The efficacy of subcutaneous versus vaginal progesterone for luteal phase support using a rescue protocol - a comparison in 723 blastocyst HRT-FET cycles


      • Limited data exist comparing subcutaneous (sc) and vaginal progesterone (P) in HRT
      • No patient using sc P twice-daily needed additional P as a rescue protocol
      • 15.8 % of patients using vaginal P gel twice-daily needed additional P as rescue
      • sc P alone and vaginal P with rescue yield comparable ongoing pregnancy rates in HRT


      Research Question

      Does subcutaneous (sc) progesterone (P) administration support ongoing pregnancy rates (OPRs) similar to vaginal P using a rescue protocol in hormone replacement therapy (HRT) frozen embryo transfer (FET) cycles?


      Retrospective cohort study. Two sequential cohorts, vaginal P gel (December 2019-October 2021; n=474) and sc P (November 2021-November 2022; n=249) were compared. Following estrogen priming, sc P 25 mg twice-daily or vaginal P gel 90 mg twice-daily were administered. Serum progesterone (P4) was measured one day prior to warmed blastocyst transfer, i.e. day 5 of P administration. In patients with serum P4 levels <8.75 ng/ml, additional sc P (rescue; 25 mg) was provided.


      In the vaginal P group, a total of 15.8 % had serum P4 <8.75 ng/ml and received rescue whereas no patient in the sc P group received rescue. The OPRs were comparable between the sc P group without rescue and the vaginal P group with rescue. After rescue, the route of P administration was not a significant predictor of ongoing pregnancy. The impact of different serum P4 levels on reproductive outcomes was evaluated by percentiles (<10th, 10–49th, 50–90th and >90th percentiles), taking the >90th percentile as the reference subgroup. In the vaginal as well as the sc P group all serum P4 percentile sub-groups had similar OPR`s.


      Subcutaneous P 25 mg, twice-daily secures a serum P4 above 8.75 ng/ml whereas additional exogenous P (rescue) was needed in 15.8% of patients receiving vaginal P. The sc and vaginal P routes, with rescue if needed, yield comparable OPRs.

      Key words

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      Hakan Yarali is a specialist in reproductive endocrinology at Anatolia IVF, one of the busiest IVF centres in Turkey, and is also Professor at Hacettepe University, Ankara, Turkey. His special interests are in all clinical aspects of IVF. He has authored more than 130+ articles, eight book chapters and delivered over 50 lectures worldwide.