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Large, Non-Cavity Distorting Intramural Leiomyomas Decrease Leukemia Inhibitory Factor in the Secretory Phase Endometrium

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Abstract

Despite mounting evidence that large intramural leiomyomas decrease fecundity during in vitro fertilization cycles, few studies have demonstrated a mechanism for this impact. We hypothesize that large intramural leiomyomas (IM) decrease the expression of endometrial implantation factors during the window of implantation. We prospectively recruited sub-fertile patients with IM 3 cm or greater in size planning myomectomy and performed endometrial biopsies the day of planned myomectomy (n = 9). Preoperative screening demonstrated no intercavitary lesions. Control endometrial samples were obtained from young, normally menstruating women free of uterine leiomyomas (n = 8). Endometrial samples were obtained in the mid-secretory phase (average cycle day for control patients and intramural leiomyoma patients were 24.5 and 21.3, respectively). Expression of implantation markers HOXA10, leukemia inhibitory factor (LIF), ER-α, and PR was compared using quantitative immunohistochemistry. Standard descriptive statistics were used to compare H-scores between the cohorts. Patients with intramural leiomyomas were found to have decreased LIF compared to controls (p value < 0.001). Expressions of HOXA10 and PR were no different between cohorts; however, ER-α showed a trend toward increased expression in the fibroid cohort (p value 0.07). LIF is downregulated in the endometrium of patients with large IM. This study is among the first to show decreased LIF expression in patients with uterine leiomyomas. We hypothesize that this difference from previously published work is due to sampling the endometrium at the height of LIF expression. Further work is needed to show if LIF downregulation is corrected with leiomyoma resection.

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Acknowledgments

This research was completed at the University of Alabama at Birmingham.

Funding

This study was supported by a Research Grant from the Scientific Advisory Board of Vivere Health (2014–2015).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Tripler Army Medical Center, Jarrett White Road, Honolulu, Hawaii, 96859, USA

    Bruce Pier & Christopher Crellin

  2. Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, USA

    Ashwini Katre & Rebecca Arend

  3. Department of Pathology, University of Alabama at Birmingham, Birmingham, USA

    Michael G. Conner & Lea Novak

  4. Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of North Carolina at Chapel Hill, North Carolina, USA

    Steven L Young

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  1. Bruce Pier
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Correspondence to Bruce Pier.

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The views expressed in this abstract/manuscript are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the US Government.

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Pier, B., Crellin, C., Katre, A. et al. Large, Non-Cavity Distorting Intramural Leiomyomas Decrease Leukemia Inhibitory Factor in the Secretory Phase Endometrium. Reprod. Sci. 27, 569–574 (2020). https://doi.org/10.1007/s43032-019-00056-x

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