title: Presence of bile acids in human follicular fluid and their relation with embryo development in modified natural cycle IVF.
abstract: OBJECTIVE
  Are bile acids (BA) and their respective subspecies present in human follicular fluid (FF) and do they relate to embryo quality in modified natural cycle IVF (MNC-IVF)?
  
  
  CONCLUSIONS
  BA concentrations are 2-fold higher in follicular fluid than in serum and ursodeoxycholic acid (UDCA) derivatives were associated with development of top quality embryos on Day 3 after fertilization.
  
  
  BACKGROUND
  Granulosa cells are capable of synthesizing BA, but a potential correlation with oocyte and embryo quality as well as information on the presence and role of BA subspecies in follicular fluid have yet to be investigated.
  
  
  METHODS
  Between January 2001 and June 2004, follicular fluid and serum samples were collected from 303 patients treated in a single academic centre that was involved in a multicentre cohort study on the effectiveness of MNC-IVF.
  
  
  METHODS
  Material from patients who underwent a first cycle of MNC-IVF was used. Serum was not stored from all patients, and the available material comprised 156 follicular fluid and 116 matching serum samples. Total BA and BA subspecies were measured in follicular fluid and in matching serum by enzymatic fluorimetric assay and liquid chromatography-mass spectrometry, respectively. The association of BA in follicular fluid with oocyte and embryo quality parameters, such as fertilization rate and cell number, presence of multinucleated blastomeres and percentage of fragmentation on Day 3, was analysed.
  
  
  RESULTS
  Embryos with eight cells on Day 3 after oocyte retrieval were more likely to originate from follicles with a higher level of UDCA derivatives than those with fewer than eight cells (P < 0.05). Furthermore, follicular fluid levels of chenodeoxycholic derivatives were higher and deoxycholic derivatives were lower in the group of embryos with fragmentation compared with those without (each P < 0.05). Levels of total BA were 2-fold higher in follicular fluid compared with serum (P < 0.001), but had no predictive value for oocyte and embryo quality.
  
  
  CONCLUSIONS
  Only samples originating from first cycle MNC-IVF were used, which resulted in 14 samples only from women with an ongoing pregnancy, therefore further prospective studies are required to confirm the association of UDCA with IVF pregnancy outcomes. The inter-cycle variability of BA levels in follicular fluid within individuals has yet to be investigated. We checked for macroscopic signs of contamination of follicular fluid by blood but the possibility that small traces of blood were present within the follicular fluid remains. Finally, although BA are considered stable when stored at -20°C, there was a time lag of 10 years between the collection and analysis of follicular fluid and serum samples.
  
  
  CONCLUSIONS
  The favourable relation between UDCA derivatives in follicular fluid and good embryo development and quality deserves further prospective research, with live birth rates as the end-point.
  
  
  BACKGROUND
  This work was supported by a grant from the Netherlands Organisation for Scientific Research (VIDI Grant 917-56-358 to U.J.F.T.). No competing interests are reported.
authors.affiliation: Department of Obstetrics and Gynaecology, Section Reproductive Medicine, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: Nagy
authors.affiliation: Department of Obstetrics and Gynaecology, Section Reproductive Medicine, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands Department of Obstetrics & Gynaecology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: A P A
authors.initials: AP
authors.lastname: van Montfoort
authors.affiliation: Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Dikkers
authors.affiliation: Department of Obstetrics and Gynaecology, Section Reproductive Medicine, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van Echten-Arends
authors.affiliation: Department of Obstetrics and Gynaecology, Section Reproductive Medicine, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Homminga
authors.affiliation: Department of Obstetrics and Gynaecology, Section Reproductive Medicine, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Land
authors.affiliation: Department of Obstetrics and Gynaecology, Section Reproductive Medicine, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Hoek
authors.affiliation: Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands u_tietge@yahoo.com.
authors.forename: U J F
authors.initials: UJ
authors.lastname: Tietge
mesh_terms: D000328:Adult; D001647:Bile Acids and Salts / Q000737:chemistry*; D001757:Blastomeres / Q000378:metabolism; D002853:Chromatography, Liquid; D015331:Cohort Studies; D047108:Embryonic Development; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D015571:Follicular Fluid / Q000378:metabolism*; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D013997:Time Factors; D014580:Ursodeoxycholic Acid / Q000097:blood
chemical_list: D001647:Bile Acids and Salts; D014580:Ursodeoxycholic Acid
keywords: IVF; bile acids; fertility; follicular fluid; modified natural cycle