Abstract
INTRODUCTION: Human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone agonist (GnRHa) are widely used for final maturation of follicles in fertility treatment, yet the detailed dynamics of follicle stimulating hormone (FSH), luteinizing hormone (LH)/hCG and their receptor expression (i.e. FSHR and LHR) during the ovulatory process remain insufficiently characterized. MATERIAL AND METHODS: This prospective, single-center study included 50 women undergoing ovarian stimulation during 2016-2018. Each participant contributed one follicle aspirated at T = 0,12,17 or 32h after trigger administration (0.5 mg GnRHa (buserelin) or 6,500 IU hCG) and a second follicle aspirated at oocyte pickup (T = 36h). Follicular fluid (FF) and plasma were analyzed for gonadotropins, and granulosa cells for FSHR and LHR transcript levels. RESULTS: GnRHa triggered a rapid endogenous surge in plasma: LH peaked at ≈120-140 IU/L at 12h and remained elevated until 36h; FSH rose from ≈17 to ≈25 IU/L within 12h. In FF, LH exceeded 100 IU/L at 17 h, whereas FSH remained low with a small peak at 12h (8-9 IU/L). With hCG triggering, circulating FSH declined to ≈40% of baseline by 17h, while FF FSH was constantly low (≈5 IU/L) and unchanged. FF hCG concentrations increased sharply between 17-32h. Consequently, LH appeared earlier (12-17h) in FF than hCG (17-32h). LHR granulosa cell expression decreased to ≈3-5% of baseline by 32h, indicating substantial downregulation as ovulation progressed. FSHR was downregulated even faster, between 0-12h. DISCUSSION: GnRHa induces a stronger and more physiologic gonadotropin surge than commonly assumed, with timely entry of LH and FSH into FF coinciding with high FSHR and LHR expression and with the known timing of intrafollicular oocyte-maturation signals (12-17h). In contrast, hCG enters the follicle later, when LHR expression is markedly reduced, and does not provide an FSH component. This may explain reports of slightly higher MII rates using the GnRHa trigger. These findings highlight the importance of temporal receptor dynamics in optimizing final oocyte maturation and support the use of GnRHa as a stand-alone trigger in freeze-all antagonist cycles and in combination with hCG (i.e., dual triggering) in fresh cycles to optimize oocyte maturation.