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A Case–Control Study of Follicular Fluid Cytokine Profiles in Women with Diminished Ovarian Reserve

  • Reproductive Biology: Original Article
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Abstract

Ovarian reserve is an important determinant of a woman’s reproductive potential, and women with diminished ovarian reserve (DOR) often seek in vitro fertilization (IVF). The underlying etiology of DOR is unknown, but follicular fluid cytokine concentrations likely play a role in follicular development and maturation. The present study seeks to investigate the expression of cytokines in follicular fluid (FF) of women with DOR undergoing IVF and explore correlated functional pathways. One hundred ninety-four women undergoing ovarian stimulation were recruited at the time of oocyte retrieval. Women were classified as having DOR if they met one or more of the following criteria: AMH < 1 ng/ml, FSH > 10 mIU/ml, and/or AFC < 10. Controls included women undergoing IVF for male factor, tubal factor due to tubal ligation, or planned oocyte cryopreservation (non-oncologic). The concentrations of 480 cytokines and related growth factors in follicular fluid were determined using a multiplex immunoassay. Fifty-nine cytokines had significantly different concentrations (53 higher and 6 lower) in the DOR relative to the control group after adjusting for age and body mass index (BMI) (false discovery rate; FDR < 0.1). Using the most informative 44 biomarkers as indicated by a random forest (RF) model, an area under the curve (AUC) of 0.78 was obtained. Thus, follicular microenvironment differs between women with DOR and normal ovarian reserve. The differentially expressed cytokines belong to diverse processes that are primarily involved in follicular maturation and ovulation. These changes may play an important role in treatment outcomes in women with DOR.

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Data is available from the authors upon reasonable request.

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Acknowledgements

We wish to thank Dawayland Cobb and Laura Sheckter for their assistance with this project.

Funding

This study was supported by RayBiotech Life, Inc.’s Collaborative Research Grant, Guangzhou Innovation Leadership Team (CXLJTD-201602). Additional support was from the National Institutes of Health (UL1TR002378), and the Building Interdisciplinary Research Careers in Women’s Health Program (K12HD085850). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Author notes

  1. Ruo-Pan Huang and Anna K Knight contributed equally to this work

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Division of Reproductive Endocrinology and Infertility, Emory University School of Medicine, 550 Peachtree Street, NE Suite 1800, Atlanta, GA, 30308, USA

    Sina Abhari, Heather S. Hipp, Quinton S. Katler & Weirong Shang

  2. RayBiotech Life, Inc, 3607 Parkway Lane, Peachtree Corners, GA, 30092, USA

    **gqiao Lu, Brianne Petritis, Haw-Han Yen, Yingqing Mao, Hao Tang & Ruo-Pan Huang

  3. IVF MD, 9960 Central Park Boulevard, Boca Raton, FL, 33428, USA

    Sabrina A. Gerkowicz

  4. Division of Reproductive Endocrinology and Infertility, Baylor College of Medicine, Houston, TX, USA

    Laurie J. McKenzie

  5. Department of Gynecology and Obstetrics, Division of Research, Emory University School of Medicine, Woodruff Memorial Research Building, Atlanta, GA, 30322, USA

    Alicia K. Smith & Anna K. Knight

Authors
  1. Sina Abhari
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  2. **gqiao Lu
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  9. Hao Tang
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Correspondence to Anna K. Knight.

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Competing Interests

RayBiotech manufactures the Quantibody® Human Cytokine Antibody Array Q440 and Quantibody Human Cytokine Antibody Array Q12. RPH is the founder and CEO of RayBiotech, JL, BP, HHY, YM, and HT are employees of RayBiotech.

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Abhari, S., Lu, J., Hipp, H.S. et al. A Case–Control Study of Follicular Fluid Cytokine Profiles in Women with Diminished Ovarian Reserve. Reprod. Sci. 29, 2515–2524 (2022). https://doi.org/10.1007/s43032-021-00757-2

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