Abstract

Poor ovarian response (POR) is a barrier to assisted reproductive technology (ART) success because oxidative stress damages granulosa cells. Follicular fluid samples were prospectively collected from 156 poor ovarian response (POR) patients. A retrospective 1:1 matched analysis was subsequently performed on 60 selected patients (30 with astaxanthin use and 30 without), with the aim of evaluating astaxanthin’s impact on reproductive outcomes and exploring its regulatory effects on oxidative stress and cell survival pathway. Patients who received 37.5 mg astaxanthin (Haematococcus pluvialis oil) twice daily for 60–90 days before ovarian stimulation were compared with those who did not. Baseline characteristics and stimulation indices were similar. The astaxanthin group achieved a higher cumulative clinical pregnancy rate (72.0 % vs. 41.7 %, P = 0.032), while oocyte yield, fertilization and embryo quality were comparable. In follicular fluid, astaxanthin supplementation reduced superoxide dismutase and malondialdehyde, increased catalase and showed a trend towards higher glutathione. Granulosa cells from supplemented patients displayed lower reactive oxygen species and apoptosis. Pro‑apoptotic proteins (Bax, caspase‑3, caspase‑9 and cytochrome c) were down‑regulated and anti‑apoptotic Bcl‑2 and mitophagy markers (LC3B, PINK1 and Parkin) were up‑regulated. Astaxanthin supplementation was associated with improved cumulative pregnancy rates in POR patients undergoing ART. The benefit may involve reduced oxidative stress, upregulation of mitophagy-related markers, and inhibition of granulosa-cell apoptosis, supporting its potential as an adjunct therapy for poor ovarian responders.