Abstract

Abstract Study question Is there a suitable range of serum progestereone level at triggering day to optimize the cumulative live birth rate (LBR) in high responders? Summary answer Fom the point of view of cLBR, the optimal P4 range for triggering is between 1.5 to 2.5 ng/ml generally and in the high responders. What is known already It is well established that premature progesterone rise (PPR) affect adversely the pregnancy outcome in fresh embryo transfer cycle. It is inferred that PPR alters synchrony between endometrium and the embryos. However, detailed study of the effect of PPR on efficiency of oocyte retrieval , embryo quality and the subsequent cumulative pregnancy outcome is still lacking. Hence we sort to analyze the effect of PPR on the final cumulative LBR in our program especially focused on high responders. Study design, size, duration ART Database in our center was retrospectively reviewed. Total 1523 cycles between 20160101 and 20191231 were recruited under the condition of GnRH antagonist cycle with duration of ovulation induction for more than 5 days and available serum P4 level data on triggering day for data analysis for the relationship between serum P4 value and final cumulative LBRs. Participants/materials, setting, methods Cycles with serum P4 level < 1.5 ng/ml were defined as without PPR (Group A: n = 1383). Cycles with serum P4 level >1.5 were defined as with PPR: P4 between 1.5 and 2.5 as Group B (n = 113), P4 > 2.5 as Group C (n = 27). Those high responding cycles (n = 404) were analyzed similarly and separately as Group A’ (n = 304), B’ (n = 81) and C’(n = 19). The statistics were carried out by SPSS-PC ver. 22.0 with p < 0.05 as statistical significance. Main results and the role of chance Group A had significantly lower number of oocytes (9.8 + 8.0) retrieved as compared to Group B (19.3 + 11.2) and Group C (18.2 + 9.9). However there were no differences in fertilization rate, good embryo rates and BC formation rates between groups. The cumulative LBR (cLBR) were significantly higher in Group B (65.1%) as compared to Group A (40.9%, p < 0.001) and Group C (37.0%, p = 0.008). For the high responding cycles, Group B’ also had marginally significant higher cLBR (75.3%) as compared to group A’(63.8% ; p=0.051) and Group C’ (52.6%; p = 0.050). Comparisons between Group A’ and C revealed significantly less oocytes retrieved but significantly higher blastocyst formation rates in Group A’ and the resultant cLBR were comparable between these two groups. Comparisons between Groups B’ and C’ revealed comparable oocytes retrieved but significant lower blastocyst formation rates and cLBRs in Group C’. The baseline of the first part analysis revealed higher age and lower AMH in Group A, but comparable age and AMH between groups B and C.The lower cLBR in group A could be due to selection bias.The second part (high responders) showed comparable baselines between three groups. However, the case numbers are too few in group C’ which might also result in uncertainty. Limitations, reasons for caution Although the data revealed interesting, significantly different results between groups, this is only a retrospective analysis from our ART patient series. Selection bias could not be precluded. Analysis restricted to high responders could have a more balanced population for comparisons. However, more cases are needed to affirm the findings. Wider implications of the findings: We still do not know the tolerable ceiling of serum P4 at the triggering day in high responders if future FET already planned. Pushing P4 value too high not only could not increase mature oocyte yields and possibly may decrease the number of available good blastocysts for optimizing final cLBRs. Trial registration number Not applicable

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