O-098 Improved pregnancy rates following day 5 eSET with early hatching/hatched blastocysts (116-118 hours) compared to expanded blastocysts in a strictly selected cohort: a prospective study

Abstract Study question To investigate whether blastocysts hatching early on day 5 following IVF are developmentally superior and lead to better clinical outcomes in non PGT-A eSET cycles. Summary answer Fresh eSET on day 5 with spontaneously early hatching blastocysts (116-118 hrs) results in significantly better pregnancy rates compared to top quality expanded blastocyst transfers. What is known already Most studies seem to indicate that transfer of blastocysts at more advanced stages of development result in higher pregnancy rates. However, most studies comparing results between full/expanded vs hatching/hatched blastocyst transfers are either retrospective, have relaxed inclusion criteria, or perform transfers following assisted hatching or extended culture. Moreover, there appears to be no data on proportion of blastocysts that spontaneously hatch early on day 5, or how well they perform comparatively. Yet it has been reported that earlier time-points of blastocyst development are associated with higher euploidy. We felt the need for a well-designed prospective study to address these questions. Study design, size, duration This prospective study to compare pregnancy rates between early hatching/hatched blastocysts and top quality expanded blastocysts (4 BB or higher) in fresh, non PGT-A eSET cycles took place between October 2021 and October 2022 following institutional ethical clearance. 115 patients<37 years with AMH>1.5 undergoing 1st IVF cycles for tubal, mild male factor, unexplained infertility consented for the study and 94 patients completed it to eSET. Patients with PCOS, endometriosis or previous pelvic surgery were excluded. Participants/materials, setting, methods The study was conducted at a tertiary IVF centre. All patients underwent antagonist cycles, egg retrievals and IVF as per standard protocol. Blastocyst culture decision was taken at 2-PN examination. Embryos were examined at 116-118 hours as per our practise and decisions made to exclude from data analysis patients without at least one blastocyst at 4BB or above. eSETs performed at 120-122 hours with hatching/hatched blastocysts where available, expanded blastocysts in others. Luteal support initiated. Main results and the role of chance Demographic parameters of the patient cohort such as age (30.79±4.06), BMI (25.53±3.11) and AMH (3.23±1.68) are presented as mean± SD. Data was analysed using IBM SPSS V.26 statistical package. Differences in pregnancy rates between early hatching/hatched vs expanded blastocyst eSET groups were tested using Z test for proportions at 5% level of significance. Data was analysed for 94 patients of whom 62 had single expanded blastocyst transfers (22 achieved pregnancies) and 32 had eSET with early hatching/hatched blastocysts (of whom 18 became pregnant). 55 out of a total 261 blastocysts in the whole cohort were found to have initiated spontaneous hatching (n = 39) or fully hatched (n = 16) at 116-118 hours post-fertilisation resulting in an early hatching rate of 21.1% per blastocyst. Clinical pregnancy rate (CPR) defined as fetal heartbeat on ultrasound at 6 weeks of gestation and ongoing pregnancy rate (OPR) defined as pregnancy continuing beyond 10 weeks were found to be significantly superior in early hatching/hatched group vs expanded blastocyst group (CPR: 56.3% vs 35.5%, p = 0.002; OPR: 50% vs 30.6%, p = 0.003). Difference between miscarriage rate in the hatching/hatched group (11.1%, n = 2) and expanded blastocyst group (13.6%, n = 3) was not statistically significant. Limitations, reasons for caution Our sample size was relatively small in order to rigorously select a homogeneous group of good prognosis patients and adhere to strict study criteria- only 1st cycle, autologous, fresh, non PGT-A, day 5 eSET cycles were included. Larger controlled prospective studies would be valuable to confirm these findings. Wider implications of the findings To our knowledge this is the first report of improved pregnancy rates with early hatching blastocyst eSETs compared with expanded blastocysts. Basic science studies may shed more light on the biological underpinnings of these findings. Such transfer strategy may also prove useful to select the best blastocysts in non-PGT-A cycles. Trial registration number not applicable