Left-sided follicular dominance characterizes advanced ovarian insufficiency: a retrospective cohort study of 2181 stimulation cycles

RESEARCH QUESTION: Does follicular growth under ovarian stimulation show right-left asymmetry in patients with premature ovarian insufficiency (POI) and diminished ovarian reserve (DOR)? DESIGN: Retrospective single-centre cohort study of 1084 women with POI or DOR who underwent ovarian stimulation for IVF between April 2015 and March 2021. Inclusion criteria were POI or DOR diagnosis, intact bilateral ovaries, five or more ovarian stimulation cycles and no history of ovarian surgery or endometriomas. Forty-six women with normal ovarian reserve (61 cycles) served as controls. RESULTS: Asymmetrical follicular growth was observed in 91.6% (241/263) of patients with POI and DOR versus 78.3% (36/46) of controls (P = 0.006), with 6.9% (18/263) showing follicular growth from only one ovary. Asymmetry of 70% or more was more frequent in POI and DOR than controls (40.7% [107/263] versus 13.0% [6/46], P < 0.001), and 100% asymmetry occurred exclusively in POI and DOR. Among patients with 70% or more asymmetry, left-sided and right-sided dominance frequencies were similar: 60/107 (56.1%) and 47/107 (43.9%), respectively. In patients with 100% asymmetry, left-sided dominance was five times more frequent (15/18 [83.3%] versus 3/18 [16.7%], P = 0.0075). In patients with DOR, lower serum anti-Müllerian hormone concentrations were weakly correlated with higher asymmetry (Spearman's ρ = -0.23, P = 0.026). Chromosomal abnormalities were observed more frequently in patients with POI and DOR with 100% asymmetry (3/18 [16.7%]) than in symmetry (0/22 [0%]) and less than 100% asymmetry (8/223 [3.6%]) groups. Patient-level paired analyses revealed comparable oocyte quality (maturation, fertilization, high-quality embryo rates) and clinical pregnancy rates between right- and left-derived oocytes. CONCLUSIONS: Follicular development shows significant right-left asymmetry with left-sided dominance in POI and DOR, although oocyte quality is comparable between ovaries. These findings may inform ovary selection for ovarian tissue cryopreservation in fertility preservation.