Abstract

Abstract Study question Is there a relationship between progesterone levels on the day of frozen blastocyst transfer and ongoing pregnancy rate (OPR), in hormonal replacement therapy (HRT) cycles? Summary answer Women undergoing HRT-frozen embryo transfer with progesterone levels≤9.76ng/ml on the day of blastocyst transfer had a significantly lower OPR than those with progesterone levels>9.76 ng/ml. What is known already The importance of serum progesterone levels around the time of frozen embryo transfer (FET) is a burning issue, in view of the growing number of FET worldwide. However, the optimal range of serum progesterone levels is not clearly determined and discrepancies arise from the current literature. Study design, size, duration: Observational cohort study with 915 patients undergoing HRT-FET at a tertiary care university hospital, between January 2019 and March 2020. Participants/materials, setting, methods Patients undergoing single autologous blastocyst FET under HRT using exogenous estradiol and vaginal micronized progesterone for endometrial preparation. Women were only included once during the study period. The serum progesterone level was measured in the morning of the FET, in a single laboratory. The primary endpoint was OPR beyond pregnancy week 12. Statistical analysis was conducted using univariate and multivariate logistic regression models. Main results and the role of chance Mean serum progesterone level on the day of FET was 12.90 ± 4.89 ng/ml). The OPR was 35.5% (325/915) in the overall population. Patients with a progesterone level ≤ 25th percentile (≤9.76ng/ml) had a significantly lower OPR and a higher miscarriage rate (MR) compared with women with progesterone level over Centile 25 (29.6% versus 37.4%; p = 0.033 and 34.8% versus 21.3%; p = 0.008, respectively). After adjustment for the potential confounders in a multivariate analysis, a serum progesterone level ≤ 9.76 ng/ml on the day of FETand FET of a Day 6-blastocyst (versus Day 5-blastocyst) were found as independent risks factor of lower OPR. Limitations, reasons for caution The main limitation of our study is linked to its observational design. Extrapolation of our results to other laboratories, or other routes and/or doses of administering progesterone also needs to be validated. Wider implications of the findings: This study suggests that a minimum serum progesterone level is needed to optimize reproductive outcomes in autologous blastocyst FET, in HRT-cycles. Further studies are needed to evaluate if modifications of progesterone routes and/or doses may improve pregnancy chances, in an approach to individualize the management of ART patients. Trial registration number NA

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