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AzTrials

In Vitro FertilizationsGDF-9NCT06766604

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

A study testing Super-GDF9 supplementation during CAPA-IVM and Conventional CAPA-IVM in people with In Vitro Fertilization, run by Mỹ Đức Hospital at 1 site in Vietnam.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 38 years, women only
Conditions the study is for
In Vitro Fertilization
What is being tested?
Super-GDF9 supplementation during CAPA-IVM and Conventional CAPA-IVM
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteVietnam
Study dates
10 Jan 2025to 30 Apr 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 38 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Kha T Huynh contact

+84946699470

kha.ht@myduchospital.vn

Vietnam1 site, 1 recruiting

  • My Duc Hospital

    Ho Chi Minh City

    Tuong M Ho, MSc, MD, +84 90 3633377, tuongho.ivfmd@gmail.com

    Recruiting

Other trials in Vietnam

About this study

Official title: Exploratory In-vitro Study Evaluating the Addition of Super-GDF9 During Capacitation-in-vitro Maturation (CAPA-IVM) of Donated Human Cumulus-oocyte Complexes (COCs) Derived From Small Antral Follicles

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.

Read the detailed description

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) - who typically present with a high number of antral follicles (constituting nearly 15% of all patients). Although the live birth rate following the first transfer in the CAPA-IVM group is 35.2%, which is not statistically different from the conventional IVF group at 43.2% (risk difference: -8.1%; 95% confidence interval: -16.6% to 0.5%), the number of good-quality embryos per cycle and the cumulative clinical pregnancy rate remain lower than in conventional IVF. Therefore, improving the CAPA-IVM culture process to achieve the optimal number and quality of oocytes is essential.

Concurrently, adding growth factors commonly found in follicular fluid to the culture medium represents a remarkable advancement in improving oocyte quality in CAPA-IVM. Some somatic compartments, such as expansion, metabolism, and apoptosis, are regulated by soluble growth factors, known as oocyte secretion factors (OSFs). Two OSFs, Growth differentiation factor 9 (GDF9) and Bone morphogenetic protein 15 (BMP15), have been identified as critical for follicular development and fertility in various species such as mice, sheep, and humans. During IVM culture, both the immature and mature forms of these factors as well as their homo- and heterodimer structures have been tested. Notably, the heterodimer structure has shown the most positive effects on cumulus-oocyte complexes (COCs) during IVM culture.

Although both growth factors exist in homodimeric forms, recent studies have found that the GDF9 and BMP15 heterodimer can also form a more potent growth factor called cumulin. BMP15 activates latent GDF9 in cumulin, leading to strong signaling in granulosa cells via type I receptors (ALK4/5) and SMAD2/3 transcription factors. Biomedically engineered cumulin has been proposed to noticeably improve embryo outcomes in mouse and porcine models. Recently, a modified version of wild-type GDF9, called super GDF9, has been demonstrated to be >1000 times more potent than GDF9 and 4 times more activity than cumulin in SMAD2/3-responsive transcriptional assays in granulosa cells. Previous research has illustrated that adding super GDF9 to CAPA-IVM media in mice induces gene expression in the ovulatory cascade during CAPA-IVM maturation that closely resembles in vivo maturation. Super GDF9 effectively promotes cumulus cell expansion and enhances oocyte developmental competence in vitro. Hence, super GDF9 can potentially replace cumulin, which faces challenges in production and purification.

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.

This study will recruit 300 COCs (an estimated 10 needed patients). 100 COCs will be allocated to the research arm (sGDF-9), while 200 COCs will be allocated to the control arm.

  • Screening for eligibility
  • This study will be conducted at My Duc Hospital, Ho Chi Minh City, Vietnam.
  • Women who are potentially eligible will be provided information about the study at the time of IVM treatment indication.
  • Screening for eligibility will be performed on the day of the first visit when the IVM treatment is indicated.
  • Patients will be provided information about the study and informed consent documents. The investigators will obtain signed informed consent forms from all women before enrollment.
  • Eligible women will be scheduled to undergo oocyte pick-up procedures within 1-7 days from informed consent.
  • Oocytes retrieval The oocyte pick-up procedure will be conducted according to the center's standard practices for CAPA-IVM cycles.

Cumulus-oocyte complexes (COCs) from small follicles after OPU will be divided into 2 groups:

  • Group 1 (sGDF-9): donated COCs will be cultured in the CAPA and IVM steps, adding 50ng/ml Super-GDF9 during both steps in CAPA-IVM
  • Group 2 (Control): The subject's remaining COCs will be cultured in the CAPA and IVM steps without adding Super-GDF9 during CAPA-IVM.

Groups 1 and 2: Collecting after the capacitation step: spent media and blank wells. Collecting after the maturation step: spent media, cumulus cell, and blank wells.

+ CAPA and Maturation culture: CAPA and Maturation culture will be performed routinely following current laboratory protocols. ICSI will be used to fertilize mature oocytes.

Being tested
Super-GDF9 supplementation during CAPA-IVM, Conventional CAPA-IVM
Keywords
CAPA-IVM, super-GDF9, Culture, OSFs, PCOS

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Super-GDF9 supplementation during CAPA-IVMOther

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

  • Conventional CAPA-IVMOther

    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.

Study groups in NCT06766604
Study groupRoleWhat they receive
Super-GDF9 supplementation during CAPA-IVMExperimentalGroup 1: donated COCs will be cultured in the CAPA step and the IVM step, with the addition of Super-GDF9 during CAPA-IVM.
Receives: Other: Super-GDF9 supplementation during CAPA-IVM
Conventional CAPA-IVMActive comparatorGroup 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.
Receives: Other: Conventional CAPA-IVM

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maturation rate per COC

    Number of MII / COCs

    Measured: Two days after oocyte retrieval

Secondary outcomes (39)

  1. Maturation rate per patient

    Number of MII / patient

    Measured: Two days after oocyte retrieval

  2. Degeneration rate per COC

    Number of degenerated oocytes after IVM / COCs

    Measured: 16-18 hours after Intra-cytoplasmic sperm injection

  3. Degeneration rate per MII

    Number of degenerated oocytes after IVM / MII

    Measured: 16-18 hours after Intra-cytoplasmic sperm injection

  4. Degeneration rate per patient

    Number of degenerated oocytes after IVM / patients

    Measured: 16-18 hours after Intra-cytoplasmic sperm injection

  5. t2PN

    Time of two pronuclei appearance

    Measured: 16-18 hours after Intra-cytoplasmic sperm injection

  6. Fertilization rate per COC

    Number of fertilized oocytes / COCs

    Measured: 16-18 hours after Intra-cytoplasmic sperm injection

  7. Fertilization rate per MII

    Number of fertilized oocytes / MII

    Measured: 16-18 hours after Intra-cytoplasmic sperm injection

  8. Fertilization rate per patient

    Number of fertilized oocytes / patients

    Measured: 16-18 hours after Intra-cytoplasmic sperm injection

  9. Abnormal fertilization rate per COC

    The percentage of zygotes with 1,3, or more than 3 pronuclei after Intra-cytoplasmic sperm injection / COCs

    Measured: 16-18 hours after Intra-cytoplasmic sperm injection

  10. Abnormal fertilization rate per MII

    The percentage of zygotes with 1,3, or more than 3 pronuclei after Intra-cytoplasmic sperm injection / MII

    Measured: 16-18 hours after Intra-cytoplasmic sperm injection

  11. Abnormal fertilization rate per patient

    The percentage of zygotes with 1,3, or more than 3 pronuclei after Intra-cytoplasmic sperm injection / patients

    Measured: 16-18 hours after Intra-cytoplasmic sperm injection

  12. tPNf

    Time of pronuclei fading

    Measured: 23-25 hours after Intra-cytoplasmic sperm injection

  13. t2

    First time frame at which an embryo reaches 2-cell stage blastomeres

    Measured: 25-27 hours after Intra-cytoplasmic sperm injection

  14. t3

    First time frame at which an embryo reaches 3-cell stage blastomeres

    Measured: 25-42 hours after Intra-cytoplasmic sperm injection

  15. t4

    First time frame at which an embryo reaches 4-cell stage blastomeres

    Measured: 42-44 hours after Intra-cytoplasmic sperm injection

  16. t5

    First time frame at which an embryo reaches 5-cell stage blastomeres

    Measured: 44-67 hours after Intra-cytoplasmic sperm injection

  17. t8

    First time frame at which an embryo reaches 8-cell stage blastomeres

    Measured: 67-69 hours after Intra-cytoplasmic sperm injection

  18. tSC

    First evidence of compaction

    Measured: During day 3 after intracytoplasmic sperm injection (beginning of the compaction of blastomeres)

  19. Day-3 embryo rate per COC

    Counting the number of patients with Day-3 embryo/COCs

    Measured: Five days after oocyte retrieval

  20. Day-3 embryo rate per MII

    Counting the number of patients with Day-3 embryo/ MII

    Measured: Three days after Intra-cytoplasmic sperm injection

  21. Day-3 embryo rate per patient

    Counting the number of patients with Day-3 embryo / patients

    Measured: Three days after Intra-cytoplasmic sperm injection

  22. Good quality Day-3 embryos per COC

    Number of grade 1 and grade 2 Day-3 embryos / COCs

    Measured: Three days after Intra-cytoplasmic sperm injection

  23. Good quality Day-3 embryos per MII

    Number of grade 1 and grade 2 Day-3 embryos / MII

    Measured: Three days after Intra-cytoplasmic sperm injection

  24. Good quality Day-3 embryos per patient

    Number of grade 1 and grade 2 Day-3 embryos / patients

    Measured: Three days after Intra-cytoplasmic sperm injection

  25. tM

    Time of completion of compaction process

    Measured: During day 4 after Intra-cytoplasmic sperm injection

  26. tSB

    Initiation of blastulation

    Measured: During day 4 after Intra-cytoplasmic sperm injection (in which the blastocoel is visible)

  27. tB

    Full blastocyst

    Measured: During day 4 after Intra-cytoplasmic sperm injection (before zona starts to thin)

  28. Blastocyst rate per COC (day 5 or 6 embryo)

    Counting the number of patients with Day-5 or Day-6 embryo/COCs

    Measured: Five or six days after Intra-cytoplasmic sperm injection

  29. Blastocyst rate per MII

    Counting the number of patients with Day-5 or Day-6 embryo/MII

    Measured: Five or six days after Intra-cytoplasmic sperm injection

  30. Blastocyst rate per patient

    Counting the number of patients with Day-5 or Day-6 embryo/patient

    Measured: Five or six days after Intra-cytoplasmic sperm injection

  31. Good quality blastocysts per COC

    Number of grade 1 and grade 2 blastocysts / COCs

    Measured: Five or six days after Intra-cytoplasmic sperm injection

  32. Good quality blastocysts per MII

    Number of grade 1 and grade 2 blastocysts / MII

    Measured: Five or six days after Intra-cytoplasmic sperm injection

  33. Good quality blastocysts per patient

    Number of grade 1 and grade 2 blastocysts / patients

    Measured: Five or six days after Intra-cytoplasmic sperm injection

  34. Frozen blastocysts rate per COC

    Counting the number of frozen blastocysts/ COCs

    Measured: Five or six days after Intra-cytoplasmic sperm injection

  35. Frozen blastocysts rate per MII

    Counting the number of frozen blastocysts/ MII

    Measured: Five or six days after Intra-cytoplasmic sperm injection

  36. Frozen blastocysts rate per patient

    Counting the number of frozen blastocysts/ patient

    Measured: Five or six days after Intra-cytoplasmic sperm injection

  37. The relative expression ratio (R) of human cumulus cell genes

    Cumulus cells will be collected, cDNA synthesis after mRNA purification, relative quantification PCR for detecting gene expression (results potentially reported separately)

    Measured: Cumulus cells will be collected and frozen within 30-50 minutes after oocyte denudation, stored at -80oC until RNA purification

  38. Rates of Blastocysts by Chromosomal Status in PGT

    PGT will be performed to classify blastocysts as euploid, aneuploid or mosaic (results potentially reported separately)

    Measured: After study completion, an average of 1 year.

  39. Epigenetic Evaluation

    Epigenetic evaluation of blastocysts will be performed by post-bisulfite adaptor tagging (PBAT), and the average DNA-methylation (%) at imprinted germline differentially methylated regions (gDMRs) will be calculated (results potentially reported separately)

    Measured: After study completion, an average of 1 year.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jan 2025
  2. Study start10 Jan 2025
  3. Primary completion17 Feb 2025
  4. Study completion30 Apr 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Sibling oocytes
Masking
None (open label)
Enrolment
9 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06766604
Sponsor's protocol ID
12/24/DD-BVMD
Acronym
sGDF-9
Status last verified
Jul 2025
First submitted
24 Dec 2024
Last updated
10 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 33358333

  • 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.

    PubMed 32974672

  • 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.

    PubMed 37639630

  • 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.

    PubMed 35717588

  • 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.

    PubMed 32350111

  • 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.

    PubMed 37531262

  • 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.

    PubMed 10230813

  • 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.

    PubMed 24858415

  • 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.

    PubMed 26254468

  • 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.

    PubMed 14688154

  • Endometriosis and infertility: a committee opinion (2012). [cited 2024 Oct 28]. Available from: https://www.asrm.org/practice-guidance/practice-committee-documents/endometriosis-and-infertility-a-committee-opinion-2012

  • A variant of human growth differentiation factor-9 that improves oocyte developmental competence - ScienceDirect [Internet]. [cited 2024 Oct 13]. Available from: https://www.sciencedirect.com/science/article/pii/S0021925817494373

  • 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.

    PubMed 31398248

  • 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.

    PubMed 35595193

Questions about this trial

What is this clinical trial studying?

A study testing Super-GDF9 supplementation during CAPA-IVM and Conventional CAPA-IVM in people with In Vitro Fertilization, run by Mỹ Đức Hospital at 1 site in Vietnam.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kha T Huynh (+84946699470, kha.ht@myduchospital.vn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maturation rate per COC (time frame: Two days after oocyte retrieval). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06766604, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2025.

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