Endometrin®/prometrium® versus intramuscular progesterone administration for luteal phase support

BackgroundThe ideal method of endometrial preparation for a frozen embryo transfer (FET) is not defined1. Intramuscular (IM) progesterone has been the standard approach, but is uncomfortable and sometimes intolerable to patients. Alternative routes of progesterone administration include oral and vaginal. Oral progesterone is rapidly metabolized and is generally accepted to be inferior to the IM or vaginal route1-4. Several studies comparing outcomes of progesterone vaginal gel (Crinone®) vs. IM have shown mixed results2-5. A comparison of progesterone vaginal inserts (Endometrin®) with IM found that Endometrin® alone was inferior to the combination of IM and Endometrin® in FET cycles5-6. Others have shown increased pregnancy loss rates with Endometrin® alone vs. IM.ObjectiveTo compare a novel combination of vaginal Endometrin® and oral progesterone (Prometrium®) (Endo-Prom) with IM for luteal support in FETs. Primary outcomes were biochemical and ongoing pregnancy rates. Secondary outcomes were adverse effects of different routes of progesterone including injection site reaction, vaginal irritation, gastro-intestinal symptoms, and vaginal bleeding.Materials and methodsA retrospective review was conducted of non-donor oocyte FETs in patients from a private practice under 41 years in 2014. Patients in the study group were those who self-elected to use Endo-Prom (n=55), rather than IM (n=321) (control group), mainly due to patients’ desire to avoid pain with IM injections.ResultsThe IM and Endo-Prom groups were similar in age (33.3 vs. 33.7 years) and average number of embryos transferred (1.7 vs. 1.7). No significant differences in the IM vs. Endo-Prom group were seen in biochemical pregnancy rate (65.1% vs. 65.4%, p=1.0) and ongoing pregnancy rates (45.5% vs. 49%, p=0.66). Rates of significant vaginal bleeding were lower in the IM group than Endo-Prom (10.0% vs. 21.8%, p=0.02). There were no significant reactions with Endometrin® and all patients tolerated Prometrium®. Substantial injection site reactions were noted in 3% of patients.ConclusionsA novel combination of vaginal and oral progesterone yields similar pregnancy rates to IM injection in patients undergoing FET. This combination is well tolerated and helps avoid significant discomfort and stress experienced by patients using IM injections. This study appears to be the first to demonstrate that Endometrin® may be used for FETs with equivalent efficacy to IM progesterone. Although vaginal bleeding was noted to be more frequent in the Endo-Prom group the ongoing pregnancy rates were unaffected. Further prospective study of a combination of oral and vaginal progesterone in FET cycles is warranted.Financial supportDr. Griffith participates in the Ferring Pharmaceutical Speaker’s Bureau.References1.Linden, M., Van Der, K. Buckingham, C. Farquhar, J. A. M. Kremer, and M. Metwally. “Luteal Phase Support in Assisted Reproduction Cycles (Review).” The Cochrane Library 10(2011): 1-211.2.Salehpour, S, M. Tamimi, and N. Saharkhiz. “Comparison of Oral Dydrogesterone with Suppository Vaginal Progesterone for Luteal-phase Support in in Vitro Fertilization (IVF): A Randomized Clinical Trial.” Iran J Reprod Med 11.11 (2013): 913-18.3.Ganesh, A., N. Chakravorty, R. Mukherjee, S. Goswami, K. Chaudhury, and B. Chakravarty. “Comparison of Oral Dydrogestrone with Progesterone Gel and Micronized Progesterone for Luteal Support in 1,373 Women Undergoing in Vitro Fertilization: A Randomized Clinical Study.” Fertility and Sterility 95.6 (2011): 1961-965.4.Pouly, J.L., S. Bassil, R. Frydman, B. Hedon, B. Nicollet, Y. Prada, J.M. Antoine, R. Zambrano and J. Donnez. “Luteal support after in-vitro fertilization: Crinone 8%, a sustained release vaginal progesterone gel, versus Utrogestan, an oral micronized progesterone.” Human Reproduction 11.10 (1996): 2085-89.5.Khan, N., K. S. Richter, T. L. Newsome, E. J. Blake, and V. I. Yankov. “Matched-samples Comparison of Intramuscular versus Vaginal Progesterone for Luteal Phase Support after in Vitro Fertilization and Embryo Transfer.” Fertility and Sterility 91.6 (2009): 2445-450.6.Feinberg, E. C., A. N. Beltsos, E. Nicolaou, E. L. Marut, and M. L. Uhler. “Endometrin as Luteal Phase Support In assisted Reproduction.” Fertility and Sterility 99.1 (2013): 174-78. BackgroundThe ideal method of endometrial preparation for a frozen embryo transfer (FET) is not defined1. Intramuscular (IM) progesterone has been the standard approach, but is uncomfortable and sometimes intolerable to patients. Alternative routes of progesterone administration include oral and vaginal. Oral progesterone is rapidly metabolized and is generally accepted to be inferior to the IM or vaginal route1-4. Several studies comparing outcomes of progesterone vaginal gel (Crinone®) vs. IM have shown mixed results2-5. A comparison of progesterone vaginal inserts (Endometrin®) with IM found that Endometrin® alone was inferior to the combination of IM and Endometrin® in FET cycles5-6. Others have shown increased pregnancy loss rates with Endometrin® alone vs. IM. The ideal method of endometrial preparation for a frozen embryo transfer (FET) is not defined1. Intramuscular (IM) progesterone has been the standard approach, but is uncomfortable and sometimes intolerable to patients. Alternative routes of progesterone administration include oral and vaginal. Oral progesterone is rapidly metabolized and is generally accepted to be inferior to the IM or vaginal route1-4. Several studies comparing outcomes of progesterone vaginal gel (Crinone®) vs. IM have shown mixed results2-5. A comparison of progesterone vaginal inserts (Endometrin®) with IM found that Endometrin® alone was inferior to the combination of IM and Endometrin® in FET cycles5-6. Others have shown increased pregnancy loss rates with Endometrin® alone vs. IM. ObjectiveTo compare a novel combination of vaginal Endometrin® and oral progesterone (Prometrium®) (Endo-Prom) with IM for luteal support in FETs. Primary outcomes were biochemical and ongoing pregnancy rates. Secondary outcomes were adverse effects of different routes of progesterone including injection site reaction, vaginal irritation, gastro-intestinal symptoms, and vaginal bleeding. To compare a novel combination of vaginal Endometrin® and oral progesterone (Prometrium®) (Endo-Prom) with IM for luteal support in FETs. Primary outcomes were biochemical and ongoing pregnancy rates. Secondary outcomes were adverse effects of different routes of progesterone including injection site reaction, vaginal irritation, gastro-intestinal symptoms, and vaginal bleeding. Materials and methodsA retrospective review was conducted of non-donor oocyte FETs in patients from a private practice under 41 years in 2014. Patients in the study group were those who self-elected to use Endo-Prom (n=55), rather than IM (n=321) (control group), mainly due to patients’ desire to avoid pain with IM injections. A retrospective review was conducted of non-donor oocyte FETs in patients from a private practice under 41 years in 2014. Patients in the study group were those who self-elected to use Endo-Prom (n=55), rather than IM (n=321) (control group), mainly due to patients’ desire to avoid pain with IM injections. ResultsThe IM and Endo-Prom groups were similar in age (33.3 vs. 33.7 years) and average number of embryos transferred (1.7 vs. 1.7). No significant differences in the IM vs. Endo-Prom group were seen in biochemical pregnancy rate (65.1% vs. 65.4%, p=1.0) and ongoing pregnancy rates (45.5% vs. 49%, p=0.66). Rates of significant vaginal bleeding were lower in the IM group than Endo-Prom (10.0% vs. 21.8%, p=0.02). There were no significant reactions with Endometrin® and all patients tolerated Prometrium®. Substantial injection site reactions were noted in 3% of patients. The IM and Endo-Prom groups were similar in age (33.3 vs. 33.7 years) and average number of embryos transferred (1.7 vs. 1.7). No significant differences in the IM vs. Endo-Prom group were seen in biochemical pregnancy rate (65.1% vs. 65.4%, p=1.0) and ongoing pregnancy rates (45.5% vs. 49%, p=0.66). Rates of significant vaginal bleeding were lower in the IM group than Endo-Prom (10.0% vs. 21.8%, p=0.02). There were no significant reactions with Endometrin® and all patients tolerated Prometrium®. Substantial injection site reactions were noted in 3% of patients. ConclusionsA novel combination of vaginal and oral progesterone yields similar pregnancy rates to IM injection in patients undergoing FET. This combination is well tolerated and helps avoid significant discomfort and stress experienced by patients using IM injections. This study appears to be the first to demonstrate that Endometrin® may be used for FETs with equivalent efficacy to IM progesterone. Although vaginal bleeding was noted to be more frequent in the Endo-Prom group the ongoing pregnancy rates were unaffected. Further prospective study of a combination of oral and vaginal progesterone in FET cycles is warranted. A novel combination of vaginal and oral progesterone yields similar pregnancy rates to IM injection in patients undergoing FET. This combination is well tolerated and helps avoid significant discomfort and stress experienced by patients using IM injections. This study appears to be the first to demonstrate that Endometrin® may be used for FETs with equivalent efficacy to IM progesterone. Although vaginal bleeding was noted to be more frequent in the Endo-Prom group the ongoing pregnancy rates were unaffected. Further prospective study of a combination of oral and vaginal progesterone in FET cycles is warranted.