Time-Lapse Incubation for Embryo Culture - The Impact of Morphokinetics and Environmental Stability on Reproductive Outcomes
试验速览
- 阶段
- 不适用
- 入组人数
- 372
- 试验地点
- 2
- 主要终点
- Ongoing pregnancy rate
研究概览
简要总结
Embryo culture and selection has been a continuous challenge in evolution since the birth of In Vitro Fertilization (IVF). Traditionally, embryo quality and its presumed suitability for transfer were assessed based on morphologic features. However, the consensus as to the optimal time points for embryo assessment and as to 'preferable' characteristics have been challenging. Alongside this has been the challenge of achieving balance between multiple points of assessment, yet stabilizing the embryo environment for growth. In standard incubation, each new morphological assessment of embryos in culture theoretically creates an additional disruption to culture.
Most recently, time-lapse incubators (TLI) have been introduced as a novel embryo culture system attempting to limit culture disturbances. These incubators have been integrated with digital imaging, allowing for a substantial limitation in embryo handling and environmental disturbances. They have also introduced new morphokinetic parameters to embryo assessment and to optimizing selection of embryos. Thus far, a limited number of studies have examined the clinical outcomes and value of time lapse monitoring systems versus the more ubiquitous incubators (e.g. multichamber) for reproductive outcomes. In particular, the isolated value of morphokinetics in embryo assessment and of this new stable culture environment in TLI are still in question.
The objectives of this study are to prospectively assess and compare fertility outcomes when embryos are cultured in the TLI system versus more traditional bench incubators (BI). We will specifically assess the added value of the closed and isolated TLI compared to BI on reproductive outcomes, as well as the value of morphokinetic grading in IVF.
详细描述
Research Objectives:
We are now reaching a new age with an opportunity to advance to theoretically better culture environments and improvements on measures of embryo assessment.
The objectives of this research study will be to evaluate and compare the reproductive outcomes in isolating one of two new interventions introduced by the Time-Lapse Incubator (TLI) system. The first will be an assessment of the TLI environment compared to the standard Bench Incubator (BI) environment. The second will be an assessment of the added morphokinetic grading of embryos compared to the traditional morphologic grading alone.
Although the primary objective of this study will focus on clinical pregnancy rates and fresh embryo transfers, further research using embryos frozen from this study will be conducted to also evaluate cumulative pregnancy rates per oocyte pick-up (OPU) cycle in the future.
Methods The current study will be a prospective randomized and double-blinded study using three patient arms. The first arm will include patients randomized to embryo culture in a tri-gas bench incubator (Miri, Benchtop Multi-room incubator). These embryos will undergo multiple evaluations using light microscopy and traditional morphologic assessment according to accepted criteria. The second arm will include patients randomized to embryo culture in a time-lapse incubator (Miri TL, Time-Lapse Incubator). These embryos will remain in the TLI and undergo both morphologic and morphokinetic evaluation and grading according to a multivariable scoring model. They will not be removed from incubation for the duration of culture. The third arm will include patients also randomized to embryo culture in a time-lapse incubator (Miri TL, Time-Lapse Incubator). These embryos will remain in the TLI and undergo only traditional morphologic assessment according to accepted criteria with no additional imaging. They will also not be removed from incubation for the duration of culture. The time points and evaluated parameters will be identical to those in arm 1 of the study.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients requiring assisted reproductive technologies for one or more of the following reasons:
- •Male factor infertility
- •Unexplained infertility
- •Mechanical factor infertility
- •Ovulatory infertility
- •Patients undergoing fertility treatment at Shaare Zedek Medical Centre alone.
- •Patients attempting pregnancy with autologous gametes.
- •Patients receiving embryo transfers according to the Israel Society of Obstetrics and Gynecology guideline on number of embryos for transfer during in vitro fertilization.
- •Patients undergoing their first or second ICSI cycle (cumulative to all other institutions involved in prior treatment) since their previous pregnancy.
- •BMI criteria: >18 and <30 kg/m2
排除标准
- •An infertility diagnosis that includes the following:
- •Severe male factor infertility requiring testicular aspiration, testicular biopsy for sperm retrieval, or less than 1000 sperm per ejaculate.
- •Untreated hydrosalpinx
- •Persistently thin endometrial lining or endometrial factor
- •Severe Endometriosis
- •Low ovarian reserve (≤8 antral follicle count (AFC) follicles measuring 2 to 10 mm in diameter on day 2-4 of menstrual cycle, or day 3 follicle stimulating hormone (FSH) ≥10 milli-International unit (mIU) /mL)
- •High risk for Ovarian Hyperstimulation Syndrome (Estradiol level >13 000 pmol/L or >20 follicles ≥16 mm diameter during controlled ovarian hyper stimulation, ≥20 oocytes collected).
- •Patients obtaining GnRH agonist for final follicular maturation
- •Patients requiring preimplantation genetic diagnosis (PGD)
- •Patients who require freezing of all oocytes or embryos
- •More than 2 previous cycles of IVF since previous pregnancy
- •Current smokers
结局指标
主要结局
Ongoing pregnancy rate
时间窗: 12 weeks gestation
The number of women with a viable pregnancy (including gestational sac and fetal heart beat) at 12 weeks gestation divided by the number of women having an embryo transfer.
次要结局
- Embryo morphology - Inner Cell Mass (ICM) grade(Day 5 post-fertilization)
- Biochemical pregnancy rate(14 days after embryo transfer)
- Embryo morphology - Number of cells present(Day 2 and Day 3 post-fertilization)
- Embryo morphology - % fragmentation(Day 2 and Day 3 post-fertilization)
- Embryo morphokinetics - Time of cleavage to five-blastomere embryo(Day 0 to Day 3 post-fertilization)
- Embryo morphology - Number of pronuclei present following fertilization(Day 1 post-fertilization)
- Embryo morphology - Presence of multi nucleation(Day 2 post-fertilization)
- Embryo morphology - Symmetry(Day 2 and Day 3 post-fertilization)
- Embryo morphology - Stage of development at day 5(Day 5 post-fertilization)
- Embryo morphology - Trophectoderm grade(Day 5 post-fertilization)
- Embryo morphokinetics - Time from two to three-blastomere embryo(Day 1 to Day 3 post-fertilization)
- Oocyte characteristics - Polar body presence(Oocyte retrieval until fertilization - less than 1 day)
- Embryo morphokinetics - Time from two to four-blastomere embryo(Day 1 to Day 3 post-fertilization)
- Embryo morphokinetics - Abrupt division(Day 0 to Day 3 post-fertilization)
- Spontaneous abortion rate(First 20 weeks of gestation)
- Cumulative ongoing pregnancy rate(One year from oocyte pickup)
- Live birth rate(One year and forty weeks)
研究者
Ruthie Ronn
Dr. Ruth Ronn
Shaare Zedek Medical Center