P-681 LH priming before ovarian stimulation in POSEIDON-4 patients: effects on oocyte recovery and post ICSI/IVF pregnancy rates

Abstract Study question Can a seven-day long LH priming treatment preceding ovarian stimulation (OS) improve follicular responses, oocyte yields and ICSI/IVF outcomes of POSEIDON-4 patients? Summary answer A seven-day long LH priming can substantially increase pregnancy rates through specific benefits in different subgroups of POSEIDON-4 patients. What is known already The combination of advanced maternal age (AMA) with diminished ovarian reserve (DOR) has become one of the most relevant and complex topics in the field of reproductive medicine. AMA/DOR patients appear to be refractory to increased gonadotropin dose and may benefit from strategies specifically capable of increasing the population of FSH-responsive small follicles before the onset of ovarian stimulation (OS). Androgen mediated LH intra-ovarian activity stimulates early follicular development. Pre-treatment with LH has been suggested to improve ICSI/IVF outcomes in normal responders but has not been assessed in AMA/DOR patients, despite the prevalence and relevance of this population. Study design, size, duration Retrospective cohort study from 2022 to 2023, including 235 POSEIDON-4 patients stimulated with FSH+LH in a flexible antagonist protocol with oestradiol pre-treatment (n = 129) or with the same stimulatory treatment preceded by a seven-day LH priming (150 IU/day) combined with GnRH agonist downregulation (n = 106). Follicular responses, oocyte recovery and ICSI/IVF outcomes were compared between treatment-groups in overall POSEIDON-4 patients and in a subgroup of patients with AMH <0.75 ng/mL (n = 77/Control, n = 59/LH priming). Participants/materials, setting, methods All participants were POSEIDON-4 caucasian patients aged 35 to 44 years undergoing a single homologous ICSI/IVF cycle in our clinic. Outcomes in the form of percentages were compared with the Fisher’s exact test, whereas differences in continuous variables were assessed with the Wilcoxon sum rank test. A multivariate analysis was performed to control for the interference of unequal variations in maternal age, AMH, insemination method and presence of male subfertility. Main results and the role of chance Patients in different treatment groups did not differ (p > 0.05) regarding maternal age (39.2±2.5 vs. 39.3±2.5), basal FSH serum concentrations (11.0±4.6 vs. 10.1±4.3) and antral follicle count (6.3±3.0 vs. 6.4±3.3, for patients stimulated with and without LH priming, respectively), but patients treated with LH priming presented slightly lower AMH serum levels (0.56±0.3 vs. 0.63±0.3; p = 0.05). Nevertheless, patients treated with LH priming achieved a twice higher clinical pregnancy rate per cycle (19.8% vs. 9.3%; p = 0.02), accompanied by a 40% reduction in cycle cancellation (32.1% vs. 45.0%; p = 0.03) and increased production of viable embryos (transferred fresh + frozen) per cycle (1.22±1.09 vs. 0.94±1.07; p = 0.02) and per oocyte inseminated (48.3% vs. 38.5%; p = 0.01), but did not differ regarding follicular outputs or oocyte yield. The multivariate analysis indicated a robust association between LH priming and pregnancy achievement, independently of potential confounding variables (OR = 2.52; p = 0.02). A two-fold increase in pregnancy achievement was also observed in severely restricted POSEIDON 4 patients (AMH <0.75 ng/mL) subjected to the LH priming (p = 0.05), which in this case was accompanied by higher oocyte yields per cycle (3.3±2.8 vs. 2.2±2.0; p = 0.04) and per pick (3.9±2.6 vs. 2.3±2.0; p < 0.01). Limitations, reasons for caution This study is limited by its retrospective nature and the data may be potentially influenced by the use of different downregulation strategies in the treatment-groups, even if the literature indicates equivalent performance for these strategies in the population under analysis. Wider implications of the findings The present data strongly suggest that a seven-day LH priming preceding OS can markedly improve ICSI/IVF outcomes of POSEIDON-4 patients, while indicating that this strategy benefits in different ways subgroups of this increasingly prevalent patient category. These findings thus represent new valuable parameters for the progress of ovarian stimulation. Trial registration number NA