title: Intrafollicular endocrine milieu after addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization.
abstract: BACKGROUND
  The role of human chorionic gonadotropin (hCG) supplementation on the intrafollicular steroid milieu has been studied.
  
  
  OBJECTIVE
  The objective of the study was to assess the impact on steroid levels in follicular fluids (FFs) after different doses of hCG supplementation to recombinant FSH for controlled ovarian stimulation.
  
  
  METHODS
  This was a prospective randomized dose-response study conducted at Copenhagen University Hospital, Rigshospitalet, Denmark.
  
  
  METHODS
  From 62 in vitro fertilization patients, 334 FFs were selected for analyses.
  
  
  METHODS
  Patients were treated using a GnRH agonist protocol with recombinant FSH 150 IU/d and randomized from stimulation day 1 to supplementation with hCG: D0, 0 IU/d; D50, 50 IU/d; D100, 100 IU/d; and D150, 150 IU/d.
  
  
  METHODS
  Intrafollicular hormone concentrations in relation to treatment groups, follicular sizes, and embryo quality were measured.
  
  
  RESULTS
  In large follicles, hCG supplementation induced a nearly 3-fold increase of estradiol (nanomoles per liter) [D0: 1496; D50: 3138; D100: 4338; D150: 4009 (P < .001)], a significant 3-fold increase of androstenedione, and a 5-fold increase of T (nanomoles per liter) [D0: 15; D50: 38; D100: 72; D150: 56 (P < .001)]. The estradiol to T ratio decreased significantly, with the lowest ratio in D100 and the highest in D0. Large follicles giving rise to good-quality embryos had significantly higher estradiol and progesterone levels and estradiol to T, estradiol to androstenedione, and progesterone to estradiol ratios, compared with small follicles, leading to poor-quality embryos.
  
  
  CONCLUSIONS
  Increasing doses of hCG supplementation markedly stimulated the intrafollicular concentration of both estradiol and androgens, with a shift toward a more androgenic milieu. In large follicles with oocytes giving rise to good-quality embryos, the FFs were significantly more estrogenic than in small follicles with oocytes developing into poor quality embryos.
authors.affiliation: The Fertility Clinic (L.L.T., A.N.A., A.L.), Section 4071, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark; and Follicle Biology Laboratory (J.S.), Vrije Universiteit Brussel, UZ Brussel, 1090 Brussels, Belgium.
authors.forename: L L
authors.initials: LL
authors.lastname: Thuesen
authors.forename: A Nyboe
authors.initials: AN
authors.lastname: Andersen
authors.forename: A
authors.initials: A
authors.lastname: Loft
authors.forename: J
authors.initials: J
authors.lastname: Smitz
mesh_terms: D000328:Adult; D000735:Androstenedione / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D005640:Follicle Stimulating Hormone / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism; D010062:Ovulation Induction / Q000379:methods*; D011374:Progesterone / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013739:Testosterone / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D011994:Recombinant Proteins; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D004958:Estradiol; D005640:Follicle Stimulating Hormone