title: Transcriptional characteristics of different sized follicles in relation to embryo transferability: potential role of hepatocyte growth factor signalling.
abstract: We hypothesized that a better discrimination between follicles containing oocytes with high developmental competence and those containing oocytes with low competence, based on a combination of a follicle's size and transcriptomic signature, will provide a reliable method to predict embryonic outcome of IVF.
  
  
  
  This study provides new insights on the impact of follicular size on oocyte quality as measured by embryonic development and demonstrates that medium follicles yield a better percentage of transferable embryos.
  
  
  
  Although it is generally accepted that large ovarian follicles contain better eggs, other studies report that a better follicular size subdivision and a better characterization are needed.
  
  
  
  Individual follicles (n = 136), from a total of 33 women undergoing IVF, were aspirated and categorized on the basis of their follicular liquid volume (small, medium or large) and the embryonic outcome of the enclosed oocyte: poor or good development. Comprehensive gene expression analysis between cells from the different sized follicles was performed using microarrays and quantitative RT-PCR to find molecular markers associated with follicular maturity and oocyte developmental competence.
  
  
  
  The analysis of embryonic outcome in relation to follicular size indicates that the medium-sized follicles category yielded more transferable embryos (35%) compared with the largest follicles (30%) (NS). Gene expression analysis revealed expression markers with significant (P < 0.05) discrimination between the poor development groups for all three follicle sizes, and good development medium-size follicles, including up-regulation of thrombomodulin, transforming growth factor, beta receptor II and chondrolecti, and those associated with hyaluronan synthesis, coagulation and hepatocyte growth factor signalling.
  
  
  
  These analyses were performed in a single cohort of patients coming from a single clinic and the biomarkers generated will require validation in different geographical and biological contexts to ensure their global applicability.
  
  
  
  Medium-size follicles seem to be the optimal size for a positive embryonic outcome and are associated with competence markers that may help in understanding the ideal differentiation status during late folliculogenesis.
  
  
  
  The data discussed in this publication have been deposited in The National Center for Biotechnology Information Gene Expression Omnibus database and are accessible through GEO Series accession number GSE52851.
  
  
  
  This study was supported by Canadian Institutes of Health Research (CIHR) and Natural Sciences and Engineering Research Council of Canada (NSERC) to M.A.S. There are no competing interests to declare.
authors.affiliation: Département des Sciences Animales, Centre de Recherche en Biologie de la Reproduction, Institut sur la Nutrition et les Aliments fonctionnels, Université Laval, 2440 Boulevard Hochelaga, Quebec, QC G1V 0A6, Canada.
authors.forename: A L
authors.initials: AL
authors.lastname: Nivet
authors.affiliation: Ottawa Fertility Clinic, 100-955 Green Valley Crescent, Ottawa, ON K2C 3V4, Canada.
authors.forename: M C
authors.initials: MC
authors.lastname: Léveillé
authors.affiliation: Ottawa Fertility Clinic, 100-955 Green Valley Crescent, Ottawa, ON K2C 3V4, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Leader
authors.affiliation: Département des Sciences Animales, Centre de Recherche en Biologie de la Reproduction, Institut sur la Nutrition et les Aliments fonctionnels, Université Laval, 2440 Boulevard Hochelaga, Quebec, QC G1V 0A6, Canada marc-andre.sirard@fsaa.ulaval.ca.
authors.forename: M A
authors.initials: MA
authors.lastname: Sirard
mesh_terms: D005260:Female; D015571:Follicular Fluid / Q000166:cytology / Q000378:metabolism; D006107:Granulosa Cells / Q000166:cytology* / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D006080:Ovarian Follicle / Q000166:cytology* / Q000378:metabolism*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D017228:Hepatocyte Growth Factor
keywords: follicular cells; follicular size; gene expression; granulosa cells; hepatocyte growth factor; oocyte competence