Embryo Selection by Noninvasive Preimplantation Genetic Test (ESNi-PGT)

• ClinicalTrials.gov Identifier: NCT04339166
• Recruitment Status: Recruiting
• First Posted: April 9, 2020
• Last Update Posted: April 3, 2024
• Sponsor: Peking University Third Hospital
• Collaborators: Jinling Hospital,Nanjing University,School Medicine; Reproductive Medical Center of Hebei Maternity 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
• Information provided by (Responsible Party): Jie Qiao, Peking University Third Hospital

Tracking Information

• First Submitted Date: April 1, 2020
• First Posted Date: April 9, 2020
• Last Update Posted Date: April 3, 2024
• Actual Study Start Date: April 16, 2020
• Actual Primary Completion Date: February 28, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 7, 2020)

Ongoing pregnancy rate [ Time Frame: 12 weeks after the first embryo transfer ]

Number of women with ongoing pregnancies after the first transfer/ number of women randomized to the specific group

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 7, 2020)

• Clinical pregnancy rate [ Time Frame: 7 weeks after the first embryo transfer ]
  Number of women with clinical pregnancies after the first transfer / number of women randomized to the specific group
• Miscarriage rate [ Time Frame: 28 weeks of after the first embryo transfer ]
  Number of pregnancy losses / number of clinical pregnancies after the first transfer.
• Live birth rate [ Time Frame: within 2 weeks after live birth ]
  Number of women with live births after the first transfer / number of women randomized to the specific group.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Embryo Selection by Noninvasive Preimplantation Genetic Test
• Official Title: A Multicenter Clinical Study on Embryo Selection by Using the Ploidy of Cell Free DNA in Embryo Culture Medium
• 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

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Screening

Condition

• Infertility
• Chromosome Abnormality

Intervention

Diagnostic Test: Non-invasive chromosome screening（NICS）

NICS is noninvasive chromosome screening approach to analysis the euploidy by free DNA in embryo culture medium

Study Arms

• Experimental: Group A
  Single thawed blastocyst transfer with blastocyst selection according to the analysis of NICS and morphologic score.
  Intervention: Diagnostic Test: Non-invasive chromosome screening（NICS）
• No Intervention: Group B
  Single thawed blastocyst transfer with blastocyst selection according to morphologic score.

• Publications *: 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 7, 2020): 1148
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2024
• Actual Primary Completion Date: February 28, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Infertile couples receiving IVF- ICSI procedure for assisted reproduction cycle
2. Female age: 35 - 42 years old
3. 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.
4. Culture embryos to blastocyst stage and all the blastocysts will be single cryopreserved.
5. Single frozen-thawed blastocyst Transferred for the first time
6. The number of blastocysts ≥2, morphology grade (above 4BC/4CB)
7. Written informed consent

Exclusion Criteria:

1. 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.)
2. PGT cycles
3. 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
4. Untreated hyperprolactinemia, thyroid disease, adrenal disease
5. Women with endometrial polyps that were not treated before embryo transfer

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: IVF patients

• Ages: 35 Years to 42 Years (Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Jie Qiao; 010-82265080; jie.qiao@263.net

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04339166
• Other Study ID Numbers: ESNi-PGT
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Data may be shared with proper internal and ethical approval. De-identified data may also be shared with approved study investigators.
• Supporting Materials: Study Protocol
• Time Frame: After the study has been completed
• Access Criteria: Proper internal and ethical approval; protect patient confidentiality; approve by study investigators

• Current Responsible Party: Jie Qiao, Peking University Third Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Peking University Third Hospital
• Original Study Sponsor: Same as current

Collaborators

• Jinling Hospital,Nanjing University,School Medicine
• Reproductive Medical Center of Hebei Maternity 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

Investigators

• Principal Investigator: Jie Qiao; Peking University Third Hospital

• PRS Account: Peking University Third Hospital
• Verification Date: April 2024