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

NCT03118141 | Unknown DMC

• 1 other identifier: CESE-PGS
• Study Type: interventional
• Target: 1,215
• Locations: 1 country
• Sites: 1

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.

Conditions

Infertility

Keywords

preimplantation genetic screening; single embryo transfer; frozen embryo transfer; cumulative live birth rate

Outcome Measures

Primary Outcomes (1)

• 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.

  22 months

Secondary Outcomes (8)

• Rate of Good Birth Outcomes

  22 months

• Cumulative pregnancy rate

  14 months

• Cumulative pregnancy loss rate

  19 months

• Multiple pregnancy rate

  22 months

• Duration of pregnancy

  22 months

Other Outcomes (3)

• Clinical pregnancy rate after the first transfer

  4 months

• Pregnancy loss rate after the first transfer

  9 months

• Live birth rate after the first transfer

  12 months

Study Arms (2)

PGS group

ACTIVE COMPARATOR

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.

Procedure: blastocyst morphologic score; Procedure: blastocyst biopsy and sequencing; Procedure: freeze-all and single thawed blastocyst transfer

IVF group

ACTIVE COMPARATOR

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.

Procedure: blastocyst morphologic score; Procedure: freeze-all and single thawed blastocyst transfer

Interventions

blastocyst morphologic score PROCEDURE

Blastocysts will be scored by Gardner morphologic criteria.

IVF group; PGS group

blastocyst biopsy and sequencing PROCEDURE

Three blastocysts will be biopsied on trophectoderm, sequenced with next-generation sequencing (NGS). Euploidy will transferred one by one according to morphologic score.

PGS group

freeze-all and single thawed blastocyst transfer PROCEDURE

All blastocysts will be vitrified in fresh cycle. Single blastocyst will be thawed and transferred.

IVF group; PGS group

Eligibility Criteria

• Age: 20 Years - 37 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chen Zi-Jiang: lead
• The First Affiliated Hospital with Nanjing Medical University: collaborator
• Peking University Third Hospital: collaborator
• ShangHai Ji Ai Genetics & IVF Institute: collaborator
• RenJi Hospital: collaborator
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: collaborator
• Suzhou Municipal Hospital: collaborator
• Renmin Hospital of Wuhan University: collaborator
• Yantai Yuhuangding Hospital: collaborator
• Tang-Du Hospital: collaborator
• Nanjing Maternity and Child Health Care Hospital: collaborator
• Guangxi Maternal and Child Health Hospital: collaborator
• Women's Hospital School Of Medicine Zhejiang University: collaborator
• Guangdong Women and Children Hospital: collaborator
• Tianjin Central Hospital of Gynecology Obstetrics: collaborator
• Shengjing Hospital: collaborator
• The First Affiliated Hospital of Anhui Medical University: collaborator

Study Sites (1)

Shandong University

Jinan, Shandong, China

RECRUITING

Related Publications (12)

• 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.

  PMID: 26385405 BACKGROUND

• 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.

  PMID: 23548942 BACKGROUND

• 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.

  PMID: 22551456 BACKGROUND

• 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.

  PMID: 23731996 BACKGROUND

• 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.

  PMID: 25772770 BACKGROUND

• 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.

  PMID: 25006207 BACKGROUND

• 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.

  PMID: 26902859 BACKGROUND

• Guo L, Guo A, Lan X, Tian S, Sun F, Su Y, Chen ZJ, Cao Y, Li Y. Oligoasthenospermia is correlated with increased preeclampsia incidence in subfertile couples undergoing in vitro fertilization and embryo transfer: a secondary analysis of a randomized clinical trial. F S Sci. 2024 Nov;5(4):386-394. doi: 10.1016/j.xfss.2024.08.003. Epub 2024 Aug 15.

  PMID: 39153572 DERIVED

• Ni T, Zhou W, Liu Y, Cui W, Liu Y, Lu J, Zhang Q, Chen ZJ, Li Y, Yan J. Excessive Exogenous Gonadotropins and Genetic and Pregnancy Outcomes After Euploidy Embryo Transfer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024 Apr 1;7(4):e244438. doi: 10.1001/jamanetworkopen.2024.4438.

  PMID: 38564220 DERIVED

• Hu M, Liu M, Tian S, Guo L, Zang Z, Chen ZJ, Li Y. Comparative analysis of pregnancy outcomes in preimplantation genetic testing for aneuploidy and conventional in vitro fertilization and embryo transfer: a stratified examination on the basis of the quantity of oocytes and blastocysts from a multicenter randomized controlled trial. Fertil Steril. 2024 Jul;122(1):121-130. doi: 10.1016/j.fertnstert.2024.02.023. Epub 2024 Feb 15.

  PMID: 38367687 DERIVED

• 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.

  PMID: 34818479 DERIVED

• 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.

  PMID: 32898291 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

Base Sequence

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena

Central Study Contacts

Zi-Jiang Chen, Professor

CONTACT

+0086 531 85651190; chenzijiang@vip.163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 27, 2017
• First Posted: April 18, 2017
• Study Start: July 9, 2017
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: September 20, 2019

Record last verified: 2019-09

Locations

CN (1)