title: GnRH agonist versus GnRH antagonist in IVF/ICSI cycles with recombinant LH supplementation: DNA fragmentation and apoptosis in granulosa cells.
abstract: OBJECTIVE
  To compare the level of apoptosis and DNA fragmentation in the human granulosa cell (GC) layer exposed to an agonist or antagonist of GnRH in intracytoplasmic sperm injection (ICSI) cycles supplemented with recombinant LH (rLH).
  
  
  METHODS
  Patients without ovulatory dysfunction, aged ≤37 years and in their first ICSI cycle were prospectively randomised to receive either a long GnRH agonist protocol or a multi-dose antagonist protocol. In both groups, recombinant FSH supplemented with rLH was used for ovarian stimulation, and the GCs were collected during oocyte denudation. The GCs were then analysed for DNA fragmentation by TUNEL assay and for apoptosis using the annexin-V assay. The outcomes were given as the percentage of GCs with DNA fragmentation and apoptosis out of the total number of GCs analysed. Comparison of the agonist versus the antagonist group was performed using the Mann-Whitney test.
  
  
  RESULTS
  DNA fragmentation: 32 patients were included in either the GnRH agonist group (n=16) or the antagonist group (n=16). The percentage of GCs with positive DNA fragmentation did not differ significantly (P=0.76) between the agonist group (15.5 ± 9.4%) and the antagonist group (18.8 ± 13.3%). Apoptosis: 28 patients were included in either the GnRH agonist group (n=14) or the antagonist group (n=14). The percentage of GCs positive for apoptosis did not differ significantly (P=0.78) between the agonist group (34.6 ± 14.7%) and the antagonist group (36.5 ± 22%).
  
  
  CONCLUSIONS
  The results suggest that therapy with either an agonist or antagonist of GnRH is associated with comparable levels of DNA fragmentation and apoptosis in granulosa cells in ICSI cycles supplemented with rLH.
authors.affiliation: Department of Gynaecology and Obstetrics, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil.
authors.forename: Heloisa L
authors.initials: HL
authors.lastname: Lavorato
authors.forename: Joao Batista A
authors.initials: JB
authors.lastname: Oliveira
authors.forename: Claudia G
authors.initials: CG
authors.lastname: Petersen
authors.forename: Laura
authors.initials: L
authors.lastname: Vagnini
authors.forename: Ana L
authors.initials: AL
authors.lastname: Mauri
authors.forename: Mario
authors.initials: M
authors.lastname: Cavagna
authors.forename: Ricardo L R
authors.initials: RL
authors.lastname: Baruffi
authors.forename: Jose G
authors.initials: JG
authors.lastname: Franco
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D002469:Cell Separation; D053938:DNA Fragmentation / Q000187:drug effects*; D005191:Family Characteristics; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000009:adverse effects / Q000819:agonists* / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects* / Q000473:pathology; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007246:Infertility / Q000628:therapy; D016729:Leuprolide / Q000009:adverse effects / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000235:genetics / Q000494:pharmacology*; D008297:Male; D054315:Oocyte Retrieval; D010062:Ovulation Induction / Q000379:methods*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology; D020554:Sperm Injections, Intracytoplasmic
chemical_list: D006727:Hormone Antagonists; D011994:Recombinant Proteins; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D016729:Leuprolide; C062876:cetrorelix