IVMNCT06087354
Low vs. Air Oxygen Concentration CAPA-IVM Culture of Cumulus-oocyte Complexes
A study testing The way of Cumulus-oocyte complexes (COC) CAPA-IVM culture condition in people with IVM and PCOS (Polycystic Ovary Syndrome), run by Mỹ Đức Hospital at 1 site in Vietnam.
Trial summary
IVM with a pre-maturation step, known as capacitation IVM (CAPA-IVM), has demonstrated enhanced maturation of human oocytes in vitro and successful live births. However, CAPA-IVM has shown lower rates of embryo formation when compared to conventional in vitro fertilization/ intra cytoplasmic sperm injection (IVF/ICSI)… Read more about this study
- Who is it for?
- Ages 18 to 37 years, women only
- Conditions the study is for
- IVM, PCOS (Polycystic Ovary Syndrome)
- What is being tested?
- The way of Cumulus-oocyte complexes (COC) CAPA-IVM culture condition
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteVietnam
- Study dates
- 9 Nov 2023to 22 May 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 37 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- ≤38 years
- Having polycystic ovarian morphology: at least 25 follicles (2-9 mm) throughout the whole ovary and/or increased ovarian volume (>10ml)
- Having at least 20 follicles on the Oocyte Pick-up day
- Patients consent to culture embryos to the blastocyst
Who cannot join
- Cases with severe male factor (concentration <5 million/ml, cryptozoospermia, azoospermia)
- Oocyte donation
- Pre-implantation genetic testing
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Low Versus Air Oxygen Concentration in In-vitro Maturation With Biphasic Capacitation-IVM (CAPA-IVM) Culture of Human Cumulus-oocyte Complexes in PCOS Patients: a Sibling Oocyte Pilot Study
IVM with a pre-maturation step, known as capacitation IVM (CAPA-IVM), has demonstrated enhanced maturation of human oocytes in vitro and successful live births. However, CAPA-IVM has shown lower rates of embryo formation when compared to conventional in vitro fertilization/ intra cytoplasmic sperm injection (IVF/ICSI) cycles. To optimize the CAPA-IVM culture system, this pilot study aims to evaluate the impact of low oxygen versus air oxygen concentrations on embryological outcomes in PCOS patients.
Read the detailed description
Oocyte in vitro maturation (IVM) is an alternative approach to assisted reproductive technology (ART) that has the advantage of minimal stimulation, resulting in reduced hormone-related side effects and risks, especially in women with polycystic ovary syndrome (PCOS). Oocytes retrieved for IVM procedures are derived from a diverse pool of follicles with an average diameter of between 2 and 10mm and are characterized by variable cellular and molecular attributes that indicate their immature status. Therefore, the development of an IVM culture system that could enable and enhance the acquisition and synchronization of meiotic and developmental competence prior to the meiotic resumption is essential for optimizing human IVM protocols.
IVM with a pre-maturation step, known as capacitation IVM (CAPA-IVM), has been shown to improve the competence of human oocytes matured in vitro and result in live births. The pre-maturation culture of CAPA-IVM utilizes C-type natriuretic peptide (CNP), and maturation takes place in the presence of amphiregulin (AREG), both of which are physiological compounds that have been shown to prevent spontaneous meiotic resumption of oocytes (CNP) and enhance oocyte competence (AREG) during IVM.
To date, the results of pilot studies have shown that CAPA-IVM increases the rates of oocyte maturation, good-quality embryos on day 3 and good-quality blastocysts, resulting in a result, a higher embryo yield was obtained compared with standard IVM. Additionally, the reported cumulative live birth rate after use of CAPA-IVM, and its non-inferiority to the cumulative live birth rate with standard in vitro fertilization highlight the clinical utility and potential of this approach. Improvements in the culture system could make CAPA-IVM more effective, but these need to be investigated.
The oxygen concentration during the IVM process plays a crucial role in oocyte maturation. The use of oxygen concentrations higher than physiological levels can lead to cell damage and affect embryo development. Recent studies in mice have suggested using lower oxygen concentrations to improve IVM outcomes. However, the effectiveness of using lower oxygen concentrations in human IVM remains unproven. Therefore, this pilot study aims to compare the effectiveness of lower oxygen concentration conditions versus air oxygen in CAPA-IVM on embryology outcomes in PCOS women.
- Conditions
- IVM, PCOS (Polycystic Ovary Syndrome)
- Being tested
- The way of Cumulus-oocyte complexes (COC) CAPA-IVM culture condition
- Keywords
- Low oxygen, CAPA-IVM, Cumulus-oocyte complexes
- Medical subject headings
- Polycystic Ovary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The way of Cumulus-oocyte complexes (COC) CAPA-IVM culture conditionOther
Cumulus-oocyte complexes (COC) will be cultured in CAPA-IVM 24 hrs capacitation followed by 30h maturation. The first group will be cultured in low oxygen concentration (5%Oxygen), 6% carbon dioxide at 37 degree. The second group will be cultured in air oxygen concentration (20%Oxygen), 6% carbon dioxide at 37 degree.
| Study group | Role | What they receive |
|---|---|---|
| Low Oxygen Concentration CAPA-IVM culture | Experimental | Half of COCs were cultured in the CAPA step and IVM step in a low oxygen concentration (5%) and 6% carbon dioxide at 37 degree Receives: Other: The way of Cumulus-oocyte complexes (COC) CAPA-IVM culture condition |
| Air Oxygen Concentration CAPA-IVM culture | Experimental | Half of COCs were cultured in the CAPA step and IVM step in a air oxygen concentration (20%) and 6% carbon dioxide at 37 degree Receives: Other: The way of Cumulus-oocyte complexes (COC) CAPA-IVM culture condition |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of blastocyst
Number of blastocyst obtained
Measured: At least 5 days after intra-cytoplasmic sperm injection
Secondary outcomes (12)
Number of matured oocytes
Number of oocytes which have a polar body after maturation
Measured: Two days after oocytes pick-up
Number of normal fertilized oocytes
Number of oocytes which have 2 pronuclear
Measured: 16-18 hours after intra-cytoplasmic sperm injection
Number of day-3 embryos
Number of day-3 embryos obtained
Measured: At least 3 days after intra-cytoplasmic sperm injection
Number of good-quality day-3 embryos
Number of good quality Day 3 embryos obtained
Measured: At least 3 days after intra-cytoplasmic sperm injection
Number of good-quality blastocyst
Number of good quality blastocyst obtained
Measured: At least 5 days after intra-cytoplasmic sperm injection
Number of vitrified blastocyst
Number of vitrified blastocyst obtained
Measured: At least 5 days after intra-cytoplasmic sperm injection
Positive pregnancy test
Serum human chorionic gonadotropin level greater than 25 mIU/mL
Measured: At 2 weeks after the completion of the first frozen embryo transfer
Clinical pregnancy
At least one gestational sac on ultrasound at 7 weeks' gestation with the detection of heart beat activity
Measured: 5 weeks after embryo placement after the completion of the first transfer
Ongoing pregnancy
Defined as pregnancy with detectable heart rate at 12 weeks' gestation or beyond, after the completion of the first transfer
Measured: At 12 weeks' gestation
Implantation rate
Defined as the number of gestational sacs per number of embryos transferred
Measured: 3 weeks after embryo transferred after the completion of the first transfer
Multiple pregnancy
Defined as presence of more than one sac at early pregnancy ultrasound (6-8 weeks gestation)
Measured: 5 weeks after embryo placement after the completion of the first transfer
Miscarriage
pregnancy loss at <12 weeks
Measured: at 12 weeks of gestation after the completion of the first transfer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2023
- Study start9 Nov 2023
- Primary completion30 Jan 2024
- Study completion22 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for IVMStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mỹ Đức Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tuong M Ho, Principal investigator, Mỹ Đức Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06087354
- Sponsor's protocol ID
- 11/23/DD-BVMD
- Status last verified
- Oct 2023
- First submitted
- 12 Oct 2023
- Last updated
- 3 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sanchez F, Le AH, Ho VNA, Romero S, Van Ranst H, De Vos M, Gilchrist RB, Ho TM, Vuong LN, Smitz J. Biphasic in vitro maturation (CAPA-IVM) specifically improves the developmental capacity of oocytes from small antral follicles. J Assist Reprod Genet. 2019 Oct;36(10):2135-2144. doi: 10.1007/s10815-019-01551-5. Epub 2019 Aug 9.
PubMed 31399916Vuong 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 32974672Vuong LN, Le AH, Ho VNA, Pham TD, Sanchez F, Romero S, De Vos M, Ho TM, Gilchrist RB, Smitz J. Live births after oocyte in vitro maturation with a prematuration step in women with polycystic ovary syndrome. J Assist Reprod Genet. 2020 Feb;37(2):347-357. doi: 10.1007/s10815-019-01677-6. Epub 2020 Jan 4.
PubMed 31902102Preis KA, Seidel GE Jr, Gardner DK. Reduced oxygen concentration improves the developmental competence of mouse oocytes following in vitro maturation. Mol Reprod Dev. 2007 Jul;74(7):893-903. doi: 10.1002/mrd.20655.
PubMed 17192892Akin 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
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Low Versus Air Oxygen Concentration in In-vitro Maturation With Biphasic Capacitation-IVM (CAPA-IVM) Culture of Human Cumulus-oocyte Complexes in PCOS Patients: a Sibling Oocyte Pilot Study
- ClinicalTrials.gov ID
- NCT06087354
- Acronym / sponsor ID
- 11/23/DD-BVMD
- Conditions
- IVM, PCOS (Polycystic Ovary Syndrome)
- Keywords
- Low oxygen, CAPA-IVM, Cumulus-oocyte complexes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Mỹ Đức HospitalUniversity, hospital or other
- Study start
- 9 Nov 2023 (actual)
- Primary completion
- 30 Jan 2024 (actual)
- Study completion
- 22 May 2024 (actual)
- First posted
- 17 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
IVM with a pre-maturation step, known as capacitation IVM (CAPA-IVM), has demonstrated enhanced maturation of human oocytes in vitro and successful live births. However, CAPA-IVM has shown lower rates of embryo formation when compared to conventional in vitro fertilization/ intra cytoplasmic sperm injection (IVF/ICSI) cycles. To optimize the CAPA-IVM culture system, this pilot study aims to evaluate the impact of low oxygen versus air oxygen concentrations on embryological outcomes in PCOS patients.
Detailed description
Oocyte in vitro maturation (IVM) is an alternative approach to assisted reproductive technology (ART) that has the advantage of minimal stimulation, resulting in reduced hormone-related side effects and risks, especially in women with polycystic ovary syndrome (PCOS). Oocytes retrieved for IVM procedures are derived from a diverse pool of follicles with an average diameter of between 2 and 10mm and are characterized by variable cellular and molecular attributes that indicate their immature status. Therefore, the development of an IVM culture system that could enable and enhance the acquisition and synchronization of meiotic and developmental competence prior to the meiotic resumption is essential for optimizing human IVM protocols.
IVM with a pre-maturation step, known as capacitation IVM (CAPA-IVM), has been shown to improve the competence of human oocytes matured in vitro and result in live births. The pre-maturation culture of CAPA-IVM utilizes C-type natriuretic peptide (CNP), and maturation takes place in the presence of amphiregulin (AREG), both of which are physiological compounds that have been shown to prevent spontaneous meiotic resumption of oocytes (CNP) and enhance oocyte competence (AREG) during IVM.
To date, the results of pilot studies have shown that CAPA-IVM increases the rates of oocyte maturation, good-quality embryos on day 3 and good-quality blastocysts, resulting in a result, a higher embryo yield was obtained compared with standard IVM. Additionally, the reported cumulative live birth rate after use of CAPA-IVM, and its non-inferiority to the cumulative live birth rate with standard in vitro fertilization highlight the clinical utility and potential of this approach. Improvements in the culture system could make CAPA-IVM more effective, but these need to be investigated.
The oxygen concentration during the IVM process plays a crucial role in oocyte maturation. The use of oxygen concentrations higher than physiological levels can lead to cell damage and affect embryo development. Recent studies in mice have suggested using lower oxygen concentrations to improve IVM outcomes. However, the effectiveness of using lower oxygen concentrations in human IVM remains unproven. Therefore, this pilot study aims to compare the effectiveness of lower oxygen concentration conditions versus air oxygen in CAPA-IVM on embryology outcomes in PCOS women.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low Oxygen Concentration CAPA-IVM culture | Experimental | Other: The way of Cumulus-oocyte complexes (COC) CAPA-IVM culture conditionHalf of COCs were cultured in the CAPA step and IVM step in a low oxygen concentration (5%) and 6% carbon dioxide at 37 degree |
| Air Oxygen Concentration CAPA-IVM culture | Experimental | Other: The way of Cumulus-oocyte complexes (COC) CAPA-IVM culture conditionHalf of COCs were cultured in the CAPA step and IVM step in a air oxygen concentration (20%) and 6% carbon dioxide at 37 degree |
Who may qualify
- Ages
- 18 to 37 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- ≤38 years
- Having polycystic ovarian morphology: at least 25 follicles (2-9 mm) throughout the whole ovary and/or increased ovarian volume (>10ml)
- Having at least 20 follicles on the Oocyte Pick-up day
- Patients consent to culture embryos to the blastocyst
Key exclusion criteria (3 listed)
- Cases with severe male factor (concentration <5 million/ml, cryptozoospermia, azoospermia)
- Oocyte donation
- Pre-implantation genetic testing
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| The way of Cumulus-oocyte complexes (COC) CAPA-IVM culture conditionCumulus-oocyte complexes (COC) will be cultured in CAPA-IVM 24 hrs capacitation followed by 30h maturation. The first group will be cultured in low oxygen concentration (5%Oxygen), 6% carbon dioxide at 37 degree. The second group will be cultured in air oxygen concentration (20%Oxygen), 6% carbon dioxide at 37 degree. | Other | Air Oxygen Concentration CAPA-IVM culture, Low Oxygen Concentration CAPA-IVM culture |
Primary outcome
Number of blastocyst
Time frame: At least 5 days after intra-cytoplasmic sperm injection
Number of blastocyst obtained
12 secondary outcomes
Number of matured oocytes
Time frame: Two days after oocytes pick-up
Number of normal fertilized oocytes
Time frame: 16-18 hours after intra-cytoplasmic sperm injection
Number of day-3 embryos
Time frame: At least 3 days after intra-cytoplasmic sperm injection
Number of good-quality day-3 embryos
Time frame: At least 3 days after intra-cytoplasmic sperm injection
Number of good-quality blastocyst
Time frame: At least 5 days after intra-cytoplasmic sperm injection
Number of vitrified blastocyst
Time frame: At least 5 days after intra-cytoplasmic sperm injection
Positive pregnancy test
Time frame: At 2 weeks after the completion of the first frozen embryo transfer
Clinical pregnancy
Time frame: 5 weeks after embryo placement after the completion of the first transfer
Ongoing pregnancy
Time frame: At 12 weeks' gestation
Implantation rate
Time frame: 3 weeks after embryo transferred after the completion of the first transfer
Multiple pregnancy
Time frame: 5 weeks after embryo placement after the completion of the first transfer
Miscarriage
Time frame: at 12 weeks of gestation after the completion of the first transfer
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2024.
- Background: PubMed 31399916Sanchez F, Le AH, Ho VNA, Romero S, Van Ranst H, De Vos M, Gilchrist RB, Ho TM, Vuong LN, Smitz J. Biphasic in vitro maturation (CAPA-IVM) specifically improves the developmental capacity of oocytes from small antral follicles. J Assist Reprod Genet. 2019 Oct;36(10):2135-2144. doi: 10.1007/s10815-019-01551-5. Epub 2019 Aug 9.
- Background: PubMed 32974672Vuong 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.
- Background: PubMed 31902102Vuong LN, Le AH, Ho VNA, Pham TD, Sanchez F, Romero S, De Vos M, Ho TM, Gilchrist RB, Smitz J. Live births after oocyte in vitro maturation with a prematuration step in women with polycystic ovary syndrome. J Assist Reprod Genet. 2020 Feb;37(2):347-357. doi: 10.1007/s10815-019-01677-6. Epub 2020 Jan 4.
- Background: PubMed 17192892Preis KA, Seidel GE Jr, Gardner DK. Reduced oxygen concentration improves the developmental competence of mouse oocytes following in vitro maturation. Mol Reprod Dev. 2007 Jul;74(7):893-903. doi: 10.1002/mrd.20655.
- Background: PubMed 37531262Akin 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tuong M Ho principal investigator
Mỹ Đức Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing The way of Cumulus-oocyte complexes (COC) CAPA-IVM culture condition in people with IVM and PCOS (Polycystic Ovary Syndrome), 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 4 inclusion and 3 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: finished, as of the sponsor's last update on 3 Jun 2024. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of blastocyst (time frame: At least 5 days after intra-cytoplasmic sperm injection). 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 NCT06087354, which also lists 5 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 3 Jun 2024.