ObjectiveProgesterone elevation on the day of human chorionic gonadotropin (hCG) administration remains one of the most controversial topics in reproductive endocrinology. Factors associated with these increases have not been fully determined. The purpose of our study is to investigate factors associated with extreme progesterone elevation on the day of human chorionic gonadotropin (hCG) administration. Materials and methodsThis retrospective observational, single-center cohort study recruited 2000 fresh in vitro fertilization (IVF) and/or intracytoplasmic sperm injection(ICSI)-embryo transfer cycles from January 2000 to December 2014 in our institution. ResultsWhen cycles were divided into those with progesterone <1.94 ng/mL (n = 1791) and ≧1.94 ng/mL (n = 209) on the day of hCG administration, five factors were positively associated with highly elevated progesterone concentration: protocol (GnRH agonist versus antagonist; odds ratio [OR = 2.786]), number of dominant follicles (OR = 1.098), total dose of follicle stimulating hormone (FSH) used (OR = 1.023), elevated luteinizing hormone (LH) (OR = 1.085) and estradiol (E2; OR = 1.001) concentrations on the day of hCG administration (p < 0.001 each). After omitting the protocol effect, the remaining factors showed limited contributions to highly elevated progesterone (ORs = 0.95–1.2). ConclusionsThe factor showing the greatest association with extreme progesterone elevation was use of the GnRH agonist protocol.