Embryo Selection by Noninvasive Preimplantation Genetic Test (ESNi-PGT)
Primary Purpose
Infertility, Chromosome Abnormality
Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Non-invasive chromosome screening(NICS)
Sponsored by
About this trial
This is an interventional screening trial for Infertility focused on measuring Culture media, Embryonic cell-free DNA, Euploidy
Eligibility Criteria
Inclusion Criteria:
- Infertile couples receiving IVF- ICSI procedure for assisted reproduction cycle
- Female age: 35 - 42 years old
- Women receiving controlled ovarian hyperstimulation treatment (including ultra-long protocol、long-protocol 、short protocol treatment with GnRH agonist and GnRH antagonist treatment protocol); and the number of oocytes ≥6; The female BMI is from 18 to 30kg/m2.
- Culture embryos to blastocyst stage and all the blastocysts will be single cryopreserved.
- Single frozen-thawed blastocyst Transferred for the first time
- The number of blastocysts ≥2, morphology grade (above 4BC/4CB)
- Written informed consent
Exclusion Criteria:
- One of couples with IVF or ICSI contraindications(such as poorly controlled type I or type II diabetes; liver disease or dysfunction; kidney disease or renal function abnormality; significant anemia; history of deep venous thrombosis, pulmonary embolus; history of cerebrovascular accident; uncontrolled hypertension or diagnosed heart disease; history of cervical, endometrial or breast cancer; undiagnosed vaginal bleeding.)
- PGT cycles
- Women who have pathologies or malformations that affect the pregnancy outcome: genital malformations, untreated hydrosalpinx, untreated uterine infections, intramural myomas > 4cm , benign tumor of pelvic and abdominal cavity> 4cm, intimal thickness<8mm, pituitary tumors and malignant tumors of various tissues and organs during the patient's participation in the study
- Untreated hyperprolactinemia, thyroid disease, adrenal disease
- Women with endometrial polyps that were not treated before embryo transfer
Sites / Locations
- The First Affiliated Hospital,Sun Yat-sen UniversityRecruiting
- Peking University Shenzhen HospitalRecruiting
- The Second Hospital of Hebei Medical UniversityRecruiting
- Hebei Maternity and Reproductive hospitalRecruiting
- The Third Affiliated Hospital of Zhengzhou UniversityRecruiting
- Reproductive & Genetic Hospital of Citic-XiangyaRecruiting
- Jinling Hospital,Nanjing University,School MedicineRecruiting
- Shengjing Hospital of China Medical UniversityRecruiting
- West China Second Hospital of Sichuan UniversityRecruiting
- The Second Affiliated Hospital of Wenzhou Medical UniversityRecruiting
- Peking University Third HospitalRecruiting
- The First Medical Center of Chinese People's Liberation Army General HospitalRecruiting
- Northwest women's and children's hospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Group A
Group B
Arm Description
Single thawed blastocyst transfer with blastocyst selection according to the analysis of NICS and morphologic score.
Single thawed blastocyst transfer with blastocyst selection according to morphologic score.
Outcomes
Primary Outcome Measures
Ongoing pregnancy rate
Number of women with ongoing pregnancies after the first transfer/ number of women randomized to the specific group
Secondary Outcome Measures
Clinical pregnancy rate
Number of women with clinical pregnancies after the first transfer / number of women randomized to the specific group
Miscarriage rate
Number of pregnancy losses / number of clinical pregnancies after the first transfer.
Live birth rate
Number of women with live births after the first transfer / number of women randomized to the specific group.
Full Information
NCT ID
NCT04339166
First Posted
April 1, 2020
Last Updated
October 31, 2022
Sponsor
Peking University Third Hospital
Collaborators
Jinling Hospital,Nanjing University,School Medicine, Hebei Maternity and Reproductive hospital, Northwest Women's and Children's Hospital, Xi'an, Shaanxi, The First Medical Center of Chinese People's Liberation Army General Hospital, Shengjing Hospital, First Affiliated Hospital, Sun Yat-Sen University, Reproductive & Genetic Hospital of CITIC-Xiangya, Yikon Genomics Company, Ltd, Peking University Shenzhen Hospital, The Second Hospital of Hebei Medical University, West China Second University Hospital, Second Affiliated Hospital of Wenzhou Medical University, Third Affiliated Hospital of Zhengzhou University
1. Study Identification
Unique Protocol Identification Number
NCT04339166
Brief Title
Embryo Selection by Noninvasive Preimplantation Genetic Test
Acronym
ESNi-PGT
Official Title
A Multicenter Clinical Study on Embryo Selection by Using the Ploidy of Cell Free DNA in Embryo Culture Medium
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 16, 2020 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University Third Hospital
Collaborators
Jinling Hospital,Nanjing University,School Medicine, Hebei Maternity and Reproductive hospital, Northwest Women's and Children's Hospital, Xi'an, Shaanxi, The First Medical Center of Chinese People's Liberation Army General Hospital, Shengjing Hospital, First Affiliated Hospital, Sun Yat-Sen University, Reproductive & Genetic Hospital of CITIC-Xiangya, Yikon Genomics Company, Ltd, Peking University Shenzhen Hospital, The Second Hospital of Hebei Medical University, West China Second University Hospital, Second Affiliated Hospital of Wenzhou Medical University, Third Affiliated Hospital of Zhengzhou University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The objective of this study is to explore whether non-invasive chromosome screening (NICS) can be used as an effective indicator for embryos selection besides morphology through a multicenter randomized controlled trial, by comparing the differences of live birth rate, pregnancy rate and miscarriage rate between the two groups of embryo selection by "NICS+ morphology" and embryo selection only by "morphology" in IVF cycle.
Detailed Description
Chromosomal abnormalities commonly exist in early human embryos, and often cause embryo implantation failure and pregnancy loss in in-vitro fertilization (IVF) treatments. Preimplantation genetic testing for aneuploidies (PGT-A) by comprehensive chromosome screening (CCS) has been widely applied in IVF practices to select embryos with normal ploidy. Although multiple clinical trials have demonstrated improved clinical outcomes with PGT-A, it's in controversial for whether PGT-A is truly worthwhile to be offered to all IVF patients. One of the main concerns is that it involves an embryo biopsy procedure, which is invasive and the long-term safety issue of the embryo biopsy remains to be fully investigated.
In recent years, researchers have found that the spent medium of embryo culture contains trace amount of cell-free DNA, which may reflect the ploidy of the embryo. The non-invasive chromosome screening (NICS) approach utilizing spent culture medium samples has been evaluated in studies. However, the clinical value of NICS as a new effective indicator to evaluate embryo competence so far has not been justified by randomized clinical trials.
The main purpose of this project is to verify whether NICS can be used as a new effective indicator for evaluating embryo developmental potential through multi-center, randomized clinical trials
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility, Chromosome Abnormality
Keywords
Culture media, Embryonic cell-free DNA, Euploidy
7. Study Design
Primary Purpose
Screening
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
1148 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Experimental
Arm Description
Single thawed blastocyst transfer with blastocyst selection according to the analysis of NICS and morphologic score.
Arm Title
Group B
Arm Type
No Intervention
Arm Description
Single thawed blastocyst transfer with blastocyst selection according to morphologic score.
Intervention Type
Diagnostic Test
Intervention Name(s)
Non-invasive chromosome screening(NICS)
Intervention Description
NICS is noninvasive chromosome screening approach to analysis the euploidy by free DNA in embryo culture medium
Primary Outcome Measure Information:
Title
Ongoing pregnancy rate
Description
Number of women with ongoing pregnancies after the first transfer/ number of women randomized to the specific group
Time Frame
12 weeks after the first embryo transfer
Secondary Outcome Measure Information:
Title
Clinical pregnancy rate
Description
Number of women with clinical pregnancies after the first transfer / number of women randomized to the specific group
Time Frame
7 weeks after the first embryo transfer
Title
Miscarriage rate
Description
Number of pregnancy losses / number of clinical pregnancies after the first transfer.
Time Frame
28 weeks of after the first embryo transfer
Title
Live birth rate
Description
Number of women with live births after the first transfer / number of women randomized to the specific group.
Time Frame
within 2 weeks after live birth
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
IVF patients
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
42 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Infertile couples receiving IVF- ICSI procedure for assisted reproduction cycle
Female age: 35 - 42 years old
Women receiving controlled ovarian hyperstimulation treatment (including ultra-long protocol、long-protocol 、short protocol treatment with GnRH agonist and GnRH antagonist treatment protocol); and the number of oocytes ≥6; The female BMI is from 18 to 30kg/m2.
Culture embryos to blastocyst stage and all the blastocysts will be single cryopreserved.
Single frozen-thawed blastocyst Transferred for the first time
The number of blastocysts ≥2, morphology grade (above 4BC/4CB)
Written informed consent
Exclusion Criteria:
One of couples with IVF or ICSI contraindications(such as poorly controlled type I or type II diabetes; liver disease or dysfunction; kidney disease or renal function abnormality; significant anemia; history of deep venous thrombosis, pulmonary embolus; history of cerebrovascular accident; uncontrolled hypertension or diagnosed heart disease; history of cervical, endometrial or breast cancer; undiagnosed vaginal bleeding.)
PGT cycles
Women who have pathologies or malformations that affect the pregnancy outcome: genital malformations, untreated hydrosalpinx, untreated uterine infections, intramural myomas > 4cm , benign tumor of pelvic and abdominal cavity> 4cm, intimal thickness<8mm, pituitary tumors and malignant tumors of various tissues and organs during the patient's participation in the study
Untreated hyperprolactinemia, thyroid disease, adrenal disease
Women with endometrial polyps that were not treated before embryo transfer
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jie Qiao
Phone
010-82265080
Email
jie.qiao@263.net
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jie Qiao
Organizational Affiliation
Peking University Third Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital,Sun Yat-sen University
City
Guanzhou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
yanwen xu, professor
Phone
020-87606345
Email
xuyanwen@live.cn
Facility Name
Peking University Shenzhen Hospital
City
Shenzhen
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weiping Qian, professor
Facility Name
The Second Hospital of Hebei Medical University
City
Shijia Zhuang
State/Province
Hebei
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guimin Hao, professor
Phone
0311-66002721
Email
haoguimin@163.com
Facility Name
Hebei Maternity and Reproductive hospital
City
Shijiazhuang
State/Province
Hebei
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liyi Cai
Phone
0311-82626066
Email
cai760829@163.com
Facility Name
The Third Affiliated Hospital of Zhengzhou University
City
Zhengzhou
State/Province
Henan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yichun Guan, professor
Phone
0371-66903686
Email
lisamayguan@126.com
Facility Name
Reproductive & Genetic Hospital of Citic-Xiangya
City
Changsha
State/Province
Hunan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liang Hu
Phone
0731-82355100-8973
Email
lianghu7@gmail.com
Facility Name
Jinling Hospital,Nanjing University,School Medicine
City
Nanjing
State/Province
Jiangsu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bing Yao
Phone
025-80860174
Email
yaobing@nju.edu.cn
Facility Name
Shengjing Hospital of China Medical University
City
Shenyang
State/Province
Liaoning
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiuxia Wang
Phone
024-9661540131
Email
wangxxsj@sina.cn
Facility Name
West China Second Hospital of Sichuan University
City
Chengdu
State/Province
Sichuan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yan Wang, professor
Phone
028-88570494
Email
wangyy1210@163.com
Facility Name
The Second Affiliated Hospital of Wenzhou Medical University
City
Wenzhou
State/Province
Zhejiang
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Junzhao Zhao, professor
Phone
0577-88002304
Email
z.joyce08@163.com
Facility Name
Peking University Third Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie Qiao
Phone
010-82265080
Email
jie.qiao@263.net
First Name & Middle Initial & Last Name & Degree
Jie Qiao
Facility Name
The First Medical Center of Chinese People's Liberation Army General Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuanqing Yao
Phone
010-66939258
Email
yqyao@126.com
Facility Name
Northwest women's and children's hospital
City
Xi'an
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juanzi Shi
Phone
029-87219120
Email
shijuanzi123@126.com
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data may be shared with proper internal and ethical approval. De-identified data may also be shared with approved study investigators.
IPD Sharing Time Frame
After the study has been completed
IPD Sharing Access Criteria
Proper internal and ethical approval; protect patient confidentiality; approve by study investigators
Citations:
PubMed Identifier
35896299
Citation
Huang J, Rong L, Zeng L, Hu L, Shi J, Cai L, Yao B, Wang XX, Xu Y, Yao Y, Wang Y, Zhao J, Guan Y, Qian W, Hao G, Lu S, Liu P, Qiao J. Embryo selection through non-invasive preimplantation genetic testing with cell-free DNA in spent culture media: a protocol for a multicentre, double-blind, randomised controlled trial. BMJ Open. 2022 Jul 27;12(7):e057254. doi: 10.1136/bmjopen-2021-057254.
Results Reference
derived
Learn more about this trial
Embryo Selection by Noninvasive Preimplantation Genetic Test
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