Clinical trial NCT03642574: Preimplantation DNA Methylation Test (PIMT) in ART
Official title: Cumulative Live Birth Rate With eSET After Preimplantation DNA Methylation Test (PIMT) in ART
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: DNA Methylation
Keywords: Preimplantation Methylome Screening
Preimplantation Genetic Screening
single embryo transfer
cumulative live birth rate
Lead sponsor: Shandong University
Sponsor class: OTHER
Collaborators: name: Chinese Academy of Sciences
First posted: 2018-08-22
Enrollment: 182
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

1. 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).
2. 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:

1. 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.
2. Women with untreated hydrosalpinx.
3. Women who use donated oocytes or sperm to achieve pregnancy.
4. 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.

Primary outcomes:
measure: The effect of DNA methylation level on live birth rate
timeFrame: 22 months
Secondary outcomes:
measure: The effect of DNA methylation level on pregnant rate, pregnant loss rate.
timeFrame: 22 months
measure: Duration of pregnancy
timeFrame: 22 months
measure: Birth weight
timeFrame: 22 months
measure: Cumulative incidence of maternal complications during whole
timeFrame: 22 months
measure: Cumulative incidence of neonatal complications during whole
timeFrame: 22 months
measure: Number of embryo transfers to achieve live birth
timeFrame: 22 months
Other outcomes:
measure: Clinical pregnancy rate after the first transfer
timeFrame: 4 months
measure: Pregnancy loss rate after the first transfer
timeFrame: 9 months
measure: Live birth rate after the first transfer
timeFrame: 12 months
Locations:
city: Jinan
country: China
facility: Shandong University
state: Shandong
Study officials:
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