Intramuscular versus Vaginal Progesterone Administration in Medicated Frozen Embryo Transfer Cycles: a Randomized Clinical Trial Assessing Sub-Endometrial Contractions (in press)

Objective: The study aimed to assess whether sub‐endometrial contractility is reduced by the use of intramuscular (IM) progesterone. Design: This is a randomized clinical trial. Patients assigned to a medicated day 5 frozen embryo transfer (FET) were randomly allocated to 'vaginal progesterone' or 'IM progesterone': patients randomized to the vaginal arm were treated with 200 mg micronized progesterone 3 times daily while patients randomized into the IM progesterone arm were treated with a single daily injection of 50 mg progesterone in oil. The main outcome measure was the number of sub‐endometrial contractions (waves) per minute 1 day before a blastocyst embryo transfer. Results: Thirty‐four patients were enrolled. The progesterone serum concentration was significantly higher in patients using the IM progesterone (85.2 +/‐ 50.1 vs. 30.3 +/‐ 11.2 nmol/L, respectively) but this did not translate into a lower sub‐endometrial contractility (2.4 +/‐ 4.8 vs. 1.4 +/‐ 1.1 contraction/min, respectively). Clinical pregnancy rates were comparable between groups. The number of sub‐endometrial waves was significantly lower among pregnant patients (p = 0.02). Conclusions: The use of IM progesterone in medicated FET cycles does not reduce the sub‐endometrial activity compared to vaginal progesterone administration. Our data support a poor clinical pregnancy outcome with high wave activity, regardless of the progesterone mode.