What to expect from a ‘standard vaginal progesterone regimen’ in hormone replacement therapy frozen embryo transfer (HRT-FET) – a PRISMA review and meta-analysis

Abstract

A mid-luteal serum progesterone concentration below 9–11 ng/ml has been shown to have a negative impact on reproductive outcomes in hormone replacement therapy frozen embryo transfer (HRT-FET), and as no corpus luteum is present, this concentration reflects the absorption of the progesterone products administered. However, the composition and dosing regimens of vaginal products vary. In total, 24 studies were included in this review, selected according to the following criteria: the use of vaginal progesterone products, with serum progesterone concentration and regimens reported; the absence of additional progesterone or progestin treatments; and the use of both prospective and retrospective study designs. Abstracts and full texts published in languages other than English were excluded. A random-effects proportional meta-analysis of five different vaginal micronized progesterone products was performed, including a total of 11,014 patients. Significant differences were found when comparing Cyclogest (800 mg) with Crinone (180 mg or 270 mg) (P = 0.01); Cyclogest (800 mg) with Utrogestan/Progestan (600 mg or 800 mg) (P = 0.03); and Cyclogest (800 mg) with Lutinus (300 mg) (P = 0.01). However, no significant differences were identified between products with an equivalent daily dose. In conclusion, significant differences in serum progesterone concentration exist between different vaginal progesterone products and dosing regimens, which must be taken into account when performing HRT-FET.