Capacitation IVM, Cumulus Cell, PCOS (Polycystic Ovary Syndrome), Transcriptomic Profiling
Conditions
Keywords
In vitro maturation, CAPA-IVM, Cumulus cells, Transcriptomics
Brief summary
Capacitation in vitro maturation (CAPA-IVM) has improved oocyte maturation and resulted in live births. Because cumulus cells (CCs) communicate bidirectionally with the oocyte, their transcriptomic profile may serve as a non-invasive biomarker of oocyte and embryo competence. This prospective pilot study will analyze CCs gene expression after CAPA-IVM using RNA sequencing and pathway analysis, and correlate findings with embryological outcomes including fertilization, day-3 cleavage, and blastocyst formation. Results are expected to provide insights into the molecular basis of oocyte competence and support development of non-invasive embryo selection strategies.
Detailed description
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.
Interventions
None listed
Sponsors
Vrije Universiteit Brussel
Mỹ Đức Hospital
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 38 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of cumulus cell transcriptomic profiles with embryological outcomes | Through study completion, an average of 1 year | Association between cumulus cell gene expression (RNA-seq-based transcriptomic profiles) and embryological outcomes, including cleavage and embryo quality (Day 3), and blastocyst formation and grading (Days 5-6). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of matured oocyte | At day 2 after the Oocyte Pick-Up day | The number of oocytes that have first polar body after denudation |
| Number of normal fertilized oocytes | 16-18 hours after intracytoplasmic sperm injection | Oocytes that show the presence of two pronuclei |
| Number of day-3 embryos | 68 ±1 hours after intra-cytoplasmic sperm injection | Day-3 embryo morphology assessed according to the Istanbul Consensus (2011), with reference to the revised criteria (2024) |
| CCs transcriptomic profiles | Through study completion, an average of 1 year | RNA sequencing of CCs collected from individual COCs after CAPA-IVM. Differential gene expression will be analyzed using DESeq2, followed by Gene Ontology enrichment and Ingenuity Pathway Analysis to identify pathways, molecular functions, and regulatory networks associated with oocyte competence. |
| Number of blastocyst | Day 5 (116 ± 2 hours) and Day 6 (140 ± 2 hours) after intra-cytoplasmic sperm injection | Blastocyst quality assessed on Day 5/6 according to the Istanbul Consensus (2011), with reference to the revised criteria (2024). |
| Number of good-quality blastocyst | Day 5 (116 ± 2 hours) and Day 6 (140 ± 2 hours) after intracytoplasmic sperm injection | Good-quality blastocysts defined and graded according to the Istanbul Consensus (2011), with reference to the revised criteria (2024). |
| Number of frozen embryos | At the time of embryo cryopreservation | Embryos that meet morphology and developmental criteria for cryopreservation by vitrification |
| Number of good-quality day-3 embryos | 68±1 hours after intra-cytoplasmic sperm injection | Day-3 embryo morphology assessed according to the Istanbul Consensus (2011), with reference to the revised criteria (2024) |
Countries
Vietnam
Contacts
Primary ContactHuy H Pham, MSc.
Outcome results
None listed