NCT05442125

Brief Summary

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

Trial Health

47
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
1,146

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Sep 2022

Typical duration for not_applicable

Geographic Reach
2 countries

28 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 28, 2022

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 1, 2022

Completed
3 months until next milestone

Study Start

First participant enrolled

September 16, 2022

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2024

Completed
12 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 31, 2025

Completed
Last Updated

January 18, 2024

Status Verified

January 1, 2024

Enrollment Period

1.7 years

First QC Date

June 28, 2022

Last Update Submit

January 15, 2024

Conditions

Reproductive Techniques, AssistedDNA Methylation

Outcome Measures

Primary Outcomes (1)

  • live birth rate of initial embryo transfer

    Live birth rate is defined as delivery of any viable infant at 28 weeks or more of gestation, after initial embryo transfer in women using the embryos selected through PIMS or PGT-A or morphological criteria alone.

    22 months

Secondary Outcomes (8)

  • Good Birth Outcome rate

    36 months

  • Clinical pregnancy rate

    36 months

  • Pregnancy loss rate

    36 months

  • Multiple pregnancy rate

    36 months

  • Duration of pregnancy

    36 months

  • +3 more secondary outcomes

Study Arms (2)

PIMS group

EXPERIMENTAL

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.

Other: Using DNA methylome to select embryos

Conventional-IVF group

ACTIVE COMPARATOR

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.

Other: Using morphologic score to select embryos

Interventions

Using DNA methylome to select embryosOTHER

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

PIMS group
Using morphologic score to select embryosOTHER

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.

Conventional-IVF group

Eligibility Criteria

Age20 Years+
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Women who plan to undergo IVF/ICSI/PGT-A treatment.
  • 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.

You may not qualify if:

  • 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.
  • Women who are indicated and planned to undergo preimplantation genetic testing for structural rearrangements (PGT-SR) or preimplantation genetic testing for monogenic (PGT-M).
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (28)

Shandong University

Jinan, Shandong, China

RECRUITING

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

Changchun, China

RECRUITING

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

Changsha, 410008, China

RECRUITING

900 th Hospital of Joint Logistics Support Force

Fuzhou, China

RECRUITING

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

Fuzhou, China

RECRUITING

Guangzhou Womenand Children's Medical Center

Guanzhou, China

RECRUITING

The Sixth Affiliated Hospital of Sun Yat-sen University

Guanzhou, China

NOT YET RECRUITING

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

Guiyang, China

RECRUITING

The first affiliated hospital of Hainan Medical University

Haikou, China

RECRUITING

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

Hangzhou, China

RECRUITING

The First Affiliated Hospital of Anhui Medical University

Hefei, China

RECRUITING

Center for Reproductive Medicine, Shandong University

Jinan, 250012, China

RECRUITING

Affiliated Hospital of Jining Medical University

Jining, China

RECRUITING

Liuzhou Hospital of Guangzhou Women and Children's Medical Center

Liuchow, China

RECRUITING

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

Nanjing, China

RECRUITING

The First Affiliated Hospital with Nanjing Medical University

Nanjing, China

RECRUITING

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

Shanghai, 200135, China

RECRUITING

Changhai Hospital

Shanghai, China

NOT YET RECRUITING

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

Shanghai, China

NOT YET RECRUITING

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

Shanghai, China

NOT YET RECRUITING

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

Shanghai, China

NOT YET RECRUITING

Shenzhen Maternity & Child Healthcare Hospital

Shenzhen, China

RECRUITING

The Second Hospital of Hebei Medical University

Shijiazhuang, China

RECRUITING

Center for reproduction and genetics,suzhou municipal hospital

Suzhou, China

RECRUITING

The General Hospital of Ningxia Medical University

Yinchuan, China

RECRUITING

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

Zhengzhou, China

RECRUITING

Reproductive Medical Center, Henan Provincial People's Hospital

Zhengzhou, China

RECRUITING

Siriraj hospital, Mahidol university

Bangkok, Thailand

NOT YET RECRUITING

Related Publications (14)

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

    PMID: 25697663RESULT

  • 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.

    PMID: 7316468RESULT

  • 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.

    PMID: 26168107RESULT

  • 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.

    PMID: 8280893RESULT

  • 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.

    PMID: 28433371RESULT

  • 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.

    PMID: 31713776RESULT

  • 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.

    PMID: 34818479RESULT

  • 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.

    PMID: 23400093RESULT

  • 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.

    PMID: 22641018RESULT

  • 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.

    PMID: 23663777RESULT

  • 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.

    PMID: 29037989RESULT

  • 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.

    PMID: 22763375RESULT

  • 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.

    PMID: 10927046RESULT

  • 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.

    PMID: 24613537RESULT

MeSH Terms

Conditions

Helping Behavior

Condition Hierarchy (Ancestors)

Social BehaviorBehavior

Study Officials

  • Yuan Gao, Professor

    Center for Reproductive Medicine, Shandong University

    STUDY DIRECTOR

  • Yun Sun, Professor

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

    PRINCIPAL INVESTIGATOR

  • Ge Lin, Professor

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

    PRINCIPAL INVESTIGATOR

  • Xiufeng Ling, Professor

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

    PRINCIPAL INVESTIGATOR

  • Xiaoxi Sun, Professor

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

    PRINCIPAL INVESTIGATOR

  • Hong Li, Professor

    Center for reproduction and genetics,suzhou municipal hospital

    PRINCIPAL INVESTIGATOR

  • Ruizhi Liu, Professor

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

    PRINCIPAL INVESTIGATOR

  • Songying Zhang, Professor

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

    PRINCIPAL INVESTIGATOR

  • Shuyun Zhao, Professor

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

    PRINCIPAL INVESTIGATOR

  • Guimin Hao, Professor

    The Second Hospital of Hebei Medical University

    PRINCIPAL INVESTIGATOR

  • Yichun Guan, Professor

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

    PRINCIPAL INVESTIGATOR

  • Aijun Zhang, Professor

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

    PRINCIPAL INVESTIGATOR

  • Wen Li, Professor

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

    PRINCIPAL INVESTIGATOR

  • Cuilian Zhang, Professor

    Reproductive Medical Center, Henan Provincial People's Hospital

    PRINCIPAL INVESTIGATOR

  • Yanlin Ma, Professor

    The First Affiliated Hospital of Hainan Medical University

    PRINCIPAL INVESTIGATOR

  • Yunxia Cao, Professor

    The First Affiliated Hospital of Anhui Medical University

    PRINCIPAL INVESTIGATOR

  • Beihong Zhen, Professor

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

    PRINCIPAL INVESTIGATOR

  • Junli Zhao, Professor

    The General Hospital of Ningxia Medical University

    PRINCIPAL INVESTIGATOR

  • Xiang Ma, Professor

    The First Affiliated Hospital with Nanjing Medical University

    PRINCIPAL INVESTIGATOR

  • Yun Liu, Professor

    900 Hospital of Joint Logistics Support Force of PLA

    PRINCIPAL INVESTIGATOR

  • Ling Sun, Professor

    Guangzhou Womenand Children's Medical Center

    PRINCIPAL INVESTIGATOR

  • Hongli Yan, Professor

    Changhai Hospital

    PRINCIPAL INVESTIGATOR

  • Xuemei Li, Professor

    Shenzhen Maternity & Child Healthcare Hospital

    PRINCIPAL INVESTIGATOR

  • Haitao Zeng, Professor

    Sixth Affiliated Hospital, Sun Yat-sen University

    PRINCIPAL INVESTIGATOR

  • Li Fan, Professor

    Liuzhou Hospital of Guangzhou Women and Children's Medical Center

    PRINCIPAL INVESTIGATOR

  • Aijun Yang, Professor

    Jining Medical University

    PRINCIPAL INVESTIGATOR

  • Isarin Thanaboonyawat, Doctor

    Siriraj Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuan Gao, Professor

CONTACT

0531-86569866gaoyuan@sduivf.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Academician

Study Record Dates

First Submitted

June 28, 2022

First Posted

July 1, 2022

Study Start

September 16, 2022

Primary Completion

June 1, 2024

Study Completion

May 31, 2025

Last Updated

January 18, 2024

Record last verified: 2024-01

Data Sharing

IPD Sharing
Will not share

Locations

CN(27)TH(1)