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Cumulative Live Birth Rate With eSET After Preimplantation Genetic Screening Versus Conventional In-vitro Fertilization (CESE-PGS)

Primary Purpose

Infertility

Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
blastocyst morphologic score
blastocyst biopsy and sequencing
freeze-all and single thawed blastocyst transfer
Sponsored by
Chen Zi-Jiang
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infertility focused on measuring preimplantation genetic screening, single embryo transfer, frozen embryo transfer, cumulative live birth rate

Eligibility Criteria

20 Years - 37 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Women who are participating in their first cycle of IVF or ICSI
  2. Women ages 20 to 37 years.
  3. Women who obtain 3 or more good-quality blastocysts 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 will be randomized.

Exclusion Criteria:

  1. Women with a uterine cavity abnormality, such as a uterine congenital malformation (uterus uni-cornate, bicornate, or duplex); untreated uterine septum, adenomyosis, submucous myoma, or endo-metrial polyp(s); or with history of intrauterine adhesions.
  2. Women with untreated hydrosalpinx;
  3. Women who are indicated and planned to undergo PGD, for example, parental abnormal karyo-type or diagnosed with monogenic disease;
  4. Women who use donated oocytes or sperm to achieve pregnancy;
  5. 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 se-rum liver enzyme testing); renal disease or abnormal serum renal function; significant anemia; history of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident; uncontrolled hyper-tension, known symptomatic heart disease; history of or suspected cervical carcinoma, endometrial carcinoma, or breast carcinoma; undiagnosed vaginal bleeding.

Sites / Locations

  • Shandong UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

PGS group

IVF group

Arm Description

Subjects in the PGS group will have blastocyst biopsy and sequencing done with 3 good-quality embryos on Day 5. Principle of freeze-all and single thawed blastocyst transfer will be applied. The transfer order of euploid embryos will be determined by blastocyst morphologic score. The outcome of all euploids transfers within 1 year after randomization will be followed up. During study, every subject will have at most one live birth.

Subjects in the IVF group will also comply with the principle of freeze-all and single thawed blastocyst transfer. The order of transfer will be determined by blastocyst morphologic score. The outcome of up to 3 transfers within 1 year after randomization will be followed up. During study, every subject will have at most one live birth.

Outcomes

Primary Outcome Measures

Cumulative live birth rate
Live birth is defined as the delivery of any viable infant at 28 weeks or more of gestation after our interventions, and cumulative live birth rate is calculated by dividing the number of women achieving live birth after transfers of all study-specific embryos (up to 3 transfers of single blastocycst within 1 year after randomization), by the total number of women randomized to the specific group.

Secondary Outcome Measures

Rate of Good Birth Outcomes
Number of good birth outcomes / number of clinical pregnancies over (up to) 3 transfers within 1 year.Good Birth Outcome is defined as live birth of an infant born at ≥ 37 weeks, with a birth weight between 2500 and 4000g and without a major congenital anomaly.
Cumulative pregnancy rate
Number of women with clinical pregnancies over (up to) 3 transfers within 1 year / number of women randomized to the specific group. Clinical pregnancy will be diagnosed with detection of an intrauterine gestational sac.
Cumulative pregnancy loss rate
Number of pregnancy losses / number of clinical pregnancies over (up to) 3 transfers within 1 year.Pregnancy loss refers to a complete spontaneous abortion or a nonviable pregnancy before 28 weeks of gestation.
Multiple pregnancy rate
Number of multiple pregnancies / number of clinical pregnancies over (up to) 3 transfers within 1 year.
Duration of pregnancy
The time from the first day of last menstrual period to the day of delivery.
Birth weight
Weight of newborns at delivery.
Cumulative incidence of maternal and neonatal complications during whole gestation and prenatal stage
Number of pregnancies with complications / number of pregnancies over (up to) 3 transfers within 1 year;number of live births with neonatal complications / number of live births over (up to)3 transfers within 1 year.
Number of embryo transfers to achieve live birth
Number of embryo transfers the patients have gone through to achieve live birth.

Full Information

First Posted
March 27, 2017
Last Updated
September 19, 2019
Sponsor
Chen Zi-Jiang
Collaborators
The First Affiliated Hospital with Nanjing Medical University, Peking University Third Hospital, ShangHai Ji Ai Genetics & IVF Institute, RenJi Hospital, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Suzhou Municipal Hospital, Renmin Hospital of Wuhan University, Yantai Yuhuangding Hospital, Tang-Du Hospital, Nanjing Maternity and Child Health Care Hospital, Guangxi Maternal and Child Health Hospital, Women's Hospital School Of Medicine Zhejiang University, Guangdong Women and Children Hospital, Tianjin Central Hospital of Gynecology Obstetrics, Shengjing Hospital, The First Affiliated Hospital of Anhui Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT03118141
Brief Title
Cumulative Live Birth Rate With eSET After Preimplantation Genetic Screening Versus Conventional In-vitro Fertilization
Acronym
CESE-PGS
Official Title
Cumulative Live Birth Rate With eSET After In-vitro Fertilization With Preim-plantation Genetic Screening by Next Generation Sequencing Versus Conventional In-vitro Fertilization: A Pragmatic Randomized Controlled Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Unknown status
Study Start Date
July 9, 2017 (Actual)
Primary Completion Date
June 2020 (Anticipated)
Study Completion Date
June 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Chen Zi-Jiang
Collaborators
The First Affiliated Hospital with Nanjing Medical University, Peking University Third Hospital, ShangHai Ji Ai Genetics & IVF Institute, RenJi Hospital, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Suzhou Municipal Hospital, Renmin Hospital of Wuhan University, Yantai Yuhuangding Hospital, Tang-Du Hospital, Nanjing Maternity and Child Health Care Hospital, Guangxi Maternal and Child Health Hospital, Women's Hospital School Of Medicine Zhejiang University, Guangdong Women and Children Hospital, Tianjin Central Hospital of Gynecology Obstetrics, Shengjing Hospital, The First Affiliated Hospital of Anhui Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this randomized clinical trial is to compare the efficacy and safety with transfer of embryos selected by next generation sequencing (NGS) versus conventional morphological criteria. Subjects with 3 or more blastocysts on day 5 of embryo culture will be randomized to the PGS or IVF group. A Freeze-all strategy and a single frozen blastocyst transfer will be performed in both PGS and IVF groups. The primary outcome is the cumulative live birth after transfers of up to 3 single blastocycsts in both groups.
Detailed Description
This is a multicenter, randomized clinical trial comparing the efficacy and safety with transfer of embryos selected by next generation sequence (NGS) and morphologic criteria versus by morphological criteria alone. Subjects who obtain 3 or more good-quality blastocysts will be randomized to PGS or IVF group. All embryos will be frozen and a single thawed blastocyst will be transferred in both PGS and IVF group. Subjects in the PGS group will have 3 blastocysts sequenced and euploid embryos will be subsequently transferred. Subjects in the IVF group will have blastocysts selected by morphology assessment. The cumulative live birth rate will be counted after transfers of all euploid embryo in the PGS group and 3 blastocysts in the IVF group within 1 year after randomization.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility
Keywords
preimplantation genetic screening, single embryo transfer, frozen embryo transfer, cumulative live birth rate

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1215 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PGS group
Arm Type
Active Comparator
Arm Description
Subjects in the PGS group will have blastocyst biopsy and sequencing done with 3 good-quality embryos on Day 5. Principle of freeze-all and single thawed blastocyst transfer will be applied. The transfer order of euploid embryos will be determined by blastocyst morphologic score. The outcome of all euploids transfers within 1 year after randomization will be followed up. During study, every subject will have at most one live birth.
Arm Title
IVF group
Arm Type
Active Comparator
Arm Description
Subjects in the IVF group will also comply with the principle of freeze-all and single thawed blastocyst transfer. The order of transfer will be determined by blastocyst morphologic score. The outcome of up to 3 transfers within 1 year after randomization will be followed up. During study, every subject will have at most one live birth.
Intervention Type
Procedure
Intervention Name(s)
blastocyst morphologic score
Intervention Description
Blastocysts will be scored by Gardner morphologic criteria.
Intervention Type
Procedure
Intervention Name(s)
blastocyst biopsy and sequencing
Intervention Description
Three blastocysts will be biopsied on trophectoderm, sequenced with next-generation sequencing (NGS). Euploidy will transferred one by one according to morphologic score.
Intervention Type
Procedure
Intervention Name(s)
freeze-all and single thawed blastocyst transfer
Intervention Description
All blastocysts will be vitrified in fresh cycle. Single blastocyst will be thawed and transferred.
Primary Outcome Measure Information:
Title
Cumulative live birth rate
Description
Live birth is defined as the delivery of any viable infant at 28 weeks or more of gestation after our interventions, and cumulative live birth rate is calculated by dividing the number of women achieving live birth after transfers of all study-specific embryos (up to 3 transfers of single blastocycst within 1 year after randomization), by the total number of women randomized to the specific group.
Time Frame
22 months
Secondary Outcome Measure Information:
Title
Rate of Good Birth Outcomes
Description
Number of good birth outcomes / number of clinical pregnancies over (up to) 3 transfers within 1 year.Good Birth Outcome is defined as live birth of an infant born at ≥ 37 weeks, with a birth weight between 2500 and 4000g and without a major congenital anomaly.
Time Frame
22 months
Title
Cumulative pregnancy rate
Description
Number of women with clinical pregnancies over (up to) 3 transfers within 1 year / number of women randomized to the specific group. Clinical pregnancy will be diagnosed with detection of an intrauterine gestational sac.
Time Frame
14 months
Title
Cumulative pregnancy loss rate
Description
Number of pregnancy losses / number of clinical pregnancies over (up to) 3 transfers within 1 year.Pregnancy loss refers to a complete spontaneous abortion or a nonviable pregnancy before 28 weeks of gestation.
Time Frame
19 months
Title
Multiple pregnancy rate
Description
Number of multiple pregnancies / number of clinical pregnancies over (up to) 3 transfers within 1 year.
Time Frame
22 months
Title
Duration of pregnancy
Description
The time from the first day of last menstrual period to the day of delivery.
Time Frame
22 months
Title
Birth weight
Description
Weight of newborns at delivery.
Time Frame
22 months
Title
Cumulative incidence of maternal and neonatal complications during whole gestation and prenatal stage
Description
Number of pregnancies with complications / number of pregnancies over (up to) 3 transfers within 1 year;number of live births with neonatal complications / number of live births over (up to)3 transfers within 1 year.
Time Frame
22 months
Title
Number of embryo transfers to achieve live birth
Description
Number of embryo transfers the patients have gone through to achieve live birth.
Time Frame
22 months
Other Pre-specified Outcome Measures:
Title
Clinical pregnancy rate after the first transfer
Description
Number of women with clinical pregnancies after the first transfer / number of women randomized to the specific group.
Time Frame
4 months
Title
Pregnancy loss rate after the first transfer
Description
Number of pregnancy losses / number of clinical pregnancies after the first transfer .
Time Frame
9 months
Title
Live birth rate after the first transfer
Description
Number of women with live births after the first transfer / number of women randomized to the specific group.
Time Frame
12 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
37 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Women who are participating in their first cycle of IVF or ICSI Women ages 20 to 37 years. Women who obtain 3 or more good-quality blastocysts 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 will be randomized. Exclusion Criteria: Women with a uterine cavity abnormality, such as a uterine congenital malformation (uterus uni-cornate, bicornate, or duplex); untreated uterine septum, adenomyosis, submucous myoma, or endo-metrial polyp(s); or with history of intrauterine adhesions. Women with untreated hydrosalpinx; Women who are indicated and planned to undergo PGD, for example, parental abnormal karyo-type or diagnosed with monogenic disease; 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 se-rum liver enzyme testing); renal disease or abnormal serum renal function; significant anemia; history of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident; uncontrolled hyper-tension, known symptomatic heart disease; history of or suspected cervical carcinoma, endometrial carcinoma, or breast carcinoma; undiagnosed vaginal bleeding.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zi-Jiang Chen, Professor
Phone
+0086 531 85651190
Email
chenzijiang@vip.163.com
Facility Information:
Facility Name
Shandong University
City
Jinan
State/Province
Shandong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zi-Jiang Chen, Professor
Phone
+0086 531 85651190
Email
chenzijiang@vip.163.com

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
26385405
Citation
Dahdouh EM, Balayla J, Garcia-Velasco JA. Comprehensive chromosome screening improves embryo selection: a meta-analysis. Fertil Steril. 2015 Dec;104(6):1503-12. doi: 10.1016/j.fertnstert.2015.08.038. Epub 2015 Sep 16.
Results Reference
background
PubMed Identifier
23548942
Citation
Forman EJ, Hong KH, Ferry KM, Tao X, Taylor D, Levy B, Treff NR, Scott RT Jr. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril. 2013 Jul;100(1):100-7.e1. doi: 10.1016/j.fertnstert.2013.02.056. Epub 2013 Mar 30.
Results Reference
background
PubMed Identifier
22551456
Citation
Yang Z, Liu J, Collins GS, Salem SA, Liu X, Lyle SS, Peck AC, Sills ES, Salem RD. Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet. 2012 May 2;5(1):24. doi: 10.1186/1755-8166-5-24.
Results Reference
background
PubMed Identifier
23731996
Citation
Scott RT Jr, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, Tao X, Treff NR. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril. 2013 Sep;100(3):697-703. doi: 10.1016/j.fertnstert.2013.04.035. Epub 2013 Jun 1.
Results Reference
background
PubMed Identifier
25772770
Citation
Murugappan G, Ohno MS, Lathi RB. Cost-effectiveness analysis of preimplantation genetic screening and in vitro fertilization versus expectant management in patients with unexplained recurrent pregnancy loss. Fertil Steril. 2015 May;103(5):1215-20. doi: 10.1016/j.fertnstert.2015.02.012. Epub 2015 Mar 13.
Results Reference
background
PubMed Identifier
25006207
Citation
Mastenbroek S, Repping S. Preimplantation genetic screening: back to the future. Hum Reprod. 2014 Sep;29(9):1846-50. doi: 10.1093/humrep/deu163. Epub 2014 Jul 8.
Results Reference
background
PubMed Identifier
26902859
Citation
Huang J, Yan L, Lu S, Zhao N, Xie XS, Qiao J. Validation of a next-generation sequencing-based protocol for 24-chromosome aneuploidy screening of blastocysts. Fertil Steril. 2016 Jun;105(6):1532-6. doi: 10.1016/j.fertnstert.2016.01.040. Epub 2016 Feb 19.
Results Reference
background
PubMed Identifier
34818479
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 or without Preimplantation Genetic Testing for Aneuploidy. N Engl J Med. 2021 Nov 25;385(22):2047-2058. doi: 10.1056/NEJMoa2103613.
Results Reference
derived
PubMed Identifier
32898291
Citation
Cornelisse S, Zagers M, Kostova E, Fleischer K, van Wely M, Mastenbroek S. Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation. Cochrane Database Syst Rev. 2020 Sep 8;9(9):CD005291. doi: 10.1002/14651858.CD005291.pub3.
Results Reference
derived

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Cumulative Live Birth Rate With eSET After Preimplantation Genetic Screening Versus Conventional In-vitro Fertilization

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