Abstract

Abstract Study question Is the endogenous progesterone level (EPL) on the day of hCG administration associated with pregnancy outcomes in modified natural cycles before embryo transfer? Summary answer The present analysis suggested the negative effect of EPL on clinical pregnancy when progesterone was above 1,1 ng/ml on the day of HCG triggering. What is known already Endogenous progesterone levels (EPL) experience an abrupt increase following the ovulatory LH surge. It is described that this change in basal EPL contributes to modulating the endometrial receptivity in preparation for embryo implantation. Several authors reported a negative impact on the pregnancy of high serum EPL on the day of HCG. These studies revealed accelerated endometrial changes and a subsequent decoupling of the implantation window. These observations involved only patients who underwent ovarian stimulation before the embryo transfer. However, studies based on EPL in modified natural cycles before blastocyst transfer are very limited. Study design, size, duration The present non-interventional pilot cohort study aimed to determine the EPL in patients undergoing an endometrium preparation for frozen-thawed embryo transfer in non-stimulated cycles, and its association with clinical pregnancy rates. A total of 46 participants were included in this analysis. To reduce variability, the mean EPL was calculated excluding 2 outlier values in our dataset. The cut-off value of EPL was established using the Youden-index, and the T-student was used for further statistical comparisons. Participants/materials, setting, methods Patients following our IVF program, who underwent frozen-thawed embryo transfer during the period of study. Our data includes cycles with own and with donated oocytes. The total oocyte average age was 33,5±6,7. All transfers were performed at blastocyst stage. Main results and the role of chance The overall clinical pregnancy rate per embryo transfer was 70,5% (31/44), with an implantation rate of 66,7% (32/48). The mean number of transferred embryos was 1,09, with a single embryo transfer rate of 90,9%. The total mean of EPL was 0,31±0,26 [IC95% 0,23-0,39], with patients who achieved a clinical pregnancy (0,30±0,21; n = 31) showing significantly lower EPL (p-value=0,04) than the non-pregnant participants (0,41±0,40; n = 10). Three out of 44 patients had a biochemical pregnancy, with a mean EPL of 0,12±0,01. EPL cut-off value was establish at 1,1 ng/ml. The evaluation of the total dataset (n = 46 patients, including 2 outliers) showed that 8,7 % of a total of these cases had an EPL above the threshold of 1,1 ng/ml. The clinical pregnancy rate in this subgroup of patients was 25,0%. Limitations, reasons for caution This study includes a limited number of cases. Further analysis is required to confirm the present results and to allow data stratification for additional inter-group comparisons. Wider implications of the findings Evaluating EPL may contribute to improving the clinical outcome in natural modified cycles. We observed that EPL is expected to be lower in non-stimulated than in stimulated cycles, compared to previously published studies. These observations highlight the importance to manage treatment-related EPL thresholds, in particular, to establish transfer decision-making policies. Trial registration number n/a

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