Clinical trial NCT04734769: Embryos With Preimplantation Genetic Testing for Aneuploidies (PGT-A) Inconclusive Result: Clinical Implications
Official title: Embryos With Preimplantation Genetic Testing for Aneuploidies (PGT-A) Inconclusive Result: Clinical Implications
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Embryo Disorder
Lead sponsor: IVI Vigo
Sponsor class: OTHER
Collaborators: name: Instituto Valenciano de Infertilidad, IVI VALENCIA
name: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company
First posted: 2021-02-02
Enrollment: 600
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Implantation rate
timeFrame: Since July 2019 to December 2020
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: IVI Vigo
name: Elkin Muñoz
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.