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Analysis of Follicular Fluid Retinoids in Women Undergoing In Vitro Fertilization: Retinoic Acid Influences Embryo Quality and Is Reduced in Women With Endometriosis

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Abstract

Retinol (ROL) and its biologically active metabolite, all-trans retinoic acid (ATRA), are essential for a number of reproductive processes. However, there is a paucity of information regarding their roles in ovarian folliculogenesis, oocyte maturation, and early embryogenesis. The objectives of this study were to quantify and compare peripheral plasma (PP) and follicular fluid (FF) retinoid levels, including ATRA in women undergoing in vitro fertilization (IVF) and to investigate the relationship between retinoid levels and embryo quality. Retinoid levels were evaluated in PP and FF from 79 women undergoing IVF at the time of oocyte retrieval and corresponding embryo quality assessed on a daily basis after retrieval for 3 days until uterine transfer. Analysis compared the retinoid levels with day 3 embryo grades and between endometriosis versus control patients. Results demonstrated distinctive levels of retinoid metabolites and isomers in FF versus PP. There was a significantly larger percentage of high-quality grade I embryos derived from the largest versus smallest follicles. An increase in follicle size also correlated with a >50% increase in FF ROL and ATRA concentrations. Independent of follicle size, FF yielding grade I versus nongrade I embryos showed higher mean levels of ATRA but not ROL. In a nested case–control analysis, control participants had 50% higher mean levels of ATRA in their FF and PP than women with endometriosis. These findings strongly support the proposition that ATRA plays a fundamental role in oocyte development and quality, and that reduced ATRA synthesis may contribute to decreased fecundity of participants with endometriosis.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA, 30322, USA

    Samuel A. Pauli MD, Donna R. Session MD, Weirong Shang PhD, Friedrich Wieser MD & Neil Sidell PhD

  2. Department of Biostatistics, Emory University School of Medicine, Atlanta, GA, USA

    Kirk Easley MS

  3. Department of Gynecology and Obstetrics, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Robert N. Taylor MD, PhD

  4. Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA

    Keely Pierzchalski PhD & Maureen A. Kane PhD

  5. Department of Nutritional Science and Toxicology, University of California, Berkeley, CA, USA

    Joseph L. Napoli PhD

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  1. Samuel A. Pauli MD
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  2. Donna R. Session MD
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Correspondence to Neil Sidell PhD.

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Pauli, S.A., Session, D.R., Shang, W. et al. Analysis of Follicular Fluid Retinoids in Women Undergoing In Vitro Fertilization: Retinoic Acid Influences Embryo Quality and Is Reduced in Women With Endometriosis. Reprod. Sci. 20, 1116–1124 (2013). https://doi.org/10.1177/1933719113477487

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  • DOI: https://doi.org/10.1177/1933719113477487

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