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| Name | Class |
|---|---|
| RenJi Hospital | OTHER |
| Reproductive & Genetic Hospital of CITIC-Xiangya | OTHER |
| Nanjing Maternity and Child Health Care Hospital | OTHER |
| ShangHai Ji Ai Genetics & IVF Institute |
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To determine whether using DNA methylome to select embryos can increase the live birth rate.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Using DNA methylome to select embryos | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Clinical pregnancy rate |
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Inclusion Criteria:
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
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yuan Gao, Professor | Contact | 0531-86569866 | gaoyuan@sduivf.com |
| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shandong University | Recruiting | Jinan | Shandong | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25697663 | Result | Brezina PR, Kutteh WH. Clinical applications of preimplantation genetic testing. BMJ. 2015 Feb 19;350:g7611. doi: 10.1136/bmj.g7611. | |
| 7316468 | Result | 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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| OTHER |
| Suzhou Municipal Hospital | OTHER |
| The First Hospital of Jilin University | OTHER |
| Sir Run Run Shaw Hospital | OTHER |
| The Affiliated Hospital Of Guizhou Medical University | OTHER |
| The Second Hospital of Hebei Medical University | OTHER |
| Third Affiliated Hospital of Zhengzhou University | OTHER |
| Ruijin Hospital | OTHER |
| International Peace Maternity and Child Health Hospital | OTHER |
| Henan Provincial People's Hospital | OTHER |
| The First Affiliated Hospital of Hainan Medical University | OTHER_GOV |
| The First Affiliated Hospital of Anhui Medical University | OTHER |
| Fujian Maternity and Child Health Hospital | OTHER |
| General Hospital of Ningxia Medical University | OTHER |
| The First Affiliated Hospital with Nanjing Medical University | OTHER |
| 900th Hospital of PLA Joint Logistic Support Force | OTHER |
| Guangzhou Women and Children's Medical Center | OTHER |
| Changhai Hospital | OTHER |
| Shenzhen Maternity & Child Healthcare Hospital | OTHER |
| Sixth Affiliated Hospital, Sun Yat-sen University | OTHER |
| Liuzhou Hospital of Guangzhou Women and Children's Medical Center | UNKNOWN |
| Jining Medical University | OTHER |
| Siriraj Hospital | OTHER |
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| Using morphologic score to select embryos | 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. |
|
Twenty days after conception, transvaginal ultrasonography will be performed. Clinical pregnancy will be diagnosed with detection of an intrauterine gestational sac.
| 36 months |
| Pregnancy loss rate | Number of pregnancy losses / number of clinical pregnancies after transfer. | 36 months |
| Multiple pregnancy rate | Number of multiple pregnancy/number of clinical pregnancies after transfer. | 36 months |
| Duration of pregnancy | Duration of pregnancy is the period between conception and birth. | 36 months |
| Birth weight | Weight of newborns at delivery. | 36 months |
| Maternal complications | Number of pregnancies with complications / number of pregnancies. | 48 months |
| Neonatal complications | Number of live births with neonatal complications / number of live births. | 48 months |
| 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 | 900th Hospital of PLA Joint Logistic Support Force | Principal Investigator |
| Ling Sun, Professor | Guangzhou Women and 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 |
| Center for Reproductive Medicine, Center for Prenatal Diagnosis First Hospital, Jilin University | Recruiting | Changchun | China |
|
| Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA | Recruiting | Changsha | 410008 | China |
|
| 900 th Hospital of Joint Logistics Support Force | Recruiting | Fuzhou | China |
|
| Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University | Recruiting | Fuzhou | China |
|
| Guangzhou Womenand Children's Medical Center | Recruiting | Guanzhou | China |
|
| The Sixth Affiliated Hospital of Sun Yat-sen University | Not yet recruiting | Guanzhou | China |
|
| Center for Reproductive Medicine, The Affiliated Hospital of Guizhou Medical University | Recruiting | Guiyang | China |
|
| The first affiliated hospital of Hainan Medical University | Recruiting | Haikou | China |
|
| Assisted Reproduction Unit, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine | Recruiting | Hangzhou | China |
|
| The First Affiliated Hospital of Anhui Medical University | Recruiting | Hefei | China |
|
| Center for Reproductive Medicine, Shandong University | Recruiting | Jinan | 250012 | China |
|
| Affiliated Hospital of Jining Medical University | Recruiting | Jining | China |
|
| Liuzhou Hospital of Guangzhou Women and Children's Medical Center | Recruiting | Liuzhou | China |
|
| Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital | Recruiting | Nanjing | China |
|
| The First Affiliated Hospital with Nanjing Medical University | Recruiting | Nanjing | China |
|
| Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine,Shanghai Jiao Tong University | Recruiting | Shanghai | 200135 | China |
|
| Changhai Hospital | Not yet recruiting | Shanghai | China |
|
| International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University | Not yet recruiting | Shanghai | China |
|
| Reproductive Medical Center of Ruijin Hospital, School of Medicine,Shanghai Jiao Tong University | Not yet recruiting | Shanghai | China |
|
| Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University | Not yet recruiting | Shanghai | China |
|
| Shenzhen Maternity & Child Healthcare Hospital | Recruiting | Shenzhen | China |
|
| The Second Hospital of Hebei Medical University | Recruiting | Shijiazhuang | China |
|
| Center for reproduction and genetics,suzhou municipal hospital | Recruiting | Suzhou | China |
|
| The General Hospital of Ningxia Medical University | Recruiting | Yinchuan | China |
|
| Department of Reproductive Medicine, the Third Affiliated Hospital of Zhengzhou University | Recruiting | Zhengzhou | China |
|
| Reproductive Medical Center, Henan Provincial People's Hospital | Recruiting | Zhengzhou | China |
|
| Siriraj hospital, Mahidol university | Not yet recruiting | Bangkok | Thailand |
|
| 26168107 | Result | 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. |
| 8280893 | Result | 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. |
| 28433371 | Result | 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. |
| 31713776 | Result | 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. |
| 34818479 | Result | 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. |
| 23400093 | Result | 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. |
| 22641018 | Result | 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. |
| 23663777 | Result | 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. |
| 29037989 | Result | 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. |
| 22763375 | Result | 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. |
| 10927046 | Result | 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. |
| 24613537 | Result | 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. |
| ID | Term |
|---|---|
| D006379 | Helping Behavior |
| ID | Term |
|---|---|
| D012919 | Social Behavior |
| D001519 | Behavior |
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