Fertility and Sterility
Volume 92, Issue 5 , Pages 1569-1578, November 2009

A proteomic analysis of IVF follicular fluid in women ≤32 years old

  • Stephanie J. Estes, M.D.

      Affiliations

    • Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
  • ,
  • Bin Ye, Ph.D.

      Affiliations

    • Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
  • ,
  • Weiliang Qiu, Ph.D.

      Affiliations

    • Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
  • ,
  • Daniel Cramer, M.D.

      Affiliations

    • Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
    • Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
  • ,
  • Mark D. Hornstein, M.D.

      Affiliations

    • Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
  • ,
  • Stacey A. Missmer, Sc.D.

      Affiliations

    • Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
    • Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
    • Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    • Corresponding Author InformationReprint requests: Stacey A. Missmer, Sc.D., OB/GYN Epidemiology Center, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115–5804 (FAX: 617-732-4899).

Received 2 February 2008; received in revised form 16 August 2008; accepted 24 August 2008. published online 03 November 2008.

Objective

To address the lack of predictors of IVF success by using proteomic biometrics.

Design

Experimental study of follicular fluid specimens from a prospective cohort of IVF patients.

Setting

Academic research laboratory and IVF program.

Patient(s)

Women ≤32 years old with <11 oocytes retrieved and no pregnancy were matched to women who had ≥11 oocytes and live birth (10 pairs). Year of cycle start and IVF down-regulation protocol were also matched.

Intervention(s)

Follicular fluid was separated by two-dimensional polyacrylamide gel electrophoresis followed by Sypro Ruby staining and comparison with PDQuest software. Logistic regression was incorporated to calculate the likelihood of live birth in relation to the protein spot of interest.

Main Outcome Measure(s)

Protein markers.

Result(s)

Liquid chromatography–tandem mass spectrometry and searching of sequence databases revealed 11 potential protein candidates. Haptoglobin alpha, predominantly fetal expressed T1 domain, mitochondrial integrity genome (ATPase), apolipoprotein H (beta-2 glycoprotein I), dihydrolipoyl dehydrogenase, lyzozyme C, fibrinogen alpha-chain, and immunoglobulin heavy chain V-III (region BRO) were found to have increased expression in the live birth group, whereas antithrombin, vitamin D–binding protein, and complement 3 were decreased. An ELISA confirmed a significantly lower level of antithrombin.

Conclusion(s)

Proteomic evaluation of follicular fluid is able to identify potential biomarkers of good versus poor responders in matched pairs of IVF patients.

Key Words: Follicular fluid, infertility, IVF, pregnancy, proteomics

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 S.E. has nothing to disclose. B.Y. has nothing to disclose. W.Q. has nothing to disclose. D.C. has nothing to disclose. M.H. has nothing to disclose. S.M. has nothing to disclose.

 Supported by National Institutes of Health grant no. HD32153 and the research fund of the Department of Obstetrics and Gynecology, Brigham and Women's Hospital.

PII: S0015-0282(08)03830-2

doi:10.1016/j.fertnstert.2008.08.120

Fertility and Sterility
Volume 92, Issue 5 , Pages 1569-1578, November 2009