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

ObjectiveTo study the efficacy of a new P preparation in aqueous solution for subcutaneous injection for inducing the predecidual transformation of the endometrium.DesignProspective, single-blinded, randomized, parallel pilot trial.SettingUniversity-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/m2, 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 NumberNCT00377923. To study the efficacy of a new P preparation in aqueous solution for subcutaneous injection for inducing the predecidual transformation of the endometrium. Prospective, single-blinded, randomized, parallel pilot trial. University-affiliated clinical research center. Twenty-five regularly cycling female volunteers. Volunteers, aged 18–45 years, body mass index 19–25 kg/m2, 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. Predecidual changes in endometrial biopsies obtained after 11 days of subcutaneous administration of P. 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. 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.