First Live Birth Rate With eSET After Preimplantation Methylome Screening (PIMS) Versus Conventional In-vitro Fertilization

NCT ID: NCT05442125

Last Updated: 2024-01-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

1146 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-16

Study Completion Date

2025-05-31

Brief Summary

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To determine whether using DNA methylome to select embryos can increase the live birth rate.

Detailed Description

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The rationale for the study is to establish the risk/benefit ratio of PIMS in women with in vitro fertilization (IVF) treatment, as DNA methylome is a potential biomarker in blastocyst selection in assited reproductive technology (ART). DNA methylation plays an important role during embryogenesis, global abnormal methylome reprogramming often occurs in human embryos, and DNA methylome pattern is associated with live birth rate. However, there is still no technology using DNA methylome as an indicator in preimplantation embryo screening. Recent paper reported that using Pre-implantation Methylome Screening (PIMS) can select embryos with better methylation state and euploid chromosomes. The efficiency of PIMS needs further validation through randomized clinical trial.

Conditions

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Reproductive Techniques, Assisted DNA Methylation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PIMS group

Couples in the PIMS group will have up to 6 blastocysts screened with PIMS and a single euploid embryo with the optimal state of whole-genome DNA methylation and the highest morphologic score will be selected for the initial transfer. The optimal state of whole-genome DNA methylation includes methylation level closest to the optimal level (0.26 according to our preliminary results) and proper methylation state for some specific regions.

Group Type EXPERIMENTAL

Using DNA methylome to select embryos

Intervention Type OTHER

DNA methylation level Embryo with methylation level closest to the optimal level (from one couple patients) is the one for embryonic transfer to uterus

Conventional-IVF group

For women between 20 and 37 years of age,couples in the conventional-IVF group will have a single best blastocyst by morphologic criteria selected for the initial transfer.For women over 37 years old, couples in the PGT-A group will have up to 6 blastocysts tested with PGT-A and a single euploid embryo with the highest morphologic score will be selected for the initial transfer.

Group Type ACTIVE_COMPARATOR

Using morphologic score to select embryos

Intervention Type OTHER

blastocyst will transferred according to morphologic score or blastocysts will be biopsied on trophectoderm, sequenced with next-generation sequencing (NGS). Euploidy will transferred one by one according to morphologic score.

Interventions

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Using DNA methylome to select embryos

DNA methylation level Embryo with methylation level closest to the optimal level (from one couple patients) is the one for embryonic transfer to uterus

Intervention Type OTHER

Using morphologic score to select embryos

blastocyst will transferred according to morphologic score or blastocysts will be biopsied on trophectoderm, sequenced with next-generation sequencing (NGS). Euploidy will transferred one by one according to morphologic score.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Women who plan to undergo IVF/ICSI/PGT-A treatment.
2. Women aged 20 years and older.

b) 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 5 of embryo culture.

Exclusion Criteria

1. Women with a uterine cavity abnormality, such as a uterine congenital malformation (uterus unicornate, bicornate, or duplex); untreated uterine septum, submucous myoma, or endometrial polyp(s); or with history of intrauterine adhesions.
2. Women who are indicated and planned to undergo preimplantation genetic testing for structural rearrangements (PGT-SR) or preimplantation genetic testing for monogenic (PGT-M).
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.
Minimum Eligible Age

20 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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RenJi Hospital

OTHER

Sponsor Role collaborator

Reproductive & Genetic Hospital of CITIC-Xiangya

OTHER

Sponsor Role collaborator

Nanjing Maternity and Child Health Care Hospital

OTHER

Sponsor Role collaborator

ShangHai Ji Ai Genetics & IVF Institute

OTHER

Sponsor Role collaborator

Suzhou Municipal Hospital

OTHER

Sponsor Role collaborator

The First Hospital of Jilin University

OTHER

Sponsor Role collaborator

Sir Run Run Shaw Hospital

OTHER

Sponsor Role collaborator

The Affiliated Hospital Of Guizhou Medical University

OTHER

Sponsor Role collaborator

The Second Hospital of Hebei Medical University

OTHER

Sponsor Role collaborator

Third Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role collaborator

Ruijin Hospital

OTHER

Sponsor Role collaborator

International Peace Maternity and Child Health Hospital

OTHER

Sponsor Role collaborator

Henan Provincial People's Hospital

OTHER

Sponsor Role collaborator

The First Affiliated Hospital of Hainan Medical University

OTHER_GOV

Sponsor Role collaborator

The First Affiliated Hospital of Anhui Medical University

OTHER

Sponsor Role collaborator

Fujian Maternity and Child Health Hospital

OTHER

Sponsor Role collaborator

General Hospital of Ningxia Medical University

OTHER

Sponsor Role collaborator

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role collaborator

900 Hospital of Joint Logistics Support Force of PLA

OTHER

Sponsor Role collaborator

Guangzhou Womenand Children's Medical Center

UNKNOWN

Sponsor Role collaborator

Changhai Hospital

OTHER

Sponsor Role collaborator

Shenzhen Maternity & Child Healthcare Hospital

OTHER

Sponsor Role collaborator

Sixth Affiliated Hospital, Sun Yat-sen University

OTHER

Sponsor Role collaborator

Liuzhou Hospital of Guangzhou Women and Children's Medical Center

UNKNOWN

Sponsor Role collaborator

Jining Medical University

OTHER

Sponsor Role collaborator

Siriraj Hospital

OTHER

Sponsor Role collaborator

Shandong University

OTHER

Sponsor Role lead

Responsible Party

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Chen Zi-Jiang

Academician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yuan Gao, Professor

Role: STUDY_DIRECTOR

Center for Reproductive Medicine, Shandong University

Yun Sun, Professor

Role: PRINCIPAL_INVESTIGATOR

Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine,Shanghai Jiao Tong University

Ge Lin, Professor

Role: PRINCIPAL_INVESTIGATOR

Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA

Xiufeng Ling, Professor

Role: PRINCIPAL_INVESTIGATOR

Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital

Xiaoxi Sun, Professor

Role: PRINCIPAL_INVESTIGATOR

Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University

Hong Li, Professor

Role: PRINCIPAL_INVESTIGATOR

Center for reproduction and genetics,suzhou municipal hospital

Ruizhi Liu, Professor

Role: PRINCIPAL_INVESTIGATOR

Center for Reproductive Medicine, Center for Prenatal Diagnosis First Hospital, Jilin University

Songying Zhang, Professor

Role: PRINCIPAL_INVESTIGATOR

Assisted Reproduction Unit, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Shuyun Zhao, Professor

Role: PRINCIPAL_INVESTIGATOR

Center for Reproductive Medicine, The Affiliated Hospital of Guizhou Medical University

Guimin Hao, Professor

Role: PRINCIPAL_INVESTIGATOR

The Second Hospital of Hebei Medical University

Yichun Guan, Professor

Role: PRINCIPAL_INVESTIGATOR

Department of Reproductive Medicine, the Third Affiliated Hospital of Zhengzhou University

Aijun Zhang, Professor

Role: PRINCIPAL_INVESTIGATOR

Reproductive Medical Center of Ruijin Hospital, School of Medicine,Shanghai Jiao Tong University

Wen Li, Professor

Role: PRINCIPAL_INVESTIGATOR

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University

Cuilian Zhang, Professor

Role: PRINCIPAL_INVESTIGATOR

Reproductive Medical Center, Henan Provincial People's Hospital

Yanlin Ma, Professor

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Hainan Medical University

Yunxia Cao, Professor

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Anhui Medical University

Beihong Zhen, Professor

Role: PRINCIPAL_INVESTIGATOR

Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University

Junli Zhao, Professor

Role: PRINCIPAL_INVESTIGATOR

The General Hospital of Ningxia Medical University

Xiang Ma, Professor

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital with Nanjing Medical University

Yun Liu, Professor

Role: PRINCIPAL_INVESTIGATOR

900 Hospital of Joint Logistics Support Force of PLA

Ling Sun, Professor

Role: PRINCIPAL_INVESTIGATOR

Guangzhou Womenand Children's Medical Center

Hongli Yan, Professor

Role: PRINCIPAL_INVESTIGATOR

Changhai Hospital

Xuemei Li, Professor

Role: PRINCIPAL_INVESTIGATOR

Shenzhen Maternity & Child Healthcare Hospital

Haitao Zeng, Professor

Role: PRINCIPAL_INVESTIGATOR

Sixth Affiliated Hospital, Sun Yat-sen University

Li Fan, Professor

Role: PRINCIPAL_INVESTIGATOR

Liuzhou Hospital of Guangzhou Women and Children's Medical Center

Aijun Yang, Professor

Role: PRINCIPAL_INVESTIGATOR

Jining Medical University

Isarin Thanaboonyawat, Doctor

Role: PRINCIPAL_INVESTIGATOR

Siriraj Hospital

Locations

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Shandong University

Jinan, Shandong, China

Site Status RECRUITING

Center for Reproductive Medicine, Center for Prenatal Diagnosis First Hospital, Jilin University

Changchun, , China

Site Status RECRUITING

Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA

Changsha, , China

Site Status RECRUITING

900 th Hospital of Joint Logistics Support Force

Fuzhou, , China

Site Status RECRUITING

Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University

Fuzhou, , China

Site Status RECRUITING

Guangzhou Womenand Children's Medical Center

Guanzhou, , China

Site Status RECRUITING

The Sixth Affiliated Hospital of Sun Yat-sen University

Guanzhou, , China

Site Status NOT_YET_RECRUITING

Center for Reproductive Medicine, The Affiliated Hospital of Guizhou Medical University

Guiyang, , China

Site Status RECRUITING

The first affiliated hospital of Hainan Medical University

Haikou, , China

Site Status RECRUITING

Assisted Reproduction Unit, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, , China

Site Status RECRUITING

The First Affiliated Hospital of Anhui Medical University

Hefei, , China

Site Status RECRUITING

Center for Reproductive Medicine, Shandong University

Jinan, , China

Site Status RECRUITING

Affiliated Hospital of Jining Medical University

Jining, , China

Site Status RECRUITING

Liuzhou Hospital of Guangzhou Women and Children's Medical Center

Liuzhou, , China

Site Status RECRUITING

Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital

Nanjing, , China

Site Status RECRUITING

The First Affiliated Hospital with Nanjing Medical University

Nanjing, , China

Site Status RECRUITING

Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine,Shanghai Jiao Tong University

Shanghai, , China

Site Status RECRUITING

Changhai Hospital

Shanghai, , China

Site Status NOT_YET_RECRUITING

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University

Shanghai, , China

Site Status NOT_YET_RECRUITING

Reproductive Medical Center of Ruijin Hospital, School of Medicine,Shanghai Jiao Tong University

Shanghai, , China

Site Status NOT_YET_RECRUITING

Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University

Shanghai, , China

Site Status NOT_YET_RECRUITING

Shenzhen Maternity & Child Healthcare Hospital

Shenzhen, , China

Site Status RECRUITING

The Second Hospital of Hebei Medical University

Shijiazhuang, , China

Site Status RECRUITING

Center for reproduction and genetics,suzhou municipal hospital

Suzhou, , China

Site Status RECRUITING

The General Hospital of Ningxia Medical University

Yinchuan, , China

Site Status RECRUITING

Department of Reproductive Medicine, the Third Affiliated Hospital of Zhengzhou University

Zhengzhou, , China

Site Status RECRUITING

Reproductive Medical Center, Henan Provincial People's Hospital

Zhengzhou, , China

Site Status RECRUITING

Siriraj hospital, Mahidol university

Bangkok, , Thailand

Site Status NOT_YET_RECRUITING

Countries

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China Thailand

Central Contacts

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Yuan Gao, Professor

Role: CONTACT

0531-86569866

Facility Contacts

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Zi-Jiang Chen, Professor

Role: primary

+0086 531 85651190

Yuan Gao, Professor

Role: backup

+0086 531 86569866

Ruizhi Liu, Professor

Role: primary

Lin Ge, Professor

Role: primary

Yun Liu, Professor

Role: primary

Beihong Zhen, Professor

Role: primary

Ling Sun, Professor

Role: primary

Haitao Zeng, Professor

Role: primary

Shunyun Zhao, Professor

Role: primary

Yanlin Ma, Professor

Role: primary

Songying Zhang, Professor

Role: primary

Yunxia Cao, Professor

Role: primary

Yuan Gao, Professor

Role: primary

Aijun Yang, Professor

Role: primary

Li Fan, Professor

Role: primary

Xiufeng Ling, Professor

Role: primary

Xiang Ma, Professor

Role: primary

Yun Sun, Professor

Role: primary

Hongli Yan, Professor

Role: primary

Wen Li, Professor

Role: primary

Aijun Zhang, Professor

Role: primary

Xiaoxi Sun, Professor

Role: primary

Xuemei Li, Professor

Role: primary

Guimin Hao, Professor

Role: primary

Hong Li, Professor

Role: primary

Junli Zhao, Professor

Role: primary

Yichun Guan, Professor

Role: primary

Cuilian Zhang, Professor

Role: primary

Isarin Thanaboonyawat, Doctor

Role: primary

References

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Brezina PR, Kutteh WH. Clinical applications of preimplantation genetic testing. BMJ. 2015 Feb 19;350:g7611. doi: 10.1136/bmj.g7611.

Reference Type RESULT
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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.

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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.

Reference Type RESULT
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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.

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Rubio C, Bellver J, Rodrigo L, Castillon G, Guillen A, Vidal C, Giles J, Ferrando M, Cabanillas S, Remohi J, Pellicer A, Simon C. In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study. Fertil Steril. 2017 May;107(5):1122-1129. doi: 10.1016/j.fertnstert.2017.03.011. Epub 2017 Apr 19.

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Sacchi L, Albani E, Cesana A, Smeraldi A, Parini V, Fabiani M, Poli M, Capalbo A, Levi-Setti PE. Preimplantation Genetic Testing for Aneuploidy Improves Clinical, Gestational, and Neonatal Outcomes in Advanced Maternal Age Patients Without Compromising Cumulative Live-Birth Rate. J Assist Reprod Genet. 2019 Dec;36(12):2493-2504. doi: 10.1007/s10815-019-01609-4. Epub 2019 Nov 12.

Reference Type RESULT
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Yan J, Qin Y, Zhao H, Sun Y, Gong F, Li R, Sun X, Ling X, Li H, Hao C, Tan J, Yang J, Zhu Y, Liu F, Chen D, Wei D, Lu J, Ni T, Zhou W, Wu K, Gao Y, Shi Y, Lu Y, Zhang T, Wu W, Ma X, Ma H, Fu J, Zhang J, Meng Q, Zhang H, Legro RS, Chen ZJ. Live Birth with or without Preimplantation Genetic Testing for Aneuploidy. N Engl J Med. 2021 Nov 25;385(22):2047-2058. doi: 10.1056/NEJMoa2103613.

Reference Type RESULT
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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.

Reference Type RESULT
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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.

Reference Type RESULT
PMID: 22641018 (View on PubMed)

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.

Reference Type RESULT
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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.

Reference Type RESULT
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Hardarson T, Van Landuyt L, Jones G. The blastocyst. Hum Reprod. 2012 Aug;27 Suppl 1:i72-91. doi: 10.1093/humrep/des230. Epub 2012 Jul 3. No abstract available.

Reference Type RESULT
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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.

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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.

Reference Type RESULT
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Other Identifiers

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PIMS-IVF

Identifier Type: -

Identifier Source: org_study_id

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