Transcriptomic Profiling of Cumulus Cells From CAPA-IVM

In vitro maturation (IVM) is an alternative to conventional ovarian stimulation, particularly for women with polycystic ovary syndrome (PCOS) or at risk of ovarian hyperstimulation syndrome (OHSS). A novel technique, known as capacitation IVM (CAPA-IVM), introduces a pre-maturation step that improves both nuclear and cytoplasmic maturation and has been associated with live births. Cumulus-oocyte complexes (COCs) represent the functional unit of oocyte competence, with cumulus cells (CCs) providing bidirectional signaling that regulates oocyte development. Because CCs are routinely removed during ICSI, they serve as a readily accessible and non-invasive source of information about oocyte and embryo potential.

This prospective observational cohort study will be conducted at the IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam. Eligible participants are women diagnosed with PCOS according to the Rotterdam 2003 criteria, with serum AMH ≥ 4 ng/mL and antral follicle count (AFC) ≥ 24, indicated for CAPA-IVM treatment. From each participant, 15 COCs will be allocated to single-culture CAPA-IVM condition. CCs from each COC will be collected for transcriptomic analysis, while the oocytes are assessed for embryological outcomes. The remaining COCs will follow the standard CAPA-IVM protocol at the center.

RNA sequencing will be performed using low-input protocols. Data will undergo differential expression analysis (DESeq2), and functional interpretation using Gene Ontology and Ingenuity Pathway Analysis. Laboratory outcomes including day-3 cleavage, and blastocyst formation will be correlated with CC transcriptomic profiles. This study aims to identify non-invasive biomarkers of oocyte and embryo competence, supporting future embryo selection strategies in assisted reproduction. By correlating cumulus cell transcriptomic profiles with oocyte and embryo outcomes, this study seeks to establish preliminary non-invasive biomarkers for embryo selection in assisted reproduction.

Inclusion criteria

• Women 18-38 years
• BMI =< 32kg/m2
• Diagnosed with polycystic ovary syndrome (PCOS) according to the Rotterdam 2003 criteria, meet at least 2 of the following 3 features: (1) Oligo-ovulation or anovulation. (2) Clinical and/or biochemical signs of hyperandrogenism (3) Polycystic ovarian morphology on ultrasound.
• Indicated for CAPA-IVM treatment.
• Serum AMH ≥ 4 ng/mL (28.57 pmol/L).
• Antral follicle count (AFC) ≥ 24 follicles in both ovaries at the time of CAPA-IVM indication.
• Signed informed consent to participate in the study.

Exclusion criteria

• Retrieved sperm from surgical procedures
• Previous IVF cycle with total immature oocytes