Differential immunologic response to GnRHa alone vs. dual trigger for final follicular maturation: a proof-of-concept pilot study.

Objective: To explore the impact of GnRH agonist (GnRHa) vs. dual trigger (GnRHa plus hCG) for final follicular maturation on peripheral immune profiles in women undergoing oocyte cryopreservation. Design: Prospective proof-of-concept hypothesis-generating pilot study. Setting: University-affiliated single center. Patients: Five healthy women undergoing fertility preservation ( Interventions: Ovarian stimulation with either GnRHa alone or dual trigger (GnRHa + hCG). Immune profiling was performed at two time points: (1) before trigger, and (2) on the day of oocyte retrieval. Main outcome measures: Percent change (%Δ) in peripheral immune blood T, B, and NK cell populations using flow cytometry. Results: Baseline characteristics were similar. Compared with GnRHa alone, dual trigger was associated with a trend toward lower CD4/CD8 (helper/cytotoxic) T cell ratio, and an apparent increase in highly differentiated cytotoxic (CD57+) cell populations. However, given the small sample size, findings should not be interpreted as definitive but as exploratory trends. There were no cases of OHSS. Conclusions: In this small, exploratory hypothesis-generating study, the addition of hCG to GnRHa trigger was associated with a shift toward a more cytotoxic lymphocyte profile post trigger. Findings require validation in larger, randomized cohorts to better understand their implications for reproductive outcomes and OHSS risk.