Low vs. Air Oxygen Concentration CAPA-IVM Culture of Cumulus-oocyte Complexes

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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IVM, PCOS (Polycystic Ovary Syndrome)

Intervention / Treatment
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* Other: The way of Cumulus-oocyte complexes (COC) CAPA-IVM culture condition


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≤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 Exclusion Criteria: Cases with severe male factor (concentration <5 million/ml, cryptozoospermia, azoospermia) Oocyte donation Pre-implantation genetic testing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 37 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Oxygen Concentration CAPA-IVM culture<br>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 | Other: The way of Cumulus-oocyte complexes (COC) CAPA-IVM culture condition<br>* 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.<br>|
| Experimental: Air Oxygen Concentration CAPA-IVM culture<br>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 | Other: The way of Cumulus-oocyte complexes (COC) CAPA-IVM culture condition<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of blastocyst | Number of blastocyst obtained | At least 5 days after intra-cytoplasmic sperm injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of matured oocytes | Number of oocytes which have a polar body after maturation | Two days after oocytes pick-up | 
| Number of normal fertilized oocytes | Number of oocytes which have 2 pronuclear | 16-18 hours after intra-cytoplasmic sperm injection | 
| Number of day-3 embryos | Number of day-3 embryos obtained | At least 3 days after intra-cytoplasmic sperm injection | 
| Number of good-quality day-3 embryos | Number of good quality Day 3 embryos obtained | At least 3 days after intra-cytoplasmic sperm injection | 
| Number of good-quality blastocyst | Number of good quality blastocyst obtained | At least 5 days after intra-cytoplasmic sperm injection | 
| Number of vitrified blastocyst | Number of vitrified blastocyst obtained | At least 5 days after intra-cytoplasmic sperm injection | 
| Positive pregnancy test | Serum human chorionic gonadotropin level greater than 25 mIU/mL | 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 | 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 | At 12 weeks' gestation | 
| Implantation rate | Defined as the number of gestational sacs per number of embryos transferred | 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) | 5 weeks after embryo placement after the completion of the first transfer | 
| Miscarriage | pregnancy loss at <12 weeks | at 12 weeks of gestation after the completion of the first transfer | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low oxygen, CAPA-IVM, Cumulus-oocyte complexes