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Follicular fluid PlGF/sFlt-1 ratio and soluble receptor for advanced glycation end–products correlate with ovarian sensitivity index in women undergoing A.R.T.

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Abstract

Purpose

Considering potential roles of soluble receptor for advanced glycation end products (sRAGE) and placental growth factor (PlGF) in ovarian function and embryo implantation, in the present study we have evaluated the association of these factors and also PlGF/sFlt-1 ratio with the ovarian response and implantation rate by dividing patients according to the OSI.

Methods

In a cross-sectional study, 90 infertile women who were undergoing ICSI cycle using long protocol were recruited. The patients were divided according to ovarian sensitivity index (OSI). ICSI cycle outcomes were evaluated for each patient and PlGF, sFlt-1 and sRAGE levels of follicular fluid were assayed using commercial ELISA kits.

Results

Follicular fluid (FF) sRAGE levels and PlGF/sFlt-1 ratio were statistically greater in high-responder women than other responders (p < 0.05). Positive correlations were obtained between sRAGE level with the number of oocytes, follicles and OSI level. sRAGE levels with cutoff value of 4.83 (ng/ml) for evaluating the pregnancy outcome showed 81.8 % sensitivity and 60.7 % specificity. Furthermore, there were positive associations between PlGF/sFlt-1 ratio with the number of oocytes, embryos and OSI level.

Conclusion

In conclusion, the results of current study supported that good ovarian response is independent of pregnancy outcome. Our results showed that FF levels of sRAGE and PlGF/sFlt-1 ratio could be used as markers for determining the high-responder women. Also, FF sRAGE levels could be a good predictor for ART outcome.

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Abbreviations

OSI:

Ovarian sensitivity index

PlGF:

Placental growth factor

AMH:

Anti-mullerian hormone

sFlt-1:

Soluble fms-like tyrosine kinase-1

AGEs:

Advanced glycation end products

RAGE:

Receptor for advanced glycation end products

sRAGE:

Soluble receptor for advanced glycation end-products

References

  1. Li HW, Lee VC, Lau EY, Yeung WS, Ho P, Ng EH (2013) Role of baseline antral follicle count and anti-Mullerian hormone in prediction of cumulative live birth in the first in vitro fertilisation cycle: a retrospective cohort analysis. PLoS One 8(4):e61095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Delvigne A (2009) Epidemiology of OHSS. Reprod Biomed Online 19(1):8–13

    Article  PubMed  Google Scholar 

  3. Li HW, Lee VC, Ho P, Ng EH (2014) Ovarian sensitivity index is a better measure of ovarian responsiveness to gonadotrophin stimulation than the number of oocytes during in-vitro fertilization treatment. J Assist Reprod Genet 31(2):199–203

    Article  PubMed  Google Scholar 

  4. Huber M, Hadziosmanovic N, Berglund L, Holte J (2013) Using the ovarian sensitivity index to define poor, normal, and high response after controlled ovarian hyperstimulation in the long gonadotropin-releasing hormone-agonist protocol: suggestions for a new principle to solve an old problem. Fertil Steril 100(5):1270–1276 (e1273)

    Article  CAS  PubMed  Google Scholar 

  5. Carmeliet P, Moons L, Luttun A, Vincenti V, Compernolle V, De Mol M, Wu Y, Bono F, Devy L, Beck H (2001) Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med 7(5):575–583

    Article  CAS  PubMed  Google Scholar 

  6. Tal R, Seifer DB, Grazi RV, Malter HE (2014) Follicular fluid placental growth factor is increased in polycystic ovarian syndrome: correlation with ovarian stimulation. Reprod Biol Endocrinol 12(1):82

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hou L, Taylor R, Shu Y, Johnston-MacAnanny E, Yalcinkaya T (2014) Vascular endothelial growth factor (VEGF) and placental growth factor (PLGF) directly correlate with ovarian follicle size in women undergoing in vitro fertilization (IVF). Fertil Steril 3(102):e256

    Article  Google Scholar 

  8. Santi A, Felser RS, Mueller MD, Wunder DM, McKinnon B, Bersinger NA (2011) Increased endometrial placenta growth factor (PLGF) gene expression in women with successful implantation. Fertil Steril 96(3):663–668

    Article  CAS  PubMed  Google Scholar 

  9. Merhi Z (2013) Advanced glycation end products and their relevance in female reproduction. Hum Reprod:det383

  10. Basta G, Sironi AM, Lazzerini G, Del Turco S, Buzzigoli E, Casolaro A, Natali A, Ferrannini E, Gastaldelli A (2006) Circulating soluble receptor for advanced glycation end products is inversely associated with glycemic control and S100A12 protein. J Clin Endocrinol Metab 91(11):4628–4634

    Article  CAS  PubMed  Google Scholar 

  11. Malíčková K, Jarošová R, Řežábek K, Fait T, Jr Mašata, Janatková I, Zima T, Kalousova M (2009) Concentrations of sRAGE in serum and follicular fluid in assisted reproductive cycles–a preliminary study. Clin Lab 56(9–10):377–384

    Google Scholar 

  12. Merhi Z, Irani M, Doswell AD, Ambroggio J (2013) Follicular fluid soluble receptor for advanced glycation end-products (sRAGE): a potential indicator of ovarian reserve. J Clin Endocrinol Metab 99(2):E226–E233

    Article  PubMed  Google Scholar 

  13. Broer S, Dolleman M, Opmeer B, Fauser B, Mol B, Broekmans F (2011) AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis. Hum Reprod Updat 17(1):46–54

    Article  CAS  Google Scholar 

  14. Setti PL, Alviggi C, Colombo G, Pisanelli C, Ripellino C, Longobardi S, Canonico P, De Placido G (2015) Human recombinant follicle stimulating hormone (rFSH) compared to urinary human menopausal gonadotropin (HMG) for ovarian stimulation in assisted reproduction: a literature review and cost evaluation. J Endocrinol Invest 38(5):497–503

    Article  Google Scholar 

  15. Broer SL, Mol BWJ, Hendriks D, Broekmans FJ (2009) The role of antimullerian hormone in prediction of outcome after IVF: comparison with the antral follicle count. Fertil Steril 91(3):705–714

    Article  CAS  PubMed  Google Scholar 

  16. Heidar Z, Bakhtiyari M, Mirzamoradi M, Zadehmodarres S, Sarfjoo F, Mansournia M (2015) Prediction of different ovarian responses using anti-Müllerian hormone following a long agonist treatment protocol for IVF. J Endocrinol Invest 38(9):1007–1015

    Article  CAS  PubMed  Google Scholar 

  17. Broekmans F, Kwee J, Hendriks D, Mol B, Lambalk C (2006) A systematic review of tests predicting ovarian reserve and IVF outcome. Hum Reprod Updat 12(6):685–718

    Article  CAS  Google Scholar 

  18. Biasoni V, Patriarca A, Dalmasso P, Bertagna A, Manieri C, Benedetto C, Revelli A (2011) Ovarian sensitivity index is strongly related to circulating AMH and may be used to predict ovarian response to exogenous gonadotropins in IVF. Reprod Biol Endocrinol 9(112):b19

    Google Scholar 

  19. Saldeen P, Källen K, Sundström P (2007) The probability of successful IVF outcome after poor ovarian response. Acta Obstet Gynecol Scand 86(4):457–461

    Article  PubMed  Google Scholar 

  20. Wei Z, Cheng X, Li H, Cao Y, Cong L, Zhou P, Li J (2010) Effects of prolonging administration gonadotropin on unexpectedly poor ovarian responders undergoing in vitro fertilization. Reprod Biol Endocrinol 8(1):26

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kan A, Ng EH, Yeung WS, Ho PC (2006) Perifollicular vascularity in poor ovarian responders during IVF. Hum Reprod 21(6):1539–1544

    Article  CAS  PubMed  Google Scholar 

  22. Lashen H, Ledger W, Lopez-Bernal A, Barlow D (1999) Poor responders to ovulation induction: is proceeding to in-vitro fertilization worthwhile? Hum Reprod 14(4):964–969

    Article  CAS  PubMed  Google Scholar 

  23. Tayade C, Fang Y, Hilchie D, Croy BA (2007) Lymphocyte contributions to altered endometrial angiogenesis during early and midgestation fetal loss. J Leukoc Biol 82(4):877–886

    Article  CAS  PubMed  Google Scholar 

  24. Catteau-Jonard S, Jamin SP, Leclerc A, Gonzalès J, Dewailly D, di Clemente N (2008) Anti-Mullerian hormone, its receptor, FSH receptor, and androgen receptor genes are overexpressed by granulosa cells from stimulated follicles in women with polycystic ovary syndrome. J Clin Endocrinol Metab 93(11):4456–4461

    Article  CAS  PubMed  Google Scholar 

  25. Weerakiet S, Lertvikool S, Tingthanatikul Y, Wansumrith S, Leelaphiwat S, Jultanmas R (2007) Ovarian reserve in women with polycystic ovary syndrome who underwent laparoscopic ovarian drilling. Gynecol Endocrinol 23(8):455–460

    Article  PubMed  Google Scholar 

  26. Dewerchin M, Carmeliet P (2012) PlGF: a multitasking cytokine with disease-restricted activity. Cold Spring Harb Perspect Med 2(8):a011056

    Article  PubMed  PubMed Central  Google Scholar 

  27. Savchev SI, Moragianni VA, Senger D, Penzias AS, Thornton K, Usheva A (2010) Follicular fluid-specific distribution of vascular endothelial growth factor isoforms and sFlt-1 in patients undergoing IVF and their correlation with treatment outcomes. Reprod Sci 17(11):1036–1042

    Article  CAS  PubMed  Google Scholar 

  28. Neulen J, Wenzel D, Hornig C, Wünsch E, Weissenborn U, Grunwald K, Büttner R, Weich H (2001) Poor responder–high responder: the importance of soluble vascular endothelial growth factor receptor 1 in ovarian stimulation protocols. Hum Reprod 16(4):621–626

    Article  CAS  PubMed  Google Scholar 

  29. Kaczmarek M, Kiewisz J, Schams D, Ziecik A (2009) Expression of VEGF-receptor system in conceptus during peri-implantation period and endometrial and luteal expression of soluble VEGFR-1 in the pig. Theriogenology 71(8):1298–1306

    Article  CAS  PubMed  Google Scholar 

  30. Irani M, Minkoff H, Seifer DB, Merhi Z (2014) Vitamin D increases serum levels of the soluble receptor for advanced glycation end products in women with PCOS. J Clin Endocrinol Metab 99(5):E886–E890

    Article  CAS  PubMed  Google Scholar 

  31. Bonetti TC, Borges E, Braga DP, Iaconelli A, Kleine JP, Silva ID (2013) Intrafollicular soluble receptor for advanced glycation end products (sRAGE) and embryo quality in assisted reproduction. Reprod Biomed Online 26(1):62–67

    Article  CAS  PubMed  Google Scholar 

  32. Bhutada S, Basak T, Savardekar L, Katkam R, Jadhav G, Metkari S, Chaudhari U, Kumari D, Kholkute S, Sengupta S (2014) High mobility group box 1 (HMGB1) protein in human uterine fluid and its relevance in implantation. Hum Reprod 29(4):763–780

    Article  CAS  PubMed  Google Scholar 

  33. Jinno M, Takeuchi M, Watanabe A, Teruya K, Hirohama J, Eguchi N, Miyazaki A (2011) Advanced glycation end-products accumulation compromises embryonic development and achievement of pregnancy by assisted reproductive technology. Hum Reprod 26(3):604–610

    Article  PubMed  Google Scholar 

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Acknowledgments

The current work was supported by a Grant (Research Project Number 5/4/1870) from the Women’s Reproductive Health Research Center of Tabriz University of Medical Sciences and this article was extracted from the M.Sc. thesis of Hamid Reza Nejabati.

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Authors and Affiliations

  1. Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    H. R. Nejabati, L. Farzadi, A. Fattahi, K. Hamdi & M. Nouri

  2. Department of Clinical Biochemistry, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    A. Mota

  3. Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    M. Ghojazadeh

Authors
  1. H. R. Nejabati
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  2. A. Mota
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  5. A. Fattahi
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  6. K. Hamdi
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Correspondence to K. Hamdi or M. Nouri.

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The authors declare that there is no conflict of interest.

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The agreement of the Ethical Committee of Tabriz University of Medical Sciences was obtained.

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All patients gave written informed consent.

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Nejabati, H.R., Mota, A., Farzadi, L. et al. Follicular fluid PlGF/sFlt-1 ratio and soluble receptor for advanced glycation end–products correlate with ovarian sensitivity index in women undergoing A.R.T.. J Endocrinol Invest 40, 207–215 (2017). https://doi.org/10.1007/s40618-016-0550-5

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  • DOI: https://doi.org/10.1007/s40618-016-0550-5

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