title: Ovulation stimulation protocols utilizing GnRH-antagonist/hCG, promote cytotoxic cell populations, predominant in patients with embryo implantation complications.
abstract: OBJECTIVE
  Gonadotropin-releasing hormone (GnRH) antagonist combined with the human chorionic gonadotropin hormone (hCG) is commonly used in assisted reproduction techniques (ARTs) to induce controlled ovarian hyperstimulation (COH) and to synchronize oocyte maturation. While hCG is known to have immunomodulatory properties, we aimed to assess its effect on immunological changes, with respect to HLA-G binding receptors and embryo implantation success.
  
  
  METHODS
  The study involved 103 subjects, including patients undergoing COH protocols (n=66), divided on the basis of the pair's fertility disorder (FD) causes (female FD, n=29; male FD, n=37), and age matched healthy women (n=37). The relative distribution of T cell (CD3+/CD4+, CD3+/CD8+) and NK cell (CD56bright/CD16-, CD56dim/CD16+) populations was evaluated together with HLA-G ligands KIR2DL4 and LILRB1 expression by flow cytometry in the peripheral blood of all subjects, as well as in patient follicular fluids.
  
  
  RESULTS
  Both groups of patients exhibited a significant decrease of their CD4/CD8 index, a down-modulation of LILRB1-positive CD8 T cells, and increased KIR2DL4-positive NK cell distribution, when compared to the healthy donors. We attribute these changes to the COH protocol, since the only significant change between the patient groups was in the number of cytotoxic CD56dim NK cells (elevated in the female FD group). Patients with male FD causes, having an above-average CD4/CD8 index (≥3.17) and below-average KIR2DL4+/CD56bright NK cell levels(≤13.3%), exhibited higher embryo implantation rates.
  
  
  CONCLUSIONS
  The GnRH antagonist/hCG protocol promotes CD3+/CD8+ and KIR2DL4+ NK cell levels, more abundant in subjects with lower implantation rates, and thus decreases the embryotransfer success in otherwise fertile women.
authors.affiliation: Department of Immunology and Gnotobiology, Institute of Microbiology, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Svoboda
authors.forename: Zaneta
authors.initials: Z
authors.lastname: Ruzickova
authors.forename: Lucie
authors.initials: L
authors.lastname: Cuchalova
authors.forename: Milena
authors.initials: M
authors.lastname: Kralickova
authors.forename: Jitka
authors.initials: J
authors.lastname: Rezacova
authors.forename: Milena
authors.initials: M
authors.lastname: Vrana
authors.forename: Anna
authors.initials: A
authors.lastname: Fiserova
authors.forename: Jan
authors.initials: J
authors.lastname: Richter
authors.forename: Jindrich
authors.initials: J
authors.lastname: Madar
mesh_terms: D000328:Adult; D000858:Anovulation / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D016516:CD4-CD8 Ratio; D006063:Chorionic Gonadotropin / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D010064:Embryo Implantation / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy* / Q000276:immunology; D007248:Infertility, Male / Q000188:drug therapy / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D010060:Ovulation / Q000187:drug effects* / Q000276:immunology; D011247:Pregnancy; D027724:Reproductive Techniques, Assisted; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
chemical_list: D015415:Biomarkers; D006063:Chorionic Gonadotropin; D007987:Gonadotropin-Releasing Hormone