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

NCT ID: NCT03118141

Last Updated: 2019-09-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

1215 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-09

Study Completion Date

2020-06-30

Brief Summary

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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

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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.

Conditions

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Infertility

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PGS group

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.

Group Type ACTIVE_COMPARATOR

blastocyst morphologic score

Intervention Type PROCEDURE

Blastocysts will be scored by Gardner morphologic criteria.

blastocyst biopsy and sequencing

Intervention Type PROCEDURE

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

freeze-all and single thawed blastocyst transfer

Intervention Type PROCEDURE

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

IVF group

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.

Group Type ACTIVE_COMPARATOR

blastocyst morphologic score

Intervention Type PROCEDURE

Blastocysts will be scored by Gardner morphologic criteria.

freeze-all and single thawed blastocyst transfer

Intervention Type PROCEDURE

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

Interventions

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blastocyst morphologic score

Blastocysts will be scored by Gardner morphologic criteria.

Intervention Type PROCEDURE

blastocyst biopsy and sequencing

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

freeze-all and single thawed blastocyst transfer

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

Intervention Type PROCEDURE

Eligibility Criteria

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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.
Minimum Eligible Age

20 Years

Maximum Eligible Age

37 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role collaborator

Peking University Third Hospital

OTHER

Sponsor Role collaborator

ShangHai Ji Ai Genetics & IVF Institute

OTHER

Sponsor Role collaborator

RenJi Hospital

OTHER

Sponsor Role collaborator

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

OTHER

Sponsor Role collaborator

Suzhou Municipal Hospital

OTHER

Sponsor Role collaborator

Renmin Hospital of Wuhan University

OTHER

Sponsor Role collaborator

Yantai Yuhuangding Hospital

OTHER

Sponsor Role collaborator

Tang-Du Hospital

OTHER

Sponsor Role collaborator

Nanjing Maternity and Child Health Care Hospital

OTHER

Sponsor Role collaborator

Guangxi Maternal and Child Health Hospital

OTHER

Sponsor Role collaborator

Women's Hospital School Of Medicine Zhejiang University

OTHER

Sponsor Role collaborator

Guangdong Women and Children Hospital

OTHER

Sponsor Role collaborator

Tianjin Central Hospital of Gynecology Obstetrics

OTHER

Sponsor Role collaborator

Shengjing Hospital

OTHER

Sponsor Role collaborator

The First Affiliated Hospital of Anhui Medical University

OTHER

Sponsor Role collaborator

Chen Zi-Jiang

OTHER

Sponsor Role lead

Responsible Party

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Chen Zi-Jiang

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Shandong University

Jinan, Shandong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Zi-Jiang Chen, Professor

Role: CONTACT

+0086 531 85651190

Facility Contacts

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Zi-Jiang Chen, Professor

Role: primary

+0086 531 85651190

References

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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.

Reference Type BACKGROUND
PMID: 26385405 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23548942 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22551456 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23731996 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25772770 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25006207 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26902859 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39153572 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38564220 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38367687 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34818479 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32898291 (View on PubMed)

Other Identifiers

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CESE-PGS

Identifier Type: -

Identifier Source: org_study_id

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