Effect of Super-GDF9 on CAPA-IVM of COCs From Small Antral Follicles

NCT06766604 | Recruiting DMC

• 1 other identifier: 12/24/DD-BVMD
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

CAPA-IVM (In Vitro Maturation) technology is an assisted reproductive method offering significant benefits in terms of safety and treatment costs, particularly for high-risk patients. These include individuals with ovarian hyperstimulation syndrome (OHSS), venous thrombosis, ovarian torsion, or polycystic ovary syndrome (PCOS). However, while the live birth rate in the CAPA-IVM group (35.2%) is comparable to conventional IVF (43.2%), the number of good-quality embryos and cumulative clinical pregnancy rates remain lower. Improving the CAPA-IVM culture process, particularly through the addition of growth factors found in follicular fluid, has shown promise in enhancing oocyte quality. Growth differentiation factor 9 (GDF9) and Bone morphogenetic protein 15 (BMP15) play critical roles in follicular development, with their heterodimer structure demonstrating the most positive effects on cumulus-oocyte complexes (COCs). Recent studies have identified a potent variant, super GDF9, which is \>1000 times more effective than GDF9 and surpasses cumulin, a heterodimeric growth factor. Super GDF9 enhances cumulus cell expansion and oocyte developmental competence, closely mimicking in vivo maturation. This study investigates the impact of supplementing super GDF9 during CAPA-IVM culture, aiming to improve outcomes of cumulus-oocyte complexes (COCs) from small follicles and ultimately enhance treatment success.

Conditions

In Vitro Fertilization

Keywords

CAPA-IVM; super-GDF9; Culture; OSFs; PCOS

Outcome Measures

Primary Outcomes (1)

• Maturation rate per COC

  Number of MII / COCs

  Two days after oocyte retrieval

Secondary Outcomes (39)

• Maturation rate per patient

  Two days after oocyte retrieval

• Degeneration rate per COC

  16-18 hours after Intra-cytoplasmic sperm injection

• Degeneration rate per MII

  16-18 hours after Intra-cytoplasmic sperm injection

• Degeneration rate per patient

  16-18 hours after Intra-cytoplasmic sperm injection

• t2PN

  16-18 hours after Intra-cytoplasmic sperm injection

Study Arms (2)

Super-GDF9 supplementation during CAPA-IVM

EXPERIMENTAL

Group 1: donated COCs will be cultured in the CAPA step and the IVM step, with the addition of Super-GDF9 during CAPA-IVM.

Other: Super-GDF9 supplementation during CAPA-IVM

Conventional CAPA-IVM

ACTIVE COMPARATOR

Group 2: The subject's remaining COCs will be cultured in the CAPA step and the IVM step without the addition of Super-GDF9 during CAPA-IVM.

Other: Conventional CAPA-IVM

Interventions

Super-GDF9 supplementation during CAPA-IVM OTHER

Group 1: donated COCs will be exposed to Super-GDF9 at 50 ng/ml in both the CAPACITATION and MATURATION culture steps.

Super-GDF9 supplementation during CAPA-IVM

Conventional CAPA-IVM OTHER

Group 2: The subject's remaining COCs will be cultured in the CAPA step and the IVM step without the addition of Super-GDF9 during CAPA-IVM.

Conventional CAPA-IVM

Eligibility Criteria

• Age: 18 Years - 38 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women between the ages of 18 and 38 years (both inclusive)
• BMI ≤ 32 kg/m2
• PCOS women according to the Rotterdam criteria (2003)
• Indicating CAPA-IVM treatment.
• Serum AMH ≥ 4 ng/mL (28.57 pmol/L) at screening and having at least 24 antral follicles in two ovaries by transvaginal ultrasound at the time of CAPA-IVM indication
• Willing to donate COCs for research purposes
• Agreeing for frozen embryo
• Signed informed consent before any study-related procedures

You may not qualify if:

• Known endometrioma or grade 3-4 endometriosis according to ASRM classification
• Uterine abnormalities
• Couples with severe male factor (sperm concentration \<5 million/ml, motility \< 10%), surgical sperm retrieval.
• Previous history of unexplained immature oocytes after IVF treatment
• Cycles using donor oocytes

Sponsors & Collaborators

• Mỹ Đức Hospital: lead
• Vrije Universiteit Brussel: collaborator

Study Sites (1)

My Duc Hospital

Ho Chi Minh City, Vietnam

RECRUITING

Related Publications (13)

• Practice Committees of the American Society for Reproductive Medicine, the Society of Reproductive Biologists and Technologists, and the Society for Assisted Reproductive Technology. Electronic address: jgoldstein@asrm.org. In vitro maturation: a committee opinion. Fertil Steril. 2021 Feb;115(2):298-304. doi: 10.1016/j.fertnstert.2020.11.018. Epub 2020 Dec 24.

  PMID: 33358333 BACKGROUND

• 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 BACKGROUND

• Gilchrist RB, Ho TM, De Vos M, Sanchez F, Romero S, Ledger WL, Anckaert E, Vuong LN, Smitz J. A fresh start for IVM: capacitating the oocyte for development using pre-IVM. Hum Reprod Update. 2024 Jan 3;30(1):3-25. doi: 10.1093/humupd/dmad023.

  PMID: 37639630 BACKGROUND

• Herta AC, von Mengden L, Akin N, Billooye K, Coucke W, van Leersum J, Cava-Cami B, Saucedo-Cuevas L, Klamt F, Smitz J, Anckaert E. Characterization of carbohydrate metabolism in in vivo- and in vitro-grown and matured mouse antral folliclesdagger. Biol Reprod. 2022 Oct 11;107(4):998-1013. doi: 10.1093/biolre/ioac124.

  PMID: 35717588 BACKGROUND

• Stocker WA, Walton KL, Richani D, Chan KL, Beilby KH, Finger BJ, Green MP, Gilchrist RB, Harrison CA. A variant of human growth differentiation factor-9 that improves oocyte developmental competence. J Biol Chem. 2020 Jun 5;295(23):7981-7991. doi: 10.1074/jbc.RA120.013050. Epub 2020 Apr 29.

  PMID: 32350111 BACKGROUND

• Akin N, Ates G, von Mengden L, Herta AC, Meriggioli C, Billooye K, Stocker WA, Ghesquiere B, Harrison CA, Cools W, Klamt F, Massie A, Smitz J, Anckaert E. Effects of lactate, super-GDF9, and low oxygen tension during bi-phasic in vitro maturation on the bioenergetic profiles of mouse cumulus-oocyte complexdagger. Biol Reprod. 2023 Oct 13;109(4):432-449. doi: 10.1093/biolre/ioad085.

  PMID: 37531262 BACKGROUND

• Krisher RL, Bavister BD. Enhanced glycolysis after maturation of bovine oocytes in vitro is associated with increased developmental competence. Mol Reprod Dev. 1999 May;53(1):19-26. doi: 10.1002/(SICI)1098-2795(199905)53:13.0.CO;2-U.

  PMID: 10230813 BACKGROUND

• Ortmann B, Druker J, Rocha S. Cell cycle progression in response to oxygen levels. Cell Mol Life Sci. 2014 Sep;71(18):3569-82. doi: 10.1007/s00018-014-1645-9. Epub 2014 May 25.

  PMID: 24858415 BACKGROUND

• Mottershead DG, Sugimura S, Al-Musawi SL, Li JJ, Richani D, White MA, Martin GA, Trotta AP, Ritter LJ, Shi J, Mueller TD, Harrison CA, Gilchrist RB. Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-beta Family, Is a Potent Activator of Granulosa Cells and Improves Oocyte Quality. J Biol Chem. 2015 Sep 25;290(39):24007-20. doi: 10.1074/jbc.M115.671487. Epub 2015 Aug 8.

  PMID: 26254468 BACKGROUND

• 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 BACKGROUND

• Practice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility: a committee opinion. Fertil Steril. 2012 Sep;98(3):591-8. doi: 10.1016/j.fertnstert.2012.05.031. Epub 2012 Jun 15.

  PMID: 22704630 BACKGROUND

• Saenz-de-Juano MD, Ivanova E, Romero S, Lolicato F, Sanchez F, Van Ranst H, Krueger F, Segonds-Pichon A, De Vos M, Andrews S, Smitz J, Kelsey G, Anckaert E. DNA methylation and mRNA expression of imprinted genes in blastocysts derived from an improved in vitro maturation method for oocytes from small antral follicles in polycystic ovary syndrome patients. Hum Reprod. 2019 Sep 29;34(9):1640-1649. doi: 10.1093/humrep/dez121.

  PMID: 31398248 BACKGROUND

• Vuong LN, Nguyen MHN, Nguyen NA, Ly TT, Tran VTT, Nguyen NT, Hoang HLT, Le XTH, Pham TD, Smitz JEJ, Mol BW, Norman RJ, Ho TM. Development of children born from IVM versus IVF: 2-year follow-up of a randomized controlled trial. Hum Reprod. 2022 Jul 30;37(8):1871-1879. doi: 10.1093/humrep/deac115.

  PMID: 35595193 BACKGROUND

Study Officials

• Lan N Vuong

  University of Medicine and Pharmacy at Ho Chi Minh City

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kha T Huynh

CONTACT

+84946699470; kha.ht@myduchospital.vn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Sibling oocytes

Study Record Dates

• First Submitted: December 24, 2024
• First Posted: January 9, 2025
• Study Start: January 10, 2025
• Primary Completion: February 17, 2025
• Study Completion: April 30, 2026
• Last Updated: July 10, 2025

Record last verified: 2025-07

Locations

VN (1)