NCT04758819

Brief Summary

Preimplantation embryo aneuploidy is a major source of adverse outcomes in human reproduction since it leads to implantation failure, early pregnancy loss or severe chromosomal diseases. The risk of embryos aneuploidy is drastically increased after 35 years old. The intra uterine transfer of euploid embryos assessed through such techniques as next-generation sequencing (NGS) based Comprehensive chromosomal Testing of Trophectoderm (TE) biopsies of Blastocysts (CTTEB), may improve implantation and live birth rates, and decrease miscarriage rates. But no randomized controlled trial (RCT) was ever performed to test the interest of CTTEB for women that really needed it (≥35 to ≤ 41 years old). In this multicentre randomized-controlled-trial, the investigators will compare live birth rate obtained after the first single frozen-thawed blastocyst transfer cycle following the freeze-all-Intracytoplasmic sperm injection cycle in infertile and old couples between two different strategies of Day 5/6 blastocyst selection:

  • Control group: morphological criteria (Istanbul consensus)
  • Interventional group: international recommendations after CTTEB (www.pgdis.org; Newsletter May 27, 2019).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
700

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jul 2021

Longer than P75 for not_applicable

Geographic Reach
1 country

10 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 30, 2020

Completed
3 months until next milestone

First Posted

Study publicly available on registry

February 17, 2021

Completed
5 months until next milestone

Study Start

First participant enrolled

July 12, 2021

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2026

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2026

Completed
Last Updated

January 19, 2024

Status Verified

January 1, 2024

Enrollment Period

4.5 years

First QC Date

November 30, 2020

Last Update Submit

January 18, 2024

Conditions

Infertility

Keywords

embryo aneuploidyIntracytoplasmic Sperm Injectionin vitro fertilizationNext-Generation Sequencingrandomized controlled trial

Outcome Measures

Primary Outcomes (1)

  • Number of live birth

    To compare live birth rate (LBR) obtained after the first single frozen-thawed blastocyst transfer cycle following the freeze-all-Intracytoplasmic sperm injection (ICSI) cycle

    One year

Secondary Outcomes (13)

  • Number of live birth taking in consideration further single frozen-thawed blastocyst cycles

    Until 48 months

  • Biological ICSI parameters

    30 months (inclusion period)

  • Pregnancy outcome

    18 months (participation period)

  • Ratio between the proportion of women with live birth and days after randomization

    Until 48 months

  • Cost of the procedure

    18 months (participation period)

  • +8 more secondary outcomes

Study Arms (2)

Control group

NO INTERVENTION

Embryo selection according to Day 5/6 usual morphological criteria (Istanbul consensus)

Comprehensive chromosomal Testing of Trophectoderm biopsies of Blastocysts: CTTEB group

EXPERIMENTAL

Trophectoderm cells will be analyzed by NGS. Culture media will also be stored for further non-invasive chromosomal testing. Embryo selection will be done according to international guidelines (www.pgdis.org; Newsletter May 27, 2019).

Procedure: Comprehensive chromosomal Testing of Trophectoderm biopsies of Blastocysts (CTTEB)

Interventions

Comprehensive chromosomal Testing of Trophectoderm biopsies of Blastocysts (CTTEB)PROCEDURE

In vitro Fertilization by ICSI then embryo culture until Day 5/6; all blastocysts with morphological scores compatible with TE biopsy and vitrification will be submitted to Comprehensive chromosomal Testing of Trophectoderm biopsies of Blastocysts (CTTEB) and vitrified.

Comprehensive chromosomal Testing of Trophectoderm biopsies of Blastocysts: CTTEB group

Eligibility Criteria

Age35 Years - 41 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Women :
  • Age ≥35 to ≤ 41 years old (according to date of birth at time of informed consent) who are eligible for ovarian stimulation and ART treatment, including intracytoplasmic sperm injection (ICSI)
  • BMI=18-35 kg/m2 inclusive
  • No intrauterine and/or endometrial abnormalities that would interfere with implantation or pregnancy (for instance polyp, fibroid, …)
  • Use of ejaculated motile sperm (donated and/or cryopreserved sperm is allowed)
  • Age ≤ 50 years old
  • Primary or secondary infertility
  • Dated and signed inform consent
  • Affiliated to National Insurance
  • French speaking, able to understand the study
  • Criteria after randomization
  • Couple having at least one blastocyst with morphological score on Day 5/6 of in vitro embryo development (blastocoel expansion ≥3 and inner cell mass graded A, B or C and trophectoderm graded A or B

You may not qualify if:

  • Women:
  • Recurrent implantation failure (previous transfer of least 5 good grade blastocysts in at least 3 fresh or frozen cycles)
  • Personal history of recurrent miscarriages (more than two miscarriages)
  • Altered ovarian reserve: Identified risk of poor ovarian response (history of oocyte puncture with less than 3 oocytes) or AMH\<1.1 ng/mL and AFC\<5)
  • Presence of non isolated uni- or bilateral hydrosalpinx
  • History or presence of ovarian, uterine or mammary cancer
  • Contraindication to being pregnant and/or carrying a pregnancy to term
  • Women with uterine polyps diagnosed during COS
  • Known allergy or hypersensitivity to human gonadotropin preparations or to compounds that are structurally similar to any of the other medications administered during the trial
  • Substance abuse that would interfere with trial conduct, as determined by the investigator
  • Pregnant patient, nursing patient
  • Men:
  • \- Use of testicular or epididymal sperm
  • Couples:
  • Known infection with human immunodeficiency virus, active hepatitis B or C virus in the female or male partner
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Hôpital Jean Verdier

Bondy, 93, France

RECRUITING

Hôpital Antoine Béclère

Clamart, 92140, France

RECRUITING

CHU Clermont-Ferrand

Clermont-Ferrand, 63000, France

RECRUITING

CHU Dijon

Dijon, 21079, France

RECRUITING

Hôpital Arnaud de Villeneuve

Montpellier, 34295, France

RECRUITING

CHU Nantes

Nantes, 44093, France

RECRUITING

Hôpital Cochin

Paris, 75014, France

RECRUITING

Hopital Tenon

Paris, 75020, France

NOT YET RECRUITING

CHU Strasbourg

Schiltigheim, 67300, France

RECRUITING

Hôpital Foch

Suresnes, 92, France

RECRUITING

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital DiseasesUrogenital Diseases

Study Officials

  • Nelly Frydman, Pharm D, PhD

    Assistance Publique - Hôpitaux de Paris

    STUDY DIRECTOR

Central Study Contacts

Catherine Patrat, MD, PhD

CONTACT

+33 1 58 41 37 34catherine.patrat@aphp.fr

Christelle Auger

CONTACT

+33 1 58 41 11 86christelle.auger@aphp.fr

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 30, 2020

First Posted

February 17, 2021

Study Start

July 12, 2021

Primary Completion

January 1, 2026

Study Completion

January 1, 2026

Last Updated

January 19, 2024

Record last verified: 2024-01

Data Sharing

IPD Sharing
Will not share

Locations

FR(10)