P-718 Preimplantation genetic testing in Belgium: recommendations for the genetic centres

Abstract Study question How do genetic centres in Belgium apply international guidelines on preimplantation genetic testing (PGT)? Summary answer We present the national consensus on how to practice PGT, starting from initial patient uptake and embryo selection to follow-up of pregnancies. What is known already PGT includes PGT-M for monogenic disorders, PGT-SR for structural rearrangements and PGT-A for aneuploidy screening. The application of whole-genome technologies to trophectoderm biopsies for PGT-M and PGT-SR/A has evidenced the high prevalence of mosaicism due to chromosome segregation errors during the first mitotic divisions, making biopsy results interpretation and embryo transfer policy more challenging and complex. Guidelines from several international societies have been published in recent years to leverage the standardization of the whole PGT service. Although these are based on expertise and continuously acquiring evidence, it is widely recognized that variations in local and national regulations diversify PGT practices. Study design, size, duration Recommendations regarding PGT indications, patient counselling, embryo transfer policy, reporting, quality and pregnancy follow-up have been built to harmonize PGT services nationally. With a special focus on mosaicism, aiming to balance the highest chance for a pregnancy with the lowest risk for a chromosomally abnormal ongoing pregnancy or child. Participants/materials, setting, methods The Belgian PGT working group consists of laboratory geneticists, clinical geneticists and IVF specialists from eight nationally accredited centres. The group operates under the BeSHG umbrella and meets quarterly to formulate opinions and statements on PGT practice with the main goal of guaranteeing a high standard of care, exchange knowledge and implement a harmonized workflow. The Belgian social security system provides reimbursement of six genetic testing cycles for all PGT-M/SR patients but not for PGT-A. Main results and the role of chance PGT is offered for all monogenic and chromosomal disorders, if the causal genetic variants are known and documented. PGT for HLA-typing is allowed for the therapeutic benefit of an existing child after couple's psychological evaluation. Aneuploidy screening can be offered to specific patient groups to increase IVF success rate. However, social sexing and testing for non-medical or eugenic purposes is prohibited. At intake, the couple is counselled about the genetic aspect of the disease, psychological and financial aspects of PGT, applied methodology, including average success and misdiagnosis rate, and embryo transfer policies. Affected embryos, and embryos without diagnosis for PGT-M/SR are not transferred. For PGT-A (combined or not with PGT-M/SR), embryos are categorized as: (A) Euploid - suitable for transfer, if mosaicism is absent or below the detection threshold. (B) Mosaic transferable - suitable for transfer, but only following ranking and/or counselling and follow up, if mosaicism for any chromosome not described in (C) is detected; (C) Aneuploid or Mosaic - not suitable for transfer, if mosaicism of 8, 9, 13, 16, 18, 21 and X or full aneuploidy of any chromosome is detected. Non-invasive prenatal testing is strongly recommended to all women pregnant after PGT and is nationally reimbursed. Limitations, reasons for caution The practical recommendations, which are supplementary to the recently published ESHRE PGT recommendations, are based on expertise and data from the literature available at the time of preparation. As such, they will need regular reconsideration and an update or extension may follow when new solid scientific evidence arises. Wider implications of the findings As international recommendations represent a greatest common denominator over many local regulations, this work serves as example for drawing country-specific agreements for genetic centres. The process of consensus expert opinion formation on best practice may be applicable in other countries where PGT service is not overseen by a designated agency. Trial registration number Not applicable