Effect of the CAPA Culture Step on Meiotic and Developmental Competence of Human Oocytes After Using Two (Previously Used) Meiotic Maturation Triggers in a SIBLING Oocyte Study Design
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Meiotic maturation efficiency
研究概览
简要总结
Clinical use of IVM was pioneered in the nineties, but has not yet become a realistic option for wide-scale practice, for several reasons. Fundamentally, despite recent progress in improving the implantation and the pregnancy rates using in-vitro matured oocytes, results of IVM remain lower than treatment cycles utilizing conventional ART. To improve the outcome of IVM cycles, this study focuses on improving in-vitro culture conditions.
In-vitro maturation (IVM) of human oocytes obtained from minimally stimulated or unstimulated ovaries offers a more "patient friendly" treatment option than the conventional Assisted Reproductive Technology (ART) treatment with controlled ovarian hyperstimulation (COH). Typically, IVM will be offered to women with polycystic ovaries (PCO/PCOS), or to patients with an excellent ovarian reserve, i.e. a high antral follicle count. IVM treatment is characterized by minimal administration of FSH or hMG and NO hCG trigger. The IVM approach is less disruptive to patients' daily life through the reduced need for hormonal and ultrasound monitoring, avoids a range of minor and major complications, such as ovarian hyperstimulation syndrome, and aims to reduce the total cost of infertility treatment for the patient and for the health care budget.
Human oocytes retrieved from small antral follicles are able to resume meiosis by undergoing germinal vesicle breakdown and extrusion of the first polar body, if oocytes have reached meiotic competence. These oocytes can be fertilized although only a proportion (less than 50%) of them can develop further into viable embryos. It has been hypothesized that failure of embryonic development may, at least in part, be due to an immature oocyte cytoplasm. A novel human in vitro maturation (IVM) culture system (named CAPACITATION-IVM is being investigated, hereafter named "CAPA") using 1°) natural compounds known to influence cAMP levels within the cumulus-oocyte-complex and 2°) compounds that are crucial for the oocyte-cumulus cross-talk. Keeping cyclic AMP high after retrieval in the GV oocyte prevents the occurrence of nuclear maturation, enabling increased communication between the oocyte and the cumulus cells. This allows for the improvement in the synchronization of nuclear and cytoplasmic maturation processes in the oocyte, to the benefit of embryo quality.
详细描述
There are two types of patients can be distinguished in this study:
- Polycystic ovarian morphology + normal cycle length (up to 35 days). The majority of subjects in this group have non-syndromic polycystic ovaries and do not have PCOS. In these patients, AMH is only moderately elevated and cyclical follicular development occurs under the influence of FSH.
- PCOS - Polycystic ovarian morphology + oligomenorrhoea (menstrual periods occurring at intervals of greater than 35 days, with only four to nine periods in a year) or amenorrhea. In these patients, with often strongly elevated AMH levels and concomitant hyperandrogenemia, relative FSH resistance results in arrest of follicular growth at the small antral follicular state. Spontaneous selection of a dominant follicle does not occur or occurs rarely. A large proportion of follicles are atretic. An important proportion of these patients have a BMI higher than 25. These patients generally receive the same standard gonadotropin stimulation regimen as the patients of the previous group, but if the largest follicles have a diameter of less than 8 mm on the third day of stimulation, patients receive one or two supplementary days of gonadotropin stimulation. Moreover, these patients generally take two-three weeks of OCP before the start of the IVM cycle and start stimulation approximately on day five after OCP withdrawal. However, since these patients do not have endogenous FSH-driven recruitment of follicles, the start of stimulation is rather flexible.
- The use of OCP (oral contraceptive pill) before the IVM cycle is obligate. OCP (for example Microgynon 30 micrograms) will be administered daily, to clear the atretic follicles in the ovary. OCP will be given for between 14 and 21 days (this method allows for better programming the cycles and the workload in the embryology lab).
Before the first IVM cycle (Screening visit): All subjects will undergo a pelvic ultrasound scan to evaluate suitability to undergo IVM treatment. Patients will undergo a blood test for serology (Hepatitis B, HIV, syphilis) and baseline hormonal profiling (LH, FSH, E2, progesterone, AMH, SHBG, Testosterone). Additional analysis of TSH, thyroperoxidase antibodies, prolactin. Any concomitant medication taken in the last 3 months prior to the IVM attempt should be notified.
First IVM treatment cycle:
- First clinic visit:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 37 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Having polycystic ovarian morphology: at least 24 follicles in both ovaries and/or increased ovarian volume (>10ml) (it is sufficient that 1 ovary fits these criteria)
- •Undergoing ≤ 2 previous IVM or IVF attempts
- •Agreeing to have ≤ 2 embryos transferred
排除标准
- •High grade endometriosis
- •Oocyte donation and pre-implantation genetic diagnosis cycles
- •Cases with extremely poor sperm quality.
研究组 & 干预措施
AREG-TRIGGER
Per case (6mL) 5940 µL "Basal Medium"
- 60 µL "IVM MIX" Do not need to filtrate media.
干预措施: AREG-TRIGGER (Drug)
CONTROL-TRIGGER
Per case (5 mL) 4.3 ml IVM Medicult Medium (Vial 2) 0.5 ml HSA (from stock 10% solution) 50µl FSH (from stock 7.5 IU/ml) 5µl hCG (from stock 100 IU/ml) 75 µl GH (from stock 0.66mg/ml)
干预措施: CONTROL-TRIGGER (Drug)
结局指标
主要结局
Meiotic maturation efficiency
时间窗: Two days after oocytes pick-up
Percentage of PB, GVBD, GV by the two types of trigger. The PB (or MII) oocyte displays the first PB in the PVS. GVBD oocytes have neither a visible GV nor PBI. GV oocyte presents an intracytoplasmic nucleus called the 'germinal vesicle'.
Number of transferable day 3 embryos
时间窗: Five days after oocytes pick-up
Number of transferable day 3 embryos obtained by the two meiotic trigger types
次要结局
- Ongoing pregnancy rate(At a minimum of 12 weeks from the beginning of the last menstrual cycle (each cycle is 4 weeks) up to the time of delivery)
- Live birth rate(At least 24 weeks of gestation up to the time of delivery)
- Genetic and epigenetic analysis of cord blood of newborns (Will be done in a separate study)(1 day (Prior to the initiation of IVF/IVM) and 1 day (at the time of delivery))
- Genetic and epigenetic analysis of cells from buccal smears of newborns (Will be done in a separate study)(1 day (Prior to the initiation of IVF/IVM) and 1 day (at the time of delivery))
- Genetic and epigenetic analysis of placenta of newborns (Will be done in a separate study)(1 day (Prior to the initiation of IVF/IVM) and 1 day (at the time of delivery))