P-709 Predictive heatmap in Preimplantation Genetic Testing for Monogenic disorders (PGT-M) and Structural Rearrangements (PGT-SR)

Abstract

Abstract Study question What is the predicted cumulative live birth rate (CLBR) relative to AMH-level for women undergoing preimplantation genetic testing (PGT) for monogenic disorders and structural rearrangements? Summary answer Anti-müllerian hormone (AMH) and age allow to give an estimate of the CLBR in PGT and becomes poor when AMH is ≤ 2µg/L and age ≥42y. What is known already Ovarian response is an important contributory factor in PGT in order to obtain a sufficient number of embryos for genetic analysis. A proportion of the obtained embryos will be carrier of the disease tested, and another small proportion of the embryos will fail to have a genetic diagnosis hence will not be available for embryo transfer. The number of embryos not suitable for embryo transfer as a result of PGT varies between 25-81% according to the indication for PGT. The combination of female age and AMH are good predictors for CLBR in conventional IVF. Study design, size, duration This is a single-centre retrospective cohort study including 1,522 females undergoing 3,130 PGT cycles over a 6-year period (01/01/2015-31/12/2020) at a university-based referral centre for PGT. The principal outcome measure was CLBR per intention to treat (ITT), and the secondary outcome was live birth rate (LBR) per embryo transfer, in couples undergoing PGT-M and PGT-SR either by polymerase chain reaction (PCR), single nucleotide polymorphism (SNP) array, microarray-based comparative genomic hybridization (aCGH), or next-generation sequencing (NGS). Participants/materials, setting, methods Mean ±SD was applied for continuous outcomes, whereas (relative) frequency was applied for dichotomous outcomes. Multivariable logistic regression analysis was applied with dependent variable being the CLBR or LBR and the independent variables the AMH, female age, BMI, inheritance mode and PGT-technique. Best-fit (Akaike information criterion (AIC)) versus polynomials were analysed. Non-inferiority testing between different technologies was performed. A 3D-prediction mosaic (including AMH, age and CLBR) was created, which can be used for counseling purposes. Main results and the role of chance The mean female age is 32.46 years (SD 4.43), with a mean AMH level of 2.75 µg/L (SD 2.58) and a mean BMI of 24.24 (SD 4.43). Age and AMH significantly affect CLBR irrespective of the inheritance mode or PGT technique used. There is a gradual decline of CLBR from a female age of 25 years onwards reaching a critical threshold of less than 10% CLBR per ITT over the age of 42 with AMH levels ≤2 µg/L. Between cleavage stage biopsy techniques (PCR) and trophectoderm biopsy PGT techniques (SNP array, aCGH, NGS) used there was no significant difference in outcome per ITT, however per embryo transfer there is a significantly higher chance of live birth in SNP array, aCGH and NGS cycles compared to PCR cycles. Limitations, reasons for caution Despite the large sample size, the findings are confined by limited confounder adjustment. Wider implications of the findings In a PGT-program, couples need to be informed on the limited prognosis, if the combination of female age and AMH is unfavourable, in order to allow them to make other reproductive choices. The prediction mosaic produced in this study can be used as an insightful visual tool in counseling PGT-couples. Trial registration number Not applicable