Network meta-analysis of progestogen administration routes for luteal phase support in fresh embryo transfer IVF cycles.

The route of administration significantly influences the pharmacokinetics of progestogens. For luteal phase support (LPS) after fresh embryo transfer in IVF, ESHRE recommends vaginal, intramuscular, subcutaneous progesterone or oral dydrogesterone. This network meta-analysis evaluated the relative effectiveness of progestogen administration routes on clinical pregnancy rate (CPR) and live birth rate (LBR) in fresh IVF cycles. A systematic review identified peer-reviewed, published randomized controlled trials (RCTs) comparing individual progestogens (versus placebo or other progestogens) and reporting CPR. Studies involving frozen-thawed transfers, non-progestogenic LPS or non-available formulations were excluded. Of the 24 RCTs included, oral administration was the only route reaching statistical significance for increased CPR, although overlapping confidence intervals across comparisons indicate uncertainty in clinically relevant superiority. For LBR, only oral and intramuscular routes demonstrated statistically significant improvement versus placebo; vaginal and subcutaneous did not. These findings, supported by sensitivity analyses excluding low-quality and older studies, suggest that oral and intramuscular progestogens may be more effective in improving IVF outcomes, but outcome differences require further studies. This study substantially advances the evidence base by integrating recent data, applying rigorous quality assessment standards and using state-of-the-art network meta-analytic methodology, contributing to refining recommendations for optimal progestogenic LPS in fresh IVF cycles.