Abstract

Abstract Study question Does the outcome of the first, euploid transfer affect the success rate of the second PGT-A transfer cycle? Summary answer Live birth rate is higher in the second euploid transfer if the first euploid transfer results in at least a biochemical pregnancy versus no implantation. What is known already There is limited evidence on counselling patients for a second euploid embryo transfer based on previous outcomes. The existing literature is reassuring showing very high implantation rates even following two or more successive failed euploid transfers. Achieving implantation is a major step towards success. The association between a PGT-A embryo transfer cycle where implantation was achieved (at least biochemical pregnancy, miscarriage or live birth) with the outcome of the subsequent embryo transfer is interesting to explore and incorporate in patient counselling. Study design, size, duration This is a retrospective analysis of patients who underwent PGT-A treatment in a single centre from 2015-2021. Live birth rate was the main outcome of interest. Pregnancy rate and miscarriage rate were secondary outcomes. Means and standard deviations were used for demographic parameters. Embryos were biopsied at blastocyst stage for PGT-A and next generation sequencing was used. Embryo transfers were performed with uniform protocols by different, experienced clinicians. Participants/materials, setting, methods Patients who had their second euploid embryo transfer were included in the analysis. Outcomes were assessed in relation to the outcome of the first euploid cycle; whether at least a biochemical pregnancy was achieved versus a negative pregnancy test. Patients with uterine anomalies / suboptimal endometrial thickness were excluded. Protocols for endometrial preparation and add-ons were individualised and were not uniform for the two cycles. Protocols included both medicated cycles and ovulatory cycles. Main results and the role of chance 331 women were included in the analysis undergoing their second euploid embryo transfer cycle. 152 had one previous euploid implantation (the first cycle resulted in a biochemical pregnancy, miscarriage, or live birth) (group 1) and 179 had one previous failed implantation of a euploid embryo (the first cycle resulted in a negative pregnancy test) (group 2). There was no significant difference between the two groups in patient demographic characteristics including age, body mass index and age at egg collection. No significant difference was documented for embryo quality, day 5 versus day 6 embryos or endometrial thickness. More cycles were medicated in group 1 compared to group 2. All patients had an elective single embryo transfer. Live birth rate was significantly higher for group 1 versus group 2, 58% vs 44%, p = 0.013, OR 1.75 (1.12-2.70). No significant difference was observed for pregnancy rate or miscarriage rate. Limitations, reasons for caution This is a retrospective analysis in a single fertility centre, therefore prone to bias and results cannot be generalised unless validated by larger prospective multi-centre studies. There are multiple possible cofounders such as background and duration of subfertility, endometrial preparation protocols and add-on interventions which cannot be accounted for. Wider implications of the findings These findings suggest that the first euploid transfer outcome is important for future euploid transfer cycles. Women who achieved at least a positive pregnancy test in the first cycle seem to have higher success rates in subsequent PGT-A transfer. Further research is warranted to explore this association for patient counselling. Trial registration number not applicable

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