Progesterone Suppository

Vaginal progesterone suppositories (such as Endometrin) or vaginal gel (Crinone 8%) deliver progesterone directly to the uterus via the vaginal-uterine first-pass effect, achieving high local concentrations with relatively low systemic exposure. They are inserted 2–3 times daily.

They are a common alternative to intramuscular (IM) progesterone-in-oil injections, which some patients find painful and difficult to self-administer. Multiple studies show comparable IVF pregnancy rates between vaginal and IM routes for most patients, though some high-risk subgroups may benefit from IM.

Vaginal discharge and minor irritation are the most common side effects; serum progesterone levels are lower than with IM injections but do not reliably reflect endometrial levels.