- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03642574
Preimplantation DNA Methylation Test (PIMT) in ART
October 1, 2022 updated by: Chen Zi-Jiang
Cumulative Live Birth Rate With eSET After Preimplantation DNA Methylation Test (PIMT) in ART
The purpose of this clinical trial is to determine the safety and effect of methylation level of DNA methylation in embryos on the outcome of assisted reproductive technology (ART) during blastocyst embryo screening.
Subjects with blastocysts on day 5-7 of embryo culture will be biopsied.
A Freeze-all strategy and a single frozen blastocyst transfer will be performed till all study-specific embryos have been transferred.
Then whole genome bisulfate sequencing will be performed on all cells that obtained from biopsy.
Study Overview
Detailed Description
The purpose of this clinical trial is to determine the safety and affect of DNA methylation level on ART.
Subjects with blastocysts on day 5-7 of embryo culture will be biopsied.
A Freeze-all strategy and a single frozen blastocyst transfer will be performed till all study-specific embryos have been transferred.
Then whole genome bisulfate sequencing will be performed on all cells that obtained from biopsy.
The investigators will perform whole genome DNA methylation sequence for two to seven blastocysts from one couple.
The methylation level and genomic copy number variation will be analyzed by using the methylome data.
Embryos with aneuploid chromosomes will be rejected for embryo transfer to uterus.
The study will examine which kind of methylation level can produce the best clinical outcome for ART.
Biopsied cells will perform with preimplnatation DNA methylation test (PIMT).
DNA methylation level and chromosome copy number variation will be calculated by using whole genome DNA methylation sequencing data.
As we do not kown which kind of methylation state can produce the best outcome in ART practice.
This study will try to find a standard of selection embryos according to DNA methylation information.
Under current stage, the selection of embryo is according to chromosome copy number.
The embryo selection will not consider DNA methylation information for this study.
Study Type
Interventional
Enrollment (Actual)
182
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Shandong
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Jinan, Shandong, China
- Shandong University
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
20 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
Inclusion Criteria:
- Women who are participating in preimplantation screening with PGS indications,defined as maternal age above 38 years, repeated implantation failure (RIF) usually defined as three or more transfers of morphologically high-quality embryos without the establishment of pregnancy, recurrent miscarriage (RM) in patients with normal karyotypes (usually at least three previous consecutive miscarriages) and severe male factor infertility (usually defined as abnormal semen parameters).
- Women who obtain 2 or more good-quality blastocysts that defined as morphological score of inner cell mass B or A, trophectoderm C or better, and grade 4 or better on Day five of embryo culture will be randomized.
Exclusion Criteria:
- Women with a uterine cavity abnormality, such as a uterine congenital malformation (uterus unicornate, bicornate, or duplex); untreated uterine septum, adenomyosis, submucous myoma, or endometrial polyp(s); or with history of intrauterine adhesions.
- Women with untreated hydrosalpinx.
- Women who use donated oocytes or sperm to achieve pregnancy.
- Women with contraindication for assisted reproductive technology or for pregnancy, such as poorly controlled Type I or Type II diabetes; undiagnosed liver disease or dysfunction (based on serum liver enzyme testing); renal disease or abnormal serum renal function; significant anemia; history of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident; uncontrolled hypertension, known symptomatic heart disease; history of or suspected cervical carcinoma, endometrial carcinoma, or breast carcinoma; undiagnosed vaginal bleeding.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: PIMT methylation
Subjects will have blastocyst biopsy and whole genome DNA methylation sequencing done with 2 or 7 good-quality embryos on Day 5 to 7. Principle of freeze-all and single thawed blastocyst transfer will be applied.
Only embryos with euploid chromosome will be transfered to the uterus.
The outcome of all euploids transfers within 1 year will be followed up.
During study, every subject will have at most one live birth.
|
Embryo with euploid chromosome will transfer to uterus.
The order of transfer is accroding to morphological grade.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The effect of DNA methylation level on live birth rate
Time Frame: 22 months
|
The rate of live birth at different methylation level will be calculated.
Live birth is defined as the delivery of any viable infant at 28 weeks or more of gestation, and cumulative live birth rate is calculated by dividing the number of women achieving live birth after transfers (up to 3 transfers of single blastocycst within 1 year).
|
22 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The effect of DNA methylation level on pregnant rate, pregnant loss rate.
Time Frame: 22 months
|
The rate of pregnant and pregnant loss at different methylation level will be calculated.
Pregnancy loss refers to a complete spontaneous abortion or a nonviable pregnancy before 28 weeks of gestation.
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22 months
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Duration of pregnancy
Time Frame: 22 months
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The time from the first day of last menstrual period to the day of delivery.
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22 months
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Birth weight
Time Frame: 22 months
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Weight of newborns at delivery.
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22 months
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Cumulative incidence of maternal complications during whole
Time Frame: 22 months
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Number of pregnancies with complications / number of pregnancies over (up to) 3 transfers within 1 year;
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22 months
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Cumulative incidence of neonatal complications during whole
Time Frame: 22 months
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Number of live births with neonatal complications / number of live births over (up to)3 transfers within 1 year
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22 months
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Number of embryo transfers to achieve live birth
Time Frame: 22 months
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Number of embryo transfers the patients have gone through to achieve live birth.
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22 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical pregnancy rate after the first transfer
Time Frame: 4 months
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Number of women with clinical pregnancies after the first transfer / number of women.
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4 months
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Pregnancy loss rate after the first transfer
Time Frame: 9 months
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Number of pregnancy losses / number of clinical pregnancies after the first transfer .
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9 months
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Live birth rate after the first transfer
Time Frame: 12 months
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Number of women with live births after the first transfer / number of women.
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12 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Chen ZJ, Shi Y, Sun Y, Zhang B, Liang X, Cao Y, Yang J, Liu J, Wei D, Weng N, Tian L, Hao C, Yang D, Zhou F, Shi J, Xu Y, Li J, Yan J, Qin Y, Zhao H, Zhang H, Legro RS. Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome. N Engl J Med. 2016 Aug 11;375(6):523-33. doi: 10.1056/NEJMoa1513873. Erratum In: N Engl J Med. 2016 Nov 17;375(20):2010.
- Shi Y, Sun Y, Hao C, Zhang H, Wei D, Zhang Y, Zhu Y, Deng X, Qi X, Li H, Ma X, Ren H, Wang Y, Zhang D, Wang B, Liu F, Wu Q, Wang Z, Bai H, Li Y, Zhou Y, Sun M, Liu H, Li J, Zhang L, Chen X, Zhang S, Sun X, Legro RS, Chen ZJ. Transfer of Fresh versus Frozen Embryos in Ovulatory Women. N Engl J Med. 2018 Jan 11;378(2):126-136. doi: 10.1056/NEJMoa1705334. Erratum In: N Engl J Med. 2021 Nov 4;385(19):1824.
- Brezina PR, Kutteh WH. Clinical applications of preimplantation genetic testing. BMJ. 2015 Feb 19;350:g7611. doi: 10.1136/bmj.g7611.
- Hassold T, Chen N, Funkhouser J, Jooss T, Manuel B, Matsuura J, Matsuyama A, Wilson C, Yamane JA, Jacobs PA. A cytogenetic study of 1000 spontaneous abortions. Ann Hum Genet. 1980 Oct;44(2):151-78. doi: 10.1111/j.1469-1809.1980.tb00955.x.
- Dahdouh EM, Balayla J, Audibert F; Genetics Committee; Wilson RD, Audibert F, Brock JA, Campagnolo C, Carroll J, Chong K, Gagnon A, Johnson JA, MacDonald W, Okun N, Pastuck M, Vallee-Pouliot K. RETIRED: Technical Update: Preimplantation Genetic Diagnosis and Screening. J Obstet Gynaecol Can. 2015 May;37(5):451-63. doi: 10.1016/s1701-2163(15)30261-9.
- Kalousek DK, Pantzar T, Tsai M, Paradice B. Early spontaneous abortion: morphologic and karyotypic findings in 3,912 cases. Birth Defects Orig Artic Ser. 1993;29(1):53-61. No abstract available.
- Smith ZD, Meissner A. DNA methylation: roles in mammalian development. Nat Rev Genet. 2013 Mar;14(3):204-20. doi: 10.1038/nrg3354. Epub 2013 Feb 12.
- Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012 May 29;13(7):484-92. doi: 10.1038/nrg3230.
- Jiang L, Zhang J, Wang JJ, Wang L, Zhang L, Li G, Yang X, Ma X, Sun X, Cai J, Zhang J, Huang X, Yu M, Wang X, Liu F, Wu CI, He C, Zhang B, Ci W, Liu J. Sperm, but not oocyte, DNA methylome is inherited by zebrafish early embryos. Cell. 2013 May 9;153(4):773-84. doi: 10.1016/j.cell.2013.04.041.
- Li G, Yu Y, Fan Y, Li C, Xu X, Duan J, Li R, Kang X, Ma X, Chen X, Ke Y, Yan J, Lian Y, Liu P, Zhao Y, Zhao H, Chen Y, Sun X, Liu J, Qiao J, Liu J. Genome wide abnormal DNA methylome of human blastocyst in assisted reproductive technology. J Genet Genomics. 2017 Oct 20;44(10):475-481. doi: 10.1016/j.jgg.2017.09.001. Epub 2017 Sep 6.
- Schieve LA, Meikle SF, Peterson HB, Jeng G, Burnett NM, Wilcox LS. Does assisted hatching pose a risk for monozygotic twinning in pregnancies conceived through in vitro fertilization? Fertil Steril. 2000 Aug;74(2):288-94. doi: 10.1016/s0015-0282(00)00602-6.
- Fiorentino F, Biricik A, Bono S, Spizzichino L, Cotroneo E, Cottone G, Kokocinski F, Michel CE. Development and validation of a next-generation sequencing-based protocol for 24-chromosome aneuploidy screening of embryos. Fertil Steril. 2014 May;101(5):1375-82. doi: 10.1016/j.fertnstert.2014.01.051. Epub 2014 Mar 6.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
September 5, 2018
Primary Completion (ACTUAL)
August 28, 2021
Study Completion (ACTUAL)
June 30, 2022
Study Registration Dates
First Submitted
August 16, 2018
First Submitted That Met QC Criteria
August 21, 2018
First Posted (ACTUAL)
August 22, 2018
Study Record Updates
Last Update Posted (ACTUAL)
October 4, 2022
Last Update Submitted That Met QC Criteria
October 1, 2022
Last Verified
October 1, 2022
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- PIMT
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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