Endometrin as Luteal Phase Support in Assisted Reproduction

Endometrin monotherapy provided comparable pregnancy rates (PRs) in fresh autologous and fresh donor oocyte cycles. The addition of P in oil to Endometrin improved PRs in frozen transfer cycles.

Eve C. Feinberg, M.D., Angeline N. Beltsos, M.D., Elitsa Nicolaou, B.S., Edward L. Marut, M.D., Meike L. Uhler, M.D.

Volume 99, Issue 1, Pages 174-178.e1, January 2013


To compare clinical pregnancy rate (CPR) and live birth rate (LBR) between Endometrin monotherapy vs. Endometrin and progesterone in oil (PIO) combination therapy in ART cycles.

Retrospective analysis.

Large private practice.

Patients undergoing autologous fresh IVF cycles, autologous frozen embryo transfer (FET) cycles and fresh oocyte donor (OD) cycles were included for analysis.

Endometrin as a single agent for luteal support, Endometrin monotherapy or Endometrin with P in oil used at least once every three days for luteal support, Endometrin combination therapy.

Main Outcome Measures:
Clinical pregnancy and live birth rates.

A total of 1,034 ART cycles were analyzed. Endometrin monotherapy was utilized in 694/1034 (67%) cycles and Endometrin combination therapy was used in 340/1034 (33%) cycles. In all fresh cycles, CPR was not significantly different (IVF autologous: Endometrin monotherapy 46.9% vs. Endometrin combination therapy 55.6%; donor oocyte Endometrin monotherapy 45.2% vs. Endometrin combination therapy 52.0%). Frozen embryo transfer cycles had a significantly higher CPR and live birth rate (LBR) with combination therapy group compared to monotherapy (CPR 47.9% vs 23.5%, P=0.004, LBR 37.5% vs. 17.3%, P=0.0015).

Endometrin monotherapy was sufficient for the progesterone component of luteal support and provided high pregnancy rates for fresh cycles in both autologous and donor oocyte cycles. CPR and LBR in FET cycles were significantly improved with the addition of IM progesterone to Endometrin therapy. This may reflect the fact that lesser quality embryos are transferred in FET cycles, and more intense progesterone support is required for comparable pregnancy rates.

  • Juan Garcia-Velasco, MD

    Very interesting study. Although it lacks the strength of an RCT, numbers are large enough as to make us wonder what is the rationale behind. If progesterone concentration in the endometrium is much higher with vaginal P than with P in oil, why do you think frozen embryos behave differently? Just because of embryo quality? Sample size? Different placentation in HRT cycles?

    • Thank you for your interest in our study. I found the results to be interesting as I was not expecting to find a difference between groups. I am uncertain as to whether the difference is due to some inherent difference in frozen embryos themselves or whether vaginal progesterone is just simply not as effective when used in a cycle where there is no ovarian contribution of progesterone. It may also be due to difference in embryo quality between groups. I am currently doing a follow up study using all PGS euploid frozen transfers and evaluating luteal support between PIO and Endometrin to understand this further

  • Recalculation of the chi-square on the patients without a corpus luteum reveals a LBR of 27.5% vs 40.3% with a p value of <0.01. So, when you look from a slightly different angle you can achieve sufficient sample size to power the study to answer the question you are asking.

  • I wonder if the failure to prove that a 20% higher LBR with combined therapy in a donor egg recipient is due to small sample size in a particular subgroup.

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