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Effects of vaginal vs oral progesterone supplementation before embryo transfer on live birth rates and levels: a randomized trial

Barrenetxea G, Prego O, Celis R, Martínez E, De Las Heras M, Gómez O, Aguirre O, Samojluk S et al.

Reproduction & fertility, 2025

500 participants · 1 citation

Abstract

Abstract: The increase in frozen embryo transfers (FETs) is a consequence of advances in embryo vitrification and the implementation of genetic screening of embryos. There is debate over the best progesterone administration route in substituted cycles and the relationship between progesterone levels on embryo transfer (ET) day and reproductive outcomes. This trial aimed to compare the clinical results of different progesterone supplementation schedules before ET and assess the relationship between plasmatic progesterone levels on transfer day and clinical outcomes. In a prospective, randomized, controlled study, 500 patients were randomly divided into two groups based on the progesterone administration route (oral or vaginal) before ET. Progesterone levels were measured on ET day (PP1) and B-HCG determination (PP2). The primary endpoint was the live birth rate according to different progesterone schedules and levels on transfer day. Despite higher plasmatic progesterone levels with oral administration compared to the vaginal route, there were no significant differences in clinical pregnancy (50.20 vs 47.37%), live birth (43.67 vs 40.89%) or miscarriage rates (13.01 vs 13.68%). Progesterone levels on transfer day were significantly higher among ongoing pregnancies (24.96 ± 1.00 ng/mL) compared to non-ongoing pregnancies (19.39 ± 1.47 ng/mL) and non-pregnancies (17.56 ± 0.99 ng/mL) (P = 0.0001).

Lay summary: The use of FET for the treatment of infertility is increasing. There…

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 500 participants or records.

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