Embryos With Preimplantation Genetic Testing for Aneuploidies (PGT-A) Inconclusive Result: Clinical Implications

One of the most remarkable improvements in trophoectoderm cells biopsy is the robustness of diagnosis as result of analyzing multiple cells. However, there is a proportion of embryos that lack of diagnosis due to amplification failure or inconclusive results ranging between 0,4% and 6%. Information about embryo repeated biopsy after an inconclusive result in a first biopsy is very scarce. No specific conclusions can be drawn, due to the limited information currently available concerning reproductive outcomes for patients who had embryo transfer after a second biopsy, due to a first one having an inconclusive result. Investigators purpose a multicenter retrospective observational study with the aim to evaluate the reproductive potential of re-biopsied blastocyst with inconclusive results on preimplantation genetic screening for aneuploidy (PGT-A) using the implantation rate (IR) and ongoing pregnancy rate (OPR) as principal variables.

Study Overview

• Status: Not yet recruiting
• Conditions: Embryo Disorder
• Intervention / Treatment: Other: Collect retrospectively clinical data on reproductive outcomes

Detailed Description

The main objective of assisted reproduction technologies (ART) is to achieve a healthy live newborn. The selection of an euploid embryo using PGT-A, offers theoretical advantages including increased implantation rate, reduced abortion rate, and reduces the time to achieve an ongoing pregnancy.

Certain advances in ART such as vitrification or improvement in culture media makes safer the PGT-A procedure. As a result of these improvements, embryo biopsy has been driven from blastomere to trophectoderm biopsy at blastocyst stage for preimplantional genetic testing for aneuploidy analysis (PGT-A 2.0) and it is now the method of choice for PGT-A in many centers. Trophectoderm biopsy presents advantages over the use of blastomere biopsy: 1. It allows obtaining around 6-10 cells without reducing the potential for pre-embryo development or its ability to implant. 2. Greater strength in the results, since it reduces false diagnoses associated with factors such as mosaicism. 3. It allows a combined study for monogenic mutations, aneuploidy screening and / or structural alterations.

The frequency of inconclusive results in PGT-A varies depending on the embryonic stage used, with values of 9-10% of the total embryos analyzed for single blastomere biopsy and between 2-6% when trophectoderm cells are biopsied.

These inconclusive results, mainly in couples without euploid embryos available to transfer, cause them uncertainty and disappointment. In these situations, it is advisable to guide patients in making decisions about what to do with these pre-embryos through genetic counselling. Patients must decide if they wish to reject them, to transfer them without the certainty of a reliable diagnosis or to re-analyze them. Scientific literature reporting these types of inconclusive results and that give advice about its possible etiology are scarce. There is no clear evidence about the impact of double biopsy, double vitrification-warming or if transferring embryos with inconclusive results, is safe for achieving a healthy newborn. The objective of this review is to learn from the published studies about the safety of embryo re-analysis and its potential reproductive outcome when there are embryos with inconclusive results after PGT, in order to offer adequate counselling for patients.

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

• Study Contact: Name: Elkin Muñoz; Phone Number: 986021860; Email: elkin.munoz@ivirma.com
• Study Contact Backup: Name: Agustina Ramos Gutierrez; Phone Number: 986021860; Email: agustina.ramos@ivirma.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

All patients with indication of PGT-A (advanced maternal age, male factor, recurrent pregnancy loss, recurrent implantation failure, previous aneuploidy pregnancy) with differed single embryo transfer.

Description

Inclusion Criteria:

• Cycles of embryo transfer from patients with at least one euploid embryo (no rebiopsy group):
• Women age 18-45 years.
• PGT-A Indication.
• All embryos with informative results.
• Women age 18-45 years.
• PGT-A Indication.
• At least one embryo result with lack of diagnosis.
• At least one rebiopsied embryo.
• At least one euploid result from rebiopsied embryo.
• Single embryo transfer.

Exclusion Criteria:

Double embryo transfer

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cycles of embryo transfer from patients with at least one euploid embryo (no rebiopsy group); Collect retrospectively clinical data on reproductive outcomes	Other: Collect retrospectively clinical data on reproductive outcomes; Collect retrospectively clinical data on reproductive outcomes
Rebiopsy group: Collect retrospectively clinical data on reproductive outcomes	Other: Collect retrospectively clinical data on reproductive outcomes; Collect retrospectively clinical data on reproductive outcomes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation rate	Analyze implantation rate in the groups	Since July 2019 to December 2020

Collaborators and Investigators

• Sponsor: IVI Vigo
• Collaborators: Instituto Valenciano de Infertilidad, IVI VALENCIA; Juno Therapeutics, Inc.

Publications and helpful links

General Publications

• Cobo A, Castello D, Vallejo B, Albert C, de los Santos JM, Remohi J. Outcome of cryotransfer of embryos developed from vitrified oocytes: double vitrification has no impact on delivery rates. Fertil Steril. 2013 May;99(6):1623-30. doi: 10.1016/j.fertnstert.2013.01.106. Epub 2013 Feb 14.
• Chen HH, Huang CC, Cheng EH, Lee TH, Chien LF, Lee MS. Optimal timing of blastocyst vitrification after trophectoderm biopsy for preimplantation genetic screening. PLoS One. 2017 Oct 5;12(10):e0185747. doi: 10.1371/journal.pone.0185747. eCollection 2017.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 20, 2021
• Primary Completion (Anticipated): February 21, 2021
• Study Completion (Anticipated): November 25, 2022

Study Registration Dates

• First Submitted: January 27, 2021
• First Submitted That Met QC Criteria: February 1, 2021
• First Posted (Actual): February 2, 2021

Study Record Updates

• Last Update Posted (Actual): February 2, 2021
• Last Update Submitted That Met QC Criteria: February 1, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chromosome Aberrations; Aneuploidy
• Other Study ID Numbers: 2011-VGO-095-EM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No