A randomized trial comparing the endometrial effects of daily subcutaneous administration of 25 mg and 50 mg progesterone in aqueous preparation

Abstract

Objective: To study the efficacy of a new P preparation in aqueous solution for subcutaneous injection for inducing the predecidual transformation of the endometrium.

Design: Prospective, single-blinded, randomized, parallel pilot trial.

Setting: University-affiliated clinical research center.

Patient(s): Twenty-five regularly cycling female volunteers.

Intervention(s): Volunteers, aged 18-45 years, body mass index 19-25 kg/m(2), whose ovaries were suppressed with a GnRH agonist were estrogenized for 14 or 21 days with the use of transdermal systems delivering 0.1 mg/d E₂. After confirming that the endometrial thickness was >7 mm, the women were randomized to 25 mg or 50 mg of subcutaneous P injections daily for 11 days, after which the endometrium was sampled with the use of a Pipelle device. The endometrial biopsies were evaluated by two independent pathologists. Adverse events and subjective tolerance were checked every day by the study investigator.

Main outcome measure(s): Predecidual changes in endometrial biopsies obtained after 11 days of subcutaneous administration of P.

Result(s): Of 24 biopsies performed (one dropout), 22 provided tissue for histologic analysis. Evidence of predecidual changes in the endometrial stroma was found in 100% of the cases, with no differences between the two studied doses.

Conclusion(s): Both doses of the new aqueous P preparation available for subcutaneous administration demonstrated predecidual changes in 100% of the interpretable endometrial biopsies in total absence of endogenous P. This offers good prospect of efficacy in luteal phase support for the lowest dose tested, 25 mg/d, the physiologic amount produced daily by the ovary during the midluteal phase.

Clinical trial registration number: NCT00377923.

Keywords: Progesterone; aqueous; decidualization; luteal phase support; subcutaneous.