Prospective Observational Study of the Morphokinetics and Ploidy of Blastocysts With Abnormal Fertilization (1PN, 2.1PN and 3PN) to Identify the Origin of Fertilization Alterations
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- Igenomix
- 入组人数
- 300
- 试验地点
- 2
- 主要终点
- Diploidy rate in haploid embryos from IVF/ICSI
研究概览
简要总结
The goal of this observational study is to determine the diploidy rate of haploid and triploid embryos from in vitro fertilization (IVF) cycles. The main questions it aims to answer are:
- Can a molecular genetic fertilization check of abnormally fertilized embryos be used to expand opportunities for couples undergoing assisted reproduction treatment?
- Is the chromosomal loss or gain present in abnormally fertilized embryos predominantly maternal in origin?
For this purpose, we will evaluate the morphokinetics and ploidy of about 300 embryos with different types of abnormal pronuclear patterns (1PN, 2.1PN, and 3PN) that reach the blastocyst stage. Whenever possible, embryos with a non-diploid chromosomal complement will also be assessed to determine the origin (maternal or paternal) of the chromosomal set that has been lost or gained.
Study subjects will follow their previously scheduIed IVF/ICSI treatment and no additional visits/interventions will be required for participating.
详细描述
Chromosomes are cellular structures containing the majority of the genetic information of a living organism. Gametes (oocytes and spermatozoa) contain only a single set of 23 chromosomes within structures known as pronuclei (PN). Upon fertilization, the 23 chromosomes from the oocyte and the 23 chromosomes from the sperm combine to form a 2PN zygote, which contains a total of 46 chromosomes.
In assisted reproduction (ART) laboratories, the embryologists can determine through morphological evaluation whether the fertilization process was normal (2PN) or abnormal (0PN, 1PN, or >2PN). For an ART treatment, only a successfully fertilized oocyte (2PN) that develops to the blastocyst stage may be suitable for embryo transfer. However, previous studies have demonstrated that some embryos from oocytes with abnormal fertilization may possess a normal chromosomal content and could be used in ARTs when embryos from normal fertilization are not available.
There are genetic analysis techniques to determine not only if an embryo is euploid (contains a normal number of chromosomes) but also to assess if it is haploid, diploid or triploid (1PN, 2.1PN, and 3PN respectively). These techniques may be applied to "rescue" embryos with abnormal fertilization that are currently being discarded. This approach could be beneficial for IVF patients with a limited number of viable embryos available (diminished ovarian reserve cases, advanced maternal age, poor response to ovarian stimulation, etc.).
The current prospective and observational study has been approved by the competent Research Ethics Committee and every potential participant will be asked to sign the study informed consent.
The 300 embryos that will be part of the study will be recruited in the laboratory of the collaborating center on the day of fertilization after performing the conventional IVF procedures. Following these same routine procedures, biological samples from both parents will also be stored to perform the genetic analysis to determine the origin of the chromosomal anomalies. A biopsy will be taken from the selected embryos when they reach the blastocyst stage for the genetic analysis that will allow detecting whether there is indeed any chromosomal anomaly. All embryos not confirmed as chromosomally normal will be thawed, washed, and cultured for a second biopsy to confirm their previous diagnosis and the origin of the chromosomal abnormalities. For this new analysis, in addition to the biopsies, individual samples of the culture media of the thawed blastocysts will be collected and stored. Samples will be shipped to Igenomix for the genetic research and further data analysis.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ART patients who sign the Informed Consent of the study.
- •Age: oocytes from women ≤ 49 years and semen from men ≤ 60 years. Donation of gametes is allowed.
- •≥1 blastocysts from oocytes with an abnormal pronuclear pattern (1PN, 2.1PN, and/or 3PN) and with the presence of 2 polar bodies (PB), cultured in a time-lapse incubator.
排除标准
- •No exclusion criteria have been considered for this study.
研究组 & 干预措施
Blastocysts from abnormally fertilized oocytes during assisted reproduction
During the conventional ICSI/IVF procedures in the laboratory, the embryologist observing fertilization will identify embryos with an abnormal pronuclear pattern and preselect them for the study. These embryos will be cultured in a time-lapse incubator following the laboratory's standard practice. All recorded morphokinetic parameters, along with the corresponding images, will be documented. Each embryo will be monitored, its developmental quality assessed and recorded to determine whether it reaches the blastocyst stage. If so, the researchers will contact the patient to ask consent for these embryos to be included in the study.
Embryos with an abnormal pronuclear pattern that fail to reach the blastocyst stage due to developmental blockage will be discarded.
No drugs or medical devices will be used.
干预措施: Parental samples (Genetic)
Blastocysts from abnormally fertilized oocytes during assisted reproduction
During the conventional ICSI/IVF procedures in the laboratory, the embryologist observing fertilization will identify embryos with an abnormal pronuclear pattern and preselect them for the study. These embryos will be cultured in a time-lapse incubator following the laboratory's standard practice. All recorded morphokinetic parameters, along with the corresponding images, will be documented. Each embryo will be monitored, its developmental quality assessed and recorded to determine whether it reaches the blastocyst stage. If so, the researchers will contact the patient to ask consent for these embryos to be included in the study.
Embryos with an abnormal pronuclear pattern that fail to reach the blastocyst stage due to developmental blockage will be discarded.
No drugs or medical devices will be used.
干预措施: PGT-A (Diagnostic Test)
Blastocysts from abnormally fertilized oocytes during assisted reproduction
During the conventional ICSI/IVF procedures in the laboratory, the embryologist observing fertilization will identify embryos with an abnormal pronuclear pattern and preselect them for the study. These embryos will be cultured in a time-lapse incubator following the laboratory's standard practice. All recorded morphokinetic parameters, along with the corresponding images, will be documented. Each embryo will be monitored, its developmental quality assessed and recorded to determine whether it reaches the blastocyst stage. If so, the researchers will contact the patient to ask consent for these embryos to be included in the study.
Embryos with an abnormal pronuclear pattern that fail to reach the blastocyst stage due to developmental blockage will be discarded.
No drugs or medical devices will be used.
干预措施: TE rebiopsies and spent blastocyst media collection (Genetic)
结局指标
主要结局
Diploidy rate in haploid embryos from IVF/ICSI
时间窗: 3 months
Number of 2PN blastocysts from abnormally fertilized oocytes (1PN)
Diploidy rate in triploid embryos from IVF/ICSI
时间窗: 3 months
Number of 2PN blastocysts from abnormally fertilized oocytes (2.1PN and 3PN)
次要结局
- Origin of the chromosomal abnormalities in embryos with a non-diploid chromosomal content(6 months)
- Ectopic pregnancy rate of euploid embryos from abnormal fertilization(4-5 weeks after the embryo transfer)
- Pregnancy rate of euploid embryos from abnormal fertilization(2 weeks after the embryo transfer)
- Implantation rate of euploid embryos from abnormal fertilization(Up to 4 weeks after the embryo transfer)
- Clinical miscarriage rate of euploid embryos from abnormal fertilization(Up to 12 gestational weeks)
- Ongoing pregnancy rate of euploid embryos from abnormal fertilization(Over 12 gestational weeks)
- Voluntary termination rate of euploid embryos from abnormal fertilization(Up to 12 gestational weeks)
- Biochemical pregnancy rate of euploid embryos from abnormal fertilization(4 weeks after the embryo transfer with euploid embryos from abnormal fertilization)