MON-141 The Feasibility of Pulsatile Intravenous Follicle Stimulating Hormone to Mitigate Reprometabolic Syndrome in Women with Obesity

Abstract Disclosure: D.R. Siegel: None. K. Kuhn: None. K. Duffy: None. A.P. Bradford: None. N.F. Santoro: Novo Nordisk, scientific advisory board. Background: Women with obesity have subfertility and increased miscarriage risks due to reduced gonadotropin secretion from a suppressed hypothalamic-pituitary-ovarian axis and impaired ovarian response. The relative hypogonadotropic hypogonadism characteristic of obesity has been termed the Reprometabolic Syndrome (RMS) and requires higher doses of exogenous gonadotropins to achieve adequate ovarian stimulation (OS) during fertility treatment. Pre-clinical data indicate that follicle stimulating hormone (FSH) delivered in a pulsatile manner results in superior follicular growth and survival. We have previously shown that a 6-hour infusion of pulsatile intravenous (IV) FSH significantly improved inhibin and estradiol production in women with obesity. This current exploratory proof-of-concept study hypothesizes that pulsatile IV FSH administration via an ambulatory portable pump is feasible and may improve impaired folliculogenesis and luteal function in RMS. Aims: To assess feasibility and effectiveness of ambulatory pulsatile IV FSH administered to women with obesity. Methods: We performed a preliminary crossover interventional study of two reproductive-aged women with BMI > 30 kg/m2. Participants both underwent OS cycles with pulsatile FSH, and one participant then underwent OS with conventional subcutaneous (SQ) FSH dosing. Pulsatile FSH was delivered via a portable infusion pump with q 90-minute boluses calibrated to deliver the same 24-hour dosing as conventional SQ FSH. A GnRH antagonist was given throughout stimulation in both conventional and pulsatile FSH cycles to abolish endogenous gonadotropin production. To verify that a pulsatile pattern of FSH was achieved with the infusion protocol, participants underwent frequent blood sampling every 10 minutes for 4 hours in the mid follicular phase (cycle days 3 and 5). The OS protocol was otherwise carried out in accord with typical clinical practice. Daily urine samples were collected after ovulatory trigger to assess luteal progesterone metabolite secretion. Results: Participants were 28 and 29 years old with BMIs of 35.8 kg/m2 and 36 kg/m2. Pulsatile IV FSH resulted in a 14.37% average increase in serum FSH levels that was maintained from a baseline of 4.5 mIU/mL throughout the frequent blood sampling session to a maximum of 6.3 mIU/mL post bolus. Ovulation criteria (1-2 follicles > 18mm) was achieved in 4-5 days with pulsatile FSH. Each participant had 2 mature follicles with pulsatile FSH and the patient who underwent conventional FSH dosing had 1 mature follicle after 8 days of stimulation. Urinary luteal progesterone evaluation is in progress. Conclusion: This pilot study verifies that a pulsatile pattern of FSH can be achieved with IV infusion and may result in more rapid folliculogenesis. Presentation: Monday, July 14, 2025