Skip to main content
Log in

Variability in follicular fluid high density lipoprotein particle components measured in ipsilateral follicles

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to examine the biological variability of follicular fluid (FF) high density lipoprotein (HDL) particle components measured in ipsilateral ovarian follicles.

Methods

We collected FF from two ipsilateral follicles among six women undergoing in vitro fertilization (IVF). We measured concentrations of 19 FF HDL particle components, including HDL cholesterol, free cholesterol, four cholesteryl esters, phospholipids, triglycerides, paraoxonase and arylesterase activities, apolipoproteins A-1 and A-2 (ApoA-1 and ApoA-2), and seven lipophilic micronutrients, by automated analysis and with high-performance liquid chromatography. We assessed biological variability using two-stage nested analysis of variance and compared values with those previously published for contralateral follicles.

Results

For most FF HDL analytes, there was little variability between follicles relative to the variability between women (i.e., %σ2 F:%σ2 B <0.5). Intraclass correlation coefficients were >0.80 for HDL cholesterol (0.82), phospholipids (0.89), paraoxonase (0.96), and arylesterase (0.91) activities, ApoA-1 (0.89), and ApoA-2 (0.90), and single specimen collections were required to estimate the subject-specific mean, demonstrating sufficient reliability for use as biomarkers of the follicular microenvironment in epidemiologic and clinical studies.

Conclusions

These preliminary results raise the possibility for tighter regulation of HDL in follicles within the same ovary vs. between ovaries. Thus, collection of a single FF specimen may be sufficient to estimate HDL particle components concentrations within a single ovary. However, our results should be interpreted with caution as the analysis was based on a small sample.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Fukuda M, Fukuda K, Andersen CY, Byskov AG. Contralateral selection of dominant follicle favours pre-embryo development. Hum Reprod. 1996;11:1958–62.

    Article  CAS  PubMed  Google Scholar 

  2. Ecochard R, Gougeon A. Side of ovulation and cycle characteristics in normally fertile women. Hum Reprod. 2000;15:752–5.

    Article  CAS  PubMed  Google Scholar 

  3. Mikolajczyk RT, Stanford JB, Ecochard R. Multilevel model to assess sources of variation in follicular growth close to the time of ovulation in women with normal fertility: a multicenter observational study. Reprod Biol Endocrinol. 2008;6.

  4. Singh AK, Chattopadhyay R, Chakravarty B, Chaudhury K. Markers of oxidative stress in follicular fluid of women with endometriosis and tubal infertility undergoing IVF. Reprod Toxicol. 2013;42:116–24.

    Article  CAS  PubMed  Google Scholar 

  5. Revelli A, Piane LD, Casano S, Molinari E, Massobrio M, Rinaudo P. Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics. Reprod Biol Endocrinol. 2009;7:40.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Benedict MD, Missmer SA, Vitonis AF, Cramer DW, Meeker JD. Cotinine concentrations in follicular fluid as a measure of secondhand tobacco smoke exposure in women undergoing in vitro fertilization: inter-matrix comparisons with urine and temporal variability. Chemosphere. 2011;84:110–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zamah AM, Hassis ME, Albertolle ME, Williams KE. Proteomic analysis of human follicular fluid from fertile women. Clin Proteomics. 2015;12:5.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Oktem O, Urman B. Understanding follicle growth in vivo. Hum Reprod. 2010;25:2944–54.

    Article  PubMed  Google Scholar 

  9. Pasqualotto EB, Agarwal A, Sharma RK, Izzo VM, Pinotti JA, Joshi NJ, et al. Effect of oxidative stress in follicular fluid on the outcome of assisted reproductive procedures. Fertil Steril. 2004;81:973–6.

    Article  CAS  PubMed  Google Scholar 

  10. Mehdizadeh A, Rahimipour A, Farzadi L, Darabi M, Shahnazi V, Shaaker M, et al. Correlation between the level of cholesteryl ester transfer protein in follicular fluid with fertilization rates in IVF/ICSI cycles. Iran J Reprod Med. 2011;9:193–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Le Goff D. Follicular fluid lipoproteins in the mare: evaluation of HDL transfer from plasma to follicular fluid. Biochim Biophys Acta. 1994;1210:226–32.

    Article  CAS  PubMed  Google Scholar 

  12. Ansell BJ, Navab M, Hama S, Kamranpour N, Fonarow G, Hough G, et al. Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation. 2003;108:2751–6.

    Article  CAS  PubMed  Google Scholar 

  13. Kontush A, Chantepie S, Chapman MJ. Small, dense HDL particles exert potent protection of atherogenic LDL against oxidative stress. Atertio Thromb Vasc Biol. 2003;23:1881–8.

    Article  CAS  Google Scholar 

  14. Negre-Salvayre A, Dousset N, Ferretti G, Bacchetti T, Curatola G, Salvayre R. Antioxidant and cytoprotective properties of high-density lipoproteins in vascular cells. Free Radic Biol Med. 2006;41:1031–40.

    Article  CAS  PubMed  Google Scholar 

  15. Azhar S, Tsai L, Medicherla S, Chandrasekher Y, Giudice L, Reaven E. Human granulosa cells use high density lipoprotein cholesterol for steroidogenesis. J Clin Endocrinol Metab. 1998;83:983–91.

    CAS  PubMed  Google Scholar 

  16. Li XL, Peegel H, Menon KMJ. Regulation of high density lipoprotein receptor messenger ribonucleic acid expression and cholesterol transport in theca-interstitial cells by insulin and human chorionic gonadotropin. Endocrinology. 2001;142:174–81.

    CAS  PubMed  Google Scholar 

  17. Browne RW, Shelly WB, Bloom MS, Ocque AJ, Sandler JR, Huddleston HG, et al. Distributions of high-density lipoprotein particle components in human follicular fluid and sera and their associations with embryo morphology parameters during IVF. Hum Reprod. 2008;23:1884–94.

    Article  CAS  PubMed  Google Scholar 

  18. Browne RW, Bloom MS, Shelly WB, Ocque AJ, Huddleston HG, Fujimoto VY. Follicular fluid high density lipoprotein-associated micronutrient levels are associated with embryo fragmentation during IVF. J Assist Reprod Genet. 2009;26:557–60.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Valckx SDM, De Pauw I, De Neubourg D, Inion I, Berth M, Fransen E, et al. BMI-related metabolic composition of the follicular fluid of women undergoing assisted reproductive treatment and the consequences for oocyte and embryo quality. Hum Reprod. 2012;27:3531–9.

    Article  CAS  PubMed  Google Scholar 

  20. Bloom MS, Kim K, Fujimoto VY, Browne RW. Variability in the components of high-density lipoprotein particles measured in human ovarian follicular fluid: a cross-sectional analysis. Fertil Steril. 2014;101:1431–U59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Levay PF, Huyser C, Fourie FLR, Rossouw DJ. The detection of blood contamination in human follicular fluid. J Assist Reprod Genet. 1997;14:212–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Browne RW, Koury ST, Marion S, Wilding G, Muti P, Trevisan M. Accuracy and biological variation of human serum paraoxonase 1 activity and polymorphism (Q192R) by kinetic enzyme assay. Clin Chem. 2007;53:310–7.

    Article  CAS  PubMed  Google Scholar 

  23. Kitchens LJ. Exploring statistics: a modern introduction to data analysis and inference. Pacific Grove: Duxbury Press; 1998. p. 940.

    Google Scholar 

  24. Lachin JM. The role of measurement reliability in clinical trials. Clin Trials. 2004;1:553–66.

    Article  PubMed  Google Scholar 

  25. Fraser CG, Harris EK, Petersen PH. Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci. 1989;27:409–30.

    Article  CAS  PubMed  Google Scholar 

  26. Fujimoto VY, Kane JP, Ishida BY, Bloom MS, Browne RW. High-density lipoprotein metabolism and the human embryo. Hum Reprod Update. 2010;16:20–38.

    Article  CAS  PubMed  Google Scholar 

  27. van Montfoort APA, Plosch T, Hoek A, Tietge UJF. Impact of maternal cholesterol metabolism on ovarian follicle development and fertility. J Reprod Immunol. 2014;104:32–6.

    Article  PubMed  Google Scholar 

  28. Ginther OJ, Kastelic JP, Knopf L. Intraovarian relationships among dominant and subordinate follicles and the corpus luteum in heifers. Theriogenology. 1989;32:787–95.

    Article  CAS  PubMed  Google Scholar 

  29. Baker SJ, Srsen V, Lapping R, Spears N. Combined effect of follicle-follicle interactions and declining follicle-stimulating hormone on murine follicle health in vitro. Biol Reprod. 2001;65:1304–10.

    Article  CAS  PubMed  Google Scholar 

  30. Taioli E, Kinney P, Zhitkovich A, Fulton H, Voitkun V, Cosma G, et al. Application of reliability models to studies of biomarker validation. Environ Health Perspect. 1994;102:306–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Schulte PA, Rothman N, Schottenfeld D. Design considerations in molecular epidemiology. In: Schulte PA, Perera FP, editors. Molecular epidemiology: principles and practices. San Diego: Academic Press; 1993. p. 159–98.

    Chapter  Google Scholar 

  32. Kim K, Bloom MS, Fujimoto VY, Browne RW. Number of specimens required to estimate average follicular fluid high-density lipoprotein particle components in women undergoing in vitro fertilization (letter). Fertil Steril. 2014;101, e44.

    Article  PubMed  Google Scholar 

  33. Nandi S, Kumar VG, Manjunatha BM, Gupta PSP. Biochemical composition of ovine follicular fluid in relation to follicle size. Dev Growth Differ. 2007;49:61–6.

    Article  CAS  PubMed  Google Scholar 

  34. Browne RW, Bloom MS, Schisterman EF, Hovey K, Trevisan M, Xu C, et al. Analytical and biological variation of biomarkers of oxidative stress during the menstrual cycle. Biomarkers. 2008;13:160–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Ying Wang, PhD for providing critical feedback for this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael S. Bloom.

Ethics declarations

Funding

This work was funded through grant R21 AG031957-01A2, provided by the National Institute on Aging, National Institutes of Health.

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures were performed in accordance with the ethical standards of the UCSF Committee on Human Research and with the 1964 Helsinki declaration and its later amendments. The study protocol was approved by the UCSF Committee on Human Research.

Informed consent

Informed consent was obtained prior to participation in the study.

Additional information

Capsule The variability of FF HDL analytes from ipsilateral follicles was smaller than variability that was previously reported in follicles from contralateral ovaries.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, K., Bloom, M.S., Fujimoto, V.Y. et al. Variability in follicular fluid high density lipoprotein particle components measured in ipsilateral follicles. J Assist Reprod Genet 33, 423–430 (2016). https://doi.org/10.1007/s10815-016-0648-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-016-0648-x

Keywords

Navigation