title: Homocysteine metabolism in the pre-ovulatory follicle during ovarian stimulation.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Jolanda C
authors.initials: JC
authors.lastname: Boxmeer
authors.forename: Régine P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
authors.forename: Jan
authors.initials: J
authors.lastname: Lindemans
authors.forename: Mark F
authors.initials: MF
authors.lastname: Wildhagen
authors.forename: Elena
authors.initials: E
authors.lastname: Martini
authors.forename: Eric A P
authors.initials: EA
authors.lastname: Steegers
authors.forename: Nick S
authors.initials: NS
authors.lastname: Macklon
mesh_terms: 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
chemical_list: D015415:Biomarkers; D006063:Chorionic Gonadotropin; D006710:Homocysteine; D004958:Estradiol; D011732:Pyridoxal Phosphate; D005492:Folic Acid; D014805:Vitamin B 12