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Hum. Reprod. Advance Access published online on February 15, 2009
Human Reproduction, doi:10.1093/humrep/dep009
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© The Author 2009. 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

IVF outcomes are associated with biomarkers of the homocysteine pathway in monofollicular fluid

Jolanda C. Boxmeer1, Nick S. Macklon1,2, Jan Lindemans3, Nicole G.M. Beckers1, Marinus J.C. Eijkemans2,4, Joop S.E. Laven1, Eric A.P. Steegers1 and Régine P.M. Steegers-Theunissen1,5,6,7,8

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

8 Correspondence address. Department of Obstetrics and Gynecology, Division of Obstetrics and Prenatal Medicine, Erasmus MC, University Medical Center, Ee 22-71a, PO Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail: r.steegers{at}erasmusmc.nl

BACKGROUND: Maternal hyperhomocysteinemia is detrimental for reproduction, but the effects on embryo quality are unknown. The aim of this study was to investigate whether biomarkers of the homocysteine pathway are associated with in vitro fertilization (IVF) outcome.

METHODS: In a prospective study, we investigated biomarkers of the homocysteine pathway for associations with embryo quality and biochemical pregnancy in women undergoing IVF or intracytoplasmic sperm injection treatment (n = 181). In the treatment cycle, blood and monofollicular fluid samples were collected for determination of folate, cobalamin and total homocysteine (tHcy) concentrations.

RESULTS: Of all the women in the study, 67% used folic acid supplements. In blood, a significant correlation was established between high cobalamin and better embryo quality [standardized adjusted regression coefficient: –0.17, 95% confidence interval (CI): –0.30, –0.01]. In monofollicular fluid of non-supplemented women, high cobalamin correlated with better embryo quality (estimate: –0.87; 95% CI: –1.68, –0.06), whereas high tHcy resulted in poor embryo quality (estimate: 1.01; 95% CI: 0.08, 1.95). However, in monofollicular fluid of supplemented women, high tHcy correlated with better embryo quality (estimate: –0.58; 95% CI: –1.12, –0.04). In the total group, a 2-fold increase of monofollicular fluid folate corresponded with a 3.3 times higher chance (95% CI: 1.09, 9.71) of achieving pregnancy.

CONCLUSIONS: An optimal homocysteine pathway in follicular fluid is associated with a better embryo quality and chance of pregnancy.

Key words: cobalamin/embryo quality/folic acid/homocysteine/pregnancy

Submitted on June 15, 2008; resubmitted on October 28, 2008; accepted on November 28, 2008.


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