In Vitro FertilizationNCT06367985
CAPA-IVM Culture With Low Oxygen Tension
A study testing Air Oxygen Concentration CAPA-IVM culture and Low Oxygen Concentration CAPA-IVM culture in people with In Vitro Fertilization, run by Mỹ Đức Hospital at 1 site in Vietnam.
Trial summary
Capacitation in-vitro maturation (CAPA-IVM) has recently been advanced in culturing oocytes from the germinal vesicle (GV) stage following mild or no controlled ovarian stimulation. Read more about this study
- Who is it for?
- Ages 18 to 42 years, women only
- Conditions the study is for
- In Vitro Fertilization
- What is being tested?
- Air Oxygen Concentration CAPA-IVM culture and Low Oxygen Concentration CAPA-IVM culture
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteVietnam
- Study dates
- 13 May 2024to 1 Jun 2025
- 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 42 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 18-42 years of age
- Diagnosed with polycystic ovary syndrome according to the Rotterdam criteria (2003)
- Indicating CAPA-IVM treatment
- Having at least 40 antral follicles in two ovaries by transvaginal ultrasound at the time of CAPA-IVM indication
- Agreeing to have frozen embryo transfer
- Agreeing to participate in the trial
Who cannot join
- Cycles with oocyte donation, preimplantation Genetic Testing (PGT)
- Couples with severe male factor (sperm concentration <5 million/ml, motility < 10%), surgical sperm retrieval
- Previous history of unexplained immature oocytes after IVF treatment
- Uterine abnormalities
Trial locations and contacts
1 site in 1 country.
About this study
Capacitation in-vitro maturation (CAPA-IVM) has recently been advanced in culturing oocytes from the germinal vesicle (GV) stage following mild or no controlled ovarian stimulation. Recent research suggested that O2 concentration may significantly regulate oocyte maturation and early embryo development through hypoxia-inducible factor (HIF). Nonetheless, it has been challenging to create the environmental culture conditions for addressing the optimal number of oocytes and the highest possibility of embryo development since consensus on the oxygen (O2) concentration index in the IVM culture environment has not been reached. Based on the outcomes of atmospheric O2 concentration (20%) and low O2 concentration (5%) during CAPA-IVM culture in mice, it has been hypothesized that a 5% O2 was the optimal culture condition for the pre-IVM step. A 20% O2 was more suitable for the IVM culture step. Therefore, this study is designed to enhance the CAPA-IVM culture system, improving treatment efficiency and providing various benefits for patients undergoing assisted reproductive technology.
Read the detailed description
Capacitation in-vitro maturation (CAPA-IVM) has recently been advanced in culturing oocytes from the germinal vesicle (GV) stage. This approach is a modified version of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), following mild stimulation or no controlled ovarian stimulation occurred. Specifically, IVM can be indicated for patients diagnosed with polycystic ovary syndrome (PCOS), a higher number of secondary follicles (constituting nearly 15% of total patients), and treat a range of patients with the risks of ovarian hyperstimulation, venous thromboembolism or ovarian torsion. Additionally, CAPA-IVM helps shorten treatment time, is less expensive, and upgrades patient convenience without multiple follow-up examinations. The live birth rate after the first embryo transfer in the CAPA-IVM group was 35.2%, which was not statistically significantly different from the IVF group at 43.2% (risk difference -8.1%; 95% confidence interval from -16.6% to 0.5%). However, the number of high-quality embryos in each cycle and the cumulative clinical pregnancy rate in CAPA-IVM were still lower than in cIVF.
Moreover, further investigation should be considered due to the lack of high-quality evidence of concurrent reports. Therefore, improving the oocyte maturation conditions in CAPA-IVM to harvest the optimal number of oocytes and the highest possibility of embryo development is essential. Many studies conducted on both animal and human models have demonstrated that the effectiveness of CAPA-IVM depends on various factors. Among these, the environmental culture conditions such as oxygen (O2) concentration play a crucial role in producing healthy mature oocytes. O2 is a vital physical and chemical component of the fallopian tube, uterus and ovarian follicle, it is closely related to metabolic activity, oocyte maturation, and early embryo development. Recent research suggested that O2 concentration may significantly regulate oocyte maturation and early embryo development through hypoxia-inducible factor (HIF). A consensus on the O2 concentration index in the IVM culture environment has not been reached. Oocyte-embedded culture systems have been commonly used in two O2 concentrations, 5% and 20% worldwide. In the human body, cumulus-oocyte complexes (COCs) mature in conditions with low O2 concentrations ranging from 2% to 9%.
Conversely, COCs are exposed to an atmospheric O2 concentration of 20% during IVM manipulation and culture. Although the concentration of 5% mimics the most proper environment in the fallopian tube and uterus, the 20% O2 is widely applied in IVM techniques. The use of high concentrations facilitates a better progression of differentiation processes and increases the maturation rate of oocytes. However, some referential frames indicated that a 20% O2 may pose a risk of reactive oxidative stress (ROS), leading to an imbalance in the ratio of pro-oxidants to antioxidants, resulting in cellular damage. Furthermore, real-time respiration analysis of oocytes cultured at 5% O2 is similar to in vivo-developed oocytes but induced cellular activity and oxygen consumption at 20% O2. The impact of atmospheric O2 concentration (20%) and low O2 concentration (5%) during CAPA-IVM culture in mice shown in the study of Vrije Universiteit Brussel (VUB) - Belgium that the respiratory capability of COCs cultured at 5% O2 was relatively similar to COCs developing and maturing in vivo.
Nonetheless, COCs cultured at 20% O2 increased respiratory activity and oxygen consumption remarkably. The study observed that pre-IVM culture of COCs at 20% O2 caused developmental disruptions. Also, the result was unfavorable if mouse COCs were cultured at the IVM step with 5% O2. Based on these analyses, the researchers hypothesized that a 5% O2 was the optimal culture condition for the pre-IVM step, while a 20% O2 was more relevant to the IVM culture step. Combining these findings with results from VUB and characteristics of the differentiation process in CAPA-IVM oocytes, this study is divided into two main groups, including 5% pre-IVM and 20% IVM versus 20% pre-IVM and IVM) and demonstrates whether this hypothesis should be applied CAPA-IVM in human. The enhancement of the CAPA-IVM culture system leads to improved treatment efficiency of this technique and provides various benefits for patients undergoing assisted reproductive technology.
Study procedure:
Screening for eligibility
- This trial will be conducted at My Duc Hospital, Ho Chi Minh City, Viet Nam.
- Women who are potentially eligible will be provided information about the trial 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 related to the study together with the informed consent documents. Signed informed consent forms will be obtained by the investigators from all women before the enrolment.
Oocytes will be divided into 2 groups:
Group 1 (includes 2 subgroups: 1A and 1B): Air Oxygen Concentration CAPA-IVM culture T = Total number of oocytes after OR and there are two subgroups.
The number of oocytes is divided below:
If T is an even number:
- Number of oocytes in Group 1A: One oocyte.
- Number of oocytes in Group 1B: T1B = (T-2)/2.
If T is an odd number:
- Number of oocytes in Group 1A: One oocyte.
- Number of oocytes in Group 1B: T1B = ([T-1]-2)/2. One oocyte remainder of the first patient will be assigned to group 1B, and the remainder of the next patient will be assigned to group 2B. Continuing to do so sequentially for the next remainder.
Group 2 (includes 2 subgroups: 2A and 2B): Low Oxygen Concentration CAPA- IVM culture T = Total number of oocytes after OR and there are two subgroups.
The number of oocytes is divided below:
If T is an even number:
- Number of oocytes in Group 2A: One oocyte.
- Number of oocytes in Group 2B: T2B = (T-2)/2.
If T is an odd number:
- Number of oocytes in Group 2A: One oocyte.
- Number of oocytes in Group 2B: T2B = ([T-1]-2)/2. One oocyte remainder of the first patient will be assigned to group 1B, and the remainder of the next patient will be assigned to group 2B. Continuing to do so sequentially for the next remainder.
Group 1A, 2A: Collecting after capacitation: oocyte and cumulus cell.
Group 1B, 2B: Collecting after capacitation: spent media, blank well. Collecting after maturation: spent media, cumulus cell, blank well.
- Conditions
- In Vitro Fertilization
- Being tested
- Air Oxygen Concentration CAPA-IVM culture, Low Oxygen Concentration CAPA-IVM culture
- Keywords
- CAPA-IVM, Low Oxygen Tension, Oxygen, Culture, PCOS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Air Oxygen Concentration CAPA-IVM cultureOther
- Group 1A: COC will be cultured in the CAPA step at an air oxygen concentration (20%) for 24 hours and 6% carbon dioxide at 37 degrees Celsius.
- Group 1B: COCs will be cultured in the CAPA step at an air oxygen concentration (20%) for 24 hours and in the IVM step at an air oxygen concentration (20%) for 30 hours; all two steps combine 6% carbon dioxide at 37 degrees Celsius.
Low Oxygen Concentration CAPA-IVM cultureOther
- Group 2A: COC will be cultured in the CAPA step at a low oxygen concentration (5%) for 24 hours and 6% carbon dioxide at 37 degrees Celsius.
- Group 2B: COCs will be cultured in the CAPA step at a low oxygen concentration (5%) for 24 hours and the IVM step at an air oxygen concentration (20%) for 30 hours; all two steps combine 6% carbon dioxide at 37 degrees Celsius.
| Study group | Role | What they receive |
|---|---|---|
| Air Oxygen Concentration CAPA-IVM culture | Experimental | Half of the COCs will be cultured in the CAPA step and IVM step at 37 degrees Celsius in air oxygen concentration (20%) and 6% carbon dioxide. Receives: Other: Air Oxygen Concentration CAPA-IVM culture |
| Low Oxygen Concentration CAPA-IVM culture | Active comparator | Half of the COCs will be cultured in the CAPA step at a low oxygen concentration (5%) and IVM step at an air oxygen concentration (20%); all two steps combine 6% carbon dioxide at 37 degrees Celsius. Receives: Other: Low Oxygen Concentration CAPA-IVM culture |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maturation rate
The oocyte maturation rate was usually defined by MII oocyte number divided by total COCs number
Measured: Two day after oocyte retrieval
Secondary outcomes (46)
Total number of oocytes retrieval
Counting the number of oocytes retrieved
Measured: On the day of oocyte retrieval
Number of patients with no oocyte retrieved
Counting the number of patients with no oocyte retrieved
Measured: On the day of oocyte retrieval
Number of MII oocytes
The oocyte maturation was usually defined by MII oocyte number
Measured: Two day after oocyte retrieval
Number of GV oocytes
Counting the number of GV oocytes
Measured: Two day after oocyte retrieval
Number of patients with no matured oocyte
Counting the number of patients with no matured oocyte
Measured: Two day after oocyte retrieval
Number of 2PN oocytes
Number of zygotes with 2 pronuclei after ICSI
Measured: 16-18 hours after ICSI
Fertilization rate
Number of fertilized oocytes / number of oocytes inseminated
Measured: 16-18 hours after ICSI
Abnormal fertilization rate
The percentage of zygotes with 1,3, or 4 pronuclei after ICSI / number of oocytes inseminated
Measured: 16-18 hours after ICSI
Number of patients with no day-3 embryo
Counting the number of patients with no embryo
Measured: Five day after oocyte retrieval
Number of day-3 embryos
Counting the number of day-3 embryos at 64±2h after ICSI
Measured: Three days after intra-cytoplasmic sperm injection
Number of good quality Day-3 embryos
Number of grade 1 and grade 2 day-3 embryos
Measured: Three days after intra-cytoplasmic sperm injection
Number of frozen day-3 embryos
Counting the numer of frozen day-3 embryos
Measured: Three days after ICSI
Number of blastocyst (day 5 or day 6 embryo)
Counting the number of blastocyst at 114±2h/140±2h after ICSI
Measured: Five or six days after ICSI
Number of patients with no blastocyst
Counting the number of patients with no blastocyst
Measured: Five or six days after ICSI
Number of good quality blastocysts
Number of grade 1 and grade 2 blastocysts
Measured: Five days after intra-cytoplasmic sperm injection
Number of frozen blastocysts
Counting the numer of frozen blastocysts
Measured: Three days after ICSI
Number of embryos transferred
Total embryos transferred
Measured: On the day of embryo transfer
Quality of embryos transferred (Grade 1, Grade 2, Grade 3)
The quality of transferred embryo is classified according to Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology, 2011; D. Gardner, 1999; D. K. Gardner \& Schoolcrati, 1999
Measured: On the day of embryo transfer
Positive pregnancy test rate
Positive pregnancy test defined as serum human chorionic gonadotropin level greater than 25 mIU/mL
Measured: 11 days after the day of blastocyst transfer and 13 days after the day of day-3 embryo transfer
Implantation rate
Implantation rate is explained as the number of gestational sacs per number of embryos transferred.
Measured: At 3 weeks after embryo transfer after the completion of the embryo transfer
Clinical pregnancy rate
Diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy at 6 weeks or more after the onset of last menstrual period. In addition to intra-uterine pregnancy, it includes a clinically documented ectopic pregnancy
Measured: 5 weeks after embryo transfer
Ectopic pregnancy rate
A pregnancy outside the uterine cavity, diagnosed by ultrasound, surgical visualization or histopathology
Measured: 3 weeks after embryo transfer
Ongoing pregnancy rate
Ongoing pregnancy is defined as pregnancy with a detectable heart rate at 12 weeks' gestation or beyond.
Measured: 10 weeks after embryo transfer
Miscarriage <12 weeks rate (Early miscarriage)
Spontaneous loss of pregnancy up to 12 weeks of gestation is referred to as an early
Measured: 2-10 weeks after embryo transfer
Miscarriage <22 weeks rate (late miscarriage)
Spontaneous loss of pregnancy between 12 to 22 weeks is termed as late miscarriage
Measured: At >10 to 20 weeks after the transfer
Live birth rate
Live birth is defined as the complete expulsion or extraction from a woman of a product of fertilization, after 22 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heartbeat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. A birth weight of 500 grams or more can be used if gestational age is unknown. Twins counted as one live birth.
Measured: At 22 weeks of gestation
Multiple pregnancy rate
Defined as the presence of more than one gestational sac at early pregnancy ultrasound (6-9 weeks gestation)
Measured: 4 weeks after embryo transfer
Multiple delivery rate
Defined as the complete expulsion or extraction from a woman of more than one fetus, after 22 completed weeks of gestational age, irrespective of whether it is a live birth or stillbirth
Measured: At 22 weeks' gestation
Mode of delivery
Vaginal delivery, C-section (elective, suspected fetal distress, non-progressive labor)
Measured: At birth
Gestational age at birth
Calculated by gestational age of all live births
Measured: At birth
Birth weight
in grams; of singletons and twins
Measured: At the time of delivery
Very low birth weight rate
Birth weight less than 1.500 g
Measured: At birth
Low birth weight rate
Birth weight less than 2.500 g
Measured: At birth
High birth weight rate
Implies growth beyond an absolute birth weight, historically 4.000 g or 4.500 g, regardless of the gestational age
Measured: At birth
Very high birth weight rate
Birth weight over than 4.500 g for women with diabetes, and a threshold of 5000 g for women without diabetes
Measured: At birth
Small for gestational age rate
Large for gestational age was defined as a birth weight below the 10th percentile
Measured: At birth
Large for gestational age rate
Large for gestational age was defined as a birth weight above the 90th percentile
Measured: At birth
Hypertension in pregnancy rate
Comprising pregnancy-induced hypertension (PIH), pre-eclampsia (PET), eclampsia, and HELLP syndrome.
Measured: At 20 weeks of gestation or beyond
Gestational diabetes mellitus rate
Diagnosed according to the latest version of ADA guidelines. a 75-g OGTT, with plasma glucose measurement when patient is fasting and at 1 and 2 h, at 24-28 weeks of gestation in women not previously diagnosed with diabetes.
- Fasting: 92 mg/dL (5.1 mmol/L)
- 1 h: 180 mg/dL (10.0 mmol/L)
- 2 h: 153 mg/dL (8.5 mmol/L)
Measured: At 24 to 28 weeks of gestation
Still birth rate
defined as the death of a fetus prior to the complete expulsion or extraction from its mother after 20 completed weeks of gestational age. The death is determined by the fact that, after such separation, the fetus does not breathe or show any other evidence of life, such as heartbeat, umbilical cord pulsation, or definite movement of voluntary muscles. It includes deaths occurring during labor
Measured: After 20 completed weeks of gestational age
Premature birth rate
Defined as delivery at <24, <28, <32, <37 completed weeks. A birth that takes place after 22 weeks and before 37 completed weeks of gestational age.
Measured: On the day of delivery
Antepartum haemorrhage rate
Defined as bleeding from or into the genital tract, occurring from 24 weeks of pregnancy and prior to the birth of the baby.
Measured: At birth
Major congenital abnormalities rate
Structural, functional, and genetic anomalies, that occur during pregnancy, and identified antenatally, at birth, or later in life, and require surgical repair of a defect, or are visually evident, or are life-threatening, or cause death. Any congenital anomaly will be included as followed definition of congenital abnormalities in Surveillance of Congenital Anomalies by Division of Birth Defects and Developmental Disabilities, NCBDDD, Centers for Disease Control and Prevention (2020).
Measured: At birth
Neonatal mortality rate
Neonatal mortality defined as the death of a live-born baby within 28 days of birth. This can be divided into early neonatal mortality, if death occurs in the first seven days after birth, and late neonatal if death occurs between eight and 28 days after delivery
Measured: between eight and 28 days after delivery
NICU admission rate
Counting number of babies admited to neonatal intensive care unit
Measured: At birth
Reason for NICU admission
Respiratory distress, Intraventricular Hemorrhage, Necrotizing enterocolitis, Sepsis
Measured: At birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2024
- Study start13 May 2024
- Primary completion11 Jul 2024
- Study completion1 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for In Vitro FertilizationStudies 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
- Model description
- Sibling oocytes
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mỹ Đức Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Vrije Universiteit Brussel
- Responsible party
- Sponsor
- Investigators
- Lan N Vuong, MD, PhD, Principal investigator, University of Medicine and Pharmacy at Ho Chi Minh City
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06367985
- Sponsor's protocol ID
- 03/24/DD-BVMD
- Status last verified
- Jun 2025
- First submitted
- 26 Mar 2024
- Last updated
- 12 Jun 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 33358333Paulson RJ, Fauser BCJM, Vuong LTN, Doody K. Can we modify assisted reproductive technology practice to broaden reproductive care access? Fertil Steril. 2016 May;105(5):1138-1143. doi: 10.1016/j.fertnstert.2016.03.013. Epub 2016 Apr 4.
PubMed 27054309Vuong 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 32974672Gilchrist 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 37639630Zhao X, Liu X, Feng Y, Shi D, Lu F. Regulation of hypoxia-inducible factor 1alpha by optimal oxygen concentration enhances oocyte maturation and early embryonic development in buffalo. Theriogenology. 2023 Aug;206:50-59. doi: 10.1016/j.theriogenology.2023.05.006. Epub 2023 May 8.
PubMed 37187055Fischer B, Bavister BD. Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits. J Reprod Fertil. 1993 Nov;99(2):673-9. doi: 10.1530/jrf.0.0990673.
PubMed 8107053Bahrami M, Cottee PA. Culture conditions for in vitro maturation of oocytes - A review. Reproduction and Breeding. 2022 Jun 1;2(2):31-6
Increased susceptibility to oxidative stress as a proximate cost of reproduction - Alonso-Alvarez - 2004 - Ecology Letters - Wiley Online Library [Internet]. [cited 2023 Sep 19]. Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1461-0248.2004.00594.x
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 37531262Herta 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 35717588Rotterdam 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
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CAPA-IVM Culture With Low Oxygen Tension
- ClinicalTrials.gov ID
- NCT06367985
- Acronym / sponsor ID
- 03/24/DD-BVMD
- Conditions
- In Vitro Fertilization
- Keywords
- CAPA-IVM, Low Oxygen Tension, Oxygen, Culture, PCOS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Mỹ Đức HospitalUniversity, hospital or other
- Collaborators
- Vrije Universiteit Brussel
- Study start
- 13 May 2024 (actual)
- Primary completion
- 11 Jul 2024 (actual)
- Study completion
- 1 Jun 2025 (actual)
- First posted
- 16 Apr 2024 (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.
Capacitation in-vitro maturation (CAPA-IVM) has recently been advanced in culturing oocytes from the germinal vesicle (GV) stage following mild or no controlled ovarian stimulation. Recent research suggested that O2 concentration may significantly regulate oocyte maturation and early embryo development through hypoxia-inducible factor (HIF). Nonetheless, it has been challenging to create the environmental culture conditions for addressing the optimal number of oocytes and the highest possibility of embryo development since consensus on the oxygen (O2) concentration index in the IVM culture environment has not been reached. Based on the outcomes of atmospheric O2 concentration (20%) and low O2 concentration (5%) during CAPA-IVM culture in mice, it has been hypothesized that a 5% O2 was the optimal culture condition for the pre-IVM step. A 20% O2 was more suitable for the IVM culture step. Therefore, this study is designed to enhance the CAPA-IVM culture system, improving treatment efficiency and providing various benefits for patients undergoing assisted reproductive technology.
Detailed description
Capacitation in-vitro maturation (CAPA-IVM) has recently been advanced in culturing oocytes from the germinal vesicle (GV) stage. This approach is a modified version of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), following mild stimulation or no controlled ovarian stimulation occurred. Specifically, IVM can be indicated for patients diagnosed with polycystic ovary syndrome (PCOS), a higher number of secondary follicles (constituting nearly 15% of total patients), and treat a range of patients with the risks of ovarian hyperstimulation, venous thromboembolism or ovarian torsion. Additionally, CAPA-IVM helps shorten treatment time, is less expensive, and upgrades patient convenience without multiple follow-up examinations. The live birth rate after the first embryo transfer in the CAPA-IVM group was 35.2%, which was not statistically significantly different from the IVF group at 43.2% (risk difference -8.1%; 95% confidence interval from -16.6% to 0.5%). However, the number of high-quality embryos in each cycle and the cumulative clinical pregnancy rate in CAPA-IVM were still lower than in cIVF.
Moreover, further investigation should be considered due to the lack of high-quality evidence of concurrent reports. Therefore, improving the oocyte maturation conditions in CAPA-IVM to harvest the optimal number of oocytes and the highest possibility of embryo development is essential. Many studies conducted on both animal and human models have demonstrated that the effectiveness of CAPA-IVM depends on various factors. Among these, the environmental culture conditions such as oxygen (O2) concentration play a crucial role in producing healthy mature oocytes. O2 is a vital physical and chemical component of the fallopian tube, uterus and ovarian follicle, it is closely related to metabolic activity, oocyte maturation, and early embryo development. Recent research suggested that O2 concentration may significantly regulate oocyte maturation and early embryo development through hypoxia-inducible factor (HIF). A consensus on the O2 concentration index in the IVM culture environment has not been reached. Oocyte-embedded culture systems have been commonly used in two O2 concentrations, 5% and 20% worldwide. In the human body, cumulus-oocyte complexes (COCs) mature in conditions with low O2 concentrations ranging from 2% to 9%.
Conversely, COCs are exposed to an atmospheric O2 concentration of 20% during IVM manipulation and culture. Although the concentration of 5% mimics the most proper environment in the fallopian tube and uterus, the 20% O2 is widely applied in IVM techniques. The use of high concentrations facilitates a better progression of differentiation processes and increases the maturation rate of oocytes. However, some referential frames indicated that a 20% O2 may pose a risk of reactive oxidative stress (ROS), leading to an imbalance in the ratio of pro-oxidants to antioxidants, resulting in cellular damage. Furthermore, real-time respiration analysis of oocytes cultured at 5% O2 is similar to in vivo-developed oocytes but induced cellular activity and oxygen consumption at 20% O2. The impact of atmospheric O2 concentration (20%) and low O2 concentration (5%) during CAPA-IVM culture in mice shown in the study of Vrije Universiteit Brussel (VUB) - Belgium that the respiratory capability of COCs cultured at 5% O2 was relatively similar to COCs developing and maturing in vivo.
Nonetheless, COCs cultured at 20% O2 increased respiratory activity and oxygen consumption remarkably. The study observed that pre-IVM culture of COCs at 20% O2 caused developmental disruptions. Also, the result was unfavorable if mouse COCs were cultured at the IVM step with 5% O2. Based on these analyses, the researchers hypothesized that a 5% O2 was the optimal culture condition for the pre-IVM step, while a 20% O2 was more relevant to the IVM culture step. Combining these findings with results from VUB and characteristics of the differentiation process in CAPA-IVM oocytes, this study is divided into two main groups, including 5% pre-IVM and 20% IVM versus 20% pre-IVM and IVM) and demonstrates whether this hypothesis should be applied CAPA-IVM in human. The enhancement of the CAPA-IVM culture system leads to improved treatment efficiency of this technique and provides various benefits for patients undergoing assisted reproductive technology.
Study procedure:
Screening for eligibility
- This trial will be conducted at My Duc Hospital, Ho Chi Minh City, Viet Nam.
- Women who are potentially eligible will be provided information about the trial 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 related to the study together with the informed consent documents. Signed informed consent forms will be obtained by the investigators from all women before the enrolment.
Oocytes will be divided into 2 groups:
Group 1 (includes 2 subgroups: 1A and 1B): Air Oxygen Concentration CAPA-IVM culture T = Total number of oocytes after OR and there are two subgroups.
The number of oocytes is divided below:
If T is an even number:
- Number of oocytes in Group 1A: One oocyte.
- Number of oocytes in Group 1B: T1B = (T-2)/2.
If T is an odd number:
- Number of oocytes in Group 1A: One oocyte.
- Number of oocytes in Group 1B: T1B = ([T-1]-2)/2. One oocyte remainder of the first patient will be assigned to group 1B, and the remainder of the next patient will be assigned to group 2B. Continuing to do so sequentially for the next remainder.
Group 2 (includes 2 subgroups: 2A and 2B): Low Oxygen Concentration CAPA- IVM culture T = Total number of oocytes after OR and there are two subgroups.
The number of oocytes is divided below:
If T is an even number:
- Number of oocytes in Group 2A: One oocyte.
- Number of oocytes in Group 2B: T2B = (T-2)/2.
If T is an odd number:
- Number of oocytes in Group 2A: One oocyte.
- Number of oocytes in Group 2B: T2B = ([T-1]-2)/2. One oocyte remainder of the first patient will be assigned to group 1B, and the remainder of the next patient will be assigned to group 2B. Continuing to do so sequentially for the next remainder.
Group 1A, 2A: Collecting after capacitation: oocyte and cumulus cell.
Group 1B, 2B: Collecting after capacitation: spent media, blank well. Collecting after maturation: spent media, cumulus cell, blank well.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Sibling oocytes
| Arm | Type | Receives |
|---|---|---|
| Air Oxygen Concentration CAPA-IVM culture | Experimental | Other: Air Oxygen Concentration CAPA-IVM cultureHalf of the COCs will be cultured in the CAPA step and IVM step at 37 degrees Celsius in air oxygen concentration (20%) and 6% carbon dioxide. |
| Low Oxygen Concentration CAPA-IVM culture | Active comparator | Other: Low Oxygen Concentration CAPA-IVM cultureHalf of the COCs will be cultured in the CAPA step at a low oxygen concentration (5%) and IVM step at an air oxygen concentration (20%); all two steps combine 6% carbon dioxide at 37 degrees Celsius. |
Who may qualify
- Ages
- 18 to 42 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 18-42 years of age
- Diagnosed with polycystic ovary syndrome according to the Rotterdam criteria (2003)
- Indicating CAPA-IVM treatment
- Having at least 40 antral follicles in two ovaries by transvaginal ultrasound at the time of CAPA-IVM indication
- Agreeing to have frozen embryo transfer
Key exclusion criteria (4 listed)
- Cycles with oocyte donation, preimplantation Genetic Testing (PGT)
- Couples with severe male factor (sperm concentration <5 million/ml, motility < 10%), surgical sperm retrieval
- Previous history of unexplained immature oocytes after IVF treatment
- Uterine abnormalities
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 |
|---|---|---|
| Air Oxygen Concentration CAPA-IVM culture* Group 1A: COC will be cultured in the CAPA step at an air oxygen concentration (20%) for 24 hours and 6% carbon dioxide at 37 degrees Celsius. * Group 1B: COCs will be cultured in the CAPA step at an air oxygen concentration (20%) for 24 hours and in the IVM step at an air oxygen concentration (20%) for 30 hours; all two steps combine 6% carbon dioxide at 37 degrees Celsius. | Other | Air Oxygen Concentration CAPA-IVM culture |
| Low Oxygen Concentration CAPA-IVM culture* Group 2A: COC will be cultured in the CAPA step at a low oxygen concentration (5%) for 24 hours and 6% carbon dioxide at 37 degrees Celsius. * Group 2B: COCs will be cultured in the CAPA step at a low oxygen concentration (5%) for 24 hours and the IVM step at an air oxygen concentration (20%) for 30 hours; all two steps combine 6% carbon dioxide at 37 degrees Celsius. | Other | Low Oxygen Concentration CAPA-IVM culture |
Primary outcome
Maturation rate
Time frame: Two day after oocyte retrieval
The oocyte maturation rate was usually defined by MII oocyte number divided by total COCs number
46 secondary outcomes
Total number of oocytes retrieval
Time frame: On the day of oocyte retrieval
Number of patients with no oocyte retrieved
Time frame: On the day of oocyte retrieval
Number of MII oocytes
Time frame: Two day after oocyte retrieval
Number of GV oocytes
Time frame: Two day after oocyte retrieval
Number of patients with no matured oocyte
Time frame: Two day after oocyte retrieval
Number of 2PN oocytes
Time frame: 16-18 hours after ICSI
Fertilization rate
Time frame: 16-18 hours after ICSI
Abnormal fertilization rate
Time frame: 16-18 hours after ICSI
Number of patients with no day-3 embryo
Time frame: Five day after oocyte retrieval
Number of day-3 embryos
Time frame: Three days after intra-cytoplasmic sperm injection
Number of good quality Day-3 embryos
Time frame: Three days after intra-cytoplasmic sperm injection
Number of frozen day-3 embryos
Time frame: Three days after ICSI
Number of blastocyst (day 5 or day 6 embryo)
Time frame: Five or six days after ICSI
Number of patients with no blastocyst
Time frame: Five or six days after ICSI
Number of good quality blastocysts
Time frame: Five days after intra-cytoplasmic sperm injection
Number of frozen blastocysts
Time frame: Three days after ICSI
Number of embryos transferred
Time frame: On the day of embryo transfer
Quality of embryos transferred (Grade 1, Grade 2, Grade 3)
Time frame: On the day of embryo transfer
Positive pregnancy test rate
Time frame: 11 days after the day of blastocyst transfer and 13 days after the day of day-3 embryo transfer
Implantation rate
Time frame: At 3 weeks after embryo transfer after the completion of the embryo transfer
Clinical pregnancy rate
Time frame: 5 weeks after embryo transfer
Ectopic pregnancy rate
Time frame: 3 weeks after embryo transfer
Ongoing pregnancy rate
Time frame: 10 weeks after embryo transfer
Miscarriage <12 weeks rate (Early miscarriage)
Time frame: 2-10 weeks after embryo transfer
Miscarriage <22 weeks rate (late miscarriage)
Time frame: At >10 to 20 weeks after the transfer
Live birth rate
Time frame: At 22 weeks of gestation
Multiple pregnancy rate
Time frame: 4 weeks after embryo transfer
Multiple delivery rate
Time frame: At 22 weeks' gestation
Mode of delivery
Time frame: At birth
Gestational age at birth
Time frame: At birth
Birth weight
Time frame: At the time of delivery
Very low birth weight rate
Time frame: At birth
Low birth weight rate
Time frame: At birth
High birth weight rate
Time frame: At birth
Very high birth weight rate
Time frame: At birth
Small for gestational age rate
Time frame: At birth
Large for gestational age rate
Time frame: At birth
Hypertension in pregnancy rate
Time frame: At 20 weeks of gestation or beyond
Gestational diabetes mellitus rate
Time frame: At 24 to 28 weeks of gestation
Still birth rate
Time frame: After 20 completed weeks of gestational age
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 12 Jun 2025.
- Background: PubMed 33358333Practice 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.
- Background: PubMed 27054309Paulson RJ, Fauser BCJM, Vuong LTN, Doody K. Can we modify assisted reproductive technology practice to broaden reproductive care access? Fertil Steril. 2016 May;105(5):1138-1143. doi: 10.1016/j.fertnstert.2016.03.013. Epub 2016 Apr 4.
- 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 37639630Gilchrist 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.
- Background: PubMed 37187055Zhao X, Liu X, Feng Y, Shi D, Lu F. Regulation of hypoxia-inducible factor 1alpha by optimal oxygen concentration enhances oocyte maturation and early embryonic development in buffalo. Theriogenology. 2023 Aug;206:50-59. doi: 10.1016/j.theriogenology.2023.05.006. Epub 2023 May 8.
- Background: PubMed 8107053Fischer B, Bavister BD. Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits. J Reprod Fertil. 1993 Nov;99(2):673-9. doi: 10.1530/jrf.0.0990673.
- BackgroundBahrami M, Cottee PA. Culture conditions for in vitro maturation of oocytes - A review. Reproduction and Breeding. 2022 Jun 1;2(2):31-6
- BackgroundIncreased susceptibility to oxidative stress as a proximate cost of reproduction - Alonso-Alvarez - 2004 - Ecology Letters - Wiley Online Library [Internet]. [cited 2023 Sep 19]. Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1461-0248.2004.00594.x
- 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.
- Background: PubMed 35717588Herta 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.
- Background: PubMed 14688154Rotterdam 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.
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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.
Lan N Vuong, MD, PhD principal investigator
University of Medicine and Pharmacy at Ho Chi Minh City
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Air Oxygen Concentration CAPA-IVM culture and Low Oxygen Concentration CAPA-IVM culture 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 6 inclusion and 4 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 12 Jun 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?
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?
Maturation rate (time frame: Two day 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 NCT06367985, which also lists 11 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 12 Jun 2025.