Impact of serum progesterone levels at embryo transfer on HRT-FET outcomes: A systematic review

Relevance: The effectiveness of assisted reproductive technologies (ART) remains a primary goal of reproductive medicine. Despite significant breakthroughs in the field, a significant proportion of patients fail to achieve a successful outcome of in vitro fertilization (IVF) treatment. The impact of various factors, including serum progesterone (P4) level on embryo transfer day, on ART outcomes remains poorly understood and requires further research. This study aimed to evaluate the relationship between serum progesterone levels at embryo transfer and outcomes of hormone replacement therapy in frozen embryo transfer cycles. Materials and Methods: This literature review analyzes publications in English, Kazakh and Russian for 2015-2025, indexed in the PubMed, Scopus and Web of Science databases. Results: P4 levels at embryo transfer play a pivotal role in determining the success of HRT-FET cycles, with robust evidence corroborating a lower threshold of approximately 8-10 ng/mL in women undergoing vaginal progesterone administration for luteal phase support (LPS). In patients with parenteral or combined progesterone regimens for LPS, the lower threshold is different and appears to be higher or even non-existent. A detrimental upper P4 level at embryo transfer remains unconvincing. Individual patient and treatment characteristics, along with hormone assay variability, underscore the need for personalized P4 monitoring and LPS. Conclusion: This review emphasizes the need for large, methodologically rigorous prospective studies to elucidate the impact of P4 levels at embryo transfer in HRT-FET cycles. A deeper understanding of individualized progesterone thresholds and their interaction with patient and treatment variables could transform current strategies for LPS, shifting toward more personalized protocols that optimize implantation and live birth outcomes in ART.