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Hum. Reprod. Advance Access published online on July 29, 2008
Human Reproduction, doi:10.1093/humrep/den292
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Homocysteine metabolism in the pre-ovulatory follicle during ovarian stimulation

Jolanda C. Boxmeer1, Régine P.M. Steegers-Theunissen1,2,3,4, Jan Lindemans5, Mark F. Wildhagen1,6, Elena Martini1, Eric A.P. Steegers1 and Nick S. Macklon1,7,8

1 Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands 2 Department of Epidemiology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands 3 Department of Pediatric Cardiology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands 4 Department of Clinical Genetics, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands 5 Department of Clinical Chemistry, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands 6 Department of Urology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands 7 Department of Reproductive Medicine and Gynaecology, University Medical Centre, Utrecht, The Netherlands

8 Correspondence address. Department of Reproductive Medicine and Gynaecology, University Medical Centre, PO Box 85500, 3508 GA Utrecht, The Netherlands. Tel: +31-30-2507524; E-mail: n.s.macklon{at}umcutrecht.nl

BACKGROUND: Ovarian stimulation gives rise to supraphysiological estradiol levels, which may affect oocyte quality. This study aims to investigate whether ovarian stimulation deranges the homocysteine pathway thereby affecting the pre-ovulatory follicle.

METHODS: Blood samples were collected on cycle day 2 and the day of hCG administration in 181 women undergoing ovarian stimulation for IVF. In each subject, the diameter of the two leading follicles was measured and the corresponding follicular fluids were collected. In blood and follicular fluid samples, total homocysteine (tHcy), folate, cobalamin and pyridoxal’5-phosphate (PLP) were determined. According to the blood folate levels, women were classified as either folic acid supplemented (n = 113) or non-supplemented (n = 32).

RESULTS: Ovarian stimulation resulted in a significant decrease in blood tHcy and cobalamin levels (both P ≤ 0.001). The blood concentrations of tHcy, folate, cobalamin and PLP were significantly correlated with the corresponding follicular fluid concentrations (all P ≤ 0.001). Follicular fluid tHcy concentrations were inversely correlated with follicular diameter (P ≤ 0.05). In folic acid supplemented women, follicular fluid folate was inversely correlated with follicular diameter (P ≤ 0.05).

CONCLUSIONS: Ovarian stimulation deranges blood and follicular fluid biomarkers of the homocysteine pathway. High ovarian follicular fluid tHcy and folate levels may have detrimental effects on follicular development.

Key words: folic acid/cobalamin/pyridoxine/assisted reproduction/follicular fluid

Submitted on March 8, 2008; resubmitted on June 20, 2008; accepted on July 3, 2008.


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B. Berker, C. Kaya, R. Aytac, and H. Satiroglu
Homocysteine concentrations in follicular fluid are associated with poor oocyte and embryo qualities in polycystic ovary syndrome patients undergoing assisted reproduction
Hum. Reprod., September 1, 2009; 24(9): 2293 - 2302.
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