Skip to main content
Log in

The association between homocysteine in the follicular fluid with embryo quality and pregnancy rate in assisted reproductive techniques

  • ASSISTED REPRODUCTION TECHNOLOGIES
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To investigate the association between follicular fluid homocysteine levels and embryo quality and pregnancy rates in patients undergoing assisted reproduction.

Methods

Fifty infertile women who were admitted to our clinic were enrolled in the study. Ovulation induction was performed by using GnRH agonist and gonadotropins. For each patient, homocysteine level in the follicular fluid was measured by using nephelometric method after the oocyte pick-up. The association between the homocysteine concentration in the follicular fluid and the oocyte–embryo quality, pregnancy rates and hormone levels were investigated.

Results

Mean ± SD Hcy was 9.6 ± 2.02 μmol/L and 14.9 ± 2.93 μmol/L in pregnant and non-pregnant women, respectively (p < 0.0001). There were no statistically significant differences between pregnant and non-pregnant women in mean age, duration of infertility, body mass index, the oocyte–embryo quality parameters, and hormone levels. Homocystein did not have any correlation with M2, late M2, and total number of oocytes, number of fertilized oocytes and transferred embryos, and embryo quality grade. Area under curve (AUC) of hcy for prediction of pregnancy failure was 0.922 (p = 0.0001, 95% Confidence interval 0.85–0.99). A threshold of 11.9 μmol/L of hcy had a sensitivity of 82%, specificity of 100%, positive predictive value of 100% and negative predictive value of 91.6% for prediction of pregnancy failure. The subgroup analysis in male factor infertility group (n = 28), showed that mean homocystein was 9.9 ± 2.44 μmol/L and 14.1 ± 2.72 μmol/L in pregnant and non-pregnant women, respectively (p = 0.002).

Conclusion

Low follicular fluid homocysteine level is associated with a better chance of clinical pregnancy.

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

Similar content being viewed by others

References

  1. Ebisch IMW, Peters WH, Thomas CM, Wetzels AM, Peer PG, Steegers RP. Homocysteine, glutathione and related thiols affect fertility parameters in the (sub) fertile couple. Hum Reprod. 2006;21:1725–33.

    Article  CAS  PubMed  Google Scholar 

  2. Steegers-Theunissen RP, Steegers EA, Thomas CMG, Hollanders HM, Peereboom-Stegeman JH, Trijbels FJ, et al. Study on the presence of homocysteine in ovarian follicular fluid. Fertil Steril. 1993;60:1006–10.

    CAS  PubMed  Google Scholar 

  3. Verkleij-Hagoort AC, Verlinde M, Ursem NT, Lindemans J, Helbing WA, Ottenkamp J, et al. Maternal hyperhomocysteinaemia is a risk factor for congenital heart disease. BJOG. 2006;113:1412–8.

    Article  CAS  PubMed  Google Scholar 

  4. Cotter AM, Molloy AM, Scott JM, Daly SF. Elevated plasma homocysteine in early pregnancy: a risk factor for the development of severe preeclampsia. Am J Obstet Gynecol. 2001;185:781–5.

    Article  CAS  PubMed  Google Scholar 

  5. Boxmeer JC, Brouns RM, Lindemans J, Steegers EA, Martini E, Macklon NS, Steegers-Theunissen RP. Preconception folic acid treatment affects the microenvironment of the maturing oocyte in humans. Fertil Steril. 2008;89(6):1766–70.

    Article  CAS  PubMed  Google Scholar 

  6. Mohanty D, Das KC. Effect of folate deficiency on the reproductive organs of female rhesus monkeys: a cytomorphological and cytokinetic study. J Nutr. 1982;112:1565–76.

    CAS  PubMed  Google Scholar 

  7. Raijmakers MT, Steegers EA, Peters WH. Glutathione S-transferases and thiol concentrations in embryonic and early fetal tissues. Hum Reprod. 2001;16:2445–50.

    CAS  PubMed  Google Scholar 

  8. Maul H, Longo M, Saade GR, et al. Nitric oxide and its role during pregnancy: from ovulation to delivery. Curr Pharm Des. 2003;9:359–80.

    Article  CAS  PubMed  Google Scholar 

  9. Szymanski W, Kazdepka-Zieminska A. Effect of homocysteine concentration in follicular fluid on a degree of oocyte maturity. Gynekol Pol. 2003;74:1392–6.

    Google Scholar 

  10. Riley JC, Behrman HR. Oxygen radicals and reactive oxygen species in reproduction. Proc Soc Exp Biol Med. 1991;198:781–91.

    CAS  PubMed  Google Scholar 

  11. Rodriguez-Gonzalez E, Lopez-Bejar M, Mertens MJ, Paramio MT. Effects on in vitro embryo development and intracellular glutathione content of the presence of thiol compounds during maturation of prepubertal goat oocytes. Mol Reprod Dev. 2003;65:446–53.

    Article  CAS  PubMed  Google Scholar 

  12. Shan XQ, Aw TY, Jones DP. Glutathione-dependent protection against oxidative injury. Pharmacol Ther. 1990;47:61–71.

    Article  CAS  PubMed  Google Scholar 

  13. Forges T, Monnier-Barbarino P, Alberto JM, Gueant-Rodriguez RM, Daval JL, Gueant JL. Impact of folate and homocysteine metabolism on human reproductive health. Hum Reprod Update. 2007;13:225–38.

    Article  CAS  PubMed  Google Scholar 

  14. Irez T, Ocal P, Guralp O, Cetin M, Aydogan B, Sahmay S. Different serum anti-Müllerian hormone concentrations are associated with oocyte quality, embryo development parameters and IVF-ICSI outcomes. Arch Gynecol Obstet. 2011;284(5):1295–301.

    Article  CAS  PubMed  Google Scholar 

  15. Veeck LL. Oocyte assessment and biological performance. Ann NY Acad Sci. 1999;541:259–74.

    Article  Google Scholar 

  16. Gardner DK, Lane M, Stevens J. Non-invasive assessment of human embryo nutrient consumption as a measure of developmental potential. Fertil Steril. 2001;76:1175–80.

    Article  CAS  PubMed  Google Scholar 

  17. Attaran M, Pasqualotto E, Falcone T, Goldberg JM, Miller KF, Agarwal A, et al. The effect of follicular fluid reactive oxygen species on the outcome of in vitro fertilization. Int J Fertil Womens Med. 2000;45:314–20.

    CAS  PubMed  Google Scholar 

  18. Kim IH, Van Langendonckt A, Van Soom A, Vanroose G, Casi AL, Hendriksen PJ, et al. Effect of exogenous glutathione on the in vitro fertilization of bovine oocytes. Theriogenology. 1999;52:537–47.

    Article  CAS  PubMed  Google Scholar 

  19. Berker B, Kaya C, Aytac R, Satiroglu H. Homocysteine concentrations in follicular fluid are associated with poor oocyte and embryo qualities in polycystic ovary syndrome patients undergoing assisted reproduction. Hum Reprod. 2009;24(9):2293–302.

    Article  CAS  PubMed  Google Scholar 

  20. Aitken RJ, Irvine DS, Wu FC. Prospective analysis of sperm-oocyte fusion and reactive oxygen species generation as criteria for the diagnosis of infertility. Am J Obstet Gynecol. 1991;164:542–51.

    CAS  PubMed  Google Scholar 

  21. Bettahar LK, Feugeas O, Wittemer C, Ohl J, Rongieres C, Nisand I. Evolution of homocysteine during ovarian stimulation for IVF or ICSI. Gynecol Obstet Fertil. 2002;30(2):121–8.

    Article  Google Scholar 

  22. Bean CJ, Hassold TJ, Judis L, Hunt PA. Fertilization in vitro increases non-disjunction during early cleavage divisions in a mouse model system. Hum Reprod. 2002;17(9):2362–7.

    Article  PubMed  Google Scholar 

  23. Miyazaki T, Sueoka K, Dharmarajan AM, Atlas SJ, Bulkley GB, Wallach EE. Effect of inhibition of oxygen free radical on ovulation and progesterone production by the in-vitro perfused rabbit ovary. J Reprod Fertil. 1991;91:207–12.

    Article  CAS  PubMed  Google Scholar 

  24. Bedawy MA, Miller K, Goldberg JM, Nelson DR, Agarwal A, Falcone T. Assessment of the predictive value of follicular fluid cytokines and reactive oxygen species in IVF cycles. Fertil Steril. 2002;78:5–6.

    Article  Google Scholar 

  25. 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 

  26. Oyawoye O, Abdel GA, Gamer A, Constantinovici N, Perrett C, Hardiman P. Antioxidants and reactive oxygen species in follicular fluid of women undergoing IVF: relationship to outcome. Hum Reprod. 2003;18:2270–4.

    Article  CAS  PubMed  Google Scholar 

  27. Pacchiarotti A, Mohamed MA, Micara G, Linari A, Tranquilli D, Espinola SB, Aragona C. The possible role of hyperhomocysteinemia on IVF outcome. Assist Reprod Genet. 2007;24:459–62.

    Article  Google Scholar 

Download references

Conflict of interest

Authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pelin Ocal.

Additional information

Capsule

Low follicular fluid homocysteine level is associated with a better chance of clinical pregnancy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ocal, P., Ersoylu, B., Cepni, I. et al. The association between homocysteine in the follicular fluid with embryo quality and pregnancy rate in assisted reproductive techniques. J Assist Reprod Genet 29, 299–304 (2012). https://doi.org/10.1007/s10815-012-9709-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-012-9709-y

Keywords

Navigation