Homocysteine metabolism in the pre-ovulatory follicle during ovarian stimulation.
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 <or= 0.001). The blood concentrations of tHcy, folate, cobalamin and PLP were significantly correlated with the corresponding follicular fluid concentrations (all P <or= 0.001). Follicular fluid tHcy concentrations were inversely correlated with follicular diameter (P <or= 0.05). In folic acid supplemented women, follicular fluid folate was inversely correlated with follicular diameter (P <or= 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.
Boxmeer
Jolanda C
JC
Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
Steegers-Theunissen
Régine P M
RP
Lindemans
Jan
J
Wildhagen
Mark F
MF
Martini
Elena
E
Steegers
Eric A P
EA
Macklon
Nick S
NS
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods; D005492:Folic Acid / Q000378:metabolism; D015571:Follicular Fluid / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D006080:Ovarian Follicle / Q000378:metabolism* / Q000502:physiology*; D010062:Ovulation Induction / Q000379:methods*; D011732:Pyridoxal Phosphate / Q000378:metabolism; D011795:Surveys and Questionnaires; D014805:Vitamin B 12 / Q000378:metabolism
D015415:Biomarkers; D006063:Chorionic Gonadotropin; D006710:Homocysteine; D004958:Estradiol; D011732:Pyridoxal Phosphate; D005492:Folic Acid; D014805:Vitamin B 12