Trial Investigating the Developmental Potential of Embryos Obtained After Biphasic in Vitro Oocyte Maturation (IVM) of Oocytes Including a Pre Maturation Culture Step ('capacitation Step') Compared with Standard IVM.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- oocyte maturation
研究概览
简要总结
In vitro maturation is a valid option for PCO(S) patients in the daily ART clinic, however maturation and embryologic development are not yet matching the efficiency levels obtained by standard COS treatment. To further enhance embryo quality after IVM, it was hypothesized to keep the connection and communication between oocyte and cumulus cells intact for a prolonged pre-maturation culture before IVM was initiated. This has been investigated and established using a meiotic blocker C-type Natriuretic peptide (CNP).
The CNP peptide is present in high concentrations in the growing follicle, is produced by the mural granulosa cell compartment and binds to the Natriuretic peptide receptor 2 (NRP2) present in the cumulus cells. Binding of CNP on NRP2 leads to intracellular cGMP increase in cumulus cells, which travels through the transzonal projections to the oocyte. In the oocyte, cGMP will block the resumption of meiosis.
Using CNP as natural inhibitor of meiosis, a new medium was designed to allow oocyte and surrounding cumulus cells to communicate and hence gain in competence for an additional culture period: the pre-maturation phase or Capacitation phase (CAPA). This system was devel-oped in mouse, tested in human in UZ Brussel on research material (toelating federaal EC: CFE-FCE ADV_073_ZUBrussel, toelating lokaal EC: 2016/411 BUN 143201630723) and used in a clinical setting in Vietnam.
详细描述
The current IVM system in use in the clinic has a single step approach and seems to be less efficient compared to research and literature findings using a biphasic CAPA-IVM system in terms of maturation.
To ascertain the efficiency of the biphasic CAPA-IVM system, both standard IVM and CAPA-IVM will be performed on sibling oocytes: maturation in standard IVM in the investigator's center is on average 47.5%, where CAPA-IVM reaches 62% maturation in literature.
The investigators aim to prove superiority of the CAPA-IVM system in terms of maturation. Also fertilization and embryo development will be compared.
The participants admitted to the study will be receiving both the standard IVM treatment for part of the participant's oocytes and the biphasic CAPA IVM system for the second part of the participant's oocytes.
In one ovary a regular oocyte pick up (OPU) will take place with oocytes assigned to the standard IVM treatment, in the other ovary the CAPA IVM system will be applied. This means oocytes that are liberated from the follicular environment need to be exposed immediately to the inhibiting CNP peptide and herefore the tubes to collect the follicle fluid from the punctured follicles are prefilled with CNP supplemented medium. The OPU procedure is identical for both ovaries and according to our standard OPU IVM procedure with the sole difference of empty or prefilled tubes to collect follicle fluid.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 36 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •PCO(S) patients
- •Anti-Mullerian Hormone ≥ 3.6 ng/mL
- •Basal Antral Follicle Count ≥ 20
- •All ranks of trial
排除标准
- •Surgically obtained semen sample
- •Grade 3 or 4 endometriosis, minor or major uterine abnormalities
- •Preimplantation Genetic Testing
- •Priming with Letrozole
研究组 & 干预措施
CAPA IVM
CAPA IVM is a 2-step In vitro Maturation system in which an additional culture step, in which the oocytes are kept in meiotic arrest by the presence of the C-type Natriuretic peptide (CNP) for 22-24 hours, is preceding the in vitro maturation step in which maturation medium is supplemented with amphiregulin (AREG). The 'IVM System' of Medicult-Origio is used as a base medium.
干预措施: CAPA-IVM (Device)
Standard IVM
The IVM is performed as a single step protocol in which oocytes are immediately exposed to in vitro maturation medium for 30 hours. This is the current standard procedure in the clinical practice using the commercially available 'IVM System' of Medicult-Origio. Standard IVM medium: 10% HSA + 75mIU/ml FSH + 100mIU/ml hCG
结局指标
主要结局
oocyte maturation
时间窗: oocyte maturation is assessed after 30 hours in the standard IVM protocol and after 54 hours after CAPA IVM
the ability of the oocyte to extrude the first polar body
次要结局
- Fertilization rate(The presence of 2 pronuclei is assessed between 18-20 hours after ICSI)
- morphologic parameters describing embryo quality per fertilized oocyte(embryo developmental assessment is performed 3 days after ICSI)
- utilization rate(utilization rate will be established 3 days after ICSI)
- embryo cryotolerance(First warming is done within one month after OPU in a new HRT cycle and repeated untill pregnancy up to 1 year after egg retrieval.)