P-627 Premature Progesterone increase during the luteal phase was not associated with the Follicular Output Rate (FORT)

Abstract Study question Is premature follicular progesterone increase associated with the Follicular Output Rate (FORT) during controlled ovarian stimulation for IVF? Summary answer Premature progesterone increase during controlled ovarian stimulation was unrelated to follicular response but linked to granulosa cell hypersensitivity and hyperresponse to exogenous gonadotropins. What is known already Premature progesterone elevation during the follicular phase in IVF cycles was associated with endometrial-embryonic asynchrony and, consequently, a decrease in pregnancy rates. Several protocols recommend the freeze-all strategy or hormonal (progesterone) monitoring during the late follicular phase. Some studies have linked this premature progesterone increase to hyper-responders after exogenous gonadotropin stimulation. Therefore, age, higher antral follicle count, and anti-Müllerian hormone (AMH) may help predict this condition. However, the literature lacks information on the intrinsic response to exogenous gonadotropins, as measured by FORT, and its relationship with premature progesterone elevation in the late follicular phase. Study design, size, duration We conducted a prospective cohort study at an infertility clinic, including patients undergoing IVF cycles in 2023–2024. Serum hormone levels (luteinizing hormone, estradiol, and progesterone) were measured on the human chorionic gonadotropin (hCG) trigger day and analyzed in relation to various reproductive outcomes. Participants/materials, setting, methods We included 269 patients (23–44 years). Premature progesterone increase (>1.5 ng/mL on hCG trigger day) was analyzed in two groups based on serum progesterone levels: higher (n = 216) and lower (n = 53). All patients underwent the same controlled ovarian stimulation protocol with recombinant FSH and a fixed GnRH antagonist. FORT was calculated as the ratio of the preovulatory follicle count on the hCG trigger day × 100 to the antral follicle count (AFC). Main results and the role of chance Comparing both groups, they were equivalent in infertility aetiology and BMI (P > 0.05). However, age (36.7±4.6 vs. 34.8±3.8 years), AMH (1.72±1.6 vs. 3.88±3.2 ng/mL), antral follicle count (8.6±5.4 vs. 14.0±5.2), number of collected oocytes (7±5 vs. 12±8), serum oestradiol (2,283±2,122 vs. 5,034±4,884 pg/mL), and LH levels (3.5±3.4 vs. 2.0±2.4 mIU/mL) significantly differed between the lower and higher progesterone groups, respectively (P < 0.001). Moreover, in multivariable linear regression analysis, serum progesterone levels were considered the dependent variable. After adjusting for multiple confounders, only serum oestradiol remained significantly associated with premature progesterone elevation (P < 0.001). Additionally, logistic regression analysis demonstrated that serum LH levels were negatively and AMH levels positively associated with premature progesterone secretion. Furthermore, FORT did not differ between the lower (38%) and higher (41%) progesterone groups, and multivariable analysis failed to demonstrate any association between FORT and progesterone secretion (P > 0.05). Limitations, reasons for caution The main limitation is the cohort design of our study, which has an inherent risk of bias (selection bias). Moreover, we utilised a single-centre analysis, which could limit our external validation. The progesterone threshold (1.5) could also be discussed and analysed cautiously. Wider implications of the findings This is the first study analyzing FORT as a marker of ovarian response and premature progesterone rise. Results confirm that granulosa cells are the primary progesterone source in the late luteal phase of GnRH antagonist cycles, with this phenomenon being more common in hyper-responders. Trial registration number No