Abstract

Abstract Study question Which factors are associated with low serum progesterone (P) levels on the day of frozen embryo transfer (FET), in hormonal replacement therapy (HRT) cycles? Summary answer Body Mass Index (BMI), parity, and non-European geographic origin are factors associated with low serum P levels on the day of FET in HRT cycles. What is known already While the detrimental impact of low serum P concentrations on HRT-FET outcomes is unanimously recognized, the factors accounting for P levels disparities among patients receiving the same luteal phase support treatment remain to be elucidated, in order to help clinicians predicting which subgroups of patients would benefit from a tailored P supplementation. 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. Independent factors associated with low serum P levels (defined as ≤ 9.8 ng/mL, according to a previous published study) were analyzed using univariate and multivariate logistic regression models. Main results and the role of chance The live birth rate was 31.5% (288/915) in the overall population. Two hundred and twenty-six patients (24.7%) had a low serum P level, on the day of the FET. Univariate analysis showed that BMI (p < 0.001), parity (p = 0.001), non-European geographic origin (p = 0.001), and the duration of infertility (p = 0.018) were significantly associated with low serum P levels. Moreover, the proportion of active smokers was significantly lower in the “low P concentrations” group (p = 0.002). After multivariate analysis, BMI (OR 1.06 95%CI [1.02-1.11], p = 0.002), parity (OR 1.31 95%CI [1.04-1.65], p = 0.024), non-European geographic origin (OR 1.67 95%CI [1.19-2.35], p = 0.003), and active smoking (OR 0.43 95%CI [0.21-0.85], p = 0.016) remained independent factors associated with serum P levels ≤ 9.8 ng/mL.  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 There is urgent need for future research on clinical factors affecting P concentrations to help clinicians predicting which subgroups of patients would benefit from individualized luteal phase support. More data are also needed on the underlying mechanisms explaining the relationship between patients’ characteristics and serum P levels in HRT-cycles. Trial registration number NA

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