Serum Progesterone Variability on Embryo Transfer Day in Hormone Replacement Therapy Cycles Using Intramuscular Injections During Frozen Embryo Transfers

Abstract

Purpose To assess the intra-individual variability of serum progesterone (P) levels on embryo transfer (ET) day, when the same dose of intramuscular progesterone (IM-P) was used in two consecutive hormone replacement therapy (HRT) frozen embryo transfer (FET) cycles. Methods A total of 75 patients undergoing two consecutive HRT-FET cycles in one year performed at Bahceci Ankara IVF Center between November 2019 and February 2022 were retrospectively analyzed. Serum P levels were measured at the 117th-119th hours of support by a single laboratory. The two measurements of P levels performed on the day of the first and the second FET were compared to evaluate the intra-individual variability of serum P levels. Results Comparisons between the 1st and 2nd FET cycles revealed statistically significant intra-individual variation, with an average difference of -2.47 ng/mL (95% CI: -4.65 to -0.29, p = 0.027) between the two consecutive measurements. To assess their consistency, the limit of agreement was also tested with the Bland-Altman method, in which the mean difference (+ 1.96 x SD and -1.96 x SD) was -2.47 (16.1 and -21.1). Based on a previous study, the frequency of low P levels, as expressed by being > 20.6 ng/mL on ET day, was similar between the 1st and 2nd FET cycles (14.7% vs. 9.3%, p = 0.31). Notably, most patients had improved P levels in the second cycle if initially low, while decreases were rare among those with initially higher levels. Conclusion Serum P levels may vary within the same individual across FET cycles despite the use of the same dosage of IM-P. Increasing maternal age, high body mass index, and fluctuating estradiol levels on the day of ET were identified as risk factors contributing to this variability.