor’ OR ‘mullerian inhibiting factor’ OR ‘mullerian inhibiting substance’ OR ‘mullerian inhibitor’ OR ‘mullerian inhibiting hormone’ OR ‘mullerian-inhibitory substance’ OR ‘mullerian inhibitory substance’ OR ‘mullerian-inhibiting factor’ OR ‘mullerian-inhibiting hormone’ OR ‘anti-mullerian factor’ OR ‘anti mullerian factor’ OR ‘mullerian regression factor’) NOT ([animals]/lim NOT [humans]/lim) AND [english]/lim
PubMed
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(“Methotrexate”[Mesh] OR “methotrexate” OR “MTX” OR “4 amino 10 methylfolic acid” OR “4 amino n10 methylpteroylglutamic acid” OR “a methopterine” OR “amethopterin” OR “amethopterine” OR “ametopterine” OR “emthexat” OR “emtrexate” OR “folex” OR “ledertrexate” OR “metex” OR “methotrexat” OR “methoxtrexate” OR “methrotrexate” OR “methylaminopterin” OR “metoject” OR “metothrexate” OR “metotrexat” OR “metotrexate” OR “metrex” OR “mexate” OR “neotrexate” OR “nsc 740” OR “rheumatrex” OR “texate”) AND (“Ovarian Follicle”[Mesh] OR “Follicle Stimulating Hormone”[Mesh] OR “Anti-Mullerian Hormone”[Mesh] OR “ovarian reserve” OR “oocyte development” OR “ovary function” OR “ovary follicle” OR “ovary cycle” OR “follitropin” OR “Mullerian inhibiting factor” OR “oocyte reserve” OR “ovarian reserve” OR “ovarian responsiveness” OR “ovarian stimulation” OR “ovarian cycle” OR “ovulation cycle” OR “reproductive cycle” OR “ovarian activity” OR “ovarian function” OR “egg development” OR “oocyte growth” OR “oocytogenesis” OR “oogenesis” OR “ovogenesis” OR “ovum development” OR “oocyte maturation” OR “egg maturation” OR “follicle maturation” OR “fertiline” OR “follicle stimulating hormone” OR “follicotropin” OR “folliculostimulating hormone” OR “follitrophin” OR “follitropine” OR “folltropin” OR “FSH” OR “ovagen” OR “super ov” OR “Ovarian Follicles” OR “Ovarian Follicle” OR “Graafian Follicle” OR “Graafian Follicles” OR “Atretic Follicle” OR “Atretic Follicles” OR “hFSH” OR “Anthrogon” OR “Antral follicle count” OR “AFC” OR “Anti-Mullerian Hormone” OR “AMH” OR “anti mullerian hormone” OR “antimullerian hormone” OR “muellerian inhibiting substance” OR “mullerian inhibiting substance” OR “mullerian inhibitor” OR “Mullerian Inhibiting Hormone” OR “Mullerian-Inhibitory Substance” OR “Mullerian Inhibitory Substance” OR “Mullerian-Inhibiting Factor” OR “Mullerian-Inhibiting Hormone” OR “Anti-Mullerian Factor” OR “Anti Mullerian Factor” OR “Mullerian Regression Factor”) NOT ((“Animals”[Mesh]) NOT (“Animals”[Mesh] AND “Humans”[Mesh]))
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Boots, C.E., Hill, M.J., Feinberg, E.C. et al. Methotrexate does not affect ovarian reserve or subsequent assisted reproductive technology outcomes. J Assist Reprod Genet 33, 647–656 (2016). https://doi.org/10.1007/s10815-016-0683-7
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DOI: https://doi.org/10.1007/s10815-016-0683-7