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

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.