Dydrogesterone and 20α-dihydrodydrogesterone plasma levels on day of embryo transfer and clinical outcome in an anovulatory programmed frozen-thawed embryo transfer cycle: a prospective cohort study

STUDY QUESTION What are the plasma concentrations of dydrogesterone (DYD) and its metabolite, 20α-dihydrodydrogesterone (DHD), measured on day of embryo transfer (ET) in programmed anovulatory frozen embryo transfer (FET) cycles using 10 mg per os ter-in-die (tid) oral DYD, and what is the association of DYD and DHD levels with ongoing pregnancy rate? SUMMARY ANSWER DYD and DHD plasma levels reach steady state by Day 3 of intake, are strongly correlated and vary considerably between and within individual subjects, women in the lowest quarter of DYD or DHD levels on day of FET have a reduced chance of an ongoing pregnancy. WHAT IS KNOWN ALREADY DYD is an oral, systemic alternative to vaginal progesterone for luteal phase support. The DYD and DHD level necessary to sustain implantation, when no endogenous progesterone is present, remains unknown. While DYD is widely used in fresh IVF cycles, circulating concentrations of DYD and DHD and inter- and intraindividual variation of plasma levels versus successful treatment have never been explored as measurement of DYD and DHD is currently only feasible by high-sensitivity chromatographic techniques such as liquid chromatography/tandem mass spectroscopy (LC-MS/MS). STUDY DESIGN, SIZE, DURATION Prospective, clinical cohort study (May 2018–November 2020) (NCT03507673); university IVF-center; women (n = 217) undergoing a programmed FET cycle with 2 mg oral estradiol (tid) and, for luteal support, 10 mg oral DYD (tid); main inclusion criteria: absence of ovulatory follicle and low serum progesterone on Days 12–15 of estradiol intake; serum and plasma samples were taken on day of FET and stored at −80°C for later analysis by LC-MS/MS; in 56 patients, two or more FET cycles in the same protocol were performed. PARTICIPANTS/MATERIALS, SETTING, METHODS Women undergoing FET on Day 2 or Day 3 (D2, D3, cleavage) or Day 5 (D5, blastocyst) of embryonic development had blood sampling on the 3rd, 4th or 6th day of 10 mg (tid) DYD oral intake, respectively. The patient ...