Oral dydrogesterone has been used for luteal phase support on an empirical basis since the early days of in vitro fertilization (IVF) treatment. Systematic comparisons of oral dydrogesterone with vaginal progesterone, so far considered to be the standard of care, started to appear in the middle 2000s.
Recently, a large, randomized, double-blind, double-dummy phase III trial on the use of daily 30 mg oral dydrogesterone versus daily 600 mg micronized vaginal progesterone for LPS in IVF was published. This company-sponsored trial confirmed the efficacy findings from previous independent researchers and firmly established the noninferiority of daily 30 mg oral dydrogesterone for luteal phase support.
Despite oral administration and first pass through the liver, dydrogesterone was as well tolerated as vaginal progesterone in safety analyses. Moreover, no new fetal safety concerns have arisen from that trial. Given the widespread preference of women for an oral compound, dydrogesterone may well become the new standard for luteal phase support in fresh embryo transfer IVF cycles.