Effect of super-growth differentiation factor-9 (GDF9) during capacitation in vitro maturation of oocytes from small antral follicles: an exploratory pilot study

This pilot study determined the effect of adding Super-growth differentiation factor-9 (GDF9) to capacitation in-vitro maturation (CAPA-IVM) culture media on oocyte maturation and blastocyst formation. The study was conducted at an academic infertility center in Vietnam in January–February 2025. Cumulus-oocyte complexes (COCs) were obtained from consenting subfertile women aged 18–35 years who had polycystic ovary syndrome, ≥30 COCs at oocyte pick-up (OPU) in a CAPA-IVM cycle, and were willing to donate ≥10 COCs for research purposes. COCs from sibling human oocytes were treated without (control) or with Super-GDF9 (50 ng/mL) added to CAPA-IVM capacitation and maturation cultures. All metaphase II (MII) oocytes were inseminated using intracytoplasmic sperm injection. The primary endpoint was proportion of blastocysts at end of culture (per patient/per COCs). For per-patient outcomes, only the median [interquartile range] rate of good-quality blastocysts per total blastocysts differed significantly between the Super-GDF9 (0.0 [0.0, 0.0]) and control (83.3 [16.7, 100.0]) groups (effect size [95% confidence interval] –50.0 [–100.0, 0.0]; p=0.02). There were no good-quality blastocysts in the Super-GDF9 group. The rate of blastocysts (per COCs and per day-3 embryos) tended to be lower in the Super-GDF9 group. Adding Super-GDF9 to the current CAPA-IVM protocol did not improve blastocyst formation and showed a trend toward lower blastocyst formation, which requires confirmation in adequately powered studies.