The importance of serum progesterone concentration at embryo transfer day and effect of rescue additional progesterone during programmed artificial frozen embryo transfer cycles

What is the efficacy and possible positive effect of additional rescue subcutaneous (s.c.) progesterone therapy for restoration of progesterone concentration on embryo transfer day and pregnancy rates during programmed artificial frozen embryo transfer (FET) cycles with vaginal progesterone tablet plus i.m. progesterone?Multicentre prospective cohort study (NCT04769401) including a total of 238 programmed artificial FET between February 2021 and September 2021. Patients were divided into ≥10 ng/ml and <10 ng/ml according to serum progesterone concentrations on embryo transfer day; 25 mg of s.c. progesterone was added to patients with <10 ng/ml; blood samples were taken 2 days later. The primary outcome was the ongoing pregnancy rate.The proportion of patients having ≥10 ng/ml serum progesterone concentrations on embryo transfer day was 70.7%. There was no statistically significant difference with regard to cumulative pregnancy rate, ongoing pregnancy rate and miscarriage between the groups (55.4% versus 61.5%, P = 0.4; 78.2% versus 72.5% per pregnancy, P = 0.5; 21.8% versus 27.5%, P = 0.5, respectively, ≥10 ng/ml and <10 ng/ml). Eighty-three per cent of patients with low serum progesterone concentrations on embryo transfer day reached an adequate progesterone concentration with rescue s.c. progesterone treatment; 90% of pregnancy rates in patients with serum progesterone concentrations <10 ng/ml on embryo transfer day were in patients who reached adequate serum progesterone concentrations with daily rescue s.c. progesterone treatment.The measurement of serum progesterone concentrations on embryo transfer day may create the opportunity for rescue progesterone administration on that day for patients who fail to reach adequate serum progesterone concentrations, achieving similar pregnancy rates without cancellation of the cycle.