Purpose To examine the live birth and other outcomes reported with and without preimplantation genetic testing for aneuploidy (PGT-A) in the United Kingdom (UK) Human Embryology and Fertilization Authority (HFEA) data collection. Methods A retrospective cohort analysis was conducted following freedom of information (FoI) requests to the HFEA for the PGT-A and non-PGT-A cycle outcomes for 2016–2018. Statistical analysis of differences between PGT-A and non-PGT-A cycles was performed. Other than grouping by maternal age, no further confounders were controlled for; fresh and frozen transfers were included. Results Outcomes collected between 2016 and 2018 included total number of cycles, cycles with no embryo transfer, total number of embryos transferred, live birth rate (LBR) per embryo transferred and live birth rate per treatment cycle. Data was available for 2464 PGT-A out of a total 190,010 cycles. LBR per embryo transferred and LBR per treatment cycle (including cycles with no transfer) were significantly higher for all PGT-A vs non-PGT-A age groups (including under 35), with nearly all single embryo transfers (SET) after PGT-A (significantly more in non-PGT-A) and a reduced number of transfers per live birth particularly for cycles with maternal age over 40 years. Conclusion The retrospective study provides strong evidence for the benefits of PGT-A in terms of live births per embryo transferred and per cycle started but is limited in terms of matching PGT-A and non-PGT-A cohorts (e.g. in future studies, other confounders could be controlled for). This data challenges the HFEA “red traffic light” guidance that states there is “no evidence that PGT-A is effective or safe” and hence suggests the statement be revisited in the light of this and other new data.
Preimplantation genetic diagnosis (PGD), first successfully carried out in humans in the early 1990s, initially involved the PCR sexing of embryos by Y-(and later also X-) chromosome specific detection. Because of the problems relating to misdiagnosis and contamination of this technology however the PCR based test was superseded by a FISH-based approach involving X and Y specific probes. Sexing by FISH heralded translocation screening, which was shortly followed by preimplantation genetic screening (PGS) for Aneuploidy. Aneuploidy is widely accepted to be the leading cause of implantation failure in assisted reproductive technology (ART) and a major contributor to miscarriage, especially in women of advanced maternal age. PGS (AKA PGD for aneuploidy PGD-A) has had a chequered history, with conflicting lines of evidence for and against its use. The current practice of trophectoderm biopsy followed by array CGH or next generation sequencing is gaining in popularity however as evidence for its efficacy grows. PGS has the potential to identify viable embryos that can be transferred thereby reducing the chances of traumatic failed IVF cycles, miscarriage or congenital abnormalities and facilitating the quickest time to live birth of chromosomally normal offspring. In parallel to chromosomal diagnoses, technology for PGD has allowed for improvements in accuracy and efficiency of the genetic screening of embryos for monogenic disorders. The number of genetic conditions available for screening has increased since the early days of PGD, with the human fertilization and embryology authority currently licensing 419 conditions in the UK [1]. A novel technique known as karyomapping that involves SNP chip screening and tracing inherited chromosomal haploblocks is now licensed for the PGD detection of monogenic disorders. Its potential for the universal detection of chromosomal and monogenic disorders simultaneously however, has yet to be realized.
Study question Are there significant differences in PGT-A “no result” rates and clinical outcomes following rebiopsy between ART clinics, and do rebiopsied embryos perform better than transferring with no result? Summary answer There is significant differences between clinics in terms of “no result rate” in PGT-A and utilisation of rebiopsy. What is known already: With any testing platform used in PGT-A, there is always a chance that a sample will not yield a result and rebiopsy may be considered to ascertain an embryos cytogenetic status. Studies have demonstrated rebiopsy yields results and adds to embryos genetically suitable for transfer. Clinical outcome data, however, remains scarce, leading to difficulty for clinics in benchmarking their performance when rebiopsied embryos are transferred. Study design, size, duration A retrospective analysis was performed of trophectoderm samples submitted for PGT-A via NGS over a 5yr period, 2015–2019. The no result (NR) rate was calculated per year and per clinic. Clinics were contacted for follow up data on NR embryos in terms of usage and clinical outcomes. Clinical outcomes from rebiopsied embryos were compared with those transferred as NR without rebiopsy. Participants/materials, setting, methods Data was collected on 22833 trophectoderm samples, submitted by 30 IVF laboratories. NR rate was analysed by year and by clinic. Clinics were asked if NR embryos had undergone rebiopsy, and if so if they had survived warming and rebiopsy. Clinics were asked if embryos selected for transfer had survived (re)warming, and to provide clinical follow-up including hCG test, clinical pregnancies, miscarriage and livebirth. The two tailed Fishers exact test was used for statistical analysis. Main results and the role of chance There was a wide range in sample numbers submitted by clinics over the time period, ranging from 9 samples through to 2633. In tclinics submitting over 500 samples the NR rate ranged from 0.6% to 7.4%, and in the those submitting 100–499 samples it ranged from 1.1% to 5.8%. Both these differences proved to be statistically significant (p < 0.05) between the best and worst performing clinics, and shows that a gap in performance exists between clinics. Less than 50% of NR embryos underwent rebiopsy. While the majority of embryos undergoing rebiopsy yielded a result (92.3%) and 31.4% of these were euploid or mosaic, almost half still remain in storage. The rate of livebirth/ongoing implantation in the rebiopsy group is 35.5% and 17.1% in the non rebiopsy group, illustrating a non significant trend towards a higher chance of implantation and livebirth in the rebiopsy group. Of 58 patients undergoing rebiopsy without any euploids in their initial cycle, 18 had a euploid embryo identified for future use. The additional manipulations involved in rebiopsy do not impact on survival at warming for transfer, but clinical outcomes in rebiopsied embryos appear poorer than those where a result was generated at first biopsy. Limitations, reasons for caution Despite starting with 22833 samples, 1115 of which were classified as NR, there were only 31 rebiopsied and 42 NR embryos transferred. It was therefore not possible to analyse transfer data by clinic or by embryo quality. Wider implications of the findings: Rebiopsy yields genetic results and embryos suitable for patient use, including for patients who produced no other euploid/mosaic embryos in their cycle. However, it is not offered/performed in many cases. Clinical outcome data must continue to be compiled and analysed to confirm performance exceeds transfer of NR embryos. Trial registration number Not applicable
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