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

DNA Methylation Clinical Trial

Official title:

Whether Using DNA Methylome to Select Embryos Can Increase the Live Birth Rate During Assisted Reproductive Technology: A Multicenter, Randomized , Open-label Clinical Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05442125
• Other study ID #: PIMS-IVF
• Status: Recruiting
• Phase: N/A
• Start date: September 16, 2022
• Est. completion date: May 31, 2025

Study information

• Verified date: January 2024
• Source: Shandong University
• Contact: Yuan Gao, Professor
• Phone: 0531-86569866
• Email: gaoyuan[@]sduivf.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1146
• Est. completion date: May 31, 2025
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years and older

Eligibility

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:

4.2 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.

Related Conditions & MeSH terms

• DNA Methylation
• Reproductive Techniques, Assisted

Intervention

Other:
• 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
• 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.

Locations

Country	Name	City	State
China	Center for Reproductive Medicine, Center for Prenatal Diagnosis First Hospital, Jilin University	Changchun
China	Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA	Changsha
China	900 th Hospital of Joint Logistics Support Force	Fuzhou
China	Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University	Fuzhou
China	Guangzhou Womenand Children's Medical Center	Guanzhou
China	The Sixth Affiliated Hospital of Sun Yat-sen University	Guanzhou
China	Center for Reproductive Medicine, The Affiliated Hospital of Guizhou Medical University	Guiyang
China	The first affiliated hospital of Hainan Medical University	Haikou
China	Assisted Reproduction Unit, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou
China	The First Affiliated Hospital of Anhui Medical University	Hefei
China	Center for Reproductive Medicine, Shandong University	Jinan
China	Shandong University	Jinan	Shandong
China	Affiliated Hospital of Jining Medical University	Jining
China	Liuzhou Hospital of Guangzhou Women and Children's Medical Center	Liuzhou
China	Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital	Nanjing
China	The First Affiliated Hospital with Nanjing Medical University	Nanjing
China	Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine,Shanghai Jiao Tong University	Shanghai
China	Changhai Hospital	Shanghai
China	International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University	Shanghai
China	Reproductive Medical Center of Ruijin Hospital, School of Medicine,Shanghai Jiao Tong University	Shanghai
China	Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University	Shanghai
China	Shenzhen Maternity & Child Healthcare Hospital	Shenzhen
China	The Second Hospital of Hebei Medical University	Shijiazhuang
China	Center for reproduction and genetics,suzhou municipal hospital	Suzhou
China	The General Hospital of Ningxia Medical University	Yinchuan
China	Department of Reproductive Medicine, the Third Affiliated Hospital of Zhengzhou University	Zhengzhou
China	Reproductive Medical Center, Henan Provincial People's Hospital	Zhengzhou
Thailand	Siriraj hospital, Mahidol university	Bangkok

Sponsors (27)

Lead Sponsor

Collaborator

Shandong University

900 th Hospital of Joint Logistics Support Force, Changhai Hospital, Fujian Maternity and Child Health Hospital, General Hospital of Ningxia Medical University, Guangzhou Womenand Children's Medical Center, Henan Provincial People's Hospital, International Peace Maternity and Child Health Hospital, Jining Medical University, Liuzhou Hospital of Guangzhou Women and Children's Medical Center, Nanjing Maternity and Child Health Care Hospital, RenJi Hospital, Reproductive & Genetic Hospital of CITIC-Xiangya, Ruijin Hospital, ShangHai Ji Ai Genetics & IVF Institute, Shenzhen Maternity & Child Healthcare Hospital, Sir Run Run Shaw Hospital, Siriraj hospital, Mahidol university, Thailand, Sixth Affiliated Hospital, Sun Yat-sen University, Suzhou Municipal Hospital, The Affiliated Hospital Of Guizhou Medical University, The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital of Hainan Medical University, The First Affiliated Hospital with Nanjing Medical University, The First Hospital of Jilin University, The Second Hospital of Hebei Medical University, Third Affiliated Hospital of Zhengzhou University

Countries where clinical trial is conducted

China,  Thailand, 

References & Publications (14)

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

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 — View Citation

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):137 — View Citation

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. — View Citation

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. — View Citation

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):7 — View Citation

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. — View Citation

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. — View Citation

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 Genomic — View Citation

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, contro — View Citation

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 Cu — View Citation

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- — View Citation

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. — View Citation

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 — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Good Birth Outcome rate	Defined as a live birth of an infant born at = 37 weeks, with a birth weigh between 2500 and 4000g and without a major congenital anomaly	36 months
Secondary	Clinical pregnancy rate	Twenty days after conception, transvaginal ultrasonography will be performed. Clinical pregnancy will be diagnosed with detection of an intrauterine gestational sac.	36 months
Secondary	Pregnancy loss rate	Number of pregnancy losses / number of clinical pregnancies after transfer.	36 months
Secondary	Multiple pregnancy rate	Number of multiple pregnancy/number of clinical pregnancies after transfer.	36 months
Secondary	Duration of pregnancy	Duration of pregnancy is the period between conception and birth.	36 months
Secondary	Birth weight	Weight of newborns at delivery.	36 months
Secondary	Maternal complications	Number of pregnancies with complications / number of pregnancies.	48 months
Secondary	Neonatal complications	Number of live births with neonatal complications / number of live births.	48 months