Abstract

Abstract Study question Is a change of embryo quality through vitrification and thawing associated with a reduced LBR when a single euploid frozen embryo transfer is performed? Summary answer Live birth rates are not influenced by a change in embryo quality through embryo cryopreservation and thawing in single euploid frozen embryo transfer. What is known already Embryo aneuploidy is the most significant single factor and accounts for about 50% of implantation failure and miscarriage in human reproduction. Preimplantation genetic test for aneuploidy (PGT-A) presents a mean to identify euploid embryos, thereby improving pregnancy rates and reducing early pregnancy losses. However, after PGT-A on trophectoderm cells at blastocyst stage, embryos have to be cryopreserved and warmed later for the embryo transfer procedure. Embryo quality is known to impact implantation and ongoing pregnancy rates, therefore, the aim of this analysis was to evaluate the impact of a change in embryo quality between pre-vitrification and post-thaw on the outcome. Study design, size, duration This retrospective observational study included a total of 611 pregnant patients after frozen-thawed euploid single embryo transfer (FET) at a tertiary IVF centre between April 2017 and December 2020. All embryos transferred were cryopreserved after trophectoderm biopsy for PGT-A, performed either on day 5 or day 6. Each patient was only included once into the analysis. Endometrial preparation for FET was performed either in a natural cycle (NC) or as a hormonal replacement cycle (HRT). Participants/materials, setting, methods Patients with infertility, undergoing ovarian stimulation and FET in either a HRT or a NC as endometrial preparation approach, and who achieved a pregnancy, were included. Embryos were morphologically graded pre-vitrification and post-thaw based on inner cell mass and trophectoderm morphology on the day of cryopreservation. Four groups were initially established (top, good, fair, poor), hence for the analysis, fair and poor qualities were combined. Main results and the role of chance A total of 591 patient were analysed after exclusion of 20 patients due to the occurrence of late miscarriage and ectopic pregnancy. Patients’ characteristics are as follows (mean±SD (min-max)): age 33.87±5.55(20-47) years; AMH 3.20±3.28ng/mL(0.01-35.72); BMI(body mass index) 26.61±4.86kg/m2(14.84-40.31) and AFC 14.00±7.33(1-35). The changes in the embryo quality pre-vitrification and post-thaw were categorized in “no change”, “improved” or “degraded”. All groups were compared to top-quality-no change group. A binary logistic analysis evaluated the following groups regarding their combined impact on LB: top quality-degraded (odds ratio (OR)0.702; 95% confidence interval (CI)0.302-1.635, p = 0.413); good quality-no change (OR 1.022; CI:0.457-2.287; p = 0.958); good quality-degraded (OR 0.787; CI:0.330-1.880; P = 0.590); good quality-improved (OR 0.301; 0.056-1.628; P = 0.163); fair+poor quality-no change(OR 0.521; 0.203-1.340; P = 0.176); fair+poor quality-degraded (OR 0.283; 0.056-1.438; P = 0.128) and fair+poor quality-improved (OR 1.917; 0.431-8.534; P = 0.393). No impact on the probability of LB was seen in any combined group of change in embryo quality with its pre-grades. Furthermore, no association was found for age, BMI, AMH, pre-vitrification and post-thaw quality. Embryos biopsied on day 6 instead day 5 had a decreased chance of a LB (OR 0.516; 0.305-0.875, p = 0.014). Further on, NC was associated with significantly higher chance of LB compared to HRT cycle (OR 2.629; 1.606-4.305, p = <0.001). Limitations, reasons for caution Limitation is the retrospective design of the study and the grading of the embryos, which might be subjective and bearing interobserver variability. Wider implications of the findings Whereas a change in the embryo quality does not impact the chance of LB after single euploid FET, a NC approach increases the odds for LB. This fact should be considered for a personalized treatment approach and in the choice of the endometrial preparation protocol. Trial registration number not applicable

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