Dose-dependent modulation of luteinizing hormone receptor expression in human granulosa cells and progesterone production during ovarian stimulation

Abstract

Objective To assess the impact of different recombinant follicle-stimulating hormone (recFSH) dosages in ovarian stimulation (OS) on luteinizing hormone (LH)–receptor and FSH-receptor expression in granulosa cells (GCs) and progesterone level. Design Prospective interventional study (07/2023–02/2024). Subjects Six volunteers with regular cycles and normal ovarian reserve undergoing two OS cycles for oocyte vitrification as a means of elective fertility preservation. Exposure Different recFSH dosages (150 IU vs. 300 IU) in two OS cycles, performed in a gonadotropin-releasing hormone–antagonist protocol. Main Outcome Measures The LH receptor expression on GCs. Results Volunteers had a median age of 34 years (range: 28–36), a median antimüllerian hormone–level of 2.28 ng/mL (interquartile range [IQR]: 2.41–3.35) and a median antral follicle count of 13.5 (IQR:12–14) in the 150 IU and 13 (12–15) in the 300 IU OS cycle. Median total recFSH dosages were 1650 IU (IQR: 1350–1800IU)/3150 IU (IQR: 3000–3300) in the 150 IU/300 IU OS cycle, respectively. The number of retrieved cumulus-oocyte-complexes was (median and IQR) 11.5 (10–14)/12.5 (7–15), the number of mature oocytes (median and IQR) of 10.5 (7–12)/10 (6–12), respectively, without a statistically significant difference. Besides the stimulation start, serum FSH levels of the 300 IU-cycle were significantly higher compared with the 150 IU-cycle. Estradiol levels were significantly higher in the 300 IU-group on day 5 and at follicle size of 14–16 mm. Progesterone (P4) levels were not statistically significantly different between the stimulation cycles. The LH receptor expression in the GCs at oocyte-pick up was significantly higher and FSH-receptor expression was significantly lower in the 300 IU-group compared with the 150 IU-group. The P4 levels on oocyte-pick up day were significantly associated with LH receptor levels after adjusting for the recFSH dose. Furthermore, a significant and independent association of the recFSH dose between the P4 levels and the LH receptor levels was seen on the day of oocyte retrieval. Conclusion Higher recFSH dosages during OS are associated with increased LH receptor expression, and LH receptor count had a significant association with serum P4 levels.