A Randomized Double Blind Controlled Trial of Non-invasive Preimplantation Genetic Testing for Aneuploidy in Women With Recurrent Pregnancy Loss
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 152
- 试验地点
- 1
- 主要终点
- Miscarriage rate
研究概览
简要总结
Objectives: To compare the efficacy in embryo selection based on morphology alone compared to morphology and non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) in women with recurrent pregnancy loss (RPL) undergoing in vitro fertilization (IVF).
Hypothesis to be tested: The embryo selection based on morphology and niPGT-A results in a lower miscarriage rate and a higher live birth rate in IVF as compared with that based on morphology alone.
Design and subjects: Randomized double-blind randomized controlled trial. Women with RPL undergoing IVF will be enrolled.
Interventions: Spent culture medium (SCM) of each blastocyst will be frozen individually. They will be randomly allocated into two groups: (1) the intervention group based on morphology and niPGT-A and (2) the control group based on morphology alone.
In the control group, blastocysts with the best quality morphology will be replaced first. In the intervention group, blastocysts with the best morphology and euploid result of SCM will be replaced first.
Main outcome measures: The primary outcome is the miscarriage rate per the first embryo transfer.
Data analysis: Comparison of quantitative variables will be performed using Student's t, while categorical variables will be compared using a Chi-square analysis. All statistical analyses will be performed with the intention to treat and per protocol, and a p-value <0.05 will be considered statistically significant.
Expected outcome results: The embryo selection based on morphology and niPGT-A results in a lower miscarriage rate and a higher live birth rate in IVF as compared with the control group based on morphology alone.
详细描述
Trial Objectives and Purpose The primary objective of this randomized double blind controlled trial is to compare the efficacy in embryo selection based on morphology alone versus morphology and niPGT-A in women with RPL undergoing the first frozen embryo transfer. The secondary objectives are to evaluate the impact of eNK cells on the miscarriage and live birth rates and the prediction of live birth using spheroid/BAP-EB attachment assay.
Main hypotheses to be tested:
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The embryo selection based on morphology and niPGT-A for aneuploidy results in a higher live birth rate of IVF in women with RPL as compared with the control group based on morphology alone.
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The embryo selection based on morphology and niPGT-A for aneuploidy results in a lower miscarriage rate following IVF in women with RPL as compared with the control group based on morphology alone.
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Trial Design This is a randomized double blind controlled trial. Eligible women will be recruited for the study and informed written consent will be obtained after counseling.
Endometrial assessment All women will have an endometrial biopsy using a Pipelle sampler 7 days after luteinizing hormone surge (LH+7) prior to the month of having IVF. Part of the endometrial samples will be fixed in paraformaldehyde for immunohistochemical staining of endometrial uNK cells with CD56 antibody [26,27]. The other part of the endometrial samples will be used for epithelial and stromal cell isolation for spheroid/BAP-EB attachment assay [28], to predict the embryo attachment rate in a laboratory setting. Due to ethical issues and practical difficulty, the use of human embryos for endometrial assessment is not feasible. BAP-EB model [28] will be used as the embryo (blastocyst) surrogate in this study. BAP-EB spheroid model are differentiated from human embryonic stem cells. The BAP-EB after 72h of differentiation (BAP-EB-72h) have molecular signature of Day 7 trophectoderm cells of blastocysts [28]. In this study, BAP-EB will be co-cultured with primary endometrial epithelial cells and the attachment rate will be determined according to our established protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- Double (Participant, Care Provider)
盲法说明
The embryologist will grade the morphology of blastocysts according to Gardner's criteria stated above and enter the grading of blastocysts into an online database, which will be managed by an IT technician. The laboratory staff in the PGT laboratory will enter the PGT result into a local database when the NIPGT results are available. The IT technician will collect the database from the PGT laboratory and enter it into the online software to compile the sequence of embryo transfer according to a pre-determined algorithm which depends on the day of blastocyst development (day 5 better than day 6), blastocyst morphology and niPGT-A result. The IT technician will issue the sequence of embryo transfer which does not contain information on the grading of the blastocyst and the NIPGT result to the embryologists in the IVF laboratory. Therefore, the subjects recruited, the clinicians and the embryologists will be blinded to the group allocation.
入排标准
- 年龄范围
- 18 Years 至 39 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged less than 40 years at the time of ovarian stimulation and
- •>=two spontaneous miscarriages in the first trimester
- •Unexplained recurrent pregnancy loss after standard investigation
- •At least one blastocyst available on day 5 or 6 after the retrieval.
排除标准
- •Women undergoing PGT for monogenic diseases or structural rearrangement of chromosomes;
- •Use of donor oocytes;
- •Hydrosalpinx shown on pelvic scanning and not surgically treated
- •Uterine anomalies distorting the uterine cavity in three dimensional ultrasound
- •No usable blastocysts on day 5 or 6 after the retrieval
结局指标
主要结局
Miscarriage rate
时间窗: 12 weeks
Miscarriage rate in the first FET and is defined as a clinically recognized pregnancy loss before the 22 weeks of pregnancy and whose denominator is the clinical pregnancy. • Miscarriage rate in the first FET and is defined as a clinically recognized pregnancy loss before the 22 weeks of pregnancy and whose denominator is the clinical pregnancy.
次要结局
- Congenital anomaly(2 years)
- positive urine pregnancy test(at 2 weeks after embryo tranfer)
- Ongoing pregnancy(10 weeks)
- Clinical pregnancy(6 weeks)
- Multiple pregnancy(more than one intrauterine sac at 6-8 weeks)
- Ectopic pregnancy(12 weeks)
- Live birth(1 year)
- Placental weight(2 year)
- Preterm delivery(2 years)
- Spheroid attachment rate(one month before start of IVF)
- Gestational hypertension(2 year)
- Pre-eclampsia(2 year)
- Antepartum haemorrhage(2 year)
- Birthweight of newborn(2 year)
- Number of CD56 cells(one month before start of IVF)
- Gestational diabetes(2 year)
- Perinatal mortality(2 year)
- Gestational proteinuria(2 year)
研究者
Cheng Hiu Yee Heidi
Associate Consultant
Queen Mary Hospital, Hong Kong