Comparison of Patient Satisfaction, Convenience and Tolerability Between Two Vaginal Progesterone Formulations During Frozen Embryo Transfer

Over the past few decades, assisted reproductive technology (ART) treatments have seen their protocols updated by advances in cryopreservation methods, leading to the mainstream use of the frozen embryo transfer (FET) strategy (Nagy, Shapiro, & Chang, 2020). FET protocols are generally subdivided in either natural cycle (NC-FET) or artificial cycle (AC-FET), with several centers preferring the latter due to its flexibility in scheduling and ease of monitoring. Nonetheless, previous reports positing that AC-FET may be associated with an increased risk of miscarriage and hypertensive disorders during pregnancy have put this preference into question (Roelens, et al., 2022). Having said that, the natural proliferative phase frozen embryo transfer protocol (NPP-FET) has recently be proposed as a strategy which potentially allows for easier cycle scheduling while potentially maintaining the benefits of the natural cycle in terms of safer pregnancy outcomes (Godinho, Soares, & Ribeiro, 2021). Both AC-FET and NPP-FET protocols rely immensely on the use exogenous progesterone for luteal phase support (LPS), with the vaginal route being the most common in Europe due to its ease of use compared to intramuscular or subcutaneous alternatives.

Progesterone is a natural hormone produced mainly by the theca cells of the corpus luteum. When supplemented vaginally, endometrial progesterone concentrations reach a steady-state within 5 hours after administration, while serum progesterone levels remain elevated for about 48 hours with prolonged bioavailability (Bulletti, et al., 1997). In a systematic review of 18 randomized clinical trials comparing vaginal preparations for LPS, all tested preparations seemed to be equally effective and safe for assisted reproductive technology cycles (Child, Leonard, Evans, & Lass, 2018). However, studies assessing patient satisfaction are lacking (Beltsos, et al., 2014). Hence, the main objective of this study is to assess the level of satisfaction as well as understand the convenience and tolerability of two of the most common vaginal LPS formulations (soft capsules versus pessaries). The study will compare satisfaction levels, convenience and tolerability, serum progesterone levels on the FET day and pregnancy rates between the two therapeutic formulations.