Transcriptomic Profiling of Cumulus Cells From CAPA-IVM

Official title

Transcriptomic Profiling of Cumulus Cells From CAPA-IVM Cycles in Women With PCOS: A Prospective Pilot Study

Overview

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.

Primary outcome measures

• Correlation of cumulus cell transcriptomic profiles with embryological outcomes [Time frame: Through study completion, an average of 1 year]

Secondary outcome measures (8)

• CCs transcriptomic profiles [Time frame: Through study completion, an average of 1 year]
• Number of matured oocyte [Time frame: At day 2 after the Oocyte Pick-Up day]
• Number of normal fertilized oocytes [Time frame: 16-18 hours after intracytoplasmic sperm injection]
• Number of day-3 embryos [Time frame: 68 ±1 hours after intra-cytoplasmic sperm injection]
• Number of good-quality day-3 embryos [Time frame: 68±1 hours after intra-cytoplasmic sperm injection]
• Number of blastocyst [Time frame: Day 5 (116 ± 2 hours) and Day 6 (140 ± 2 hours) after intra-cytoplasmic sperm injection]
• Number of good-quality blastocyst [Time frame: Day 5 (116 ± 2 hours) and Day 6 (140 ± 2 hours) after intracytoplasmic sperm injection]
• Number of frozen embryos [Time frame: At the time of embryo cryopreservation]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-only

Study locations

Vietnam · 1 center

• My Duc Hospital — Ho Chi Minh City

Publications

• Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004 Jan;19(1):41-7. doi: 10.1093/humrep/deh098. PMID 14688154
• Working Group on the update of the ESHRE/ALPHA Istanbul Consensus; Coticchio G, Ahlstrom A, Arroyo G, Balaban B, Campbell A, De Los Santos MJ, Ebner T, Gardner DK, Kovacic B, Lundin K, Magli MC, Mcheik S, Morbeck DE, Rienzi L, Sfontouris I, Vermeulen N, Alikani M. The Istanbul consensus update: a revised ESHRE/ALPHA consensus on oocyte and embryo static and dynamic morphological assessmentdagger,d PMID 40288770
• Russell DL, Gilchrist RB, Brown HM, Thompson JG. Bidirectional communication between cumulus cells and the oocyte: Old hands and new players? Theriogenology. 2016 Jul 1;86(1):62-8. doi: 10.1016/j.theriogenology.2016.04.019. Epub 2016 Apr 21. PMID 27160446
• Assou S, Haouzi D, Mahmoud K, Aouacheria A, Guillemin Y, Pantesco V, Reme T, Dechaud H, De Vos J, Hamamah S. A non-invasive test for assessing embryo potential by gene expression profiles of human cumulus cells: a proof of concept study. Mol Hum Reprod. 2008 Dec;14(12):711-9. doi: 10.1093/molehr/gan067. Epub 2008 Nov 21. PMID 19028806
• Gebhardt KM, Feil DK, Dunning KR, Lane M, Russell DL. Human cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer. Fertil Steril. 2011 Jul;96(1):47-52.e2. doi: 10.1016/j.fertnstert.2011.04.033. Epub 2011 May 14. PMID 21575950
• Pham HH, Le AH, Nguyen TC, Ma MPQ, Akin N, Pham TD, Nguyen MHN, Le HL, Huynh BG, Smitz J, Ho TM, Vuong LN. Effect of single versus grouped culture of human cumulus-oocyte complexes in PCOS women treated with biphasic in vitro maturation: A sibling oocyte pilot study. Reprod Med Biol. 2024 Jun 7;23(1):e12587. doi: 10.1002/rmb2.12587. eCollection 2024 Jan-Dec. PMID 38854775
• Akin N, Richani D, Liao X, Zhao Y, Herta AC, Billooye K, Stocker WA, Mottershead DG, Harrison CA, Smitz J, Anckaert E, Gilchrist RB. Effect of cumulin and super-GDF9 in standard and biphasic mouse IVM. J Assist Reprod Genet. 2022 Jan;39(1):127-140. doi: 10.1007/s10815-021-02382-z. Epub 2022 Jan 4. PMID 34984599
• Vuong LN, Ho VNA, Ho TM, Dang VQ, Phung TH, Giang NH, Le AH, Pham TD, Wang R, Smitz J, Gilchrist RB, Norman RJ, Mol BW. In-vitro maturation of oocytes versus conventional IVF in women with infertility and a high antral follicle count: a randomized non-inferiority controlled trial. Hum Reprod. 2020 Nov 1;35(11):2537-2547. doi: 10.1093/humrep/deaa240. PMID 32974672

Identifiers

NCT: NCT07197255 · 09/25/DD-BVMD

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗