IVF, IVM, PCOS
Conditions
Keywords
CAPA-IVM, Single culture, Group culture
Brief summary
Oocyte in vitro maturation (IVM) is a minimal-stimulation ART with reduced hormone-related side effects and risks for the patients. However, the approach is not widely used because of an efficiency gap compared to conventional ART. In order to further optimize and adapt the CAPA-IVM system in the IVM clinic, this pilot study aims to check the feasibility of applying a single COC CAPA-IVM strategy versus the group COC culture CAPA-IVM
Detailed description
Oocyte in vitro maturation (IVM) is a minimal-stimulation ART with reduced hormone-related side effects and risks for the patients. However, the approach is not widely used because of an efficiency gap compared to conventional ART. Oocytes retrieved for IVM procedures derive from a heterogeneous pool with variable cellular and molecular characteristics that indicate its immature status. Thus, in vitro systems that permit and enhance acquisition and synchronization of meiotic competence (ability to resume meiosis in response to an ovulatory stimulus) and developmental competence (ability to be fertilized and support early embryo development) before the meiotic trigger are crucial for the optimization of human IVM systems. A novel two-step IVM culture system (named CAPA-IVM) involving a pre-maturation culture with C-type natriuretic peptide (CNP) and a maturation step in presence of Amphiregulin (AREG), both more physiological compounds improving oocyte competence, have been introduced in previous clinical studies. So far these pilot studies proved to increase the rates of oocyte maturation, good quality embryos on day 3, good quality blastocyst, and as a result a higher embryo yield. CAPA-IVM blastocysts have shown similar rates of methylation and gene expression at gDMRs compared to COS embryos; and the expression of ma-jor epigenetic regulators was similar between both groups. Furthermore, an improvement in pregnancy rates strengthens the clinical relevance of the use of CAPA-IVM strategy. In order to further optimize and adapt the CAPA-IVM system in the IVM clinic, this pilot study aims to check the feasibility of applying a single COC CAPA-IVM strategy versus the group COC culture CAPA-IVM. A single COC culture would permit to perform a non-invasive molecular analysis per matured oocyte, in order to identify quality genes ex-pressed in cumulus cells post-IVM (cumulus biomarkers), which could be subsequently used to identify the embryo(s) with highest potential of implantation.
Interventions
OTHERThe way of Cumulus-oocyte complexes (COC) culture
Cumulus-oocyte complexes (COC) will be cultured in CAPA-IVM standard conditions: 24 hrs capacitation followed by 30h maturation. The first group will be culture in pools (group culture). The second group will be culture individually in 20µl droplets.
Sponsors
Mỹ Đức Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 37 Years
Healthy volunteers
Yes
Inclusion criteria
* Having polycystic ovarian morphology: at least 25 follicles (2-9 mm) throughout the whole ovary and/or increased ovarian volume (\>10ml) (it is sufficient that 1 ovary fits these criteria) * No major uterine or ovarian abnormalities * Having at least 15 follicles on the OPU day * Patients consent to participate in the study
Exclusion criteria
* High (\>grade 2) grade endometriosis * Cases with extremely poor sperm (serve OAT: density \<1 million, mobility \<10% and sperm from testicular surgery)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of good quality embryos | At least 3 days after intra-cytoplasmic sperm injection | Number of good quality Day 3 embryos obtained |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fertilization rate | 16-18 hours after intra-cytoplasmic sperm injection | Percentage of fertilized oocytes by 2 types of COC culture |
| Cleavage rate | At least 3 days after intra-cytoplasmic sperm injection | Percentage of day-3 embryos over fertilized oocytes by 2 types of COC culture |
| Expansion rate | After at least 30 hours of maturation culture | Percentage of cumulus-oocyte complexes expanded after culture by 2 types of COC culture |
| The relative expression ratio ( R ) of human cumulus cell genes | cumulus cells will be collected after at least 30 hours of maturation culture, storaged at -80oC until RNA purification | Cumulus cells will be collected, cDNA synthesis after mRNA purification, relative quantification PCR for detecting gene expression |
| Positive pregnancy test | at 2 weeks after the embryo placement after the completion of the first transfer | Serum human chorionic gonadotropin level greater than 25 mIU/mL |
| Clinical pregnancy | 5 weeks after embryo placement after the completion of the first transfer | at least one gestational sac on ultrasound at 7 weeks' gestation with the detection of heart beat activity |
| Maturation rate | Two days after oocytes pick-up | Percentage of mature oocytes by 2 types of COC culture |
| Implantation rate | 3 weeks after embryo transferred after the completion of the first transfer | as the number of gestational sacs per number of embryos transferred |
| Multiple pregnancy | 5 weeks after embryo placement after the completion of the first transfer | Defined as presence of more than one sac at early pregnancy ultrasound (6-8 weeks gestation) |
| Multiple delivery | At 24 weeks' gestation | Birth of more than one baby beyond 24 weeks |
| Miscarriage | at 24 weeks of gestation after the completion of the first transfer | pregnancy loss at \< 24 weeks |
| Live birth | At 24 weeks of gestation | defined as at least one newborn after 24 weeks of gestation and exhibiting any sign of life; twins were counted as a single birth |
| Ongoing pregnancy | At 12 weeks' gestation | Ongoing pregnancy is defined as pregnancy with detectable heart rate at 12 weeks' gestation or beyond, after the completion of the first transfer |
Countries
Vietnam
Outcome results
None listed